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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.

How the ensemble encoding of social and anxiety-related behaviors interacts with encoding of context in the prefrontal cortex of mice is not fully understood. Here authors examine how prefrontal neurons encode socioemotional behaviors in different contexts and reveal that the prefrontal cortex encodes context-invariant representations of these behaviors in parallel with representations of context.

Analysis of 10 years of satellite radar data with a deep learning model reveals historical flood patterns often missed in prior datasets. This dataset also enables analysis of trends in flooding, showing hints of increases in flood extent over time.

Cluster states are a key resource in quantum technologies, but generation of large-scale 2D cluster states faces several difficulties. Here, the authors show how to generate a 2 × n ladder-like cluster state via sequential emission of time- and frequency multiplexed photonic qubits from a transmon-based device.

Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathogenic variants in RNU4-2.

Thirty years ago, I had the privilege of launching Nature Genetics, the first spin-off journal bearing the famous Nature logo. Spurred on by the Human Genome Project, there were high hopes for the new journal and indeed the future of human genetics. But there was little expectation that we would launch a science publishing franchise of more than 30 sister journals — or be able to therapeutically rewrite the faulty genomes of patients. Here, I reflect on the humble beginnings of Nature Genetics and 30 years of progress in genetics.

Environmental justice and drinking water in the US: Higher proportions of Hispanic/Latino, American Indian/Alaskan Native, and non-Hispanic Black residents were associated with higher public water arsenic and uranium at the county-level, findings differed by region.

As large-scale neurodevelopmental MRI studies gain prominence, the authors identify tradeoffs between sample size and quality control that can dramatically affect results, and they evaluate a range of approaches to mitigate risk for error.

This study used fine-mapping to analyze genetic regions associated with bipolar disorder, identifying specific risk genes and providing new insights into the biology of the condition that may guide future research and treatment approaches.

Transcranial focused ultrasound can be used for neuromodulation, but its use in wearable systems remains challenging. The authors present a miniaturised wearable ultrasound device, integrated with a bioadhesive hydrogel for stable, long-term somatosensory cortical stimulation.

A CRISPR knock-in strategy that uses endogenous gene regulatory mechanisms can engineer ‘armoured’ CAR T cells that secrete proinflammatory cytokines directly within a tumour without causing toxicity, leading to prolonged survival in mice.

Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

Endosomal sequestration of lipid-based nanoparticles is a barrier to delivery of nucleic acids. Here the authors test an array of cholesterol variants and perform in-depth investigation of nanoparticle shape, internal structure and intracellular trafficking.

A study presents a strategy based on human pluripotent stem cells for treating neurodegenerative disorders of the gastrointestinal tract.

Toxic chemicals can transform in the environment, often forming more harmful products. This study provides evidence for the aqueous formation of organophosphate esters (OPEs) in aerosols, highlighting their fate and implications for risk assessment.

Current intracortical brain-computer interfaces are subject to recording interface instabilities that degrade decoding performance. Here, the authors present a platform for Nonlinear Manifold Alignment with Dynamics (NoMAD), which stabilizes decoding using models of dynamics for at least 3 months.

Rhine et al. find that neuronal aging leads to widespread dysregulation of RNA biology, including mislocalization of splicing proteins like TDP-43, chronic cellular stress and reduced resiliency.

Arctic marine ecosystems have experienced significant change through the Holocene. Here, the authors used sedaDNA from Northern Greenland to reconstruct marine mammal occurrence, demonstrating the impact of air temperature and sea ice cover over the past 12000 years.

Analysis of data from multiple instruments reveals a giant exoplanet in orbit around the 0.2-solar-mass star TOI-6894. The existence of this exoplanetary system challenges assumptions about planet formation and it is an excellent target for atmospheric characterization.

N-terminal acetylation dysregulation in the heart causes severe arrhythmia and cardiomyopathy. The authors show that stem cell models demonstrate ion channel trafficking defects and sarcomeric disarray as the underlying mechanisms, with gene therapy reversing both phenotypes

The chromatin-remodelling enzyme ATRX and the transcription factor HNF4A are identified as pivotal regulators of colonic epithelial identity, with roles in metastasis in colorectal cancer.

The histone methyltransferase ASH1L has been linked to tumorigenesis, mainly in leukemia. Here, authors report that ASH1L cooperates with HIF-1α to induce a pro-metastatic transcriptome in prostate cancer cells, and promotes conversion of monocytes to lipid-associated tumor-associated macrophages in the bone metastatic niche.

Single and multiple intravenous infusions with laromestrocel, an allogeneic cell therapy, is safe in patients with mild AD and may reduce the impact of cognitive decline and brain atrophy within 9 months of treatment.

Bellaart et al. address how the ubiquitin ligase tripartite motif-containing protein 37, the gene for which is mutated in Mulibrey nanism, uses peptide motif recognition and substrate-directed oligomerization to prevent the formation of ectopic spindle poles that cause chromosome missegregation.

