Gene Symbol Research Articles

Study on the mechanism of Plantago asiatica L in the treatment of viral pneumonia based on network pharmacology

Objective: Viral pneumonia has caused great harm to human health and is infectious, and if it is not treated in time, the consequences will be immeasurable. Chinese medicine treatment of viral pneumonia is promising in clinical research at present. Here, we explore potential targets and mechanisms of Plantago asiatica L in the treatment of viral pneumonia. Methods: Traditional Chinese medicine (TCM) system and traditional Chinese medicine pharmacology database system pharmacology (TCMSP) (https://tcmspw.com/index.php) were used for screening active ingredients of Plantago asiatica L and targets related to active ingredients. The target proteins obtained from the TCMSP database were searched in the UniProt database (https://www.uniprot.org/) to obtain their corresponding gene names. GeneCards database (https://www. Genecards.org) was used to explore related targets closely associated with viral pneumonia. Subsequently, the Venny 2.1 database (https://bioinfogp.cnb.csic.es/tools/venny/) was applied before building a protein-protein interaction (PPI) network. The PPI network was constructed using the String database (https://string-db.org/), decoding the core anti-viral genes in viral pneumonia. Intersected genes were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to construct a network of "Disease-drug-active component-key target-KEGG pathway". Results: 9 active components, 96 targets, 402 important disease targets, and 3 common targets of viral pneumonia and plantain were obtained. The top 10 GO biological processes, 10 GO cell components, 10 GO molecular functions and the top 10 KEGG signaling pathways were screened out. Conclusion: Apoptosis regulator Bcl-2; CASP3: Caspase - 3; CASP8: Caspase - 8. Those targets act on viral pneumonia by participating in the biological process and regulating the signaling pathway of Kaposi sarcoma-associated herpes virus infection, which provides a basis for future experimental verification and clinical research.

MVAR: A Mouse Variation Registry

The Mouse Variation Registry (MVAR) resource is a scalable registry of mouse single nucleotide variants and small indels and variant annotation. The resource accepts data in standard Variant Call Format (VCF) and assesses the uniqueness of the submitted variants via a canonicalization process. Novel variants are assigned a unique, persistent MVAR identifier; variants that are equivalent to an existing variant in the resource are associated with the existing identifier. Annotations for variant type, molecular consequence, impact, and genomic region in the context of specific transcripts and protein sequences are generated using Ensembl’s Variant Effect Predictor (VEP) and Jannovar. Access to the data and annotations in MVAR are supported via an Application Programming Interface (API) and web application. Researchers can search the resource by gene symbol, genomic region, variant (expressed in Human Genome Variation Society syntax), refSNP identifiers, or MVAR identifiers. Tabular search results can be filtered by variant annotations (variant type, molecular consequence, impact, variant region) and viewed according to variant distribution across mouse strains. The registry currently comprises more than 99 million canonical single nucleotide variants for 581 strains of mice. MVAR is accessible from https://mvar.jax.org.

Targeting postsynaptic glutamate receptor scaffolding proteins PSD-95 and PICK1 for obesity treatment.

Human genome-wide association studies (GWAS) suggest a functional role for central glutamate receptor signaling and plasticity in body weight regulation. Here, we use UK Biobank GWAS summary statistics of body mass index (BMI) and body fat percentage (BF%) to identify genes encoding proteins known to interact with postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptors. Loci in/near discs large homolog 4 (DLG4) and protein interacting with C kinase 1 (PICK1) reached genome-wide significance (P < 5 × 10-8) for BF% and/or BMI. To further evaluate the functional role of postsynaptic density protein-95 (PSD-95; gene name: DLG4) and PICK1 in energy homeostasis, we used dimeric PSD-95/disc large/ZO-1 (PDZ) domain-targeting peptides of PSD-95 and PICK1 to demonstrate that pharmacological inhibition of PSD-95 and PICK1 induces prolonged weight-lowering effects in obese mice. Collectively, these data demonstrate that the glutamate receptor scaffolding proteins, PICK1 and PSD-95, are genetically linked to obesity and that pharmacological targeting of their PDZ domains represents a promising therapeutic avenue for sustained weight loss.

