FEBS Letters最新文献

{"title":"Two new oligomers of E. coli small heat‐shock protein IbpB identified under heat stress exhibit maximum holding chaperone activity","authors":"Md Azaharuddin, Rakhi Dasgupta, Abhijit Das, Susmita Nandi, Anabadya Pal, Soumajit Chakrabarty, Pathikrit Bandopadhyay, Sourav Ghosh, Sanchita Nandy, Upasana Sett, Tarakdas Basu","doi":"10.1002/1873-3468.15019","DOIUrl":"https://doi.org/10.1002/1873-3468.15019","url":null,"abstract":"<jats:italic>Escherichia coli</jats:italic> small heat‐shock protein IbpB (MW: 16 KDa) has holding chaperone activity and is present in cells at 30 °C as two large oligomers of MW 2.0–3.0 MDa and 600–700 KDa. We report here about the presence of two additional oligomers of MW around 400 and 130 KDa in cells under heat‐stress at 50 °C. These two smaller oligomers possess the most chaperone activity, as observed from the extent of inhibition of inactivation and aggregation separately, of L‐Lactate dehydrogenase in the presence of the individual oligomers at 52 and 60 °C, respectively. It is suggested here that the two larger oligomers act as poorly active storage forms, which under heat stress dissociate partially into smaller oligomers with high holdase activity.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"14 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Five problems plaguing publishing in the life sciences—and one common cause","authors":"Duncan E. Wright","doi":"10.1002/1873-3468.15018","DOIUrl":"10.1002/1873-3468.15018","url":null,"abstract":"<p>Although publication in scholarly peer-reviewed journals remains the gold standard for communication of findings in the life sciences, the gold has been debased in the digital age by various impurities, including (a) reviewer fatigue, (b) fraud, paper mills, and the perils of artificial intelligence, (c) predatory journals, (d) the ongoing use of journal impact factor as a proxy for individual article quality, and (e) salami-slicing and other unethical practices. In this article, I present a detailed overview of these problems, as well as solutions proposed and implemented to counter them. Finally, I suggest that these are all symptomatic of a wider problem, namely the culture of ‘publish or perish’ and ongoing issues with how researcher performance is evaluated for grant, hiring, and promotion decisions. Only by working towards a global shift in the way scientists view the purpose of publication can we finally remove the impurities and refine the gold.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"598 18","pages":"2227-2239"},"PeriodicalIF":3.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.15018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of novel anti‐leishmanials targeting glutathione synthetase of the parasite: a drug repurposing approach","authors":"Manash Sarma, Kushal Bora, Preeti Ranjan, Vikash Kumar Dubey","doi":"10.1002/1873-3468.15016","DOIUrl":"https://doi.org/10.1002/1873-3468.15016","url":null,"abstract":"Drug repurposing has emerged as an effective strategy against infectious diseases such as visceral leishmaniasis. Here, we evaluated four FDA‐approved drugs–valrubicin, ciclesonide, deflazacort, and telithromycin—for their anti‐leishmanial activity on <jats:italic>Leishmania donovani</jats:italic> parasites, especially their ability to target the enzyme glutathione synthetase (<jats:italic>Ld</jats:italic>GS), which enables parasite survival under oxidative stress in host macrophages. Valrubicin and ciclesonide exhibited superior inhibitory effects compared to deflazacort and telithromycin, inhibiting the promastigotes at very low concentrations, with IC<jats:sub>50</jats:sub> values of 1.09 ± 0.09 μ<jats:sc>m</jats:sc> and 2.09 ± 0.09 μ<jats:sc>m</jats:sc>, respectively. Subsequent testing on amastigotes revealed the IC<jats:sub>50</jats:sub> values of 1.74 ± 0.05 μ<jats:sc>m</jats:sc> and 3.32 ± 0.21 μ<jats:sc>m</jats:sc> for valrubicin and ciclesonide, respectively. Molecular and cellular level analysis further elucidated the mechanisms underlying the anti‐leishmanial activity of valrubicin and ciclesonide.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"191 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging current insights on IL‐10‐producing dendritic cells for developing effective immunotherapeutic approaches","authors":"Konstantina Morali, Gloria Giacomello, Michela Vuono, Silvia Gregori","doi":"10.1002/1873-3468.15017","DOIUrl":"https://doi.org/10.1002/1873-3468.15017","url":null,"abstract":"Dendritic cells (DC) are professional antigen‐presenting cells involved in promoting and controlling immune responses. Different subsets of DC, named tolerogenic (tol)DC, play a critical role in the maintenance of tissue homeostasis and in fostering tolerance. These unique skills make tolDC especially attractive for strategies aimed at re‐establishing/inducing tolerance in immune‐mediated conditions. The generation of potent tolDC <jats:italic>in vitro</jats:italic> from peripheral blood monocytes has seen remarkable advancements. TolDC modulate T cell dynamics by favoring regulatory T cells (Tregs) and curbing effector/pathogenic T cells. Among the several methods developed for in vitro tolDC generation, IL‐10 conditioning has been proven to be the most efficient, as IL‐10‐modulated tolDC were demonstrated to promote Tregs with the strongest suppressive activities. Investigating the molecular, metabolic, and functional profiles of tolDC uncovers essential pathways that facilitate their immunoregulatory functions. This Review provides an overview of current knowledge on the role of tolDC in health and disease, focusing on IL‐10 production, functional characterization of <jats:italic>in vitro</jats:italic> generated tolDC, molecular and metabolic changes occurring in tolDC induced by tolerogenic agents, clinical applications of tolDC‐based therapy, and finally new perspectives in the generation of effective tolDC.