生物学最新文献

{"title":"Enterovirus 2B protein: From viroporin to membrane stress sensor, mechanistic principles of multi-pathway regulation.","authors":"Zengjun Ji, Yikun Chen, Hongxing Shen","doi":"10.1080/21505594.2026.2739074","DOIUrl":"10.1080/21505594.2026.2739074","url":null,"abstract":"<p><p>Enterovirus 2B is a highly conserved, functionally versatile, nonstructural protein. The classic viroporin model, which restricts its role to ion channel formation, cannot account for its interactions with host factors such as Bcl-2-associated X protein, interleukin enhancer-binding factor 2, and karyopherin subunit alpha 1, nor its functional divergence among enteroviruses. We propose a novel, testable membrane stress sensor hypothesis: the transmembrane helices of 2B sense lipid composition and pH changes, and through conformational dynamics, spatiotemporally coordinate calcium signaling, cell death pathway selection, including apoptosis, pyroptosis, autophagy, and ferroptosis, and immune evasion. We elaborate on this framework across six dimensions: structure-function mapping, calcium signaling, cell death pathways, immune evasion, evolutionary footprint, and antiviral targeting, along with cross-virus comparisons. We highlight key evidence gaps and limitations, and propose several future research directions. This framework establishes a mechanistic foundation for understanding 2B function and guiding rational anti-enteroviral drug designs.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"18 1","pages":"2739074"},"PeriodicalIF":6.8,"publicationDate":"2027-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota and metabolic characteristics in PWHIV with metabolic dysfunction-associated steatotic liver disease (MASLD).","authors":"Huiting Liu, Tianzhen Xu, Yongzheng Guo, Xiaotang Zhou, Chunhui Yan, Biao Zhu, Yirui Xie","doi":"10.1080/21505594.2026.2739091","DOIUrl":"10.1080/21505594.2026.2739091","url":null,"abstract":"<p><p>The global prevalence of Metabolic dysfunction-associated steatotic liver disease (MASLD) among persons with HIV (PWHIV) is estimated at 34%. This study examined the influence of gut microbial and metabolic alterations in PWHIV with MASLD. We conducted 16S rRNA sequencing on 60 fecal samples (24 from HIV group and 36 from HIV-MASLD group) to assess microbial composition, and employed LC/MS-based metabolomics on both fecal and plasma samples to identify variations in metabolites. An exploratory analysis was performed to compare plasma cytokines and oxidative stress markers between the two groups. Sequencing in the HIV-MASLD group showed lower <i>Faecalibacterium</i> and <i>Anaerobutyricum</i>, and higher <i>Klebsiella</i>, <i>Escherichia</i>, and <i>Enterococcus</i>. Metabolomic analysis revealed a reduction in anti-inflammatory metabolites (Dodecanedioic acid, 5-Phenylvaleric acid, Kynurenic acid) and antioxidant metabolites, coupled with an increase in the pro-inflammatory metabolite Gamma-Glutamyl-L-Putrescine in the HIV-MASLD group. And plasma analysis indicated a decline in 20-carboxy arachidonic acid. Additionally, <i>Faecalibacterium</i> and <i>Anaerobutyricum</i> correlated positively with anti-inflammatory metabolites, while <i>Klebsiella</i>, <i>Enterobacter</i>, and <i>Citrobacter</i> correlated negatively. Furthermore, <i>Faecalibacterium</i> and <i>Anaerobutyricum</i> also showed a moderate negative correlation with MDA levels. A random forest model using plasma metabolites showed the optimal discriminative ability for HIV-MASLD (AUC = 0.819 ± 0.0059). Differences in gut microbiota and metabolites in PWHIV may affect MASLD progression by influencing inflammation and oxidative stress. Modulating gut microbiota, such as adding <i>Faecalibacterium</i> and <i>Anaerobutyricum</i>, could be a treatment strategy for HIV-MASLD. Plasma metabolites have potential as noninvasive markers.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"18 1","pages":"2739091"},"PeriodicalIF":6.8,"publicationDate":"2027-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From bench to farm: leveraging <i>Drosophila</i> as a model insect for agricultural pest management.","authors":"Yao D Cai, Joanna C Chiu","doi":"10.1080/19336934.2026.2749209","DOIUrl":"10.1080/19336934.2026.2749209","url":null,"abstract":"<p><p>The vinegar fly, <i>Drosophila melanogaster</i>, has contributed tremendously to advancing our understanding of the fundamentals of biology, from the chromosomal theory of inheritance to the survival of multi-cellular organisms in spaceflight. The use of this insect as a model organism has provided insights into all branches of life sciences, including agricultural and environmental sciences. In the context of integrated pest management (IPM), which often relies on species-specific natural history and phenology of pest insects and biological control, <i>D. melanogaster</i> flies