Tim4 deficiency reduces CD301b+ macrophage and aggravates periodontitis bone loss

Periodontitis is a common chronic inflammatory disease that causes the periodontal bone destruction and may ultimately result in tooth loss. With the progression of periodontitis, the osteoimmunology microenvironment in periodontitis is damaged and leads to the formation of pathological alveolar bone resorption. CD301b+ macrophages are specific to the osteoimmunology microenvironment, and are emerging as vital booster for conducting bone regeneration. However, the key upstream targets of CD301b+ macrophages and their potential mechanism in periodontitis remain elusive. In this study, we concentrated on the role of Tim4, a latent upstream regulator of CD301b+ macrophages. We first demonstrated that the transcription level of Timd4 (gene name of Tim4) in CD301b+ macrophages was significantly upregulated compared to CD301b− macrophages via high-throughput RNA sequencing. Moreover, several Tim4-related functions such as apoptotic cell clearance, phagocytosis and engulfment were positively regulated by CD301b+ macrophages. The single-cell RNA sequencing analysis subsequently discovered that Cd301b and Timd4 were specifically co-expressed in macrophages. The following flow cytometric analysis indicated that Tim4 positive expression rates in total macrophages shared highly synchronized dynamic changes with the proportions of CD301b+ macrophages as periodontitis progressed. Furthermore, the deficiency of Tim4 in mice decreased CD301b+ macrophages and eventually magnified alveolar bone resorption in periodontitis. Additionally, Tim4 controlled the p38 MAPK signaling pathway to ultimately mediate CD301b+ macrophages phenotype. In a word, Tim4 might regulate CD301b+ macrophages through p38 MAPK signaling pathway in periodontitis, which provided new insights into periodontitis immunoregulation as well as help to develop innovative therapeutic targets and treatment strategies for periodontitis.

Research on the mechanism of Angelicae dahurica in treating viral pneumonia based on network pharmacology

Objective: Network pharmacology was used to investigate the mechanism of Angelica dahurica in the treatment of viral pneumonia. Methods: The active components and their targets of Angelica dahurica were searched in systematic pharmacology database and analysis platform of Traditional Chinese Medicine, and then the targets were converted to gene names in UniProt database. After that, the related targets of viral pneumonia were searched by GeneCards database. The application of Venny 2.1 database could construct the "active components key targets" network. Cytoscape 3.7.0 software was used to construct the " Angelica dahurica-active components-viral pneumonia-targets" interaction network. After acquiring four overlapping target genes, it is crucial to utilize the STRING database to get the protein-protein interaction (PPI) network. The Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of core target genes were performed by using R language software for the intersection of drug action targets and disease targets. Results: In total, six effective active components were obtained by searching, including beta-sitosterol, sitosterol, kaempferol, stigmasterol, luteolin and quercetin. The PPI network was made by taking the four key target proteins after intersection. The biological functions involved in GO enrichment analysis include maturation of proteins, response to oxygen levels, regulation of mitochondrial outer membrane permeability in apoptotic signaling pathways, and response to decreased oxygen levels, etc. The biological pathways and biological processes involved in KEGG incorporate Apoptosis - multiple species, Platinum drug resistance, p53 signaling pathway, and Toxoplasmosis, etc. Conclusions: These findings will provide insights into Angelicae dahurica treatment for viral pneumonia.

