Biochemical Society transactions最新文献_第4页

Multifaceted roles of mycobacterial HflX: ribosome splitting, rRNA disordering, and drug resistance. 分枝杆菌HflX的多面作用：核糖体分裂、rRNA紊乱和耐药性。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-20 DOI: 10.1042/BST20253084

Soneya Majumdar, Pallavi Ghosh, Rajendra K Agrawal

{"title":"Multifaceted roles of mycobacterial HflX: ribosome splitting, rRNA disordering, and drug resistance.","authors":"Soneya Majumdar, Pallavi Ghosh, Rajendra K Agrawal","doi":"10.1042/BST20253084","DOIUrl":"10.1042/BST20253084","url":null,"abstract":"High frequency of lysogenization X (HflX) is an enigmatic protein that has been implicated in rescuing translationally stalled ribosomes and macrolide-lincosamide antibiotic resistance, as well as in ribosome biogenesis. The protein shows significant sequence and structural variation across species, including variation among paralogs within the same organism. Recent cryo-EM structure determination of ribosome-HflX complexes from different eubacterial species has provided important mechanistic clues to HflX function. Mycobacterial HflXs carry a distinct N-terminal extension (NTE) and a small insertion, as compared with their eubacterial homologs, suggesting that the mycobacterial HflX could have distinct functional mechanisms. This article presents a brief overview of these studies highlighting (i) what we have learned from recent multiple mycobacterial ribosome-HflX complex structures and (ii) the roles of mycobacteria-specific segments in ribosomal RNA disordering that leads to ribosome splitting to rescue translation by removing the drug-bound stalled ribosome from the translationally active polysome pool. Future studies needed to resolve some of the outstanding issues related to HflX function and dynamics are also discussed.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12493154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Control of epithelial homeostasis by apical polarity: it takes a network. 顶端极性对上皮稳态的控制：需要一个网络。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-18 DOI: 10.1042/BST20243002

Sophie A Lelièvre, Joséphine Briand

{"title":"Control of epithelial homeostasis by apical polarity: it takes a network.","authors":"Sophie A Lelièvre, Joséphine Briand","doi":"10.1042/BST20243002","DOIUrl":"10.1042/BST20243002","url":null,"abstract":"The maintenance of cell functions in response to various stimuli is fulfilled by tightly controlled homeostatic processes. The basoapical structure of normal epithelia is increasingly recognized as the guardian of homeostasis. It has recently been demonstrated that apical polarity, depicted by lateroapical tight junctions, is controlled by gap junctions and sets the resting membrane potential, itself essential for homeostasis, in the breast luminal epithelium. In the breast, the disruption of apical polarity is recognized as a necessary step toward cancer onset, which calls for a better understanding of its consequences on the mechanisms of homeostasis all the way to the genome. Here, we extend the traditional apical junctional complex to include gap junctions and investigate its relation with epigenetically- driven and higher order chromatin organization. The disruption of apical polarity affects different types of molecular networks that remodel chromatin with a tendency toward openness or relaxation, a status typically associated with instability and cancer onset. Events known to foster the development of cancers, such as chronic inflammation, oxidative stress, stiffer microenvironment, and aging, are all triggering the disruption of apical polarity, which leads us to explore possibilities to re-establish full polarity. Focusing on gap junction intercellular communication mediated by Connexin 43 might be an interesting therapeutic option for retinoic acid derivatives. However, in light of the different degrees of apical polarity loss, we surmise that the resulting chromatin alterations might depend on the way apical polarity is disrupted initially, which suggests that therapeutic combinations targeted also toward these alterations might be required.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12493189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Anticancer drug development against ribosome synthesis and the nucleolus. 抗核糖体合成和核仁抗癌药物的开发。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-04 DOI: 10.1042/BST20253011

Andrew Loiacono, Sui Huang

引用次数: 0

Redesigning miR-34a: structural and chemical advances in the therapeutic development of an miRNA anti-cancer agent. 重新设计miR-34a: miRNA抗癌药物治疗发展中的结构和化学进展。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-04 DOI: 10.1042/BST20253010

