Ultrastrong adhesion to human skin: Calcium as a key regulator of noncovalent interactions.

Calcium is a critical regulator of skin adhesion, stabilizing one of the strongest noncovalent biomolecular interactions ever recorded. Using in vitro and in silico single-molecule force spectroscopy, we demonstrate that calcium ions (Ca) are essential for the ultrastrong binding between the serine-aspartate repeat protein D (SdrD) adhesin and the human skin protein desmoglein-1 (DSG-1), withstanding forces exceeding 2 nanonewtons. Ca ions stabilize both the SdrD complex and the mechanically robust SdrD B-domains, which exhibit unprecedented folding strength.

Structures of two LarA-like nickel-pincer nucleotide cofactor-utilizing enzymes with a single catalytic histidine residue.

The nickel pincer nucleotide (NPN) cofactor catalyzes the racemization/epimerization of α-hydroxy acids in enzymes of the LarA family. The established proton-coupled hydride transfer mechanism requires two catalytic histidine residues that alternately act as general acids and general bases. Notably, however, a fraction of LarA homologs (LarAHs) lack one of the active site histidine residues, replacing it with an asparaginyl side chain that cannot participate in acid/base catalysis.

Engineering the ovarian niche: Environmental control of folliculogenesis in vitro.

Advancements in cancer therapies have significantly improved patient survival, but gonadotoxic treatments often compromise fertility, particularly in female patients. While ovarian tissue cryopreservation and transplantation are well-established fertility preservation options, they are not recommended for patients with blood-borne cancers or highly metastatic malignancies due to the risk of ovarian involvement. In these cases, follicle in vitro culture offers a promising alternative.

Multiplexed bacteriocin synthesis to combat and prevent antimicrobial resistance.

Bacteriocins are underexplored yet promising candidates to combat antimicrobial resistance (AMR) and enable targeted therapy due to their natural origin, abundance and narrow spectrum of activity. In this study, we used a collection of engineered DNA devices and cell-free gene expression (CFE) to rapidly produce combinations (cocktails) of bacteriocins comprising both linear and circular proteins. Other cocktails were designed to target a specific bacterial species by leveraging insights into bacteriocin pathways for cell envelope penetration.

Bioaccessibility of pomegranate seed oil using INFOGEST in vitro digestion model.

Pomegranate seed oil has been widely studied for its health-promoting properties. However, the bioavailability of its conjugated linolenic acids, an essential factor for assessing their impact on health, remains poorly understood. This study used the harmonized in vitro protocol INFOGEST to investigate the bioaccessibility of pomegranate seed oil in comparison to olive oil.

Of travelling homeoproteins and medulloblastomas.

Medulloblastomas are the most common solid paediatric cancers. Their prognosis largely depends on tumour subtype and expression level of transcription factor such as Orthodenticle homeobox 2 (OTX2). OTX2 is an homeoprotein that maintains stemness and initiates oncogenic pathways.

Acidosis Forces Fatty Acid Uptake and Metabolism in Cancer Cells Regardless of Genotype.

While proteins facilitate fatty acid (FA) partitioning into plasma membranes, movement between membrane leaflets occurs through a "flip-flop" mechanism. This study provides evidence that biological acidosis, as encountered in tumors and ischemic diseases, promotes FA protonation, thereby enhancing neutral, non-ionized FA uptake. This positions the altered lipid metabolism in acid-exposed cells as a consequence, rather than a cause, of preferential FA uptake.

Late histopathological impacts on the female prostate of gerbils exposed to BPA during pregnancy and lactation.

The female prostate is regulated by steroid hormones, mainly androgens and estrogens. Exposure to exogenous chemical compounds leads to effects via endocrine pathways that alter prostate morphophysiology. Bisphenol A (BPA) is a widespread endocrine disruptor, which influences estrogenic pathways, facilitating pre-neoplastic and neoplastic alterations in hormone-sensitive organs.

Recruitment of Mre11 to recombination sites during meiosis.