NNOS in Erbb4-positive neurons regulates GABAergic transmission in mouse hippocampus

Neuronal nitric oxide synthase (nNOS, gene name Nos1) orchestrates the synthesis of nitric oxide (NO) within neurons, pivotal for diverse neural processes encompassing synaptic transmission, plasticity, neuronal excitability, learning, memory, and neurogenesis. Despite its significance, the precise regulation of nNOS activity across distinct neuronal types remains incompletely understood. Erb-b2 receptor tyrosine kinase 4 (ErbB4), selectively expressed in GABAergic interneurons and activated by its ligand neuregulin 1 (NRG1), modulates GABA release in the brain. Our investigation reveals the presence of nNOS in a subset of GABAergic interneurons expressing ErbB4. Notably, NRG1 activates nNOS via ErbB4 and its downstream phosphatidylinositol 3-kinase (PI3K), critical for NRG1-induced GABA release. Genetic removal of nNos from Erbb4-positive neurons impairs GABAergic transmission, partially rescued by the NO donor sodium nitroprusside (SNP). Intriguingly, the genetic deletion of nNos from Erbb4-positive neurons induces schizophrenia-relevant behavioral deficits, including hyperactivity, impaired sensorimotor gating, and deficient working memory and social interaction. These deficits are ameliorated by the atypical antipsychotic clozapine. This study underscores the role and regulation of nNOS within a specific subset of GABAergic interneurons, offering insights into the pathophysiological mechanisms of schizophrenia, given the association of Nrg1, Erbb4, Pi3k, and Nos1 genes with this mental disorder.

Predicting Cancer Risk from Genome Data: A Multilayer Perceptron Approach

This paper proposes a deep learning method to predict cancer risk from gene symbols using a multilayer perceptron (MLP) feed forward neural network. The paper uses a data set of gene symbols and their corresponding cancer risk labels, obtained from a DNA microarray analysis. The paper then builds and compares different machine learning models, such as logistic regression, linear discriminant analysis, quadratic discriminant analysis, decision tree classifier, gaussian nb, ada boost classifier, gaussian process classifier, support vector machine, and random forest. Deep learning MLP model is built, tuned and optimized for hyperparameters which improves the accuracy significantly by 9.09% compared to the best machine learning model. The paper evaluates the performance of the MLP model on the data set using accuracy, precision, recall, and F1-score metrics. This paper contributes to the field of machine learning and bioinformatics by providing a novel and effective way to predict cancer risk from gene symbols.

Higher evolutionary dynamics of gene copy number for Drosophila glue genes located near short repeat sequences

BackgroundDuring evolution, genes can experience duplications, losses, inversions and gene conversions. Why certain genes are more dynamic than others is poorly understood. Here we examine how several Sgs genes encoding glue proteins, which make up a bioadhesive that sticks the animal during metamorphosis, have evolved in Drosophila species.ResultsWe examined high-quality genome assemblies of 24 Drosophila species to study the evolutionary dynamics of four glue genes that are present in D. melanogaster and are part of the same gene family - Sgs1, Sgs3, Sgs7 and Sgs8 - across approximately 30 millions of years. We annotated a total of 102 Sgs genes and grouped them into 4 subfamilies. We present here a new nomenclature for these Sgs genes based on protein sequence conservation, genomic location and presence/absence of internal repeats. Two types of glue genes were uncovered. The first category (Sgs1, Sgs3x, Sgs3e) showed a few gene losses but no duplication, no local inversion and no gene conversion. The second group (Sgs3b, Sgs7, Sgs8) exhibited multiple events of gene losses, gene duplications, local inversions and gene conversions. Our data suggest that the presence of short “new glue” genes near the genes of the latter group may have accelerated their dynamics.ConclusionsOur comparative analysis suggests that the evolutionary dynamics of glue genes is influenced by genomic context. Our molecular, phylogenetic and comparative analysis of the four glue genes Sgs1, Sgs3, Sgs7 and Sgs8 provides the foundation for investigating the role of the various glue genes during Drosophila life.

