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Viruses represent a major threat to human health, while simultaneously exhibiting great potential in a wide range of applications, from virus-inspired devices to therapeutic delivery agents. Addressing virus-related questions from an interdisciplinary standpoint promises to open new avenues, both in the fight against viral diseases and in the exploitation of viral structures to advance technology. This has stimulated the development of 'physical virology', a growing research field gathering researchers from various scientific disciplines with a common interest in viruses. The FEBS|EMBO Lecture course on Physical Virology brought together top researchers working with viruses to inspire and further educate a new generation of transdisciplinary virus-oriented scientists and to cement the growing physical virology community.
Q. Jiang , F. Li , K. Shi , P. Wu , J. An , Y. Yang and C. Xu , "ATF4 Activation by the p38MAPK-eIF4E Axis Mediates Apoptosis and Autophagy Induced by Selenite in Jurkat Cells," FEBS Letters 587, no. 15 (2013): 2420-2429, https://doi.org/10.1016/j.febslet.2013.06.011. The above article, published online on 19 June 2013 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor-in-Chief, Michael Brunner; the Federation of European Biochemical Societies; and John Wiley & Sons Ltd. The retraction has been agreed upon following concerns raised by a third party. An investigation identified several instances in which elements appear to be duplicated across different figures, including between Figures 1B and 3F, 2C and 5F, 5F and 6A, and 3E and 5E. Additional duplications were identified within Figures 1C and 5B. Further duplications were observed involving elements from Figures 1A, 1C, 3E, and 6D of this article and figures published in a later article elsewhere by some of the same authors. The authors acknowledged some of the duplications and indicated that these arose during figure preparation. Due to the time that has elapsed since publication, the original data are no longer available. The editors consider the results and conclusions of this article to be unreliable. The authors did not respond to our notice of retraction.
K. Dey , S. M. Rahaman , T. Chakraborti , and S. Chakraborti , "Role of Phospholemman and the 70 kDa Inhibitor Protein in Regulating Na+/K+ ATPase Activity in Pulmonary Artery Smooth Muscle Cells under U46619 Stimulation," FEBS Letters 587, no. 21 (2013): 3535-3540. https://doi.org/10.1016/j.febslet.2013.09.011. The above article, published online on 18 September 2013 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Michael Brunner; the Federation of European Biochemical Societies; and John Wiley & Sons Ltd. A third party reported on PubPeer [1] that there was evidence of duplication of bands in Figure 1D and duplication and manipulation of image elements in Figure 4C. An investigation by the journal and publisher confirmed that Figures 1D and 4C had been manipulated. They also found evidence of duplication and manipulation between Figures 2A and 2B, as well as evidence of duplication between Figure 4B and the first three bands in Figure 5B. The authors did not initially respond to an inquiry about these concerns by the publisher. The retraction has been agreed to because the evidence of image manipulation within this article fundamentally compromises the editors' confidence in the results and conclusions as presented. The authors were informed of the retraction. References [1] Brachystigma wrightii. Comments on "Role of phospholemman and the 70 kDa inhibitor protein in regulating Na+/K+ ATPase activity in pulmonary artery smooth muscle cells under U46619 stimulation," PubPeer, March 2026. https://pubpeer.com/publications/1E450411C9E5FB2DC607F7D229B95A.
Aminoacyl-tRNA synthetases (ARSs) are a family of enzymes that attach amino acids to tRNAs. To date, all 37 human ARS genes have been implicated in genetic diseases, affecting over a thousand patients worldwide. At the 2025 Federation of European Biochemical Societies (FEBS) Special Meeting 'Expanding Frontiers in Aminoacyl-tRNA Synthetase Research', patients, families, and advocacy groups communicated the need for a unified approach for reporting on ARS gene names and associated conditions in the scientific literature. This request stemmed from the current use of multiple nomenclature systems and the desire of these individuals to rapidly identify published data on specific ARS genes. Here, we summarize ARS gene nomenclature and request that the scientific community adhere to a single nomenclature system.
