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Cancer Progression and the Calcium Signaling Toolkit: Expanding Dimensions and Perspectives. 癌症进展和钙信号工具箱：扩展的维度和观点。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-06-16 DOI: 10.1101/cshperspect.a041767
Mélanie Robitaille, Gregory R Monteith
{"title":"Cancer Progression and the Calcium Signaling Toolkit: Expanding Dimensions and Perspectives.","authors":"Mélanie Robitaille, Gregory R Monteith","doi":"10.1101/cshperspect.a041767","DOIUrl":"https://doi.org/10.1101/cshperspect.a041767","url":null,"abstract":"<p><p>Calcium signaling is a key controller of numerous cellular events and is intricately linked to many processes that are critical pathways in cancer progression. This review revisits the calcium signaling toolkit in cancer, with a focus on calcium regulation of processes that go beyond the originally defined \"classic\" hallmarks of cancer such as those associated with proliferation, metastasis, and resistance to cell death pathways. We will consider calcium signaling in the context of the more recently proposed hallmarks of cancer, emerging hallmarks, and cancer-enabling characteristics. This broader examination of calcium signaling and its toolkit members will encompass processes such as metabolic reprogramming, evasion of immune destruction, cellular phenotypic plasticity, senescence, genome instability, and nonmutational epigenetic reprogramming. These cancer features and their interactions with calcium signaling will frequently be analyzed through the lenses of therapy resistance and the complexities of the tumor microenvironment.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309660","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
Mendel's Pea Genes. 孟德尔的豌豆基因。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-06-09 DOI: 10.1101/cshperspect.a041872
Julie M I Hofer, Noel Ellis
{"title":"Mendel's Pea Genes.","authors":"Julie M I Hofer, Noel Ellis","doi":"10.1101/cshperspect.a041872","DOIUrl":"https://doi.org/10.1101/cshperspect.a041872","url":null,"abstract":"<p><p>Mendel conducted his studies on the transmission of genetic elements from one generation to the next using pea varieties commercially available at that time. He presented segregation data for seven character differences in detail. The molecular basis of five of these character differences is known, round versus wrinkled seeds, yellow versus green cotyledons, green versus yellow pods, colored versus uncolored seed coats, and tall versus short stems. Wrinkled peas available in Mendel's time resulted from a transposon insertion in the gene encoding starch-branching enzyme I. Allelic variants in the gene encoding magnesium dechelatase are known to condition pea seeds with green cotyledons, while yellow pods are conditioned by a deletion variant that disrupts chlorophyll synthase gene function. Cultivars with unpigmented seed coats and white flowers are explained by a splicing defect in a gene encoding a basic helix-loop-helix transcription factor. Short cultivars used by Mendel were deficient in bioactive forms of the phytohormone gibberellin because they carried a missense allele of a gene encoding gibberellin 3-oxidase. The allelic diversity of the pea genes Mendel studied and the genetic heterogeneity of corresponding traits are discussed below. The identification of two of Mendel's genes remains to be formally confirmed.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257510","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
Mechanochemical Principles of Epidermal Tissue Dynamics. 表皮组织动力学的机械化学原理
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-06-02 DOI: 10.1101/cshperspect.a041518
Carien M Niessen, M Lisa Manning, Sara A Wickström
{"title":"Mechanochemical Principles of Epidermal Tissue Dynamics.","authors":"Carien M Niessen, M Lisa Manning, Sara A Wickström","doi":"10.1101/cshperspect.a041518","DOIUrl":"10.1101/cshperspect.a041518","url":null,"abstract":"<p><p>How tissue architecture and function emerge during development and what facilitates their resilience and homeostatic dynamics during adulthood is a fundamental question in biology. Biological tissue barriers such as the skin epidermis have evolved strategies that integrate dynamic cellular turnover with high resilience against mechanical and chemical stresses. Interestingly, both dynamic and resilient functions are generated by a defined set of molecular and cell-scale processes, including adhesion and cytoskeletal remodeling, cell shape changes, cell division, and cell movement. These traits are coordinated in space and time with dynamic changes in cell fates and cell mechanics that are generated by contractile and adhesive forces. In this review, we discuss how studies on epidermal morphogenesis and homeostasis have contributed to our understanding of the dynamic interplay between biochemical and mechanical signals during tissue morphogenesis and homeostasis, and how the material properties of tissues dictate how cells respond to these active stresses, thereby linking cell-scale behaviors to tissue- and organismal-scale changes.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300242","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