Abstract A071: Identification and characterization of functionally distinct isoforms of estrogen receptor alpha in breast cancer

Abstract We used long- and short-read RNA sequencing of breast tumor tissue, breast cancer cell lines, and healthy tissues to create a comprehensive annotation of alternative mRNA isoforms of estrogen receptor alpha (ER, gene symbol ESR1) and combined this with functional studies of alternative protein isoforms. The ER is frequently overexpressed in breast cancer and is used in the clinic as a prognostic and treatment-predictive factor. It is also a drug target. The ER is a transcription factor and regulates gene expression in response to estrogen, a hormone that can stimulate breast cell proliferation and contribute to tumor growth. The gene has multiple promoters, and alternative mRNA isoforms have been linked to more aggressive breast tumors, suggesting that the splicing pattern of ER transcripts may influence breast cancer biology and clinical outcome. We cloned and characterized six alternative protein isoforms of ER. They were selected based on expression level in sequencing data, splice junction support, and only contained one alternative splicing event each compared to the full-length ER. Experimental characterization was done in cell lines and included transcription factor activity, alone and upon co-expression with full-length ER, response to the ER-targeting drugs tamoxifen and fulvestrant, as well as subcellular localization. Two alternative isoforms exhibited transcription factor activity, although at lower levels than the full-length ER, while isoforms with larger deletions in the DNA-binding domain or lacking parts of the ligand-binding domain were inactive. One isoform had a dominant negative effect on the activity of the full-length protein. Furthermore, full-length ER and three alternative isoforms were found in both cytoplasm and nucleus, while the remaining isoforms were only present in the cytoplasm. Isoforms capable of entering the nucleus showed increased nuclear localization upon estradiol treatment, with one isoform accumulating significantly higher and one lower than the full-length ER. Co-transfection of full-length ER and isoforms lacking transcription factor activity did not alter their distribution, suggesting a possible role of heterodimerization with full-length ER for the dominant negative isoform in the nucleus. In ongoing experiments, we are studying the regulation, expression, and function of alternative isoforms of ER in cell line models of drug resistance. These findings highlight the complexity and diversity of ER isoforms in breast cancer and suggest that specific isoforms may have distinct functional roles in tumor progression and response to therapy. Our work provides insights into the role of alternative mRNA splicing in breast cancer development and progression. Citation Format: Juliane Albrecht, Carlos Enrique Balcazar, Helena Persson, Völundur Hafstað, Cornelia Börjesson Freitag, Johan Vallon-Christersson, Jari Häkkinen. Identification and characterization of functionally distinct isoforms of estrogen receptor alpha in breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A071.

Bioinformatics Architecture for Integrating Genomics Data into Electronic Health Records.

The adequate management of patients' genomic information is essential for any health institution pursuing the Precision Medicine model. Here we approach a bioinformatic architecture that allows the Institution to store its whole genetic test data in a scalable database, and also the integration of that genetic data with the Electronic Health Record through a Clinical Decision Support System. The system complements patient care by suggesting referral to genetic counseling for patients who are potentially at risk of hereditary breast/ovarian cancer, and allowing for proper follow-up of patients with pathogenic variants in BRCA1 or BRCA2 genes. The implemented solution uses the FHIR standard and genetic nomenclatures from the Human Genome Variation Society and the HUGO Gene Nomenclature Committee. The architecture is flexible enough to allow any other health institution to integrate -to their information ecosystem- the whole solution or some of the modules according to its degree of digitization progress.

DrosOMA: the Drosophila Orthologous Matrix browser.

