In vitro induction and selection of fluoroquinolone-resistant mutants in Elizabethkingia anophelis.

For 29 parent strains, recognized by pulsed-field gel electrophoresis, the MICs multiplied significantly in the ciprofloxacin group than levofloxacin group, following the first and third induction cycle. Ser83Arg in GyrA was the most common site of mutations. No mutation in ParC nor ParE was identified in the selected mutants.

Sequentially Regulating Potential-Determining Step for Lowering CO2 Electroreduction Overpotential over Te-Doped Bi Nanotips.

Electrocatalytic conversion of CO2 into formate is recognized an economically-viable route to upgrade CO2, but requires high overpotential to realize the high selectivity owing to high energy barrier for driving the involved proton-coupled electron transfer (PCET) processes and serious ignorance of the second PCET. Herein, we surmount the challenge through sequential regulation of the potential-determining step (PDS) over Te-doped Bi (TeBi) nanotips. Computational studies unravel the incorporation of Te heteroatoms alters the PDS from the first PCET to the second one by substantially lowering the formation barrier for *OCHO intermediate, and the high-curvature nanotips induce enhanced electric field that can steer the formation of asymmetric *HCOOH. In this scenario, the thermodynamic barrier for *OCHO and *HCOOH can be sequentially decreased, thus enabling a high formate selectivity at low overpotential. Experimentally, distinct TeBi nanostructures are obtained via controlling Te content in the precursor and TeBi nanotips achieve >90% of Faradaic efficiency for formate production over a comparatively positive potential window (-0.57 V to -1.08 V). The strong Bi-Te covalent bonds also afford a robust stability. In an optimized membrane electrode assembly device, the formate production rate at 3.2 V reaches 10.1 mmol h-1 cm-2, demonstrating great potential for practical application.

Blastocyst-like Structures in the Peripheral Retina of Young Adult Beagles.

In this immunohistological study on the peripheral retina of 3-year-old beagle dogs, excised retina specimens were immunostained with antibodies against nestin, Oct4, Nanog, Sox2, CDX2, cytokeratin 18 (CK 18), RPE65, and YAP1, as well as hematoxylin and DAPI, two nuclear stains. Our findings revealed solitary cysts of various sizes in the inner retina. Intriguingly, a mass of small round cells with scant cytoplasms was observed in the cavity of small cysts, while many disorganized cells partially occupied the cavity of the large cysts. The small cysts were strongly positive for nestin, Oct4, Nanog, Sox2, CDX2, CK18, and YAP1. RPE65-positive cells were exclusively observed in the tissue surrounding the cysts. Since RPE65 is a specific marker of retinal pigment epithelial (RPE) cells, the surrounding cells of the peripheral cysts were presumably derived from RPE cells that migrated intraretinally. In the small cysts, intense positive staining for nestin, a marker of retinal stem cells, seemed to indicate that they were derived from retinal stem cells. The morphology and positive staining for markers of blastocyst and RPE cells indicated that the small cysts may have formed structures resembling the blastocyst, possibly caused by the interaction between retinal stem cells and migrated RPE cells.

Dysfunction of Complementarity Determining Region 1 Encoded by T Cell Receptor Beta Variable Gene Is Potentially Associated with African Swine Fever Virus Infection in Pigs.

The beta T-cell receptor (TRB) expressed by beta T cells is essential for foreign antigen recognition. The TRB locus contains a TRBV family that encodes three complementarity determining regions (CDRs). CDR1 is associated with antigen recognition and interactions with MHC molecules. In contrast to domestic pigs, African suids lack a 284-bp segment spanning exons 1 and 2 of the TRBV27 gene that contains a sequence encoding CDR1. In this study, we used the African swine fever virus (ASFV) as an example to investigate the effect of deleting the TRBV27-encoded CDR1 on the resistance of domestic pigs to exotic pathogens. We first successfully generated TRBV27-edited fibroblasts with disruption of the CDR1 sequence using CRISPR/Cas9 technology and used them as donor cells to generate gene-edited pigs via somatic cell nuclear transfer. The TRBV-edited and wild-type pigs were selected for synchronous ASFV infection. White blood cells were significantly reduced in the genetically modified pigs before ASFV infection. The genetically modified and wild-type pigs were susceptible to ASFV and exhibited typical fevers (>40 °C). However, the TRBV27-edited pigs had a higher viral load than the wild-type pigs. Consistent with this, the gene-edited pigs showed more clinical signs than the wild-type pigs. In addition, both groups of pigs died within 10 days and showed similar severe lesions in organs and tissues. Future studies using lower virulence ASFV isolates are needed to determine the relationship between the TRBV27 gene and ASFV infection in pigs over a relatively long period.