Shreyas G Iyer, Ikjot S Sohal, Andrea L Kasinski

{"title":"Redesigning miR-34a: structural and chemical advances in the therapeutic development of an miRNA anti-cancer agent.","authors":"Shreyas G Iyer, Ikjot S Sohal, Andrea L Kasinski","doi":"10.1042/BST20253010","DOIUrl":"10.1042/BST20253010","url":null,"abstract":"MicroRNAs (miRNAs) represent a promising class of therapeutics due to their ability to down-regulate multiple genes simultaneously. This offers a significant therapeutic advantage in cancer, where heterogeneity often activates different pathways in different patients. Chemical modifications to the miRNA help overcome challenges associated with nuclease susceptibility, high immunogenicity, and the need for high or repeated dosing to achieve therapeutic effects. The main chemical modifications include changes to the ribose and backbone. Ribose modifications, including 2'-O-methyl and 2'-fluoro, improve nuclease resistance and plasma stability and lower the immunogenicity of the miRNA. Phosphorothioate (PS) backbone modifications increase resistance to nucleases and prolong circulation by enhancing serum protein affinity. Integrating these stabilizing chemical modifications with ligand targeting allows for specific delivery of the chemically modified miRNAs to tumors and metastases, bypassing bulky delivery vehicles and improving penetration into dense tumor architectures. Enhancements to ligand chemistry can also overcome endosomal entrapment. Incorporating many of the modifications discussed in this mini-review, the first fully modified version of miR-34a (FM-miR-34a) was developed, marking a significant milestone as the first fully modified miRNA to demonstrate substantial in vivo activity. Ongoing optimization of the chemical modifications and ligand chemistry, and integrating artificial intelligence into the design process are expected to further extend the potential for delivering on the promise of using these Nobel Prize-winning miRNAs as anti-cancer agents.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advances in mechanochemical modelling of vertebrate gastrulation. 脊椎动物原肠形成的力学化学模型研究进展。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-07-22 DOI: 10.1042/BST20240469

Alex M Plum, Mattia Serra, Cornelis J Weijer

{"title":"Advances in mechanochemical modelling of vertebrate gastrulation.","authors":"Alex M Plum, Mattia Serra, Cornelis J Weijer","doi":"10.1042/BST20240469","DOIUrl":"10.1042/BST20240469","url":null,"abstract":"Gastrulation is an essential process in the early embryonic development of all higher animals. During gastrulation, the three embryonic germ layers, the ectoderm, mesoderm and endoderm, form and move to their correct positions in the developing embryo. This process requires the integration of cell division, differentiation and movement of thousands of cells. These cell behaviours are coordinated through shortand long-range signalling and must involve feedback to execute gastrulation in a reproducible and robust manner. Mechanosensitive signalling pathways and processes are being uncovered, revealing that shortand long-range mechanical stresses integrate cell behaviours at the tissue and organism scale. Because the interactions between cell behaviours, signalling and feedback are complex, combining experimental and modelling approaches is necessary to elucidate the regulatory mechanisms that drive development. We highlight how recent experimental and theoretical studies provided key insights into mechanical feedback that coordinates relevant cell behaviours at the organism scale during gastrulation. We outline advances in modelling the mechanochemical processes controlling primitive streak formation in the early avian embryo and discuss future developments.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Why are imprints unstable in pluripotent stem cells? 为什么印迹在多能干细胞中不稳定？

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-07-17 DOI: 10.1042/BST20243003

