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It remains unclear why some BRCA-deficient high-grade serous carcinomas (HGSC) do not respond to platinum-based therapy. Here, multi-omic analysis of BRCA1- and BRCA2-deficient HGSC attributes co-occurring mutations, DNA repair deficiency and tumor microenvironment features to short survival in these patients.

Proteomic data from natural isolates of Saccharomyces cerevisiae provide insight into how these cells tolerate aneuploidy (an imbalance in the number of chromosomes), and reveal differences between lab-engineered aneuploids and diverse natural yeasts.

Perovskite/silicon tandem solar cells face challenges in efficiency and stability. Agresti et al. introduce a MXene-based surface dipole passivation to form a field-effect junction in semi-transparent perovskite modules, achieving efficiencies above 16% on 60 cm². Integrated four-terminal tandems exceeds 19% efficiency and retain 95% of initial after three months of outdoor operation.

Here the authors report that brown adipocyte-derived vaspin reduces heat-producing activity in brown fat by blocking adrenergic signals, helping to regulate energy expenditure and maintain metabolic balance.

Glaciers lost 408 ± 132 Gt of mass during the hydrological year 2025, equivalent to 1.1 ± 0.4 mm sea-level rise. Since 1975, glacier mass loss has totalled 9,583 ± 1,211 Gt, equivalent to 26.4 ± 3.3 mm of sea-level rise, with six of the highest mass-loss years on record occurring in the past seven years.

Neural crest cells differentiate into skeletogenic mesenchyme and neuro-glial lineages, thereby contributing to craniofacial formation. Here, single-cell analysis of cranial neural crest shows that specific rRNA modification and ribosome assembly factors contribute to skeletogenic fate. Their disruption causes craniofacial defects, while high levels in neuroblastoma predict poor survival.

Rearrangement of the B cell receptor is sequential, and pairing of the successfully assembled heavy chain with the surrogate light chain proteins VpreB and λ5 to form the pre-B cell receptor is an important checkpoint signal for continued B cell development. Here, the authors show that λ5 plays a key role in the multi-step assembly process involving association-induced folding reactions.

Here, the authors solve a series of cryo-electron microscopy structures that show how transfer RNAs (tRNAs) can guide the assembly of the multisubunit poxvirus RNA polymerase, uncovering a role of tRNA as an assembly chaperone.

Molecular glue degraders have consistently been discovered retrospectively, despite their increasing importance. Herein, a high-throughput approach is described that modifies existing ligands into molecular glue degraders.

Acinic cell carcinoma (AciCC) is a rare salivary gland carcinoma that is poorly understood. Here the authors perform genomic, transcriptomic and epigenomic profiling of AciCC and find highly recurrent and specific rearrangements [t(4;9)(q13;q31)], which lead to enhancer hijacking that activates oncogenic transcription factor NR4A3.

During synthesis, modification and maturation of the ribosomal RNA, correct subdomain folding without additional guidance poses a major challenge. Here, the authors observe the snR30 H/ACA snoRNP forming a “satellite particle” with the 90S, the earliest known pre-ribosome, where localized structural interactions guide its independent folding.

The function of VCP/p97 AAA-ATPase cofactor UBXD1 and its UBX domain has been elusive. Here the authors show that the extended UBXD1 UBX domain is located at the p97 pore exit where it binds ubiquitin, suggesting that UBXD1 receives unfolded substrates and hands them off for down-stream processing.

Extensive lysosomal damage can result in cell death but how limited protease leakage affects cytoplasmic organelles in viable cells is not well understood. Here the authors show that limited lysosomal damage leads to changes in the mitochondrial proteome and the modulation of macrophage immunometabolism.

Characterizing proteases in their native environment is still challenging. Here, the authors develop a proteomics workflow for analyzing protease-specific peptides from cell lysates in 96-well format, providing mechanistic insights into blood proteases and enabling the prediction of protease substrates.

Wang, Kronenberg-Tenga, Rosti and colleagues use several structural approaches to analyze the distribution of nucleosomes at the lamin–chromatin interface, test the impact of lamins on nucleosome density and identify a lamin A nucleosome-binding motif.

A fundamental step in membrane protein biogenesis is their integration into the lipid bilayer with a defined orientation of each transmembrane segment. Here, the authors show that mutations in connexin 32 can cause failures in membrane integration which is detected by the ER chaperone machinery.

Conversion of one-carbon feedstocks to more complex structures is vital for the production of bulk chemicals. Here, the authors report a highly selective method for the conversion of carbon monoxide to ethylene glycol by means of an oxamide intermediate.

Early development is controlled by maternally deposited mRNAs and the RNA-binding proteins (RBPs) that regulate them. Here the authors describe the identification of a large number of RBPs bound to polyadenylated RNAs in Drosophilaembryos before and after the maternal-to-zygotic transition, revealing changes in RBPs activity during development.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

In order to use early, non-noble transition metals in homogeneous catalysis, complex ligands are typically needed, offsetting the benefits of inexpensive metals. Here the authors show that a simple manganese complex can be used in the hydrogenation of N-heteroarenes, without the need for additional ligands.

Methylmalonic acidemia is an inherited metabolic disease caused by loss or mutation of the enzyme MMUT. Here the authors use cell and animal models to show that MMUT mutations lead to defective mitophagy and stress in kidney cells, contributing to the pathogenesis in methylmalonic acidemia patients.