Molecular Pathways and Animal Models of Tricuspid Atresia and Univentricular Heart.

The process of valve formation is a complex process that involves intricate interplay between various pathways at precise times. Although we have not completely elucidated the molecular pathways that lead to normal valve formation, we have identified a few major players in this process. We are now able to implicate TGF-ß, BMP, and NOTCH as suspects in tricuspid atresia (TA), as well as their downstream targets: NKX2-5, TBX5, NFATC1, GATA4, and SOX9. We know that the TGF-ß and the BMP pathways converge on the SMAD4 molecule, and we believe that this molecule plays a very important role to tie both pathways to TA. Similarly, we look at the NOTCH pathway and identify the HEY2 as a potential link between this pathway and TA. Another transcription factor that has been implicated in TA is NFATC1. While several mouse models exist that include part of the TA abnormality as their phenotype, no true mouse model can be said to represent TA. Bridging this gap will surely shed light on this complex molecular pathway and allow for better understanding of the disease process.

Kinetic isotope effect reveals rate-limiting step in green-to-red photoconvertible fluorescent proteins.

Photoconvertible fluorescent proteins (pcFPs) undergo a slow photochemical transformation when irradiated with blue light. Since their emission is shifted from green to red, pcFPs serve as convenient fusion tags in several cutting-edge biological imaging technologies. Here, a pcFP termed the Least Evolved Ancestor (LEA) was used as a model system to determine the rate-limiting step of photoconversion. Perdeuterated histidine residues were introduced by isotopic enrichment and chromophore content was monitored by absorbance. pH-dependent photoconversion experiments were carried out by exposure to 405-nm light followed by dark equilibration. The loss of green chromophore correlated well with the rise of red, and maximum photoconversion rates were observed at pH 6.5 (0.059 ± 0.001 min-1 for red color acquisition). The loss of green and the rise of red provided deuterium kinetic isotope effects (DKIEs) that were identical within error, 2.9 ± 0.9 and 3.8 ± 0.6, respectively. These data indicate that there is one rate-determining step in the light reactions of photoconversion, and that CH bond cleavage occurs in the transition state of this step. We propose that these reactions are rate-limited on the min time scale by the abstraction of a proton at the His62 beta-carbon. A conformational intermediate such as a twisted or isomerized chromophore is proposed to slowly equilibrate in the dark to generate the red form. Additionally, His62 may shuttle protons to activate Glu211 to serve as a general base, while also facilitating beta-elimination. This idea is supported by a recent X-ray structure of methylated His62.

CDR grafting and site-directed mutagenesis approach for the generation and affinity maturation of Anti-CD20 nanobody.

BACKGROUND: Recently, new and advanced techniques have been adopted to design and produce nanobodies, which are used in diagnostic and immunotherapy treatments. Traditionally, nanobodies are prepared from camelid immune libraries that require animal treatments. However, such approaches require large library sizes and complicated selection procedures. The current study has employed CDR grafting and site-directed mutagenesis techniques to create genetically engineered nanobodies against the tumor marker CD20 (anti-CD20 nanobodies) used in leukemia treatment. METHODS AND RESULTS: In this study, we utilized the swapping method to graft CDRs from the VH Rituximab antibody to VHH CDRs. We aimed to enhance the binding affinity of the nanobodies by substituting the amino acids (Y101R-Y102R-Y107R) in the VHH-CDR3. To assess the binding capacity of the mutated nanobodies, we conducted an ELISA test. Moreover, through flow cytometry analysis, we compared the fluorescence intensity of the grafted CD20 and mutant nanobodies with that of the commercially available human anti-CD20 in Raji cells. The results showed a significant difference in the fluorescence intensity of the grafted nanobodies and mutant nanobodies when compared to the commercially available human anti-CD20. CONCLUSION: The approach we followed in this study makes it possible to create multiple anti-CD20 nanobodies with varying affinities without the need for extensive selection efforts. Additionally, our research has demonstrated that computational tools are highly reliable in designing functional nanobodies.

Facet-switching of rate-determining step on copper in CO2-to-ethylene electroreduction.

