Open Biology最新文献

Perspectives on tissue-selective insulin derivatives. 组织选择性胰岛素衍生物的研究进展。

IF 3.1 3区生物学

Open Biology Pub Date : 2026-10-14 DOI: 10.1098/rsob.260175

Maxmilián Hejl, Jiří Jiráček

{"title":"Perspectives on tissue-selective insulin derivatives.","authors":"Maxmilián Hejl, Jiří Jiráček","doi":"10.1098/rsob.260175","DOIUrl":"https://doi.org/10.1098/rsob.260175","url":null,"abstract":"Insulin is a central regulator of metabolic homoeostasis with diverse, tissue-specific actions across multiple organs. Despite major advances in insulin formulations, current therapies rely on systemic delivery and do not reproduce the physiological distribution of endogenous insulin, resulting in non-physiological tissue exposure and associated metabolic limitations. In this perspective, we discuss emerging strategies aimed at achieving tissue-selective insulin action, including molecular engineering of insulin analogues, modulation of insulin receptor isoform specificity and targeted delivery approaches. Attention is given to hepato-preferential, muscle-directed, brain-targeted and adipose-modulating strategies, highlighting their mechanistic basis, therapeutic potential and inherent limitations. While proof of principle has been established for several approaches, challenges remain in balancing tissue selectivity with whole-body metabolic control. Advances in protein design and delivery technologies may ultimately enable the development of next-generation insulin therapies that better mimic physiological insulin action and improve clinical outcomes in metabolic and neurodegenerative diseases.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"16 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183723","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

Hsp90 as a master regulator in autoimmunity: from cellular stress to clinical opportunity. Hsp90作为自身免疫的主要调节因子：从细胞应激到临床机会

IF 3.1 3区生物学

Open Biology Pub Date : 2026-10-14 DOI: 10.1098/rsob.260040

Scott Scarneo, Robert Freeze, Timothy A Haystead

{"title":"Hsp90 as a master regulator in autoimmunity: from cellular stress to clinical opportunity.","authors":"Scott Scarneo, Robert Freeze, Timothy A Haystead","doi":"10.1098/rsob.260040","DOIUrl":"https://doi.org/10.1098/rsob.260040","url":null,"abstract":"Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that governs the folding, stabilization and activity of a wide range of client proteins, many of which are critical regulators of immune cell signalling and inflammatory responses. Recent research has underscored the role of Hsp90 in orchestrating both innate and adaptive immune functions, particularly in the context of autoimmune diseases. In autoimmune diseases, dysregulated immune pathways often involve Hsp90-dependent client proteins, including key kinases and transcription factors. By modulating the activation, differentiation and survival of immune cells Hsp90 emerges as a central node in autoimmune pathogenesis. Importantly, the pharmacological inhibition of Hsp90 has shown promise in preclinical models of autoimmunity, where it attenuates pro-inflammatory pathways. In this review, we examine the immunoregulatory functions of Hsp90 with a focus on autoimmune disorders, highlighting its role in disease-driving pathways, such as Nuclear Factor Kappa B (NF-κB), Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) and Mitogen-Activated Protein Kinase (MAPK). We also discuss the current landscape of Hsp90 inhibitors, their mechanism of action, and emerging data on their efficacy in autoimmune disease models. Understanding how Hsp90 shapes immune cell behaviour and inflammation provides a compelling framework for its development as a novel therapeutic target in chronic autoimmune conditions.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"16 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183720","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

TEAD4 Regulates apical domain homeostasis and cell-positioning to maintain the trophectoderm lineage during mouse blastocyst development. TEAD4在小鼠囊胚发育过程中调节顶域稳态和细胞定位以维持滋养外胚层谱系。

IF 3.1 3区生物学

Open Biology Pub Date : 2026-10-07 DOI: 10.1098/rsob.250441

Rebecca Collier, Martina Bohuslavová, Michaela Vaškovičová, Aleksandar I Mihajlović, Andrea Hauserová, Valeriya Zabelina, Monika Fluks, Lenka Gahurová, Dávid Drutovič, Alexander W Bruce

{"title":"TEAD4 Regulates apical domain homeostasis and cell-positioning to maintain the trophectoderm lineage during mouse blastocyst development.","authors":"Rebecca Collier, Martina Bohuslavová, Michaela Vaškovičová, Aleksandar I Mihajlović, Andrea Hauserová, Valeriya Zabelina, Monika Fluks, Lenka Gahurová, Dávid Drutovič, Alexander W Bruce","doi":"10.1098/rsob.250441","DOIUrl":"10.1098/rsob.250441","url":null,"abstract":"In mammalian preimplantation embryos, distinct cell lineages occupy defined spatial niches. The outer trophectoderm (TE) forms an epithelial monolayer surrounding the inner cell mass (ICM) and blastocyst cavity. In mice, the Tead4 gene encodes a polarity-dependent transcription factor required for TE specification. Here, we demonstrate that Tead4 also preserves TE integrity during blastocyst maturation. Clonal siRNA-mediated Tead4 knockdown (KD) disrupts outer cell apical domain morphology, causing abnormal allocation of these clones to an enlarged ICM, despite minimal impact on established polarity. Fixed sample and live embryo light-sheet microscopy imaging reveal that TEAD4-deficient outer cells atypically migrate into the blastocyst ICM, sometimes via apical domain abscission, or are repositioned post-division, linking disrupted apical domain morphology to altered spatial positioning and fate. Transcriptomic analysis indicates that TEAD4 regulates genes involved in cytoskeletal organization, particularly those related to actin and cell adhesion, which we propose are critical for maintaining outer cell TE positioning. Combined KD of Tead4 and two of its targets, the atypical GTPases Rnd1 and Rnd3, partially rescues misallocation but does not prevent apical morphological abnormalities. These findings indicate TEAD4 and its downstream regulatory network actively contribute to blastocyst TE maintenance, beyond initial specification, up until the peri-implantation stage, ensuring proper lineage segregation.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"16 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112939","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