Comparative genomic analyses to delineate gene evolutionary histories inform the understanding of organismal biology by characterising gene and gene family origins, trajectories, and dynamics, as well as enabling the tracing of speciation, duplication, and loss events, and facilitating the transfer of gene functional information across species. Genomic data are available for an increasing number of species from the genus Drosophila, however, a dedicated resource exploiting these data to provide the research community with browsable results from genus-wide orthology delineation has been lacking. Using the OMA Orthologous Matrix orthology inference approach and browser deployment framework, we catalogued orthologues across a selected set of Drosophila species with high-quality annotated genomes. We developed and deployed a dedicated instance of the OMA browser to facilitate intuitive exploration, visualisation, and downloading of the genus-wide orthology delineation results. DrosOMA - the Drosophila Orthologous Matrix browser, accessible from https://drosoma.dcsr.unil.ch/ - presents the results of orthology delineation for 36 drosophilids from across the genus and four outgroup dipterans. It enables querying and browsing of the orthology data through a feature-rich web interface, with gene-view, orthologous group-view, and genome-view pages, including comprehensive gene name and identifier cross-references together with available functional annotations and protein domain architectures, as well as tools to visualise local and global synteny conservation. The DrosOMA browser demonstrates the deployability of the OMA browser framework for building user-friendly orthology databases with dense sampling of a selected taxonomic group. It provides the Drosophila research community with a tailored resource of browsable results from genus-wide orthology delineation.

Common dihydropyrimidinase ( DPYS ) genetic variations do not predict fluoropyrimidine-related chemotherapy toxicity in a Canadian cohort.

Known genetic variations in dihydropyrimidine dehydrogenase (gene name DPYD ) do not fully predict patients at risk for severe fluoropyrimidine-associated chemotherapy toxicity. Dihydropyrimidinase (gene name DPYS ), the second catabolic enzyme in fluoropyrimidine metabolism, has been noted as a potential determinant of variation in fluoropyrimidine metabolism and response. In this study, we genotyped for DPYS c.-1T>C (rs2959023), c.265-58T>C (rs2669429) and c.541C>T (rs36027551) in a Canadian cohort of 248 patients who were wild type for Clinical Pharmacogenetics Implementation Consortium recommended DPYD variants and had received a standard dose of fluoropyrimidine chemotherapy. None of our patients were found to carry the DPYS c.541C>T variant, while the minor allele frequencies were 63% and 54% for c.-1T>C and c.265-58T>C, respectively. There was no association between DPYS c.-1T>C wild type and heterozygote [odds ratio (OR) (95% confidence interval, CI) = 1.10 (0.51-2.40)] or homozygote variant carriers [OR (95% CI) = 1.22 (0.55-2.70)], or between DPYS c.265-58T>C wild-type patients and heterozygote [OR (95% CI) = 0.93 (0.48-1.80)] or homozygote variant carriers [OR (95% CI) = 0.76 (0.37-1.55)] in terms of fluoropyrimidine-associated toxicity. Therefore, in our cohort of mostly Caucasian Canadians, genetic variations in DPYS do not appear to be a significant contributor to severe fluoropyrimidine-associated toxicity.

Novel lncRNA regulatory elements in milk somatic cells of Holstein dairy cows associated with mastitis

Despite regulatory elements such as long non - coding RNAs representing most of the transcriptome, the functional understanding of long non - coding RNAs in relation to major health conditions including bovine mastitis is limited. This study examined the milk somatic cell transcriptome from udder quarters of 6 Holstein dairy cows to identify differentially expressed long non - coding RNAs using RNA - Sequencing. Ninety - four differentially expressed long non - coding RNAs are identified, 5 of which are previously annotated for gene name and length, 11 are annotated for gene name and 78 are novel, having no gene name or length previously annotated. Significant inflammatory response and regulation of immune response pathways (false discovery rate < 0.05) are associated with the differentially expressed long non - coding RNAs. QTL annotation analysis revealed 31 QTL previously annotated in the genomic regions of the 94 differentially expressed long non - coding RNAs, and the majority are associated with milk traits. This research provides a better understanding of long non - coding RNAs regulatory elements in milk somatic cells, which may enhance current breeding strategies for more adaptable or high mastitis resistant cattle.

