BioEssaysPub Date : 2026-03-31DOI: 10.1002/bies.70131
Armando Aranda-Anzaldo, Myrna A. R. Dent, Alejandro Martínez-Gómez, Edith Segura-Anaya
{"title":"The Cellular Stress Responses and the Resolution of Peto's Paradox","authors":"Armando Aranda-Anzaldo, Myrna A. R. Dent, Alejandro Martínez-Gómez, Edith Segura-Anaya","doi":"10.1002/bies.70131","DOIUrl":"10.1002/bies.70131","url":null,"abstract":"<div>\u0000 \u0000 <p>Peto's paradox (Pp) results from the evidence that in mammals there is no obvious positive correlation between body size, lifespan, and cancer incidence. Posing the question of which mechanisms are responsible for this. Comparative studies searching for specific anticancer mechanisms as putative solutions to Pp have been undertaken in mammals. The result of these efforts are further inconsistencies leading to ad-hoc hypotheses and unnecessary complexity. In contrast to this, we present evidence that the cellular stress responses (CSRs), aimed at curtailing proteotoxic stress and assuring cell survival are necessary for enabling carcinogenesis. Yet, natural selection adjusts the performance of the CSRs according to the life history of each species and because of this, cancer is mostly delayed to the post-reproductive stage in all mammalian species, resulting in a limited impact of cancer on species fitness and viability. From this perspective, the need of evolving anticancer mechanisms, suggested by Pp is weakened or disappears and the paradox is likely resolved.</p>\u0000 </div>","PeriodicalId":9264,"journal":{"name":"BioEssays","volume":"48 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580543","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}
BioEssaysPub Date : 2026-03-31DOI: 10.1002/bies.70133
Gregory K. Hodgson, Stefania Impellizzeri
{"title":"Metal-Enhanced Fluorescence for the Biologist's Cellular Imaging Toolkit: Design Principles and Recent Applications","authors":"Gregory K. Hodgson, Stefania Impellizzeri","doi":"10.1002/bies.70133","DOIUrl":"10.1002/bies.70133","url":null,"abstract":"<p>Fluorescence microscopy is essential in modern cell biology but remains constrained by photobleaching, autofluorescence, and the intrinsic quantum yields of emitters. Metal-enhanced fluorescence (MEF) is a photophysical phenomenon in which interactions between luminescent species and metal nanostructures markedly increase emission, enabling a route to brighter, high-contrast, noninvasive bioimaging by reshaping photophysical pathways without modifying fluorophore chemistry. This review translates MEF fundamentals into an experimental playbook for biologists, distinguishing MEF mechanisms and explaining how distance, spectral overlap, and nanoparticle morphology govern whether emission is boosted or quenched. We synthesize recent live-cell applications—using gold and silver nanoparticles—to illustrate gains in signal-to-noise at lower excitation power, improved photostability, and opportunities where small-molecule dyes often suffer low quantum yield, and provide practical guidelines for pairing dyes with metal nanostructures to lower the barrier to adopting MEF in cellular imaging.</p>","PeriodicalId":9264,"journal":{"name":"BioEssays","volume":"48 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13037458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580531","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}
BioEssaysPub Date : 2026-03-25DOI: 10.1002/bies.70132
{"title":"BioEssays 3/2026","authors":"","doi":"10.1002/bies.70132","DOIUrl":"https://doi.org/10.1002/bies.70132","url":null,"abstract":"<p>The cover image is based on the article Vimentin Intermediate Filaments: A Paradigm Shift From Static Structure to Dynamic Cytoplasmic Network by Bhuvanasundar Renganathan et al., 70125.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":9264,"journal":{"name":"BioEssays","volume":"48 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bies.70132","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147579805","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}
BioEssaysPub Date : 2026-03-25DOI: 10.1002/bies.70129
Yuzhen Li, Richard D. Wood
