Blocking the FAM19A5-LRRC4B complex enhances neurite growth and synapse assembly.

Blocking the FAM19A5-LRRC4B complex enhances neurite growth and synapse assembly. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Blocking the FAM19A5-LRRC4B complex enhances neurite growth and synapse assembly. Jae Young Seong This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2589038/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Disruption in dynamic balance of synapse build-and-removal process is a major cause of neurological diseases, although the mechanisms underlying the brain fine-tunes and balances this process remain poorly understood. Here, we show that FAM19A5 binds to the postsynaptic adhesion molecule LRRC4B via the FAM19A5 binding (FB) domain, suppressing the interaction of LRRC4B with a presynaptic adhesion molecule PTPRF. Decoys with the FB domain bind to FAM19A5 and redirect it away from the FAM19A5-LRRC4B complex, promoting neurite growth and synapse formation of neurons. The anti-FAM19A5 monoclonal antibody NS101 breaks apart the FAM19A5-LRRC4B complex and enables the transfer of FAM19A5 from the brain into the bloodstream, leading to the restoration of synaptic integrity and improve cognitive function in mouse models of Alzheimer’s disease. Together, our findings suggest that blocking the complex with NS101 may offer therapeutic strategy for treating neurodegenerative diseases requiring regeneration of neurites and formation of new synapses. Cognitive Neuroscience Neurology Cellular & Molecular Neuroscience FAM19A5 LRRC4B PTPRF Anti-FAM19A5 antibodies Decoy with FB Neurite growth Synapse assembly Neurological diseases Alzheimer’s disease Hippocampus Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction Synapses are specialized adhesive junctions that allow neurons to transmit and process information by connecting to various neural circuits in the brain. The number of synapses in the brain changes throughout life as a result of a dynamic process of synapse build-up and removal. 1 , 2 This process is known as synaptic plasticity and is essential for the normal development and function of the brain. 3 The increase in synapse numbers is essential for the formation of new neural connections and the establishment of functional neural circuits. However, as the brain matures, a process of synaptic pruning begins, where unnecessary or under-used synapses are selectively removed. 1 , 3 , 4 Synaptic pruning continues throughout life and can be influenced by a range of factors including experience, hormones, and microenvironment surrounding neurons. 5 , 6 The number of synapses decreases as people age. 7 This decline in synapse numbers is thought to contribute to age-related cognitive decline and the increased risk of neurodegenerative disorders such as Alzheimer's disease (AD). 8 Therefore, the dynamic nature of synapse numbers in the brain is essential for its normal development, function, and adaptation to changes in the environment. Abnormalities in this process can lead to a range of neurological and psychiatric disorders, 9 , 10 and as such, understanding the regulation of synapse build-and-removal dynamics may guide the development of effective therapeutic strategies for treating neurological and neurodegenerative diseases. Synaptic adhesion molecules participate in regulating synapse numbers via molecular processes, including formation, maturation, and continuous reorganization. 11 , 12 The role of synaptic adhesion molecules extends beyond just adhesive contacts between membranes, as they play a critical role in organizing synapses, preserving their functional integrity, and facilitating changes to pre-existing synapse. 13 The leucine-rich repeat-containing 4s (LRRC4s, also known as Netrin-G ligands, NGLs), are a family of three postsynaptic adhesion molecules: LRRC4, LRRC4B, and LRRC4C. 14 – 16 The LRRC4 members share similar structures, including leucine-rich repeat (LRR) domains flanking LRR N-terminus and C-terminus, an immunoglobulin-like C2-type (IgC) domain, a transmembrane domain, and a postsynaptic density-binding (PB) domain. LRRC4B can form excitatory synapses by transsynaptic interacting with presynaptic protein tyrosine phosphatase receptors (PTPR-F, -D, and -S), also known as LAR-RPTPs. 17 – 19 It also, via its PDZ-binding domain, binds to the postsynaptic scaffolding protein postsynaptic density-95 (PSD-95) and promotes clustering of NMDA and AMPAR receptors at the postsynaptic site. 15 , 19 Thus, LRRC4B plays a crucial role in various stages of excitatory synapse formation and function, such as inducing the initial transsynaptic connection between axon and dendrite, clustering postsynaptic proteins, and controlling synaptic plasticity. 19 , 20 This is evidenced by Lrrc4b knockout (KO) mice that exhibited major impairments in brain development, synaptic transmission, and plasticity, which are accompanied by behavioral hyperactivity and reduced cognitive function. 21 However, the exact mechanism by which LRRC4B regulates synapse dynamics is yet to be understood. Additionally, it is possible that LRRC4B interacts with other unknown proteins that regulates dynamic synapse formation and disassembly, besides the known LRRC4B-interacting proteins. The family with sequence similarity 19 member A (FAM19A, also known as TAFA) family consists of five paralogous members that encode small, secreted proteins. 22 These proteins are predominantly expressed in the central nervous system. 22 The amino acid (aa) sequence of the secreted FAM19A5 domain is highly conserved across vertebrate species, suggesting a physiologically relevant function in vertebrates. 22 , 23 FAM19A5 transcripts are abundant in the brain but less so in peripheral tissues. 24 Recent advances in single-cell RNA-seq (scRNA-seq) analysis of mouse brain tissue have provided more detailed expression pattern of Fam19a5 transcripts, 25 showing that Fam19a5 transcripts are mainly found in excitatory and inhibitory neurons in various regions including layers 2/3 and 5 of the cortex and in the CA1 and CA3 regions of the hippocampus. 25 A recent study showed that FAM19As, other than FAM19A5, interact with the neurexins, 26 which play a role in synaptic adhesion. This suggests that FAM19A5, similar to its relatives, may act as a ligand for other synaptic adhesion molecules and be involved in synapse formation and function, thereby impacting nervous system function. This is supported by finding from Fam19a5 KO mice, which exhibited hyperactivity, depressive-like behaviors, and reduced spatial learning and memory, as well as a decrease in dendritic spine density, glutamate signaling, and neuronal activity. 27 Recent genome-wide association studies have revealed the association of FAM19A5 with neurological disorders including AD, attention deficit hyperactivity disorder, and autism. 28 – 30 Furthermore, a recent single-nucleus RNA-seq (snRNA-seq) in human AD brain samples showed that FAM19A5 transcript levels in neurons were higher in those with early AD pathology compared to those without. 31 This result aligns with human serum assay results, 32 which showed increased FAM19A5 levels in patients with vascular dementia compared to controls, suggesting a potential contribution of FAM19A5 to the progression of AD pathology. However, exact role of FAM19A5 function in pathophysiological condition remains elusive due to limited research on its interacting partner proteins. Previous studies proposed that FAM19A5 may interact with N-formyl peptide receptor 2 or sphingosine 1-phosphate receptor 2, 33 – 35 but our recent study refutes these claims. 24 In the present study, we found that LRRC4B interacts with FAM19A5 with high affinity. FAM19A5 binds to a core domain within LRRC4B, hereafter referred to as FAM19A5 binding (FB) domain. Decoy peptides or proteins containing the FB domain (FB decoy) can capture FAM19A5 and disrupt the endogenous FAM19A5-LRRC4B complex. Both the FB decoys and an anti-FAM19A5 antibody called NS101 36 induced neurite outgrowth and synapse formation in mouse primary neurons. This led us to propose that FAM19A5 regulates neurite growth and synapse formation as a suppressor, by forming the FAM19A5-LRRC4B complex. Given that the FAM19A5-LRRC4B complex hinders new synapse formation, it may serve as a target for treating synapse loss in AD. In mouse models of AD, treatment with NS101 facilitated transport of FAM19A5 from the brain into the blood, which may reduce the level of the FAM19A5-LRRC4B complex in the brain. This resulted in increased synaptic density, function, and plasticity in the hippocampus, as well as improved cognitive ability in the AD mice. Our findings suggest that blocking the formation of the FAM19A5-LRRC4B complex could be a promising therapeutic strategy for AD. Results FAM19A5 binds to LRRC4B via the FB domain. To uncover potential binding partners for FAM19A5, we searched the mouse brain scRNA-seq database ( http://mousebrain.org ) 25 and found synapse adhesion molecules whose transcript levels showed strong correlation with Fam19a5 transcript levels across 168 different types of neurons (Figs. 1 A and S1A). Notably, the expression of Lrrc4b was found to be highly correlated with Fam19a5 transcripts (Fig. 1 A), raising a possible interaction between FAM19A5 and LRRC4B. To access this possibility, we performed coimmunoprecipitation (co-IP) assays using various anti-FAM19A5 antibodies that target the N-terminal (N-A5-Ab) and C-terminal (C-A5-Ab) regions of FAM19A5. 24 V5-tagged LRRC4B transfected into HEK293 cells, treated with recombinant FAM19A5 (rcFAM19A5), was coimmunoprecipitated with C-A5-Ab (Fig. 1 B) and vice versa (Figure S1B). Two FAM19A5 transcripts, isoform 1 and isoform 2, produce two FAM19A5 isoform proteins that differ in their N-terminal sequences. 24 , 34 To assess the interactions between the FAM19A5 isoforms and LRRC4B, we cotransfected HEK293 cells with cDNA encoding the FLAG-tagged LRRC4B protein and either FAM19A5 isoform 1 or isoform 2. Immunofluorescence revealed that both FAM19A5 isoforms colocalized strongly with LRRC4B (Fig. 1 C). Similarly, immunoprecipitates of LRRC4B from cell lysates using an anti-FLAG antibody also included both FAM19A5 isoforms (Figure S1C), and immunoprecipitates using C-A5-Ab showed interactions between LRRC4B and both FAM19A5 isoforms (Figure S1D). However, the anti-FAM19A5 antibody N-A5-Ab only weakly coimmunoprecipitated LRRC4B, as an epitope of FAM19A5 recognized by N-A5-Ab is involved in LRRC4B binding. LRRC4B can be released into the culture medium by cleavage at the juxta-membrane region (Fig. 1 D). 20 When FAM19A5 isoform 1 was coexpressed with LRRC4B, there was less FAM19A5 in the culture medium, and more was retained in the cell (Fig. 1 D), indicating that LRRC4B traps soluble FAM19A5 in the plasma membrane. LRRC4B expressed in neurons can be secreted into the cerebrospinal fluid (CSF) of humans where FAM19A5 is also found. 37 – 39 Therefore, the FAM19A5-LRRC4B complex may be present in the CSF, as seen in immunoblots of human CSF showing both FAM19A5 and LRRC4B (Fig. 1 E). In addition, rcFAM19A5-treated primary cortical neurons showed FAM19A5 localization to neurites where LRRC4B is highly expressed (Fig. 1 F). To identify FAM19A5-binding sequences in LRRC4B, various FLAG-tagged deletion constructs for LRRC4B were generated (Fig. 1 G). HEK293 cells expressing these deletion constructs were treated with rcFAM19A5, and the cell lysates were coimmunoprecipitated with an anti-FLAG antibody. We found that all constructs containing the 484–498 aa sequence of LRRC4B were able to bind to FAM19A5, whereas deletion of the 484–498 aa sequence abolished FAM19A5 binding (Figs. 1 G and S1E). Since this 484–498 sequence is highly conserved among LRRC4 family members in mammals (Fig. 1 H), we designated this core sequence as the FAM19A5 binding (FB) domain. An enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) revealed that LRRC4B(453–576) conjugated with human Fc [hereafter, LRRC4B(453–576)-hFc] demonstrated ~ 100 picomolar affinity by ELISA (Fig. 1 I) and ~ 30 picomolar affinity for FAM19A5 by SPR (Fig. 1 J). FB peptides inhibited binding between FAM19A5 and LRRC4B(453–576)-hFc/LRRC4B(36–576)-hFc in a competitive manner. However, peptides lacking one or more aa from the FB domain (positions 484–498) gradually lose their ability to inhibit the FAM19A5-LRRC4B interaction (Figure S1F). Recent advances in deep learning methods allow the construction of structures for the protein complexes. Using combination of AlphaFold2 40 and RoseTTAFold 41 , 42 , we modeled the structure of the FAM19A5-LRRC4B complex (Figs. 2 A-C and S2A), showing that the FB sequence from Tyr484 to Glu496 of LRRC4B directly interacted with FAM19A5. In particular, the sequence of FB, which had a disordered structure before binding to FAM19A5 (Fig. 2 A), became a β-strand constituting a β-sheet structure together with β-strands formed from FAM19A5 (Figs. 2 B and 2 C). Then, we further identified the residues responsible for the interaction between FAM19A5 and FB via in silico Ala scanning where each non-Ala residue of the complex was replaced to Ala using Schrodinger Bioluminate®. This calculates changes in protein-peptide binding affinity based on a large increase in the binding free energy following the Ala mutation (Figure S2B). For FB, Ala substitution for residues that actively participate in β-sheet formation with FAM19A5 increased the binding free energy, which means weakened binding, except for Thr494 and Leu495 in FB. These two residues are unlikely to contribute significantly to the interaction, consistent with the biochemical results (Fig. 2 D). Besides residues participating in β-sheet formation, residues from Glu496 to Pro499 are likely involved in interaction with FAM19A5 as substitution of residues to Ala increased the binding free energy (Figure S2B). Full-length LRRC4B(36–716) and LRRC4B(453–576) fragments in which Thr488 and Thr489 were substituted with Ala showed a very weak binding to FAM19A5 by a co-IP assay (Figures S2C and S2D) and ELISA (Fig. 2 E). For FAM19A5, the basic residues Arg58, Arg59, Arg125, and Lys127 were found to be involved in the interaction with the FB domain via in silico Ala scanning (Figure S2E). These four residues from FAM19A5 participate in b-sheet formation through hydrogen bond interactions with the b-strand formed in the FB domain (Figure S2A). Furthermore, anionic carboxylate (RCOO−) of Glu493 of LRRC4B and the cationic ammonium (RNH3+) from Lys127 can form salt-bridge (Fig. 2 C). Indeed, a double mutation substituting Ala for Arg125 and Lys127 of FAM19A5 reduced the binding affinity to LRRC4B. Arg58 and Arg59 may also play role in the interaction with FB, as their Ala substitution reduced affinity to LRRC4B and quadruple mutations of Arg58, Arg59, Arg125, and Lys127 further reduced the binding affinity to LRRC4B (Fig. 2 F). In particular, N-A5-Ab epitope mapping via Ala mutation indicated that Arg52, Pro57, Arg58, and Arg59 of FAM19A5 were found to be epitopes for N-A5-Ab (Figure S2F); thus, N-A5-Ab and LRRC4B partly compete at Arg58 and Arg59 for FAM19A5 binding (Figures S2A and S2F). Because FB-containing peptides/proteins bound to FAM19A5 with high affinity, we determined whether they compete with LRRC4B to dissociate the FAM19A5-LRRC4B complex (Fig. 2 G). The cell-free ELISA revealed that WT LRRC4B(453–576)-hFc (Fig. 2 H) and FB-containing peptides (Fig. 2 I) resulted in a dose-dependent decrease in the binding between FAM19A5 and LRRC4B. However, the mutant (MT) peptide in which Ala was substituted for Thr488 and Thr489 in MT LRRC4B(453–576)-hFc only slightly inhibited binding (Fig. 2 H). Treatment with WT LRRC4B(453–576)-hFc for 30 min caused a substantial dissociation of FAM19A5 from full-length LRRC4B in HEK293 cells expressing both FAM19A5 isoform 2 and LRRC4B (Fig. 2 J). In contrast, in HEK293 cells treated with MT LRRC4B(453–576)-hFc, FAM19A5 remained largely bound to LRRC4B (Fig. 2 J), suggesting that FB-containing peptides and proteins can act as a decoy to steer FAM19A5 away from the complex. FAM19A5 inhibits interaction between LRRC4B and PTPRF via the FB domain. We then examined the role of FAM19A5 in regulating LRRC4B function. LRRC4B is known to interact physically with the presynaptic protein PTPRF, facilitating synapse formation between neurons. 43 Hence, it is likely that alterations in FAM19A5 levels during synapse formation or elimination can affect the dynamic equilibrium of LRRC4B and PTPRF interaction (Fig. 3 A). To assess the impact of FAM19A5 on this interaction, we transfected HEK293 cells with FLAG-tagged PTPRF and V5-tagged LRRC4B cDNAs and treated the cells with rcFAM19A5. The binding between LRRC4B and PTPRF was examined through immunoprecipitation with anti-V5 antibody and revealed a dose-dependent decrease in interaction upon FAM19A5 treatment (Fig. 3 B). This result was further confirmed using an ELISA. PTPRF(30-1263)-hFc bound to HIS-TEV-LRRC4B(36–576) in a dose-dependent manner. Preincubation of LRRC4B-coated plate with 1 µM WT rcFAM19A5 significantly reduced the binding, whereas the binding was not inhibited by a MT FAM19A5(R58A, R59A, R125A, K127A) that weakly binds to the FB domain (Fig. 2 F and 3 C). Increasing doses of WT rcFAM19A5 competitively inhibited the binding, but MT rcFAM19A5 was less effective in doing so (Fig. 3 D). These findings suggest that FAM19A5 suppresses synapse dynamics through its interaction with LRRC4B, potentially slowing synapse formation or promoting synapse disassembly. Therefore, the FB decoys can play a positive role in synapse dynamics by redirecting FAM19A5 away from the FAM19A5-LRRC4B complex. FB decoys promote neurite growth and synapse formation. We addressed the effect of the FB decoy in neuronal cells. We first measured transcript levels of various synapse-related genes including Fam19a5 , Lrrc4b , and Ptprf in cultured neurons by RNA-seq. Fam19a5 transcript levels in the mouse hippocampal neurons were already high at day in vitro 1 (DIV 1) compared to those of other Fam19a family members (Fig. 4 A). Lrrc4b and Ptprf transcripts were also notably high in hippocampal neurons at DIV 1 compared to other synaptic molecules, and the Lrrc4b transcript level remained high until DIV 16 (Fig. 4 A). High expression levels of Fam19a5, Lrrc4b , and Ptprf in early stages of cultured neurons suggest their involvement in neurite outgrowth and synaptogenesis, potentially via formation of the FAM19A5-LRRC4B complex. Therefore, we studied the impact of the FB decoy LRRC4B(453–576)-hFc on neurite and synapse development in cultured neurons. Treatment with WT LRRC4B(453–576)-hFc led to a dose-dependent increase in neurite length and number of primary neurites and branching points in primary cortical neurons (Figs. 4 B and 4 C). In contrast, treatment with MT LRRC4B(453–576)-hFc had no impact on neurite growth and was comparable to the control group (Figs. 4 B and 4 C). It is shown that the addition of FAM19A5 to primary culture neurons caused to a significant decrease in the length of neurites and number of primary neurites (Figure S3A and S3B). Furthermore, it also decreased the number of puncta colabled for the presynaptic marker synaptophysin (SYP) and the postsynaptic marker postsynaptic density 95 (PSD95) (Figure S3C). These results suggest that FAM19A5, through the formation of the FAM19A5-LRRC4B complex, may function as a suppressor of neurite growth and synapse formation. Neurites grow and differentiate into dendrites or axons which eventually form a synapse. 44 – 46 Therefore, we determined whether disruption of the FAM19A5-LRRC4B complex promoted synapse formation. The addition of WT LRRC4B(453–576)-hFc, but not MT LRRC4B(453–576)-hFc, increased the intensities of SYP and PSD95 (Figs. 4 D and 4 E). In addition, the number of SYP and PSD95 colocalized puncta, indicative of pre- and postsynaptic connections, 47 increased in response to WT LRRC4B(453–576)-hFc (Figs. 4 D and 4 E). Together, these results suggest that the FB decoys, by disrupting the FAM19A5-LRRC4B complex, promote the neural development process from neurite growth to the formation of initial contacts between dendrites and axons. NS101, the anti-FAM19A5 antibody, enhances synapse formation. Antibody therapeutics have high specificity and affinity for their targets and offer a unique advantage over peptides and Fc-conjugated proteins with their prolonged half-life in the blood, 48 thereby providing more opportunities for the drug to reach the brain with a single systemic administration. Therefore, we developed NS101, an optimized anti-FAM19A5 antibody derived from N-A5-Ab. NS101 was more potent than WT LRRC4B(453–576)-hFc in blocking FAM19A5-LRRC4B complex formation (Fig. 5 A), and its ability to dissociate the FAM19A5-LRRC4B complex was corroborated by a co-IP assay using HEK293 cells expressing FLAG-tagged LRRC4B treated with rcFAM19A5 in the presence of NS101 (Figure S4A). NS101 significantly increased the release of FAM19A5 into the culture medium from HEK293 cells cotransfected with LRRC4B and FAM19A5 isoform 1 or 2 but not from cells transfected only with FAM19A5 in a time- and dose- dependent manner (Figs. 5 B and S4B). Considering that most of FAM19A5 isoform 1 was captured by LRRC4B in the plasma membrane (Fig. 1 D), NS101 can release FAM19A5 into the medium through dissociation of the FAM19A5-LRRC4B complex. NS101 separated FAM19A5 isoform 2 from LRRC4B in living cells (Figure S4C). Additionally, NS101 increased the release of endogenous FAM19A5 into the culture medium from primary hippocampal neurons (Fig. 5 C). We evaluated the ability of systemically administered NS101 to capture FAM19A5 proteins in the brain and transport them to the peripheral circulation. We measured the baseline levels of FAM19A5 in blood and CSF of mice, rats, monkeys, and humans, and found that FAM19A5 concentrations were lower in plasma compared to CSF in all species (Fig. 5 D). This was confirmed using samples from FAM19A5 KO mice (Figures S5A and S5B). Following a single intravenous (iv) administration of NS101 in rats, the plasma FAM19A5 levels promptly increased, reaching the highest point at 24–36 hours and declining gradually over the next 28 days (Fig. 5 E). An increased dose of NS101 led to higher plasma FAM19A5 levels (Figure S5C). The peak time and overall change in concentrations of both CSF NS101 and plasma FAM19A5 were comparable after iv administration of NS101 (Fig. 5 E). This correlation indicates that the increase in plasma FAM19A5 levels was likely due to action of NS101 in the brain and CSF. To visualize the NS101-FAM19A5 complex, we used disuccinimidyl glutarate to irreversibly crosslink proteins in CSF samples and detected them in immunoblots using N-A5-Ab. The NS101-FAM19A5 complex was found to be greater than 250 kDa in size, while the FAM19A5 protein bands were 12 and 15 kDa (Figure S5D). The formation of the complex in the CSF started immediately after an iv administration of NS101, peaked at 24 hours, and gradually decreased until 672 hours (Fig. 5 F). This shows a correlation between the formation of the complex and the residual concentration of NS101 in the CSF. We then further traced the FAM19A5 migration in vivo using a version of FAM19A5 in which Ala was substituted for Arg58 and Arg59 [FAM19A5(R58A, R59A)] that binds poorly to NS101, but strongly to LRRC4B (Figure S5E). The WT and MT FAM19A5 were intracranially injected to the mouse brain and NS101 was administered iv one day later. Plasma FAM19A5 levels were significantly higher in WT FAM19A5-treated mice than in the sham group (Fig. 5 G). However, plasma FAM19A5 levels were not significantly different between FAM19A5(R58A, R59A)-treated and sham groups (Fig. 5 G). Therefore, it is likely that NS101 dissociates FAM19A5 from LRRC4B, forms an NS101-FAM19A5 complex in the brain, and migrates to the CSF, where the complex drains into the peripheral blood. We then examined the effects of NS101 on neurite outgrowth and synapse formation. NS101 significantly promoted neurite growth in terms of length, primary neurite number, and branching point number of cultured neurons at DIV 3 compared to untreated or control human immunoglobulin G (hIgG)-treated neurons (Figures S6A and S6B). At DIV 7, the contribution of NS101 to synapse formation was revealed by the high immunoreactivity of SYP and PSD95 and the increased number of SYP/PSD95 colocalized puncta (Figures S6C and S6D). To determine if NS101 is also involved in structural changes at the synapse, and not just a secondary effect of increased neurite growth, we calculated the number of spines per unit length of dendrites (i.e., spine density) using the classic DiI staining method to visualize dendritic spines. 49 Our findings showed a significant increase in spine density after NS101 treatment (Figs. 5 H and 5 I), indicating that NS101 contributes to synaptic connectivity through both guiding neurite formation and promoting synapse formation. We then tested if NS101 could enhance synaptic connectivity under pathological conditions where Aβ 1–42 oligomers reduce synaptic connections between neurons in vitro. 50 To do this, NS101 was treated to mouse hippocampal neurons treated with Aβ 1–42 oligomers at DIV 15 and DIV 18. Immunohistochemistry using SYP and PSD95 antibodies showed that Aβ 1–42 significantly reduced the number of synapses, however, the addition of NS101 prevented this reduction, particularly the number of puncta that were colabeled by SYP and PSD95 (Figs. 5 J and 5 K). NS101 restores synapse number, function, and plasticity in the hippocampus in AD mouse models. Treatment of hippocampal neurons with rcFAM19A5 reduced neurite growth and synapse formation (Figure S3), raising a possibility that FAM19A5 can serve as a risk factor for neurodegenerative diseases. To further explore this idea, we measured FAM19A5 levels in human CSFs and found a high correlation with age (Fig. 6 A) and with total tau (t-tau) and phosphorylated tau (p-tau) (Fig. 6 B). Given that t-tau and p-tau levels are closely associated with synapse pathology, 51 we investigated the effect of NS101 in mouse models of AD. AD is characterized by the loss of synapses outpacing the acquisition of new synapses, which is can be attributed to external environmental factors and/or internal neuronal factors. 8,52−54 A recent article emphasized the significance of restoring synapse function in the amyloidopathy mouse model, even without removing amyloid β (Aβ). The study showed that using a synthetic synaptic organizer that physically connects presynapses and postsynapses can help restore neural circuits and cognitive function in an AD animal model. 55 This study also supports the notion that blocking a synaptic suppressor like FAM19A5 can help to restore neural circuits in AD patients. As seen in rat models (Fig. 5 E), the systemic iv administration of NS101 to AD mouse models led to the release of FAM19A5 from the brain into the blood (Figure S7), suggesting a reduction in the FAM19A5-LRRC4B complex in the brain. In the AD-relevant APP/PS1 murine model of amyloidopathy, 56 , 57 there was a significant reduction in SYP immunoreactivities in both CA1 and CA3 of the hippocampus compared to WT mice (Fig. 6 C). PSD95 immunoreactivity was markedly reduced in CA1 but less so in CA3. NS101 treatment of APP/PS1 mice restored SYP and PSD95 immunoreactivity to WT levels (Fig. 6 C). Similarly, NS101 significantly increased the intensity of synaptic vesicle glycoprotein 2A (SV2A), an essential synaptic vesicular protein and a biomarker of synaptic density, 58 in the CA1 region of APP/PS1(Fig. 6 D). Collectively, these results suggest that NS101 enhances synaptic density by promoting structural synaptic connections. We then determined if NS101-induced structural recovery is accompanied by improved basal synaptic transmission and function of neuronal circuits in hippocampal slices of APP/PS1 mice. NS101-treated APP/PS1 mice showed an increased frequency of miniature excitatory postsynaptic currents (mEPSCs) in CA1 pyramidal neurons compared to the hIgG-treated group (Fig. 6 E). Furthermore, NS101 restored the mean frequency to a level comparable to that of normal mice, demonstrating enhanced excitatory synaptic transmission. The amplitude of mEPSCs remained unchanged in all groups, suggesting that NS101 did not impact excitatory postsynaptic receptor responsiveness (Fig. 6 E). Field extracellular recordings verified that the excitatory postsynaptic potentials (fEPSPs) of Schaffer collateral (SC)-CA1 circuits, which play a major role in memory formation and emotional networks, were reduced in hippocampal slices from hIgG-treated APP/PS1 mice (Fig. 6 F), as previously reported. 59 NS101 significantly restored the diminished strength of SC-CA1 circuits (Fig. 6 F). These findings align with NS101's impact on synaptic connections and indicate that it may normalize the reduced excitatory synaptic transmission of CA1 pyramidal cells to levels found in WT mice. Long-term potentiation (LTP) is a sustained enhancement of synaptic strength after repetitive or strong stimulation. 60 , 61 LTP is linked to the creation of new dendritic spines and associated synapses in the hippocampus. 62 , 63 Thus, the LTP impairment observed in various AD mouse models has been suggested as a potential cause of cognitive deficits. 64 To measure LTP at SC-CA1 synapses, we triggered SC fibers with the theta burst stimulation and monitored the changes in fEPSP responses. NS101 restored the reduced amplitude of fEPSPs (during the last 5 min) in APP/PS1 slices, similar to WT (Fig. 6 G). In addition, post-tetanic potentiation (PTP), a form of presynaptic plasticity and an indicator of the probability of neurotransmitter release, 65 was unchanged in the test groups (Fig. 6 H), suggesting no alteration in presynaptic release probability. 66 Thus, NS101 restored LTP by stabilizing and fortifying synaptic connections, potentially aiding in the recovery of cognitive deficits in AD mice. NS101 ameliorates cognitive deficits in mouse models of AD. Since NS101 has the ability to reinstate synapse formation under pathological conditions (Figs. 5 J and 5 K), the new synapses formed in the hippocampus may help to recover cognitive abilities. APP/PS1 mice treated with iv hIgG once a week for 8 weeks showed a significant short-term memory decline compared to WT mice, as measured by the reduced alteration index in the Y-maze test. In contrast, NS101-treated APP/PS1 mice showed increased spontaneous alteration compared to hIgG-treated mice (Fig. 7 A), indicating an improvement in short-term memory. Spatial learning and memory were evaluated using the Morris water maze (MWM). APP/PS1 mice treated with hIgG learned poorly in the training phase (Figures S8A and S8B), with memory impairment in the probe test (Figures S8C and S8D), compared to WT mice. Despite the positive effect of NS101 on short-term memory in the Y-maze (Fig. 7 A), NS101 partially improved the degraded spatial learning and memory of APP/PS1 mice in the MWM test, as indicated by the parameters of spatial memory (Figure S8). APP/PS1 mice underwent a passive avoidance test to assess associative learning and memory after receiving a foot shock during the training period. hIgG-treated mice showed a significant reduction in the latency compared to WT mice, suggesting a problem in associative learning and memory. Whereas NS101-treated APP/PS1 mice displayed a tendency to recover latency compared to hIgG-treated mice (Fig. 7 B). Taken together, these results demonstrated that NS101 improved short-term memory and had partial effects on associative learning and memory in APP/PS1 mice. We administered iv NS101 to P301S mice, a transgenic model of tauopathy, to determine whether it restored cognitive function. NS101 significantly improved spatial learning and memory without affecting locomotion, as shown by the total distance mice moved in the MWM (Figs. 7 C- 7 E). NS101 also increased the immunoreactivity of the synapse molecules SYP and PSD95 in the hippocampus compared to hIgG-treated control mice (Figure S9). These results suggest that NS101 may ameliorate cognitive decline in AD pathology, including amyloidopathy and tauopathy. Discussion One possible mechanism by with FAM19A5 suppresses neurite growth and synapse formation can be blocking the binding between LRRC4B at postsynapse and PTPRF at the presynapse. These two molecules form a bridge across the synaptic cleft and enables coordinated assembly of the presynaptic terminal, 17 which holds machinery for neurotransmitter release, and the postsynaptic side, which has neurotransmitter receptors, ion channels, and signaling molecules. 13 , 67 Alterations in FAM19A5 levels can impact interactions at the initial contact stage to form a synapse, or at the elimination stage to weaken the binding. This interaction, prior to synapse assembly, also plays a role in triggering postsynaptic and presynaptic differentiation, thus extending their roles from neurite outgrowth and guidance. 18,68−70 The slowing of neurite growth by FAM19A5 and the enhancement of neurite growth by the FB-decoys and NS101 suggest a suppressive role of FAM19A5 in this process through its binding to LRRC4B. Precise regulation of neurite growth and synapse formation is crucial for maintaining homeostatic neural plasticity under normal conditions and for controlling the rate and extent of neuro-regeneration following nerve injury. 71 Thus, our study proposes that FAM19A5 plays an active role in controlling the dynamic balance of neurite growth/retraction and synapse formation/elimination by suppressing the process. An intriguing finding of the present study is that systemic administration of NS101 can cross the blood-brain barrier and facilitate the transport of FAM19A5 from the brain to peripheral blood in both mice and rats in the present study, as well as in humans in a clinical trial study. 36 This consistency of effect across species is likely due to the 100% identical aa sequence of the FAM19A5 protein in these species. The transport of target molecules from the brain to peripheral blood via antibody-mediated means was recently demonstrated in another study, where an anti-tau antibody captured brain tau proteins and transported them to the periphery in both transgenic mice and humans. 