Open Biology最新文献_第8页

High-density lipoprotein cholesterol: how studying the 'good cholesterol' could improve cardiovascular health. 高密度脂蛋白胆固醇：研究“好胆固醇”如何改善心血管健康。

IF 4.5 3区生物学

Open Biology Pub Date : 2025-02-01 Epub Date: 2025-02-19 DOI: 10.1098/rsob.240372

Lucy Diaz, Ewa Bielczyk-Maczynska

{"title":"High-density lipoprotein cholesterol: how studying the 'good cholesterol' could improve cardiovascular health.","authors":"Lucy Diaz, Ewa Bielczyk-Maczynska","doi":"10.1098/rsob.240372","DOIUrl":"10.1098/rsob.240372","url":null,"abstract":"High cholesterol levels are associated with an increased risk of cardiovascular disease, specifically atherosclerosis, a leading cause of death worldwide. Atherosclerosis occurs when cholesterol and fat build up in plaques along blood vessel walls, restricting blood flow and preventing nutrients and oxygen from diffusing in and out of the bloodstream. High-density lipoprotein cholesterol (HDL) particles prevent the build-up of such plaques, removing excess cholesterol from the peripheral tissues and delivering it to the liver, where it can be removed from the body. This pathway is known as reverse cholesterol transport (RCT). Because HDL plays a key role in preventing plaque buildup, understanding how this molecule and RCT function in the body could help us develop much-needed new atherosclerosis therapies and prevention strategies. However, HDL metabolism is complex, and research on HDL has been less favoured than research investigating a much better-understood molecule, low-density lipoprotein cholesterol, as a treatment target. More specifically, the receptors involved in the process of taking up HDL within the liver and their relationships to one another, along with the mechanism of whole, or holoparticle uptake of HDL remain to be clarified. In this review, we discuss several outstanding mysteries in HDL metabolism, consider why previous clinical trials to improve cardiovascular health by modulating HDL levels have been unsuccessful and argue that understanding HDL metabolism is essential for crafting interventions to reduce cardiovascular disease risk.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"15 2","pages":"240372"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449644","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 fundamental role of mitochondria-endoplasmic reticulum contacts in ageing and declining healthspan. 线粒体-内质网接触在衰老和健康寿命下降中的基本作用。

IF 4.5 3区生物学

Open Biology Pub Date : 2025-02-01 Epub Date: 2025-02-12 DOI: 10.1098/rsob.240287

Richard M Monaghan

{"title":"The fundamental role of mitochondria-endoplasmic reticulum contacts in ageing and declining healthspan.","authors":"Richard M Monaghan","doi":"10.1098/rsob.240287","DOIUrl":"10.1098/rsob.240287","url":null,"abstract":"This open question research article highlights mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), which have emerged as crucial cellular structures that challenge our traditional understanding of organelle function. This review highlights the critical importance of MAMs as a frontier in cell biology with far-reaching implications for health, disease and ageing. MAMs serve as dynamic communication hubs between the ER and mitochondria, orchestrating essential processes such as calcium signalling, lipid metabolism and cellular stress responses. Recent research has implicated MAM dysfunction in a wide array of conditions, including neurodegenerative diseases, metabolic disorders, cardiovascular diseases and cancer. The significant lack of biological knowledge behind MAM function emphasizes the need to study these enigmatic subcellular sites in greater detail. Key open questions include the mechanisms controlling MAM formation and disassembly, the full complement of MAM-associated proteins and how MAMs contribute to cellular decision-making and ageing processes. Advancing our understanding of MAMs through interdisciplinary approaches and cutting-edge technologies promises to reveal new insights into fundamental cellular signalling pathways and potentially lead to innovative therapeutic strategies for a range of diseases. As such, MAM research represents a critical open question in biology with the potential to transform our understanding of cellular life and human health.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"15 2","pages":"240287"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11813573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399641","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

Multifunctional roles of Sec13 paralogues in the euglenozoan Trypanosoma brucei. Sec13亲本在真核动物布鲁氏锥虫中的多功能作用。

IF 4.5 3区生物学

Open Biology Pub Date : 2025-02-01 Epub Date: 2025-02-26 DOI: 10.1098/rsob.240324

