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Oxidative Stress and DNA Damage at Telomeres.
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-02-10 DOI: 10.1101/cshperspect.a041707
Patricia L Opresko, Samantha L Sanford, Mariarosaria De Rosa
{"title":"Oxidative Stress and DNA Damage at Telomeres.","authors":"Patricia L Opresko, Samantha L Sanford, Mariarosaria De Rosa","doi":"10.1101/cshperspect.a041707","DOIUrl":"10.1101/cshperspect.a041707","url":null,"abstract":"<p><p>Oxidative stress is associated with increasing telomere shortening and telomere dysfunction, as well as with numerous pathologies in humans, including inflammatory diseases and cancer. Critically short and dysfunctional telomeres lose their ability to protect chromosome ends, which triggers irreversible growth arrest, termed senescence, or genomic instability. Telomeres are highly sensitive to damage from reactive oxygen species, which increase under conditions of oxidative stress. This work covers the evidence that oxidative damage to telomeric DNA alters telomere maintenance by various mechanisms and describes the DNA repair pathways important for preserving telomere function under oxidative stress conditions.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390447","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}
引用次数: 0
Modeling the Emergence of Circuit Organization and Function during Development. 模拟发育过程中电路组织和功能的出现
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-02-03 DOI: 10.1101/cshperspect.a041511
Shreya Lakhera, Elizabeth Herbert, Julijana Gjorgjieva
{"title":"Modeling the Emergence of Circuit Organization and Function during Development.","authors":"Shreya Lakhera, Elizabeth Herbert, Julijana Gjorgjieva","doi":"10.1101/cshperspect.a041511","DOIUrl":"10.1101/cshperspect.a041511","url":null,"abstract":"<p><p>Developing neural circuits show unique patterns of spontaneous activity and structured network connectivity shaped by diverse activity-dependent plasticity mechanisms. Based on extensive experimental work characterizing patterns of spontaneous activity in different brain regions over development, theoretical and computational models have played an important role in delineating the generation and function of individual features of spontaneous activity and their role in the plasticity-driven formation of circuit connectivity. Here, we review recent modeling efforts that explore how the developing cortex and hippocampus generate spontaneous activity, focusing on specific connectivity profiles and the gradual strengthening of inhibition as the key drivers behind the observed developmental changes in spontaneous activity. We then discuss computational models that mechanistically explore how different plasticity mechanisms use this spontaneous activity to instruct the formation and refinement of circuit connectivity, from the formation of single neuron receptive fields to sensory feature maps and recurrent architectures. We end by highlighting several open challenges regarding the functional implications of the discussed circuit changes, wherein models could provide the missing step linking immature developmental and mature adult information processing capabilities.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 Role of Microhomology-Mediated End Joining (MMEJ) at Dysfunctional Telomeres. 微同源物介导的端接（MMEJ）在功能障碍端粒中的作用
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-02-03 DOI: 10.1101/cshperspect.a041687
David Billing, Agnel Sfeir
{"title":"The Role of Microhomology-Mediated End Joining (MMEJ) at Dysfunctional Telomeres.","authors":"David Billing, Agnel Sfeir","doi":"10.1101/cshperspect.a041687","DOIUrl":"10.1101/cshperspect.a041687","url":null,"abstract":"<p><p>DNA double-strand break (DSB) repair pathways are crucial for maintaining genome stability and cell viability. However, these pathways can mistakenly recognize chromosome ends as DNA breaks, leading to adverse outcomes such as telomere fusions and malignant transformation. The shelterin complex protects telomeres from activation of DNA repair pathways by inhibiting nonhomologous end joining (NHEJ), homologous recombination (HR), and microhomology-mediated end joining (MMEJ). The focus of this paper is on MMEJ, an error-prone DSB repair pathway characterized by short insertions and deletions flanked by sequence homology. MMEJ is critical in mediating telomere fusions in cells lacking the shelterin complex and at critically short telomeres. Furthermore, studies suggest that MMEJ is the preferred pathway for repairing intratelomeric DSBs and facilitates escape from telomere crisis. Targeting MMEJ to prevent telomere fusions in hematologic malignancies is of potential therapeutic value.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Glia at Transition Zones. 过渡区的胶质细胞
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-02-03 DOI: 10.1101/cshperspect.a041369
Sarah Kucenas, Pernelle Pulh, Piotr Topilko, Cody J Smith