72 In both studies, the transfer of target molecules from the brain to peripheral blood was easily observed, as baseline levels of the target molecules were much higher in the brain than in the periphery. These findings, along with our results, suggest that antibodies can be an effective tool for removing target molecules in the brain, potentially offering a treatment approach for various neurological diseases. Given that a single iv administration of NS101 induced the transport of brain FAM19A5 to blood over a month, antibody therapy has a clear advantage in clinical studies over other biologics that require direct administration to the brain and have a short half-life in the blood. 55 , 73 Synapse loss is a critical early pathological event in AD, yet most clinical studies have focused on clearing hallmark pathologies like accumulated Aβ and p-tau. Despite their efficacy in removing these proteins, many antibody drugs targeting Aβ and p-tau have not shown significant improvement in cognitive decline in AD patients. 74 , 75 Only a few drugs have been recently approved for further evaluation of their ability to improve cognitive function in these patients. 76 , 77 Hence, finding a target protein that can normalize synapse dynamics in the AD brain could open up new avenues for therapeutic intervention that complement strategies for eliminating Aβ and p-tau. In this context, FAM19A5, as a suppressor of synapse formation, could be a promising target for AD. Recent snRNA-seq data revealed a significant increase in FAM19A5 transcript levels in neurons of the brain in early AD pathology compared to a control group. 31 , 78 , 79 Elevated levels of FAM19A5 have been observed in the CSF of elderly individuals over 60 years, which might be increased risk for diseases characterized by synapse loss. Reducing FAM19A5 levels in the brain could therefore help improve cognitive function in patients with synapse loss. NS101 prevents synapse loss in cultured neurons treated with Aβ oligomers. Furthermore, systemic administration of NS101 restored synaptic function in the hippocampus of mice with AD pathologies, regardless of the presence of Aβ and p-tau pathologies. This indicates that reducing FAM19A5 levels in the brain may help normalize synapse dynamics that have been impaired by toxic external or internal factors. These findings support previous research that artificially enhancing the connections between synapses through a synthetic fusion protein can effectively restore synapse function in mice with amyloid-related conditions. 55 Both studies aimed to increase synapse number and function, either through the use of a synthetic synapse connector or an antibody that removes the suppressor of synapse dynamics. As a result, these studies provide structure-guided molecular tools to normalize synapse function in patients with neurodegeneration. Restoring or enhancing the synaptic structure, even under adverse conditions, can help normalize synaptic transmission function, triggering a positive feedback loop between healthier neurons and their environments. Taken together, our study shows that FAM19A5 acts as a suppressor by interacting with the postsynaptic molecule LRRC4B. Removing FAM19A5 from the LRRC4B complex, either using the FB-decoys or NS101, significantly improves neural integrity in terms of neurite growth and synapse formation in cultured neurons. Systemic administration of NS101 enhances synapse integrity and cognitive function in mouse models of AD. Therefore, inhibiting the FAM19A5-mediated suppressor function could thus provide a promising new therapeutic approach for treating AD. Limitations of the study Our study demonstrated the role of FAM19A5 in synapse assembly and its implications. However, further research may be necessary to address questions raised by the study, such as the possibility that FAM19A5 regulates the function of LRRC4B's paralogs LRRC4 and LRRC4C, which share the similar FB domain. FAM19A5 may also impact other PTPRF family members such as PTPRS and PTPRD. In addition to the trans-synaptic interaction between LRRC4B and PTPRF, LRRC4B may have a cis-acting interaction with uncharacterized proteins at the same plasma membrane to regulate neurite growth and axon guidance. FAM19A5 may also participate in these interactions by binding to LRRC4B or its paralogs. FAM19A5 may also impact the clustering of synaptic molecules in the postsynapse through interfering with LRRC4B's interaction with PSD95. Gaining a deeper understanding of the molecular mechanism behind the FAM19A5-LRRC4B complex's contribution to neurite growth and synapse formation could lead to the development of new strategies for treating neurological diseases and promoting neuro-regeneration by normalizing neurite growth and synapse dynamics. Declarations ACKNOWLEDGEMENTS This work was supported by grants from the Neuracle Science Co., Ltd. The authors acknowledge Eun Bee Cho, Yongwoo Jeong, and Sitaek Oh for assisting in manuscript preparation. The authors also acknowledge Kyungho Seong for performing in silico residue scanning on the FAM19A5-FB complex using the Schrodinger Platform. AUTHOR CONTRIBUTIONS Conceptualization, JY.S.; methodology, RH.K., HY.K., SX.M.; validation, RH.K., HY.K., HB.K., MH.L., N.H., EH.C., SM.L. M.B.; investigation, RH.K. SX.M.; resources, WK.K., JI.H.; data curation, RH.K., SX.M.; writing, original draft, RH.K, SX.M., HB.K., JY.S.; writing, review and editing, RH.K, SX.M., HB.K., JY.S.; SW.H., M.B., HC.P.; visualization, RH.K., SX.M., JY.S.; supervision, JY.S.; project administration, JY.S.; funding acquisition, JY.S. DECLARATION OF INTERESTS RH.K., HY.K., SX.M., HB.K., MH.L., N.H., EH.C., SM.L., JW.J., WK.K., and JY.S. are employed by Neuracle Science, Co., Ltd. MH.L., SM.L., WK.K., SW.H., HC.P., and JY.S. are shareholders of Neuracle Science, Co., Ltd. The remaining authors have no conflicts of interest to declare. STAR★METHODS Key resources table REAGENT or RESOURCE SOURCE IDENTIFIER Antibodies Mouse monoclonal anti-Synaptophysin Sigma-Aldrich Cat# S5768 Mouse monoclonal anti-PSD95 Invitrogen Cat# MA1-045 Mouse monoclonal anti-Tau5 Invitrogen Cat# AHB0042 Mouse monoclonal anti-NGL-3/LRRC4B R&D Systems Cat# MAB69191 Mouse monoclonal anti-FLAG M2 Sigma-Aldrich Cat# F1804 Mouse monoclonal anti-V5 Invitrogen Cat# R960CUS Donkey anti-Human IgG-HRP Jackson ImmunoResearch Cat# 715-035-149 Donkey anti-Mouse IgG-HRP Jackson ImmunoResearch Cat# 715-035-150 Donkey anti-Human IgG-Cy3 Jackson ImmunoResearch Cat# 709-165-149 Rabbit anti-Human IgG Heavy chain Invitrogen Cat# SA5-10223 Rabbit anti-Human IgG Fc-HRP Invitrogen Cat# 31423 Goat anti-Human kappa light chain-HRP Invitrogen Cat# A18853 anti-Human isotype control Invitrogen Cat# 31154 Anti-Human IgG1, kappa isotype control Sino Biological Cat# HG1K Biological samples Pooled normal human cerebrospinal fluid Innovative Research, Inc. Cat# IPLA-CSFP Individual Human CSF and Plasma BIOIVT & ELEVATING SCIENCE N/A Chemicals Opti-MEM Reduced Serum Medium, GlutaMAX Supplement Gibco Cat# 51985034 Expi293 ™ Expression Medium Gibco Cat# A1435101 Fetal bovine serum Gibco Cat# 16000-044 Penicillin-Streptomycin (10,000 U/mL) Gibco Cat# 15140122 DPBS (1X) Gibco Cat# 14190250 Trypsin-EDTA (0.25%) Gibco Cat# 25200-072 Imidazole Sigma-Aldrich Cat# 56750-500G Amicon Ultra-15 (Ultracel-10K) Millipore Cat# UFC901024 AcTEV Protease Invitrogen Cat# 12575023 rProtein A GraviTrap Cytiva Cat# 28985254 Ab buffer kit Cytiva Cat# 28903059 Dynabead Protein G for Immunoprecipitation Invitrogen Cat# 10003D Protein A/G Plus Agarose Thermo Scientific Cat# 20424 DSG (disuccinimidyl glutarate) Thermo Scientific Cat# 20593 Paraformaldehyde Sigma-Aldrich Cat# P6148 Bovine serum albumin Sigma-Aldrich Cat# A7030 Triton X-100 Sigma-Aldrich Cat# T8787 Hoechst 33342 Solution Thermo Scientific Cat# 62249 CellTracker CM-DiI Dye invitrogen Cat# C7000 Sucrose Sigma-Aldrich Cat# 1888 Potassium chloride Sigma-Aldrich Cat# P9541 Sodium phosphate monobasic Sigma-Aldrich Cat# S0751 Sodium bicarbonate Sigma-Aldrich Cat# S5761 Sodium pyruvate Sigma-Aldrich Cat# P5280 Sodium L-ascorbate Sigma-Aldrich Cat# A4034 Sodium chloride Sigma-Aldrich Cat# S9888 Magnesium sulfate Sigma-Aldrich Cat# M2643 Calcium chloride Sigma-Aldrich Cat# 4901 Glycerol SPL Cat# G9012 Peptides Amino acid sequence for FAM19A5 fragment peptides, see table S1 Amino acid sequence for point mutation FAM19A5 fragment peptides, see table S2 Amino acid sequence for FB fragment peptides, see S1F Beta-Amyloid (1-42) AnaSpec Cat# AS-20276 FAM19A5 fragment peptide F1 Peptron N/A FAM19A5 fragment peptide F2 Peptron N/A FAM19A5 fragment peptide F3 Peptron N/A FAM19A5 fragment peptide F4 Peptron N/A FAM19A5 fragment peptide F5 Peptron N/A FAM19A5 fragment peptide F6 Peptron N/A Point-mutated fragment peptide F2-01 Peptron N/A Point-mutated fragment peptide F2-02 Peptron N/A Point-mutated fragment peptide F2-03 Peptron N/A Point-mutated fragment peptide F2-04 Peptron N/A Point-mutated fragment peptide F2-05 Peptron N/A Point-mutated fragment peptide F2-06 Peptron N/A Point-mutated fragment peptide F2-07 Peptron N/A Point-mutated fragment peptide F2-08 Peptron N/A Point-mutated fragment peptide F2-09 Peptron N/A Point-mutated fragment peptide F2-10 Peptron N/A Point-mutated fragment peptide F2-11 Peptron N/A Point-mutated fragment peptide F2-12 Peptron N/A Point-mutated fragment peptide F2-13 Peptron N/A Point-mutated fragment peptide F2-14 Peptron N/A Point-mutated fragment peptide F2-15 Peptron N/A Point-mutated fragment peptide F2-16 Peptron N/A Point-mutated fragment peptide F2-17 Peptron N/A Point-mutated fragment peptide F2-18 Peptron N/A Point-mutated fragment peptide F2-19 Peptron N/A Point-mutated fragment peptide F2-20 Peptron N/A FB 28 mer Anygen N/A FB 20 mer Anygen N/A FB 16 mer Anygen N/A FB-m11dC Anygen N/A FB-m10dC Anygen N/A FB-m9dC Anygen N/A FB-m8dC Anygen N/A FB-m7dC Anygen N/A FB-20[Y484A] Anygen N/A FB-20[Y484N] Anygen N/A FB-20[T485A] Anygen N/A FB-20[T485N] Anygen N/A FB-20[Y486A] Anygen N/A FB-20[T486N] Anygen N/A FB-20[F487A] Anygen N/A FB-20[F487N] Anygen N/A FB-20[T488A] Anygen N/A FB-20[F488N] Anygen N/A FB-20[T489A] Anygen N/A FB-20[F489N] Anygen N/A FB-20[V490A] Anygen N/A FB-20[F490N] Anygen N/A FB-20[T491A] Anygen N/A FB-20[T491N] Anygen N/A FB-20[V492A] Anygen N/A FB-20[V492N] Anygen N/A FB-20[E493A] Anygen N/A FB-20[E493N] Anygen N/A FB-20[T494A] Anygen N/A FB-20[T494N] Anygen N/A FB-20[Y495A] Anygen N/A FB-20[E496A] Anygen N/A Critical Commercial Assays Neon™ Transfection System Kit Invitrogen Cat# MPK10096 INNOTEST® PHOSPHO-TAU (181P) FULIREBIO Cat# 81574 INNOTEST® hTAU Ag FULIREBIO Cat# 81579 Recombinant proteins FAM19A5 This study N/A FAM19A5(R58A, R59A) This study N/A FAM19A5(R125A, K127A) This study N/A FAM19A5(R58A, R59A, R125A, K127A) This study N/A 6xHis-LRRC4B (36-576) This study N/A 6xHis-LRRC4B (453-576) This study N/A 6xHis-LRRC4B (453-576), (T488A, T489A) This study N/A LRRC4B (36-576)-hFc This study N/A LRRC4B(453-576)-hFc This study N/A LRRC4B(453-576)-hFc (T488A, T489A) This study N/A LRRC4B(484-576)-hFc This study N/A LRRC4B(498-576)-hFc This study N/A PTPRF(30-1263)-hFc This study N/A Experimental models: Cell lines HEK293 cells ATCC Cat# CRL-1573 Expi293F cells Gibco Cat# A14527 Experimental models: Organisms/strains Mouse: C57BL/6 The Jackson Laboratory Strain# 000664 Mouse: P301S The Jackson Laboratory Strain# 008169 Mouse: APP/PS1 The Jackson Laboratory Strain# 034832-JAX Mouse: 5XFAD The Jackson Laboratory Strain# 034840-JAX Mouse: FAM19A5 KO ToolGen N/A Sprague-Dawley rats ORIENT BIO N/A Cynomolgus monkeys ORIENT BIO N/A Oligonucleotides Primers used for LRRC4B cloning, see table S3 This study N/A Recombinant DNA pCAG1.1-IgK_SP-His-TEV-FAM19A5 This study N/A pCAG1.1-IgK_SP-His-TEV-FAM19A5(R58A, R59A) This study N/A pCAG1.1-IgK_SP-His-TEV-FAM19A5(R125A, K127A) This study N/A pCAG1.1-IgK_SP-His-TEV-FAM19A5(R58A, R59A, R125A, K127A) This study N/A pCAG1.1-IgK_SP-His-TEV-LRRC4B 36-576 This study N/A pCAG1.1-IgK_SP-His-TEV-LRRC4B 453-576 This study N/A pcDNA3.1 FAM19A5 Isoform 1 This study N/A pcDNA3.1 FAM19A5 Isoform 2 This study N/A pcDNA3.1(+)-C-FLAG-LRRC4B Genscript Clone ID: OHu30422 pcDNA3.1(+)-C-FLAG-PTPRF Genscript Clone ID: OHu02063 pcDNA6 V5-His A-LRRC4B This study N/A pCMV20-IgK_SP-FLAG-LRRC4B 36-713 This study N/A pCMV20-IgK_SP-FLAG-LRRC4B 36-713 (T488A, T489A) This study N/A pCMV20-IgK_SP-FLAG-LRRC4B 157-713 This study N/A pCMV20-IgK_SP-FLAG-LRRC4B 230-713 This study N/A pCMV20-IgK_SP-FLAG-LRRC4B 364-713 This study N/A pCMV20-IgK_SP-FLAG-LRRC4B 453-713 This study N/A pCMV20-IgK_SP-FLAG-LRRC4B 577-713 This study N/A pCMV20-IgK_SP-FLAG-LRRC4B 36-576 This study N/A pCMV20-IgK_SP-FLAG-LRRC4B Δ364-576 This study N/A pCMV20-IgK_SP-FLAG-LRRC4B 364-576 This study N/A pCMV20-IgK_SP-FLAG-LRRC4B 453-576 This study N/A pCMV20-IgK_SP-FLAG-LRRC4B 453-576 (T488A, T489A) This study N/A pCMV20-IgK_SP-FLAG-LRRC4B 453-576 (T488S, T489S) This study N/A pCMV20-IgK_SP-FLAG-LRRC4B 484-576 This study N/A pCMV20-IgK_SP-FLAG-LRRC4B 498-576 This study N/A pCMV20-IgK_SP-LRRC4B 36-576-hFc This study N/A pCMV20-IgK_SP-LRRC4B 453-576-hFc This study N/A pCMV20-IgK_SP-LRRC4B 453-576 (T488A, T489A)-hFc This study N/A pCMV20-IgK_SP-PTPRF 30-1263-hFc This study N/A Software and algorithms Prism GraphPad https://www.graphpad.com/scientific-software/prism/ Fiji Image J https://imagej.net/software/fiji/ IMARIS Bitplane https://imaris.oxinst.com/ Las X Leica https://www.leica-microsystems.com/products/microscope-software/p/leica-las-x-ls/downloads/ AlphaFold v2.0 Jumper et al. https://alphafold.ebi.ac.uk/ RoseTTAFold Baek et al. https://github.com/RosettaCommons/RoseTTAFold Bioluminate® Schrodinger https://www.schrodinger.com/downloads/releases PyMOL Schrodinger https://pymol.org/2/#page-top Adobe Illustrator CC Adobe https://www.adobe.com/uk/products/ illustrator Other Leica DMi8 confocal microscope Leica N/A Neon transfection system Thermo MP924681 VERSA max microplate reader Molecular device BNR-07668 MiniHD9 Chemi/gel DOC Uvitec 16-200248 SimpliAmp thermal cycler Applied biosystems A24812 Detailed methods are provided in the online version of this paper and include the following: KEY RESOURCES TABLE CONTACT FOR REAGENT AND RESOURCE SHARING EXPERIMENTAL MODEL AND SUBJECT DETAILS Human samples Vertebrate animals Cell lines METHODS DETAILS Purification of recombinant FAM19A5 protein Production of anti-FAM19A5 antibodies DNA constructs Production of fragment peptides Electroporation transfection and co-IP Immunoblots ELISA Surface plasmon resonance (SPR) In silico modeling of the FAM19A5-LRRC4B complex structure using AlphaFold2 an RoseTTAFold In silico residue scanning of the FAM19A5-FB complex HEK293 cell culture and immunocytochemistry Primary neuron culture and immunocytochemistry DiI staining and spine density analysis in vitro Aβ 1–42 preparation Immunohistochemistry Hippocampal slice preparation and electrophysiology Stereotaxic FAM19A5 injection Animal behavioral tests QUANTIFICATION AND STATISTICAL ANALYSIS SUPPLEMENTAL INFORMATION Supplemental information can be found online. CONTACT FOR REAGENT AND RESOURCE SHARING Further information and requests for resources and reagents may be directed to and will be fulfilled by the Lead Contact, Jae Young Seong ( [email protected] ). EXPERIMENTAL MODEL AND SUBJECT DETAILS Human samples Pooled normal human cerebrospinal fluid (CSF) was obtained from Innovative Research, Inc. with catalog number IPLA-CSFP, and used for the Co-IP experiment to determine the association between FAM19A5 and LRRC4B. Individual human CSF and plasma samples were obtained from BIOIVT & ELEVATING SCIENCE and were used to measure age-dependent FAM19A5 levels in CSF and the basal level of FAM19A5 in plasma, respectively. Additionally, individual human CSF samples were also used to determine total tau and phospho-tau levels. Vertebrate animals Obtained from the Jackson Laboratory were APP/PS1 [B6.Cg-Tg (APPswe, PSEN1dE9) 85Dbo/J] mice, P301S [B6.C3-Tg (Prnp-MAPT*P301S) PS19Vle/J] mice, and 5xFAD [B6SJL-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax] mice. Obtained from Orient Bio were WT C57BL/6J mice, Sprague-Dawley rats, and cynomolgus monkeys. The FAM19A5 KO mice were generated using the CRISPR/Cas9 system by ToolGen as previously described. 24 Homozygous FAM19A5 KO mice were generated through intercross breeding of heterozygous mice. The mice were housed under temperature-controlled conditions (22–23°C) with a 12-h light/12-h dark-light cycle (lights on at 8:00 am) and had ad libitum access to standard chow and water. All animal experiments were designed to minimize the number of mice used and anesthesia was administered for the procedures. The behavioral tests performed by CRO companies were approved by the Animal Experimentation Ethics Committee of KPC Co., Ltd. (approval number: P191005) in accordance with the Animal Protection Act (Law No. 4372 enacted on May 31, 1991, partially revised Act No. 13023 on January 20, 2016). The procedures related to the analysis of animal samples were further approved by the Institutional Animal Care and Use Committee of Korea University (KOREA-2020-0031, KOREA-2020-0037, and KOREA-2021-0002). Ethical regulations were followed throughout. Cell lines HEK293 cells (ATCC, CRL-1573) were cultured in humidified incubator at 37 °C with 5 % CO 2 . HEK293 cells were propagated in MEM with GlutaMAX TM (Gibco) supplemented with 10% fetal bovine serum (Gibco) and 100 U/ml penicillin-streptomycin (Gibco). For sub-culture, cells were washed with DPBS (Gibco) and dissociated in 0.25% Trypsin-EDTA (Gibco) for 5 min at 37 °C. METHODS DETAILS Purification of recombinant proteins Recombinant His-tagged proteins were purified according to the method described previously. 24 In brief, FAM19A5 (WT and MT) and LRRC4B(36-576) with N-terminal 6xHis tags, followed by a tobacco etch virus protease (TEV) recognition sequence, were cloned into the pCAG1.1 vector and expressed in Expi 293F cells. The supernatant containing His-TEV-FAM19A5 was collected for Ni-NTA affinity chromatography (Cytiva). After washing with a binding buffer containing 20 mM Tris-HCl (pH 7.5) and 200 mM NaCl, the proteins were eluted using binding buffers with increasing concentrations of imidazole (from 5 to 500 mM). Proteins eluted from the 50 to 500 mM imidazole fractions were concentrated using Amicon® Ultra-15 Centrifugal Filter Units (Millipore), and the buffer was exchanged for 1xDPBS (Gibco). The purified His-TEV-FAM19A5 proteins were digested overnight at 30°C with AcTEV protease (Invitrogen) to remove the His-tag and TEV sequence. The AcTEV protease containing the His-tag was then eliminated by overnight incubation with Ni-NTA, and digestion was confirmed using an anti-His tag antibody (Abcam). LRRC4B (ectodomain and fragments) and PTPRF (ectodomain) were cloned into the pCMV Igκ-SP human Fc (hFc) vector and expressed in Expi 293F cells. The supernatant containing hFc-fused proteins was collected using rProtein A GraviTrap (Cytiva), and the hFc-fused proteins were eluted using an Ab buffer kit (Cytiva) following the manufacturer's instructions. Production of anti- FAM19A5 antibodies We generated two chimeric chicken/human monoclonal antibodies against FAM19A5, named N-A5-Ab and C-A5-Ab, by immunizing chickens (Gallus gallusdomesticus) with purified recombinant FAM19A5 (rcFAM19A5) using a method previously described. 24 In addition, we obtained an antibody called 2-13 that recognizes a conformational structure of FAM19A5, rather than a specific linear aa sequence. We further improved the N-A5-Ab and C-A5-Ab antibodies by a process called deimmunization and optimization of its physicochemical properties, resulting in the creation of the antibody NS101 and SS01, respectively. DNA constructs Full-length human LRRC4B and full-length human FAM19A5 were cloned sequentially into the pcDNA3.1(+) vector. Cloning was performed using the AccuRapid™ Cloning Kit (Bioneer) according to the manufacturer’s instructions. The pCMV-IgK-SP-hFc vector was constructed by inserting a human immunoglobulin kappa signal peptide sequence in front of the human Fc. Fragments of LRRC4B (F1; 36–713 aa, F2; 157–713 aa, F3; 230–713 aa, F4; 364–713 aa; F5; 453–714 aa; F6; 577–713 aa; F7; 36–576 aa; F8; 36–63 aa; F9; 364–576 aa; F10; 453–576 aa; F11; 484–576 aa; F12; 498–576 aa) were constructed in the pCMV-IgK-SP-hFc vector. Full-length human LRRC4B and PTPRF plasmid DNAs were purchased from Genscript. For Ala and Asn substitutions, point mutations in genes were created using the In-Fusion HD Cloning Kit (Clontech Laboratories) using synthetic PCR primers with site-directed mutated bases. Production of fragment peptides Aa sequences of FB-related peptides are listed in Table S1 and S2 and were custom-made from Anygen. To identify the epitope of the FAM19A5 antibodies, the FAM19A5 linear sequence was divided into six groups, labeled F1 to F6. Further analysis was conducted to determine the crucial residue for binding, in which each aa sequence in F2 was replaced with Ala. The relevant name and aa sequences are listed in the Supplemental Table S1 and S2. All peptides related to FAM19A5 were custom-made from Peptron or Anygen. Electroporation transfection and co-IP HEK293 cells were transfected with the Neon TM transfection kit (Thermo) according to the manufacturer’s description. For the general co-IP experiments, after transfection, cells were treated with rcFAM19A5 for 30 min. The cells were washed twice with cold phosphate-buffered saline (PBS) and resuspended in lysis buffer containing 20 mM Tris-HCl (pH 7.4), 150 nM NaCl, 0.5% NP40, and a protease and phosphatase inhibitor cocktail (Thermo) in PBS. The supernatants were isolated by centrifugation at 12,000 × g at 4°C for 30 min and then mixed with 30 μl of Protein G Dynabeads that had been preincubated with antibodies. The mixtures were incubated at 4°C overnight in a rotating mixer. The Protein G Dynabeads were spun down and washed three times with 20 mM Tris-HCl (pH 7.4), 300 mM NaCl, and 0.5% NP40 in washing buffer. After adding 30 μl of 2× sample buffer containing a reducing agent to the Protein G Dynabeads and boiling at 100°C for 10 min, the proteins were separated by SDS-PAGE. For the human CSF co-IP, the pooled human CSFs (Innovative Research) were mixed with 0.5% NP40 and 50 μl of Pierce Protein A/G Plus Agarose (Thermo) that had been preincubated with 10 μg anti-hIgG (H+L), N-A5-Ab, and C-A5-Ab antibodies. For measurement of FAM19A5 level released to the culture medium, cells were treated with NS101 for 30, 60, and 120 min followed by transfection. Culture media were collected and subjected to ELISA. Immunoblots Mouse biofluid samples and cells were homogenized and prepared in lysis buffer containing 20 mM Tris-HCl (pH 7.5), 500 mM NaCl, 5 mM MgCl 2 , and protease inhibitor cocktail (Thermo Fisher Scientific). The primary antibodies are described in Supplementary Table 1. Immunoblots of biofluid samples and cells were performed as described previously 24 . FAM19A5-NS101 complex in sample was captured by interacting with crosslinker DSG (Thermo) according to the manufacturer’s protocol. ELISA Total and phosphorylated tau levels were assessed using the commercial ELISA Kit, hTAU Ag and PHOSPHO-TAU (181P) (FULIREBIO) according to the manufacturer’s protocol. FAM19A5 and NS101 levels were assessed using our in-house developed kit. To evaluate the binding affinity between FAM19A5 and LRRC4B, several LRRC4B deletion proteins, including LRRC4B(36-576), LRRC4B(453-576), LRRC4B(484-576), and LRRC4B(498-576) proteins were utilized as capture agents. WT and MT FAM19A5, including FAM19A5(R58A, R59A), FAM19A5(R125A, K127A), and FAM19A5(R58A, R59A, R125A, K127A) proteins were used for the binding. Detection was performed using the SS01. The cell culture medium of FAM19A5 was measured using 2-13 and the SS01 was used for capture and detection, respectively. For measuring FAM19A5 in biofluids, LRRC4B(453-576) protein and a horseradish peroxidase (HRP)-conjugated SS01 was used for capture and detection, respectively. For measurement of CSF NS101, a pair of rabbit anti-human IgG heavy chain antibody (Invitrogen) and HRP-conjugated goat α-human IgG kappa light chain antibody (Thermo) were used. For testing the inhibition of FAM19A5-LRRC4B binding, LRRC4B(453-576) protein was first coated onto the plate, followed by the addition of the test sample and FAM19A5 protein. The binding inhibition was calculated by detecting FAM19A5 through SS01. For the PTPRF-LRRC4B binding inhibition test, LRRC4B(36-576) protein was coated on the plate and followed by the addition of the test sample and PTPRF protein. The binding inhibition was calculated by detecting PTPRF-hFc through the anti-human IgG Fc antibody. Surface plasmon resonance (SPR) All SPR experiments were carried out on a Biacore 8K (Cytiva) with active temperature control at 25°C following the manufacturer’s protocols. The running buffer was 1 × HBS-EP (10 mM HEPES, 150 mM NaCl, 3 mM EDTA, 0.05% Tween 20, pH 7.4). For immobilization, His-TEV-LRRC4B(453–576) in 10 mM sodium acetate, pH 4.5 buffer equivalent to 632–638 Resonance Unit (RU) was injected onto a nitrilotriacetic acid (NTA) chip at a 30 µl/min flow rate. Another flow cell without the immobilized His-TEV-LRRC4B(453–576) coating was used to evaluate nonspecific binding. Increasing concentrations (0.78, 1.56, 3.12, 6.25, and 12.5 nM) of rcFAM19A5 were diluted in running buffer and flowed across the immobilized His-TEV-LRRC4B(453–576) for 180 s at a flow rate of 30 μl/min (association). The sample was replaced with a running buffer for 240 s (disassociation). The chip surface was regenerated with 350 mM EDTA and HBS-P+ 500 mM imidazole. For all samples, blank injection with buffer alone was subtracted from the resulting reaction surface data. Data were analyzed using Biacore 8K evaluation software (Cytiva). In silico modeling of the FAM19A5-LRRC4B complex structure using AlphaFold2 and RoseTTAFold We used AlphaFold2 40 to model the structure of the FAM19A5-LRRC4B complex. An input paired multiple sequence alignments (paired MSAs) were generated following RoseTTAFold’s input generation protocol. hMSAs for the FAM19A5 protein and LRRC4B extracellular domain were generated by iterative sequence search against the UniClust30 database 80 using HHblits. 81 To predict a complex structure, we generated a paired MSA based on individual MSA by pairing sequences from the same species. To provide pseudo-multimer inputs to AlphaFold2, we used a gap insertion trick that has been previously applied to RoseTTAFold 41 . The final models were ranked by predicted TM score (pTM score), and the best scored model was used for further study after structural relaxation using Rosetta. 42 In silico residue scanning of the FAM19A5-FB complex We used the residue scanning module (Schrodinger Bioluminate®) for in silico residue scanning (e.g., Ala scanning) and to calculate the perturbation of protein-peptide binding affinity, which was defined as the binding free energy change. To evaluate the potential impact of a mutation, we used Δ Affinity and Δ Stability (solvated) values. HEK293 cell culture and immunocytochemistry Cells were seeded at a density of 3 × 10 4 cells/well on fibronectin-coated plastic film coverslips in 12-well plates. After 24 hours, the cells were cotransfected with 150 ng of FLAG-taggedLRRC4B and His-tagged FAM19A5 isoform 1 or 2. After 24 hours of incubation, the cells were washed once with ice-cold Dulbecco’s PBS (DPBS) and fixed with 4% paraformaldehyde (PFA) in PBS for 20 min. After washing three times with ice-cold DPBS, the cells were blocked with blocking buffer containing 3% bovine serum albumin (BSA) and 0.1% Triton X-100 in PBS for 30 min and incubated with primary antibodies overnight at 4°C. After three washes with DPBS, the cells were incubated with secondary antibodies and 20 mM Hoechst solution (Thermo) for 1 hour at room temperature. After three washes with DPBS, fluorescent images were acquired via a confocal microscope (Leica) using coverslips mounted with mounting solution (Biomeda). All images were processed using Las X software (Leica). NS101 and the recombinant proteins containing the FB domain were treated for 30 min before the fixation. Primary neuronal culture and immunocytochemistry Primary cortical or hippocampal neurons were prepared from postnatal C57BL/6 pups (postnatal day 1) (Nara Biotech) as previously described. 82 The cells were maintained at 37°C in a 5% CO 2 -humified incubator. Every 3–4 days, half of the medium from the culture dish was replaced with fresh culture medium. Neurons were cultured for DIV16, and total RNA was isolated and subjected to RNA-seq analysis as previously described. 83 Cells were fixed with 4% PFA, except for the spine density assay (2% PFA, 4% sucrose). The cells were permeabilized and blocked with a blocking buffer containing 3% BSA and 0.1% Triton X-100 in PBS for 1 hour at room temperature. Then, the samples were incubated with primary antibodies diluted in blocking buffer overnight at 4°C and washed three times with PBS. Cells were incubated with the appropriate fluorescently labeled secondary antibodies and with Hoechst 33342 (Invitrogen) diluted in PBS for 30 min at room temperature. Cells were washed three times with PBS, and then coverslips were mounted using Crystal Mount (Biomeda). Images were acquired using a confocal microscope (Leica). For the analysis of neurite growth, cultured neurons were treated with hIgG or NS101, or rcFAM19A5 at DIV 1 and DIV 2. At DIV 3, neurons were fixed and immunostained with anti-Tau5 (Thermo), and three parameters (total neurite length per neuron, number of primary neurites, and number of branch points) were measured using ImageJ (NIH). For the quantification of pre- and postsynaptic molecules, cultured neurons were treated with or rcFAM19A5, hIgG or NS101 at DIV 3 and DIV 6. At DIV 7, neurons were fixed and immunostained with anti-SYP (Sigma) and anti-PSD95 (Invitrogen). Z-stack images (depth, 3 μm) were acquired with a confocal microscope (Leica), and 3D reconstruction and analysis were performed with Imaris software (Bitplane). For measurement of FAM19A5 level released to the culture medium, neurons were treated with hIgG or NS101 at DIV 9 and DIV 10. At DIV 11, culture media were collected and subjected to ELISA. For measurement culture media of FAM19A5, 2-13 and C-term FAM19A5 antibody was used for capture and detection, respectively. DiI staining and spine density analysis in vitro To visualize dendritic spines, we used the well-characterized fluorescent lipophilic dye DiI (Invitrogen) according to the manufacturer’s instructions. Primary neurons were treated with hIgG or NS101 every 3 days starting at DIV 3. On the appropriate DIV, primary neurons were fixed with 2% PFA + 4% sucrose in PBS for 15 min at room temperature and washed three times with DPBS. The cells were incubated with DiI solution diluted in DPBS (5 μl/ml) for 20 min at room temperature and washed three times with DPBS. After labeling, the coverslips incubated in DPBS were stored in the dark overnight at 4°C to allow the DiI dye to diffuse. The following day, the coverslips were rinsed twice with sterile H 2 O to reduce the background. The coverslips were mounted on slides using Crystal Mount (Biomeda) and cured for at least 2 days to allow complete migration of the dye into the spines. All images were acquired under a 552 nm laser using a confocal microscope (63× oil immersion objective) at a pixel resolution of 1024 × 1024 with a 3× optical zoom. Serial Z-stacks (0.2 μm intervals) were performed from top to bottom, covering all dendrites and protrusions. The 3D reconstruction of stacked images and analysis were performed using Imaris software, and the analysis was blinded. A protrusion width greater than 0.2 μm was defined as a dendritic spine. Aβ 1–42 preparation Aβ 1–42 peptide was purchased from AnaSpec (Fremont) and prepared as previously described. 