Oxidative Stress and DNA Damage at Telomeres. 氧化应激和端粒DNA损伤。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-06-02 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":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128872/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Teaching School Genetics in the 2020s: Why "Naive" Mendelian Genetics Has to Go. 2020 年代的学校遗传学教学：为什么 "天真 "的孟德尔遗传学必须退出历史舞台？
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-06-02 DOI: 10.1101/cshperspect.a041679
Kostas Kampourakis
{"title":"Teaching School Genetics in the 2020s: Why \"Naive\" Mendelian Genetics Has to Go.","authors":"Kostas Kampourakis","doi":"10.1101/cshperspect.a041679","DOIUrl":"10.1101/cshperspect.a041679","url":null,"abstract":"<p><p>Whereas Mendelian genetics is an important research program in the life sciences, its school version is problematic. On the one hand, it contains stereotypical representations of Gregor Mendel's work that misrepresent his findings and the historical context. This deprives students from gaining an authentic picture of how science is done. On the other hand, what most students end up learning in schools are extremely simplistic accounts of heredity, whereby alleles directly control traits and phenotypes, and thus exclusively depend on which allele an individual has. Such oversimplifications of Mendelian genetics as those that we still teach in schools were exploited by ideologues in the beginning of the twentieth century to provide the presumed \"scientific\" basis for eugenics. This paper addresses these problems of the school version of Mendelian genetics, which I call \"naive\" Mendelian genetics. It also proposes a shift in school education from teaching how the science of genetics is done using model systems to teaching the complexities of development through which heredity is materialized.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582605","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
Modeling Normal and Abnormal Circuit Development with Recurrent Neural Networks. 用递归神经网络模拟正常和异常电路发展
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-06-02 DOI: 10.1101/cshperspect.a041507
Daniel Zavitz, ShiNung Ching, Geoffrey Goodhill
{"title":"Modeling Normal and Abnormal Circuit Development with Recurrent Neural Networks.","authors":"Daniel Zavitz, ShiNung Ching, Geoffrey Goodhill","doi":"10.1101/cshperspect.a041507","DOIUrl":"10.1101/cshperspect.a041507","url":null,"abstract":"<p><p>Neural development must construct neural circuits that can perform the computations necessary for survival. However, many theoretical models of development do not explicitly address the computational goals of the resulting networks, or computations that evolve in time. Recurrent neural networks (RNNs) have recently come to prominence as both models of neural circuit computation and building blocks of powerful artificial intelligence systems. Here, we review progress in using RNNs for understanding how developmental processes lead to effective computations, and how abnormal development disrupts these computations.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619507","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
Regulation of Human Telomerase: from Molecular Interactions to Population Genetics. 人类端粒酶的调控：从分子相互作用到群体遗传学。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-05-19 DOI: 10.1101/cshperspect.a041693
Annika Martin, Dirk Hockemeyer
{"title":"Regulation of Human Telomerase: from Molecular Interactions to Population Genetics.","authors":"Annika Martin, Dirk Hockemeyer","doi":"10.1101/cshperspect.a041693","DOIUrl":"https://doi.org/10.1101/cshperspect.a041693","url":null,"abstract":"<p><p>Human telomeres play critical roles in protecting chromosome ends and preserving genomic integrity. Telomerase, essential for maintaining telomere length and cellular replicative capacity, is only expressed in a small subset of human cells: stem and progenitor populations. Conversely, most somatic cells' telomeres shorten with each cell division; this shortening provides a potent tumor suppressor mechanism. Thus, telomerase regulation shapes not only cellular life span and differentiation, but also the regenerative capacity and long-term integrity of tissues. Here, we review the current understanding of telomere length control and telomerase regulation in humans, from molecular interactions at chromosome ends to the tissue-specific variation of telomere length dynamics, drawing insight from pluripotent and adult stem cell populations, as well as telomerase dysregulation in cancer and telomere biology disorders.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101472","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