have continued to be a powerhouse. In this review, we seek to summarize the use of the <i>D. melanogaster</i> model in studying insect biology relevant to IPM, with a focus on investigating the mechanisms underlying insecticide resistance. We sample case studies that adopt forward genetic approaches to reveal molecular underpinnings of IPM-relevant phenotypes and reverse genetic approaches that elucidate genotype-phenotype relationships. In particular, we highlight the contribution of <i>D. melanogaster</i> in understanding the biology and in developing IPM for the spotted-wing drosophila, also known as <i>D. suzukii</i>, a pest <i>Drosophila</i> species that devastates fruit production worldwide. Finally, we summarize recently developed research tools and resources in <i>D. melanogaster</i> that have potential utility for agricultural pest management.</p>","PeriodicalId":12128,"journal":{"name":"Fly","volume":"21 1","pages":"2749209"},"PeriodicalIF":1.4,"publicationDate":"2027-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13690281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149230995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Slender lobes is a spindle matrix protein regulated by spindle envelope kinase Greatwall in oocytes.","authors":"Rayane Kaade, Emma Peat, Charlotte Repton, Julia Niziol, Carmela Silva Mason, Li Ern Yap, Gera Pavlova, Hiroyuki Ohkura","doi":"10.1083/jcb.202606020","DOIUrl":"10.1083/jcb.202606020","url":null,"abstract":"<p><p>Chromosome segregation is mediated by microtubule-based machinery, the spindle. Microtubule-independent structures, often called the spindle matrix or the spindle envelope, have been reported to embed or surround the spindle, respectively. The concepts have been around for several decades, but they still remain enigmatic. Here, we show the spindle matrix and the spindle envelope form one functional unit crucial for spindle structure and function in oocytes. We found that in Drosophila oocytes, Slender lobes (Sle) protein is an integral component of the spindle matrix, which has a composition different from that in mitotic cells. We further found that Greatwall (Gwl) kinase localizes to the spindle envelope tightly surrounding the Sle spindle matrix in oocytes. Gwl promotes assembly of the Sle spindle matrix, which in turn determines the location of the Gwl spindle envelope. sle silencing in oocytes resulted in spindle abnormalities. Cosilencing experiments revealed that Sle buffers the impacts of compromised kinetochore-microtubule interaction on centromere bi-orientation in meiotic metaphase I.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"226 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2027-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13701656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adhesion integrity activates mechanosensitive proliferative signaling.","authors":"Lídia Faria, Carine M Gonçalves, Inês Fidalgo, Carlotta Mix, Maria M Azevedo, Carla S Lopes, Olena Kostylenko, Vanessa Rodrigues, Ricardo Braguês, Paula Sampaio, Sandra Tavares, Vaibhav Mahajan, Anna V Taubenberger, Florence Janody","doi":"10.1083/jcb.202511205","DOIUrl":"https://doi.org/10.1083/jcb.202511205","url":null,"abstract":"<p><p>Weakening of adherens junctions (AJs) and focal adhesions (FAs) adhesiveness has been proposed to enable cancer initiation and progression. Here we report that E-cadherin at cell-cell contacts and vinculin at FAs are transiently under higher tension in MCF10A cells overactivating the Src proto-oncogene. Knockdown of paxillin or P-cadherin, or inhibition of focal adhesion kinase (FAK) or AJ assembly with EGTA, suppresses this force increase across both E-cadherin and vinculin. FAK and P-cadherin trans-homophilic interactions further enhance Src-dependent myosin II and extracellular signal-regulated kinase (ERK) activation. In addition, FAK and P-cadherin potentiate ERK and serum response factor (SRF) signaling, thereby supporting cell proliferation. Furthermore, knockdown of Drosophila cadherin or alpha integrin suppresses Src-induced tissue overgrowth, reinforcing the role of adhesion integrity in Src-driven proliferation. Thus, prior to the loss of cell-cell and cell-matrix adhesiveness, adhesion integrity by P-cadherin at AJs and FAK at FAs could represent a critical step enabling premalignant cells to gain a proliferative advantage.