84 On the day of Aβ 1–42 treatment, after incubation, the working solutions were centrifuged at 14000 × g at 4°C for 10 min to purify the oligomeric Aβ fraction from the fibrils. Immunohistochemistry Mice were transcardially perfused with 4% PFA in PBS, and isolated brains were postfixed in the same fixative for 24 hours. Brains were then cryoprotected in 30% sucrose, sectioned serially on a cryostat (40 mm), and stored in 50% glycerol/50% PBS at −20°C until use. Brain sections were blocked for 30 min in 3% BSA + 0.1% Triton X-100 in PBS and incubated with primary antibodies diluted in blocking buffer overnight at 4°C. After overnight incubation, sections were washed three times in PBS and incubated with secondary antibodies or Hoechst 33242 (Invitrogen) diluted in PBS for 30 min at room temperature. Subsequently, the sections were washed, mounted, and observed under a slide scanner (Zeiss) or a confocal microscope (Leica). Hippocampal slice preparation and electrophysiology APP/PS1 mice and WT mice (13 months old) were anesthetized with isoflurane (5% isoflurane, 95% O 2 ) and perfused with ice-cold sucrose artificial cerebrospinal fluid (aCSF) containing 195.5 mM sucrose, 2.5 mM KCl, 1 mM NaH 2 PO 4 , 32.5 mM NaHCO 3 , 11 mM glucose, 2 mM Na pyruvate, and 1 mM Na ascorbate (all chemicals from Sigma) bubbled with 95% O 2 /5% CO 2 at a pH of 7.4. After perfusion, the brains were quickly removed from the skull, and sagittal hippocampal slices (400 μm thick) were cut on a vibratome (Leica). The slices were incubated at 35°C for 15 min in an incubation solution containing 119 mM NaCl, 2.5 mM KCl, 1 mM NaH 2 PO 4 , 26.2 NaHCO 3 , 11 mM glucose, 2 mM Na pyruvate, 1 mM Na ascorbate, 3 mM MgSO 4 , and 1.5 mM CaCl 2 . After incubation, the slices were transferred to aCSF solution at 23–24°C for 1 hour. Field recordings were made with a concentric bipolar electrode positioned in the stratum radiatum of the CA1 region using an extracellular glass pipette (3–5 MΩ) filled with aCSF. Stimulation was delivered through a bipolar electrode (FHC, Bowdoin, ME, USA) placed in the SC-CA1. The SC circuit was visualized using differential interference contrast (DIC) microscopy at 4× magnification and identified by the ability to evoke short and constant latency fEPSPs at CA1 synapses by SC input stimulation. The test stimulation in all fEPSP experiments was measured before the experiments (30–300 μA), and a test-pulse stimulation strength that evoked 50% of the maximum fEPSP was used. Baseline synaptic responses were recorded for 30 min, and then LTP was induced by theta burst stimulation (100 Hz, 10 trains, 40 ms duration, 200 ms intertrain interval). LTP was calculated by an average of fEPSP amplitudes during the last 5 min of recordings. Recordings were made every 10 s for 1 hour using an Axopatch 700A amplifier (Molecular Devices) digitized at 10 kHz and filtered at two kHz with Digidata 1440A and pClamp 10.0 software (Molecular Devise). To measure mEPSCs, the electrode was filled with an internal solution containing 135 mM Cs methane sulfonate, 8 mM NaCl, 10 mM HEPES, 0.5 mM EGTA, 4 mM Mg-ATP, 0.3 mM Na-GTP, and 5 mM QX-315 Cl; pH 7.25 with CsOH, 285 mOsm). Miniature currents were recorded in the presence of tetrodotoxin (1 μM TTX, Tocris) to block sodium currents and propagate action potentials. Stereotaxic FAM19A5 injection For stereotaxic injection of WT and MT form of FAM19A5, three-month-old male and female mice were anesthetized with xylazene and ketamine. An injection cannula was inserted stereotaxically into the striatum (mediolateral, 2.0 mm from bregma; anteroposterior, 0.5 mm; dorsoventral, 3.5 mm) unilaterally (inserted into the right hemisphere). The infusion was performed at a rate of 0.2 μl per min, and 2 μl of FAM19A5 (5 μg μl−1 in PBS) or the same volume of PBS were injected into the mouse. Animal behavioral tests Male mice used in all behavioral tests were 9–11 months old. All assays used littermates or age-matched animals. Behavioral tests were performed in a light- and noise-controlled behavioral room, where the animals were allowed to adapt for one hour before each behavioral test. All behavioral results were analyzed blindly. Y-maze test A Y-shaped maze consists of three identical arms (40 cm in length, 15 cm in height) at a 120° angle from each other. Mice were allowed to freely explore the three arms for 8 min with a luminosity of 40 lux. The sequence and the total number of arms entered were measured. Spontaneous alteration (%) was calculated as follows: the number of triads containing entries into all three arms/maximum possible alternations (the total number of arms entered – 2) × 100. Mice that constituted fewer than 10 of the total arm entries were omitted from the analysis. Morris water maze test Mice were trained to find the hidden platform (9 cm in diameter) in a stainless-steel pool (90 cm in diameter, 50 cm in height) filled with water (22 ± 1°C) to a depth of 30 cm. The platform was 1 cm below the water level. In the acquisition phase, mice were trained for six consecutive days with four trials/per day. Each trial ended either when an animal climbed onto the platform or when a maximum of 60 s had elapsed. Next, mice were allowed to remain on the platform for 10 s. If they failed to locate the platform within 60 s, they were guided to the platform and left there for 10 s, and the escape time was recorded as 60 s. On day 7, for the probe test, the platform was removed, and mice were allowed to explore freely for 60 s. The spatial memory ability of individual animals in the probe test was determined by the following parameters: latency to target, target crossing number, distance to the target, the percentage in quadrant SW, and the percentage in the target. Target and quadrant SW refer to the location and quadrant where the hidden platform was located, respectively. These parameters were analyzed by SMART video tracking software (Panlab). Mice displaying abnormal behaviors, such as freezing and floating, were excluded from the final data. Passive avoidance test The passive avoidance test, performed in plastic cages of identical size, assessed associative learning and memory by using the rodents’ innate preference for darkness. The inside of a darkened cage was designed to induce a foot shock; thus, when mice entered the dark compartment from the light compartment, a foot shock (0.5 mA intensity) was delivered for 3 s. To assess memory, we placed mice in the light compartment 24 hours later and measured the time it took to enter the dark compartment. The maximal latency was 300 s. Animals showing freezing behaviors (with acquisition time ≥ 200 s) or abnormal exploration were excluded from the final analysis. QUANTIFICATION AND STATISTICAL ANALYSIS All statistical analyses were performed using GraphPad Prism 8 with 95% confidence. Comparisons between two groups were performed using unpaired two-tailed Student’s t-test when the data followed a normal distribution, while the Mann-Whitney test was used when the data showed a nonnormal distribution. In the case of data comparing more than three groups, one-way ANOVA followed by Dunn’s multiple comparison test was used. All data are presented as the mean ± SEM. All the details of the statistical tests and results are reported in the figure legends. All experiments were duplicated or triplicated with similar results. References Abitz, M., Nielsen, R.D., Jones, E.G., Laursen, H., Graem, N., and Pakkenberg, B. (2007). Excess of neurons in the human newborn mediodorsal thalamus compared with that of the adult. Cereb. Cortex 17, 2573–2578. https://doi.org/10.1093/cercor/bhl163 . Huttenlocher, P.R. (1979). Synaptic density in human frontal cortex - developmental changes and effects of aging. Brain Res. 163, 195–205. https://doi.org/10.1016/0006-8993(79)90349-4 . Kolb, B., Mychasiuk, R., Muhammad, A., and Gibb, R. (2013). Chapter 2 - Brain plasticity in the developing brain. Prog. Brain Res. 207, 35–64. https://doi.org/10.1016/B978-0-444-63327-9.00005-9 . Feinberg, I. (1982). Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence? J. Psychiatr. Res. 17, 319–334. https://doi.org/10.1016/0022-3956(82)90038-3 . Artola, A. (2008). Diabetes-, stress- and ageing-related changes in synaptic plasticity in hippocampus and neocortex — The same metaplastic process? Eur. J. Pharmacol. 585, 153–162. https://doi.org/10.1016/j.ejphar.2007.11.084 . Kim, J.J., and Diamond, D.M. (2002). The stressed hippocampus, synaptic plasticity and lost memories. Nat. Rev. Neurosci. 3, 453–462. https://doi.org/10.1038/nrn849 . Foster, T.C. (2002). Regulation of synaptic plasticity in memory and memory decline with aging. Prog. Brain Res. 138, 283–303. https://doi.org/10.1016/s0079-6123(02)38083-x . Jackson, J., Jambrina, E., Li, J., Marston, H., Menzies, F., Phillips, K., and Gilmour, G. (2019). Targeting the synapse in Alzheimer's disease. Front. Neurosci. 13, 735. https://doi.org/10.3389/fnins.2019.00735 . Nathan, P.J., Cobb, S.R., Lu, B., Bullmore, E.T., and Davies, C.H. (2011). Studying synaptic plasticity in the human brain and opportunities for drug discovery. Curr. Opin. Pharmacol. 11, 540–548. https://doi.org/10.1016/j.coph.2011.06.008 . Sellgren, C.M., Gracias, J., Watmuff, B., Biag, J.D., Thanos, J.M., Whittredge, P.B., Fu, T., Worringer, K., Brown, H.E., Wang, J., et al. (2019). Increased synapse elimination by microglia in schizophrenia patient-derived models of synaptic pruning. Nat. Neurosci. 22, 374–385. https://doi.org/10.1038/s41593-018-0334-7 . McAllister, A.K. (2007). Dynamic aspects of CNS synapse formation. Annu. Rev. Neurosci. 30, 425–450. https://doi.org/10.1146/annurev.neuro.29.051605.112830 . Südhof, T.C. (2018). Towards an understanding of synapse formation. Neuron 100, 276–293. https://doi.org/10.1016/j.neuron.2018.09.040 . Dalva, M.B., McClelland, A.C., and Kayser, M.S. (2007). Cell adhesion molecules: signalling functions at the synapse. Nat. Rev. Neurosci. 8, 206–220. https://doi.org/10.1038/nrn2075 . DeNardo, L.A., de Wit, J., Otto-Hitt, S., and Ghosh, A. (2012). NGL-2 regulates input-specific synapse development in CA1 pyramidal neurons. Neuron 76, 762–775. https://doi.org/10.1016/j.neuron.2012.10.013 . Kim, S., Burette, A., Chung, H.S., Kwon, S.K., Woo, J., Lee, H.W., Kim, K., Kim, H., Weinberg, R.J., and Kim, E. (2006). NGL family PSD-95-interacting adhesion molecules regulate excitatory synapse formation. Nat. Neurosci. 9, 1294–1301. https://doi.org/10.1038/nn1763 . Woo, J., Kwon, S.K., and Kim, E. (2009). The NGL family of leucine-rich repeat-containing synaptic adhesion molecules. Mol. Cell. Neurosci. 42, 1–10. https://doi.org/10.1016/j.mcn.2009.05.008 . Kwon, S.K., Woo, J., Kim, S.Y., Kim, H., and Kim, E. (2010). Trans-synaptic adhesions between netrin-G ligand-3 (NGL-3) and receptor tyrosine phosphatases LAR, protein-tyrosine phosphatase delta (PTPdelta), and PTPsigma via specific domains regulate excitatory synapse formation. J. Biol. Chem. 285, 13966–13978. https://doi.org/10.1074/jbc.M109.061127 . Takahashi, H., and Craig, A.M. (2013). Protein tyrosine phosphatases PTPδ, PTPσ, and LAR: presynaptic hubs for synapse organization. Trends Neurosci. 36, 522–534. https://doi.org/10.1016/j.tins.2013.06.002 . Woo, J., Kwon, S.K., Choi, S., Kim, S., Lee, J.R., Dunah, A.W., Sheng, M., and Kim, E. (2009). Trans-synaptic adhesion between NGL-3 and LAR regulates the formation of excitatory synapses. Nat. Neurosci. 12, 428–437. https://doi.org/10.1038/nn.2279 . Lee, H., Lee, E.J., Song, Y.S., and Kim, E. (2014). Long-term depression-inducing stimuli promote cleavage of the synaptic adhesion molecule NGL-3 through NMDA receptors, matrix metalloproteinases and presenilin/γ-secretase. Phil. Trans. R. Soc. B 369, 20130158. https://doi.org/10.1098/rstb.2013.0158 . Lee, H., Shin, W., Kim, K., Lee, S., Lee, E.J., Kim, J., Kweon, H., Lee, E., Park, H., Kang, M., et al. (2019). NGL-3 in the regulation of brain development, Akt/GSK3b signaling, long-term depression, and locomotive and cognitive behaviors. PLoS Biol. 17, e2005326. https://doi.org/10.1371/journal.pbio.2005326 . Tom Tang, Y., Emtage, P., Funk, W.D., Hu, T., Arterburn, M., Park, E.E., and Rupp, F. (2004). TAFA: a novel secreted family with conserved cysteine residues and restricted expression in the brain. Genomics 83, 727–734. https://doi.org/10.1016/j.ygeno.2003.10.006 . Jeong, I., Yun, S., Shahapal, A., Cho, E.B., Hwang, S.W., Seong, J.Y., and Park, H.C. (2021). FAM19A5l affects mustard oil-Induced peripheral nociception in zebrafish. Mol. Neurobiol. 58, 4770–4785. https://doi.org/10.1007/s12035-021-02449-z . Kwak, H., Cho, E.-H., Cho, E.B., Lee, Y.-N., Shahapal, A., Yong, H.J., Reyes-Alcaraz, A., Jeong, Y., Lee, Y., Lee, M., et al. (2020). Is FAM19A5 an adipokine? Peripheral FAM19A5 in wild-type, FAM19A5 knock-out, and LacZ knock-in mice. bioRxiv. https://doi.org/10.1101/2020.02.19.955351 . Zeisel, A., Hochgerner, H., Lönnerberg, P., Johnsson, A., Memic, F., van der Zwan, J., Häring, M., Braun, E., Borm, L.E., La Manno, G., et al. (2018). Molecular architecture of the mouse nervous system. Cell 174, 999–1014.e1022. https://doi.org/10.1016/j.cell.2018.06.021 . Khalaj, A.J., Sterky, F.H., Sclip, A., Schwenk, J., Brunger, A.T., Fakler, B., and Südhof, T.C. (2020). Deorphanizing FAM19A proteins as pan-neurexin ligands with an unusual biosynthetic binding mechanism. J. Cell Biol. 219. https://doi.org/10.1083/jcb.202004164 . Huang, S., Zheng, C., Xie, G., Song, Z., Wang, P., Bai, Y., Chen, D., Zhang, Y., Lv, P., Liang, W., et al. (2021). FAM19A5/TAFA5, a novel neurokine, plays a crucial role in depressive-like and spatial memory-related behaviors in mice. Mol. Psychiatry 26, 2363–2379. https://doi.org/10.1038/s41380-020-0720-x . Kashevarova, A.A., Belyaeva, E.O., Nikonov, A.M., Plotnikova, O.V., Skryabin, N.A., Nikitina, T.V., Vasilyev, S.A., Yakovleva, Y.S., Babushkina, N.P., Tolmacheva, E.N., et al. (2018). Compound phenotype in a girl with r(22), concomitant microdeletion 22q13.32-q13.33 and mosaic monosomy 22. Mol. Cytogenet. 11, 26. https://doi.org/10.1186/s13039-018-0375-3 . Knutson, K.A., Deng, Y., and Pan, W. (2020). Implicating causal brain imaging endophenotypes in Alzheimer's disease using multivariable IWAS and GWAS summary data. NeuroImage 223, 117347. https://doi.org/10.1016/j.neuroimage.2020.117347 . Mez, J., Chung, J., Jun, G., Kriegel, J., Bourlas, A.P., Sherva, R., Logue, M.W., Barnes, L.L., Bennett, D.A., Buxbaum, J.D., et al. (2017). Two novel loci, COBL and SLC10A2, for Alzheimer's disease in african americans. Alzheimers Dement. 13, 119–129. https://doi.org/10.1016/j.jalz.2016.09.002 . Mathys, H., Davila-Velderrain, J., Peng, Z., Gao, F., Mohammadi, S., Young, J.Z., Menon, M., He, L., Abdurrob, F., Jiang, X., et al. (2019). Single-cell transcriptomic analysis of Alzheimer's disease. Nature 570, 332–337. https://doi.org/10.1038/s41586-019-1195-2 . Li, J., Li, S., Song, Y., Zhou, W., Zhu, X., Xu, S., Ma, Y., and Zhu, C. (2020). Association of serum FAM19A5 with cognitive impairment in vascular dementia. Dis. Markers. 2020, 8895900. https://doi.org/10.1155/2020/8895900 . Park, M.Y., Kim, H.S., Lee, M., Park, B., Lee, H.Y., Cho, E.B., Seong, J.Y., and Bae, Y.S. (2017). FAM19A5, a brain-specific chemokine, inhibits RANKL-induced osteoclast formation through formyl peptide receptor 2. Sci. Rep. 7, 15575. https://doi.org/10.1038/s41598-017-15586-0 . Wang, Y., Chen, D., Zhang, Y., Wang, P., Zheng, C., Zhang, S., Yu, B., Zhang, L., Zhao, G., Ma, B., et al. (2018). Novel adipokine, FAM19A5, inhibits neointima formation after injury through sphingosine-1-phosphate receptor 2. Circulation 138, 48–63. https://doi.org/10.1161/circulationaha.117.032398 . Wang, Y., Zhang, Z., Wan, W., Liu, Y., Jing, H., and Dong, F. (2022). FAM19A5/S1PR1 signaling pathway regulates the viability and proliferation of mantle cell lymphoma. J. Recept. Signal Transduct. Res. 42, 225–229. https://doi.org/10.1080/10799893.2021.1895220 . Larouche, R. (2021, November 4–2022, December 22). A FIH study to assess the safety and tolerability of NS intravenous NS101 infusion. Identifier NCT05143463. https://ClinicalTrials.gov/show/NCT05143463 . Westwood, S., Liu, B., Baird, A.L., Anand, S., Nevado-Holgado, A.J., Newby, D., Pikkarainen, M., Hallikainen, M., Kuusisto, J., Streffer, J.R., et al. (2017). The influence of insulin resistance on cerebrospinal fluid and plasma biomarkers of Alzheimer's pathology. Alz. Res. Ther. 9, 31. https://doi.org/10.1186/s13195-017-0258-6 . Xiong, L.L., Xue, L.L., Chen, Y.J., Du, R.L., Wang, Q., Wen, S., Zhou, L., Liu, T., Wang, T.H., and Yu, C.Y. (2021). Proteomics study on the cerebrospinal fluid of patients with encephalitis. ACS omega 6, 16288–16296. https://doi.org/10.1021/acsomega.1c00367 . Wang, H., Dey, K.K., Chen, P.C., Li, Y., Niu, M., Cho, J.H., Wang, X., Bai, B., Jiao, Y., Chepyala, S.R., et al. (2020). Integrated analysis of ultra-deep proteomes in cortex, cerebrospinal fluid and serum reveals a mitochondrial signature in Alzheimer's disease. Mol. Neurodegener. 15, 43. https://doi.org/10.1186/s13024-020-00384-6 . Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021). Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589. https://doi.org/10.1038/s41586-021-03819-2 . Baek, M., DiMaio, F., Anishchenko, I., Dauparas, J., Ovchinnikov, S., Lee, G.R., Wang, J., Cong, Q., Kinch, L.N., Schaeffer, R.D., et al. (2021). Accurate prediction of protein structures and interactions using a three-track neural network. Science 373, 871–876. https://doi.org/10.1126/science.abj8754 . Humphreys, I.R., Pei, J., Baek, M., Krishnakumar, A., Anishchenko, I., Ovchinnikov, S., Zhang, J., Ness, T.J., Banjade, S., Bagde, S.R., et al. (2021). Computed structures of core eukaryotic protein complexes. Science 374, eabm4805. https://doi.org/10.1126/science.abm4805 . Won, S.Y., and Kim, H.M. (2018). Structural basis for LAR-RPTP-mediated synaptogenesis. Mol. Cells 41, 622–630. https://doi.org/10.14348/molcells.2018.0202 . Cove, J., Blinder, P., Abi-Jaoude, E., Lafrenière-Roula, M., Devroye, L., and Baranes, D. (2006). Growth of neurites toward neurite- neurite contact sites increases synaptic clustering and secretion and is regulated by synaptic activity. Cereb. Cortex 16, 83–92. https://doi.org/10.1093/cercor/bhi086 . Glantz, L.A., Gilmore, J.H., Hamer, R.M., Lieberman, J.A., and Jarskog, L.F. (2007). Synaptophysin and postsynaptic density protein 95 in the human prefrontal cortex from mid-gestation into early adulthood. Neuroscience 149, 582–591. https://doi.org/10.1016/j.neuroscience.2007.06.036 . Reese, D., and Drapeau, P. (1998). Neurite growth patterns leading to functional synapses in an identified embryonic neuron. J. Neurosci. 18, 5652–5662. https://doi.org/10.1523/jneurosci.18-15-05652.1998 . Dzyubenko, E., Rozenberg, A., Hermann, D.M., and Faissner, A. (2016). Colocalization of synapse marker proteins evaluated by STED-microscopy reveals patterns of neuronal synapse distribution in vitro. J. Neurosci. Methods 273, 149–159. https://doi.org/10.1016/j.jneumeth.2016.09.001 . Chames, P., Van Regenmortel, M., Weiss, E., and Baty, D. (2009). Therapeutic antibodies: successes, limitations and hopes for the future. Br. J. Pharmacol. 157, 220–233. https://doi.org/10.1111/j.1476-5381.2009.00190.x . Kim, B.G., Dai, H.N., McAtee, M., Vicini, S., and Bregman, B.S. (2007). Labeling of dendritic spines with the carbocyanine dye DiI for confocal microscopic imaging in lightly fixed cortical slices. J. Neurosci. Methods 162, 237–243. https://doi.org/10.1016/j.jneumeth.2007.01.016 . Kuszczyk, M.A., Sanchez, S., Pankiewicz, J., Kim, J., Duszczyk, M., Guridi, M., Asuni, A.A., Sullivan, P.M., Holtzman, D.M., and Sadowski, M.J. (2013). Blocking the interaction between apolipoprotein E and Aβ reduces intraneuronal accumulation of Aβ and inhibits synaptic degeneration. Am. J. Pathol. 182, 1750–1768. https://doi.org/10.1016/j.ajpath.2013.01.034 . Coomans, E.M., Schoonhoven, D.N., Tuncel, H., Verfaillie, S.C.J., Wolters, E.E., Boellaard, R., Ossenkoppele, R., den Braber, A., Scheper, W., Schober, P., et al. (2021). In vivo tau pathology is associated with synaptic loss and altered synaptic function. Alz. Res. Ther. 13, 35. https://doi.org/10.1186/s13195-021-00772-0 . Peng, L., Bestard-Lorigados, I., and Song, W. (2022). The synapse as a treatment avenue for Alzheimer's disease. Mol. Psychiatry 27, 2940–2949. https://doi.org/10.1038/s41380-022-01565-z . Sheng, M., Sabatini, B.L., and Südhof, T.C. (2012). Synapses and Alzheimer's disease. Cold Spring Harb. Perspect. Biol. 4. https://doi.org/10.1101/cshperspect.a005777 . Spires-Jones, T.L., and Hyman, B.T. (2014). The intersection of amyloid beta and tau at synapses in Alzheimer's disease. Neuron 82, 756–771. https://doi.org/10.1016/j.neuron.2014.05.004 . Suzuki, K., Elegheert, J., Song, I., Sasakura, H., Senkov, O., Matsuda, K., Kakegawa, W., Clayton, A.J., Chang, V.T., Ferrer-Ferrer, M., et al. (2020). A synthetic synaptic organizer protein restores glutamatergic neuronal circuits. Science 369. https://doi.org/10.1126/science.abb4853 . Minkeviciene, R., Rheims, S., Dobszay, M.B., Zilberter, M., Hartikainen, J., Fülöp, L., Penke, B., Zilberter, Y., Harkany, T., Pitkänen, A., and Tanila, H. (2009). Amyloid beta-induced neuronal hyperexcitability triggers progressive epilepsy. J. Neurosci. 29, 3453–3462. https://doi.org/10.1523/jneurosci.5215-08.2009 . Radde, R., Bolmont, T., Kaeser, S.A., Coomaraswamy, J., Lindau, D., Stoltze, L., Calhoun, M.E., Jäggi, F., Wolburg, H., Gengler, S., et al. (2006). Abeta42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology. EMBO reports 7, 940–946. https://doi.org/10.1038/sj.embor.7400784 . Heurling, K., Ashton, N.J., Leuzy, A., Zimmer, E.R., Blennow, K., Zetterberg, H., Eriksson, J., Lubberink, M., and Schöll, M. (2019). Synaptic vesicle protein 2A as a potential biomarker in synaptopathies. Mol. Cell. Neurosci. 97, 34–42. https://doi.org/10.1016/j.mcn.2019.02.001 . Marchetti, C., and Marie, H. (2011). Hippocampal synaptic plasticity in Alzheimer's disease: what have we learned so far from transgenic models? Rev. Neurosci. 22, 373–402. https://doi.org/10.1515/rns.2011.035 . Caroni, P., Donato, F., and Muller, D. (2012). Structural plasticity upon learning: regulation and functions. Nat. Rev. Neurosci. 13, 478–490. https://doi.org/10.1038/nrn3258 . Kandel, E.R. (2001). The molecular biology of memory storage: a dialogue between genes and synapses. Science 294, 1030–1038. https://doi.org/10.1126/science.1067020 . Engert, F., and Bonhoeffer, T. (1999). Dendritic spine changes associated with hippocampal long-term synaptic plasticity. Nature 399, 66–70. https://doi.org/10.1038/19978 . Toni, N., Buchs, P.A., Nikonenko, I., Bron, C.R., and Muller, D. (1999). LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite. Nature 402, 421–425. https://doi.org/10.1038/46574 . Shipton, O.A., Leitz, J.R., Dworzak, J., Acton, C.E., Tunbridge, E.M., Denk, F., Dawson, H.N., Vitek, M.P., Wade-Martins, R., Paulsen, O., and Vargas-Caballero, M. (2011). Tau protein is required for amyloid β-induced impairment of hippocampal long-term potentiation. J. Neurosci. 31, 1688–1692. https://doi.org/10.1523/jneurosci.2610-10.2011 . Son, H., and Carpenter, D.O. (1996). Interactions among paired-pulse facilitation and post-tetanic and long-term potentiation in the mossy fiber-CA3 pathway in rat hippocampus. Synapse 23, 302–311. https://doi.org/10.1002/(sici)1098-2396(199608)23:43.0.Co;2-b . Ting, J.T., Kelley, B.G., Lambert, T.J., Cook, D.G., and Sullivan, J.M. (2007). Amyloid precursor protein overexpression depresses excitatory transmission through both presynaptic and postsynaptic mechanisms. Proc. Natl. Acad. Sci. USA. 104, 353–358. https://doi.org/10.1073/pnas.0608807104 . Südhof, T.C. (2021). The cell biology of synapse formation. J Cell Biol. 220. https://doi.org/10.1083/jcb.202103052 . Dunah, A.W., Hueske, E., Wyszynski, M., Hoogenraad, C.C., Jaworski, J., Pak, D.T., Simonetta, A., Liu, G., and Sheng, M. (2005). LAR receptor protein tyrosine phosphatases in the development and maintenance of excitatory synapses. Nat. Neurosci. 8, 458–467. https://doi.org/10.1038/nn1416 . Lang, B.T., Cregg, J.M., DePaul, M.A., Tran, A.P., Xu, K., Dyck, S.M., Madalena, K.M., Brown, B.P., Weng, Y.L., Li, S., et al. (2015). Modulation of the proteoglycan receptor PTPσ promotes recovery after spinal cord injury. Nature 518, 404–408. https://doi.org/10.1038/nature13974 . Lin, J.C., Ho, W.H., Gurney, A., and Rosenthal, A. (2003). The netrin-G1 ligand NGL-1 promotes the outgrowth of thalamocortical axons. Nat. Neurosci. 6, 1270–1276. https://doi.org/10.1038/nn1148 . Turrigiano, G.G., and Nelson, S.B. (2004). Homeostatic plasticity in the developing nervous system. Nat. Rev. Neurosci. 5, 97–107. https://doi.org/10.1038/nrn1327 . Yanamandra, K., Patel, T.K., Jiang, H., Schindler, S., Ulrich, J.D., Boxer, A.L., Miller, B.L., Kerwin, D.R., Gallardo, G., Stewart, F., et al. (2017). Anti-tau antibody administration increases plasma tau in transgenic mice and patients with tauopathy. Sci. Transl. Med. 9. https://doi.org/10.1126/scitranslmed.aal2029 . Jung, H., Lee, S.Y., Lim, S., Choi, H.R., Choi, Y., Kim, M., Kim, S., Lee, Y., Han, K.H., Chung, W.-S., and Kim, C.H. (2022). Anti-inflammatory clearance of amyloid-β by a chimeric Gas6 fusion protein. Nat. Med. 28, 1802–1812. https://doi.org/10.1038/s41591-022-01926-9 . Imbimbo, B.P., Balducci, C., Ippati, S., and Watling, M. (2023). Initial failures of anti-tau antibodies in Alzheimer's disease are reminiscent of the amyloid-β story. Neural. Regen. Res. 18, 117–118. https://doi.org/10.4103/1673-5374.340409 . Mullard, A. (2021). Landmark Alzheimer's drug approval confounds research community. Nature 594, 309–310. https://doi.org/10.1038/d41586-021-01546-2 . Prillaman, M. (2022). Alzheimer's drug slows mental decline in trial - but is it a breakthrough? Nature 610, 15–16. https://doi.org/10.1038/d41586-022-03081-0 . Reardon, S. (2023). FDA approves Alzheimer's drug lecanemab amid safety concerns. Nature 613, 227–228. https://doi.org/10.1038/d41586-023-00030-3 . Lau, S.F., Cao, H., Fu, A.K.Y., and Ip, N.Y. (2020). Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer's disease. Proc. Natl. Acad. Sci. USA. 117, 25800–25809. https://doi.org/10.1073/pnas.2008762117 . Otero-Garcia, M., Mahajani, S.U., Wakhloo, D., Tang, W., Xue, Y.Q., Morabito, S., Pan, J., Oberhauser, J., Madira, A.E., Shakouri, T., et al. (2022). Molecular signatures underlying neurofibrillary tangle susceptibility in Alzheimer's disease. Neuron 110, 2929–2948.e2928. https://doi.org/10.1016/j.neuron.2022.06.021 . Mirdita, M., von den Driesch, L., Galiez, C., Martin, M.J., Söding, J., and Steinegger, M. (2017). Uniclust databases of clustered and deeply annotated protein sequences and alignments. Nucleic Acids Res. 45, D170-d176. https://doi.org/10.1093/nar/gkw1081 . Remmert, M., Biegert, A., Hauser, A., and Söding, J. (2011). HHblits: lightning-fast iterative protein sequence searching by HMM-HMM alignment. Nat. Methods 9, 173–175. https://doi.org/10.1038/nmeth.1818 . Beaudoin, G.M., 3rd, Lee, S.H., Singh, D., Yuan, Y., Ng, Y.G., Reichardt, L.F., and Arikkath, J. (2012). Culturing pyramidal neurons from the early postnatal mouse hippocampus and cortex. Nat. Protoc. 7, 1741–1754. https://doi.org/10.1038/nprot.2012.099 . Martin, J.A., and Wang, Z. (2011). Next-generation transcriptome assembly. Nat. Rev. Genet. 12, 671–682. https://doi.org/10.1038/nrg3068 . Dahlgren, K.N., Manelli, A.M., Stine, W.B., Jr., Baker, L.K., Krafft, G.A., and LaDu, M.J. (2002). Oligomeric and fibrillar species of amyloid-beta peptides differentially affect neuronal viability. J Biol. Chem. 277, 32046–32053. https://doi.org/10.1074/jbc.M201750200 . Supplementary Files floatimage1.jpeg Graphical Abstract FigureS2.png Figure S2. The residues responsible for the binding between FAM19A5 and LRRC4B FB. (A) Molecular modeling of the LRRC4B FB-FAM19A5 complex. Predicted hydrogen-bond interactions between the intra-FAM19A5 β-strand (cyan) and the LRRC4B FB domain (orange) are represented as magenta dashed lines. The FB domain constituting residues (Y484- E496, orange main chain, labelled in grey); β-strand forming FB residues (T485 - L495, labelled in black). FB binding residues constituting β-strand via forming hydrogen-bonds (labelled in orange label); residues involved in constituting intra-FAM19A5 hydrogen-bonds (labelled in marine); residues affecting binding affinity of LRRC4B FB and FAM19A5 complex, identified via Ala mutagenesis (purple labels); R125 and K127; NS101 binding epitope (green main chain); R52, P57, R58, and R59; competitive binding sites for FB and NS101 (labelled in red); R58 and R59. (B) The predicted changes in binding free energy based on Ala scanning of FB. (C-D) Co-IP of FAM19A5 and LRRC4B(36-173) (C) or LRRC4B(453-573) (D). Wild type LRRC4B(TT); mutant LRRC4B(AA, T488,489A) (E) The predicted changes in binding free energy based on Ala scanning of FAM19A5. Competitive binding sites for FB and NS101 (orange); R58 and R59. Residues affecting binding affinity between FB and FAM19A5 (pink); R125 and K127. (F) Epitope mapping of NS101 for FAM19A5. Binding of NS101 to rcFAM19A5 and synthetic peptides (F1~F6 and F2 mutant peptides, see Table S1 and S2). The aa residues are numbered according to the human FAM19A5 sequence. FigureS3.png Figure S3. FAM19A5 inhibits neurite growth and synapse formation. (A) Immunofluorescence images of mouse hippocampal neurons treated with vehicle alone (NT) or 6.6 μM rcFAM19A5 at 3 DIV. (B) Quantification of the average total neurite length, number of primary neurites, and number of branching points for experiments in (A). NT (n=72), rcFAM19A5 (n=76). (C) The fluorescence intensity of SYP and PSD95 and the number of colocalized voxels between SYP and PSD95 after treatment with 6.6μM rcFAM19A5.NT (n=15), rcFAM19A5 (n=14). Data are presented in Mean ± SEM. Statistical analyses were performed using unpaired t-test (B and C). n.s, not significant, *P < 0.05, **P < 0.01, ***P < 0.001. FigureS4.png Figure S4. NS101 dissociates FAM19A5 from LRRC4B. (A) The inhibition of FAM19A5-LRRC4B binding by NS101. HEK293 cells expressing FLAG-tagged LRRC4B were treated with rcFAM19A5 (1 μg/ml) and increasing concentrations of NS101. (B) Concentration-dependent FAM19A5 release after treatment of NS101 in HEK293 cells expressing LRRC4B and FAM19A5 isoform 1. (C) Immunofluorescence images of HEK293 cells expressing FLAG-LRRC4B (blue) and FAM19A5 isoform 2 (green) after treatment with hIgG or NS101. FAM19A5 signals were dissociated from LRRC4B by NS101 treatment (arrowheads). FigureS5.png Figure S5. NS101 forms a complex with FAM19A5. (A) Immunoblot analysis of FAM19A5 protein in the CSF of WT and FAM19A5 KO mice. (B) FAM19A5 levels in the CSF and plasma of WT and FAM19A5 KO mice. WT CSF (n=7), KO CSF (n=6), WT plasma (n=7), KO plasma (n=6). (C) Plasma NS101 levels at the indicated time points after iv administration of 10 mg/kg and 50 mg/kg NS101. (D) FAM19A5 band shift induced by the crosslinker. The purple arrow indicates the band for rcFAM19A5 without crosslinker, and the green arrow indicates the FAM19A5-NS101 complex. (E) Binding affinity of WT and MT FAM19A5(R58A, R59A) for NS101, LRRC4B, and C-A5-Ab. Data are presented in Mean ± SEM. Statistical analyses were performed using unpaired t-test. ***P < 0.001. FigureS6.png Figure S6. NS101 promotes neurite outgrowth. (A) Immunofluorescence images of mouse hippocampal neurons treated with 1 μg/ml hIgG or 1, 10, 100, and 1000 ng/ml NS101. (B) Quantification of the average total neurite length, number of primary neurites, and number of branching points for experiments in (A) NT (n=105), hIgG 1000 ng/ml (n=101), NS101 1 ng/ml (n=111); NS101 10 ng/ml (n=111), NS101 100 ng/ml (n=104), NS101 1000 ng/ml (n=100). (C) Immunofluorescence images of 1000 ng/ml hIgG- or NS101-treated mouse cortical neurons labeled with SYP (green), PSD95 (red), and Hoechst (blue). (D) The fluorescence intensity of PSD95 and SYP, and the number of colocalized voxels between SYP and PSD95 for experiment in (C) (n=10). Data are presented in Mean ± SEM. Statistical analyses were performed using one-way ANOVA followed by Tukey's multiple comparisons test (B; neurite length), Kruskal-Wallis test followed by Dunn’s multiple comparison test (B; number of neurite and branching points), and Unpaired t-test (D). **P < 0.01, ***P < 0.001. FigureS7.png Figure S7. NS101 iv administration induces the release of FAM19A5 from the brain into the blood in AD mouse models. (A-C) The plasma levels of FAM19A5 in three AD mouse models were measured after iv administration of NS101. All mice received a dose of 0.05 mg/kg of NS101, and one day later, half of them received an additional dose of 10 mg/kg of NS101, while the other half received no further treatment. FAM19A5 levels in the plasma were then measured using ELISA. n=3 for all groups except n=1 for APP/PS1 mice treated with 0.05 mg/kg only. Data are presented in Mean ± SEM. Statistical analyses were performed using one-way ANOVA followed by Tukey's multiple comparisons test. n.s, not significant, *P < 0.05, ***P < 0.001. FigureS8.png Figure S8. Morris water maze assessment of APP/PS1 mice treated with NS101. (A-B) The escape latency time during the training trials of WT mice (n=12) and APP/PS1 mice treated with 10 mg/kg hIgG (APP/PS1+hIgG, n=13), or NS101 (APP/PS1+NS101, n=10). (C) Swimming trajectory of mice. (D) Behavior parameters during the test trial. Data are presented in Mean ± SEM. Statistical analyses were performed using one-way ANOVA followed by Tukey's multiple comparisons test. n.s, not significant, *P < 0.05, **P < 0.01, ***P < 0.001. FigureS9.png Figure S9. NS101 ameliorates synapse loss in P301S mice. (A-B) Immunofluorescence images and quantification of the fluorescence intensity of SYP (green) and PSD95 (red) in the CA1 and CA3 regions of WT mice (n=6) and P301S mice treated with 10 mg/kg hIgG (P301S+hIgG, n=4), or NS101 (P301S+NS101, n=6). Data are presented in Mean ± SEM. Statistical analyses were performed using one-way ANOVA followed by Tukey's multiple comparisons test. *P < 0.05, **P < 0.01. SupplementaryTables.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2589038","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":176219780,"identity":"1a4fcbe0-a317-4475-9561-a19717b6f06e","order_by":0,"name":"Jae Young Seong","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA30lEQVRIiWNgGAWjYBACxgYILScBF+IhUosx8VpgIHEG0VqYZ6Q/fPBxR236zPbehw9+MNjJM/CcfYDfYTNyjA1nnjmeO5vnuLFhD0OyYQNvuwEhLWzSvG3HcudJpLFJ8DAwJzDws+F3GOOM9Oe/gVrS5STS2H/+YagnRkuCGTNvW02CNNAWZh6GwwkMvG0EtPS8MZac2XbAcGbPMWZpGYPjhm08x/BrMWxPf/jhY1udvMTxNsaPbyqq5fl50ghomZAAog5DucCwIuATBgZ5/gMgqo6QulEwCkbBKBjJAAAK/T5cjHdFPwAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Biomedical Sciences, Graduate School of Medicine, Korea University","correspondingAuthor":true,"prefix":"","firstName":"Jae","middleName":"Young","lastName":"Seong","suffix":""}],"badges":[],"createdAt":"2023-02-15 06:28:39","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":true,"conflictsOfInterestStatement":true,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":true,"coiExplicitlySet":false},"doi":"10.21203/rs.3.rs-2589038/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2589038/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":32999134,"identity":"de583ffa-6953-4fe0-9788-3d76ff27057d","added_by":"auto","created_at":"2023-02-15 21:37:42","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1680166,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFAM19A5 binds to LRRC4B via the FB domain.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) Correlations between transcript level of \u003cem\u003eLrrc4b \u003c/em\u003eand \u003cem\u003eFam19a5\u003c/em\u003e of 168 cell types. Correlation coefficient; r.\u003c/p\u003e\n\u003cp\u003e(B) Co-IP of FAM19A5 and LRRC4B.\u003c/p\u003e\n\u003cp\u003e(C) Immunofluorescence staining of HEK293 cells cotransfected with either FAM19A5 isoform 1 or 2 (green) and FLAG-LRRC4B (red).\u003c/p\u003e\n\u003cp\u003e(D) Immunoblots of HEK 293 cell lysates and medium after transfected with LRRC4B or FAM19A5 isoform 1.\u003c/p\u003e\n\u003cp\u003e(E) Co-IP of FAM19A5 and LRRC4B in human CSF samples.\u003c/p\u003e\n\u003cp\u003e(F) Immunofluorescence staining of rcFAM19A5 (green) and LRRC4B (red) in mouse primary cortical neurons at 15 DIV. White arrowheads indicates colocalized signals.\u003c/p\u003e\n\u003cp\u003e(G) Domain architecture of LRRC4B and its interactions with FAM19A5.\u003c/p\u003e\n\u003cp\u003e(H) Aa sequence alignment of the FB domain of the LRRC4 family in mammals.\u003c/p\u003e\n\u003cp\u003e(I) Binding affinity of FAM19A5 and LRRC4B(453-576)-hFC determined via ELISA.\u003c/p\u003e\n\u003cp\u003e(J) Binding affinity of FAM19A5 and LRRC4B(453-576)-hFC by SPR.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-2589038/v1/26b4b2b1d60e579f304caeed.png"},{"id":32999135,"identity":"e5d6f6fe-027c-4c5e-b9b7-879809567e59","added_by":"auto","created_at":"2023-02-15 21:37:42","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1932206,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe FB domain of LRRC4B is critical for FAM19A5-LRRC4B complex formation.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) \u003cem\u003eIn-silico\u003c/em\u003e model of LRRC4B including leucine rich repeat (LRR), immunoglobulin C (IgC), and FB (orange) domain.