{"title":"Beyond Short Microhomologies: Mismatch-Compatible Pol θ-Mediated DNA Damage Repair","authors":"Yuzhen Li, Richard D. Wood","doi":"10.1002/bies.70129","DOIUrl":"10.1002/bies.70129","url":null,"abstract":"<p>DNA polymerase θ (Pol θ)-mediated end-joining (TMEJ), one of several pathways for repairing DNA double-strand breaks, is traditionally thought to initiate via anchoring at short, consecutive, and perfectly matched microhomologies (MHs). Emerging evidence indicates that Pol θ can utilize MHs containing mismatches both in vitro and in vivo. This revised definition of MH provides a mechanistic explanation for a broader spectrum of Pol θ-dependent repair outcomes. Here, we summarize recent findings on the revised definition of MHs utilized by Pol θ, assess the applicability of this concept across species, and compare TMEJ with other (micro)hom(e)ology-mediated repair pathways. We explore how mismatch-containing MHs expand Pol θ-associated mutational signatures and provide a framework for future studies on Pol θ’s role in DNA repair and cancer biology.</p>","PeriodicalId":9264,"journal":{"name":"BioEssays","volume":"48 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13015775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509312","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}
BioEssaysPub Date : 2026-03-25DOI: 10.1002/bies.70123
Alexios-Fotios A. Mentis, Athanasios Kossyvakis, Dimitrios Chatzidimitriou
{"title":"Host Genetic Regulation of Stem Cell–Virus Interactions in Human Health","authors":"Alexios-Fotios A. Mentis, Athanasios Kossyvakis, Dimitrios Chatzidimitriou","doi":"10.1002/bies.70123","DOIUrl":"10.1002/bies.70123","url":null,"abstract":"<div>\u0000 \u0000 <p>The interactions between human viruses and human stem cells may differ from those with differentiated cells. These differences may arise through heterogeneous intercellular mechanisms and responses to specific infectious agents, resulting in different phenotypes that affect human pathophysiology. Understanding and exploiting such differences could have clinical and translational potential. Here, we discuss the various mechanistic interactions between stem cells and viruses related to entry mechanisms, replication dynamics, and immunomodulation. In doing so, we critically assess proposed models and hypotheses about how viruses manipulate stem cell biology, while also providing new paradigms for stem cell biology and therapeutic interventions. We highlight recent discoveries on the dual role of viruses in oncogenesis and oncolysis. In parallel, we explore similarities between stem cells and complex viruses—such as giant viruses and jumbo phages—to propose novel perspectives on viral adaptability and pathogenesis. We examine both established mechanisms and emerging viral phenomena to encourage further research and debate on the clinical implications of viral interactions with stem cells.</p>\u0000 </div>","PeriodicalId":9264,"journal":{"name":"BioEssays","volume":"48 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509568","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}
BioEssaysPub Date : 2026-03-25DOI: 10.1002/bies.70126
Bassant Eldaly, Brian M. Baker
{"title":"Dynamic Allostery in T Cell Receptor Specificity: A Role for Peptides and MHC Polymorphisms in Allosterically Tuning Immune Recognition","authors":"Bassant Eldaly, Brian M. Baker","doi":"10.1002/bies.70126","DOIUrl":"10.1002/bies.70126","url":null,"abstract":"<p>T cell receptor (TCR) recognition of peptide/MHC complexes is fundamental for adaptive immunity. Many studies have described the importance of peptide/MHC motion or dynamics in TCR recognition. A role for dynamics in recognition intersects with the concept of dynamic allostery, which describes how alterations to a protein's energy landscape and thus motions influence function, often in the absence of conformational changes. Tuning of MHC protein energy landscapes by different peptides has clearly been shown. Evidence is mounting, however, that MHC polymorphisms also alter the protein's energy landscape. Here, we address this concept, summarizing findings that suggest that, in addition to dictating peptide binding and selection, naturally occurring variations within MHC proteins promote differential peptide and protein dynamics, altering TCR recognition in an MHC allele-dependent manner. We hypothesize that MHC polymorphisms have been selected evolutionarily in part to tune the protein's dynamic response, altering immune specificity and further diversifying immune responses across populations.</p>","PeriodicalId":9264,"journal":{"name":"BioEssays","volume":"48 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13015781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509374","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}
BioEssaysPub Date : 2026-03-25DOI: 10.1002/bies.70127
Chuying Zhou, Mineko Kengaku