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"226 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2027-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolutionarily diverged on-switch for actin assembly in fungal endocytosis.","authors":"Juliette Sebellin, Fabina Binth Kandiyoth, V T Bagyashree, Andrea Picco, Nicolas Carvalho, Markku Hakala, Anne-Sophie Rivier-Cordey, Alphée Michelot, Christopher P Toret, Marko Kaksonen","doi":"10.1083/jcb.202506135","DOIUrl":"10.1083/jcb.202506135","url":null,"abstract":"<p><p>Clathrin-mediated endocytosis is a conserved eukaryotic trafficking process where an Arp2/3 complex-nucleated branched actin network provides force for vesicle formation. The mechanisms that initiate endocytic actin assembly are incompletely understood. In the fission yeast, Schizosaccharomyces pombe, actin assembly is initiated by Dip1, an Arp2/3 complex activator. In the budding yeast, Saccharomyces cerevisiae, the initiation of actin assembly has remained a mystery. Here, we show that S. cerevisiae Ldb17, the homolog of Dip1, functions as an on-switch for endocytic actin assembly. Unexpectedly, the regulation of Ldb17 is more complicated than that of constitutively active Dip1. Ldb17 is controlled by a coat protein, Sla1, via separate recruitment and activation steps. This regulation was likely lost in the S. pombe lineage, and this simplification may be related to other changes in actin assembly between these species. Our findings add a key missing piece in the understanding of endocytosis in S. cerevisiae and reveal an intriguing evolutionary tinkering of the actin on-switch.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"226 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2027-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13715591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149286987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALMS1 stabilizes the proximal centriole to drive transition zone assembly and ciliogenesis.","authors":"Thao P Phan, Camille Derderian, Vicente Herranz-Pérez, Kathy H Li, Alma L Burlingame, Jeremy F Reiter","doi":"10.1083/jcb.202605019","DOIUrl":"https://doi.org/10.1083/jcb.202605019","url":null,"abstract":"<p><p>The human ciliopathy Alström syndrome is caused by mutations in ALMS1. How ALMS1 contributes to cilia function has been unclear. Unlike other ciliopathy-associated proteins, ALMS1 localizes to the proximal end of centrioles, raising the possibility that it contributes to cilia function via a distinct mechanism. We found that, without ALMS1, centrioles are short and frequently break at their proximal ends. Truncated, broken ALMS1 mutant centrioles display reduced microtubule-organizing activity and disrupted centriole linkers. Without ALMS1, Golgi-derived cargos, including transmembrane components of the transition zone, are impaired in their trafficking to the centrosome. Consequently, ALMS1 is important for transition zone assembly, ciliogenesis, and the control of ciliary membrane composition. In mice, disruption of ALMS1 causes progressive, age-dependent loss of cilia in tissues affected in Alström syndrome, including retina, kidney, and brain. We conclude that Alström syndrome is caused by disruption of proximal centriole integrity and centrosome-directed protein trafficking, compromising ciliary assembly and maintenance.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"226 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2027-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149321559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental elimination of electrical synapses by UNC-51/UNC-76-mediated vesicular transport.","authors":"Hao Huang, Yuzhi Yang, Yuanhao Xu, Yuli Jian, Shujie Qiu, Zihao Zhao, Dong Yan, Lingfeng Meng","doi":"10.1083/jcb.202602115","DOIUrl":"10.1083/jcb.202602115","url":null,"abstract":"<p><p>Neural circuit maturation requires precise elimination of transient synaptic connections, but how electrical synapses are eliminated remains unknown. Using Caenorhabditis elegans PLM mechanosensory neurons, we found that gap junctions form transiently during early development and are subsequently eliminated as the circuit matures. These transient electrical synapses drive high-frequency calcium oscillations; optogenetic ablation of early gap junctions abolishes calcium dynamics and disrupts chemical synapse formation, while restoring calcium activity independently of gap junction coupling substantially rescues this defect, directly linking electrical synapse-driven calcium dynamics to chemical synapse formation. Through forward genetic screening, we identified the conserved kinase UNC-51/ULK as essential for elimination. UNC-51 phosphorylates the kinesin adaptor UNC-76/FEZ to promote RAB-10-dependent net retrograde removal of innexins, progressively depleting innexin proteins from the synaptic site. Disrupting this pathway prevents elimination, causing persistent electrical synapses and neuronal hyperactivity. These findings establish a conserved framework for developmental elimination of functionally essential transient electrical connectivity.