Cracking the fertility code: a comprehensive review of biomarkers and functional measures. 破解生育密码：生物标志物和功能测量的全面回顾。

IF 3.1 3区生物学

Open Biology Pub Date : 2026-10-07 DOI: 10.1098/rsob.260199

Morgan F Woodman-Sousa, Kathryn Grive

{"title":"Cracking the fertility code: a comprehensive review of biomarkers and functional measures.","authors":"Morgan F Woodman-Sousa, Kathryn Grive","doi":"10.1098/rsob.260199","DOIUrl":"https://doi.org/10.1098/rsob.260199","url":null,"abstract":"Human fertility is regulated by a complex, integrated network of biological systems that collectively determine reproductive competence in males and females. Conventional fertility assessment relies on established clinical biomarkers, including reproductive hormone profiles, gamete-based functional assessments and imaging indicators of gonadal structure and function. While clinically informative, these measures capture only partial views of molecular and cellular processes underlying gametogenesis and reproductive capacity. Recent advances in reproductive medicine have expanded the biomarker landscape through genetic and epigenetic profiling, enabling identification of pathogenic variants, chromosomal abnormalities and regulatory modifications associated with infertility syndromes. In parallel, multi-omics approaches are increasingly being used to characterize molecular networks governing gamete development, meiotic integrity, DNA repair and cellular differentiation. This review presents a comprehensive synthesis of fertility biomarkers, spanning endocrine, genetic, epigenetic, structural, metabolic and inflammatory systems. Current evidence is examined on endocrine and reproductive hormone biomarkers, followed by an investigation of genetic and epigenetic markers of reproductive dysfunction, as well as structural and imaging-based biomarkers and inflammatory and metabolic indicators. Finally, emerging biomarker platforms are highlighted as key advances towards precision reproductive medicine. Collectively, these developments support a shift towards a more comprehensive, biomarker-driven framework for the evaluation and management of infertility.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"16 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228458","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

Identification of expressed endogenous retroviral element associated long terminal repeats in devil facial tumour cells. 面部肿瘤细胞中表达内源性逆转录病毒元件相关长末端重复序列的鉴定。

IF 3.1 3区生物学

Open Biology Pub Date : 2026-10-07 DOI: 10.1098/rsob.250430

Anuk Kruawan, Maximilian R Stammnitz, Richard Wilson, Sri H Ramarathinam, Chrissie E B Ong, Kirsten A Fairfax, Amanda L Patchett, A Bruce Lyons, Andy Flies

{"title":"Identification of expressed endogenous retroviral element associated long terminal repeats in devil facial tumour cells.","authors":"Anuk Kruawan, Maximilian R Stammnitz, Richard Wilson, Sri H Ramarathinam, Chrissie E B Ong, Kirsten A Fairfax, Amanda L Patchett, A Bruce Lyons, Andy Flies","doi":"10.1098/rsob.250430","DOIUrl":"10.1098/rsob.250430","url":null,"abstract":"The Tasmanian devil (Sarcophilus harrisii) population has undergone a major decline in the wild owing to the epidemics of two transmissible cancers known as devil facial tumours (DFT1 and DFT2). A multipronged conservation strategy is in place, but a vaccine that prevents devils from developing devil facial tumour disease would be a major step towards recovering the wild devil population. Critical to an effective DFT vaccine are target antigens. Putative non-coding regions of genomes have been identified as potential tumour-specific antigens for human cancer. These non-coding regions include long terminal repeats (LTRs) of endogenous retroviral elements (ERVs). We identified 11 193 ERV LTR transcripts that were expressed in DFT1 or DFT2 transcriptomes but not in healthy tissue samples. Using a proteogenomic approach, we identified 33 ERV LTR peptides unique to DFT1 and/or DFT2 immunopeptidomes; five of these were validated in subsequent screens with synthetic peptides. The ERV LTR peptides identified in this study can be tested as vaccine targets in DFT1 and DFT2 vaccines. This method can be applied to other species for the development of cancer vaccine targets that may be shared across tumour types.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"16 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112919","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

Interaction of genetic and environmental risk factors in the aetiology of keratoconus. 遗传和环境因素在圆锥角膜病因中的相互作用。

