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Native top-down proteomics reveals epidermal growth factor receptor–estrogen receptor-alpha (EGFR–ER) signaling crosstalk in breast cancer cells and dissociation of nuclear transport factor 2 (NUTF2) dimers to modulate ER signaling and cell growth.

The CMS experiment at CERN reports one of the highest-precision measurements of the W boson mass, finding it in line with standard model predictions and at odds with recent anomalous measurements.

Global Burden of Disease analysis found that in 2023, suboptimal diet was estimated to be responsible for 4 million deaths and 97 million morbidity burdens from ischemic heart disease.

The excitatory neuron diversity and specialized connectivity of complex, multilayered mammalian neocortex are driven by mammalian-specific cis-regulatory elements bound by ZBTB18, deletion of which disrupts gene expression and results in projection patterns resembling those of non-mammalian brains.

A large-scale study on the replicability of claims from social and behavioural science journals reports that about half of the results replicate in the same patterns as the original study.

Here, Deol et al. use genetic screens in gene-edited reporter cell lines to identify regulators of ferroptosis suppressor protein 1 (FSP1) expression and stability. They show that vitamin B2 metabolism stabilizes FSP1 through flavin adenine dinucleotide binding, preventing its degradation and ferroptosis sensitization.

Frenster et al. utilize mosaic mouse gastruloids as a model of cell fitness and competition, identifying a temporal window between primed pluripotency and early gastrulation during which cell competition occurs in mammalian embryogenesis.

To dissect lncRNA functions in aging, here the authors perform a CRISPRi-based single-nucleus multiomics screen systematically perturbing 32 aging- and senescence-associated lncRNAs and measuring matched changes in gene expression and chromatin accessibility. They pinpoint a role for HOTAIRM1 linked to DNA repair-related gene control and show that replenishing HOTAIRM1 in mouse lungs reduces fibrosis.

Computationally designing proteins with interfaces that bind small molecules has posed a long-standing challenge. Here, authors combine deep learning and physics-based approaches to design proteins that bind small molecules, and demonstrate their approach by designing a cortisol biosensor.

In this study, the authors present optimization and efficacy testing of apolipoprotein-based lipid nanoparticles for delivering various nucleic acid therapeutics in vivo to immune cells and their progenitors in the bone marrow.

Epigenetic programming of myeloid and CD4⁺ T cells promotes decay of the SIV reservoir in rhesus macaques and a similar molecular pathway is found in HIV elite controllers.

MAU2’s role in Cornelia de Lange syndrome was unclear. Here, the authors identify pathogenic MAU2 variants that disrupt NIPBL–MAU2 function, define MAU2‑specific episignatures, and show variable CdLS‑related phenotypes, supported by a Mau2 knockout mouse model.

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.

SWI/SNF complexes are mutated in 20% of cancers, yet the underlying mechanisms are poorly understood. Here, the authors identify a compensatory mechanism of chromatin regulation that becomes essential in cancers carrying mutations that broadly inactivate SWI/SNF.

Nudt21-mediated 3′UTR regulation orchestrates tissue regeneration through dose-dependent control of stem cell differentiation and multiprotein complex assembly, revealing alternative polyadenylation as essential for organismal survival.

The identification of cellular targets for natural products that potently inhibit the growth of cancer cell lines implicates oxysterol-binding proteins in the growth of cancer cells. These natural products, termed ORPphilins, also affect sphingomyelin biosynthesis.

Despite enormous resources expended, lead exposure in endangered California condors has risen. The authors show lead ammunition bans and outreach are effective, with changing hunting patterns and wilder condor behavior explaining exposure increases.

Catabolism of extracellular glutathione by γ-glutamyltransferases supports tumour growth and survival, and pharmacological targeting of these enzymes slows tumour growth.

Reduced fitness of the tumor microenvironment is mediated by a long non-coding RNA expressed in tumors.

APC/C activity is transiently inhibited to generate a pulse of glycolysis that is required for mammalian cell cycle entry.

The combination of within-species variation in pathogen load, the shape of the relationship between pathogen load and infectiousness, and vector feeding preferences shape transmission of multi-host vector-borne pathogens. Here, the authors use experimental and wild bird infection data to characterize the role of 17 host bird species in avian malaria transmission in Hawaii.

Markiewicz-Potoczny et al. report that the nonsense-mediated mRNA decay pathway protects telomeres in the absence of core Shelterin component TRF2 by regulating the stability and abundance of TRF1 at telomeres.