{"title":"Motor-Assisted Co-Migration of Intracellular Organelles and Microtubules as a Mechanism for Directed Cargo Transport","authors":"Chuying Zhou, Mineko Kengaku","doi":"10.1002/bies.70127","DOIUrl":"10.1002/bies.70127","url":null,"abstract":"<p>Intracellular cargo transport relies on a microtubule (MT) network and its molecular motors, dynein and kinesin. While conventional models emphasize motor-driven cargo movement along stationary MT tracks, emerging evidence suggests that dynamic movements of MTs also contribute to directional transport. We propose a model of cargo co-migration with moving MTs, exemplified by nuclear migration in developing neurons. This transport mode may operate across cell types, provided that cargo-MT tethering and directional MT movements are present. We hypothesize multiple complementary mechanisms, including motor catch-bond formation and clustering, as well as MT-associated protein-mediated anchorage. We further discuss how directional MT movements can be generated through motor-driven sliding, cortical gliding, actin-MT crosslinking, and dynamic MT instability. This coupled transport mechanism provides an additional layer of directional control that supplements motor-stepping-dependent transport. Potential experimental approaches to validate this hypothesis are discussed. Understanding MT-mediated cargo delivery could refine our current models of intracellular transport and reveal new insights into neurodevelopmental and neurodegenerative disorders.</p>","PeriodicalId":9264,"journal":{"name":"BioEssays","volume":"48 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13015778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509593","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}
BioEssaysPub Date : 2026-03-25DOI: 10.1002/bies.70130
Elvira Boršić-Mlinarič, Iva Hafner-Bratkovič
{"title":"Diverse Scaffolds Facilitate NLRP3 Clustering and Inflammasome Formation in Response to Perturbations in Cell Homeostasis","authors":"Elvira Boršić-Mlinarič, Iva Hafner-Bratkovič","doi":"10.1002/bies.70130","DOIUrl":"10.1002/bies.70130","url":null,"abstract":"<p>A central component of innate immunity, the NLRP3 inflammasome is a multiprotein complex formed in response to a chemically and morphologically diverse spectrum of stimuli. Despite extensive investigation, no single ligand or signal has emerged to account for this breadth of activation. Here, we review the landscape of NLRP3 activation across subcellular compartments and examine how this process is shaped by a network of interacting partners. Recent studies suggest that NLRP3 responds to cellular perturbations, such as changes in lipid membrane composition, protein localization, or organelle function. We propose that distinct upstream cues converge to generate diverse molecular scaffolds that recruit NLRP3. The NLRP3-scaffold interactions promote NLRP3 clustering, destabilize its autoinhibited conformation, and drive assembly of the inflammasome. NLRP3 is thus an adaptable sensor, equipped with versatile molecular interactions that allow it to integrate multiple danger signals into inflammasome activation.</p>","PeriodicalId":9264,"journal":{"name":"BioEssays","volume":"48 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13015780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509300","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}
BioEssaysPub Date : 2026-03-25DOI: 10.1002/bies.70128
Sergio P. Acebrón, Janina Hattemer, Tobias Rausch, Anchel De Jaime-Soguero
{"title":"Morphogen Gradients as Drivers of Mosaicism During Early Human Development","authors":"Sergio P. Acebrón, Janina Hattemer, Tobias Rausch, Anchel De Jaime-Soguero","doi":"10.1002/bies.70128","DOIUrl":"10.1002/bies.70128","url":null,"abstract":"<p>WNT, BMP, FGF, and Nodal signalling gradients drive naive to primed epiblast transitions and primitive endoderm specification, as well as subsequent gastrulation of the implanted embryo. Recently, these pathways were shown to control a signalling rheostat that modulates chromosome replication and segregation fidelity in human pluripotent stem cells. In particular, WNT and BMP antagonists associated with embryo anteriorization during gastrulation (DKK1, Cerberus, LEFTY2, Noggin, and Chordin) induce DNA replication stress and damage in S-phase leading to ultra-fine-bridges and whole-chromosome mis segregation in the subsequent mitosis. Of note, aneuploidy in pre- and early post-implantation embryos is the first cause of miscarriage in humans, and has also been associated with neurodevelopmental disorders. Here, we hypothesize that the antero-posterior (A–P) signalling gradient generates overlapping patterns of genome and chromosomal mosaicism in human embryos, with potential links to human infertility and lineage-specific developmental disorders.</p>","PeriodicalId":9264,"journal":{"name":"BioEssays","volume":"48 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13015771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509586","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}