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CFTR stability at the plasma membrane is controlled by a dynamic balance between trafficking, endocytosis, recycling, and degradation. Interactions with scaffold proteins such as NHERF1 and ezrin anchor CFTR to the actin cytoskeleton, reducing mobility and enhancing stability. Cytoskeletal dynamics, regulated by GTPases like RhoA, Rac1, and Rap1, further influence CFTR retention and function. Phosphorylation by kinases including PKA, LMTK2, and SYK modulates channel activity and membrane presence. Whereas rescue of F508del-CFTR with modulators can rescue its defective folding and premature degradation, reduced membrane stability persists. Overall, understanding the molecular mechanisms governing CFTR regulation provides critical insights for developing more effective treatments targeting its stability and function in cystic fibrosis.
To sustain rapid proliferation, cancer cells increase protein synthesis, intensifying reliance on protein disulfide isomerase A1 (PDIA1). It is largely unknown whether disulfide bond formation of PDIA1 substrates is driven by one or both CGHC motifs. Using active-site trapping mutants in prostate cancer cells combined with mass spectrometry, we identified 29 proteins uniquely bound to the C53GHC56 domain and 20 proteins uniquely bound to the C397GHC400 domain. Hyaluronan-mediated motility receptor (HMMR) was validated as a PDIA1 C397GHC400-specific substrate, with PDIA1 catalysing disulfide bond formation between Cys242 and Cys293. PDIA1 knockdown induced HMMR ubiquitination, blocked androgen receptor nuclear translocation, and suppressed prostate cancer cell growth, survival, and migration. These findings reveal a previously unknown role of PDIA1 in prostate cancer biology.
Phthalates are ubiquitous environmental contaminants and suspected endocrine disruptors, used as plasticizers and constituents of fragrances. Regulation of their use in consumer products has largely been guided by male reproductive outcomes. However, as evidenced in rodent models, extended contact with phthalates also affects ovarian function. Data from human ovarian samples, ovary-derived cell lines, and epidemiological studies of infertile patient cohorts have demonstrated adverse associations between phthalate-related chemical burden and female fertility. Due to the sustained use of phthalate-containing products, women may experience earlier fertility decline. These outcomes can be linked to molecular disturbances in ovarian follicles, where phthalate metabolites are frequently detected. This review synthesizes current human evidence on phthalate impacts on the ovary.
Depolarizing stimuli regulate acetylcholine (ACh) storage and release via distinct synaptic vesicle pools in cholinergic terminals, but the mechanisms remain unclear. Here, we examined the effects of preliminary depolarization on choline uptake, ACh synthesis, and release in rat striatal segments using [3H]choline incorporation and [3H]ACh release assays. Preliminary KCl depolarization significantly increased functional high-affinity choline transporter-1 (CHT1) availability, enhancing subsequent [3H]choline uptake, [3H]ACh synthesis, and release. In contrast, preliminary electrical stimulation selectively increased evoked [3H]ACh release without affecting choline uptake or tissue ACh content. These results suggest that electrical stimulation primarily mobilizes vesicles from the readily releasable pool (RRP) and recycling pool, whereas KCl depolarization additionally recruits vesicles from the reserve pool and may directly trigger ACh release.
There is considerable evidence that iron accumulation in the affected brain regions plays a role in the pathology of neurodegenerative diseases, probably because of the ability of iron ions to promote oxidative damage to important biomolecules, such as DNA, RNA, proteins and lipids (leading to lipid peroxidation). Yet recent clinical trials of iron ion-chelating agents in human neurodegenerative diseases have given unimpressive results, in several cases making the diseases worse. In using iron chelators, it is important to remember the basics of their redox chemistry, which could explain their lack of therapeutic effects. This issue is explored here, and the potential of iron ion chelation in the treatment of neurodegeneration is critically evaluated.
Lipopolysaccharides (LPS) are a key component in the defensive barrier of the outer membrane (OM) of Gram-negative bacteria; they are a major drug target and bacteriophage access point. Biomimetic platforms presenting LPS are therefore important to study OM biophysics of pathogens and initial bacteriophage infection steps. Herein, we present robust protocols for the preparation of LPS-containing supported lipid bilayers (SLBs) incorporating either Salmonella LPS or OM vesicles (OMVs). We characterized SLBs using quartz crystal microbalance with dissipation (QCM-D) and fluorescence microscopy. We probed their interactions with O-antigen specific Salmonella phages and their tailspike receptor binding proteins. Altogether, this work provides a roadmap to create versatile LPS-based platforms that facilitate studies of interactions between phages and Gram-negative bacterial membranes.