\u003c/p\u003e\n\u003cp\u003e(B) \u003cem\u003eIn-silico\u003c/em\u003e model of the FAM19A5-LRRC4B complex. Secondary structure of LRRC4B or FAM19A5 (grey) are represented as α-helix (red) and β-strand (cyan).\u003c/p\u003e\n\u003cp\u003e(C) Model showing the expected position of salt-bridge between side chains of E493 (orange) and K127 (cyan). Intra-FAM19A5 hydrogen-bonds are represented in magenta dashes. binding epitopes; R58, R59, R125, and K127 are key residues for interaction with the FB domain and R52, P57, R58, and R59 binds N-A5-Ab.\u003c/p\u003e\n\u003cp\u003e(D) Inhibition of complex formation by FB-20 peptides with either Ala or Asn substitutions.\u003c/p\u003e\n\u003cp\u003e(E) Binding affinity of WT and MT LRRC4B(453-576) for rcFAM19A5.\u003c/p\u003e\n\u003cp\u003e(F) Binding affinity of FAM19A5 mutants for LRRC4B(453-576).\u003c/p\u003e\n\u003cp\u003e(G) Schematic diagram of FB-containing peptides/proteins as competitors for FAM19A5-LRRC4B binding.\u003c/p\u003e\n\u003cp\u003e(H) Inhibition of FAM19A5-LRRC4B binding by WT- and MT-LRRC4B(453–576)-hFc.\u003c/p\u003e\n\u003cp\u003e(I) Inhibition of FAM19A5-LRRC4B binding by FB peptides.\u003c/p\u003e\n\u003cp\u003e(J) Immunofluorescence staining of HEK293 cells cotransfected with FAM19A5 isoform 2 (green) and FLAG-LRRC4B (blue) after treatment of WT-LRRC4B(453-576)-hFc (red). FAM19A5 signals dissociated from LRRC4B via WT-LRRC4B(453-576)-hFc (closed arrowheads). LRRC4B bound WT-LRRC4B(453-576)-hFc (open arrowheads).\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-2589038/v1/6ff16ffa6f1bc51122fdbee8.png"},{"id":33000080,"identity":"a69ddef9-bb08-446d-8f68-db24540aba16","added_by":"auto","created_at":"2023-02-15 22:01:42","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":242833,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFAM19A5 inhibits interaction between LRRC4B and PTPRF.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) Schematic diagram of FAM19A5 as a modulator for the dynamic equilibrium of PTPRF and LRRC4B interaction.\u003c/p\u003e\n\u003cp\u003e(B) Co-IP of V5-LRRC4B and FLAG-PTPRF with or without FAM19A5.\u003c/p\u003e\n\u003cp\u003e(C) Interference of WT- or MT- rcFAM19A5 for LRRC4B-PTPRF binding.\u003c/p\u003e\n\u003cp\u003e(D) Inhibition of WT- or MT- rcFAM19A5 for LRRC4B-PTPRF binding.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-2589038/v1/287e126aa6d6c3cee4e57091.png"},{"id":32999140,"identity":"7ad31b10-6b5e-4261-8e90-4fa35cd93e76","added_by":"auto","created_at":"2023-02-15 21:37:42","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1485848,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe FB decoys promote neurite outgrowth and synapse formation.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) Transcription levels of the FAM19A5 family and synapse adhesion molecules in primary hippocampal neurons at the indicated time points measured by RNA-seq (n=3).\u003c/p\u003e\n\u003cp\u003e(B) Immunofluorescence image of the neurite marker tau5 (red) and Hoechst (blue) in primary cortical neurons at 3 DIV treated with WT- or MT- LRRC4B(453–576)-hFc.\u003c/p\u003e\n\u003cp\u003e(C) Quantification of the neurite length, primary neurite number, and branching point number after treatment of NT (n=104), 6 or 60 nM of WT- (n=104/106) or MT- LRRC4B(453–576)-hFc (n=110).\u003c/p\u003e\n\u003cp\u003e(D) Immunofluorescence image of SYP (green), PSD95 (red), and Hoechst (blue) in hippocampal neurons at 7 DIV treated with 6 mM or 60 mM WT- and MT-LRRC4B(453–576)-hFc.\u003c/p\u003e\n\u003cp\u003e(E) Quantification of the intensity level of SYP and PSD95, and the number of colocalized voxels between SYP and PSD95 for experiments in \u003cstrong\u003e(D)\u003c/strong\u003e(n=10).\u003c/p\u003e\n\u003cp\u003eData are presented in Mean ± SEM. Statistical analyses were performed using Kruskal-Wallis test followed by Dunn’s multiple comparison test \u003cstrong\u003e(C)\u003c/strong\u003e; One-way ANOVA followed by Tukey’s multiple comparison test (\u003cstrong\u003eE\u003c/strong\u003e). n.s; not significant, *P \u0026lt; 0.05, ***P \u0026lt; 0.001.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-2589038/v1/3ae84ba7050e0a3f41789295.png"},{"id":32999148,"identity":"bad9ce5f-f8eb-4c60-a802-1293c116869d","added_by":"auto","created_at":"2023-02-15 21:37:42","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":946171,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eNS101 dissociates the FAM19A5-LRRC4B complex.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) FAM19A5-LRRC4B complex inhibition assay by NS101 and LRRC4B(453–576)-hFc.\u003c/p\u003e\n\u003cp\u003e(B) NS101-induced FAM19A5 secretion in HEK293 cells transfected with various combinations of LRRC4B and FAM19A5 isoforms 1 and 2 (n=6).\u003c/p\u003e\n\u003cp\u003e(C) NS101-induced FAM19A5 secretion from primary hippocampal neurons (n=10).\u003c/p\u003e\n\u003cp\u003e(D) FAM19A5 levels in CSF and plasma of mice (n=4), rats (n=6), monkeys (n=10/9), and humans (n=25/10) by ELISA.\u003c/p\u003e\n\u003cp\u003e(E) Plasma FAM19A5 and CSF NS101 levels in rats at the indicated time points after iv administration of 10 or 50 mg/kg NS101.\u003c/p\u003e\n\u003cp\u003e(F) Immunoblot of the NS101-FAM19A5 complex in rat CSF at the indicated time points after iv administration of 50 mg/kg NS101.\u003c/p\u003e\n\u003cp\u003e(G) The level of transported WT and MT FAM19A5 from the brain to the bloodstream after iv administration of 10 mg/kg NS101.\u003c/p\u003e\n\u003cp\u003e(H) Representative images showing dendrite spines of hIgG- or NS101-treated primary hippocampal neurons.\u003c/p\u003e\n\u003cp\u003e(I) Spine density of hIgG- or NS101-treated primary cultured hippocampal neurons at DIV 7 (n=20).\u003c/p\u003e\n\u003cp\u003e(J) Immunofluorescence images of mouse hippocampal neurons treated with vehicle alone (NT, n=12) or Aβ\u003csub\u003e42 \u003c/sub\u003etogether with either hIgG- (n=9) or NS101 (n=12). Neurons were labeled with SYP (green), PSD95 (red), and Hoechst (blue).\u003c/p\u003e\n\u003cp\u003e(K) The fluorescence intensity of SYP and PSD95, and the number of colocalized voxels between SYP and PSD95 for experiment in \u003cstrong\u003e(J)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eData are presented in Mean ± SEM. Statistical analyses were performed using two-way ANOVA followed by Sidak’s multiple comparison test (\u003cstrong\u003eB\u003c/strong\u003e), Unpaired t-test (\u003cstrong\u003eC, D\u003c/strong\u003e; rat and human, \u003cstrong\u003eG \u003c/strong\u003eand\u003cstrong\u003e I\u003c/strong\u003e), Mann-Whitney test (D, mouse and monkey,), One-way ANOVA followed by Tukey’s multiple comparison test (\u003cstrong\u003eK\u003c/strong\u003e; SYP), and \u0026nbsp;Kruskal-Wallis test followed by Dunn’s multiple comparison test (\u003cstrong\u003eK\u003c/strong\u003e; colocalizedvoxels/neuron and PSD95 intensity). n.s, not significant, *P \u0026lt; 0.05, **P \u0026lt; 0.01, ***P \u0026lt; 0.001.\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-2589038/v1/a34f7d12f71f5eeaf0b1af1a.png"},{"id":32999144,"identity":"95075dc9-386b-4b4f-89de-1f8623d80bb6","added_by":"auto","created_at":"2023-02-15 21:37:42","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":1987756,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eNS101 restores synaptic structural formation and transmission in AD mice.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) Correlation between CSF FAM19A5 and age (n=25). Linear or nonlinear regression coefficient values are indicated as R\u003csup\u003e2\u003c/sup\u003e.\u003cbr\u003e\n(B) Correlation between CSF tau and CSF FAM19A5 or age (n=25).\u003c/p\u003e\n\u003cp\u003e(C) Immunofluorescence images and quantification of the fluorescence intensity of SYP (green) and PSD95 (red) in the CA1 and CA3 regions. WT (n=12), APP/PS1+hIgG (n=13), APP/PS1+NS101 (n=11).\u003c/p\u003e\n\u003cp\u003e(D) Immunofluorescence images and quantification of SV2A signals in the CA1 and CA3 regions. WT (n=9), APP/PS1+hIgG (n=8), APP/PS1+NS101 (n=8).\u003cbr\u003e\n(E) Representative traces, frequencies, and amplitudes of mEPSCs from WT and APP/PS1 groups treated with hIgG- or NS101(10 or 30 mg/kg) (n=6).\u003c/p\u003e\n\u003cp\u003e(F) Representative input-output traces and fEPSP slopes plotted against fiber volley amplitudes from WT and APP/PS1 mice treated with hIgG- or NS101(10 or 30 mg/kg) (n=6).\u003c/p\u003e\n\u003cp\u003e(G)\u003cstrong\u003e \u003c/strong\u003eRepresentative traces showing the fEPSP response before (1) and after (2) theta burst stimulation and the average time course for fEPSP amplitude during LTP induction. WT (n=6), APP/PS1+hIgG (n=5), APP/PS1+NS101 10 mg/kg (n=6), APP/PS1+NS101 30 mg/kg (n=5).\u003c/p\u003e\n\u003cp\u003e(H) Post-tetanic potentiation 2 min after stimulation of experiment \u003cstrong\u003e(G)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eData are presented in Mean ± SEM. Statistical analyses were performed using One-way ANOVA followed by Tukey’s multiple comparison test (\u003cstrong\u003eC\u003c/strong\u003e,\u003cstrong\u003e D\u003c/strong\u003e; CA1, \u003cstrong\u003eE\u003c/strong\u003e, \u003cstrong\u003eF\u003c/strong\u003e, \u003cstrong\u003eG\u003c/strong\u003e, and \u003cstrong\u003eH\u003c/strong\u003e); Kruskal-Wallis test followed by Dunn’s multiple comparison test (\u003cstrong\u003eD\u003c/strong\u003e; CA3) n.s, not significant, *P \u0026lt; 0.05, **P \u0026lt; 0.01, ***P \u0026lt; 0.001.\u003c/p\u003e","description":"","filename":"Figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-2589038/v1/1e99c99fbbacff28a91aba75.png"},{"id":33000183,"identity":"09e349aa-7ee8-475b-a366-46548d42d631","added_by":"auto","created_at":"2023-02-15 22:09:42","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":296463,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eNS101 restores cognition in AD mice.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A)\u003cstrong\u003e \u003c/strong\u003eSpontaneous alternation and total arm entries in the Y-maze test of WT mice (n=12) and APP/PS1 mice treated with 10 mg/kg of hIgG (APP/PS1+hIgG, n=13) or 10 mg/kg of NS101 (APP/PS1+NS101, n=11).\u003c/p\u003e\n\u003cp\u003e(B) Acquisition and retention times in the passive avoidance test of mice in (\u003cstrong\u003eA\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e(C)\u003cstrong\u003e \u003c/strong\u003eThe latency time during learning trials of WT mice (n=10) and P301S mice treated with 10 mg/kg of hIgG (P301S+hIgG, n=12) or 10 mg/kg of NS101 (P301S+NS101, n=9).\u003cbr\u003e\n(D) Swimming trajectory of mice in (\u003cstrong\u003eC\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e(E) Behavior parameters during the test trial of mice in (\u003cstrong\u003eC\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eData are presented in Mean ± SEM. Statistical analyses were performed using one-way ANOVA followed by Tukey's \u003cstrong\u003e(A) \u003c/strong\u003eor Holm-Sidak \u003cstrong\u003e(E) \u003c/strong\u003emultiple comparisons test, repeated measures one-way ANOVA followed by Holm-Sidak multiple comparisons test \u003cstrong\u003e(C)\u003c/strong\u003e, and Kruskal-Wallis test followed by Dunn’s multiple comparison test \u003cstrong\u003e(B)\u003c/strong\u003e. n.s, not significant, *P \u0026lt; 0.05, **P \u0026lt; 0.01, ***P \u0026lt; 0.001. Unpaired t-test \u003cstrong\u003e(B)\u003c/strong\u003e. n.s, not significant, #P\u0026lt;0.05.\u003c/p\u003e","description":"","filename":"Figure7.png","url":"https://assets-eu.researchsquare.com/files/rs-2589038/v1/640e32d86585d910968a314e.png"},{"id":32999924,"identity":"558f34f8-71db-414a-8152-7b8033340684","added_by":"auto","created_at":"2023-02-15 21:53:42","extension":"jpeg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":354670,"visible":true,"origin":"","legend":"\u003cp\u003eGraphical Abstract\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-2589038/v1/3ccf69f83ba242ec3a067438.jpeg"},{"id":32999136,"identity":"bbeffc8b-69da-475e-975d-6fc2286a0018","added_by":"auto","created_at":"2023-02-15 21:37:42","extension":"png","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":263343,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure S2. The residues responsible for the binding between FAM19A5 and LRRC4B FB.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) Molecular modeling of the LRRC4B FB-FAM19A5 complex. Predicted hydrogen-bond interactions between the intra-FAM19A5 β-strand (cyan) and the LRRC4B FB domain (orange) are represented as magenta dashed lines. The FB domain constituting residues (Y484- E496, orange main chain, labelled in grey); β-strand forming FB residues (T485 - L495, labelled in black). FB binding residues constituting β-strand via forming hydrogen-bonds (labelled in orange label); residues involved in constituting intra-FAM19A5 hydrogen-bonds (labelled in marine); residues affecting binding affinity of LRRC4B FB and FAM19A5 complex, identified via Ala mutagenesis (purple labels); R125\u003csup\u003e \u003c/sup\u003eand K127; NS101 binding epitope (green main chain); R52, P57, R58, and R59; competitive binding sites for FB and NS101 (labelled in red); R58 and R59.\u003cbr\u003e\n(B) The predicted changes in binding free energy based on Ala scanning of FB.\u003cbr\u003e\n(C-D) Co-IP of FAM19A5 and LRRC4B(36-173) \u003cstrong\u003e(C)\u003c/strong\u003e or LRRC4B(453-573) \u003cstrong\u003e(D)\u003c/strong\u003e. Wild type LRRC4B(TT); mutant LRRC4B(AA, T488,489A)\u003cbr\u003e\n(E) The predicted changes in binding free energy based on Ala scanning of FAM19A5. Competitive binding sites for FB and NS101 (orange); R58 and R59. Residues affecting binding affinity between FB and FAM19A5 (pink); R125\u003csup\u003e \u003c/sup\u003eand K127.\u003cbr\u003e\n(F) Epitope mapping of NS101 for FAM19A5. Binding of NS101 to rcFAM19A5 and synthetic peptides (F1~F6 and F2 mutant peptides, see Table S1 and S2). The aa residues are numbered according to the human FAM19A5 sequence.\u003c/p\u003e","description":"","filename":"FigureS2.png","url":"https://assets-eu.researchsquare.com/files/rs-2589038/v1/59fc736ff7a5a7facb9108fd.png"},{"id":32999762,"identity":"ead5fd3c-850e-43aa-9672-eb4a284921d7","added_by":"auto","created_at":"2023-02-15 21:45:42","extension":"png","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":311758,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure S3. FAM19A5 inhibits neurite growth and synapse formation.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) Immunofluorescence images of mouse hippocampal neurons treated with vehicle alone (NT) or 6.6 μM rcFAM19A5 at 3 DIV.\u003c/p\u003e\n\u003cp\u003e(B) Quantification of the average total neurite length, number of primary neurites, and number of branching points for experiments in (A). NT (n=72), rcFAM19A5 (n=76).\u003cbr\u003e\n(C)\u003cstrong\u003e \u003c/strong\u003eThe fluorescence intensity of SYP and PSD95 and the number of colocalized voxels between SYP and PSD95 after treatment with 6.6μM rcFAM19A5.NT (n=15), rcFAM19A5 (n=14).\u003c/p\u003e\n\u003cp\u003eData are presented in Mean ± SEM. Statistical analyses were performed using unpaired t-test (\u003cstrong\u003eB\u003c/strong\u003e and \u003cstrong\u003eC\u003c/strong\u003e). n.s, not significant, *P \u0026lt; 0.05, **P \u0026lt; 0.01, ***P \u0026lt; 0.001.\u003c/p\u003e","description":"","filename":"FigureS3.png","url":"https://assets-eu.researchsquare.com/files/rs-2589038/v1/03aba777826bf1bb25726277.png"},{"id":32999765,"identity":"704382c3-5508-4b1c-bff2-a573f79ccf8f","added_by":"auto","created_at":"2023-02-15 21:45:42","extension":"png","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":595462,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure S4. NS101 dissociates FAM19A5 from LRRC4B.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A)\u003cstrong\u003e \u003c/strong\u003eThe inhibition of FAM19A5-LRRC4B binding by NS101. HEK293 cells expressing FLAG-tagged LRRC4B were treated with rcFAM19A5 (1 μg/ml) and increasing concentrations of NS101.\u003cbr\u003e\n(B) Concentration-dependent FAM19A5 release after treatment of NS101 in HEK293 cells expressing LRRC4B and FAM19A5 isoform 1.\u003c/p\u003e\n\u003cp\u003e(C) Immunofluorescence images of HEK293 cells expressing FLAG-LRRC4B (blue) and FAM19A5 isoform 2 (green) after treatment with hIgG or NS101. FAM19A5 signals were dissociated from LRRC4B by NS101 treatment (arrowheads).\u003c/p\u003e","description":"","filename":"FigureS4.png","url":"https://assets-eu.researchsquare.com/files/rs-2589038/v1/e5f65fdf57d8aecb4712c4ba.png"},{"id":32999926,"identity":"5a944d15-c150-43b5-940a-0783a9472121","added_by":"auto","created_at":"2023-02-15 21:53:42","extension":"png","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":312468,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure S5. NS101 forms a complex with FAM19A5.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) Immunoblot analysis of FAM19A5 protein in the CSF of WT and FAM19A5 KO mice.\u003c/p\u003e\n\u003cp\u003e(B)\u003cstrong\u003e \u003c/strong\u003eFAM19A5 levels in the CSF and plasma of WT and FAM19A5 KO mice. WT CSF (n=7), KO CSF (n=6), WT plasma (n=7), KO plasma (n=6).\u003c/p\u003e\n\u003cp\u003e(C) Plasma NS101 levels at the indicated time points after iv administration of 10 mg/kg and 50 mg/kg NS101.\u003cbr\u003e\n(D) FAM19A5 band shift induced by the crosslinker. The purple arrow indicates the band for rcFAM19A5 without crosslinker, and the green arrow indicates the FAM19A5-NS101 complex.\u003cbr\u003e\n(E) Binding affinity of WT and MT FAM19A5(R58A, R59A) for NS101, LRRC4B, and C-A5-Ab.\u003c/p\u003e\n\u003cp\u003eData are presented in Mean ± SEM. Statistical analyses were performed using unpaired t-test. ***P \u0026lt; 0.001.\u003c/p\u003e","description":"","filename":"FigureS5.png","url":"https://assets-eu.researchsquare.com/files/rs-2589038/v1/642814321fc68a21d7572ab9.png"},{"id":33000081,"identity":"f0cbfd4c-efe7-4c63-a858-b114e59cdf09","added_by":"auto","created_at":"2023-02-15 22:01:42","extension":"png","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":2190658,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure S6. NS101 promotes neurite outgrowth.\u003cbr\u003e\n\u003c/strong\u003e(A) Immunofluorescence images of mouse hippocampal neurons treated with 1 μg/ml hIgG or 1, 10, 100, and 1000 ng/ml NS101.\u003cbr\u003e\n(B) Quantification of the average total neurite length, number of primary neurites, and number of branching points for experiments in (\u003cstrong\u003eA\u003c/strong\u003e) NT (n=105), hIgG 1000 ng/ml (n=101), NS101 1 ng/ml (n=111); NS101 10 ng/ml (n=111), NS101 100 ng/ml (n=104), NS101 1000 ng/ml (n=100).\u003c/p\u003e\n\u003cp\u003e(C) Immunofluorescence images of 1000 ng/ml hIgG- or NS101-treated mouse cortical neurons labeled with SYP (green), PSD95 (red), and Hoechst (blue).\u003c/p\u003e\n\u003cp\u003e(D) The fluorescence intensity of PSD95 and SYP, and the number of colocalized voxels between SYP and PSD95 for experiment in (\u003cstrong\u003eC\u003c/strong\u003e) (n=10).\u003c/p\u003e\n\u003cp\u003eData are presented in Mean ± SEM. Statistical analyses were performed using one-way ANOVA followed by Tukey's multiple comparisons test (\u003cstrong\u003eB\u003c/strong\u003e; neurite length), Kruskal-Wallis test followed by Dunn’s multiple comparison test (\u003cstrong\u003eB\u003c/strong\u003e; number of neurite and branching points), and Unpaired t-test \u003cstrong\u003e(D)\u003c/strong\u003e. **P \u0026lt; 0.01, ***P \u0026lt; 0.001.\u003c/p\u003e","description":"","filename":"FigureS6.png","url":"https://assets-eu.researchsquare.com/files/rs-2589038/v1/57935f28a89692653556377a.png"},{"id":33000182,"identity":"434535b7-23c1-4f88-9863-74beecfd0677","added_by":"auto","created_at":"2023-02-15 22:09:42","extension":"png","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":35936,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure S7. NS101 iv administration induces the release of FAM19A5 from the brain into the blood in AD mouse models.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A-C)\u003cstrong\u003e \u003c/strong\u003eThe plasma levels of FAM19A5 in three AD mouse models were measured after iv administration of NS101. All mice received a dose of 0.05 mg/kg of NS101, and one day later, half of them received an additional dose of 10 mg/kg of NS101, while the other half received no further treatment. FAM19A5 levels in the plasma were then measured using ELISA. n=3 for all groups except n=1 for APP/PS1 mice treated with 0.05 mg/kg only.\u003c/p\u003e\n\u003cp\u003eData are presented in Mean ± SEM. Statistical analyses were performed using one-way ANOVA followed by Tukey's multiple comparisons test. n.s, not significant, *P \u0026lt; 0.05, ***P \u0026lt; 0.001.\u003c/p\u003e","description":"","filename":"FigureS7.png","url":"https://assets-eu.researchsquare.com/files/rs-2589038/v1/46ead95667fbd681574f8ca1.png"},{"id":33000084,"identity":"a83f63ca-f19c-4ba0-b60b-5c84dae8be03","added_by":"auto","created_at":"2023-02-15 22:01:42","extension":"png","order_by":9,"title":"","display":"","copyAsset":false,"role":"supplement","size":619146,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure S8. Morris water maze assessment of APP/PS1 mice treated with NS101.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A-B)\u003cstrong\u003e \u003c/strong\u003eThe escape latency time during the training trials of WT mice (n=12) and APP/PS1 mice treated with 10 mg/kg hIgG (APP/PS1+hIgG, n=13), or NS101 (APP/PS1+NS101, n=10).\u003c/p\u003e\n\u003cp\u003e(C) Swimming trajectory of mice.\u003cbr\u003e\n(D) Behavior parameters during the test trial.\u003c/p\u003e\n\u003cp\u003eData are presented in Mean ± SEM. Statistical analyses were performed using one-way ANOVA followed by Tukey's multiple comparisons test. n.s, not significant, *P \u0026lt; 0.05, **P \u0026lt; 0.01, ***P \u0026lt; 0.001.\u003c/p\u003e","description":"","filename":"FigureS8.png","url":"https://assets-eu.researchsquare.com/files/rs-2589038/v1/b762d4b90437a0b9c41fc338.png"},{"id":32999151,"identity":"0b170b09-35b0-421f-9aae-d3ec23848793","added_by":"auto","created_at":"2023-02-15 21:37:42","extension":"png","order_by":10,"title":"","display":"","copyAsset":false,"role":"supplement","size":1506528,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure S9. NS101 ameliorates synapse loss in P301S mice.\u003cbr\u003e\n\u003c/strong\u003e(A-B) Immunofluorescence images and quantification of the fluorescence intensity of SYP (green) and PSD95 (red) in the CA1 and CA3 regions of WT mice (n=6) and P301S mice treated with 10 mg/kg hIgG (P301S+hIgG, n=4), or NS101 (P301S+NS101, n=6).\u003c/p\u003e\n\u003cp\u003eData are presented in Mean ± SEM. Statistical analyses were performed using one-way ANOVA followed by Tukey's multiple comparisons test. *P \u0026lt; 0.05, **P \u0026lt; 0.01.\u003c/p\u003e","description":"","filename":"FigureS9.png","url":"https://assets-eu.researchsquare.com/files/rs-2589038/v1/445f93091a85a4a04abbb2b7.png"},{"id":32999769,"identity":"fdbc75a2-ab21-42c8-af53-9bd1d50cda27","added_by":"auto","created_at":"2023-02-15 21:45:42","extension":"docx","order_by":11,"title":"","display":"","copyAsset":false,"role":"supplement","size":21464,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTables.docx","url":"https://assets-eu.researchsquare.com/files/rs-2589038/v1/fa3b6c8bfd69ec49dd740467.docx"}],"financialInterests":"","formattedTitle":"\u003cp\u003eBlocking the FAM19A5-LRRC4B complex enhances neurite growth and synapse assembly.\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSynapses are specialized adhesive junctions that allow neurons to transmit and process information by connecting to various neural circuits in the brain. The number of synapses in the brain changes throughout life as a result of a dynamic process of synapse build-up and removal.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e This process is known as synaptic plasticity and is essential for the normal development and function of the brain.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e The increase in synapse numbers is essential for the formation of new neural connections and the establishment of functional neural circuits. However, as the brain matures, a process of synaptic pruning begins, where unnecessary or under-used synapses are selectively removed.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Synaptic pruning continues throughout life and can be influenced by a range of factors including experience, hormones, and microenvironment surrounding neurons.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e The number of synapses decreases as people age.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e This decline in synapse numbers is thought to contribute to age-related cognitive decline and the increased risk of neurodegenerative disorders such as Alzheimer's disease (AD).\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e Therefore, the dynamic nature of synapse numbers in the brain is essential for its normal development, function, and adaptation to changes in the environment. Abnormalities in this process can lead to a range of neurological and psychiatric disorders,\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e and as such, understanding the regulation of synapse build-and-removal dynamics may guide the development of effective therapeutic strategies for treating neurological and neurodegenerative diseases.\u003c/p\u003e \u003cp\u003eSynaptic adhesion molecules participate in regulating synapse numbers via molecular processes, including formation, maturation, and continuous reorganization.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e The role of synaptic adhesion molecules extends beyond just adhesive contacts between membranes, as they play a critical role in organizing synapses, preserving their functional integrity, and facilitating changes to pre-existing synapse.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e The leucine-rich repeat-containing 4s (LRRC4s, also known as Netrin-G ligands, NGLs), are a family of three postsynaptic adhesion molecules: LRRC4, LRRC4B, and LRRC4C.\u003csup\u003e\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e The LRRC4 members share similar structures, including leucine-rich repeat (LRR) domains flanking LRR N-terminus and C-terminus, an immunoglobulin-like C2-type (IgC) domain, a transmembrane domain, and a postsynaptic density-binding (PB) domain. LRRC4B can form excitatory synapses by transsynaptic interacting with presynaptic protein tyrosine phosphatase receptors (PTPR-F, -D, and -S), also known as LAR-RPTPs.\u003csup\u003e\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e It also, via its PDZ-binding domain, binds to the postsynaptic scaffolding protein postsynaptic density-95 (PSD-95) and promotes clustering of NMDA and AMPAR receptors at the postsynaptic site.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Thus, LRRC4B plays a crucial role in various stages of excitatory synapse formation and function, such as inducing the initial transsynaptic connection between axon and dendrite, clustering postsynaptic proteins, and controlling synaptic plasticity.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e This is evidenced by \u003cem\u003eLrrc4b\u003c/em\u003e knockout (KO) mice that exhibited major impairments in brain development, synaptic transmission, and plasticity, which are accompanied by behavioral hyperactivity and reduced cognitive function.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e However, the exact mechanism by which LRRC4B regulates synapse dynamics is yet to be understood. Additionally, it is possible that LRRC4B interacts with other unknown proteins that regulates dynamic synapse formation and disassembly, besides the known LRRC4B-interacting proteins.\u003c/p\u003e \u003cp\u003eThe family with sequence similarity 19 member A (FAM19A, also known as TAFA) family consists of five paralogous members that encode small, secreted proteins.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e These proteins are predominantly expressed in the central nervous system.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e The amino acid (aa) sequence of the secreted FAM19A5 domain is highly conserved across vertebrate species, suggesting a physiologically relevant function in vertebrates.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e FAM19A5 transcripts are abundant in the brain but less so in peripheral tissues.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e Recent advances in single-cell RNA-seq (scRNA-seq) analysis of mouse brain tissue have provided more detailed expression pattern of \u003cem\u003eFam19a5\u003c/em\u003e transcripts,\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e showing that \u003cem\u003eFam19a5\u003c/em\u003e transcripts are mainly found in excitatory and inhibitory neurons in various regions including layers 2/3 and 5 of the cortex and in the CA1 and CA3 regions of the hippocampus.\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eA recent study showed that FAM19As, other than FAM19A5, interact with the neurexins,\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e which play a role in synaptic adhesion. This suggests that FAM19A5, similar to its relatives, may act as a ligand for other synaptic adhesion molecules and be involved in synapse formation and function, thereby impacting nervous system function. This is supported by finding from \u003cem\u003eFam19a5\u003c/em\u003e KO mice, which exhibited hyperactivity, depressive-like behaviors, and reduced spatial learning and memory, as well as a decrease in dendritic spine density, glutamate signaling, and neuronal activity.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e Recent genome-wide association studies have revealed the association of FAM19A5 with neurological disorders including AD, attention deficit hyperactivity disorder, and autism.\u003csup\u003e\u003cspan additionalcitationids=\"CR29\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e Furthermore, a recent single-nucleus RNA-seq (snRNA-seq) in human AD brain samples showed that FAM19A5 transcript levels in neurons were higher in those with early AD pathology compared to those without.\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e This result aligns with human serum assay results,\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e which showed increased FAM19A5 levels in patients with vascular dementia compared to controls, suggesting a potential contribution of FAM19A5 to the progression of AD pathology. However, exact role of FAM19A5 function in pathophysiological condition remains elusive due to limited research on its interacting partner proteins. Previous studies proposed that FAM19A5 may interact with N-formyl peptide receptor 2 or sphingosine 1-phosphate receptor 2,\u003csup\u003e\u003cspan additionalcitationids=\"CR34\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e but our recent study refutes these claims.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn the present study, we found that LRRC4B interacts with FAM19A5 with high affinity. FAM19A5 binds to a core domain within LRRC4B, hereafter referred to as FAM19A5 binding (FB) domain. Decoy peptides or proteins containing the FB domain (FB decoy) can capture FAM19A5 and disrupt the endogenous FAM19A5-LRRC4B complex. Both the FB decoys and an anti-FAM19A5 antibody called NS101\u003csup\u003e36\u003c/sup\u003e induced neurite outgrowth and synapse formation in mouse primary neurons. This led us to propose that FAM19A5 regulates neurite growth and synapse formation as a suppressor, by forming the FAM19A5-LRRC4B complex. Given that the FAM19A5-LRRC4B complex hinders new synapse formation, it may serve as a target for treating synapse loss in AD. In mouse models of AD, treatment with NS101 facilitated transport of FAM19A5 from the brain into the blood, which may reduce the level of the FAM19A5-LRRC4B complex in the brain. This resulted in increased synaptic density, function, and plasticity in the hippocampus, as well as improved cognitive ability in the AD mice. Our findings suggest that blocking the formation of the FAM19A5-LRRC4B complex could be a promising therapeutic strategy for AD.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cb\u003eFAM19A5 binds to LRRC4B via the FB domain.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eTo uncover potential binding partners for FAM19A5, we searched the mouse brain scRNA-seq database (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://mousebrain.org\u003c/span\u003e\u003cspan address=\"http://mousebrain.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e)\u003csup\u003e25\u003c/sup\u003e and found synapse adhesion molecules whose transcript levels showed strong correlation with \u003cem\u003eFam19a5\u003c/em\u003e transcript levels across 168 different types of neurons (Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA and S1A). Notably, the expression of \u003cem\u003eLrrc4b\u003c/em\u003e was found to be highly correlated with \u003cem\u003eFam19a5\u003c/em\u003e transcripts (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA), raising a possible interaction between FAM19A5 and LRRC4B. To access this possibility, we performed coimmunoprecipitation (co-IP) assays using various anti-FAM19A5 antibodies that target the N-terminal (N-A5-Ab) and C-terminal (C-A5-Ab) regions of FAM19A5.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e V5-tagged LRRC4B transfected into HEK293 cells, treated with recombinant FAM19A5 (rcFAM19A5), was coimmunoprecipitated with C-A5-Ab (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB) and vice versa (Figure S1B). Two \u003cem\u003eFAM19A5\u003c/em\u003e transcripts, isoform 1 and isoform 2, produce two FAM19A5 isoform proteins that differ in their N-terminal sequences.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e To assess the interactions between the FAM19A5 isoforms and LRRC4B, we cotransfected HEK293 cells with cDNA encoding the FLAG-tagged LRRC4B protein and either FAM19A5 isoform 1 or isoform 2. Immunofluorescence revealed that both FAM19A5 isoforms colocalized strongly with LRRC4B (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). Similarly, immunoprecipitates of LRRC4B from cell lysates using an anti-FLAG antibody also included both FAM19A5 isoforms (Figure S1C), and immunoprecipitates using C-A5-Ab showed interactions between LRRC4B and both FAM19A5 isoforms (Figure S1D). However, the anti-FAM19A5 antibody N-A5-Ab only weakly coimmunoprecipitated LRRC4B, as an epitope of FAM19A5 recognized by N-A5-Ab is involved in LRRC4B binding. LRRC4B can be released into the culture medium by cleavage at the juxta-membrane region (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD).\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e When FAM19A5 isoform 1 was coexpressed with LRRC4B, there was less FAM19A5 in the culture medium, and more was retained in the cell (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD), indicating that LRRC4B traps soluble FAM19A5 in the plasma membrane.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eLRRC4B expressed in neurons can be secreted into the cerebrospinal fluid (CSF) of humans where FAM19A5 is also found.\u003csup\u003e\u003cspan additionalcitationids=\"CR38\" citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e Therefore, the FAM19A5-LRRC4B complex may be present in the CSF, as seen in immunoblots of human CSF showing both FAM19A5 and LRRC4B (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eE). In addition, rcFAM19A5-treated primary cortical neurons showed FAM19A5 localization to neurites where LRRC4B is highly expressed (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eF).\u003c/p\u003e \u003cp\u003eTo identify FAM19A5-binding sequences in LRRC4B, various FLAG-tagged deletion constructs for LRRC4B were generated (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eG). HEK293 cells expressing these deletion constructs were treated with rcFAM19A5, and the cell lysates were coimmunoprecipitated with an anti-FLAG antibody. We found that all constructs containing the 484\u0026ndash;498 aa sequence of LRRC4B were able to bind to FAM19A5, whereas deletion of the 484\u0026ndash;498 aa sequence abolished FAM19A5 binding (Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eG and S1E). Since this 484\u0026ndash;498 sequence is highly conserved among LRRC4 family members in mammals (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eH), we designated this core sequence as the FAM19A5 binding (FB) domain. An enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) revealed that LRRC4B(453\u0026ndash;576) conjugated with human Fc [hereafter, LRRC4B(453\u0026ndash;576)-hFc] demonstrated\u0026thinsp;~\u0026thinsp;100 picomolar affinity by ELISA (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eI) and ~\u0026thinsp;30 picomolar affinity for FAM19A5 by SPR (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eJ). FB peptides inhibited binding between FAM19A5 and LRRC4B(453\u0026ndash;576)-hFc/LRRC4B(36\u0026ndash;576)-hFc in a competitive manner. However, peptides lacking one or more aa from the FB domain (positions 484\u0026ndash;498) gradually lose their ability to inhibit the FAM19A5-LRRC4B interaction (Figure S1F).\u003c/p\u003e \u003cp\u003eRecent advances in deep learning methods allow the construction of structures for the protein complexes. Using combination of AlphaFold2\u003csup\u003e40\u003c/sup\u003e and RoseTTAFold\u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e,\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e, we modeled the structure of the FAM19A5-LRRC4B complex (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA-C and S2A), showing that the FB sequence from Tyr484 to Glu496 of LRRC4B directly interacted with FAM19A5. In particular, the sequence of FB, which had a disordered structure before binding to FAM19A5 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA), became a β-strand constituting a β-sheet structure together with β-strands formed from FAM19A5 (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB and \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC). Then, we further identified the residues responsible for the interaction between FAM19A5 and FB via in silico Ala scanning where each non-Ala residue of the complex was replaced to Ala using Schrodinger Bioluminate\u0026reg;. This calculates changes in protein-peptide binding affinity based on a large increase in the binding free energy following the Ala mutation (Figure S2B). For FB, Ala substitution for residues that actively participate in β-sheet formation with FAM19A5 increased the binding free energy, which means weakened binding, except for Thr494 and Leu495 in FB. These two residues are unlikely to contribute significantly to the interaction, consistent with the biochemical results (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD). Besides residues participating in β-sheet formation, residues from Glu496 to Pro499 are likely involved in interaction with FAM19A5 as substitution of residues to Ala increased the binding free energy (Figure S2B). Full-length LRRC4B(36\u0026ndash;716) and LRRC4B(453\u0026ndash;576) fragments in which Thr488 and Thr489 were substituted with Ala showed a very weak binding to FAM19A5 by a co-IP assay (Figures S2C and S2D) and ELISA (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eE).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFor FAM19A5, the basic residues Arg58, Arg59, Arg125, and Lys127 were found to be involved in the interaction with the FB domain via \u003cem\u003ein silico\u003c/em\u003e Ala scanning (Figure S2E). These four residues from FAM19A5 participate in b-sheet formation through hydrogen bond interactions with the b-strand formed in the FB domain (Figure S2A). Furthermore, anionic carboxylate (RCOO\u0026minus;) of Glu493 of LRRC4B and the cationic ammonium (RNH3+) from Lys127 can form salt-bridge (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC). Indeed, a double mutation substituting Ala for Arg125 and Lys127 of FAM19A5 reduced the binding affinity to LRRC4B. Arg58 and Arg59 may also play role in the interaction with FB, as their Ala substitution reduced affinity to LRRC4B and quadruple mutations of Arg58, Arg59, Arg125, and Lys127 further reduced the binding affinity to LRRC4B (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eF). In particular, N-A5-Ab epitope mapping via Ala mutation indicated that Arg52, Pro57, Arg58, and Arg59 of FAM19A5 were found to be epitopes for N-A5-Ab (Figure S2F); thus, N-A5-Ab and LRRC4B partly compete at Arg58 and Arg59 for FAM19A5 binding (Figures S2A and S2F).\u003c/p\u003e \u003cp\u003eBecause FB-containing peptides/proteins bound to FAM19A5 with high affinity, we determined whether they compete with LRRC4B to dissociate the FAM19A5-LRRC4B complex (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eG). The cell-free ELISA revealed that WT LRRC4B(453\u0026ndash;576)-hFc (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eH) and FB-containing peptides (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eI) resulted in a dose-dependent decrease in the binding between FAM19A5 and LRRC4B. However, the mutant (MT) peptide in which Ala was substituted for Thr488 and Thr489 in MT LRRC4B(453\u0026ndash;576)-hFc only slightly inhibited binding (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eH). Treatment with WT LRRC4B(453\u0026ndash;576)-hFc for 30 min caused a substantial dissociation of FAM19A5 from full-length LRRC4B in HEK293 cells expressing both FAM19A5 isoform 2 and LRRC4B (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eJ). In contrast, in HEK293 cells treated with MT LRRC4B(453\u0026ndash;576)-hFc, FAM19A5 remained largely bound to LRRC4B (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eJ), suggesting that FB-containing peptides and proteins can act as a decoy to steer FAM19A5 away from the complex.\u003c/p\u003e \u003cp\u003e \u003cb\u003eFAM19A5 inhibits interaction between LRRC4B and PTPRF via the FB domain.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eWe then examined the role of FAM19A5 in regulating LRRC4B function. LRRC4B is known to interact physically with the presynaptic protein PTPRF, facilitating synapse formation between neurons.\u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e Hence, it is likely that alterations in FAM19A5 levels during synapse formation or elimination can affect the dynamic equilibrium of LRRC4B and PTPRF interaction (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA). To assess the impact of FAM19A5 on this interaction, we transfected HEK293 cells with FLAG-tagged PTPRF and V5-tagged LRRC4B cDNAs and treated the cells with rcFAM19A5. The binding between LRRC4B and PTPRF was examined through immunoprecipitation with anti-V5 antibody and revealed a dose-dependent decrease in interaction upon FAM19A5 treatment (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB). This result was further confirmed using an ELISA. PTPRF(30-1263)-hFc bound to HIS-TEV-LRRC4B(36\u0026ndash;576) in a dose-dependent manner. Preincubation of LRRC4B-coated plate with 1 \u0026micro;M WT rcFAM19A5 significantly reduced the binding, whereas the binding was not inhibited by a MT FAM19A5(R58A, R59A, R125A, K127A) that weakly binds to the FB domain (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eF and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC). Increasing doses of WT rcFAM19A5 competitively inhibited the binding, but MT rcFAM19A5 was less effective in doing so (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eD). These findings suggest that FAM19A5 suppresses synapse dynamics through its interaction with LRRC4B, potentially slowing synapse formation or promoting synapse disassembly. Therefore, the FB decoys can play a positive role in synapse dynamics by redirecting FAM19A5 away from the FAM19A5-LRRC4B complex.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eFB decoys promote neurite growth and synapse formation.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eWe addressed the effect of the FB decoy in neuronal cells. We first measured transcript levels of various synapse-related genes including \u003cem\u003eFam19a5\u003c/em\u003e, \u003cem\u003eLrrc4b\u003c/em\u003e, and \u003cem\u003ePtprf\u003c/em\u003e in cultured neurons by RNA-seq.\u0026nbsp;\u003cem\u003eFam19a5\u003c/em\u003e transcript levels in the mouse hippocampal neurons were already high at day \u003cem\u003ein vitro\u003c/em\u003e 1 (DIV 1) compared to those of other \u003cem\u003eFam19a\u003c/em\u003e family members (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA). \u003cem\u003eLrrc4b\u003c/em\u003e and \u003cem\u003ePtprf\u003c/em\u003e transcripts were also notably high in hippocampal neurons at DIV 1 compared to other synaptic molecules, and the \u003cem\u003eLrrc4b\u003c/em\u003e transcript level remained high until DIV 16 (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA). High expression levels of \u003cem\u003eFam19a5, Lrrc4b\u003c/em\u003e, and \u003cem\u003ePtprf\u003c/em\u003e in early stages of cultured neurons suggest their involvement in neurite outgrowth and synaptogenesis, potentially via formation of the FAM19A5-LRRC4B complex. Therefore, we studied the impact of the FB decoy LRRC4B(453\u0026ndash;576)-hFc on neurite and synapse development in cultured neurons. Treatment with WT LRRC4B(453\u0026ndash;576)-hFc led to a dose-dependent increase in neurite length and number of primary neurites and branching points in primary cortical neurons (Figs.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB and \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eC). In contrast, treatment with MT LRRC4B(453\u0026ndash;576)-hFc had no impact on neurite growth and was comparable to the control group (Figs.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB and \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eC). It is shown that the addition of FAM19A5 to primary culture neurons caused to a significant decrease in the length of neurites and number of primary neurites (Figure S3A and S3B). Furthermore, it also decreased the number of puncta colabled for the presynaptic marker synaptophysin (SYP) and the postsynaptic marker postsynaptic density 95 (PSD95) (Figure S3C). These results suggest that FAM19A5, through the formation of the FAM19A5-LRRC4B complex, may function as a suppressor of neurite growth and synapse formation.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eNeurites grow and differentiate into dendrites or axons which eventually form a synapse.\u003csup\u003e\u003cspan additionalcitationids=\"CR45\" citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e Therefore, we determined whether disruption of the FAM19A5-LRRC4B complex promoted synapse formation. The addition of WT LRRC4B(453\u0026ndash;576)-hFc, but not MT LRRC4B(453\u0026ndash;576)-hFc, increased the intensities of SYP and PSD95 (Figs.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eD and \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eE). In addition, the number of SYP and PSD95 colocalized puncta, indicative of pre- and postsynaptic connections,\u003csup\u003e\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u003c/sup\u003e increased in response to WT LRRC4B(453\u0026ndash;576)-hFc (Figs.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eD and \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eE). Together, these results suggest that the FB decoys, by disrupting the FAM19A5-LRRC4B complex, promote the neural development process from neurite growth to the formation of initial contacts between dendrites and axons.\u003c/p\u003e \u003cp\u003e \u003cb\u003eNS101, the anti-FAM19A5 antibody, enhances synapse formation.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eAntibody therapeutics have high specificity and affinity for their targets and offer a unique advantage over peptides and Fc-conjugated proteins with their prolonged half-life in the blood,\u003csup\u003e\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e thereby providing more opportunities for the drug to reach the brain with a single systemic administration. Therefore, we developed NS101, an optimized anti-FAM19A5 antibody derived from N-A5-Ab. NS101 was more potent than WT LRRC4B(453\u0026ndash;576)-hFc in blocking FAM19A5-LRRC4B complex formation (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA), and its ability to dissociate the FAM19A5-LRRC4B complex was corroborated by a co-IP assay using HEK293 cells expressing FLAG-tagged LRRC4B treated with rcFAM19A5 in the presence of NS101 (Figure S4A). NS101 significantly increased the release of FAM19A5 into the culture medium from HEK293 cells cotransfected with LRRC4B and FAM19A5 isoform 1 or 2 but not from cells transfected only with FAM19A5 in a time- and dose- dependent manner (Figs.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eB and S4B). Considering that most of FAM19A5 isoform 1 was captured by LRRC4B in the plasma membrane (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD), NS101 can release FAM19A5 into the medium through dissociation of the FAM19A5-LRRC4B complex. NS101 separated FAM19A5 isoform 2 from LRRC4B in living cells (Figure S4C). Additionally, NS101 increased the release of endogenous FAM19A5 into the culture medium from primary hippocampal neurons (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eC).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eWe evaluated the ability of systemically administered NS101 to capture FAM19A5 proteins in the brain and transport them to the peripheral circulation. We measured the baseline levels of FAM19A5 in blood and CSF of mice, rats, monkeys, and humans, and found that FAM19A5 concentrations were lower in plasma compared to CSF in all species (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eD). This was confirmed using samples from FAM19A5 KO mice (Figures S5A and S5B). Following a single intravenous (iv) administration of NS101 in rats, the plasma FAM19A5 levels promptly increased, reaching the highest point at 24\u0026ndash;36 hours and declining gradually over the next 28 days (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eE). An increased dose of NS101 led to higher plasma FAM19A5 levels (Figure S5C). The peak time and overall change in concentrations of both CSF NS101 and plasma FAM19A5 were comparable after iv administration of NS101 (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eE). This correlation indicates that the increase in plasma FAM19A5 levels was likely due to action of NS101 in the brain and CSF. To visualize the NS101-FAM19A5 complex, we used disuccinimidyl glutarate to irreversibly crosslink proteins in CSF samples and detected them in immunoblots using N-A5-Ab. The NS101-FAM19A5 complex was found to be greater than 250 kDa in size, while the FAM19A5 protein bands were 12 and 15 kDa (Figure S5D). The formation of the complex in the CSF started immediately after an iv administration of NS101, peaked at 24 hours, and gradually decreased until 672 hours (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eF). This shows a correlation between the formation of the complex and the residual concentration of NS101 in the CSF. We then further traced the FAM19A5 migration \u003cem\u003ein vivo\u003c/em\u003e using a version of FAM19A5 in which Ala was substituted for Arg58 and Arg59 [FAM19A5(R58A, R59A)] that binds poorly to NS101, but strongly to LRRC4B (Figure S5E). The WT and MT FAM19A5 were intracranially injected to the mouse brain and NS101 was administered iv one day later. Plasma FAM19A5 levels were significantly higher in WT FAM19A5-treated mice than in the sham group (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eG). However, plasma FAM19A5 levels were not significantly different between FAM19A5(R58A, R59A)-treated and sham groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eG). Therefore, it is likely that NS101 dissociates FAM19A5 from LRRC4B, forms an NS101-FAM19A5 complex in the brain, and migrates to the CSF, where the complex drains into the peripheral blood.\u003c/p\u003e \u003cp\u003eWe then examined the effects of NS101 on neurite outgrowth and synapse formation. NS101 significantly promoted neurite growth in terms of length, primary neurite number, and branching point number of cultured neurons at DIV 3 compared to untreated or control human immunoglobulin G (hIgG)-treated neurons (Figures S6A and S6B). At DIV 7, the contribution of NS101 to synapse formation was revealed by the high immunoreactivity of SYP and PSD95 and the increased number of SYP/PSD95 colocalized puncta (Figures S6C and S6D). To determine if NS101 is also involved in structural changes at the synapse, and not just a secondary effect of increased neurite growth, we calculated the number of spines per unit length of dendrites (i.e., spine density) using the classic DiI staining method to visualize dendritic spines.\u003csup\u003e\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e\u003c/sup\u003e Our findings showed a significant increase in spine density after NS101 treatment (Figs.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eH and \u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eI), indicating that NS101 contributes to synaptic connectivity through both guiding neurite formation and promoting synapse formation. We then tested if NS101 could enhance synaptic connectivity under pathological conditions where Aβ\u003csub\u003e1\u0026ndash;42\u003c/sub\u003e oligomers reduce synaptic connections between neurons in vitro.\u003csup\u003e\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u003c/sup\u003e To do this, NS101 was treated to mouse hippocampal neurons treated with Aβ\u003csub\u003e1\u0026ndash;42\u003c/sub\u003e oligomers at DIV 15 and DIV 18. Immunohistochemistry using SYP and PSD95 antibodies showed that Aβ\u003csub\u003e1\u0026ndash;42\u003c/sub\u003e significantly reduced the number of synapses, however, the addition of NS101 prevented this reduction, particularly the number of puncta that were colabeled by SYP and PSD95 (Figs.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eJ and \u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eK).\u003c/p\u003e \u003cp\u003e \u003cb\u003eNS101 restores synapse number, function, and plasticity in the hippocampus in AD mouse models.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eTreatment of hippocampal neurons with rcFAM19A5 reduced neurite growth and synapse formation (Figure S3), raising a possibility that FAM19A5 can serve as a risk factor for neurodegenerative diseases. To further explore this idea, we measured FAM19A5 levels in human CSFs and found a high correlation with age (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eA) and with total tau (t-tau) and phosphorylated tau (p-tau) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eB). Given that t-tau and p-tau levels are closely associated with synapse pathology,\u003csup\u003e\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e we investigated the effect of NS101 in mouse models of AD. AD is characterized by the loss of synapses outpacing the acquisition of new synapses, which is can be attributed to external environmental factors and/or internal neuronal factors.\u003csup\u003e8,52\u0026minus;54\u003c/sup\u003e A recent article emphasized the significance of restoring synapse function in the amyloidopathy mouse model, even without removing amyloid β (Aβ). The study showed that using a synthetic synaptic organizer that physically connects presynapses and postsynapses can help restore neural circuits and cognitive function in an AD animal model.\u003csup\u003e\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e\u003c/sup\u003e This study also supports the notion that blocking a synaptic suppressor like FAM19A5 can help to restore neural circuits in AD patients.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAs seen in rat models (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eE), the systemic iv administration of NS101 to AD mouse models led to the release of FAM19A5 from the brain into the blood (Figure S7), suggesting a reduction in the FAM19A5-LRRC4B complex in the brain. In the AD-relevant APP/PS1 murine model of amyloidopathy,\u003csup\u003e\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e,\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e\u003c/sup\u003e there was a significant reduction in SYP immunoreactivities in both CA1 and CA3 of the hippocampus compared to WT mice (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eC). PSD95 immunoreactivity was markedly reduced in CA1 but less so in CA3. NS101 treatment of APP/PS1 mice restored SYP and PSD95 immunoreactivity to WT levels (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eC). Similarly, NS101 significantly increased the intensity of synaptic vesicle glycoprotein 2A (SV2A), an essential synaptic vesicular protein and a biomarker of synaptic density,\u003csup\u003e\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e\u003c/sup\u003e in the CA1 region of APP/PS1(Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eD). Collectively, these results suggest that NS101 enhances synaptic density by promoting structural synaptic connections.\u003c/p\u003e \u003cp\u003eWe then determined if NS101-induced structural recovery is accompanied by improved basal synaptic transmission and function of neuronal circuits in hippocampal slices of APP/PS1 mice. NS101-treated APP/PS1 mice showed an increased frequency of miniature excitatory postsynaptic currents (mEPSCs) in CA1 pyramidal neurons compared to the hIgG-treated group (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eE). Furthermore, NS101 restored the mean frequency to a level comparable to that of normal mice, demonstrating enhanced excitatory synaptic transmission. The amplitude of mEPSCs remained unchanged in all groups, suggesting that NS101 did not impact excitatory postsynaptic receptor responsiveness (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eE). Field extracellular recordings verified that the excitatory postsynaptic potentials (fEPSPs) of Schaffer collateral (SC)-CA1 circuits, which play a major role in memory formation and emotional networks, were reduced in hippocampal slices from hIgG-treated APP/PS1 mice (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eF), as previously reported.\u003csup\u003e\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e\u003c/sup\u003e NS101 significantly restored the diminished strength of SC-CA1 circuits (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eF). These findings align with NS101's impact on synaptic connections and indicate that it may normalize the reduced excitatory synaptic transmission of CA1 pyramidal cells to levels found in WT mice.\u003c/p\u003e \u003cp\u003eLong-term potentiation (LTP) is a sustained enhancement of synaptic strength after repetitive or strong stimulation.\u003csup\u003e\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e,\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e\u003c/sup\u003e LTP is linked to the creation of new dendritic spines and associated synapses in the hippocampus.\u003csup\u003e\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e,\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e\u003c/sup\u003e Thus, the LTP impairment observed in various AD mouse models has been suggested as a potential cause of cognitive deficits.\u003csup\u003e\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e\u003c/sup\u003e To measure LTP at SC-CA1 synapses, we triggered SC fibers with the theta burst stimulation and monitored the changes in fEPSP responses. NS101 restored the reduced amplitude of fEPSPs (during the last 5 min) in APP/PS1 slices, similar to WT (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eG). In addition, post-tetanic potentiation (PTP), a form of presynaptic plasticity and an indicator of the probability of neurotransmitter release,\u003csup\u003e\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e\u003c/sup\u003e was unchanged in the test groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eH), suggesting no alteration in presynaptic release probability.\u003csup\u003e\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e\u003c/sup\u003e Thus, NS101 restored LTP by stabilizing and fortifying synaptic connections, potentially aiding in the recovery of cognitive deficits in AD mice.\u003c/p\u003e \u003cp\u003e \u003cb\u003eNS101 ameliorates cognitive deficits in mouse models of AD.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eSince NS101 has the ability to reinstate synapse formation under pathological conditions (Figs.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eJ and \u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eK), the new synapses formed in the hippocampus may help to recover cognitive abilities. APP/PS1 mice treated with iv hIgG once a week for 8 weeks showed a significant short-term memory decline compared to WT mice, as measured by the reduced alteration index in the Y-maze test. In contrast, NS101-treated APP/PS1 mice showed increased spontaneous alteration compared to hIgG-treated mice (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003eA), indicating an improvement in short-term memory. Spatial learning and memory were evaluated using the Morris water maze (MWM). APP/PS1 mice treated with hIgG learned poorly in the training phase (Figures S8A and S8B), with memory impairment in the probe test (Figures S8C and S8D), compared to WT mice. Despite the positive effect of NS101 on short-term memory in the Y-maze (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003eA), NS101 partially improved the degraded spatial learning and memory of APP/PS1 mice in the MWM test, as indicated by the parameters of spatial memory (Figure S8). APP/PS1 mice underwent a passive avoidance test to assess associative learning and memory after receiving a foot shock during the training period. hIgG-treated mice showed a significant reduction in the latency compared to WT mice, suggesting a problem in associative learning and memory. Whereas NS101-treated APP/PS1 mice displayed a tendency to recover latency compared to hIgG-treated mice (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003eB). Taken together, these results demonstrated that NS101 improved short-term memory and had partial effects on associative learning and memory in APP/PS1 mice. We administered iv NS101 to P301S mice, a transgenic model of tauopathy, to determine whether it restored cognitive function. NS101 significantly improved spatial learning and memory without affecting locomotion, as shown by the total distance mice moved in the MWM (Figs.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003eC-\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003eE). NS101 also increased the immunoreactivity of the synapse molecules SYP and PSD95 in the hippocampus compared to hIgG-treated control mice (Figure S9). These results suggest that NS101 may ameliorate cognitive decline in AD pathology, including amyloidopathy and tauopathy.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOne possible mechanism by with FAM19A5 suppresses neurite growth and synapse formation can be blocking the binding between LRRC4B at postsynapse and PTPRF at the presynapse. These two molecules form a bridge across the synaptic cleft and enables coordinated assembly of the presynaptic terminal,\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e which holds machinery for neurotransmitter release, and the postsynaptic side, which has neurotransmitter receptors, ion channels, and signaling molecules.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e\u003c/sup\u003e Alterations in FAM19A5 levels can impact interactions at the initial contact stage to form a synapse, or at the elimination stage to weaken the binding. This interaction, prior to synapse assembly, also plays a role in triggering postsynaptic and presynaptic differentiation, thus extending their roles from neurite outgrowth and guidance.\u003csup\u003e18,68\u0026minus;70\u003c/sup\u003e The slowing of neurite growth by FAM19A5 and the enhancement of neurite growth by the FB-decoys and NS101 suggest a suppressive role of FAM19A5 in this process through its binding to LRRC4B. Precise regulation of neurite growth and synapse formation is crucial for maintaining homeostatic neural plasticity under normal conditions and for controlling the rate and extent of neuro-regeneration following nerve injury.\u003csup\u003e\u003cspan citationid=\"CR71\" class=\"CitationRef\"\u003e71\u003c/span\u003e\u003c/sup\u003e Thus, our study proposes that FAM19A5 plays an active role in controlling the dynamic balance of neurite growth/retraction and synapse formation/elimination by suppressing the process.\u003c/p\u003e \u003cp\u003eAn intriguing finding of the present study is that systemic administration of NS101 can cross the blood-brain barrier and facilitate the transport of FAM19A5 from the brain to peripheral blood in both mice and rats in the present study, as well as in humans in a clinical trial study.\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e This consistency of effect across species is likely due to the 100% identical aa sequence of the FAM19A5 protein in these species. The transport of target molecules from the brain to peripheral blood via antibody-mediated means was recently demonstrated in another study, where an anti-tau antibody captured brain tau proteins and transported them to the periphery in both transgenic mice and humans.\u003csup\u003e\u003cspan citationid=\"CR72\" class=\"CitationRef\"\u003e72\u003c/span\u003e\u003c/sup\u003e In both studies, the transfer of target molecules from the brain to peripheral blood was easily observed, as baseline levels of the target molecules were much higher in the brain than in the periphery. These findings, along with our results, suggest that antibodies can be an effective tool for removing target molecules in the brain, potentially offering a treatment approach for various neurological diseases. Given that a single iv administration of NS101 induced the transport of brain FAM19A5 to blood over a month, antibody therapy has a clear advantage in clinical studies over other biologics that require direct administration to the brain and have a short half-life in the blood.\u003csup\u003e\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e,\u003cspan citationid=\"CR73\" class=\"CitationRef\"\u003e73\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eSynapse loss is a critical early pathological event in AD, yet most clinical studies have focused on clearing hallmark pathologies like accumulated Aβ and p-tau. Despite their efficacy in removing these proteins, many antibody drugs targeting Aβ and p-tau have not shown significant improvement in cognitive decline in AD patients.\u003csup\u003e\u003cspan citationid=\"CR74\" class=\"CitationRef\"\u003e74\u003c/span\u003e,\u003cspan citationid=\"CR75\" class=\"CitationRef\"\u003e75\u003c/span\u003e\u003c/sup\u003e Only a few drugs have been recently approved for further evaluation of their ability to improve cognitive function in these patients.\u003csup\u003e\u003cspan citationid=\"CR76\" class=\"CitationRef\"\u003e76\u003c/span\u003e,\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e\u003c/sup\u003e Hence, finding a target protein that can normalize synapse dynamics in the AD brain could open up new avenues for therapeutic intervention that complement strategies for eliminating Aβ and p-tau. In this context, FAM19A5, as a suppressor of synapse formation, could be a promising target for AD. Recent snRNA-seq data revealed a significant increase in FAM19A5 transcript levels in neurons of the brain in early AD pathology compared to a control group.\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR78\" class=\"CitationRef\"\u003e78\u003c/span\u003e,\u003cspan citationid=\"CR79\" class=\"CitationRef\"\u003e79\u003c/span\u003e\u003c/sup\u003e Elevated levels of FAM19A5 have been observed in the CSF of elderly individuals over 60 years, which might be increased risk for diseases characterized by synapse loss. Reducing FAM19A5 levels in the brain could therefore help improve cognitive function in patients with synapse loss.\u003c/p\u003e \u003cp\u003eNS101 prevents synapse loss in cultured neurons treated with Aβ oligomers. Furthermore, systemic administration of NS101 restored synaptic function in the hippocampus of mice with AD pathologies, regardless of the presence of Aβ and p-tau pathologies. This indicates that reducing FAM19A5 levels in the brain may help normalize synapse dynamics that have been impaired by toxic external or internal factors. These findings support previous research that artificially enhancing the connections between synapses through a synthetic fusion protein can effectively restore synapse function in mice with amyloid-related conditions.