Segmented Filamentous Bacteria (SFB) in mice are important gut commensals in both health and disease. Here, Kiran et al. characterize a novel human SFB species that is widespread in Africa and show that humans worldwide harbor multiple SFB species and at least six SFB lineages.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

Functional studies of O-GlcNAcylation have often focused on individual modifications. Now, a systems-level approach has identified simultaneous O-GlcNAcylation events that coordinate cellular activities and tissue-specific functions.

The existence of phosphatases specialized in regulating the axon initial segment (AIS) was unclear. Here, the authors show that a PP2A-B55 subunit is selectively enriched at the AIS and contributes to its local phospho-regulation.

Assessment of how 16 taxonomic groups in a lowland tropical forest resist and recover from anthropogenic disturbance shows the potential of protecting naturally regenerating secondary forests to reverse biodiversity losses.

Hodgson, Huang, Lang et al. show that TDP-43 limits ribonucleoprotein particle condensation into paraspeckles in a concentration- and polymerization-dependent manner. They also link paraspeckle condensation to stress response and neuroprotection.

Taniuchi and colleagues show that differential phosphorylation of the terminal Y residue in Runx proteins connect MHC restriction with the helper versus cytotoxic T cell lineage choice.

Genetic analyses in more than 15,000 individuals from across the Americas, including individuals with autism and family members, define the genetic landscape of autism in Latin American populations and identify significant overlap with other ancestries.

Systematic screening of transcription factors reveals conserved mechanisms governing cortical radial glia lineage progression across primates and provides a framework for functional dissection of gene regulatory networks in human cortical neurogenesis.

N¹-Methylpseudouridine enhances the translation of synthetic mRNAs, independently of innate immunity.

In this study, long-read RNA sequencing achieves accurate single-nucleotide polymorphism calling, haplotype phasing and allele-specific expression analysis.

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.

Circulating tumor cell (CTC) clusters are key drivers of metastasis, yet their formation in tumors lacking classical adhesion molecules is unclear. Here, the authors discover that hyaluronic acid promotes homotypic and heterotypic CTC clustering by initiating early cell contacts and stabilizing mature interactions.

Taxanes, such as docetaxel or cabazitaxel, are one of the few chemotherapy options for metastatic castration-resistant prostate cancer (mCRPC). Here, the authors discover that FOXJ1 modulation of microtubule dynamics regulates resistance to docetaxel in mCRPC.

Paternal obesity impacts offspring health, though the underlying mechanisms remain poorly understood. Here, the authors show that male obesity drives adipose mitochondrial dysfunction in F₁ mouse progeny via a let-7-DICER axis, identifying a pathway for intergenerational metabolic inheritance

Glucocorticoid receptor activation is a key driver of resistance of triple-negative breast cancer to both CD8⁺ T cells and natural killer cells during initial metastatic seeding.

Smyth et al. demonstrate that a cellular inhibitor of apoptosis, cIAP2, exacerbates inflammation and cardiac injury after myocardial infarction and that its inhibition, either genetically or via Smac mimetics, offers a promising immunotherapeutic strategy to reduce post-MI damage and progression to heart failure.

Cyclin B1 is a mitotic co-factor of CDK5.

Viral ribonucleoprotein–viral protein networks form pre-replication centres that nucleate viral factories and drive respiratory syncytial virus replication.

Stanage et al. identify a role for transfer RNA nuclease SLFN11 in replication-stress-induced cell death in cisplatin-treated cells lacking PrimPol. SLFN11 is activated upon single-stranded DNA accumulation at stalled forks followed by replication protein A exhaustion and cell death.

Phylogenetic and functional analyses across 34 Lepidoptera and 183 plant species show that hexenal isomerases found in Lepidoptera exhibit functional convergence with those found in plants despite having evolved independently from unrelated enzyme families.

Targeting FSP1 in lymph nodes has considerable potential for blocking melanoma progression.

Subcellular compartmentalization of the glycolytic enzyme PFKM regulates cell fate and metabolic switch during skeletal muscle differentiation.

This article shows how mutations causing the neurodevelopmental syndrome NEDAMSS and related disorders are associated with the aberrant intracellular condensation of the IRF2BPL protein, which triggers cellular and molecular disease mechanisms.

Primary angle-closure glaucoma is a leading cause of blindness. Here, the authors identify rare deleterious variants in UBOX5 as risk factors and implicate BIP ubiquitination as a potential disease mechanism.

Structural features of DNA double-strand break (DSB) ends play key roles in determining DNA repair pathway usage and outcomes. Here, the authors identify ERCC6L2, a poorly characterized ATPase, as playing a minimal role in blunt end DSB repair but crucial for repair of staggered end DSBs.

CRISPR–Cas9 screening identifies CLCC1 as a factor that increases neutral lipid flux to prevent hepatic steatosis and promotes nuclear pore complex assembly by promoting membrane bending and fusion.