Reduction of carbon dioxide (CO2) by renewable electricity to produce multicarbon chemicals, such as ethylene (C2H4), continues to be a challenge because of insufficient Faradaic efficiency, low production rates, and complex mechanistic pathways. Here, we report that the rate-determining steps (RDS) on common copper (Cu) surfaces diverge in CO2 electroreduction, leading to distinct catalytic performances. Through a combination of experimental and computational studies, we reveal that C─C bond-making is the RDS on Cu(100), whereas the protonation of *CO with adsorbed water becomes rate-limiting on Cu(111) with a higher energy barrier. On an oxide-derived Cu(100)-dominant Cu catalyst, we reach a high C2H4 Faradaic efficiency of 72%, partial current density of 359 mA cm-2, and long-term stability exceeding 100 h at 500 mA cm-2, greatly outperforming its Cu(111)-rich counterpart. We further demonstrate constant C2H4 selectivity of >60% over 70 h in a membrane electrode assembly electrolyzer with a full-cell energy efficiency of 23.4%.

SLRfinder: A method to detect candidate sex-linked regions with linkage disequilibrium clustering.

Despite their critical roles in genetic sex determination, sex chromosomes remain unknown in many non-model organisms, especially those having recently evolved sex-linked regions (SLRs). These evolutionarily young and labile sex chromosomes are important for understanding early sex chromosome evolution but are difficult to identify due to the lack of Y/W degeneration and SLRs limited to small genomic regions. Here, we present SLRfinder, a method to identify candidate SLRs using linkage disequilibrium (LD) clustering, heterozygosity and genetic divergence. SLRfinder does not rely on specific sequencing methods or a specific type of reference genome (e.g., from the homomorphic sex). In addition, the input of SLRfinder does not require phenotypic sexes, which may be unknown from population sampling, but sex information can be incorporated and is necessary to validate candidate SLRs. We tested SLRfinder using various published datasets and compared it to the local principal component analysis (PCA) method and the depth-based method Sex Assignment Through Coverage (SATC). As expected, the local PCA method could not be used to identify unknown SLRs. SATC works better on conserved sex chromosomes, whereas SLRfinder outperforms SATC in analysing labile sex chromosomes, especially when SLRs harbour inversions. Power analyses showed that SLRfinder worked better when sampling more populations that share the same SLR. If analysing one population, a relatively larger sample size (around 50) is needed for sufficient statistical power to detect significant SLR candidates, although true SLRs are likely always top-ranked. SLRfinder provides a novel and complementary approach for identifying SLRs and uncovering additional sex chromosome diversity in nature.

Converting CO2 into natural gas within the autoclave: a kinetic study on hydrogenation of carbonates in aqueous solution.

Catalytic conversion of carbon dioxide (CO2) into value-added chemicals is of pivotal importance, well the cost of capturing CO2 from dilute atmosphere is super challenge. One promising strategy is combining the adsorption and transformation at one step, such as applying alkali solution that could selectively reduce carbonate (CO32-) as consequences of CO2 adsorption. Due to complexity of this system, the mechanistic details on controlling the hydrogenation have not been investigated in depth. Herein, Ru/TiO2 catalyst was applied as a probe to elucidate the mechanism of CO32- activation, in which with thermodynamic and kinetic investigations, a compact Langmuir-Hinshelwood reaction model was established which suggests that the overall rate of CO32- hydrogenation was controlled by a specific C-O bond rupture elementary step within HCOO- and the Ru surface was mainly covered by CO32- or HCOO- at independent conditions. This assumption was further supported by negligible kinetic isotope effects (kH/kD ≈ 1), similarity on reaction barriers of CO32- and HCOO- hydrogenation (ΔH‡hydr,Na2CO3 and ΔH‡hydr,HCOONa) and a non-variation of entropy (ΔS‡hydr ≈ 0). More interestingly, the alkalinity of the solution is certainly like a two sides in a sword and could facilitate the adsorption of CO2 while hold back catalysis during CO32- hydrogenation.

IGH Complementarity Determining Region-3-Cytomegalovirus Protein Chemical Complementarity Linked to Better Overall Survival Probabilities for Glioblastoma.

