Open Biology最新文献_第2页

Zebrafish reveal new roles for Fam83f in hatching and the DNA damage-mediated autophagic response. 斑马鱼揭示了 Fam83f 在孵化和 DNA 损伤介导的自噬反应中的新作用。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-10-01 Epub Date: 2024-10-23 DOI: 10.1098/rsob.240194

Rebecca A Jones, Fay Cooper, Gavin Kelly, David Barry, Matthew J Renshaw, Gopal Sapkota, James C Smith

{"title":"Zebrafish reveal new roles for Fam83f in hatching and the DNA damage-mediated autophagic response.","authors":"Rebecca A Jones, Fay Cooper, Gavin Kelly, David Barry, Matthew J Renshaw, Gopal Sapkota, James C Smith","doi":"10.1098/rsob.240194","DOIUrl":"https://doi.org/10.1098/rsob.240194","url":null,"abstract":"The FAM83 (Family with sequence similarity 83) family is highly conserved in vertebrates, but little is known of the functions of these proteins beyond their association with oncogenesis. Of the family, FAM83F is of particular interest because it is the only membrane-targeted FAM83 protein. When overexpressed, FAM83F activates the canonical Wnt signalling pathway and binds to and stabilizes p53; it therefore interacts with two pathways often dysregulated in disease. Insights into gene function can often be gained by studying the roles they play during development, and here we report the generation of fam83f knock-out (KO) zebrafish, which we have used to study the role of Fam83f in vivo. We show that endogenous fam83f is most strongly expressed in the hatching gland of developing zebrafish embryos, and that fam83f KO embryos hatch earlier than their wild-type (WT) counterparts, despite developing at a comparable rate. We also demonstrate that fam83f KO embryos are more sensitive to ionizing radiation than WT embryos-an unexpected finding, bearing in mind the previously reported ability of FAM83F to stabilize p53. Transcriptomic analysis shows that loss of fam83f leads to downregulation of phosphatidylinositol-3-phosphate (PI(3)P) binding proteins and impairment of cellular degradation pathways, particularly autophagy, a crucial component of the DNA damage response. Finally, we show that Fam83f protein is itself targeted to the lysosome when overexpressed in HEK293T cells, and that this localization is dependent upon a C' terminal signal sequence. The zebrafish lines we have generated suggest that Fam83f plays an important role in autophagic/lysosomal processes, resulting in dysregulated hatching and increased sensitivity to genotoxic stress in vivo.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505306","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

Haploidy-linked cell proliferation defects limit larval growth in zebrafish. 与单倍体相关的细胞增殖缺陷限制了斑马鱼幼体的生长。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-10-01 Epub Date: 2024-10-09 DOI: 10.1098/rsob.240126

Kan Yaguchi, Daiki Saito, Triveni Menon, Akira Matsura, Miyu Hosono, Takeomi Mizutani, Tomoya Kotani, Sreelaja Nair, Ryota Uehara

{"title":"Haploidy-linked cell proliferation defects limit larval growth in zebrafish.","authors":"Kan Yaguchi, Daiki Saito, Triveni Menon, Akira Matsura, Miyu Hosono, Takeomi Mizutani, Tomoya Kotani, Sreelaja Nair, Ryota Uehara","doi":"10.1098/rsob.240126","DOIUrl":"10.1098/rsob.240126","url":null,"abstract":"Haploid larvae in non-mammalian vertebrates are lethal, with characteristic organ growth retardation collectively called 'haploid syndrome'. In contrast to mammals, whose haploid intolerance is attributed to imprinting misregulation, the cellular principle of haploidy-linked defects in non-mammalian vertebrates remains unknown. Here, we investigated cellular defects that disrupt the ontogeny of gynogenetic haploid zebrafish larvae. Unlike diploid control larvae, haploid larvae manifested unscheduled cell death at the organogenesis stage, attributed to haploidy-linked p53 upregulation. Moreover, we found that haploid larvae specifically suffered the gradual aggravation of mitotic spindle monopolarization during 1-3 days post-fertilization, causing spindle assembly checkpoint-mediated mitotic arrest throughout the entire body. High-resolution imaging revealed that this mitotic defect accompanied the haploidy-linked centrosome loss occurring concomitantly with the gradual decrease in larval cell size. Either resolution of mitotic arrest or depletion of p53 partially improved organ growth in haploid larvae. Based on these results, we propose that haploidy-linked mitotic defects and cell death are parts of critical cellular causes shared among vertebrates that limit the larval growth in the haploid state, contributing to an evolutionary constraint on allowable ploidy status in the vertebrate life cycle.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392240","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