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"13 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quinone chemistry in respiratory complex I involves protonation of a conserved aspartic acid residue","authors":"Caroline Harter,&nbsp;Frédéric Melin,&nbsp;Franziska Hoeser,&nbsp;Petra Hellwig,&nbsp;Daniel Wohlwend,&nbsp;Thorsten Friedrich","doi":"10.1002/1873-3468.15013","DOIUrl":"10.1002/1873-3468.15013","url":null,"abstract":"<p>Respiratory complex I is a central metabolic enzyme coupling NADH oxidation and quinone reduction with proton translocation. Despite the knowledge of the structure of the complex, the coupling of both processes is not entirely understood. Here, we use a combination of site-directed mutagenesis, biochemical assays, and redox-induced FTIR spectroscopy to demonstrate that the quinone chemistry includes the protonation and deprotonation of a specific, conserved aspartic acid residue in the quinone binding site (D325 on subunit NuoCD in <i>Escherichia coli</i>). Our experimental data support a proposal derived from theoretical considerations that deprotonation of this residue is involved in triggering proton translocation in respiratory complex I.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"598 23","pages":"2856-2865"},"PeriodicalIF":3.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.15013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA Modifications Shape Hematopoietic Stem Cell Aging: Beyond the Code","authors":"Inge van der Werf,&nbsp;Jenna Sneifer,&nbsp;Catriona Jamieson","doi":"10.1002/1873-3468.15014","DOIUrl":"10.1002/1873-3468.15014","url":null,"abstract":"<p>Hematopoietic system aging is characterized by both hematopoietic stem cell (HSC) and niche degeneration resulting in myeloid lineage-biased differentiation, reduced B cell and T cell lymphopoiesis, increased HSC mobilization, and fat deposition in the bone marrow.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p><p>Both alterations in RNA splicing and editing during HSC aging contribute to increased myeloid lineage skewing and inflammation-responsive transcription factors, underscoring the importance of epitranscriptomic mechanisms in the acquisition of an age-related phenotype.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"598 22","pages":"2774-2775"},"PeriodicalIF":3.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.15014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redox medicine: from cellular targets to systems physiology and therapeutics","authors":"Ana Ledo,&nbsp;Bárbara S. Rocha","doi":"10.1002/1873-3468.15005","DOIUrl":"https://doi.org/10.1002/1873-3468.15005","url":null,"abstract":"&lt;p&gt;Biomedical research has long been dedicated to elucidating the determinants of human health and disease. The interaction between intrinsic and environmental factors that affect the metabolic, immune, nervous, and endocrine systems has been the focus of many efforts in the field. Yet, redox signaling, which involves the fine modulation of molecular pathways by free radicals and oxidants, is emerging as a unifying theme in the pathophysiology of human diseases [&lt;span&gt;[1, 2]&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Biological oxidants are a chemically and biologically diverse group of molecules derived from molecular oxygen, nitrogen, or sulfur (although this could be extended to include other elements such as carbon, selenium, halogens, and electrophile species that undergo redox reactions) with critical signaling functions under physiological conditions, ensuring what has been coined by Helmut Sies as oxidative eustress [&lt;span&gt;[3]&lt;/span&gt;]. Dysregulation of redox homeostasis results in supra-physiological concentrations of these species, which establish non-specific reactions with biomolecules and generate other, more reactive species with the ability to react indiscriminately with most biomolecules, producing what is commonly refered to as oxidative (dis)stress [&lt;span&gt;[4]&lt;/span&gt;]. The transition from oxidative eustress to oxidative distress is a common observation in several pathophysiological conditions [&lt;span&gt;[3, 4]&lt;/span&gt;]. As such, cells strategically employ several defense systems, including enzymes and low molecular weight antioxidants, to maintain redox homeostasis. Sensing systems detect shifts from the steady-state oxidant level and initiate appropriate defense strategies. Important redox hubs worth mentioning include NRF2, NF-κB, HIF, ERR, FOXO, PGC1α, AMPK, GAPDH, and UCP, all of which are regulated via oxidation of Cys residues either on adaptor proteins or on the transcription factor itself (reviewed in [&lt;span&gt;[5, 6]&lt;/span&gt;]).