Mohamed Sharif, Lydia Greenberg, James Bangs

{"title":"Multifunctional roles of Sec13 paralogues in the euglenozoan Trypanosoma brucei.","authors":"Mohamed Sharif, Lydia Greenberg, James Bangs","doi":"10.1098/rsob.240324","DOIUrl":"10.1098/rsob.240324","url":null,"abstract":"Secretory cargos are exported from the ER via COPII-coated vesicles that have an inner matrix of Sec23/Sec24 heterotetramers and an outer cage of Sec13/Sec31 heterotetramers. In addition to COPII, Sec13 is part of the nuclear pore complex (NPC) and the regulatory SEA/GATOR complex in eukaryotes, which typically have one Sec13 orthologue. The kinetoplastid parasite Trypanosoma brucei has two paralogues: TbSec13.1, an accepted component of both COPII and the NPC, and TbSec13.2. Little is known about TbSec13.2, but others have proposed that it, and its orthologue in the distantly related diplonemid Paradiplonema papillatum, operate exclusively in the SEA/GATOR complex, and that this represents an evolutionary diversification of function unique to the euglenozoan protists. Using RNAi silencing in trypanosomes, we show both TbSec13s are essential. Knockdown of each dramatically and equally delays transport of GPI-anchored secretory cargo, indicating roles for both in COPII-mediated trafficking from the ER. Immunofluorescence and proximity labelling studies confirm that both TbSec13.1 and TbSec13.2 co-localize with TbSec24.1 to ER exit sites, and thus are functional components of the COPII machinery. Our findings indicate that TbSec13.2 function is not restricted to the SEA/GATOR complex in trypanosomes.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"15 2","pages":"240324"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11858755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502893","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

Proximal partners of the organellar N-terminal acetyltransferase NAA60: insights into Golgi structure and transmembrane protein topology. 细胞器n端乙酰转移酶NAA60的近端伙伴：对高尔基结构和跨膜蛋白拓扑结构的见解。

IF 4.5 3区生物学

Open Biology Pub Date : 2025-02-01 Epub Date: 2025-02-19 DOI: 10.1098/rsob.240225

Sebastian Tanco, Veronique Jonckheere, Arun Kumar Tharkeshwar, Annelies Bogaert, Kris Gevaert, Wim Annaert, Petra Van Damme

{"title":"Proximal partners of the organellar N-terminal acetyltransferase NAA60: insights into Golgi structure and transmembrane protein topology.","authors":"Sebastian Tanco, Veronique Jonckheere, Arun Kumar Tharkeshwar, Annelies Bogaert, Kris Gevaert, Wim Annaert, Petra Van Damme","doi":"10.1098/rsob.240225","DOIUrl":"10.1098/rsob.240225","url":null,"abstract":"Biotin identification (BioID) is an interactomics approach that utilizes proximity labelling to map the local interactome or proxeome of proteins within a cell. This study applies BioID to investigate proteins proximal to NAA60 (N-alpha-acetyltransferase 60), an N-terminal acetyltransferase (NAT) of pathological significance in human disease, characterized by its unique Golgi localization. NAA60 is known to N-terminally acetylate transmembrane proteins that present their N-terminus on the cytosolic face of the membrane, and its involvement in maintaining Golgi structure has previously been established. Using a stable cell-line expressing an NAA60-BirA* fusion protein, we isolated biotinylated proteins through streptavidin affinity purification. Mass spectrometry analysis revealed over 100 proximal partners of NAA60, enriched in proteins localized on the trans-side of the Golgi apparatus. High-confidence proximity interactors included golgins and GRASP proteins, essential for Golgi integrity. Considering the transmembrane nature of NAA60, the identification of biotinylated peptides inferred the topology of transmembrane protein interactors within the secretory pathway. Subsequent suborganellar localization analysis revealed a more prominent medial/trans-Golgi localization of NAA60. Our findings underscore the role of NAA60 and its interactors in maintaining Golgi structural integrity and highlight the effectiveness of BioID in generating critical protein topology data, invaluable for enhancing the prediction of protein topology within cellular compartments.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"15 2","pages":"240225"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449570","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

Microsporidian parasite impairs colony fitness in bumblebees. 微孢子虫寄生虫损害大黄蜂的群体适应性。

IF 4.5 3区生物学

Open Biology Pub Date : 2025-02-01 Epub Date: 2025-02-26 DOI: 10.1098/rsob.240304

Domenic W Camenzind, Selina Bruckner, Peter Neumann, Annette Van Oystaeyen, Verena Strobl, Geoffrey R Williams, Lars Straub