IF 3.1 3区生物学

Open Biology Pub Date : 2026-09-30 DOI: 10.1098/rsob.260068

Rachel Hadvina, Yutao Liu

引用次数: 0

A luminal proteome of the endoplasmic reticulum and Golgi apparatus reveals a novel modulator of ER stress tolerance in African trypanosomes. 内质网和高尔基体的管腔蛋白质组揭示了非洲锥虫内质网应激耐受的新调节剂。

IF 3.1 3区生物学

Open Biology Pub Date : 2026-09-23 DOI: 10.1098/rsob.260178

Siqi Shen, Farnaz Zahedifard, Emmanuel A Agbebi, Anna Zavrelova, Johanna Krenzer, Carla G Carbajo, Silke Braune, Susanne Kramer, Calvin Tiengwe, Martin Zoltner

{"title":"A luminal proteome of the endoplasmic reticulum and Golgi apparatus reveals a novel modulator of ER stress tolerance in African trypanosomes.","authors":"Siqi Shen, Farnaz Zahedifard, Emmanuel A Agbebi, Anna Zavrelova, Johanna Krenzer, Carla G Carbajo, Silke Braune, Susanne Kramer, Calvin Tiengwe, Martin Zoltner","doi":"10.1098/rsob.260178","DOIUrl":"https://doi.org/10.1098/rsob.260178","url":null,"abstract":"African trypanosomes employ specialized mechanisms of membrane trafficking as a strategy to persist in both the mammalian host and insect vector. Their survival relies on continuous synthesis and surface delivery of extremely abundant surface coat proteins, imposing an extraordinary biosynthetic burden on the secretory pathway. Despite this, their ER and Golgi luminal proteomes remain incompletely characterized. Here, we exploit proximity biotinylation, using the abundant ER chaperone BiP as bait to map the ER proteome in bloodstream and procyclic lifecycle stages. Comparison with BiPN, a truncated secretory form of BiP that escapes the ER and transits the Golgi, provides differential compartmental labelling. Quantitative ranking of BiP labelling intensity identifies a candidate BiP interactor cohort including a divergent homologue to the mammalian BiP nucleotide exchange inhibitor MANF. Reciprocal manipulation of TbMANF abundance produces opposing shifts in cellular sensitivity to ER stress. These data are consistent with a role in regulating BiP ATPase cycling in an organism that, unlike opisthokonts, lacks a canonical unfolded protein response, making TbMANF the first regulator of BiP activity identified in kinetoplastids. Finally, proximity labelling anchored at the inner face of the nuclear pore via NUP65 extends our endomembrane map to the inner nuclear membrane, identifying candidate proteins of this specialized ER-continuous domain.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"16 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025628","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

Emerging role for R-loops in chromosome segregation. r环在染色体分离中的新作用。

IF 3.1 3区生物学

Open Biology Pub Date : 2026-09-16 DOI: 10.1098/rsob.260090

Prashant K Mishra, Munira A Basrai

引用次数: 0

Molecular basis and therapeutic potential of sortase A inhibitors as new antibiotics against MDR pathogens. 分类酶A抑制剂作为耐多药病原菌新抗生素的分子基础和治疗潜力。

IF 3.1 3区生物学

Open Biology Pub Date : 2026-09-09 DOI: 10.1098/rsob.250415

Ananya Dash, Christopher LaRock

引用次数: 0

Assessment of adult structural plasticity in Drosophila neurons. 果蝇神经元成体结构可塑性的评估。

IF 3.1 3区生物学

Open Biology Pub Date : 2026-09-09 DOI: 10.1098/rsob.260120

Micaela Rodriguez-Caron, Francisco Joaquin Tassara, Juan Ignacio Ispizua, Christian Mauricio Carpio-Romero, María Fernanda Ceriani

{"title":"Assessment of adult structural plasticity in Drosophila neurons.","authors":"Micaela Rodriguez-Caron, Francisco Joaquin Tassara, Juan Ignacio Ispizua, Christian Mauricio Carpio-Romero, María Fernanda Ceriani","doi":"10.1098/rsob.260120","DOIUrl":"10.1098/rsob.260120","url":null,"abstract":"Unravelling how adult neurons reshape their architecture is key to understanding post-developmental plasticity. Drosophila clock neurons, which remodel their terminals on a daily basis, offer a unique model to examine the mechanisms underlying structural plasticity. In this study, we examine the impact of the experimental design on the remodelling process. We established a simple fixation protocol that preserves tissue integrity and prevents its deformation while enabling the fixation of a larger number of individuals within the appropriate time window. We show that intrinsic (i.e. targeting fluorescent reporters to the membrane) or extrinsic (i.e. temperature) variables may influence this dynamic process. Examining ex vivo preparations, we found that the small lateral ventral neuron (s-LNv) terminals display numerous thin filopodia extending from their synaptic boutons. However, these fine membrane protrusions are lost upon fixation, as they could only be accurately visualized ex vivo. Finally, we present MorphoScope, a Python-based interface that eliminates observer bias in complexity measurements. Altogether, we present a powerful and robust model to investigate the principles of adult neuronal plasticity, with implications extending beyond circadian biology.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"16 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13561074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913088","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