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"226 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2027-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13741927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149342324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Midzone bundles of the mammalian anaphase spindle are mechanically coupled both locally and globally.","authors":"Zachary Mullin-Bernstein, Sterre van Wierst, Carly Garrison, Nathan H Cho, Sophie Dumont","doi":"10.1083/jcb.202604150","DOIUrl":"10.1083/jcb.202604150","url":null,"abstract":"<p><p>Robust chromosome segregation requires the anaphase spindle to both preserve and remodel its structure under force. How it does so remains unclear as probing mechanics during anaphase's short lifetime is challenging. Here, we use microneedles to pull on mammalian anaphase midzone bundles and ask how they respond to and transmit force across space and time. We find that midzone bundles locally transmit force to each other in the spindle's short axis over multiple timescales. Along the spindle's long axis, midzone bundles globally transmit force: rather than bundles sliding apart or detaching under force, the spindle shortens. This reveals strong anchorage and resistance to outward sliding, and that spindle elongation requires all midzone bundles to elongate. This global force transmission is stronger for short-lived forces and is strictly PRC1-dependent, indicating limited mechanistic redundancy. In sum, the anaphase spindle acts as a single mechanical unit over short timescales to resist and transmit force, while remodeling over long timescales to segregate chromosomes.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"226 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2027-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pentadecanoic acid as a potential endogenous mTOR modulator for age-related female infertility: Mechanistic insights, molecular docking evidence, and therapeutic perspectives.","authors":"Reni Kalfin, Sidharth Mehan, Rajaram Samant, Manoj Tongra, Harsh Patil, Rohit Kumar Singh","doi":"10.1016/j.jsbmb.2026.107100","DOIUrl":"10.1016/j.jsbmb.2026.107100","url":null,"abstract":"<p><p>Age-related female infertility is a major reproductive health challenge that accelerates sharply after the age of 34, primarily due to declining oocyte quality, increased chromosomal abnormalities, and impaired embryonic developmental competence. Emerging evidence identifies chronic hyperactivation of the mechanistic target of rapamycin (mTOR) signalling pathway as a central molecular driver of ovarian aging, promoting excessive ribosome biogenesis, impaired proteostasis, suppressed autophagy, mitochondrial dysfunction, and oxidative stress within oocytes and surrounding cumulus cells. Although rapamycin, the prototypical mTOR inhibitor, has demonstrated promising effects in improving ovarian function and in vitro fertilization outcomes, its teratogenic potential, immunosuppressive properties, metabolic side effects, and prolonged pre-conception washout requirements limit its clinical applicability in fertility management. This review synthesises current evidence on the role of mTOR in ovarian aging and is complemented by an original molecular docking analysis performed by the authors to evaluate the interaction between pentadecanoic acid and the mTOR kinase domain, an endogenous odd-chain saturated fatty acid, as a potential fertility-safe mTOR modulator. A comprehensive review of the literature was conducted using PubMed and related databases, encompassing pentadecanoic acid biochemistry, molecular mechanisms, mTOR signalling architecture, ovarian aging biology, rapamycin pharmacology, and molecular docking studies. Available evidence indicates that pentadecanoic acid activates AMP-activated protein kinase (AMPK), modulates PPAR-α/δ signalling, supports cellular antioxidant defence, and collectively attenuates anabolic mTOR activity while promoting autophagic recycling and metabolic homeostasis. Molecular docking analysis against the mTOR kinase domain (PDB ID: 4JSV) demonstrated that pentadecanoic acid binds within the active site with a binding energy of -4.4 kcal/mol through interactions with key hydrophobic residues, including Leu1936, Ile1939, Tyr2144, Val2227, and Gly2142, whereas rapamycin exhibited a stronger affinity (-10.1 kcal/mol). Unlike rapamycin, pentadecanoic acid is endogenously produced, compatible with pregnancy, and requires no washout period. Collectively, these findings position pentadecanoic acid as a promising endogenous mTOR modulator with potential therapeutic relevance for age-related female infertility, warranting further mechanistic investigations and well-designed human clinical trials.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"107100"},"PeriodicalIF":3.1,"publicationDate":"2027-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148714283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}