\u003csup\u003e\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e\u003c/sup\u003e Both studies aimed to increase synapse number and function, either through the use of a synthetic synapse connector or an antibody that removes the suppressor of synapse dynamics. As a result, these studies provide structure-guided molecular tools to normalize synapse function in patients with neurodegeneration. Restoring or enhancing the synaptic structure, even under adverse conditions, can help normalize synaptic transmission function, triggering a positive feedback loop between healthier neurons and their environments.\u003c/p\u003e \u003cp\u003eTaken together, our study shows that FAM19A5 acts as a suppressor by interacting with the postsynaptic molecule LRRC4B. Removing FAM19A5 from the LRRC4B complex, either using the FB-decoys or NS101, significantly improves neural integrity in terms of neurite growth and synapse formation in cultured neurons. Systemic administration of NS101 enhances synapse integrity and cognitive function in mouse models of AD. Therefore, inhibiting the FAM19A5-mediated suppressor function could thus provide a promising new therapeutic approach for treating AD.\u003c/p\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eLimitations of the study\u003c/h2\u003e \u003cp\u003eOur study demonstrated the role of FAM19A5 in synapse assembly and its implications. However, further research may be necessary to address questions raised by the study, such as the possibility that FAM19A5 regulates the function of LRRC4B's paralogs LRRC4 and LRRC4C, which share the similar FB domain. FAM19A5 may also impact other PTPRF family members such as PTPRS and PTPRD. In addition to the trans-synaptic interaction between LRRC4B and PTPRF, LRRC4B may have a cis-acting interaction with uncharacterized proteins at the same plasma membrane to regulate neurite growth and axon guidance. FAM19A5 may also participate in these interactions by binding to LRRC4B or its paralogs. FAM19A5 may also impact the clustering of synaptic molecules in the postsynapse through interfering with LRRC4B's interaction with PSD95. Gaining a deeper understanding of the molecular mechanism behind the FAM19A5-LRRC4B complex's contribution to neurite growth and synapse formation could lead to the development of new strategies for treating neurological diseases and promoting neuro-regeneration by normalizing neurite growth and synapse dynamics.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eACKNOWLEDGEMENTS\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by grants from the Neuracle Science Co., Ltd. The authors acknowledge Eun Bee Cho, Yongwoo Jeong, and Sitaek Oh for assisting in manuscript preparation. The authors also acknowledge Kyungho Seong for performing \u003cem\u003ein silico\u003c/em\u003e residue scanning on the FAM19A5-FB complex using the Schrodinger Platform.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHOR CONTRIBUTIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization, JY.S.; methodology, RH.K., HY.K., SX.M.; validation, RH.K., HY.K., HB.K., MH.L., N.H., EH.C., SM.L.\u0026nbsp;M.B.; investigation, RH.K. SX.M.; resources, WK.K., JI.H.; data curation, RH.K., SX.M.; writing, original draft, RH.K, SX.M., HB.K., JY.S.; writing, review and editing, RH.K, SX.M., HB.K., JY.S.;\u0026nbsp;SW.H., M.B., HC.P.;\u0026nbsp;visualization, RH.K., SX.M., JY.S.; supervision, JY.S.; project administration, JY.S.; funding acquisition, JY.S.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDECLARATION OF INTERESTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRH.K., HY.K., SX.M., HB.K., MH.L., N.H., EH.C., SM.L., JW.J., WK.K., and JY.S. are employed by Neuracle Science, Co., Ltd. MH.L., SM.L., WK.K., SW.H., HC.P., and JY.S. are shareholders of Neuracle Science, Co., Ltd. The remaining authors have no conflicts of interest to declare.\u0026nbsp;\u003c/p\u003e"},{"header":"STAR★METHODS","content":"\u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:6.0pt;text-align:justify;line-height:normal;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eKey resources table\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"width: 4.8e+2pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:169.95pt;border-top:black 1.5pt;border-left:black 1.0pt;border-bottom:black 1.5pt;border-right:black 1.0pt;border-style:solid;padding:0in 5.4pt 0in 5.4pt;height:.2in;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eREAGENT or RESOURCE\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:148.85pt;border-top:solid black 1.5pt;border-left:none;border-bottom:solid black 1.5pt;border-right:solid black 1.0pt;padding: 0in 5.4pt 0in 5.4pt;height:.2in;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eSOURCE\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:160.0pt;border-top:solid black 1.5pt;border-left:none;border-bottom:solid black 1.5pt;border-right:solid black 1.0pt;padding: 0in 5.4pt 0in 5.4pt;height:.2in;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eIDENTIFIER\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 6.65in;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;background: rgb(231, 230, 230);padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;color:black;'\u003eAntibodies\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eMouse monoclonal anti-Synaptophysin\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eSigma-Aldrich\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# S5768\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eMouse monoclonal anti-PSD95\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eInvitrogen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# MA1-045\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eMouse monoclonal anti-Tau5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eInvitrogen\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# AHB0042\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eMouse monoclonal anti-NGL-3/LRRC4B\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eR\u0026amp;D Systems\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# MAB69191\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eMouse monoclonal anti-FLAG M2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eSigma-Aldrich\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# F1804\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eMouse monoclonal anti-V5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eInvitrogen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# R960CUS\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eDonkey anti-Human IgG-HRP\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eJackson ImmunoResearch\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# 715-035-149\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eDonkey anti-Mouse IgG-HRP\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eJackson ImmunoResearch\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# 715-035-150\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eDonkey anti-Human IgG-Cy3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eJackson ImmunoResearch\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# 709-165-149\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;background:white;'\u003eRabbit anti-Human IgG Heavy chain\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eInvitrogen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# SA5-10223\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eRabbit anti-Human IgG Fc-HRP\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eInvitrogen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# 31423\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;background:white;'\u003eGoat anti-Human kappa light chain-HRP\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eInvitrogen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# A18853\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;background:white;'\u003eanti-Human isotype control\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eInvitrogen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# 31154\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eAnti-Human IgG1, kappa isotype control\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eSino Biological\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# HG1K\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 6.65in;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;background: rgb(231, 230, 230);padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;color:black;'\u003eBiological samples\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePooled normal human cerebrospinal fluid\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eInnovative Research, Inc.\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat#\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eIPLA-CSFP\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eIndividual Human CSF and Plasma\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eBIOIVT \u0026amp; ELEVATING SCIENCE\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 6.65in;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;background: rgb(231, 230, 230);padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;color:black;'\u003eChemicals\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eOpti-MEM Reduced Serum Medium, GlutaMAX Supplement\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eGibco\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat#\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e51985034\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eExpi293\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026trade;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;Expression Medium\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eGibco\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat#\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eA1435101\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFetal bovine serum\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eGibco\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat#\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e16000-044\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePenicillin-Streptomycin (10,000 U/mL)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eGibco\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat#\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e15140122\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eDPBS (1X)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eGibco\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat#\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e14190250\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eTrypsin-EDTA (0.25%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eGibco\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat#\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e25200-072\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eImidazole\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eSigma-Aldrich\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat#\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e56750-500G\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAmicon Ultra-15 (Ultracel-10K)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eMillipore\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat#\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eUFC901024\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAcTEV Protease\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eInvitrogen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat#\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e12575023\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003erProtein A GraviTrap\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eCytiva\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat#\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e28985254\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAb buffer kit\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eCytiva\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat#\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e28903059\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eDynabead Protein G for Immunoprecipitation\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eInvitrogen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat#\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e10003D\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eProtein A/G Plus Agarose\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:#222222;'\u003eThermo Scientific\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat#\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e20424\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eDSG (disuccinimidyl glutarate)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:#222222;'\u003eThermo Scientific\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# 20593\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eParaformaldehyde\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eSigma-Aldrich\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat#\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eP6148\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eBovine serum albumin\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eSigma-Aldrich\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat#\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eA7030\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eTriton X-100\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eSigma-Aldrich\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat#\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eT8787\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eHoechst 33342 Solution\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:#222222;'\u003eThermo Scientific\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# 62249\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eCellTracker CM-DiI Dye\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003einvitrogen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# C7000\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eSucrose\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eSigma-Aldrich\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# 1888\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePotassium chloride\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eSigma-Aldrich\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# P9541\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eSodium phosphate monobasic\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eSigma-Aldrich\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# S0751\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eSodium bicarbonate\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eSigma-Aldrich\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# S5761\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eSodium pyruvate\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eSigma-Aldrich\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# P5280\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eSodium L-ascorbate\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eSigma-Aldrich\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# A4034\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eSodium chloride\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eSigma-Aldrich\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat#\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eS9888\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eMagnesium sulfate\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eSigma-Aldrich\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# M2643\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eCalcium chloride\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eSigma-Aldrich\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# 4901\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eGlycerol\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eSPL\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# G9012\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 6.65in;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;background: rgb(231, 230, 230);padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003ePeptides\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAmino acid sequence for FAM19A5 fragment peptides, see table S1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAmino acid sequence for point mutation FAM19A5 fragment peptides, see table S2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAmino acid sequence for FB fragment peptides, see S1F\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eBeta-Amyloid (1-42)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnaSpec\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat#\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAS-20276\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFAM19A5 fragment peptide F1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFAM19A5 fragment peptide F2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFAM19A5 fragment peptide F3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFAM19A5 fragment peptide F4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFAM19A5 fragment peptide F5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFAM19A5 fragment peptide F6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePoint-mutated fragment peptide F2-01\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePoint-mutated fragment peptide F2-02\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePoint-mutated fragment peptide F2-03\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePoint-mutated fragment peptide F2-04\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePoint-mutated fragment peptide F2-05\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePoint-mutated fragment peptide F2-06\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePoint-mutated fragment peptide F2-07\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePoint-mutated fragment peptide F2-08\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePoint-mutated fragment peptide F2-09\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePoint-mutated fragment peptide F2-10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePoint-mutated fragment peptide F2-11\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePoint-mutated fragment peptide F2-12\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePoint-mutated fragment peptide F2-13\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePoint-mutated fragment peptide F2-14\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePoint-mutated fragment peptide F2-15\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:5.0pt;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePoint-mutated fragment peptide F2-16\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePoint-mutated fragment peptide F2-17\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePoint-mutated fragment peptide F2-18\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePoint-mutated fragment peptide F2-19\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePoint-mutated fragment peptide F2-20\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePeptron\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB 28 mer\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB 20 mer\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB 16 mer\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-m11dC\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-m10dC\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-m9dC\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-m8dC\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-m7dC\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[Y484A]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[Y484N]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[T485A]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[T485N]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[Y486A]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[T486N]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[F487A]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[F487N]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[T488A]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[F488N]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[T489A]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[F489N]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[V490A]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[F490N]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[T491A]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[T491N]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[V492A]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[V492N]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[E493A]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[E493N]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[T494A]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[T494N]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[Y495A]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFB-20[E496A]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAnygen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 6.65in;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;background: rgb(231, 230, 230);padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCritical Commercial Assays\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eNeon\u0026trade; Transfection System Kit\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eInvitrogen\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat#\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eMPK10096\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eINNOTEST\u0026reg; PHOSPHO-TAU (181P)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;background:white;'\u003eFULIREBIO\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat#\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e81574\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eINNOTEST\u0026reg; hTAU Ag\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;background:white;'\u003eFULIREBIO\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCat# 81579\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 6.65in;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;background: rgb(231, 230, 230);padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;color:black;'\u003eRecombinant proteins\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFAM19A5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFAM19A5(R58A, R59A)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFAM19A5(R125A, K127A)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFAM19A5(R58A, R59A, R125A, K127A)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e6xHis-LRRC4B (36-576)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e6xHis-LRRC4B (453-576)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e6xHis-LRRC4B (453-576), (T488A, T489A)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eLRRC4B (36-576)-hFc\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eLRRC4B(453-576)-hFc\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eLRRC4B(453-576)-hFc\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e(T488A, T489A)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eLRRC4B(484-576)-hFc\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eLRRC4B(498-576)-hFc\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePTPRF(30-1263)-hFc\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 6.65in;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;background: rgb(231, 230, 230);padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;color:black;'\u003eExperimental models: Cell lines\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eHEK293 cells\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eATCC\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eCat# CRL-1573\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eExpi293F cells\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eGibco\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eCat# A14527\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 6.65in;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;background: rgb(231, 230, 230);padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;color:black;'\u003eExperimental models: Organisms/strains\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eMouse: C57BL/6\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThe Jackson Laboratory\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:#333333;background:white;'\u003eStrain#\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:#333333;background:white;'\u003e000664\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eMouse: P301S\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThe Jackson Laboratory\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:#333333;background:white;'\u003eStrain# 008169\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eMouse: APP/PS1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThe Jackson Laboratory\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:#333333;background:white;'\u003eStrain# 034832-JAX\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eMouse: 5XFAD\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThe Jackson Laboratory\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:#333333;background:white;'\u003eStrain# 034840-JAX\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eMouse: FAM19A5 KO\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eToolGen\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:#333333;background:white;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black windowtext;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eSprague-Dawley rats\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eORIENT BIO\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black windowtext currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:#333333;background:white;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eCynomolgus monkeys\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eORIENT BIO\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 6.65in;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;background: rgb(231, 230, 230);padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;color:black;'\u003eOligonucleotides\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;background:white;'\u003ePrimers used for LRRC4B cloning, see table S3\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;background:white;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 6.65in;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;background: rgb(231, 230, 230);padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;color:black;'\u003eRecombinant DNA\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Arial\",sans-serif;margin:0in;color:black;'\u003e\u003cspan style='font-size:13px;font-family:\"Times New Roman\",serif;'\u003epCAG1.1-IgK_SP-His-TEV-FAM19A5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Arial\",sans-serif;margin:0in;color:black;'\u003e\u003cspan style='font-size:13px;font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCAG1.1-IgK_SP-His-TEV-FAM19A5(R58A, R59A)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCAG1.1-IgK_SP-His-TEV-FAM19A5(R125A, K127A)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCAG1.1-IgK_SP-His-TEV-FAM19A5(R58A, R59A, R125A, K127A)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCAG1.1-IgK_SP-His-TEV-LRRC4B\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e36-576\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCAG1.1-IgK_SP-His-TEV-LRRC4B\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e453-576\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epcDNA3.1 FAM19A5 Isoform 1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epcDNA3.1 FAM19A5 Isoform 2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epcDNA3.1(+)-C-FLAG-LRRC4B\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eGenscript\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eClone ID: OHu30422\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epcDNA3.1(+)-C-FLAG-PTPRF\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eGenscript\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eClone ID: OHu02063\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epcDNA6 V5-His A-LRRC4B\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCMV20-IgK_SP-FLAG-LRRC4B 36-713\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCMV20-IgK_SP-FLAG-LRRC4B 36-713 (T488A, T489A)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCMV20-IgK_SP-FLAG-LRRC4B 157-713\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCMV20-IgK_SP-FLAG-LRRC4B 230-713\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCMV20-IgK_SP-FLAG-LRRC4B 364-713\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCMV20-IgK_SP-FLAG-LRRC4B 453-713\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCMV20-IgK_SP-FLAG-LRRC4B 577-713\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCMV20-IgK_SP-FLAG-LRRC4B 36-576\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCMV20-IgK_SP-FLAG-LRRC4B\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026Delta;364-576\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCMV20-IgK_SP-FLAG-LRRC4B 364-576\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCMV20-IgK_SP-FLAG-LRRC4B 453-576\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCMV20-IgK_SP-FLAG-LRRC4B 453-576 (T488A, T489A)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCMV20-IgK_SP-FLAG-LRRC4B 453-576 (T488S, T489S)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCMV20-IgK_SP-FLAG-LRRC4B 484-576\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCMV20-IgK_SP-FLAG-LRRC4B 498-576\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCMV20-IgK_SP-LRRC4B\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e36-576-hFc\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCMV20-IgK_SP-LRRC4B\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e453-576-hFc\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCMV20-IgK_SP-LRRC4B\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e453-576 (T488A, T489A)-hFc\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003epCMV20-IgK_SP-PTPRF\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e30-1263-hFc\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThis study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:left;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 6.65in;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;background: rgb(231, 230, 230);padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;color:black;'\u003eSoftware and algorithms\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePrism\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eGraphPad\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ehttps://www.graphpad.com/scientific-software/prism/\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eFiji\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eImage J\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ehttps://imagej.net/software/fiji/\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eIMARIS\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eBitplane\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ehttps://imaris.oxinst.com/\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eLas X\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eLeica\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ehttps://www.leica-microsystems.com/products/microscope-software/p/leica-las-x-ls/downloads/\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAlphaFold v2.0\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eJumper et al.\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ehttps://alphafold.ebi.ac.uk/\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eRoseTTAFold\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eBaek et al.\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ehttps://github.com/RosettaCommons/RoseTTAFold\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eBioluminate\u0026reg;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eSchrodinger\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ehttps://www.schrodinger.com/downloads/releases\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePyMOL\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eSchrodinger\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ehttps://pymol.org/2/#page-top\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAdobe Illustrator CC\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAdobe\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ehttps://www.adobe.com/uk/products/\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eillustrator\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 6.65in;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;background: rgb(231, 230, 230);padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;color:black;'\u003eOther\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eLeica DMi8 confocal microscope\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eLeica\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eNeon transfection system\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eThermo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eMP924681\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eVERSA max microplate reader\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eMolecular device\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eBNR-07668\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eMiniHD9 Chemi/gel DOC\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eUvitec\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e16-200248\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169.95pt;border-color: currentcolor black black;border-style: none solid solid;border-width: medium 1pt 1.5pt;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eSimpliAmp thermal cycler\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148.85pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eApplied biosystems\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160pt;border-color: currentcolor black black currentcolor;border-style: none solid solid none;border-width: medium 1pt 1.5pt medium;padding: 0in 5.4pt;height: 12.