{"title":"Microsporidian parasite impairs colony fitness in bumblebees.","authors":"Domenic W Camenzind, Selina Bruckner, Peter Neumann, Annette Van Oystaeyen, Verena Strobl, Geoffrey R Williams, Lars Straub","doi":"10.1098/rsob.240304","DOIUrl":"10.1098/rsob.240304","url":null,"abstract":"Emerging infectious diseases can have a major impact on fitness of novel hosts, thereby contributing to ongoing species declines. In social insects, collaborative brood care by workers and successful mating of male sexuals are key to colony fitness. The microsporidian endoparasite Nosema ceranae has spread almost globally, shifting across honeybee species and now to bumblebees. However, despite N. ceranae being linked to recent population declines, its possible impact on bumblebee colony fitness remains poorly understood. Here, we show that N. ceranae infections can significantly impact Bombus terrestris worker feeding glands, as well as longevity, sperm quality and mating abilities of drones. In the laboratory, workers and drones were either exposed to the parasite or not. Then, parasite infection rates and loads, as well as lethal and sublethal parameters, were assessed. Infected drones revealed higher parasite infection rates and spore titres, as well as mortality compared with female workers, suggesting sex-specific susceptibility. Furthermore, infections impaired feeding glands, affected sperm traits and altered mating behaviour, all of which are key to colony fitness. Our findings provide a mechanistic explanation on how N. ceranae contributes to the ongoing decline of wild bumblebee populations, calling for respective mitigation measures.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"15 2","pages":"240304"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11858756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502599","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 human HELQ helicase and XRN2 exoribonuclease cooperate in R-loop resolution. 人类HELQ解旋酶和XRN2外核糖核酸酶协同进行r环的分解。

IF 4.5 3区生物学

Open Biology Pub Date : 2025-02-01 Epub Date: 2025-02-19 DOI: 10.1098/rsob.240112

J M Pan, H Betts, A Cubbon, L He, E L Bolt, P Soultanas

引用次数: 0

Exploring glycolytic enzymes in disease: potential biomarkers and therapeutic targets in neurodegeneration, cancer and parasitic infections. 探索糖酵解酶在疾病中的作用：神经变性、癌症和寄生虫感染的潜在生物标志物和治疗靶点。

IF 4.5 3区生物学

Open Biology Pub Date : 2025-02-01 Epub Date: 2025-02-05 DOI: 10.1098/rsob.240239

Maura Rojas-Pirela, Diego Andrade-Alviárez, Verónica Rojas, Miguel Marcos, Daniel Salete-Granado, Marirene Chacón-Arnaude, María Á Pérez-Nieto, Ulrike Kemmerling, Juan Luis Concepción, Paul A M Michels, Wilfredo Quiñones

{"title":"Exploring glycolytic enzymes in disease: potential biomarkers and therapeutic targets in neurodegeneration, cancer and parasitic infections.","authors":"Maura Rojas-Pirela, Diego Andrade-Alviárez, Verónica Rojas, Miguel Marcos, Daniel Salete-Granado, Marirene Chacón-Arnaude, María Á Pérez-Nieto, Ulrike Kemmerling, Juan Luis Concepción, Paul A M Michels, Wilfredo Quiñones","doi":"10.1098/rsob.240239","DOIUrl":"10.1098/rsob.240239","url":null,"abstract":"Glycolysis, present in most organisms, is evolutionarily one of the oldest metabolic pathways. It has great relevance at a physiological level because it is responsible for generating ATP in the cell through the conversion of glucose into pyruvate and reducing nicotinamide adenine dinucleotide (NADH) (that may be fed into the electron chain in the mitochondria to produce additional ATP by oxidative phosphorylation), as well as for producing intermediates that can serve as substrates for other metabolic processes. Glycolysis takes place through 10 consecutive chemical reactions, each of which is catalysed by a specific enzyme. Although energy transduction by glucose metabolism is the main function of this pathway, involvement in virulence, growth, pathogen-host interactions, immunomodulation and adaptation to environmental conditions are other functions attributed to this metabolic pathway. In humans, where glycolysis occurs mainly in the cytosol, the mislocalization of some glycolytic enzymes in various other subcellular locations, as well as alterations in their expression and regulation, has been associated with the development and progression of various diseases. In this review, we describe the role of glycolytic enzymes in the pathogenesis of diseases of clinical interest. In addition, the potential role of these enzymes as targets for drug development and their potential for use as diagnostic and prognostic markers of some pathologies are also discussed.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"15 2","pages":"240239"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11793985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189431","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

A high-throughput protein tagging toolkit that retains endogenous untranslated regions for studying gene regulation in kinetoplastids. 一个高通量蛋白质标记工具，保留内源性非翻译区域，用于研究着丝质体中的基因调控。

IF 4.5 3区生物学

Open Biology Pub Date : 2025-02-01 Epub Date: 2025-02-26 DOI: 10.1098/rsob.240334

Carla Gilabert Carbajo, Xiaoyang Han, Bhairavi Savur, Arushi Upadhyaya, Fatima Taha, Michele Tinti, Richard J Wheeler, Phillip A Yates, Calvin Tiengwe