Maria Arez, Simão Teixeira da Rocha

{"title":"Why are imprints unstable in pluripotent stem cells?","authors":"Maria Arez, Simão Teixeira da Rocha","doi":"10.1042/BST20243003","DOIUrl":"10.1042/BST20243003","url":null,"abstract":"Pluripotent stem cells (PSCs) possess the remarkable ability to self-renew and differentiate into nearly any cell type, making them invaluable for both research and therapeutic applications. Despite these powerful attributes, PSCs are vulnerable to genetic and epigenetic instabilities that can undermine their reliability and safety. While genetic abnormalities can be routinely monitored with established guidelines, epigenetic instabilities often go unchecked. Among the most recurrent epigenetic defects in PSCs are errors in genomic imprinting - a process that governs parent-of-origin-specific monoallelic expression of certain genes through differential marking of the two parental alleles by DNA methylation. When disrupted, it becomes a source of a dozen developmental conditions known as imprinting diseases. In PSCs, once imprinting errors arise, they remain throughout cellular differentiation, casting uncertainty over the use of PSC-derived cells for disease modelling and regenerative medicine. In this review, we provide an overview of imprinting defects in both mouse and human PSCs, delving into their origins and consequences. We also discuss potential correction strategies that aim to enhance imprinting stability, ultimately paving the way for safer, more reliable PSC use in research and clinical applications.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12410003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Progress in recapitulating morphogenesis of blood microvascular structures for microphysiological systems development. 微生理系统发育中血液微血管结构形态发生概述的研究进展。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-07-17 DOI: 10.1042/BST20240572

Ana Ximena Monroy-Romero, Mathieu Hautefeuille

{"title":"Progress in recapitulating morphogenesis of blood microvascular structures for microphysiological systems development.","authors":"Ana Ximena Monroy-Romero, Mathieu Hautefeuille","doi":"10.1042/BST20240572","DOIUrl":"10.1042/BST20240572","url":null,"abstract":"Microphysiological systems (MPSs) are complex cell culture platforms, designed to closely replicate the cellular microenvironment of tissues under physiopathological conditions. A critical aspect of these systems is the integration of a vascular network, which facilitates nutrient exchange, supports heterotypic cell interactions, and increases culture viability. A top-down engineering approach, where a prefabricated scaffold is used to introduce endothelial cells, has been widely employed. However, promoting self-organization through a bottom-up paradigm has proven more effective in recapitulating the geometric features of microvasculature, particularly the network nature of it as the capillary diameters. In vivo vasculature formation occurs primarily through two self-organization processes: vasculogenesis and angiogenesis. These processes follow a series of co-ordinated and regulated steps, driven by microenvironmental cues such as cell identity and heterogeneity, soluble factor distribution, extracellular matrix composition and mechanics, and flow-induced mechanical strains. By incorporating these parameters into in vitro platforms, researchers can develop physiologically relevant vascularized MPS for applications in drug development and disease modeling. This review explores the key mechanisms underlying vascular self-organization and highlights how they are being integrated into tissue-specific MPS platforms to achieve vascularization, which enhances the potential of MPS for studying various physiological and pathological processes.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The fantastic voyage: primordial germ cell migration through the developing mouse embryo. 奇妙的旅程：原始生殖细胞通过发育中的小鼠胚胎迁移。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-07-17 DOI: 10.1042/BST20253009

Katharine Goodwin

{"title":"The fantastic voyage: primordial germ cell migration through the developing mouse embryo.","authors":"Katharine Goodwin","doi":"10.1042/BST20253009","DOIUrl":"10.1042/BST20253009","url":null,"abstract":"During the early stages of embryonic development, a small population of cells is set aside to form the germline. These primordial germ cells (PGCs) are often specified separate in time and space from their eventual home, the developing gonads. PGCs must therefore undertake a journey through the developing tissues of the embryo to reach their destination and ensure the fertility of the organism. Despite decades of interest in this topic and significant progress made in other model organisms, there is still very little known about how this migration is accomplished in the mouse or any other mammal. In this review, I explore over half a century of work examining this enigmatic cell and its voyage through the mouse embryo, interpreting these findings in light of recent discoveries in the field of cell migration. I discuss possible migration modes used by mouse PGCs, changes in their microenvironment that could influence migration, and roles the nucleus might play in their journey. With modern advances in microscopy and transgenic reporter mice, it is time to delve into this fascinating and important model of cell migration in vivo.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DIG-DUBs: mechanisms and functions of ISG15 deconjugation by human and viral cross-reactive ubiquitin proteases. digg - dubs：人类和病毒交叉反应性泛素蛋白酶解ISG15的机制和功能。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-07-09 DOI: 10.1042/BST20240859