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:0in;text-align:justify;line-height:normal;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eA24812\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin-right:0in;margin-left:0in;font-size:13px;font-family:\"Malgun Gothic\",sans-serif;margin-top:0in;margin-bottom:8.0pt;text-align:left;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDetailed methods are provided in the online version of this paper and include the following:\u003c/p\u003e\n\u003cul start=\"12\"\u003e\n \u003cli\u003eKEY RESOURCES TABLE\u003c/li\u003e\n \u003cli\u003eCONTACT FOR REAGENT AND RESOURCE SHARING\u003c/li\u003e\n \u003cli\u003eEXPERIMENTAL MODEL AND SUBJECT DETAILS\u003cul\u003e\n \u003cli\u003eHuman samples\u003c/li\u003e\n \u003cli\u003eVertebrate animals\u003c/li\u003e\n \u003cli\u003eCell lines\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003eMETHODS DETAILS\u003cul\u003e\n \u003cli\u003ePurification of recombinant FAM19A5 protein\u003c/li\u003e\n \u003cli\u003eProduction of anti-FAM19A5 antibodies\u003c/li\u003e\n \u003cli\u003eDNA constructs\u003c/li\u003e\n \u003cli\u003eProduction of fragment peptides\u003c/li\u003e\n \u003cli\u003eElectroporation transfection and co-IP\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eImmunoblots\u003c/li\u003e\n \u003cli\u003eELISA\u003c/li\u003e\n \u003cli\u003eSurface plasmon resonance (SPR)\u003c/li\u003e\n \u003cli\u003e\u003cem\u003eIn silico\u003c/em\u003e modeling of the FAM19A5-LRRC4B complex structure using AlphaFold2 an RoseTTAFold\u003c/li\u003e\n \u003cli\u003e\u003cem\u003eIn silico\u0026nbsp;\u003c/em\u003eresidue scanning of the FAM19A5-FB complex\u003c/li\u003e\n \u003cli\u003eHEK293 cell culture and immunocytochemistry\u003c/li\u003e\n \u003cli\u003ePrimary neuron culture and immunocytochemistry\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eDiI staining and spine density analysis \u003cem\u003ein vitro\u003c/em\u003e\u003c/li\u003e\n \u003cli\u003eA\u0026beta;\u003csub\u003e1\u0026ndash;42\u003c/sub\u003e preparation\u003c/li\u003e\n \u003cli\u003eImmunohistochemistry\u003c/li\u003e\n \u003cli\u003eHippocampal slice preparation and electrophysiology \u0026nbsp;\u003c/li\u003e\n \u003cli\u003eStereotaxic FAM19A5 injection\u003c/li\u003e\n \u003cli\u003eAnimal behavioral tests\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003eQUANTIFICATION AND STATISTICAL ANALYSIS\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSUPPLEMENTAL INFORMATION\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSupplemental information can be found online.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONTACT FOR REAGENT AND RESOURCE SHARING\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFurther information and requests for resources and reagents may be directed to and will be fulfilled by the Lead Contact,\u0026nbsp;Jae Young Seong\u0026nbsp;\u003cstrong\u003e(\u003c/strong\u003e\u003ca href=\"mailto:[email protected]\"\[email protected]\u003c/a\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEXPERIMENTAL MODEL AND SUBJECT DETAILS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman samples\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePooled normal human cerebrospinal fluid (CSF) was obtained from Innovative Research, Inc. with catalog number IPLA-CSFP, and used for the Co-IP experiment to determine the association between FAM19A5 and LRRC4B. Individual human CSF and plasma samples were obtained from BIOIVT \u0026amp; ELEVATING SCIENCE and were used to measure age-dependent FAM19A5 levels in CSF and the basal level of FAM19A5 in plasma, respectively. Additionally, individual human CSF samples were also used to determine total tau and phospho-tau levels.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVertebrate animals\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eObtained from the Jackson Laboratory were APP/PS1 [B6.Cg-Tg (APPswe, PSEN1dE9) 85Dbo/J] mice, P301S [B6.C3-Tg (Prnp-MAPT*P301S) PS19Vle/J] mice, and 5xFAD [B6SJL-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax] mice. Obtained from Orient Bio were WT C57BL/6J mice, Sprague-Dawley rats, and cynomolgus monkeys. The FAM19A5 KO mice were generated using the CRISPR/Cas9 system by ToolGen as previously described.\u003ca href=\"#_ENREF_24\" title=\"Kwak, 2020 #3\"\u003e\u003csup\u003e24\u003c/sup\u003e\u003c/a\u003e Homozygous FAM19A5 KO mice were generated through intercross breeding of heterozygous mice. The mice were housed under temperature-controlled conditions (22\u0026ndash;23\u0026deg;C) with a 12-h light/12-h dark-light cycle (lights on at 8:00 am) and had ad libitum access to standard chow and water. All animal experiments were designed to minimize the number of mice used and anesthesia was administered for the procedures. The behavioral tests performed by CRO companies were approved by the Animal Experimentation Ethics Committee of KPC Co., Ltd. (approval number: P191005) in accordance with the Animal Protection Act (Law No. 4372 enacted on May 31, 1991, partially revised Act No. 13023 on January 20, 2016). The procedures related to the analysis of animal samples were further approved by the Institutional Animal Care and Use Committee of Korea University (KOREA-2020-0031, KOREA-2020-0037, and KOREA-2021-0002). Ethical regulations were followed throughout.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCell lines\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHEK293 cells (ATCC, CRL-1573) were cultured in humidified incubator at 37 \u0026deg;C with 5 % CO\u003csub\u003e2\u003c/sub\u003e. HEK293 cells were propagated in MEM with GlutaMAX\u003csup\u003eTM\u003c/sup\u003e (Gibco) supplemented with 10% fetal bovine serum (Gibco) and 100 U/ml penicillin-streptomycin (Gibco). For sub-culture, cells were washed with DPBS (Gibco) and dissociated in 0.25% Trypsin-EDTA (Gibco) for 5 min at 37 \u0026deg;C.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMETHODS DETAILS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePurification of recombinant proteins\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRecombinant His-tagged proteins were purified according to the method described previously.\u003ca href=\"#_ENREF_24\" title=\"Kwak, 2020 #3\"\u003e\u003csup\u003e24\u003c/sup\u003e\u003c/a\u003e In brief, FAM19A5 (WT and MT) and LRRC4B(36-576) with N-terminal 6xHis tags, followed by a tobacco etch virus protease (TEV) recognition sequence, were cloned into the pCAG1.1 vector and expressed in Expi 293F cells. The supernatant containing His-TEV-FAM19A5 was collected for Ni-NTA affinity chromatography (Cytiva). After washing with a binding buffer containing 20 mM Tris-HCl (pH 7.5) and 200 mM NaCl, the proteins were eluted using binding buffers with increasing concentrations of imidazole (from 5 to 500 mM). Proteins eluted from the 50 to 500 mM imidazole fractions were concentrated using Amicon\u0026reg; Ultra-15 Centrifugal Filter Units (Millipore), and the buffer was exchanged for 1xDPBS (Gibco). The purified His-TEV-FAM19A5 proteins were digested overnight at 30\u0026deg;C with AcTEV protease (Invitrogen) to remove the His-tag and TEV sequence. The AcTEV protease containing the His-tag was then eliminated by overnight incubation with Ni-NTA, and digestion was confirmed using an anti-His tag antibody (Abcam). LRRC4B (ectodomain and fragments) and PTPRF (ectodomain) were cloned into the pCMV Ig\u0026kappa;-SP human Fc (hFc) vector and expressed in Expi 293F cells. The supernatant containing hFc-fused proteins was collected using rProtein A GraviTrap (Cytiva), and the hFc-fused proteins were eluted using an Ab buffer kit (Cytiva) following the manufacturer\u0026apos;s instructions.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProduction of anti-\u003c/strong\u003e\u003cstrong\u003eFAM19A5\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;antibodies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe generated two chimeric chicken/human monoclonal antibodies against FAM19A5, named N-A5-Ab and C-A5-Ab, by immunizing chickens (Gallus gallusdomesticus) with purified recombinant FAM19A5 (rcFAM19A5) using a method previously described.\u003ca href=\"#_ENREF_24\" title=\"Kwak, 2020 #3\"\u003e\u003csup\u003e24\u003c/sup\u003e\u003c/a\u003e In addition, we obtained an antibody called 2-13 that recognizes a conformational structure of FAM19A5, rather than a specific linear aa sequence. We further improved the N-A5-Ab and C-A5-Ab antibodies by a process called deimmunization and optimization of its physicochemical properties, resulting in the creation of the antibody NS101 and SS01, respectively.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDNA constructs\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFull-length human LRRC4B and full-length human FAM19A5 were cloned sequentially into the pcDNA3.1(+) vector. Cloning was performed using the AccuRapid\u0026trade; Cloning Kit (Bioneer) according to the manufacturer\u0026rsquo;s instructions. The pCMV-IgK-SP-hFc vector was constructed by inserting a human immunoglobulin kappa signal peptide sequence in front of the human Fc. Fragments of LRRC4B (F1; 36\u0026ndash;713 aa, F2; 157\u0026ndash;713 aa, F3; 230\u0026ndash;713 aa, F4; 364\u0026ndash;713 aa; F5; 453\u0026ndash;714 aa; F6; 577\u0026ndash;713 aa; F7; 36\u0026ndash;576 aa; F8; 36\u0026ndash;63 aa; F9; 364\u0026ndash;576 aa; F10; 453\u0026ndash;576 aa; F11; 484\u0026ndash;576 aa; F12; 498\u0026ndash;576 aa) were constructed in the pCMV-IgK-SP-hFc vector. Full-length human LRRC4B and PTPRF plasmid DNAs were purchased from Genscript. For Ala and Asn substitutions, point mutations in genes were created using the In-Fusion HD Cloning Kit (Clontech Laboratories) using synthetic PCR primers with site-directed mutated bases.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProduction of fragment peptides\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAa sequences of FB-related peptides are listed in\u0026nbsp;\u003cstrong\u003eTable S1 and S2\u0026nbsp;\u003c/strong\u003eand were custom-made from Anygen. To identify the epitope of the FAM19A5 antibodies, the FAM19A5 linear sequence was divided into six groups, labeled F1 to F6. Further analysis was conducted to determine the crucial residue for binding, in which each aa sequence in F2 was replaced with\u0026nbsp;Ala. The relevant name and aa sequences are listed in the Supplemental Table S1 and S2. All peptides related to FAM19A5 were custom-made from Peptron or Anygen.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eElectroporation transfection and co-IP\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHEK293 cells were transfected with the Neon\u003csup\u003eTM\u003c/sup\u003e transfection kit (Thermo) according to the manufacturer\u0026rsquo;s description. For the general co-IP experiments, after transfection, cells were treated with rcFAM19A5 for 30 min. The cells were washed twice with cold phosphate-buffered saline (PBS) and resuspended in lysis buffer containing 20\u0026nbsp;mM Tris-HCl (pH 7.4), 150 nM NaCl, 0.5% NP40, and a protease and phosphatase inhibitor cocktail (Thermo) in PBS. The supernatants were isolated by centrifugation at 12,000 \u0026times;\u0026nbsp;g at 4\u0026deg;C for 30 min and then mixed with 30\u0026nbsp;\u0026mu;l of Protein G Dynabeads that had been preincubated with antibodies. The mixtures were incubated at 4\u0026deg;C overnight in a rotating mixer. The Protein G Dynabeads were spun down and washed three times with 20 mM Tris-HCl (pH 7.4), 300 mM NaCl, and 0.5% NP40 in washing buffer. After adding 30\u0026nbsp;\u0026mu;l of 2\u0026times; sample buffer containing a reducing agent to the Protein G Dynabeads and boiling at 100\u0026deg;C for 10 min, the proteins were separated by SDS-PAGE.\u0026nbsp;For the human CSF co-IP, the pooled human CSFs (Innovative Research) were mixed with 0.5% NP40 and 50 \u0026mu;l of Pierce Protein A/G Plus Agarose (Thermo) that had been preincubated with 10 \u0026mu;g anti-hIgG (H+L), N-A5-Ab, and C-A5-Ab antibodies.\u0026nbsp;For measurement of FAM19A5 level released to the culture medium, cells were treated with NS101 for 30, 60, and 120 min followed by transfection. Culture media were collected and subjected to ELISA.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImmunoblots\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMouse biofluid samples and cells were homogenized and prepared in lysis buffer containing 20 mM Tris-HCl (pH 7.5), 500 mM NaCl, 5 mM MgCl\u003csub\u003e2\u003c/sub\u003e, and protease inhibitor cocktail (Thermo Fisher Scientific). The primary antibodies are described in Supplementary Table 1. Immunoblots of biofluid samples and cells were performed as described previously\u003ca href=\"#_ENREF_24\" title=\"Kwak, 2020 #3\"\u003e\u003csup\u003e24\u003c/sup\u003e\u003c/a\u003e. FAM19A5-NS101 complex in sample was captured by interacting with crosslinker DSG\u0026nbsp;(Thermo) according to the manufacturer\u0026rsquo;s protocol.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eELISA\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTotal and phosphorylated tau levels were assessed using the commercial ELISA Kit, hTAU Ag and PHOSPHO-TAU (181P) (FULIREBIO) according to the manufacturer\u0026rsquo;s protocol. FAM19A5 and NS101 levels were assessed using our in-house developed kit. To\u0026nbsp;evaluate the binding affinity\u0026nbsp;between FAM19A5 and LRRC4B, several LRRC4B deletion proteins, including\u0026nbsp;LRRC4B(36-576), LRRC4B(453-576), LRRC4B(484-576), and LRRC4B(498-576) proteins were\u0026nbsp;utilized as capture agents. WT and MT FAM19A5, including FAM19A5(R58A, R59A), FAM19A5(R125A, K127A), and FAM19A5(R58A, R59A, R125A, K127A) proteins were used for the binding.\u0026nbsp;Detection was performed using the SS01. The cell culture medium of FAM19A5 was measured using 2-13 and the SS01 was used for capture and detection, respectively.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor\u0026nbsp;measuring FAM19A5 in biofluids, LRRC4B(453-576) protein and a horseradish peroxidase (HRP)-conjugated\u0026nbsp;SS01\u0026nbsp;was used for capture and detection, respectively. For measurement of CSF NS101, a pair of rabbit anti-human IgG heavy chain antibody (Invitrogen) and HRP-conjugated goat \u0026alpha;-human IgG kappa light chain antibody (Thermo) were used.\u003c/p\u003e\n\u003cp\u003eFor testing the inhibition of FAM19A5-LRRC4B binding, LRRC4B(453-576) protein was first coated onto the plate, followed by the addition of the test sample and FAM19A5 protein. The binding inhibition was calculated by detecting FAM19A5 through SS01. For the PTPRF-LRRC4B binding inhibition test, LRRC4B(36-576) protein was coated on the plate and followed by the addition of the test sample and PTPRF protein. The binding inhibition was calculated by detecting PTPRF-hFc through the anti-human IgG Fc antibody.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSurface plasmon resonance (SPR)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll SPR experiments were carried out on a Biacore 8K (Cytiva) with active temperature control at 25\u0026deg;C following the manufacturer\u0026rsquo;s protocols. The running buffer was 1 \u0026times; HBS-EP (10 mM HEPES, 150 mM NaCl, 3 mM EDTA, 0.05% Tween 20, pH 7.4). For immobilization, His-TEV-LRRC4B(453\u0026ndash;576) in 10\u0026nbsp;mM sodium acetate, pH 4.5 buffer equivalent to 632\u0026ndash;638 Resonance Unit (RU) was injected onto a nitrilotriacetic acid (NTA) chip at a 30 \u0026micro;l/min flow rate. Another flow cell without the immobilized His-TEV-LRRC4B(453\u0026ndash;576) coating was used to evaluate nonspecific binding. Increasing concentrations (0.78, 1.56, 3.12, 6.25, and 12.5 nM) of rcFAM19A5 were diluted in running buffer and flowed across the immobilized His-TEV-LRRC4B(453\u0026ndash;576) for 180 s at a flow rate of 30 \u0026mu;l/min (association). The sample was replaced with a running buffer for 240 s (disassociation). The chip surface was regenerated with 350 mM EDTA and HBS-P+ 500 mM imidazole. For all samples, blank injection with buffer alone was subtracted from the resulting reaction surface data. Data were analyzed using Biacore 8K evaluation software (Cytiva).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eIn silico\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;modeling of the FAM19A5-LRRC4B complex structure using AlphaFold2 and\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eRoseTTAFold\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe used AlphaFold2\u003ca href=\"#_ENREF_40\" title=\"Jumper, 2021 #43\"\u003e\u003csup\u003e40\u003c/sup\u003e\u003c/a\u003e to model the structure of the FAM19A5-LRRC4B complex. An input paired multiple sequence alignments (paired MSAs) were generated following RoseTTAFold\u0026rsquo;s input generation protocol. hMSAs for the FAM19A5 protein and LRRC4B extracellular domain were generated by iterative sequence search against the UniClust30 database\u003ca href=\"#_ENREF_80\" title=\"Mirdita, 2017 #55\"\u003e\u003csup\u003e80\u003c/sup\u003e\u003c/a\u003e using HHblits.\u003ca href=\"#_ENREF_81\" title=\"Remmert, 2011 #56\"\u003e\u003csup\u003e81\u003c/sup\u003e\u003c/a\u003e To predict a complex structure, we generated a paired MSA based on individual MSA by pairing sequences from the same species. To provide pseudo-multimer inputs to AlphaFold2, we used a gap insertion trick that has been previously applied to RoseTTAFold\u003ca href=\"#_ENREF_41\" title=\"Baek, 2021 #57\"\u003e\u003csup\u003e41\u003c/sup\u003e\u003c/a\u003e. The final models were ranked by predicted TM score (pTM score), and the best scored model was used for further study after structural relaxation using Rosetta.\u003ca href=\"#_ENREF_42\" title=\"Humphreys, 2021 #173\"\u003e\u003csup\u003e42\u003c/sup\u003e\u003c/a\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eIn silico\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;residue scanning of the FAM19A5-FB complex\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe used the residue scanning module (Schrodinger Bioluminate\u0026reg;) for \u003cem\u003ein silico\u003c/em\u003e residue scanning (e.g.,\u0026nbsp;Ala\u0026nbsp;scanning) and to calculate the perturbation of protein-peptide binding affinity, which was defined as the binding free energy change. To evaluate the potential impact of a mutation, we used \u0026Delta; Affinity and \u0026Delta; Stability (solvated) values.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHEK293 cell culture and immunocytochemistry\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCells were seeded at a density of 3 \u0026times; 10\u003csup\u003e4\u0026nbsp;\u003c/sup\u003ecells/well on fibronectin-coated plastic film coverslips in 12-well plates. After 24 hours, the cells were cotransfected with 150 ng of FLAG-taggedLRRC4B and His-tagged FAM19A5 isoform 1 or 2. After 24 hours of incubation, the cells were washed once with ice-cold Dulbecco\u0026rsquo;s PBS (DPBS) and fixed with 4% paraformaldehyde (PFA) in PBS for 20 min. After washing three times with ice-cold DPBS, the cells were blocked with blocking buffer containing 3% bovine serum albumin (BSA) and 0.1% Triton X-100 in PBS for 30 min and incubated with primary antibodies overnight at 4\u0026deg;C. After three washes with DPBS, the cells were incubated with secondary antibodies and 20 mM Hoechst solution (Thermo) for 1 hour at room temperature. After three washes with DPBS, fluorescent images were acquired via a confocal microscope (Leica) using coverslips mounted with mounting solution (Biomeda). All images were processed using Las X software (Leica). NS101 and the recombinant proteins containing the FB domain were treated for 30 min before the fixation.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrimary neuronal culture and immunocytochemistry\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePrimary cortical or hippocampal\u0026nbsp;neurons were prepared from postnatal C57BL/6\u0026nbsp;pups (postnatal day 1) (Nara Biotech) as previously described.\u003ca href=\"#_ENREF_82\" title=\"Beaudoin, 2012 #59\"\u003e\u003csup\u003e82\u003c/sup\u003e\u003c/a\u003e The cells were maintained at 37\u0026deg;C in a 5% CO\u003csub\u003e2\u003c/sub\u003e-humified incubator.\u0026nbsp;Every 3\u0026ndash;4 days, half of the medium from the culture dish was replaced with fresh culture\u0026nbsp;medium. Neurons were cultured for DIV16, and total RNA was isolated and subjected to RNA-seq analysis as previously described.\u003ca href=\"#_ENREF_83\" title=\"Martin, 2011 #21\"\u003e\u003csup\u003e83\u003c/sup\u003e\u003c/a\u003e\u003c/p\u003e\n\u003cp\u003eCells were fixed with 4% PFA, except for the spine density assay (2% PFA, 4% sucrose). The cells were permeabilized and\u0026nbsp;blocked with a blocking buffer containing 3% BSA and 0.1% Triton X-100 in PBS for 1\u0026nbsp;hour at\u0026nbsp;room temperature.\u0026nbsp;Then, the samples were incubated with primary antibodies diluted in blocking buffer overnight at 4\u0026deg;C and washed three times with PBS. Cells were incubated with the appropriate fluorescently labeled secondary antibodies and with\u0026nbsp;Hoechst 33342 (Invitrogen)\u0026nbsp;diluted in PBS for 30 min at\u0026nbsp;room temperature. Cells were washed three times with PBS, and then coverslips were mounted using Crystal Mount (Biomeda). Images were acquired using a confocal microscope (Leica).\u003c/p\u003e\n\u003cp\u003eFor the analysis of neurite growth, cultured neurons were treated with hIgG or NS101, or rcFAM19A5 at DIV 1 and DIV 2. At DIV 3, neurons were fixed and immunostained with anti-Tau5 (Thermo), and three parameters (total neurite length per neuron, number of primary neurites, and number of branch points) were measured using ImageJ (NIH).\u003c/p\u003e\n\u003cp\u003eFor the quantification of pre- and postsynaptic molecules, cultured neurons were treated with or rcFAM19A5, hIgG or NS101 at DIV 3 and DIV 6. At DIV 7, neurons were fixed and immunostained with anti-SYP (Sigma) and anti-PSD95 (Invitrogen). Z-stack images (depth, 3 \u0026mu;m) were acquired with a confocal microscope (Leica), and 3D reconstruction and analysis were performed with Imaris software (Bitplane).\u003c/p\u003e\n\u003cp\u003eFor measurement of FAM19A5 level released to the culture medium, neurons were treated with\u0026nbsp;hIgG or\u0026nbsp;NS101 at DIV 9 and DIV 10. At DIV 11, culture media were collected and subjected to ELISA. For measurement culture media of FAM19A5, 2-13 and C-term FAM19A5 antibody was used for capture and detection, respectively.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiI staining and spine density analysis \u003cem\u003ein vitro\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo visualize dendritic spines, we used the well-characterized fluorescent lipophilic dye DiI (Invitrogen) according to the manufacturer\u0026rsquo;s instructions. Primary neurons were treated with hIgG or NS101 every 3 days starting at DIV 3. On the appropriate DIV, primary neurons were fixed with 2% PFA + 4% sucrose in PBS for 15 min at room temperature and washed three times with\u0026nbsp;DPBS. The cells were incubated with DiI solution diluted in DPBS (5 \u0026mu;l/ml) for 20 min at room temperature and washed three times with DPBS. After labeling, the coverslips incubated in DPBS were stored in the dark overnight at 4\u0026deg;C to allow the DiI dye to diffuse. The following day, the coverslips were rinsed twice with sterile H\u003csub\u003e2\u003c/sub\u003eO to reduce the background. The coverslips were mounted on slides using Crystal Mount (Biomeda) and cured for at least 2 days to allow complete migration of the dye into the spines. All images were acquired under a 552 nm laser using a confocal microscope (63\u0026times; oil immersion objective) at a pixel resolution of 1024 \u0026times; 1024 with a 3\u0026times; optical zoom. Serial Z-stacks (0.2 \u0026mu;m intervals) were performed from top to bottom, covering all dendrites and protrusions. The 3D reconstruction of stacked images and analysis were performed using Imaris software, and the analysis was blinded. A protrusion width greater than 0.2 \u0026mu;m was defined as a dendritic spine.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA\u0026beta;\u003csub\u003e1\u0026ndash;42\u003c/sub\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;preparation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA\u0026beta;\u003csub\u003e1\u0026ndash;42\u003c/sub\u003e peptide was purchased from AnaSpec (Fremont) and prepared as previously described.\u003ca href=\"#_ENREF_84\" title=\"Dahlgren, 2002 #10\"\u003e\u003csup\u003e84\u003c/sup\u003e\u003c/a\u003e On the day of\u0026nbsp;A\u0026beta;\u003csub\u003e1\u0026ndash;42\u003c/sub\u003e treatment, after incubation,\u0026nbsp;the working solutions were centrifuged at 14000 \u0026times; g at 4\u0026deg;C for 10 min to purify the oligomeric A\u0026beta; fraction from the fibrils.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImmunohistochemistry\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMice were transcardially\u0026nbsp;perfused with 4% PFA in PBS, and isolated brains were postfixed in the same fixative for 24 hours. Brains were then cryoprotected in 30% sucrose, sectioned serially on a cryostat (40 mm), and stored in 50% glycerol/50% PBS at \u0026minus;20\u0026deg;C until use. Brain sections were blocked for 30 min\u0026nbsp;in 3% BSA + 0.1% Triton X-100 in PBS and incubated with primary antibodies diluted in blocking buffer\u0026nbsp;overnight at 4\u0026deg;C. After overnight incubation, sections were washed three times in PBS and incubated with secondary antibodies or Hoechst 33242 (Invitrogen) diluted in PBS for 30 min at room temperature.\u0026nbsp;Subsequently, the sections were washed, mounted, and observed under a slide scanner (Zeiss) or a\u0026nbsp;confocal microscope (Leica).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHippocampal slice preparation and electrophysiology\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAPP/PS1 mice and WT mice (13 months old) were anesthetized with isoflurane (5% isoflurane, 95% O\u003csub\u003e2\u003c/sub\u003e) and perfused with ice-cold sucrose artificial cerebrospinal fluid (aCSF) containing 195.5 mM sucrose, 2.5 mM KCl, 1 mM NaH\u003csub\u003e2\u003c/sub\u003ePO\u003csub\u003e4\u003c/sub\u003e, 32.5 mM NaHCO\u003csub\u003e3\u003c/sub\u003e, 11 mM glucose, 2 mM Na pyruvate, and 1 mM Na ascorbate (all chemicals from Sigma) bubbled with 95% O\u003csub\u003e2\u003c/sub\u003e/5% CO\u003csub\u003e2\u003c/sub\u003e at a pH of 7.4. After perfusion, the brains were quickly removed from the skull, and sagittal hippocampal slices (400 \u0026mu;m thick) were cut on a vibratome (Leica). The slices were incubated at 35\u0026deg;C for 15 min in an incubation solution containing 119 mM NaCl, 2.5 mM KCl, 1 mM NaH\u003csub\u003e2\u003c/sub\u003ePO\u003csub\u003e4\u003c/sub\u003e, 26.2 NaHCO\u003csub\u003e3\u003c/sub\u003e, 11 mM glucose, 2 mM Na pyruvate, 1 mM Na ascorbate, 3 mM MgSO\u003csub\u003e4\u003c/sub\u003e, and 1.5 mM CaCl\u003csub\u003e2\u003c/sub\u003e. After incubation, the slices were transferred to aCSF solution at 23\u0026ndash;24\u0026deg;C for 1 hour.\u003c/p\u003e\n\u003cp\u003eField recordings were made with a concentric bipolar electrode positioned in the stratum radiatum of the CA1 region using an extracellular glass pipette (3\u0026ndash;5 MΩ) filled with aCSF. Stimulation was delivered through a bipolar electrode (FHC, Bowdoin, ME, USA) placed in the SC-CA1. The SC circuit was visualized using differential interference contrast (DIC) microscopy at 4\u0026times; magnification and identified by the ability to evoke short and constant latency fEPSPs at CA1 synapses by SC input stimulation. The test stimulation in all fEPSP experiments was measured before the experiments (30\u0026ndash;300 \u0026mu;A), and a test-pulse stimulation strength that evoked 50% of the maximum fEPSP was used. Baseline synaptic responses were recorded for 30 min, and then LTP was induced by theta burst stimulation (100 Hz, 10 trains, 40 ms duration, 200 ms intertrain interval). LTP was calculated by an average of fEPSP amplitudes during the last 5 min of recordings. Recordings were made every 10 s for 1 hour using an Axopatch 700A amplifier (Molecular Devices) digitized at 10 kHz and filtered at two kHz with Digidata 1440A and pClamp 10.0 software (Molecular Devise).\u003c/p\u003e\n\u003cp\u003eTo measure mEPSCs, the electrode was filled with an internal solution containing 135 mM Cs methane sulfonate, 8 mM NaCl, 10 mM HEPES, 0.5 mM EGTA, 4 mM Mg-ATP, 0.3 mM Na-GTP, and 5 mM QX-315 Cl; pH 7.25 with CsOH, 285 mOsm). Miniature currents were recorded in the presence of tetrodotoxin (1 \u0026mu;M TTX, Tocris) to block sodium currents and propagate action potentials.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStereotaxic FAM19A5 injection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor stereotaxic injection of WT and MT form of FAM19A5, three-month-old male and female mice were anesthetized with xylazene and ketamine. An injection cannula was inserted stereotaxically into the striatum (mediolateral, 2.0 mm from bregma; anteroposterior, 0.5 mm; dorsoventral, 3.5 mm) unilaterally (inserted into the right hemisphere). The infusion was performed at a rate of 0.2 \u0026mu;l per min, and 2 \u0026mu;l of FAM19A5 (5 \u0026mu;g \u0026mu;l\u0026minus;1 in PBS) or the same volume of PBS were injected into the mouse.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnimal behavioral tests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMale mice used in all behavioral tests were 9\u0026ndash;11 months old. All assays used littermates or age-matched animals. Behavioral tests were performed in a light- and noise-controlled behavioral room, where the animals were allowed to adapt for one hour before each behavioral test. All behavioral results were analyzed blindly.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eY-maze test\u003c/p\u003e\n\u003cp\u003eA Y-shaped maze consists of three identical arms (40 cm in length, 15 cm in height) at a 120\u0026deg; angle from each other. Mice were allowed to freely explore the three arms for 8 min with a luminosity of 40 lux. The sequence and the total number of arms entered were measured. Spontaneous alteration (%) was calculated as follows: the number of triads containing entries into all three arms/maximum possible alternations (the total number of arms entered \u0026ndash; 2) \u0026times; 100. Mice that constituted fewer than 10 of the total arm entries were omitted from the analysis.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMorris water maze test\u003c/p\u003e\n\u003cp\u003eMice were trained to find the hidden platform (9\u0026nbsp;cm in\u0026nbsp;diameter) in a stainless-steel pool (90 cm in diameter, 50 cm in height) filled with water (22 \u0026plusmn; 1\u0026deg;C) to a depth of 30 cm. The platform was 1 cm below the water level. In the acquisition phase, mice were trained for six consecutive days with four trials/per day. Each trial ended either when an animal climbed onto the platform or when a maximum of 60 s had elapsed. Next, mice were allowed to remain on the platform for 10 s. If they failed to locate the platform within 60 s, they were guided to the platform and left there for 10 s, and the escape time was recorded as 60 s. On day 7, for the probe test, the platform was removed, and mice were allowed to explore freely for 60 s. The spatial memory ability of individual animals in the probe test was determined by the following parameters: latency to target, target crossing number, distance to the target, the percentage in quadrant SW, and the percentage in the target. Target and quadrant SW refer to the location and quadrant where the hidden platform was located, respectively. These parameters were analyzed by SMART video tracking software (Panlab). Mice displaying abnormal behaviors, such as freezing and floating, were excluded from the final data.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePassive avoidance test\u003c/p\u003e\n\u003cp\u003eThe passive avoidance test, performed in plastic cages of identical size, assessed associative learning and memory by using the rodents\u0026rsquo; innate preference for darkness. The inside of a darkened cage was designed to induce a foot shock; thus, when mice entered the dark compartment from the light compartment, a foot shock (0.5 mA intensity) was delivered for 3 s. To assess memory, we placed mice in the light compartment 24 hours later and measured the time it took to enter the dark compartment. The maximal latency was 300 s. Animals showing freezing behaviors (with acquisition time\u0026nbsp;\u0026ge; 200 s) or abnormal exploration\u0026nbsp;were excluded from the final analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eQUANTIFICATION AND STATISTICAL ANALYSIS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll statistical analyses were performed using GraphPad Prism 8 with 95% confidence. Comparisons between two groups were performed using unpaired two-tailed Student\u0026rsquo;s t-test when the data followed a normal distribution, while the Mann-Whitney test was used when the data showed a nonnormal distribution. In the case of data comparing more than three groups, one-way ANOVA followed by Dunn\u0026rsquo;s multiple comparison test was used. All data are presented as the mean \u0026plusmn; SEM. All the details of the statistical tests and results are reported in the figure legends. All experiments were duplicated or triplicated with similar results.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAbitz, M., Nielsen, R.D., Jones, E.G., Laursen, H., Graem, N., and Pakkenberg, B. (2007). Excess of neurons in the human newborn mediodorsal thalamus compared with that of the adult. Cereb. Cortex 17, 2573\u0026ndash;2578. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/cercor/bhl163\u003c/span\u003e\u003cspan address=\"10.1093/cercor/bhl163\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuttenlocher, P.R. (1979). Synaptic density in human frontal cortex - developmental changes and effects of aging. Brain Res. 163, 195\u0026ndash;205. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/0006-8993(79)90349-4\u003c/span\u003e\u003cspan address=\"10.1016/0006-8993(79)90349-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKolb, B., Mychasiuk, R., Muhammad, A., and Gibb, R. (2013). Chapter 2 - Brain plasticity in the developing brain. Prog. Brain Res. 207, 35\u0026ndash;64. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/B978-0-444-63327-9.00005-9\u003c/span\u003e\u003cspan address=\"10.1016/B978-0-444-63327-9.00005-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFeinberg, I. (1982). Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence? J. Psychiatr. Res. 17, 319\u0026ndash;334. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/0022-3956(82)90038-3\u003c/span\u003e\u003cspan address=\"10.1016/0022-3956(82)90038-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArtola, A. (2008). Diabetes-, stress- and ageing-related changes in synaptic plasticity in hippocampus and neocortex \u0026mdash; The same metaplastic process? Eur. J. Pharmacol. 585, 153\u0026ndash;162. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ejphar.2007.11.084\u003c/span\u003e\u003cspan address=\"10.1016/j.ejphar.2007.11.084\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim, J.J., and Diamond, D.M. (2002). The stressed hippocampus, synaptic plasticity and lost memories. Nat. Rev. Neurosci. 3, 453\u0026ndash;462. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/nrn849\u003c/span\u003e\u003cspan address=\"10.1038/nrn849\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFoster, T.C. (2002). Regulation of synaptic plasticity in memory and memory decline with aging. Prog. Brain Res. 138, 283\u0026ndash;303. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/s0079-6123(02)38083-x\u003c/span\u003e\u003cspan address=\"10.1016/s0079-6123(02)38083-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJackson, J., Jambrina, E., Li, J., Marston, H., Menzies, F., Phillips, K., and Gilmour, G. (2019). Targeting the synapse in Alzheimer's disease. Front. Neurosci. 13, 735. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/fnins.2019.00735\u003c/span\u003e\u003cspan address=\"10.3389/fnins.2019.00735\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNathan, P.J., Cobb, S.R., Lu, B., Bullmore, E.T., and Davies, C.H. (2011). Studying synaptic plasticity in the human brain and opportunities for drug discovery. Curr. Opin. Pharmacol. 11, 540\u0026ndash;548. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.coph.2011.06.008\u003c/span\u003e\u003cspan address=\"10.1016/j.coph.2011.06.008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSellgren, C.M., Gracias, J., Watmuff, B., Biag, J.D., Thanos, J.M., Whittredge, P.B., Fu, T., Worringer, K., Brown, H.E., Wang, J., et al. (2019). Increased synapse elimination by microglia in schizophrenia patient-derived models of synaptic pruning. Nat. Neurosci. 22, 374\u0026ndash;385. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41593-018-0334-7\u003c/span\u003e\u003cspan address=\"10.1038/s41593-018-0334-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcAllister, A.K. (2007). Dynamic aspects of CNS synapse formation. Annu. Rev. Neurosci. 30, 425\u0026ndash;450. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1146/annurev.neuro.29.051605.112830\u003c/span\u003e\u003cspan address=\"10.1146/annurev.neuro.29.051605.112830\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eS\u0026uuml;dhof, T.C. (2018). Towards an understanding of synapse formation. Neuron 100, 276\u0026ndash;293. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.neuron.2018.09.040\u003c/span\u003e\u003cspan address=\"10.1016/j.neuron.2018.09.040\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDalva, M.B., McClelland, A.C., and Kayser, M.S. (2007). Cell adhesion molecules: signalling functions at the synapse. Nat. Rev. Neurosci. 8, 206\u0026ndash;220. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/nrn2075\u003c/span\u003e\u003cspan address=\"10.1038/nrn2075\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeNardo, L.A., de Wit, J., Otto-Hitt, S., and Ghosh, A. (2012). NGL-2 regulates input-specific synapse development in CA1 pyramidal neurons. Neuron 76, 762\u0026ndash;775. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.neuron.2012.10.013\u003c/span\u003e\u003cspan address=\"10.1016/j.neuron.2012.10.013\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim, S., Burette, A., Chung, H.S., Kwon, S.K., Woo, J., Lee, H.W., Kim, K., Kim, H., Weinberg, R.J., and Kim, E. (2006). NGL family PSD-95-interacting adhesion molecules regulate excitatory synapse formation. Nat. Neurosci. 9, 1294\u0026ndash;1301. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/nn1763\u003c/span\u003e\u003cspan address=\"10.1038/nn1763\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWoo, J., Kwon, S.K., and Kim, E. (2009). The NGL family of leucine-rich repeat-containing synaptic adhesion molecules. Mol. Cell. Neurosci. 42, 1\u0026ndash;10. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.mcn.2009.05.008\u003c/span\u003e\u003cspan address=\"10.1016/j.mcn.2009.05.008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKwon, S.K., Woo, J., Kim, S.Y., Kim, H., and Kim, E. (2010). Trans-synaptic adhesions between netrin-G ligand-3 (NGL-3) and receptor tyrosine phosphatases LAR, protein-tyrosine phosphatase delta (PTPdelta), and PTPsigma via specific domains regulate excitatory synapse formation. J. Biol. Chem. 285, 13966\u0026ndash;13978. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1074/jbc.M109.061127\u003c/span\u003e\u003cspan address=\"10.1074/jbc.M109.061127\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTakahashi, H., and Craig, A.M. (2013). Protein tyrosine phosphatases PTPδ, PTPσ, and LAR: presynaptic hubs for synapse organization. Trends Neurosci. 36, 522\u0026ndash;534. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.tins.2013.06.002\u003c/span\u003e\u003cspan address=\"10.1016/j.tins.2013.06.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWoo, J., Kwon, S.K., Choi, S., Kim, S., Lee, J.R., Dunah, A.W., Sheng, M., and Kim, E. (2009). Trans-synaptic adhesion between NGL-3 and LAR regulates the formation of excitatory synapses. Nat. Neurosci. 12, 428\u0026ndash;437. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/nn.2279\u003c/span\u003e\u003cspan address=\"10.1038/nn.2279\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee, H., Lee, E.J., Song, Y.S., and Kim, E. (2014). Long-term depression-inducing stimuli promote cleavage of the synaptic adhesion molecule NGL-3 through NMDA receptors, matrix metalloproteinases and presenilin/γ-secretase. Phil. Trans. R. Soc. B 369, 20130158. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1098/rstb.2013.0158\u003c/span\u003e\u003cspan address=\"10.1098/rstb.2013.0158\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee, H., Shin, W., Kim, K., Lee, S., Lee, E.J., Kim, J., Kweon, H., Lee, E., Park, H., Kang, M., et al. (2019). NGL-3 in the regulation of brain development, Akt/GSK3b signaling, long-term depression, and locomotive and cognitive behaviors. PLoS Biol. 17, e2005326. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1371/journal.pbio.2005326\u003c/span\u003e\u003cspan address=\"10.1371/journal.pbio.2005326\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTom Tang, Y., Emtage, P., Funk, W.D., Hu, T., Arterburn, M., Park, E.E., and Rupp, F. (2004). TAFA: a novel secreted family with conserved cysteine residues and restricted expression in the brain. Genomics 83, 727\u0026ndash;734. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ygeno.2003.10.006\u003c/span\u003e\u003cspan address=\"10.1016/j.ygeno.2003.10.006\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJeong, I., Yun, S., Shahapal, A., Cho, E.B., Hwang, S.W., Seong, J.Y., and Park, H.C. (2021). FAM19A5l affects mustard oil-Induced peripheral nociception in zebrafish. Mol. Neurobiol. 58, 4770\u0026ndash;4785. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s12035-021-02449-z\u003c/span\u003e\u003cspan address=\"10.1007/s12035-021-02449-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKwak, H., Cho, E.-H., Cho, E.B., Lee, Y.-N., Shahapal, A., Yong, H.J., Reyes-Alcaraz, A., Jeong, Y., Lee, Y., Lee, M., et al. (2020). Is FAM19A5 an adipokine? Peripheral FAM19A5 in wild-type, FAM19A5 knock-out, and LacZ knock-in mice. bioRxiv. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1101/2020.02.19.955351\u003c/span\u003e\u003cspan address=\"10.1101/2020.02.19.955351\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZeisel, A., Hochgerner, H., L\u0026ouml;nnerberg, P., Johnsson, A., Memic, F., van der Zwan, J., H\u0026auml;ring, M., Braun, E., Borm, L.E., La Manno, G., et al. (2018). Molecular architecture of the mouse nervous system. Cell 174, 999\u0026ndash;1014.e1022. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.cell.2018.06.021\u003c/span\u003e\u003cspan address=\"10.1016/j.cell.2018.06.021\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhalaj, A.J., Sterky, F.H., Sclip, A., Schwenk, J., Brunger, A.T., Fakler, B., and S\u0026uuml;dhof, T.C. (2020). Deorphanizing FAM19A proteins as pan-neurexin ligands with an unusual biosynthetic binding mechanism. J. Cell Biol. 219. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1083/jcb.202004164\u003c/span\u003e\u003cspan address=\"10.1083/jcb.202004164\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang, S., Zheng, C., Xie, G., Song, Z., Wang, P., Bai, Y., Chen, D., Zhang, Y., Lv, P., Liang, W., et al. (2021). FAM19A5/TAFA5, a novel neurokine, plays a crucial role in depressive-like and spatial memory-related behaviors in mice. Mol. Psychiatry 26, 2363\u0026ndash;2379. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41380-020-0720-x\u003c/span\u003e\u003cspan address=\"10.1038/s41380-020-0720-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKashevarova, A.A., Belyaeva, E.O., Nikonov, A.M., Plotnikova, O.V., Skryabin, N.A., Nikitina, T.V., Vasilyev, S.A., Yakovleva, Y.S., Babushkina, N.P., Tolmacheva, E.N., et al. (2018). Compound phenotype in a girl with r(22), concomitant microdeletion 22q13.32-q13.33 and mosaic monosomy 22. Mol. Cytogenet. 11, 26. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s13039-018-0375-3\u003c/span\u003e\u003cspan address=\"10.1186/s13039-018-0375-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKnutson, K.A., Deng, Y., and Pan, W. (2020). Implicating causal brain imaging endophenotypes in Alzheimer's disease using multivariable IWAS and GWAS summary data. NeuroImage 223, 117347. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.neuroimage.2020.117347\u003c/span\u003e\u003cspan address=\"10.1016/j.neuroimage.2020.117347\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMez, J., Chung, J., Jun, G., Kriegel, J., Bourlas, A.P., Sherva, R., Logue, M.W., Barnes, L.L., Bennett, D.A., Buxbaum, J.D., et al. (2017). Two novel loci, COBL and SLC10A2, for Alzheimer's disease in african americans. Alzheimers Dement. 13, 119\u0026ndash;129. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jalz.2016.09.002\u003c/span\u003e\u003cspan address=\"10.1016/j.jalz.2016.09.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMathys, H., Davila-Velderrain, J., Peng, Z., Gao, F., Mohammadi, S., Young, J.Z., Menon, M., He, L., Abdurrob, F., Jiang, X., et al. (2019). Single-cell transcriptomic analysis of Alzheimer's disease. Nature 570, 332\u0026ndash;337. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41586-019-1195-2\u003c/span\u003e\u003cspan address=\"10.1038/s41586-019-1195-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi, J., Li, S., Song, Y., Zhou, W., Zhu, X., Xu, S., Ma, Y., and Zhu, C. (2020). Association of serum FAM19A5 with cognitive impairment in vascular dementia. Dis. Markers. 2020, 8895900. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1155/2020/8895900\u003c/span\u003e\u003cspan address=\"10.1155/2020/8895900\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark, M.Y., Kim, H.S., Lee, M., Park, B., Lee, H.Y., Cho, E.B., Seong, J.Y., and Bae, Y.S. (2017). FAM19A5, a brain-specific chemokine, inhibits RANKL-induced osteoclast formation through formyl peptide receptor 2. Sci. Rep. 7, 15575. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41598-017-15586-0\u003c/span\u003e\u003cspan address=\"10.1038/s41598-017-15586-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang, Y., Chen, D., Zhang, Y., Wang, P., Zheng, C., Zhang, S., Yu, B., Zhang, L., Zhao, G., Ma, B., et al. (2018). Novel adipokine, FAM19A5, inhibits neointima formation after injury through sphingosine-1-phosphate receptor 2. Circulation 138, 48\u0026ndash;63. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1161/circulationaha.117.032398\u003c/span\u003e\u003cspan address=\"10.1161/circulationaha.117.032398\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang, Y., Zhang, Z., Wan, W., Liu, Y., Jing, H., and Dong, F. (2022). FAM19A5/S1PR1 signaling pathway regulates the viability and proliferation of mantle cell lymphoma. J. Recept. Signal Transduct. Res. 42, 225\u0026ndash;229. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1080/10799893.2021.1895220\u003c/span\u003e\u003cspan address=\"10.1080/10799893.2021.1895220\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLarouche, R. (2021, November 4\u0026ndash;2022, December 22). A FIH study to assess the safety and tolerability of NS intravenous NS101 infusion. Identifier NCT05143463. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://ClinicalTrials.gov/show/NCT05143463\u003c/span\u003e\u003cspan address=\"https://ClinicalTrials.gov/show/NCT05143463\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWestwood, S., Liu, B., Baird, A.L., Anand, S., Nevado-Holgado, A.J., Newby, D., Pikkarainen, M., Hallikainen, M., Kuusisto, J., Streffer, J.R., et al. (2017). The influence of insulin resistance on cerebrospinal fluid and plasma biomarkers of Alzheimer's pathology. Alz. Res. Ther. 9, 31. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s13195-017-0258-6\u003c/span\u003e\u003cspan address=\"10.1186/s13195-017-0258-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXiong, L.L., Xue, L.L., Chen, Y.J., Du, R.L., Wang, Q., Wen, S., Zhou, L., Liu, T., Wang, T.H., and Yu, C.Y. (2021). Proteomics study on the cerebrospinal fluid of patients with encephalitis. ACS omega 6, 16288\u0026ndash;16296. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1021/acsomega.1c00367\u003c/span\u003e\u003cspan address=\"10.1021/acsomega.1c00367\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang, H., Dey, K.K., Chen, P.C., Li, Y., Niu, M., Cho, J.H., Wang, X., Bai, B., Jiao, Y., Chepyala, S.R., et al. (2020). Integrated analysis of ultra-deep proteomes in cortex, cerebrospinal fluid and serum reveals a mitochondrial signature in Alzheimer's disease. Mol. Neurodegener. 15, 43. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s13024-020-00384-6\u003c/span\u003e\u003cspan address=\"10.1186/s13024-020-00384-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Ž\u0026iacute;dek, A., Potapenko, A., et al. (2021). Highly accurate protein structure prediction with AlphaFold. Nature 596, 583\u0026ndash;589. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41586-021-03819-2\u003c/span\u003e\u003cspan address=\"10.1038/s41586-021-03819-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaek, M., DiMaio, F., Anishchenko, I., Dauparas, J., Ovchinnikov, S., Lee, G.R., Wang, J., Cong, Q., Kinch, L.N., Schaeffer, R.D., et al. (2021). Accurate prediction of protein structures and interactions using a three-track neural network. Science 373, 871\u0026ndash;876. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1126/science.abj8754\u003c/span\u003e\u003cspan address=\"10.1126/science.abj8754\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHumphreys, I.R., Pei, J., Baek, M., Krishnakumar, A., Anishchenko, I., Ovchinnikov, S., Zhang, J., Ness, T.J., Banjade, S., Bagde, S.R., et al. (2021). Computed structures of core eukaryotic protein complexes. Science 374, eabm4805. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1126/science.abm4805\u003c/span\u003e\u003cspan address=\"10.1126/science.abm4805\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWon, S.Y., and Kim, H.M. (2018). Structural basis for LAR-RPTP-mediated synaptogenesis. Mol. Cells 41, 622\u0026ndash;630. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.14348/molcells.2018.0202\u003c/span\u003e\u003cspan address=\"10.14348/molcells.2018.0202\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCove, J., Blinder, P., Abi-Jaoude, E., Lafreni\u0026egrave;re-Roula, M., Devroye, L., and Baranes, D. (2006). Growth of neurites toward neurite- neurite contact sites increases synaptic clustering and secretion and is regulated by synaptic activity. Cereb. Cortex 16, 83\u0026ndash;92. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/cercor/bhi086\u003c/span\u003e\u003cspan address=\"10.1093/cercor/bhi086\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGlantz, L.A., Gilmore, J.H., Hamer, R.M., Lieberman, J.A., and Jarskog, L.F. (2007). Synaptophysin and postsynaptic density protein 95 in the human prefrontal cortex from mid-gestation into early adulthood. Neuroscience 149, 582\u0026ndash;591. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.neuroscience.2007.06.036\u003c/span\u003e\u003cspan address=\"10.1016/j.neuroscience.2007.06.036\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eReese, D., and Drapeau, P. (1998). Neurite growth patterns leading to functional synapses in an identified embryonic neuron. J. Neurosci. 18, 5652\u0026ndash;5662. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1523/jneurosci.18-15-05652.1998\u003c/span\u003e\u003cspan address=\"10.1523/jneurosci.18-15-05652.1998\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDzyubenko, E., Rozenberg, A., Hermann, D.M., and Faissner, A. (2016). Colocalization of synapse marker proteins evaluated by STED-microscopy reveals patterns of neuronal synapse distribution in vitro. J. Neurosci. Methods 273, 149\u0026ndash;159. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jneumeth.2016.09.001\u003c/span\u003e\u003cspan address=\"10.1016/j.jneumeth.2016.09.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChames, P., Van Regenmortel, M., Weiss, E., and Baty, D. (2009). Therapeutic antibodies: successes, limitations and hopes for the future. Br. J. Pharmacol. 157, 220\u0026ndash;233. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/j.1476-5381.2009.00190.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1476-5381.2009.00190.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim, B.G., Dai, H.N., McAtee, M., Vicini, S., and Bregman, B.S. (2007). Labeling of dendritic spines with the carbocyanine dye DiI for confocal microscopic imaging in lightly fixed cortical slices. J. Neurosci. Methods 162, 237\u0026ndash;243. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jneumeth.2007.01.016\u003c/span\u003e\u003cspan address=\"10.1016/j.jneumeth.2007.01.016\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKuszczyk, M.A., Sanchez, S., Pankiewicz, J., Kim, J., Duszczyk, M., Guridi, M., Asuni, A.A., Sullivan, P.M., Holtzman, D.M., and Sadowski, M.J. (2013). Blocking the interaction between apolipoprotein E and Aβ reduces intraneuronal accumulation of Aβ and inhibits synaptic degeneration. Am. J. Pathol. 182, 1750\u0026ndash;1768. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ajpath.2013.01.034\u003c/span\u003e\u003cspan address=\"10.1016/j.ajpath.2013.01.034\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCoomans, E.M., Schoonhoven, D.N., Tuncel, H., Verfaillie, S.C.J., Wolters, E.E., Boellaard, R., Ossenkoppele, R., den Braber, A., Scheper, W., Schober, P., et al. (2021). In vivo tau pathology is associated with synaptic loss and altered synaptic function. Alz. Res. Ther. 13, 35. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s13195-021-00772-0\u003c/span\u003e\u003cspan address=\"10.1186/s13195-021-00772-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeng, L., Bestard-Lorigados, I., and Song, W. (2022). The synapse as a treatment avenue for Alzheimer's disease. Mol. Psychiatry 27, 2940\u0026ndash;2949. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41380-022-01565-z\u003c/span\u003e\u003cspan address=\"10.1038/s41380-022-01565-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSheng, M., Sabatini, B.L., and S\u0026uuml;dhof, T.C. (2012). Synapses and Alzheimer's disease. Cold Spring Harb. Perspect. Biol. 4. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1101/cshperspect.a005777\u003c/span\u003e\u003cspan address=\"10.1101/cshperspect.a005777\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpires-Jones, T.L., and Hyman, B.T. (2014). The intersection of amyloid beta and tau at synapses in Alzheimer's disease. Neuron 82, 756\u0026ndash;771. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.neuron.2014.05.004\u003c/span\u003e\u003cspan address=\"10.1016/j.neuron.2014.05.004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSuzuki, K., Elegheert, J., Song, I., Sasakura, H., Senkov, O., Matsuda, K., Kakegawa, W., Clayton, A.J., Chang, V.T., Ferrer-Ferrer, M., et al. (2020). A synthetic synaptic organizer protein restores glutamatergic neuronal circuits. Science 369. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1126/science.abb4853\u003c/span\u003e\u003cspan address=\"10.1126/science.abb4853\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMinkeviciene, R., Rheims, S., Dobszay, M.B., Zilberter, M., Hartikainen, J., F\u0026uuml;l\u0026ouml;p, L., Penke, B., Zilberter, Y., Harkany, T., Pitk\u0026auml;nen, A., and Tanila, H. (2009). Amyloid beta-induced neuronal hyperexcitability triggers progressive epilepsy. J. Neurosci. 29, 3453\u0026ndash;3462. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1523/jneurosci.5215-08.2009\u003c/span\u003e\u003cspan address=\"10.1523/jneurosci.5215-08.2009\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRadde, R., Bolmont, T., Kaeser, S.A., Coomaraswamy, J., Lindau, D., Stoltze, L., Calhoun, M.E., J\u0026auml;ggi, F., Wolburg, H., Gengler, S., et al. (2006). Abeta42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology. EMBO reports 7, 940\u0026ndash;946. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/sj.embor.7400784\u003c/span\u003e\u003cspan address=\"10.1038/sj.embor.7400784\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHeurling, K., Ashton, N.J., Leuzy, A., Zimmer, E.R., Blennow, K., Zetterberg, H., Eriksson, J., Lubberink, M., and Sch\u0026ouml;ll, M. (2019). Synaptic vesicle protein 2A as a potential biomarker in synaptopathies. Mol. Cell. Neurosci. 97, 34\u0026ndash;42. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.mcn.2019.02.001\u003c/span\u003e\u003cspan address=\"10.1016/j.mcn.2019.02.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarchetti, C., and Marie, H. (2011). Hippocampal synaptic plasticity in Alzheimer's disease: what have we learned so far from transgenic models? Rev. Neurosci. 22, 373\u0026ndash;402. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1515/rns.2011.035\u003c/span\u003e\u003cspan address=\"10.1515/rns.2011.035\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCaroni, P., Donato, F., and Muller, D. (2012). Structural plasticity upon learning: regulation and functions. Nat. Rev. Neurosci. 13, 478\u0026ndash;490. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/nrn3258\u003c/span\u003e\u003cspan address=\"10.1038/nrn3258\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKandel, E.R. (2001). The molecular biology of memory storage: a dialogue between genes and synapses. Science 294, 1030\u0026ndash;1038. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1126/science.1067020\u003c/span\u003e\u003cspan address=\"10.1126/science.1067020\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEngert, F., and Bonhoeffer, T. (1999). Dendritic spine changes associated with hippocampal long-term synaptic plasticity. Nature 399, 66\u0026ndash;70. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/19978\u003c/span\u003e\u003cspan address=\"10.1038/19978\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eToni, N., Buchs, P.A., Nikonenko, I., Bron, C.R., and Muller, D. (1999). LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite. Nature 402, 421\u0026ndash;425. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/46574\u003c/span\u003e\u003cspan address=\"10.1038/46574\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShipton, O.A., Leitz, J.R., Dworzak, J., Acton, C.E., Tunbridge, E.M., Denk, F., Dawson, H.N., Vitek, M.P., Wade-Martins, R., Paulsen, O., and Vargas-Caballero, M. (2011). Tau protein is required for amyloid β-induced impairment of hippocampal long-term potentiation. J. Neurosci. 31, 1688\u0026ndash;1692. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1523/jneurosci.2610-10.2011\u003c/span\u003e\u003cspan address=\"10.1523/jneurosci.2610-10.2011\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSon, H., and Carpenter, D.O. (1996). Interactions among paired-pulse facilitation and post-tetanic and long-term potentiation in the mossy fiber-CA3 pathway in rat hippocampus. Synapse 23, 302\u0026ndash;311. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/(sici)1098-2396(199608)23:4\u0026lt;302::Aid-syn8\u0026gt;3.0.Co;2-b\u003c/span\u003e\u003cspan address=\"10.1002/(sici)1098-2396(199608)23:4%3C302::Aid-syn8%3E3.0.Co;2-b\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTing, J.T., Kelley, B.G., Lambert, T.J., Cook, D.G., and Sullivan, J.M. (2007). Amyloid precursor protein overexpression depresses excitatory transmission through both presynaptic and postsynaptic mechanisms. Proc. Natl. Acad. Sci. USA. 104, 353\u0026ndash;358. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1073/pnas.0608807104\u003c/span\u003e\u003cspan address=\"10.1073/pnas.0608807104\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eS\u0026uuml;dhof, T.C. (2021). The cell biology of synapse formation. J Cell Biol. 220. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1083/jcb.202103052\u003c/span\u003e\u003cspan address=\"10.1083/jcb.202103052\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDunah, A.W., Hueske, E., Wyszynski, M., Hoogenraad, C.C., Jaworski, J., Pak, D.T., Simonetta, A., Liu, G., and Sheng, M. (2005). LAR receptor protein tyrosine phosphatases in the development and maintenance of excitatory synapses. Nat. Neurosci. 8, 458\u0026ndash;467. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/nn1416\u003c/span\u003e\u003cspan address=\"10.1038/nn1416\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLang, B.T., Cregg, J.M., DePaul, M.A., Tran, A.P., Xu, K., Dyck, S.M., Madalena, K.M., Brown, B.P., Weng, Y.L., Li, S., et al. (2015). Modulation of the proteoglycan receptor PTPσ promotes recovery after spinal cord injury. Nature 518, 404\u0026ndash;408. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/nature13974\u003c/span\u003e\u003cspan address=\"10.1038/nature13974\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLin, J.C., Ho, W.H., Gurney, A., and Rosenthal, A. (2003). The netrin-G1 ligand NGL-1 promotes the outgrowth of thalamocortical axons. Nat. Neurosci. 6, 1270\u0026ndash;1276. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/nn1148\u003c/span\u003e\u003cspan address=\"10.1038/nn1148\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTurrigiano, G.G., and Nelson, S.B. (2004). Homeostatic plasticity in the developing nervous system. Nat. Rev. Neurosci. 5, 97\u0026ndash;107. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/nrn1327\u003c/span\u003e\u003cspan address=\"10.1038/nrn1327\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYanamandra, K., Patel, T.K., Jiang, H., Schindler, S., Ulrich, J.D., Boxer, A.L., Miller, B.L., Kerwin, D.R., Gallardo, G., Stewart, F., et al. (2017). Anti-tau antibody administration increases plasma tau in transgenic mice and patients with tauopathy. Sci. Transl. Med. 9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1126/scitranslmed.aal2029\u003c/span\u003e\u003cspan address=\"10.1126/scitranslmed.aal2029\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJung, H., Lee, S.Y., Lim, S., Choi, H.R., Choi, Y., Kim, M., Kim, S., Lee, Y., Han, K.H., Chung, W.-S., and Kim, C.H. (2022). Anti-inflammatory clearance of amyloid-β by a chimeric Gas6 fusion protein. Nat. Med. 28, 1802\u0026ndash;1812. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41591-022-01926-9\u003c/span\u003e\u003cspan address=\"10.1038/s41591-022-01926-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eImbimbo, B.P., Balducci, C., Ippati, S., and Watling, M. (2023). Initial failures of anti-tau antibodies in Alzheimer's disease are reminiscent of the amyloid-β story. Neural. Regen. Res. 18, 117\u0026ndash;118. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.4103/1673-5374.340409\u003c/span\u003e\u003cspan address=\"10.4103/1673-5374.340409\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMullard, A. (2021). Landmark Alzheimer's drug approval confounds research community. Nature 594, 309\u0026ndash;310. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/d41586-021-01546-2\u003c/span\u003e\u003cspan address=\"10.1038/d41586-021-01546-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrillaman, M. (2022). Alzheimer's drug slows mental decline in trial - but is it a breakthrough? Nature 610, 15\u0026ndash;16. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/d41586-022-03081-0\u003c/span\u003e\u003cspan address=\"10.1038/d41586-022-03081-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eReardon, S. (2023). FDA approves Alzheimer's drug lecanemab amid safety concerns. Nature 613, 227\u0026ndash;228. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/d41586-023-00030-3\u003c/span\u003e\u003cspan address=\"10.1038/d41586-023-00030-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLau, S.F., Cao, H., Fu, A.K.Y., and Ip, N.Y. (2020). Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer's disease. Proc. Natl. Acad. Sci. USA. 117, 25800\u0026ndash;25809. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1073/pnas.2008762117\u003c/span\u003e\u003cspan address=\"10.1073/pnas.2008762117\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOtero-Garcia, M., Mahajani, S.U., Wakhloo, D., Tang, W., Xue, Y.Q., Morabito, S., Pan, J., Oberhauser, J., Madira, A.E., Shakouri, T., et al. (2022). Molecular signatures underlying neurofibrillary tangle susceptibility in Alzheimer's disease. Neuron 110, 2929\u0026ndash;2948.e2928. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.neuron.2022.06.021\u003c/span\u003e\u003cspan address=\"10.1016/j.neuron.2022.06.021\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMirdita, M., von den Driesch, L., Galiez, C., Martin, M.J., S\u0026ouml;ding, J., and Steinegger, M. (2017). Uniclust databases of clustered and deeply annotated protein sequences and alignments. Nucleic Acids Res. 45, D170-d176. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/nar/gkw1081\u003c/span\u003e\u003cspan address=\"10.1093/nar/gkw1081\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRemmert, M., Biegert, A., Hauser, A., and S\u0026ouml;ding, J. (2011). HHblits: lightning-fast iterative protein sequence searching by HMM-HMM alignment. Nat. Methods 9, 173\u0026ndash;175. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/nmeth.1818\u003c/span\u003e\u003cspan address=\"10.1038/nmeth.1818\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBeaudoin, G.M., 3rd, Lee, S.H., Singh, D., Yuan, Y., Ng, Y.G., Reichardt, L.F., and Arikkath, J. (2012). Culturing pyramidal neurons from the early postnatal mouse hippocampus and cortex. Nat. Protoc. 7, 1741\u0026ndash;1754. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/nprot.2012.099\u003c/span\u003e\u003cspan address=\"10.1038/nprot.2012.099\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMartin, J.A., and Wang, Z. (2011). Next-generation transcriptome assembly. Nat. Rev. Genet. 12, 671\u0026ndash;682. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/nrg3068\u003c/span\u003e\u003cspan address=\"10.1038/nrg3068\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDahlgren, K.N., Manelli, A.M., Stine, W.B., Jr., Baker, L.K., Krafft, G.A., and LaDu, M.J. (2002). Oligomeric and fibrillar species of amyloid-beta peptides differentially affect neuronal viability. J Biol. Chem. 277, 32046\u0026ndash;32053. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1074/jbc.M201750200\u003c/span\u003e\u003cspan address=\"10.1074/jbc.M201750200\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Neuracle Science Co., Ltd","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"FAM19A5, LRRC4B, PTPRF, Anti-FAM19A5 antibodies, Decoy with FB, Neurite growth, Synapse assembly, Neurological diseases, Alzheimer’s disease, Hippocampus","lastPublishedDoi":"10.21203/rs.3.rs-2589038/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2589038/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eDisruption in dynamic balance of synapse build-and-removal process is a major cause of neurological diseases, although the mechanisms underlying the brain fine-tunes and balances this process remain poorly understood. Here, we show that FAM19A5 binds to the postsynaptic adhesion molecule LRRC4B via the FAM19A5 binding (FB) domain, suppressing the interaction of LRRC4B with a presynaptic adhesion molecule PTPRF. Decoys with the FB domain bind to FAM19A5 and redirect it away from the FAM19A5-LRRC4B complex, promoting neurite growth and synapse formation of neurons. The anti-FAM19A5 monoclonal antibody NS101 breaks apart the FAM19A5-LRRC4B complex and enables the transfer of FAM19A5 from the brain into the bloodstream, leading to the restoration of synaptic integrity and improve cognitive function in mouse models of Alzheimer’s disease. Together, our findings suggest that blocking the complex with NS101 may offer therapeutic strategy for treating neurodegenerative diseases requiring regeneration of neurites and formation of new synapses.\u003c/p\u003e","manuscriptTitle":"Blocking the FAM19A5-LRRC4B complex enhances neurite growth and synapse assembly.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-02-15 21:37:36","doi":"10.21203/rs.3.rs-2589038/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"79c56d0f-18c5-4bcc-a3d4-a5a54137983c","owner":[],"postedDate":"February 15th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":19228868,"name":"Cognitive Neuroscience"},{"id":19228869,"name":"Neurology"},{"id":19228870,"name":"Cellular \u0026 Molecular Neuroscience"}],"tags":[],"updatedAt":"2023-02-15T21:37:37+00:00","versionOfRecord":[],"versionCreatedAt":"2023-02-15 21:37:36","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2589038","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2589038","identity":"rs-2589038","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}