Uncovering the mechanisms of MuRF1-induced ubiquitylation and revealing similarities with MuRF2 and MuRF3

MuRF1 (Muscle-specific RING finger protein 1; gene name TRIM63) is a ubiquitin E3 ligase, associated with the progression of muscle atrophy. As a RING (Really Interesting New Gene) type E3 ligase, its unique activity of ubiquitylation is driven by a specific interaction with a UBE2 (ubiquitin conjugating enzyme). Our understanding of MuRF1 function remains unclear as candidate UBE2s have not been fully elucidated. In the present study, we screened human ubiquitin dependent UBE2s in vitro and found that MuRF1 engages in ubiquitylation with UBE2D, UBE2E, UBE2N/V families and UBE2W. MuRF1 can cause mono-ubiquitylation, K48- and K63-linked polyubiquitin chains in a UBE2 dependent manner. Moreover, we identified a two-step UBE2 dependent mechanism whereby MuRF1 is monoubiquitylated by UBE2W which acts as an anchor for UBE2N/V to generate polyubiquitin chains. With the in vitro ubiquitylation assay, we also found that MuRF2 and MuRF3 not only share the same UBE2 partners as MuRF1 but can also directly ubiquitylate the same substrates: Titin (A168-A170), Desmin, and MYLPF (Myosin Light Chain, Phosphorylatable, Fast Skeletal Muscle; also called Myosin Light Regulatory Chain 2). In summary, our work presents new insights into the mechanisms that underpin MuRF1 activity and reveals overlap in MuRF-induced ubiquitylation which could explain their partial redundancy in vivo.

Insights into autotaxin- and lysophosphatidate-mediated signaling in the pancreatic ductal adenocarcinoma tumor microenvironment: a survey of pathway gene expression.

Lysophosphatidate (LPA)-mediated signaling is a vital component of physiological wound healing, but the pathway is subverted to mediate chronic inflammatory signaling in many pathologies, including cancers. LPA, as an extracellular signaling molecule, is produced by the enzyme autotaxin (ATX, gene name ENPP2) and signals through six LPA receptors (LPARs). Its signaling is terminated by turnover via the ecto-activity of three lipid phosphate phosphatases (LPPs, gene names PLPP1-3). Many pharmacological developments against the LPA-signaling axis are underway, primarily against ATX. An ATX inhibitor against pancreatic ductal adenocarcinoma (PDAC), a very aggressive disease with limited systemic therapeutic options, is currently in clinical trials, and represents the first in-class drug against LPA signaling in cancers. In the present study, we surveyed the expression of ATX, LPARs, and LPPs in human PDACs and their clinical outcomes in two large independent cohorts, the Cancer Genome Atlas (TCGA) and GSE21501. Correlation among gene expressions, biological function and the cell composition of the tumor microenvironment were analysed using gene set enrichment analysis and cell cyber-sorting with xCell. ENPP2, LPAR1, LPAR4, LPAR5, LPAR6, PLPP1, and PLPP2 were significantly elevated in PDACs compared to normal pancreatic tissue, whereas LPAR2, LPAR3, and PLPP3 where downregulated (all P≤0.003). Only ENPP2 demonstrated survival differences, with overall survival favoring ENPP2-high patients (hazard ration 0.5-0.9). ENPP2 was also the only gene with enriched gene patterns for inflammatory and tissue repair gene sets. Epithelial (cancer) cells had increased LPAR2, LPAR5 and PLPP2 expression, and decreased ENPP2, LPAR1, PLPP1, and PLPP3 gene expression (all P<0.02). Tumor fibroblasts had increased ENPP2, LPAR2, LPAR4, PLPP1, and PLPP3 expression and decreased LPAR2, LPAR5, and PLPP2 expression in both cohorts (all P≤0.01). Immune cell populations were not well correlated to gene expression in PDACs, but across both cohorts, cytolytic scores were increased in high-expressing ENPP2, LPAR1, LPAR6, PLPP1, and PLPP3 tumors (P<0.01). Overall, in PDACs, ENPP2 may switch from an anti-to-pro tumor promoting gene with disease progression. LPAR2 and PLPP2 inhibition are also predicted to have potential therapeutic utility. Future multi-omics investigations are necessarily to validate which LPA signaling components are high-value candidates for pharmacological manipulation in PDAC treatment.