{"title":"Glia at Transition Zones.","authors":"Sarah Kucenas, Pernelle Pulh, Piotr Topilko, Cody J Smith","doi":"10.1101/cshperspect.a041369","DOIUrl":"10.1101/cshperspect.a041369","url":null,"abstract":"<p><p>Neural cells are segregated into their distinct central nervous system (CNS) and peripheral nervous system (PNS) domains. However, at specialized regions of the nervous system known as transition zones (TZs), glial cells from both the CNS and PNS are uniquely present with other specialized TZ cells. Herein we review the current understanding of vertebrate TZ cells. The article discusses the distinct cells at vertebrate TZs with a focus on cells that are located on the peripheral side of the spinal cord TZs. In addition to the developmental origin and differentiation of these TZ cells, the functional importance and the role of TZ cells in disease are highlighted. This article also reviews the common and unique features of vertebrate TZs from zebrafish to mice. We propose challenges and open questions in the field that could lead to exciting insights in the field of glial biology.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 Roles of Transient Receptor Potential (TRP) Channels Underlying Aberrant Calcium Signaling in Blood-Retinal Barrier Dysfunction. 瞬态受体电位（TRP）通道在血-视网膜屏障功能障碍中的作用--钙信号传递异常的基础
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-02-03 DOI: 10.1101/cshperspect.a041763
Silvia Dragoni, Francesco Moccia, Martin D Bootman
{"title":"The Roles of Transient Receptor Potential (TRP) Channels Underlying Aberrant Calcium Signaling in Blood-Retinal Barrier Dysfunction.","authors":"Silvia Dragoni, Francesco Moccia, Martin D Bootman","doi":"10.1101/cshperspect.a041763","DOIUrl":"10.1101/cshperspect.a041763","url":null,"abstract":"<p><p>The inner blood-retinal barrier (iBRB) protects the retinal vasculature from the peripheral circulation. Endothelial cells (ECs) are the core component of the iBRB; their close apposition and linkage via tight junctions limit the passage of fluids, proteins, and cells from the bloodstream to the parenchyma. Dysfunction of the iBRB is a hallmark of many retinal disorders. Vascular endothelial growth factor (VEGF) has been identified as the primary driver leading to a dysfunctional iBRB, thereby becoming the main target for therapy. However, a complete understanding of the molecular mechanisms underlying iBRB dysfunction is elusive and alternative therapeutic targets remain unexplored. Calcium (Ca<sup>2+</sup>) is a universal intracellular messenger whose homeostasis and dynamics are dysregulated in many pathological disorders. Among the extensive components of the cellular Ca<sup>2+</sup>-signaling toolkit, cation-selective transient receptor potential (TRP) channels are broadly involved in cell physiology and disease and, therefore, are widely studied as possible targets for therapy. Albeit that TRP channels have been discovered in the photoreceptors of <i>Drosophila</i> and have been studied in the neuroretina, their presence and function in the iBRB have only recently emerged. Within this article, we discuss the structure and functions of the iBRB with a particular focus on Ca<sup>2+</sup> signaling in retinal ECs and highlight the potential of TRP channels as new targets for retinal diseases.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Developmental Control of Cell Cycle and Signaling. 细胞周期和信号的发育控制。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-02-03 DOI: 10.1101/cshperspect.a041499
Stefano Di Talia
{"title":"Developmental Control of Cell Cycle and Signaling.","authors":"Stefano Di Talia","doi":"10.1101/cshperspect.a041499","DOIUrl":"10.1101/cshperspect.a041499","url":null,"abstract":"<p><p>In most species, the earliest stages of embryogenesis are characterized by rapid proliferation, which must be tightly controlled with other cellular processes across the large scale of the embryo. The study of this coordination has recently revealed new mechanisms of regulation of morphogenesis. Here, I discuss progress on how the integration of biochemical and mechanical signals leads to the proper positioning of cellular components, how signaling waves ensure the synchronization of the cell cycle, and how cell cycle transitions are properly timed. Similar concepts are emerging in the control of morphogenesis of other tissues, highlighting both common and unique features of early embryogenesis.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Mechanisms of Alternative Lengthening of Telomeres. 端粒替代性延长的机制
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-01-07 DOI: 10.1101/cshperspect.a041690
Roderick J O'Sullivan, Roger A Greenberg
