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The enzyme ABHD18 is shown to have a key role in cardiolipin metabolism in mitochondria, offering a potential route for a small-molecule treatment of the rare genetic disease Barth syndrome.

Here the authors show how the DNA-sensing cGAS–STING pathway activates NF-κB and inflammatory gene expression with delayed kinetics via post-Golgi endolysosomal signaling.

IST2 serves as a tether between the endoplasmic reticulum and the plasma membrane in yeast. Here, Arndt et al. interrogate its interaction with OSH6, revealing that the two proteins remain associated during lipid shuttling.

Brown adipose tissue (BAT) is key for metabolic balance. Here, the authors show that RAP250 deficiency enhances BAT activity. Under these conditions, BAT-derived neuritin-1 regulates thermogenesis and fat metabolism, showing therapeutic promise for obesity and metabolic disorders.

A technique for the site-directed conjugation of antibodies via the small-protein ubiquitin allows for the efficient multivalent conjugation of antibodies and nanobodies to fusions of ubiquitin with molecular or proteinic moieties.

A report from the first 2,000 newborns enrolled in the Early Check program, which offered genome screening covering 198 genes associated with early-onset diseases, shows the feasibility and potential clinical utility of the approach, leading to 28 true positive results.

The cryo-EM structure of the receptor binding domain of Microcin V in complex with its bacterial receptor, Cir, demonstrates a conserved bacteriocin/receptor interaction and illuminates a potential path for future drug development.

Ataluren restored SBDS protein synthesis in three patients with Shwachman-Diamond syndrome, improving bone marrow cellularity and pancreatic function without side effects, highlighting its potential as therapeutic option for this genetic disease.

A minimal effector subset enables Salmonella Typhimurium to overcome bottlenecks regulated by the early innate immune response and establish infection within a CD62L⁺ monocyte niche in the spleen.

Nature-inspired catalysts strive to emulate the efficiency and selectivity of enzymes while maintaining the robustness of synthetic catalysts. Here, the authors use bioinformatics to design an eight-amino-acid peptide that self-assembles with copper ions, forming a complex that mimics the laccase enzyme’s active site, highlighting the potential of short peptides in biomimetic catalysis.

Rad51/RecA filament formation is key to homologous recombination. Here the authors combine structural studies with analyses in yeast to show that an 85-residue segment of Rad52 acts as a chaperone that binds Rad51 monomers promoting nucleation on ssDNA and counteracting the Srs2 translocase.

Tumor-associated neutrophils exhibit heterogeneity in breast cancer. Here, the authors identify a distinct precursor population (PreNeu) in estrogen receptor-positive tumors. PreNeu suppress homologous recombination in cancer cells, promoting error-prone DNA repair and enhancing sensitivity to PARP inhibitors.

Here, the authors identify and characterize three gut bacterial enzyme families that metabolize endogenous and synthetic steroid hormones, showing to act on diverse substrates, to exhibit gene fusions, and gender-linked prevalence, opening avenues for studying mechanisms of microbial-mediated steroid metabolism and host hormonal physiology.

A stimulus-responsive approach for recapitulating nonviral nucleocapsid assembly on demand under controlled conditions provides a robust platform for applications in synthetic biology and mRNA nanomedicine.

Biochemical, structural and genetic analysis of the shelterin complex reveal that by recruiting RAP1 to DNA, TRF2 directly inhibits DNA-dependent protein kinase to regulate classical non-homologous end joining at telomeres.

At the Golgi, the Dsc ubiquitin ligase complex targets proteins with shorter transmembrane domains for proteasomal or lysosomal degradation. This quality control at the sorting center of cells restricts the uncontrolled spreading of orphaned proteins.

Chromatin “breathing” at DNA lesions is controlled by different waves of histone ADP-ribosylation.

An analysis of data from the Sherlock-Lung study provides insight into the mutational processes that contribute to lung cancer in never smokers, and looks at the possible role of factors such as air pollution and passive smoking.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

Assessing the degree to which medical large language models reliably convey existing, trustworthy knowledge is crucial. This study introduces SourceCheckup, an automated framework revealing that large language models frequently cite medical references that do not fully support, or even contradict, their responses, showing significant gaps in reliability for clinical use.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A survey across 90 societies reveals that variation and change in everyday norms are explained by a single value dimension: the priority societies place on individualizing versus binding moral concerns.

Bacteria produce antibacterials to aid competition in complex communities. Here, the authors show that class II microcins, an understudied group of secreted antibacterials, are abundant, with diverse sequences and antibacterial characteristics.

The mediator protein Rad52 promotes Rad51 binding onto RPA-coated DNA to initiate homologous recombination. Here, the authors show that Rad52 sorts Rad51 into monomers and stacks the complex on to the ss-dsDNA junction. The Rad55-Rad57 paralog then promotes extension of the Rad51 filament.

Redox signalling is emerging as an important regulator of metabolism and physiology, which is dysregulated in ageing and disease. Here, the authors show that redox regulation of a key redox sensitive cysteine in Atg4a induces autophagy in vivo and extends lifespan in female Drosophila.

Genome stability is influenced by nuclear dynamics. Here, the authors show that increasing nuclear envelope deformations via Lamin A removal or sphingolipid synthesis inhibition enhances mobility and mis-repair of PARPi-induced DNA breaks in BRCA1- deficient cells.

The I-BAR protein IRSp53 senses membrane curvature but its physiological role is unclear. Here, the authors show that during early lumen morphogenesis, IRSp53 controls the shape of the apical plasma membrane and polarized trafficking and ensures the correct epithelial tubular architecture and if deleted, affects renal tubules morphogenesis in various organisms.

The transcription factor p63 mediates different cellular responses affecting epithelial and oocyte biology. Here, the authors generate a mouse model (HET Δ13p63 mice) expressing the p63β isoform and show this affects ovary development, phenocopying a human syndrome, primary ovary insufficiency.

Cancer cells can be dependent on mitochondrial respiration to survive. Here, in pancreatic cancer cells, the authors show that monounsaturated fatty acids-linked ether lipids maintain mitochondrial redox homeostasis and modulate sensitivity to inhibition to electron transport chain complex I.

Total cell cycle duration is a key hallmark of cancer initiation, and determines whether defects in apoptosis, senescence, immune surveillance, angiogenesis, DNA repair, polarity and proliferation lead to cancer development.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

The International Union for Conservation of Nature’s Global Ecosystem Typology has been developed to provide a systematic framework for data on all of Earth’s ecosystems in a unified theoretical context to support biodiversity conservation and ecosystem services.

Mitochondrial ribosome biogenesis requires the assistance of multiple assembly factors. Here, the authors provide insights into the essential role of the GTPase MTG3 during small subunit biogenesis and a potential coupling to translation initiation.

Using highly purified protein factors, we provide evidence that BRCA1–BARD1 physically interacts with EXO1, BLM and WRN and upregulates the activity of all three resection pathways.

Jackson et al. provide insight into how metabolic adaptations that accompany cell state transitions drive reliance on exogenous nutrient availability, focusing on pyruvate as a key metabolite in central carbon metabolism.

Grant Stewart, Andrew Jackson, Christopher Mathew, Fowzan Alkuraya and colleagues identify a novel replication fork protein, DONSON, which is important for maintaining genome stability. Mutations in DONSON cause microcephalic dwarfism and lead to stalled replication forks and DNA damage.

Dysfunctions of the mitochondrial OXPHOS system lead to severe human disorders. Here, the authors analyzed a mouse mutant that mimics a mitochondrial disorder patient and find that reactive oxygen species trigger RNA release and inflammatory pathway in liver.