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{"title":"Genome-wide association study and HLA genotyping for beryllium disease susceptibility in a European descent population","authors":"Shu-Yi Liao ,&nbsp;Tasha E. Fingerlin ,&nbsp;Sean Jacobson ,&nbsp;Margaret M. Mroz ,&nbsp;Kenneth D. Rosenman ,&nbsp;Milton D. Rossman ,&nbsp;MAbbas Virji ,&nbsp;Erin C. McCanlies ,&nbsp;Christine R. Schuler ,&nbsp;Berran Yucesoy ,&nbsp;Joseph Glessner ,&nbsp;Jamie L. Duke ,&nbsp;Hakon Hakonarson ,&nbsp;Dimitri S. Monos ,&nbsp;Lisa A. Maier","doi":"10.1016/j.gene.2025.149820","DOIUrl":"10.1016/j.gene.2025.149820","url":null,"abstract":"<div><h3>Background</h3><div>Workplace exposure to beryllium can result in beryllium sensitization (BeS), a cell-mediated immune response that can progress to chronic beryllium disease (CBD), a granulomatous lung disease. DPB1-E69 is highly associated with CBD and BeS, although DRB1-E71 may also be a risk factor in the absence of DPB1-E69.</div></div><div><h3>Objective</h3><div>This study 1) identified novel genetic variants associated with CBD/BeS using a genome-wide association study (GWAS) approach and 2) clarified the role of DRB1-E71 in conjunction with DPB1-E69.</div></div><div><h3>Methods</h3><div>We performed GWAS and HLA analysis on 1626 subjects with BeS, CBD and beryllium exposure without disease.</div></div><div><h3>Results</h3><div>We found that rs1042140, the first base of the codon that encodes E69, was associated with CBD and BeS. We also found two single nucleotide polymorphisms (SNPs), rs56011217 and rs72636334, near <em>SRIP1</em> on chromosome 4 associated with CBD and BeS independent of rs1042140. HLA alleles DRB1*04:04 (non E71) and DQB1*06:04 were significantly associated with CBD and BeS independent of rs1042140.</div></div><div><h3>Conclusions</h3><div>We found both DPB1-E69 and DRB1-E71 carriers have a higher risk of CBD or BeS both independently and jointly, with DPB1-E69 status having higher impact than DRB1-E71 status. DRB1-E71 also increases the risk in subjects without DPB1-E69. Our study also implies that beyond HLA, <em>SRIP1</em> should be investigated in chronic beryllium disease pathogenesis.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"971 ","pages":"Article 149820"},"PeriodicalIF":2.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145271245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolutionary dynamics of Influenza A(H3N2) virus in India from 2009 to 2023","authors":"Varsha Potdar ,&nbsp;Anam Dhawlarker ,&nbsp;Veena Vipat ,&nbsp;Satish Gaikwad ,&nbsp;Payal Kelkar ,&nbsp;Sheetal Jadhav ,&nbsp;M.L. Choudhary ,&nbsp;S. Bhardwaj ,&nbsp;Neetu Vijay ,&nbsp;Nivedita Gupta","doi":"10.1016/j.gene.2025.149798","DOIUrl":"10.1016/j.gene.2025.149798","url":null,"abstract":"<div><div>The influenza virus, with its propensity for rapid genetic evolution, remains a formidable global public health challenge. In particular, the H3N2 subtype of the Influenza A virus is known for its ability to continuously evolve, making it an ongoing concern for public health. To gain insights into the epidemiological dynamics of H3N2 in India, a comprehensive phylogenetic and phylogeographic analysis was conducted spanning the years 2009 to 2023. We analyzed 518 HA gene sequences from India (2009–2023), integrating 462 publicly available and 56 newly generated sequences from 19 different states in India (2018–2023). Bayesian phylogenetic and phylogeographic analyses revealed continuous H3N2 evolution in India since the mid-1990 s with an evolutionary rate of 4.95 × 10^-3 substitutions/site/year (R² = 0.95). The most recent common ancestor for Indian H3N2 sequences dated to 1995 (95 % HPD: 1992–2001), with 2023 strains predominantly belonging to clade 2a.3a.1 (characterized by I140K mutation) showing close match with WHO-recommended vaccine strains A/Darwin/6/2021.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"971 ","pages":"Article 149798"},"PeriodicalIF":2.