Branched-Chain Amino Acid Degradation Pathway was Inactivated in Colorectal Cancer: Results from a Proteomics Study.

Background: Colorectal cancer (CRC) ranks third in terms of cancer incidence and fourth in terms of cancer-related deaths worldwide. Identifying potential biomarkers of CRC is crucial for treatment and drug development. Methods: In this study, we established a C57B/6N mouse model of colon carcinogenesis using azoxymethane-dextran sodium sulfate (AOM-DSS) treatment for 14 weeks to identify proteins associated with colon cancer. An isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis was conducted on the cell membrane components enriched in the colonic mucosa. Additionally, tumor tissues and adjacent normal colon tissues were collected from patients with colon cancer for comparative protein and metabolite analyses. Results: In total, 74 differentially expressed proteins were identified in the tumor tissue samples from AOM/DSS-treated mice compared to both the adjacent tissue samples from AOM/DSS-treated mice and tissue samples from saline-treated control mice. Bioinformatics analysis revealed eight downregulated proteins enriched in the branched-chain amino acids pathway (valine, leucine, and isoleucine degradation). Moreover, these proteins are already known to be associated with the survival rate of patients with cancer. Targeted metabolomics showed increased levels of valine, leucine, and isoleucine in tumor tissues compared to those in adjacent normal tissues in patients with colon cancer. Furthermore, a real-time PCR experiment demonstrated that Aldehyde dehydrogenase, mitochondrial (short protein name ALDH2, gene name Aldh2) and Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (short protein name HCDH, gene name Hadh) (two genes) in the pathway of branched-chain amino acids) were downregulated in patients with colon cancer (colon tumor tissues vs. their adjacent colon tissues). ALDH2 expression was further validated by western blotting in AOM/DSS-treated mouse model and in clinical samples. Conclusion: This study highlighted the inactivation of the branched-chain amino acid degradation pathway in colon cancer and identified ALDH2 and HCDH as potential biomarkers for diagnosing colon cancer and developing new therapeutic strategies.

Vitamin D binding protein (VDBP) hijacks twist1 to inhibit vasculogenic mimicry in hepatocellular carcinoma.

Rationale: Vitamin D (VD) has been suggested to have antitumor effects, however, research on the role of its transporter vitamin D-binding protein (VDBP, gene name as GC) in tumors is limited. In this study, we demonstrated the mechanism underlying the inhibition of vasculogenic mimicry (VM) by VDBP in hepatocellular carcinoma (HCC) and proposed an anti-tumor strategy of combining anti-PD-1 therapy with VD. Methods: Three-dimensional cell culture models and mice with hepatocyte-specific GC deletion were utilized to study the correlation between VDBP expression and VM. A patient-derived tumor xenograft (PDX) model was further applied to validate the therapeutic efficacy of VD in combination with an anti-PD-1 drug. Results: The study revealed that VDBP expression is negatively correlated with VM in HCC patients and elevated VDBP expression is associated with a favorable prognosis. The mechanism studies suggested VDBP hindered the binding of Twist1 on the promoter of VE-cadherin by interacting with its helix-loop-helix DNA binding domain, ultimately leading to the inhibition of VM. Furthermore, VD facilitated the translocation of the vitamin D receptor (VDR) into the nucleus where VDR interacts with Yin Yang 1 (YY1), leading to the transcriptional activation of VDBP. We further demonstrated that the combination of VD and anti-PD-1 led to an improvement in the anti-tumor efficacy of an anti-PD-1 drug. Conclusion: Collectively, we identified VDBP as an important prognostic biomarker in HCC patients and uncovered it as a therapeutic target for enhancing the efficacy of immune therapy.