The gut microbiome changes systematically with age and associates with age-related morbidity and mortality, establishing it as a candidate biomarker and intervention target for ageing. Realising this potential requires methodological rigour, as distinguishing genuine biological signals from methodological artefacts remains challenging given variable findings across cohorts. This review provides an integrated framework for human microbiome-ageing research, organised around five methodological challenges that will collectively strengthen causal inference. We examine how age-associated factors can correlate with chronological age and may confound the microbiome-age associations, while selection biases shape old-age cohorts towards healthier profiles. We address within-host temporal dynamics and between-individual heterogeneity that require appropriate sampling to distinguish age-related signatures from transient states, and validation strategies that separate ageing from batch effects in predictive models. Mendelian randomisation provides causal leverage when triangulated with longitudinal and interventional evidence. Throughout, we examine how design choices determine the limits of analytical inference. The review concludes with a practical checklist, equipping researchers to strengthen reproducibility, improve generalisability and advance microbiome-based metrics towards validated indicators of biological ageing.
Inositol phosphates (IPs) and phosphoinositide lipids (PIPs) are regulatory molecules critical for a wide array of functions in eukaryotic cells. Membrane PIPs have clear functions in transient recruitment of signaling proteins to membranes, and IPs have been found locked in the core of proteins as structural cofactors. However, several recent studies have suggested IPs and PIPs can mediate protein-protein interactions at the interface between proteins, functioning as natural molecular glues. Here, we present recent structural biology describing how IPs and PIPs mediate these regulatory responses at protein interfaces. In addition, we describe protein-protein interactions mediated by IPs and PIPs, for which evidence supporting a natural molecular glue role is unclear or awaits further high-resolution structural analyses. Together, we put forth that PIPs and IPs have a historically under-appreciated role at protein-protein interfaces, requiring a more systematic, structural approach to elucidate.
The finding of the pyruvate generator ('mitochondrial gas pedal') arose from the observation that cytosolic Ca2+ accelerates glutamate-driven respiration. Here, we show that glutamate respiration of isolated rat brainstem mitochondria appears to be insensitive to extra-mitochondrial Ca2 +. This raises the question: Do these mitochondria lack a pyruvate generator, or is its detection masked? By reconstituting the complete malate-aspartate shuttle (MAS), we demonstrate that brainstem mitochondria possess a pyruvate generator, just like mitochondria from other brain regions. Direct measurement, however, is hindered by the high rate of Ca2+-insensitive glutamate utilization by glial mitochondria. We therefore conclude that the pyruvate generator is a universal mechanism in all tissues that contain a functional MAS and pyruvate-generating enzymes.
Atomic force microscopy-AFM enables label-free quantification of cellular and tissue mechanics with nanoscale resolution under near-physiological conditions, providing access to physical properties that are not captured by conventional approaches. In cancer, mechanical remodeling spans multiple scales, from cytoskeletal reorganization and increased cell deformability to extracellular matrix deposition and desmoplastic stiffening of solid tumors. These alterations generate reproducible nanomechanical fingerprints that distinguish cancer states at both the single-cell and tissue level. This review summarizes the principles underlying AFM, discusses their application in cancer diagnosis via tumor biopsy analysis, and highlights emerging efforts to extend mechanophenotyping toward circulating tumor-associated analytes in liquid biopsy. Finally, we illustrate the broader applicability of this framework using pulmonary fibrosis and discuss key challenges for clinical translation.
Protein aggregates threaten cellular proteostasis and are linked to aging and disease. In metazoa, aggregate resolution relies on Hsp70-J-domain protein (JDP)-based disaggregases. Previous studies showed human class A and class B JDP assemblies enhance Hsp70-mediated disaggregation, but the underlying mechanism has remained unclear. Using J-domain mutants that impair Hsp70 binding while preserving mixed-class JDP interaction, we show that synergistic disaggregation is lost when either JDP partner cannot engage Hsp70. Size-resolved disaggregation assays further reveal that mixed-class JDP assemblies influence the processing of distinct luciferase aggregate populations, including aggregate species inefficiently handled by either JDP alone. Our findings support a model in which mixed-class JDP assemblies enhance Hsp70 disaggregation through expanded aggregate-processing capacity and multivalent Hsp70 recruitment by both JDP partners.