Despite some well-characterized functions in cancer, the impact of most long non-coding RNAs remains unknown. Here, the authors discover the lncRNA lincNMR which is upregulated in cancer and drives cell proliferation by interacting with YBX1 and controlling nucleotide metabolism.

Ubiquitination is a versatile modification system in eukaryotic cells. Here, the authors unveil that the ubiquitin ligase HUWE1 can modify drug-like small-molecule substrates, beyond proteins. This discovery may be harnessed to develop specific tool substrates or inhibitors of HECT-type ligases.

Proteomic, transcriptomic, and genomic analysis has shown osteosarcoma (OS) to be a complex and heterogenous disease but revealed little about its carcinogenesis or potential therapeutic targets. Here, the authors profile the RNA interactome, transcriptome and proteome of cells derived from OS patients, identifying a targetable vulnerability to translation inhibition.

Here, the authors present the cryo-EM structure of in vitro amyloid fibrils from recombinant SAA1.1 protein that were formed by seeding with fibrils purified from systemic AA amyloidosis tissue. This in vitro fibril structure resembles the structure of the ex vivo fibrils but differs from unseeded in vitro fibrils. These findings show that fibril morphologies can be propagated in vitro by seeding.

Dysfunction in insulin secretion is a main driver of type 2 diabetes development. Here the authors monitor phosphoproteome modulation in cells stimulated with glucose and treated with drugs affecting glucose-mediated insulin secretion to reveal phosphorylation sites implicated in insulin secretion control and gene expression regulation.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Ammonium levels in Greenland ice cores track changes in soil emissions and wildfires, primarily in North America. Ice-core ammonium records show abrupt increases in wildfire activity during brief warmings in the last glacial period.

CtBP is a transcriptional master co-repressor with oncogenic activity. Here, the authors use structural and biophysical methods to show that CtBP interacts with RAI2 through SLiMs that induce CtBP polymerization and inactivation.

Medulloblastomas (MBs) are highly heterogeneous paediatric brain tumours that remain challenging to treat. Here, the authors integrate proteomics, epigenomics, transcriptomics and post-translational modification analyses to find molecular subgroups and potential therapeutic targets in MB tumours.

Kinase inhibitors are key in cancer therapy, but resistance limits their efficacy. Here, the authors develop SPIED-DIA, a phosphoproteomics method enhancing detection of key phosphorylation sites. They reveal a synergistic MEK-JNK signaling response in colorectal cancer cells, suggesting a potential therapeutic strategy.

A combination of proteomics and structural analyses reveals the assembly mechanism of transcription factor TFIID in human cells and identifies the chaperonin CCT as a checkpoint in the process.

Systemic AA amyloidosis is a protein misfolding disease caused by the formation of amyloid fibrils from serum amyloid A (SAA) protein. Here, the authors present the cryo-EM structures of AA amyloid fibrils isolated from mouse tissue and in vitro formed fibrils, which differ in their structures and they also show that the ex vivo fibrils are more resistant to proteolysis than the in vitro fibrils and propose that pathogenic amyloid fibrils might originate from proteolytic selection.

Neutrophils infiltrate the ischemic brain. Here, the authors show a disease-stage dependent neutrophil diversification in neonatal brain injury; neutrophils aggravating tissue damage in the acute phase while promoting regeneration in the later stage.

TGF-β family cytokines control essential cell fate decisions via receptor regulated SMAD (R-SMAD) transcription factors. Here the authors identify an inner nuclear membrane phosphatase complex that dephosphorylates R-SMADs to inactivate TGF-β signaling.

Leucine-rich repeat (LRR) domains are commonly present in immune regulatory proteins. Here the authors show that LRR exonic modularity and alternative splicing of an LRR-containing protein, NLRP3, modulate the ratio of functional/afunctional NLRP3 isoforms to instill a stochastic regulation of NLRP3-mediated inflammation and innate immunity.

In hepatocellular carcinoma driven by non-alcoholic steatohepatitis, aberrant T cell activation and impaired immune surveillance seem to make hepatocellular carcinoma less responsive to anti-PD1 or anti-PDL1 immunotherapy.

Task paradigms allowing studies on the core ethological function of the whiskers are lacking. Authors here present a task for freely moving mice that enables the study of how the brain processes touch and learns. The setup combines behavior, electrophysiology, and imaging, offering insights into naturalistic sensory and decision-making processes.

Hydrogen borrowing is an attractive method for C-N bond formation - avoiding multiple alkylation products and reducing waste - but often is carried out with noble metals. Here the authors show that a manganese catalyst allows the selective N-alkylation of amines with alcohols.

The conversion of alkenes to esters is performed on a large scale worldwide, but relies on the use of toxic and flammable carbon monoxide. Here, the authors show a catalytic system where carbon dioxide—normally unreactive, but cheap and abundant—can be employed instead.

TFIID is an essential transcription factor complex that controls the expression of most protein-coding genes in eukaryotes. Here the authors identify and characterize a complex containing TAF2, TAF8 and TAF10, which assembles in the cytoplasm before integration into the nuclear holo–TFIID complex.

Alborzinia et al. report that MYCN-amplified neuroblastoma undergoes ferroptosis in the absence of intracellular cysteine, suggesting a combination of cysteine depletion and concomitant GPX4 inactivation as a potential therapeutic approach.

The suppression of edge-localized modes in tokamak plasmas is crucial to prevent them from damaging the walls of the chamber. Now experiments confirm the role that magnetic islands play in suppressing these detrimental modes.