Cytomegalovirus (CMV) has long been thought to have an association with glioblastoma multiforme (GBM), although the exact role of CMV and any subsequent implications for treatment have yet to be fully understood. This study addressed whether IGH complementarity determining region-3 (CDR3)-CMV protein chemical complementarity, with IGH CDR3s representing both tumor resident and blood-sourced IGH recombinations, was associated with overall survival (OS) distinctions. IGH recombination sequencing reads were obtained from (a) the Clinical Proteomic Tumor Analysis Consortium, tumor RNAseq files; and (b) the cancer genome atlas, blood exome-derived files. The Adaptive Match web tool was used to calculate chemical complementarity scores (CSs) based on hydrophobic interactions, and those scores were used to group GBM cases and assess survival probabilities. We found a higher OS probability for cases whose hydrophobic IGH CDR3-CMV protein chemical complementarity scores (Hydro CSs) were in the upper 50th percentile for several CMV proteins, including UL99 and UL123, as well as for CSs based on known B cell epitopes representing these proteins. We also identified multiple immune signature genes, including CD79A and TNFRSF17, for which higher RNA expression was associated with higher Hydro CSs. Results were consistent with the idea that stronger immunoglobulin responses to CMV are associated with better OS probabilities for GBM.

The transcription factor sex-determining region Y-box 2 (SOX2) in bladder cancer.

Sex-determining region Y-box 2 (SOX2) is a transcription factor with a central role in embryologic development. SOX2 is also an oncogene in several cancer types. Prior work by our group has shown SOX2 activity associates with cell cycle dysregulation in early-stage bladder cancer. The present study was thus undertaken to broadly investigate SOX2 in bladder cancer, with emphasis on associations with tumor stage, clinical outcomes, and tumorigenicity. Gene expression was quantified by immunohistochemistry in an established tissue microarray (n=303 cystectomy specimens, all stages) and whole tissue sections of noninvasive papillary urothelial carcinoma (n=25). Gene expression by RNA sequencing was evaluated in non-muscle invasive and muscle-invasive cohorts from publicly available repositories. By immunohistochemistry, SOX2 was expressed in 40% of whole tissue sections of noninvasive papillary carcinoma, which correlated with SOX2 expression by RNA sequencing (r=0.6, P=0.001, Spearman correlation). Expression tended to be focal (median H-score =6). SOX2 was expressed in only 9% of TMA cases, consistent with focal expression. SOX2 expression was substantially higher in muscle-invasive compared with noninvasive papillary urothelial carcinoma by RNA sequencing (P<0.001, Wilcoxon rank sum test). SOX2 expression associated with stage progression in lamina-propria invasive cancers (hazard ratio =2, P=0.05, Cox model, binary, RNA sequencing) but not noninvasive papillary cancers (P=0.5, Cox model, binary, RNA sequencing). SOX2 expression did not associate with overall survival in muscle-invasive carcinoma. Activity of SOX2 in bladder cancer was tested in vivo using murine allografts created with MB49 cells that express human SOX2 (MB49-SOX). MB49-SOX allografts expressed this protein focally by immunohistochemistry, much like human tumors. Compared with controls, MB49 allografts demonstrated larger tumor size (P=0.03, Wilcoxon rank sum test) and higher tumor burden in mesenteric metastases (P=0.009, Wilcoxon rank sum test). Though SOX2 expression is focal within tumors, it may drive tumorigenesis, increase growth rate, and promote aggressive features of bladder cancer, particularly stage progression of early-stage disease.

Research on social and economic factors influencing regional mortality patterns in China.

Regional population mortality correlates with regional socioeconomic development. This study aimed to identify the key socioeconomic factors influencing mortality patterns in Chinese provinces. Using data from the Seventh Population Census, we analyzed mortality patterns by gender and urban‒rural division in 31 provinces. Using a functional regression model, we assessed the influence of fourteen indicators on mortality patterns. Main findings: (1) China shows notable gender and urban‒rural mortality variations across age groups. Males generally have higher mortality than females, and rural areas experience elevated mortality rates compared to urban areas. Mortality in individuals younger than 40 years is influenced mainly by urban‒rural factors, with gender becoming more noticeable in the 40-84 age group. (2) The substantial marginal impact of socioeconomic factors on mortality patterns generally becomes evident after the age of 45, with less pronounced differences in their impact on early-life mortality patterns. (3) Various factors have age-specific impacts on mortality. Education has a negative effect on mortality in individuals aged 0-29, extending to those aged 30-59 and diminishing in older age groups. Urbanization positively influences the probability of death in individuals aged 45-54 years, while the impact of traffic accidents increases with age. Among elderly people, the effect of socioeconomic variables is smaller, highlighting the intricate and heterogeneous nature of these influences and acknowledging certain limitations.

Assessing the impact of mega-city construction engineering on urban livability: an explorative study of Yan'an.