Differentially expressed lncRNAs in SOD1^G93A mice skeletal muscle: H19, Myhas and Neat1 as potential biomarkers in amyotrophic lateral sclerosis. SOD1G93A小鼠骨骼肌中差异表达的lncRNA：H19、Myhas和Neat1作为肌萎缩侧索硬化症的潜在生物标记物。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-10-01 Epub Date: 2024-10-16 DOI: 10.1098/rsob.240015

Tresa López-Royo, Laura Moreno-Martínez, Pilar Zaragoza, Alberto García-Redondo, Raquel Manzano, Rosario Osta

{"title":"Differentially expressed lncRNAs in SOD1G93A mice skeletal muscle: H19, Myhas and Neat1 as potential biomarkers in amyotrophic lateral sclerosis.","authors":"Tresa López-Royo, Laura Moreno-Martínez, Pilar Zaragoza, Alberto García-Redondo, Raquel Manzano, Rosario Osta","doi":"10.1098/rsob.240015","DOIUrl":"https://doi.org/10.1098/rsob.240015","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disease characterized by progressive motor function and muscle mass loss. Despite extensive research in the field, the underlying causes of ALS remain incompletely understood, contributing to the absence of specific diagnostic and prognostic biomarkers and effective therapies. This study investigates the expression of long-non-coding RNAs (lncRNAs) in skeletal muscle as a potential source of biomarkers and therapeutic targets for the disease. The expression profiles of 12 lncRNAs, selected from the literature, were evaluated across different disease stages in tissue and muscle biopsies from the SOD1G93A transgenic mouse model of ALS. Nine out of the 12 lncRNAs were differentially expressed, with Pvt1, H19 and Neat1 showing notable increases in the symptomatic stages of the disease, and suggesting their potential as candidate biomarkers to support diagnosis and key players in muscle pathophysiology in ALS. Furthermore, the progression of Myhas and H19 RNA levels across disease stages correlated with longevity in the SOD1G93A animal model, effectively discriminating between long- and short-term survival individuals, thereby highlighting their potential as prognostic indicators. These findings underscore the involvement of lncRNAs, especially H19 and Myhas, in ALS pathophysiology, offering novel insights for diagnostic, prognostic and therapeutic targets.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11479763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471740","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

Novel in vivo TDP-43 stress reporter models to accelerate drug development in ALS. 加速 ALS 药物开发的新型体内 TDP-43 应激报告模型。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-10-01 Epub Date: 2024-10-30 DOI: 10.1098/rsob.240073

Febe Ferro, C Roland Wolf, Christopher Henstridge, Francisco Inesta-Vaquera

{"title":"Novel in vivo TDP-43 stress reporter models to accelerate drug development in ALS.","authors":"Febe Ferro, C Roland Wolf, Christopher Henstridge, Francisco Inesta-Vaquera","doi":"10.1098/rsob.240073","DOIUrl":"10.1098/rsob.240073","url":null,"abstract":"The development of therapies to combat neurodegenerative diseases is widely recognized as a research priority. Despite recent advances in understanding their molecular basis, there is a lack of suitable early biomarkers to test selected compounds and accelerate their translation to clinical trials. We have investigated the utility of in vivo reporters of cytoprotective pathways (e.g. NRF2, p53) as surrogate early biomarkers of the ALS degenerative disease progression. We hypothesized that cellular stress observed in a model of ALS may precede overt cellular damage and could activate our cytoprotective pathway reporters. To test this hypothesis, we generated novel ALS-reporter mice by crossing the hTDP-43tg model into our oxidative stress/inflammation (Hmox1; NRF2 pathway) and DNA damage (p21; p53 pathway) stress reporter models. Histological analysis of reporter expression in a homozygous hTDP-43tg background demonstrated a time-dependent and tissue-specific activation of the reporters in tissues directly associated with ALS, before moderate clinical signs are observed. Further work is warranted to determine the specific mechanisms by which TDP-43 accumulation leads to reporter activation and whether therapeutic intervention modulates reporters' expression. We anticipate the reporter strategy could be of great value in developing treatments for a range of degenerative disorders.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546538","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 post-translational modification O-GlcNAc is a sensor and regulator of metabolism. 翻译后修饰 O-GlcNAc 是新陈代谢的传感器和调节器。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-10-01 Epub Date: 2024-10-30 DOI: 10.1098/rsob.240209