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Saffron CsSEP3 regulates flowering time and flower organ morphogenesis.","authors":"Mengqing Feng, Xiaoyuan Xi, Xingchang Zhang, Feng Qiu, Jia Song, Liqin Li","doi":"10.1016/j.gene.2025.149818","DOIUrl":"https://doi.org/10.1016/j.gene.2025.149818","url":null,"abstract":"<p><p>Saffron (Crocus sativus L.), known as \"red gold\", is a highly valued medicinal herb with significant economic benefits. Its medicinal value comes from the stigma, and increasing the weight of the stigma can enhance its yield. SEPALLATA3 (SEP3), a key MADS-box transcription factor, plays crucial roles in floral development and organ identity determination. However, the specific role of SEP3 in saffron has remained unclear. In this study, the CsSEP3 gene was cloned from saffron. Bioinformatics analysis identified highly conserved MADS-box and K-box domains within the protein. Phylogenetic analysis indicated that CsSEP3 clusters closely with the ortholog of SEP3 in Asparagus officinalis. CsSEP3 is specifically activated during the floral induction stage and rapidly up-regulated during the flower organ differentiation stage. It is primarily expressed in petals, stamens and stigmas during the yellow- and orange-stigma stages, while in the red-stigma stage and on the day of flowering, its expression is mainly detected in petals and stigmas. Subcellular localization experiments confirmed that CsSEP3 is localized in the nucleus. When CsSEP3 was ectopically expressed in Arabidopsis thaliana, it significantly accelerated flowering and led to enlarged flower organs of petals, stamens, and pistils. Protein-protein interaction predictions indicate that CsSEP3 likely forms complexes through interactions with MADS-box proteins such as CsAP3, CsSOC1, and CsAG. These findings not only enhance our understanding of CsSEP3's role in saffron but also provide a theoretical basis for boosting saffron stigma yield through molecular breeding strategies by manipulating the expression levels of CsSEP3.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149818"},"PeriodicalIF":2.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gibberellin and cytokinin are coordinately involved in regulating kiwifruit flowering.","authors":"Yumei Fang, Xiaoyu Cui, Zhijun Mei, Chao Zhang, Lina Guo","doi":"10.1016/j.gene.2025.149817","DOIUrl":"https://doi.org/10.1016/j.gene.2025.149817","url":null,"abstract":"<p><p>Flowering time critically affects kiwifruit (Actinidia deliciosa) yield and fruit quality. To uncover the molecular basis of early flowering, we compared the early-flowering cultivar 'Hanhong' with the late-flowering 'Guichang'. Phenological data showed 'Hanhong' completes flowering in eight weeks-two weeks earlier than 'Guichang'-and exhibits significantly higher endogenous gibberellin (GA) levels in both floral buds and open flowers. Integrated transcriptomic and proteomic analyses revealed strong enrichment of GA and cytokinin signaling pathways during floral development. While transcript levels of the DELLA gene REPRESSOR OF GA1-3 (AdRGA) remained stable, its protein abundance markedly declined from bud to flower stages in both cultivars, indicating post-transcriptional regulation. Functional assays in Arabidopsis confirmed that AdRGA overexpression delays flowering by suppressing FLOWERING LOCUS T (FT), establishing AdRGA as a negative flowering regulator. Conversely, Arabidopsis Histidine Phosphotransfer Protein (AdAHP), a cytokinin signaling component, was significantly upregulated at both mRNA and protein levels in 'Hanhong'. Ectopic expression of AdAHP in the ahp5-2 mutant accelerated flowering and enhanced expression of FT and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1), confirming AdAHP as a positive regulator. Additionally, Gibberellin Insensitive Dwarf1 (AdGID1) displayed stage-specific expression-enriched during floral bud development but not at anthesis-suggesting a role in bud formation rather than floral transition timing. Together, our results demonstrate that coordinated GA and cytokinin signaling, mediated by AdRGA and AdAHP, fine-tunes kiwifruit flowering through differential regulation of FT and SOC1. This work provides a molecular framework for manipulating flowering time and identifies key genetic targets for kiwifruit breeding programs aimed at optimizing production.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149817"},"PeriodicalIF":2.