{"title":"A high-throughput protein tagging toolkit that retains endogenous untranslated regions for studying gene regulation in kinetoplastids.","authors":"Carla Gilabert Carbajo, Xiaoyang Han, Bhairavi Savur, Arushi Upadhyaya, Fatima Taha, Michele Tinti, Richard J Wheeler, Phillip A Yates, Calvin Tiengwe","doi":"10.1098/rsob.240334","DOIUrl":"10.1098/rsob.240334","url":null,"abstract":"Kinetoplastid parasites cause diseases that threaten human and animal health. To survive transitions between vertebrate hosts and insect vectors, these parasites rely on precise regulation of gene expression to adapt to environmental changes. Since gene regulation in kinetoplastids is primarily post-transcriptional, developing efficient genetic tools for modifying genes at their endogenous loci while preserving regulatory mRNA elements is crucial for studying their complex biology. We present a CRISPR/Cas9-based tagging system that preserves untranslated regulatory elements and uses a viral 2A peptide from Thosea asigna to generate two separate proteins from a single transcript: a drug-selectable marker and a tagged protein of interest. This dual-function design maintains native control elements, allowing discrimination between regulation of transcript abundance, translational efficiency, and post-translational events. We validate the system by tagging six Trypanosoma brucei proteins and demonstrate (i) high-efficiency positive selection and separation of drug-selectable marker and target protein, (ii) preservation of regulatory responses to environmental cues like heat shock and iron availability, and (iii) maintenance of stage-specific regulation during developmental transitions. This versatile toolkit is applicable to all kinetoplastids amenable to CRISPR/Cas9 editing, providing a powerful reverse genetic tool for studying post-transcriptional regulation and protein function in organisms where post-transcriptional control is dominant.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"15 2","pages":"240334"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11858757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502564","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

Simple recombinant monoclonal antibody production from Escherichia coli. 从大肠杆菌中制备简单重组单克隆抗体。

IF 4.5 3区生物学

Open Biology Pub Date : 2025-02-01 Epub Date: 2025-02-19 DOI: 10.1098/rsob.240229

Karen Baker, Tara A Eastwood, Esther Garcia, Chris Lennon, Daniel P Mulvihill

引用次数: 0

AGS3-based optogenetic GDI induces GPCR-independent Gβγ signalling and macrophage migration. 基于ags3的光遗传GDI诱导gpcr非依赖性Gβγ信号传导和巨噬细胞迁移。

IF 4.5 3区生物学

Open Biology Pub Date : 2025-02-01 Epub Date: 2025-02-05 DOI: 10.1098/rsob.240181

Waruna Thotamune, Sithurandi Ubeysinghe, Chathuri Rajarathna, Dinesh Kankanamge, Koshala Olupothage, Aditya Chandu, Bryan A Copits, Ajith Karunarathne

{"title":"AGS3-based optogenetic GDI induces GPCR-independent Gβγ signalling and macrophage migration.","authors":"Waruna Thotamune, Sithurandi Ubeysinghe, Chathuri Rajarathna, Dinesh Kankanamge, Koshala Olupothage, Aditya Chandu, Bryan A Copits, Ajith Karunarathne","doi":"10.1098/rsob.240181","DOIUrl":"10.1098/rsob.240181","url":null,"abstract":"G-protein-coupled receptors (GPCRs) are efficient guanine nucleotide exchange factors (GEFs) and exchange GDP to GTP on the Gα subunit of G-protein heterotrimers in response to various extracellular stimuli, including neurotransmitters and light. GPCRs primarily broadcast signals through activated G proteins, GαGTP and free Gβγ and are major disease drivers. Evidence shows that the ambient low threshold signalling required for cells is likely supplemented by signalling regulators such as non-GPCR GEFs and guanine nucleotide dissociation inhibitors (GDIs). Activators of G-protein signalling 3 (AGS3) are recognized as a GDI involved in multiple health and disease-related processes. Nevertheless, understanding of AGS3 is limited, and no significant information is available on its structure-function relationship or signalling regulation in living cells. Here, we employed in silico structure-guided engineering of a novel optogenetic GDI, based on the AGS3's G-protein regulatory motif, to understand its GDI activity and induce standalone Gβγ signalling in living cells on optical command. Our results demonstrate that plasma membrane recruitment of OptoGDI efficiently releases Gβγ, and its subcellular targeting generated localized PIP3 and triggered macrophage migration. Therefore, we propose OptoGDI as a powerful tool for optically dissecting GDI-mediated signalling pathways and triggering GPCR-independent Gβγ signalling in cells and in vivo.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"15 2","pages":"240181"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11793977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189038","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