Murielle M Morales, Matthew R Pratt

引用次数: 0

Opening and changing: mammalian SWI/SNF complexes in organ development and carcinogenesis. 开放与变化：哺乳动物器官发育和癌变过程中的 SWI/SNF 复合物。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-10-01 Epub Date: 2024-10-30 DOI: 10.1098/rsob.240039

Fadia Abu Sailik, Bright Starling Emerald, Suraiya Anjum Ansari

{"title":"Opening and changing: mammalian SWI/SNF complexes in organ development and carcinogenesis.","authors":"Fadia Abu Sailik, Bright Starling Emerald, Suraiya Anjum Ansari","doi":"10.1098/rsob.240039","DOIUrl":"10.1098/rsob.240039","url":null,"abstract":"The switch/sucrose non-fermentable (SWI/SNF) subfamily are evolutionarily conserved, ATP-dependent chromatin-remodelling complexes that alter nucleosome position and regulate a spectrum of nuclear processes, including gene expression, DNA replication, DNA damage repair, genome stability and tumour suppression. These complexes, through their ATP-dependent chromatin remodelling, contribute to the dynamic regulation of genetic information and the maintenance of cellular processes essential for normal cellular function and overall genomic integrity. Mutations in SWI/SNF subunits are detected in 25% of human malignancies, indicating that efficient functioning of this complex is required to prevent tumourigenesis in diverse tissues. During development, SWI/SNF subunits help establish and maintain gene expression patterns essential for proper cellular identity and function, including maintenance of lineage-specific enhancers. Moreover, specific molecular signatures associated with SWI/SNF mutations, including disruption of SWI/SNF activity at enhancers, evasion of G0 cell cycle arrest, induction of cellular plasticity through pro-oncogene activation and Polycomb group (PcG) complex antagonism, are linked to the initiation and progression of carcinogenesis. Here, we review the molecular insights into the aetiology of human malignancies driven by disruption of the SWI/SNF complex and correlate these mechanisms to their developmental functions. Finally, we discuss the therapeutic potential of targeting SWI/SNF subunits in cancer.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546539","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

Fly Fam161 is an essential centriole and cilium transition zone protein with unique and diverse cell type-specific localizations. Fly Fam161是一种重要的中心粒和纤毛过渡区蛋白，具有独特而多样的细胞类型特异性定位。

IF 5.8 3区生物学

Open Biology Pub Date : 2024-09-11 DOI: 10.1098/rsob.240036

Ankit Jaiswal,Andrew Boring,Avik Mukherjee,Tomer Avidor-Reiss

引用次数: 0

In silico modelling of neuron signal impact of cytokine storm-induced demyelination. 细胞因子风暴诱发脱髓鞘的神经元信号影响的硅学建模。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-09-01 Epub Date: 2024-09-04 DOI: 10.1098/rsob.240138

Geoflly L Adonias, Harun Siljak, Sasitharan Balasubramaniam, Michael Taynnan Barros

引用次数: 0

Phylogenomic diversity of archigregarine apicomplexans. 弧菌的系统发生组多样性。

IF 4.5 3区生物学

Open Biology Pub Date : 2024-09-01 Epub Date: 2024-09-25 DOI: 10.1098/rsob.240141

Gordon Lax, Eunji Park, Ina Na, Victoria Jacko-Reynolds, Waldan K Kwong, Chloe S E House, Morelia Trznadel, Kevin Wakeman, Brian S Leander, Patrick Keeling