How Shelterin Orchestrates the Replication and Protection of Telomeres. 庇护蛋白如何协调端粒的复制和保护。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-05-19 DOI: 10.1101/cshperspect.a041685
Titia de Lange
{"title":"How Shelterin Orchestrates the Replication and Protection of Telomeres.","authors":"Titia de Lange","doi":"10.1101/cshperspect.a041685","DOIUrl":"https://doi.org/10.1101/cshperspect.a041685","url":null,"abstract":"<p><p>Efforts to determine how telomeres solve the end-protection problem led to the discovery of shelterin, a conserved six-subunit protein complex that specifically binds to the long arrays of telomeric TTAGGG repeats at vertebrate chromosome ends. The mechanisms by which shelterin prevents telomeres from being detected as sites of DNA damage and how shelterin prevents inappropriate DNA repair pathways are now largely known. More recently, shelterin has emerged as a central player in solving the second major problem at telomeres: how to complete the duplication of telomeric DNA. This end-replication problem results from the inability of the canonical DNA replication machinery to maintain the DNA at chromosome ends. Shelterin solves this problem by recruiting two enzymes that can replenish the lost telomeric repeats: telomerase and CST-Polα/primase. How shelterin accomplishes these critical tasks is reviewed here.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101515","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
Modern Modeling of Single-Cell Migration: From Membrane Tension and Galvanotaxis to Machine Learning. 单细胞迁移的现代建模：从膜张力和流原性到机器学习。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-05-19 DOI: 10.1101/cshperspect.a041745
Wenzheng Shi, Alex Mogilner
{"title":"Modern Modeling of Single-Cell Migration: From Membrane Tension and Galvanotaxis to Machine Learning.","authors":"Wenzheng Shi, Alex Mogilner","doi":"10.1101/cshperspect.a041745","DOIUrl":"https://doi.org/10.1101/cshperspect.a041745","url":null,"abstract":"<p><p>Cell migration phenomenon has inspired and benefited from computational modeling for decades. Here, we review recent applications of traditional bottom-up modeling to three aspects of cell migration: the role of membrane tension (MT) in organizing directional cell motility, the role of the electric field (EF) as the directional cue for migration, and the mechanics of three-dimensional migration. We then discuss nascent applications of machine learning (ML) to cell migration and galvanotaxis. We focus on the migratory mechanisms of the single cell and highlight the feedback between theory and experiment.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101143","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
Hidden Treasures of the Genetic Systems in Yeast Mitochondria. 酵母线粒体遗传系统的隐藏宝藏。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-05-19 DOI: 10.1101/cshperspect.a041849
Jozef Nosek, Ľubomír Tomáška
{"title":"Hidden Treasures of the Genetic Systems in Yeast Mitochondria.","authors":"Jozef Nosek, Ľubomír Tomáška","doi":"10.1101/cshperspect.a041849","DOIUrl":"https://doi.org/10.1101/cshperspect.a041849","url":null,"abstract":"<p><p>Mitochondria are the masters of evolutionary tinkering, which can be exemplified by both the remarkable variability of the mitochondrial genome architectures and numerous noncanonical features involved in the mitochondrial gene expression. Evolutionary experimentation in these living test tubes is facilitated by their polyploid nature and resulted in a number of surprising oddities identified in various eukaryotic lineages. Excellent examples of these peculiarities are provided by mitochondrial genetic systems of unicellular fungi classified as the budding yeasts. Perhaps the most perplexing eccentricity found in yeast mitochondria are the bypassing elements (byps) residing in the reading frames of protein-coding genes. Ribosomes ignore byps during translation by means of programmed translational bypassing. Massive occurrence of these coding gaps in certain yeast species raises the questions on their evolutionary origin and mobility as well as the molecular mechanism of translational bypassing.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101512","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
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