IMGT/mAb-KG: the knowledge graph for therapeutic monoclonal antibodies.

Therapeutic monoclonal antibodies (mAbs) have demonstrated promising outcomes in diverse clinical indications, including but not limited to graft rejection, cancer, and autoimmune diseases lately.Recognizing the crucial need for the scientific community to quickly and easily access dependable information on monoclonal antibodies (mAbs), IMGT®, the international ImMunoGeneTics information system®, provides a unique and invaluable resource: IMGT/mAb-DB, a comprehensive database of therapeutic mAbs, accessible via a user-friendly web interface. However, this approach restricts more sophisticated queries and segregates information from other databases. To connect IMGT/mAb-DB with the rest of the IMGT databases, we created IMGT/mAb-KG, a knowledge graph for therapeutic monoclonal antibodies connected to IMGT structures and genomics databases. IMGT/mAb-KG is developed using the most effective methodologies and standards of semantic web and acquires data from IMGT/mAb-DB. Concerning interoperability, IMGT/mAb-KG reuses terms from biomedical resources and is connected to related resources. In February 2024, IMGT/mAb-KG, encompassing a total of 139,629 triplets, provides access to 1,489 mAbs, approximately 500 targets, and over 500 clinical indications. It offers detailed insights into the mechanisms of action of mAbs, their construction, and their various products and associated studies. Linked to other resources such as Thera-SAbDab (Therapeutic Structural Antibody Database), PharmGKB (a comprehensive resource curating knowledge on the impact of genetic variation on drug response), PubMed, and HGNC (HUGO Gene Nomenclature Committee), IMGT/mAb-KG is an essential resource for mAb development. A user-friendly web interface facilitates the exploration and analyse of the content of IMGT/mAb-KG.

Deciphering Gorilla gorilla gorilla immunoglobulin loci in multiple genome assemblies and enrichment of IMGT resources.

Through the analysis of immunoglobulin genes at the IGH, IGK, and IGL loci from four Gorilla gorilla gorilla genome assemblies, IMGT® provides an in-depth overview of these loci and their individual variations in a species closely related to humans. The similarity between gorilla and human IG gene organization allowed the assignment of gorilla IG gene names based on their human counterparts. This study revealed significant findings, including variability in the IGH locus, the presence of known and new copy number variations (CNVs), and the accurate estimation of IGHG genes. The IGK locus displayed remarkable homogeneity and lacked the gene duplication seen in humans, while the IGL locus showed a previously unconfirmed CNV in the J-C cluster. The curated data from these analyses, available on the IMGT website, enhance our understanding of gorilla immunogenetics and provide valuable insights into primate evolution.

A uniform gene and chromosome nomenclature system for oat (Avena spp.)

Context Several high-quality reference genomes for oat (Avena sativa L. and relatives) have been published, with the prospect of many additional whole-genome assemblies emerging in the near future. Aims This has necessitated an effort by the International Oat Nomenclature Committee (IONC; all co-authors on this paper) to devise a universal system for naming oat genomes and subgenomes, chromosomes, genes, gene models and quantitative trait loci. Methods We evaluated existing naming practices, recent data from oat whole-genome sequencing, and the newly published convention for wheat nomenclature. Key results A framework for these rules has been posted on the GrainGenes database website (https://wheat.pw.usda.gov/GG3/oatnomenclature). The gene naming convention requires adoption of a numerical identifier for each genotype; we propose that these identifiers be assigned by contacting the GrainGenes curators, the curator of the Oat Newsletter, or a member of the IONC (as listed at the GrainGenes link above). Conclusions We encourage oat researchers to refer to these resources, policies, procedures and conventions, adopting them as an international nomenclature standard. Implications Adoption of these standards will facilitate communication and dissemination of oat research and allow programmatic access and data sharing across platforms, and will contribute to oat breeding and research worldwide.