{"title":"Phylogenomic diversity of archigregarine apicomplexans.","authors":"Gordon Lax, Eunji Park, Ina Na, Victoria Jacko-Reynolds, Waldan K Kwong, Chloe S E House, Morelia Trznadel, Kevin Wakeman, Brian S Leander, Patrick Keeling","doi":"10.1098/rsob.240141","DOIUrl":"10.1098/rsob.240141","url":null,"abstract":"Gregarines are a large and diverse subgroup of Apicomplexa, a lineage of obligate animal symbionts including pathogens such as Plasmodium, the malaria parasite. Unlike Plasmodium, however, gregarines are poorly studied, despite the fact that as early-branching apicomplexans they are crucial to our understanding of the origin and evolution of all apicomplexans and their parasitic lifestyle. Exemplifying this, the earliest branch of gregarines, the archigregarines, are particularly poorly studied: around 80 species have been described from marine invertebrates, but almost all of them were assigned to a single genus, Selenidium. Most are known only from light micrographs and largely unresolved rDNA phylogenies, where they exhibit a great deal of sequence variation, and fall into four subclades. To resolve the relationships within archigregarines, we sequenced 12 single-cell transcriptomes from species representing all four known subclades, as well as one blastogregarine (which frequently branch with Selenidium). A 190-gene phylogenomic tree confirmed four maximally supported individual clades of archigregarines and blastogregarines. These clades are discrete and distantly related, and also correlate with host identity. We propose the establishment of three novel genera of archigregarines to reflect their phylogenetic diversity and host range, and nine novel species isolated from a range of marine invertebrates.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351355","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

Can calmodulin bind to lipids of the cytosolic leaflet of plasma membranes? 钙调蛋白能与质膜细胞膜小叶的脂质结合吗？

IF 4.5 3区生物学

Open Biology Pub Date : 2024-09-01 Epub Date: 2024-09-18 DOI: 10.1098/rsob.240067

Federica Scollo, Carmelo Tempra, Hüseyin Evci, Miguel Riopedre-Fernandez, Agnieszka Olżyńska, Matti Javanainen, Arunima Uday, Marek Cebecauer, Lukasz Cwiklik, Hector Martinez-Seara, Pavel Jungwirth, Piotr Jurkiewicz, Martin Hof

{"title":"Can calmodulin bind to lipids of the cytosolic leaflet of plasma membranes?","authors":"Federica Scollo, Carmelo Tempra, Hüseyin Evci, Miguel Riopedre-Fernandez, Agnieszka Olżyńska, Matti Javanainen, Arunima Uday, Marek Cebecauer, Lukasz Cwiklik, Hector Martinez-Seara, Pavel Jungwirth, Piotr Jurkiewicz, Martin Hof","doi":"10.1098/rsob.240067","DOIUrl":"10.1098/rsob.240067","url":null,"abstract":"Calmodulin (CaM) is a ubiquitous calcium-sensitive messenger in eukaryotic cells. It was previously shown that CaM possesses an affinity for diverse lipid moieties, including those found on CaM-binding proteins. These facts, together with our observation that CaM accumulates in membrane-rich protrusions of HeLa cells upon increased cytosolic calcium, motivated us to perform a systematic search for unmediated CaM interactions with model lipid membranes mimicking the cytosolic leaflet of plasma membranes. A range of experimental techniques and molecular dynamics simulations prove unambiguously that CaM interacts with lipid bilayers in the presence of calcium ions. The lipids phosphatidylserine (PS) and phosphatidylethanolamine (PE) hold the key to CaM-membrane interactions. Calcium induces an essential conformational rearrangement of CaM, but calcium binding to the headgroup of PS also neutralizes the membrane negative surface charge. More intriguingly, PE plays a dual role-it not only forms hydrogen bonds with CaM, but also destabilizes the lipid bilayer increasing the exposure of hydrophobic acyl chains to the interacting proteins. Our findings suggest that upon increased intracellular calcium concentration, CaM and the cytosolic leaflet of cellular membranes can be functionally connected.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292803","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