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Cymoxanil (CYM) is a widely used synthetic acetamide fungicide, but its biochemical mode of action remains elusive. Since CYM inhibits cell growth, biomass production, and respiration in Saccharomyces cerevisiae, we used this model to characterize the effect of CYM on mitochondria. We found it inhibits oxygen consumption in both whole cells and isolated mitochondria, specifically inhibiting cytochrome c oxidase (CcO) activity during oxidative phosphorylation. Based on molecular docking, we propose that CYM blocks the interaction of cytochrome c with CcO, hampering electron transfer and inhibiting CcO catalytic activity. Although other targets cannot be excluded, our data offer valuable insights into the mode of action of CYM that will be instrumental in driving informed management of the use of this fungicide. [ABSTRACT FROM AUTHOR]

Accurate quantification of biodiversity can be demanding and expensive. Although environmental DNA (eDNA) metabarcoding can facilitate biodiversity assessments through non‐invasive, cost‐efficient and rapid surveys, the approach struggles to outperform traditional morphological approaches in providing reliable quantitative estimates for surveyed species (e.g. abundance and biomass).We present an integrated methodology for improving biodiversity surveys that pairs eDNA metabarcoding with morphological data, following a series of taxonomic and geographical filters. We demonstrate its power by applying it to a new spatiotemporal dataset generated on an Iberian‐wide distributed aquatic mesocosm infrastructure that spans a wide biogeographical gradient.By building upon the strengths that these two approaches offer, our framework improved taxonomic resolution for 30% of the taxa and enabled species' traits (e.g. body size) and abundance to be assigned to 85% of the taxa in hybrid datasets.These results indicate that eDNA‐based assessments can complement, but not always replace, conventional approaches. Integrating conventional and modern eDNA metabarcoding approaches, already available in the ecologist's toolbox, will greatly enhance biodiversity assessments. [ABSTRACT FROM AUTHOR]

The control of the intracellular pH is vital for the survival of all organisms. Membrane transporters, both at the plasma and intracellular membranes, are key players in maintaining a finely tuned pH balance between intra‐ and extracellular spaces, and therefore in cellular homeostasis. V‐ATPase is a housekeeping ATP‐driven proton pump highly conserved among prokaryotes and eukaryotes. This proton pump, which exhibits a complex multisubunit structure based on cell type‐specific isoforms, is essential for pH regulation and for a multitude of ubiquitous and specialized functions. Thus, it is not surprising that V‐ATPase aberrant overexpression, mislocalization, and mutations in V‐ATPase subunit‐encoding genes have been associated with several human diseases. However, the ubiquitous expression of this transporter and the high toxicity driven by its off‐target inhibition, renders V‐ATPase‐directed therapies very challenging and increases the need for selective strategies. Here we review emerging evidence linking V‐ATPase and both inherited and acquired human diseases, explore the therapeutic challenges and opportunities envisaged from recent data, and advance future research avenues. We highlight the importance of V‐ATPases with unique subunit isoform molecular signatures and disease‐associated isoforms to design selective V‐ATPase‐directed therapies. We also discuss the rational design of drug development pipelines and cutting‐edge methodological approaches toward V‐ATPase‐centered drug discovery. Diseases like cancer, osteoporosis, and even fungal infections can benefit from V‐ATPase‐directed therapies. [ABSTRACT FROM AUTHOR]

Breast cancer diagnosis remains a challenge, mostly due to its heterogeneity. This reality translates in delayed treatments, increasing treatment aggressiveness and lower chances of overall survival. The conventional detection techniques, although becoming increasingly sophisticated each year, still lack the ability to provide reliable conclusions without being time consuming, expensive, and uncomfortable for the patients. The identification of novel biomarkers for breast cancer research is therefore of utmost relevance for an early diagnosis. Moreover, breast cancer‐specific peptide moieties can be used to develop novel targeted drug delivery systems. In this work, we used phage display to identify a novel peptide with specificity to the SK‐BR‐3 breast cancer cell line. Cytometry assays confirmed its specificity, while bioinformatics and docking studies predicted the potential biomarkers at the SK‐BR‐3 cells' surface. These findings can be potentially useful in the clinical context, contributing to more specific and targeted therapeutic solutions against HER2‐positive breast cancer subtypes. [ABSTRACT FROM AUTHOR]