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editor's Corner: RESTORE-ing Hope-RNA editing as a Frontier in Cystic Fibrosis Therapy.","authors":"By Marianna Kruithof-de Julio","doi":"10.1016/j.gene.2025.149816","DOIUrl":"https://doi.org/10.1016/j.gene.2025.149816","url":null,"abstract":"","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149816"},"PeriodicalIF":2.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"A Sge1 homolog in Cytospora chrysosperma governs conidiation, virulence and the expression of putative effectors\". [GENE 778 (2021) 145474].","authors":"Zhu Han, Ran Yu, Dianguang Xiong, Chengming Tian","doi":"10.1016/j.gene.2025.149803","DOIUrl":"https://doi.org/10.1016/j.gene.2025.149803","url":null,"abstract":"","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149803"},"PeriodicalIF":2.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Murine models of lung adenocarcinoma: Valuable tools for preclinical investigation","authors":"Wenli Shang ,&nbsp;Caihong Lai ,&nbsp;Shiwen Luo ,&nbsp;Limin Chen","doi":"10.1016/j.gene.2025.149802","DOIUrl":"10.1016/j.gene.2025.149802","url":null,"abstract":"<div><div>Lung adenocarcinoma (LUAD) is a primary subtype of non-small cell lung cancer (NSCLC), notorious for its high mortality due to metastasis and poor prognosis. Utilizing various mouse models to simulate human LUAD is essential for advancing understanding of its mechanisms and developing new treatments. This review examines tumor mouse models commonly used in LUAD research, including cell-derived xenografts (CDX), patient-derived xenografts (PDX), carcinogen-induced models, and genetically engineered mouse models (GEMM). We discuss the suitability, benefits, and limitations of each model, and proposes using a combination of models to enhance research relevance for human LUAD, aiding in the discovery of new drugs and personalized treatments.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"971 ","pages":"Article 149802"},"PeriodicalIF":2.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suppressor of cytokine signaling 6 (SOCS6) mediates ubiquitination degradation of SLC7A11 to drive ferroptosis and block lipid metabolism in ovarian cancer cells","authors":"Yuelian Fan,&nbsp;Yuping Suo","doi":"10.1016/j.gene.2025.149819","DOIUrl":"10.1016/j.gene.2025.149819","url":null,"abstract":"<div><div>Ovarian cancer (OVCA) is a highly malignant gynecological tumor characterized by a dismal 5-year survival rate that is closely linked to aberrant ferroptosis regulation and lipid metabolic reprogramming. This study integrated bioinformatics analyses of TCGA and The Human Protein Atlas datasets, clinical validation in 30 pairs of OVCA tissues, in vitro functional assays using HO8910 and HEYT30 cell lines, and nude mouse xenograft models to explore the role of suppressor of cytokine signaling 6 (SOCS6) in OVCA prognosis. The results revealed that SOCS6 was significantly downregulated in OVCA tissues and cell lines, and low expression was strongly correlated with poor patient prognosis. Mechanistically, SOCS6 overexpression inhibited cellular proliferation, migration, and invasion and enhanced sensitivity to the ferroptosis inducer erastin. This effect occurs by promoting the ubiquitin-proteasomal degradation of the ferroptosis antagonist SLC7A11, reducing intracellular glutathione (GSH) levels, and augmenting reactive oxygen species (ROS) and Fe²⁺ accumulation. Additionally, SOCS6 suppressed de novo fatty acid synthesis by downregulating the key enzymes FASN and ACC, leading to decreased triglyceride and phospholipid production. <em>In vivo</em> xenograft experiments confirmed that SOCS6 overexpression inhibited tumor growth and reduced the expression of SLC7A11 and lipid metabolism-related molecules. Collectively, these results establish SOCS6 as a critical molecular hub linking ferroptosis and lipid metabolism in OVCA, highlighting its potential as both a prognostic biomarker and a therapeutic target for improving clinical outcomes in OVCA.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"971 ","pages":"Article 149819"},"PeriodicalIF":2.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional analysis of SpHMA1 N-terminus in yeast: regulation of cadmium (Cd) transport by his-rich motifs","authors":"Haixia Zhao ,&nbsp;Xiaotong Wu ,&nbsp;Hongxu Ren ,&nbsp;Wenzhong Xu","doi":"10.1016/j.gene.2025.149809","DOIUrl":"10.1016/j.gene.2025.149809","url":null,"abstract":"<div><div>Cadmium (Cd) poses significant toxicity risks to most biological systems. In<!