The Mre11 nuclease, part of the conserved MRX complex involved in the repair of DNA double-strand breaks (DSBs), is also essential to initiate meiotic recombination in budding yeast by promoting Spo11-induced DSBs. Recruitment of Mre11 to meiotic DSB sites depends on Rec114-Mei4 and Mer2 (RMM) that organize the meiotic DSB machinery by a mechanism involving biomolecular condensation. Here, we explored the role of Mre11 during meiosis and its relationship to RMM condensation.

Proximity labelling of internalizing influenza A viruses reveals a role for neogenin in virus uptake.

Influenza A virus (IAV) is a respiratory pathogen of global concern. Entry of most IAVs is mediated by binding of viral hemagglutinin to cellular sialic acid, facilitating virus attachment. A subsequent interaction with a surface receptor(s) triggers viral uptake.

Functional replacement of ancestral antibacterial secretion system in a bacterial plant pathogen.

Two distinct molecular machineries, T4SS and T6SS, have been found within the order Xanthomonadales to be involved in outcompeting other bacterial species through the secretion of toxic effector proteins. However, the ecological and evolutionary basis leading xanthomonads to evolve two secretion systems with such similar functions remain unclear. Here we show that Xanthomonas translucens (Xt) lineages have switched from an X-T4SS-mediated to T6SS-i4-mediated bacterial killing strategy.

Water availability positions auxin response maxima to determine plant regeneration fates.

Wounding and hormones serve as diverse triggers for regeneration in animals and plants. Despite important advances in understanding various types of regeneration, the mechanism by which plants determine regeneration outcomes remains largely unknown. Here we demonstrate in Arabidopsis that a trade-off between two regeneration fates, wound-induced callus and root regeneration, was driven by distinct molecular pathways related to cambium and root development, respectively.

Measuring the Carboxypeptidase and γ-Glutamyltranspeptidase Activities of Lager and Ale Yeasts to Assess Their Impact on the Release of Odorant Polyfunctional Thiols Through Fermentation.

Two enzymatic assays, based on release of -nitroaniline and its spectrophotometric detection at 405 nm, were used to screen lager and ale brewing yeasts for carboxypeptidase and γ-glutamyltranspeptidase activity. Both activities were found in all the investigated yeasts and did not significantly distinguish from species. Large between-strain differences were measured for both carboxypeptidase (from 1.

Treating seizures in SYN1-related epilepsy: a systematic review.

Introduction: Synapsin1-related epilepsy is a rare entity, in which patients typically present reflex seizures, provoked by contact with water. Moreover, patients carrying a pathogenic variant of the synapsin 1 gene (SYN1) can present developmental delay, behavior disorders, and other types of seizures. While SYN1-related epilepsy becomes better characterized, there is still no consensus on the appropriate antiseizure medication (ASM) to use.

Primary Cell Cultures in Neurobiology: Optimized Protocol for Culture of Mouse Fetal Hindbrain Neurons.

Primary cultures of neural cells are important key tools for basic and translational neuroscience research. These primary cell cultures are classically generated from the rodent brain hippocampus or cortex and optimized for enrichment in neurons at the expense of glial cells. Importantly, considerable differences exist in neuronal cell populations and in glial cell contribution between different brain regions.

Mechanically knocking out titin reveals protein tension loss as a trigger of muscle disease.

Titin, the elastic protein scaffold of muscle sarcomeres, has multifunctional roles in mechanosignalling and is implicated in muscle disease. However, the consequences of disrupting titin's mechanical function in vivo remain incompletely understood. Here, by leveraging site-directed polypeptide severing as a 'mechanical knock-out' method for abolishing force transmission across titin, we show that the loss of titin tension in homozygous mechanically knocked-out muscles reduces force generation and induces severe atrophy and widespread transcriptional dysregulation.

Reconstitution of SPO11-Mediated DNA Cleavage Sheds New Light on the Initiation of Meiotic Recombination.