Yan'an City is a typical squeezed city in China and faces the challenge of limited living space. The adoption of the "Mountain Excavation and City Construction (MECC)" program was poised to elevate the city's livability. Despite the importance of megacity construction projects, few studies have examined their impact on urban livability. This study aims to fill this gap by analyzing the effects of MECC and the satisfaction characteristics of urban livability in Yan'an City, based on survey data from both old and new urban areas. Employing factor analysis and multiple linear regression, this paper assesses the influence of MECC on urban livability across different demographic groups, including age, educational background, and occupation. The empirical findings demonstrate a significant positive effect of the MECC project on urban livability. However, during categorization discussions, some respondents expressed concerns about its negative impact. The results of multiple linear regression indicate that factors such as career prospects, residential satisfaction, interpersonal relationships, and transportation level significantly influence livability (R2 = 0.607 in ND and R2 = 0.609 in OD).

Local chicken breeds exhibit abundant TCR-V segments but similar repertoire diversity.

The thymus-derived lymphocytes of jawed vertebrates have four T-cell receptor (TCR) chains that play a significant role in immunity. As chickens have commercial value, their immune systems require a great deal of attention. Local chicken breeds are an essential part of poultry genetic resources in China. Here, we used high-throughput sequencing to analyze the TCRα and TCRß repertoires and their relative expression levels in the native chicken breeds Baier Buff, Longyou Partridge, Xiaoshan, and Xianju. We found that TCR Vα and TCR Vß were expressed and included 17, 19, 17, and six segments of the Vα2, Vα3, Vß1, and Vß2 subgroups, respectively. V-J pairing was biased; Jα11 was utilized by nearly all Vα segments and was the most commonly used. Breed-specific V segments and V-J pairings were detected as well. The results of the principal coordinate analysis (PCoA) as well as the V-J pairing and CDR3 diversity analyses suggested that the four local chicken breeds did not significantly differ in terms of TCR diversity. Hence, they expressed not significant differentiation, and they are rich genetic resources for the development and utilization of immune-related poultry breeding.

Characterizing the antigenic evolution of pandemic influenza A (H1N1) pdm09 from 2009 to 2023.

The H1N1pdm09 virus has been a persistent threat to public health since the 2009 pandemic. Particularly, since the relaxation of COVID-19 pandemic mitigation measures, the influenza virus and SARS-CoV-2 have been concurrently prevalent worldwide. To determine the antigenic evolution pattern of H1N1pdm09 and develop preventive countermeasures, we collected influenza sequence data and immunological data to establish a new antigenic evolution analysis framework. A machine learning model (XGBoost, accuracy = 0.86, area under the receiver operating characteristic curve = 0.89) was constructed using epitopes, physicochemical properties, receptor binding sites, and glycosylation sites as features to predict the antigenic similarity relationships between influenza strains. An antigenic correlation network was constructed, and the Markov clustering algorithm was used to identify antigenic clusters. Subsequently, the antigenic evolution pattern of H1N1pdm09 was analyzed at the global and regional scales across three continents. We found that H1N1pdm09 evolved into around five antigenic clusters between 2009 and 2023 and that their antigenic evolution trajectories were characterized by cocirculation of multiple clusters, low-level persistence of former dominant clusters, and local heterogeneity of cluster circulations. Furthermore, compared with the seasonal H1N1 virus, the potential cluster-transition determining sites of H1N1pdm09 were restricted to epitopes Sa and Sb. This study demonstrated the effectiveness of machine learning methods for characterizing antigenic evolution of viruses, developed a specific model to rapidly identify H1N1pdm09 antigenic variants, and elucidated their evolutionary patterns. Our findings may provide valuable support for the implementation of effective surveillance strategies and targeted prevention efforts to mitigate the impact of H1N1pdm09.

A universal method for determining the detergent effect of surfactants.

Surfactants are indispensable in industrial applications today due to their wetting, emulsifying, dispersing, cleansing, and detergent properties. The use of surfactants extends from the cosmetic industry to the petroleum industry and beyond. Their characteristics and effectiveness can be assessed through various standardized tests, and based on these methods, their applications can be determined. However, there is a lack of a universally applicable testing method for one crucial and complex property: the detergent effect. The detergent effect refers to the removal of unwanted contaminants from a solid surface. However, cleaning is not solely attributed to the surfactant but to the appropriate combination of various factors, whose synergistic effect reduces surface contamination. The most significant factors influencing detergent effect include the characteristics and nature of the contaminants, properties of the cleaning solution (surfactant concentration and composition, water hardness, enzymes, etc.), temperature, washing time, and hydrodynamic conditions. Additionally, the presence of electrolytes, pH of the cleaning solution, and detergent foaming properties may also play important roles. Our goal was to develop a detergent effect testing methodology that is not specific to any particular application domain but offers a straightforward and easy-to-implement solution for comparing the detergent effect of various types of surfactants.•The study presents a method for determining detergent effect of surfactants.•The method is universal and suitable for the evaluation of any type of surfactant.•The method is low-cost and easy to perform.