--> <!-->the hyperaccumulator <em>Sedum plumbizincicola</em>, the HMA1 plays a key role in Cd detoxification through chloroplast–mediated process. Our previous work demonstrated that SpHMA1 actively exports Cd from chloroplasts, thereby protecting photosynthesis by reducing Cd accumulation within these organelles. In this study, we identified a Cd–selective functional domain in SpHMA1 and characterizes two histidine–rich motifs within its N–terminal region. Through heterologous expression of full–length SpHMA1 and its N–terminal truncation mutants in yeast, we systematically analyzed their functional roles in heavy metal transport. Under Cd stress, SpHMA1Δ2–46–expressing cells showed altered growth patterns compared to full–length SpHMA1 transformants, despite comparable total Cd accumulation. Notably, truncation of the first 80 amino acids (SpHMA1Δ2–80) significantly increased metal sensitivity (Cd, Zn, Cu) in Δ<em>ycf1</em> yeast, accompanied by a significant increase in intracellular Cd accumulation. Complete deletion of the histidine–rich domain (SpHMA1Δ2–107) restored metal tolerance to empty vector–control levels. Our findings demonstrate functional differentiation between the dual his–rich motifs in heavy metal transport regulation, advancing understanding of HMA1′s molecular mechanisms in plant metal homeostasis.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"971 ","pages":"Article 149809"},"PeriodicalIF":2.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Haplotype-based association of CYB5A gene polymorphisms (rs1790834 and rs1790858) with polycystic ovary syndrome in a south Indian cohort","authors":"Mary Martin ,&nbsp;L.P. Rema ,&nbsp;Neetha George ,&nbsp;Roger Francis ,&nbsp;Sareena Gilvaz ,&nbsp;Jijo Francis ,&nbsp;P.J. Divya ,&nbsp;P.R. Varghese ,&nbsp;R. Suresh Kumar","doi":"10.1016/j.gene.2025.149806","DOIUrl":"10.1016/j.gene.2025.149806","url":null,"abstract":"<div><h3>Background</h3><div>Cytochrome b5 type A (<em>CYB5A</em>) augments the 17,20-lyase activity of CYP17A1, a crucial enzyme in androgen biosynthesis. A significant contributing factor to polycystic ovarian syndrome (PCOS) is dysregulated androgen production. This study examined the relationship between PCOS susceptibility and the <em>CYB5A</em> polymorphisms rs1790834 and rs1790858 in a population from South India. While <em>CYB5A</em> polymorphisms have been analysed in other diseases, this study is the first to investigate their association with PCOS.</div></div><div><h3>Methods</h3><div>A case-control study was performed with 194 patients diagnosed with PCOS and 194 age-matched controls. PCR-RFLP was used for genotyping of the rs1790834 and rs1790858 variants. Chi-square tests were used to compare allele frequencies and genotypes. Using Haploview, linkage disequilibrium and haplotype analysis were carried out, and gene-obesity interactions were evaluated through subgroup analysis based on BMI.</div></div><div><h3>Results</h3><div>No substantial correlation was detected between individual SNP genotypes or alleles and PCOS within the overall population. ANOVA analysis revealed no significant correlation between genotypes and anthropometric parameters (weight, height, BMI). Haplotype analysis also failed to identify any robust association.</div></div><div><h3>Conclusion</h3><div>While <em>CYB5A</em> plays a role in androgen biosynthesis through modulation of CYP17A1 activity, our results suggest that the studied SNPs may not independently contribute to PCOS susceptibility in this population. The genetic architecture of PCOS likely involves polygenic contributions, and variants in other steroidogenic or metabolic pathway genes may exert a greater influence than <em>CYB5A</em> alone. Larger studies with greater statistical power, multi-ethnic cohorts, genome-wide approaches, and functional validation are needed to clarify the role of CYB5A in PCOS pathogenesis fully.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"971 ","pages":"Article 149806"},"PeriodicalIF":2.4,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}