{"title":"Mechanisms of Alternative Lengthening of Telomeres.","authors":"Roderick J O'Sullivan, Roger A Greenberg","doi":"10.1101/cshperspect.a041690","DOIUrl":"10.1101/cshperspect.a041690","url":null,"abstract":"<p><p>In recent years, significant advances have been made in understanding the intricate details of the mechanisms underlying alternative lengthening of telomeres (ALT). Studies of a specialized DNA strand break repair mechanism, known as break-induced replication, and the advent of telomere-specific DNA damaging strategies and proteomic methodologies to profile the ribonucleoprotein composition of telomeres enabled the discovery of networks of proteins that coordinate the stepwise homology-directed DNA repair and DNA synthesis processes of ALT. These networks couple mediators of homologous recombination, DNA template-switching, long-range template-directed DNA synthesis, and DNA strand resolution with SUMO-dependent liquid condensate formation to create discrete nuclear bodies where telomere extension occurs. This review will discuss the recent findings of how these networks may cooperate to mediate telomere extension by the ALT mechanism and their impact on telomere function and integrity in ALT cancer cells.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Calculating Relatedness: A Pedigree of Definitions. 计算亲缘关系：定义谱系
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-01-07 DOI: 10.1101/cshperspect.a041667
Matishalin Patel, J Arvid Ågren
{"title":"Calculating Relatedness: A Pedigree of Definitions.","authors":"Matishalin Patel, J Arvid Ågren","doi":"10.1101/cshperspect.a041667","DOIUrl":"10.1101/cshperspect.a041667","url":null,"abstract":"<p><p>Biology can be viewed from both an organismal and a genic perspective. A good example is W.D. Hamilton's work on inclusive fitness and kin selection, which puts relatedness at the heart of our understanding of social behavior. Relatedness mediates how much an actor should value a specific behavior's effect on a relative compared to the cost incurred to itself. Despite its key explanatory role, relatedness is also a concept marred with misunderstanding. Part of the problem has been that the term has been used in different ways by different people. To help address this, we survey the history of how relatedness has been formally modeled, paying particular attention to how it is conceptualized from both a gene-centric and an organism-centric point of view.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Satellite Glial Cells: No Longer the Most Overlooked Glia. 卫星胶质细胞：卫星胶质细胞：不再是最被忽视的胶质细胞
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-01-07 DOI: 10.1101/cshperspect.a041367
Susan J Birren, Lisa V Goodrich, Rosalind A Segal
{"title":"Satellite Glial Cells: No Longer the Most Overlooked Glia.","authors":"Susan J Birren, Lisa V Goodrich, Rosalind A Segal","doi":"10.1101/cshperspect.a041367","DOIUrl":"10.1101/cshperspect.a041367","url":null,"abstract":"<p><p>Many glial biologists consider glia the neglected cells of the nervous system. Among all the glia of the central and peripheral nervous system, satellite glia may be the most often overlooked. Satellite glial cells (SGCs) are located in ganglia of the cranial nerves and the peripheral nervous system. These small cells surround the cell bodies of neurons in the trigeminal ganglia (TG), spiral ganglia, nodose and petrosal ganglia, sympathetic ganglia, and dorsal root ganglia (DRG). Essential SGC features include their intimate connections with the associated neurons, their small size, and their derivation from neural crest cells. Yet SGCs also exhibit tissue-specific properties and can change rapidly, particularly in response to injury. To illustrate the range of SGC functions, we will focus on three types: those of the spiral, sympathetic, and DRG, and consider both their shared features and those that differ based on location.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Understanding the Influence of Host Radiation on Symbiont Speciation through Parasites of Species Flocks. 通过种群寄生虫了解宿主辐射对共生体物种变异的影响
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-01-07 DOI: 10.1101/cshperspect.a041450
Maarten P M Vanhove, Nikol Kmentová, Christel Faes, Jorge M O Fernandes, Christoph Hahn, Niel Hens, Antoine Pariselle, Stephan Koblmüller
{"title":"Understanding the Influence of Host Radiation on Symbiont Speciation through Parasites of Species Flocks.","authors":"Maarten P M Vanhove, Nikol Kmentová, Christel Faes, Jorge M O Fernandes, Christoph Hahn, Niel Hens, Antoine Pariselle, Stephan Koblmüller","doi":"10.1101/cshperspect.a041450","DOIUrl":"10.1101/cshperspect.a041450","url":null,"abstract":"<p><p>(Adaptive) radiations have attracted evolutionary biologists for a long time as ideal model systems to study patterns and processes of often rapid speciation. However, whereas a wealth of (sometimes already genome-scale) data is available for host radiations, very few studies target the patterns of diversification in their symbionts, even though they would be excellent models to study symbiont speciation. Our review summarizes what little is known about general patterns of symbiont diversification in often iconic adaptive host radiations and to what extent these patterns are dependent on the evolutionary trajectories of their hosts. We identify research gaps that need to be addressed in the future and discuss the potential of approaches not yet typically used in these study systems, such as epidemiological disease modeling and new omics technologies, for significantly advancing our understanding of these complex eco-evolutionary relationships.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
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