Adjacent Implant Influence on Tooth Restoration in a Gastro-Esophageal Reflux Disease (GERD) Patient Using Monoblock Post-Fused Crown: A Case Report.

This case report explores how the presence of an adjacent implant influenced the restoration of a tooth with pulpitis in a gastro-esophageal reflux disease (GERD) patient. A patient with GERD requires a tooth-colored crown not only for aesthetics but also to address potential galvanic concerns arising from an adjacent implant. GERD, a condition causing non-cavity erosion, weakens tooth structure over time, presenting significant challenges in treatment. It resulted in bite relapse and insufficient occlusal clarity over time. A comprehensive treatment approach was needed to restore both function and appearance. This involved managing galvanism using non-metallic materials to ensure optimal occlusal clarity, as well as meticulously reinforcing and restoring tooth structure. Monoblock post-fused crowns were chosen for their superior durability, stability, and comfort. The ceramic layering not only effectively prevented galvanic issues by insulating the tooth structure but also significantly improved the natural appearance of teeth, thereby promoting long-term oral health and successfully managing complex dental concerns. The dental team successfully restored the damaged tooth by considering specific factors that influenced the treatment plan, including achieving optimal aesthetic outcomes.

Loss of TET2 increases B-1 cell number and IgM production while limiting CDR3 diversity.

Recent studies have demonstrated a role for Ten-Eleven Translocation-2 (TET2), an epigenetic modulator, in regulating germinal center formation and plasma cell differentiation in B-2 cells, yet the role of TET2 in regulating B-1 cells is largely unknown. Here, B-1 cell subset numbers, IgM production, and gene expression were analyzed in mice with global knockout of TET2 compared to wildtype (WT) controls. Results revealed that TET2-KO mice had elevated numbers of B-1a and B-1b cells in their primary niche, the peritoneal cavity, as well as in the bone marrow (B-1a) and spleen (B-1b). Consistent with this finding, circulating IgM, but not IgG, was elevated in TET2-KO mice compared to WT. Analysis of bulk RNASeq of sort purified peritoneal B-1a and B-1b cells revealed reduced expression of heavy and light chain immunoglobulin genes, predominantly in B-1a cells from TET2-KO mice compared to WT controls. As expected, the expression of IgM transcripts was the most abundant isotype in B-1 cells. Yet, only in B-1a cells there was a significant increase in the proportion of IgM transcripts in TET2-KO mice compared to WT. Analysis of the CDR3 of the BCR revealed an increased abundance of replicated CDR3 sequences in B-1 cells from TET2-KO mice, which was more clearly pronounced in B-1a compared to B-1b cells. V-D-J usage and circos plot analysis of V-J combinations showed enhanced usage of VH11 and VH12 pairings. Taken together, our study is the first to demonstrate that global loss of TET2 increases B-1 cell number and IgM production and reduces CDR3 diversity, which could impact many biological processes and disease states that are regulated by IgM.

High-throughput quantitative assessments of the chemical complementarity of celiac disease related IGH CDR3s and a gliadin epitope.

The long-term value of efficient antigen discovery includes gaining insights into the variety of potential cancer neoantigens, effective vaccines lacking adverse effects, and adaptive immune receptor (IR) targets for blocking adaptive IR-antigen interactions in autoimmunity. While the preceding goals have been partially addressed via big data approaches to HLA-epitope binding, there has been little such progress in the big data setting for adaptive IR-epitope binding. This delay in progress for the latter is likely due to, among other things, the much more complicated adaptive IR repertoire in an individual compared to individual HLA alleles. Thus, results described here represent the application of an algorithm for efficient assessment of IGH CDR3-gliadin epitope interactions, with a focus on epitopes known to be associated with an immune response in celiac disease. The hydrophobic, chemical complementarity between celiac case IGH CDR3s and known celiac epitopes was found to be greater in comparison to the hydrophobic, chemical complementarity between the same celiac case IGH CDR3s and a series of control epitopes. Thus, the approaches indicated here likely offer guidance for the development of conveniently applied algorithms for antigen verification and discovery.