Thomas Bonacci, Michael J Emanuele

{"title":"DIG-DUBs: mechanisms and functions of ISG15 deconjugation by human and viral cross-reactive ubiquitin proteases.","authors":"Thomas Bonacci, Michael J Emanuele","doi":"10.1042/BST20240859","DOIUrl":"10.1042/BST20240859","url":null,"abstract":"Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like protein and, as such, acts as a post-translational modifier that plays a critical role during bacterial and viral infections after interferon (IFN) production. As part of the innate immune system, ISG15 is strongly induced by type I IFNs, and its conjugation to intracellular proteins and viral proteins (ISGylation) allows cells to fight off infection. Importantly, ISGylation is a reversible process that is largely mediated by the cysteine protease USP18 (Ubp43 in mice). As a multifaceted protein, USP18 is a major negative regulator of IFN signaling and the predominant deISGylating enzyme in humans. However, in recent years, additional proteases such as USP16 and USP24 have been reported to also mediate ISG15 hydrolysis. Moreover, coronaviruses and other viral pathogens often encode proteases that possess deISGylating activity, which promotes viral infection by antagonizing ISGylation. Here, we review various enzymes and modes of action employed by human and viral proteases to regulate deISGylation under physiological or pathogenic conditions.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12410001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects and regulation of ACE2 and TMPRSS2 abundance in healthy humans and in patients with SARS-CoV-2. ACE2和TMPRSS2在健康人及SARS-CoV-2患者中的影响及调控

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-07-08 DOI: 10.1042/BST20241052

Marie Lykke Bach, Boye L Jensen

{"title":"Effects and regulation of ACE2 and TMPRSS2 abundance in healthy humans and in patients with SARS-CoV-2.","authors":"Marie Lykke Bach, Boye L Jensen","doi":"10.1042/BST20241052","DOIUrl":"https://doi.org/10.1042/BST20241052","url":null,"abstract":"The present narrative review focuses on organ distribution, co-localization, age-, and sex-dependent changes in angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) and how such changes associate with SARS-CoV-2 virus entry and disease severity in humans. ACE2 is a membrane-bound enzyme with lower abundance in children/young adults compared with elderly, with no protein abundance difference between ages 35-50 and >80 but higher in females at reproductive age. ACE2 locates predominantly in gastrointestinal (GI)-tract epithelia, kidney proximal tubules, male and female reproductive organs with very low levels in the lungs. Estrogen upregulates ACE2, which can be shed from cells into plasma by, for example ADAM17, while remaining active. TMPRSS2 is a membrane-associated serine protease with androgen dependence. The highest levels in humans are found in male reproductive organs, kidney, and GI-tract. Co-localization with ACE2 in alveolar type 2 cells is based mostly on in vitro studies. Documentation of clustering of ACE2 and TMPRSS2 in human tissues is scarce and best in oral-pharyngeal mucosa. In patients with mild-to-serious COVID-19 disease, there is no consistent change in circulating renin, aldosterone, ACE and ACE2 activities, angiotensin II (ANGII), and Ang1-7. Increased ANGII levels are reported in critically ill patients, while ACE2 is massively present in urine. Use of RAAS inhibitors is not associated with negative outcomes in patients with COVID-19. In conclusion, co-localization of ACE2 and TMPRSS2 in oral and airway epithelia may explain the primary route of infection for SARS-CoV-2 virus. Higher risk for serious disease in elderly males may not be accounted for by quantitative changes in the proteins.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590351","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}

引用次数: 0