The nuclear envelope (NE) is the central organizing unit of the eukaryotic cell serving as a genome protective barrier and mechanotransduction interface between the cytoplasm and the nucleus. The NE is mainly composed of a nuclear lamina and a double membrane connected at specific points where the nuclear pore complexes (NPCs) form. Physiological aging might be generically defined as a functional decline across lifespan observed from the cellular to organismal level. Therefore, during aging and premature aging, several cellular alterations occur, including nuclear‐specific changes, particularly, altered nuclear transport, increased genomic instability induced by DNA damage, and telomere attrition. Here, we highlight and discuss proteins associated with nuclear transport dysfunction induced by aging, particularly nucleoporins, nuclear transport factors, and lamins. Moreover, changes in the structure of chromatin and consequent heterochromatin rearrangement upon aging are discussed. These alterations correlate with NE dysfunction, particularly lamins' alterations. Finally, telomere attrition is addressed and correlated with altered levels of nuclear lamins and nuclear lamina‐associated proteins. Overall, the identification of molecular mechanisms underlying NE dysfunction, including upstream and downstream events, which have yet to be unraveled, will be determinant not only to our understanding of several pathologies, but as here discussed, in the aging process. [ABSTRACT FROM AUTHOR]

The production of highly specialized spermatozoa from undifferentiated spermatogonia is a strictly organized and programmed process requiring extensive restructuring of the entire cell. One of the most remarkable cellular transformations accompanying the various phases of spermatogenesis is the profound remodelling of the nuclear architecture, in which the nuclear envelope (NE) seems to be crucially involved. In recent years, several proteins from the distinct layers forming the NE (i.e. the inner and outer nuclear membranes as well as the nuclear lamina) have been associated with meiosis and/or spermiogenesis in different mammalian species. Among these are A‐ and B‐type lamins, Dpy‐19‐like protein 2 (DPY19L2), lamin B receptor (LBR), lamina‐associated polypeptide 1 (LAP1), LAP2/emerin/MAN1 (LEM) domain‐containing proteins, spermatogenesis‐associated 46 (SPATA46) and diverse elements of the linker of nucleoskeleton and cytoskeleton (LINC) complex, namely Sad‐1/UNC‐84 homology (SUN) and Klarsicht/ANC‐1/Syne‐1 homology (KASH) domain‐containing proteins. Herein, we summarize the current state of the art on the cellular and subcellular distribution of NE proteins expressed during mammalian spermatogenesis, and discuss the latest research developments regarding their testis‐specific functions. This review provides a comprehensive and innovative overview of the NE network as a regulatory platform and as an essential determinant of efficient meiotic chromosome recombination as well as spermiogenesis‐associated nuclear remodelling and differentiation in mammalian male germline cells. Thus, this review provides important novel insights on the biological relevance of NE proteins for male fertility. [ABSTRACT FROM AUTHOR]

Following environmental changes, communities disassemble and reassemble in seemingly unpredictable ways. Whether species respond to such changes individualistically or collectively (e.g. as functional groups) is still unclear. To address this question, we used an extensive new dataset for the lake communities in the Azores' archipelago to test whether: 1) individual species respond concordantly within trophic groups; 2) trophic groups respond concordantly to biogeographic and environmental gradients. Spatial concordance in individual species distributions within trophic groups was always greater than expected by chance. In contrast, trophic groups varied non-concordantly along biogeographic and environmental gradients revealing idiosyncratic responses to them. Whether communities respond individualistically to environmental gradients thus depends on the functional resolution of the data. Our study challenges the view that modelling environmental change effects on biodiversity always requires an individualist approach. Instead, it finds support for the longstanding idea that communities might be modelled as a cohort if the functional resolution is appropriate. [ABSTRACT FROM AUTHOR]