Three recent studies report the first biochemical reconstitution of DNA double-strand break (DSB) formation by SPO11, the topoisomerase-derived transesterase that initiates meiotic recombination in sexually reproducing organisms. A central conclusion of these studies is that SPO11 is sufficient to catalyze DSBs , but cleavage is limited by the poor propensity of SPO11 to dimerize, thereby providing an effective mechanism to prevent uncontrolled breaks. The studies yield new insights into the mechanism of DNA DSB formation and raise new questions regarding the functions of SPO11 partners, the impact of the DNA substrate, the coordination between cleavage events, and the reversibility of the reaction.

Exogenous melatonin enhances drought tolerance and germination in common buckwheat seeds through the coordinated effects of antioxidant and osmotic regulation.

Background: Drought stress is a major constraint on seed germination and crop productivity, particularly for drought-sensitive crops like common buckwheat (Fagopyrum esculentum). Exogenous melatonin has emerged as a promising strategy to mitigate drought stress by enhancing plant physiological and biochemical responses. However, its specific roles in regulating antioxidant defenses, osmotic adjustment, and plant compounds biosynthesis during buckwheat seed germination under drought stress remain poorly understood.

Effects of phthalate exposure on human ovarian extracellular matrix composition: insights from a 3D spheroid model.

Phthalates, widely used as plasticizers in consumer products, have become a significant public health concern due to their toxic effects on reproductive and endocrine systems. However, the specific mechanisms by which phthalates affect ovarian function remain poorly understood. To address this knowledge gap, we employed 3D spheroids derived from human ovarian stromal cells, which mimic the ovarian tissue.

Insights into the bioluminescence systems of three sea pens (Cnidaria: Anthozoa): from de novo transcriptome analyses to biochemical assays.

Bioluminescence is the production of visible light by living organisms. It occurs through the oxidation of luciferin substrates catalysed by luciferase enzymes. Auxiliary proteins, such as fluorescent proteins and luciferin-binding proteins, can modify the light emitted wavelength or stabilize reactive luciferin molecules, respectively.

Dehydroepiandrosterone sulphate (DHEAS) supplementation impacts adrenal cortex morphophysiology of aged female gerbils.

During the process of aging, it is common for women to take dehydroepiandrosterone sulphate (DHEAS) supplements to prevent adrenopause. However, the potential effects of this supplementation on the adrenal cortex have not yet been fully elucidated. Therefore, the present study aimed to analyze the effects of DHEAS supplementation on the adrenal cortex of female Mongolian gerbils during the aging process.

Nicotiana tabacum contains two alpha1,3-fucosyltransferase types, one of which is able to catalyze core fucosylation of high-mannose N-glycans.

N-glycosylation is a critical quality attribute to consider when expressing recombinant glycoproteins in eukaryotic cells including plant cells. N-acetylglucosaminyltransferase I (GnTI) initiates complex N-glycan maturation in the Golgi apparatus by transferring a single N-acetylglucosamine (GlcNAc) residue on the alpha1,3-arm of a Man5 N-glycan acceptor. This step is required for the processing of high mannose into hybrid and complex N-glycans.

Jacaric Acid Empowers RSL3-Induced Ferroptotic Cell Death in Two- and Three-Dimensional Breast Cancer Cell Models.

Ferroptosis has recently emerged as a promising strategy to combat therapy-resistant cancers. As lipid peroxidation is a key trigger of ferroptotic cell death, enhancing cancer cell susceptibility through the supply of highly peroxidisable fatty acids represents a novel therapeutic approach. Conjugated linolenic acids (CLnAs) fulfill this requirement, exhibiting a peroxidation propagation rate eight times higher than their non-conjugated counterpart, α-linolenic acid.

Hormonal disruption from plastic ingestion in northern fulmars: Activation and inhibition of estrogen receptors.

Plastic pollution is of global concern, yet documented harmful effects from plastic ingestion in wild species is limited. Procellariiformes, such as northern fulmars (Fulmarus glacialis, fulmar), have high levels of plastic ingestion, and we investigated their potential hormonal disruption. As human estrogen receptors (ERs) are commonly used to assess risk of hormonal disruption for wild species, we first compared human and fulmar ER responses to plastic-associated chemicals using a luciferase-reporter gene assay.