Proteostasis and the gut microbiota are two major determinants of host health and longevity. Proteostasis ensures proper protein folding and degradation thereby preventing the accumulation of unwanted proteins. Similarly, microbiota contribute to host metabolism, immunity, and protection from pathogens. However, as aging progresses, the proteostasis network declines, and the composition and functionality of gut microbiota are altered, often resulting in dysbiosis. While the impact of the microbiota on various aspects of host physiology is extensively studied, its specific influence on host protein quality control remains relatively underexplored. In this review, we provide an integrated overview of the relationship between microbiota and host proteostasis. Accumulating findings, particularly from C. elegans models, provide substantial support for the concept that microbiota-derived factors (vitamins and RNA) can shape host proteostasis and influence aging-related phenotypes. We discuss emerging evidence showing that microbial communities and their metabolites can either support or impair cellular proteostasis, highlighting their potential as prebiotics or dietary intervention candidates for promoting healthy aging. Understanding the intricate interplay between microbiota and proteostasis opens new avenues for designing microbiota-based strategies for healthy aging.
Septins are cytoskeletal GTP-binding proteins that organize microtubules and scaffold polarity complexes. Here, we uncover a polybasic (PB)-domain-dependent mechanism by which septin 9 controls apico-basal polarity in epithelial cells. Septin 9 regulates centrosome positioning and the asymmetric distribution of acetylated microtubules, which are required for ciliogenesis and lumen formation. Knockdown of septin 9 or deletion of its PB domains disrupts centrosome asymmetry, induces a symmetric distribution of acetylated tubulin, and impairs cilia formation, leading to polarity inversion. These defects are associated with increased expression of the microtubule deacetylase HDAC6. Importantly, inhibition of TGF-β signaling or selective HDAC6 inhibition with tubacin restores microtubule acetylation and rescues apico-basal polarity. Together, our findings identify septin 9 as a cytoskeletal integrator that links centrosome positioning and microtubule acetylation to epithelial morphogenesis through the TGF-β/HDAC6 pathway.
Fluorescence recovery after photobleaching (FRAP) is a widely used technique for investigating protein dynamics in live cells. FRAP enables researchers to monitor protein mobility and binding interactions in real time, providing valuable insights into cellular regulatory mechanisms. Initially developed to explore membrane fluidity, FRAP has evolved to enable study of nuclear processes, including transcription factor (TF) dynamics crucial for gene regulation. In this review, we focus on how FRAP has advanced our understanding of TF dynamics in health and disease. TFs exhibit complex interactions with DNA that are essential for cellular function. FRAP helps to quantify these interactions, revealing how TF mobility and chromatin binding influence gene expression patterns. We further explore the role of FRAP in studying TFs in disease. Research on TF dynamics in cancer, diabetes, and osteoarthritis underscores the method's potential to identify disease-related regulatory mechanisms. By providing a nuanced understanding of TF behavior, FRAP presents a promising avenue for developing targeted therapies across diverse pathologies.
Gland cells dynamically regulate their secretory granule content via balancing synthesis, maturation, secretion, and lysosomal degradation (crinophagy). However, the signal(s) leading to crinophagic breakdown of secretory granules are unknown. Here, we show that ubiquitination of unreleased or low-grade glue-containing secretory granules marks these vesicles for crinophagy in larval salivary gland cells of Drosophila. We identify the ubiquitin ligase Cnot4 as a key mediator of glue granule ubiquitination. Loss of Cnot4 prevents ubiquitination and impairs granule fusion with lysosomes. Overexpression of Cnot4 induces premature crinophagy via ectopic ubiquitination of granules. Our work establishes that Cnot4-dependent ubiquitination of secretory granules is a key trigger of crinophagy in Drosophila, paving the way for further analysis of this barely characterized degradation route in metazoans.