&lt;/p&gt;&lt;p&gt;Superoxide radical (&lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msubsup&gt;\u0000 &lt;mi&gt;O&lt;/mi&gt;\u0000 &lt;mn&gt;2&lt;/mn&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mo&gt;−&lt;/mo&gt;\u0000 &lt;mo&gt;⋅&lt;/mo&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;/msubsup&gt;\u0000 &lt;/mrow&gt;&lt;/math&gt;) and hydrogen peroxide (H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt;) are two important examples of biological oxidants produced by tightly controlled enzymatic reactions, notably NADH- (mitochondria) and NADPH-dependent systems (including NADPH oxidases—NOX) as well as superoxide dismutase (SOD), and are promptly decomposed by catalase, peroxiredoxins and phase II enzymes (discussed in [&lt;span&gt;[7]&lt;/span&gt;]). The redox signaling role of H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt; is mainly the result of oxidation of specific Cys residues to sulfenic acid and redox relay via peroxiredoxins [&lt;span&gt;[8-10]&lt;/span&gt;]. This ultimately results in the modulation of metabolism, phosphorylation cascades, regulation of transcription, and other ","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"598 17","pages":"2043-2046"},"PeriodicalIF":3.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.15005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A primer on single-cell RNA-seq analysis using dendritic cells as a case study.","authors":"Giulia Protti, Roberto Spreafico","doi":"10.1002/1873-3468.15009","DOIUrl":"https://doi.org/10.1002/1873-3468.15009","url":null,"abstract":"<p><p>Recent advances in single-cell (sc) transcriptomics have revolutionized our understanding of dendritic cells (DCs), pivotal players of the immune system. ScRNA-sequencing (scRNA-seq) has unraveled a previously unrecognized complexity and heterogeneity of DC subsets, shedding light on their ontogeny and specialized roles. However, navigating the rapid technological progress and computational methods can be daunting for researchers unfamiliar with the field. This review aims to provide immunologists with a comprehensive introduction to sc transcriptomic analysis, offering insights into recent developments in DC biology. Addressing common analytical queries, we guide readers through popular tools and methodologies, supplemented with references to benchmarks and tutorials for in-depth understanding. By examining findings from pioneering studies, we illustrate how computational techniques have expanded our knowledge of DC biology. Through this synthesis, we aim to equip researchers with the necessary tools and knowledge to navigate and leverage scRNA-seq for unraveling the intricacies of DC biology and advancing immunological research.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PIN1 is a novel interaction partner and a negative upstream regulator of the transcription factor NFIB","authors":"Sinem Saritas Erdogan,&nbsp;Ahmet Erdal Yilmaz,&nbsp;Asli Kumbasar","doi":"10.1002/1873-3468.15010","DOIUrl":"10.1002/1873-3468.15010","url":null,"abstract":"<p>NFIB is a transcription factor of the Nuclear Factor One (NFI) family that is essential for embryonic development. Post-translational control of NFIB or its upstream regulators have not been well characterized. Here, we show that PIN1 binds NFIB in a phosphorylation-dependent manner, via its WW domain. PIN1 interacts with the well-conserved N-terminal domains of all NFIs. Moreover, PIN1 attenuates the transcriptional activity of NFIB; this attenuation requires substrate binding by PIN1 but not its isomerase activity. Paradoxically, we found stabilization of NFIB by PIN1. We propose that PIN1 represses NFIB function not by regulating its abundance but by inducing a conformational change. These results identify NFIB as a novel PIN1 target and posit a role for PIN1 in post-translational regulation of NFIB and other NFIs.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"598 23","pages":"2910-2925"},"PeriodicalIF":3.5,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conjugative transfer of the IncN plasmid pKM101 is mediated by dynamic interactions between the TraK accessory factor and TraI relaxase","authors":"Yang Grace Li,&nbsp;Annika Breidenstein,&nbsp;Ronnie P.-A. Berntsson,&nbsp;Peter J. Christie","doi":"10.1002/1873-3468.15011","DOIUrl":"10.1002/1873-3468.15011","url":null,"abstract":"<p>Conjugative dissemination of mobile genetic elements (MGEs) among bacteria is initiated by assembly of the relaxosome at the MGE's origin-of-transfer (<i>oriT</i>) sequence. A critical but poorly defined step of relaxosome assembly involves recruitment of the catalytic relaxase to its DNA strand-specific nicking site within <i>oriT</i>. Here, we present evidence by AlphaFold modeling, affinity pulldowns, and <i>in vivo</i> site-directed photocrosslinking that the TraK Ribbon–Helix–Helix DNA-binding protein recruits TraI to <i>oriT</i> through a dynamic interaction in which TraI's C-terminal unstructured domain (TraI_CTD) wraps around TraK's C-proximal tetramerization domain. Upon relaxosome assembly, conformational changes disrupt this contact, and TraI_CTD instead self-associates as a prerequisite for relaxase catalytic functions or substrate engagement with the transfer channel. These findings delineate key early-stage processing reactions required for conjugative dissemination of a model MGE.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"598 21","pages":"2717-2733"},"PeriodicalIF":3.5,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}