Acquiring biomarkers from blood or sweat is limited by invasiveness or biofouling. Skin gas emissions bypass these issues, offering rich biosignals. Authors present passive sensing strategies capturing water vapor (Sweat rate), CO2, and VOCs, enabling real-time tracking of physiological changes.

Mutations of the histone H3K36-specific methyltransferase ASH1L have been linked to several human diseases. Here, the authors report the mechanism by which three C-terminal domains in ASH1L regulate its enzymatic activity and interact with chromatin.

MGAT1 is a glycosyltransferase critical for the synthesis and maturation of complex N-glycans. Here, the authors show that MGAT1 modulation of CD73 glycosylation and function regulates tumor immune response in triple-negative breast cancer.

Comparison of paired primary and recurrent glioblastomas at the single-cell transcriptomic level describes molecular and cellular trajectories associated with tumor recurrence, highlighting extensive heterogeneity and microenvironmental co-evolution.

Doa10/MARCHF6 is a conserved E3 ubiquitin ligase in the endoplasmic reticulum (ER) membrane in eukaryotes, but its molecular mechanism was unknown. The authors combine cryo-EM, computational and biochemical analyses to reveal how Doa10 recognizes its substrate proteins for ER-associated degradation.

Citizen science taps the efforts of non-experts. Here, authors describe Drugit, an extension of the crowdsourcing game Foldit, and its use in designing a non-peptide binder of Von Hippel Lindau E3 ligase for use with proteolysis targeting chimeras.

Microglia are brain macrophages that engulf and clear cellular material and protein aggregates. Here, the authors show that lipofuscin-like autofluorescence can confound microglial engulfment analyses, which they can resolve with a photobleaching protocol.

Long-circulating, transfection-competent LNP-mRNA systems are key for effective extrahepatic delivery. Here, authors show that LNPs with high bilayer lipid ratios yield high mRNA encapsulation, prolonged circulation, and enhanced transfection in extrahepatic tissues.

This study reports the structural characterization of C1q-like protein 3 (C1ql3) with adhesion-GPCR brain-specific angiogenesis inhibitor-3 (BAI3).

Spatial multi-omics analysis tools have lagged behind advancements in single-cell technologies. Here, authors introduce TACIT, a scalable tool for automated cell type and state deconvolution from spatial multi-omics datasets, improving accuracy and efficiency over existing methods.

In this work, researchers engineer HIV-1 immunogens using molecular dynamics simulations to enhance vaccine designs that select for specific antibody mutations. Their approach improved the selection of mutations crucial for broadly neutralizing antibody responses, offering a promising strategy for HIV vaccine development.

Children receiving chest radiotherapy for childhood cancer have a higher risk of developing breast cancer later in life. Here, using the data from the Childhood Cancer Survivor Study, the authors investigate the treatment and survival outcomes of breast cancer patients who previously survived childhood cancer finding them to receive altered treatment and having increased mortality.

Astrocytes perform intriguing roles in neural circuits. Here, the authors show that in striatum, astrocytes adopt a satellite-like proximity to cholinergic interneurons, modulating excitability and downstream dopamine release on subsecond timescales.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.

Bacterial proteins are often recruited to specific subcellular locations to carry out their functions. Here, the authors use the optogenetic CRY2-CIB1 system to re-direct proteins to different subcellular locations, and thus manipulate the proteins’ functions, in live bacterial cells.

Familial adenomatous polyposis (FAP) is an inherited gastrointestinal syndrome associated with duodenal adenoma formation. Here the authors show that IL17A-producing NKp44- group 3 innate lymphoid cells accumulate in FAP duodenal tissue and are associated with duodenal adenoma formation in patients with FAP.

Flood management solutions are typically local and do not consider how the space–time connectivity of floods is exacerbated by built infrastructure. Through a case study of the 2014 flood in Southeast Michigan, which flooded where there was no rainfall, this Article examines key factors contributing to urban flooding and the implications of design choices on inundation.

Nsp15 is an endoribonuclease that helps coronaviruses evade detection of host immune sensors. Here, the authors combine biochemistry, NMR, and cryo-EM to show that spontaneous base flipping drives specificity in double stranded RNA substrates.

Dynamic control of light flow in 2D synthetic landscapes is emerging as a valuable tool for the development of light-based technologies. Here the authors harness time-dependent non-Hermitian Hamiltonians to demonstrate dynamic control over the skin effect.

Atharva Deo and colleagues present a Super-Turing synaptic resistor circuit to control a morphing wing in complex aerodynamic environments. The circuit features high-speed concurrent learning and inference, ultra-low power consumption, and agile adaptability for AI systems.

Lape et al. use electronic health records and a discovery-replication cohort study design to investigate links between common pathogens and non-communicable diseases. Evidence is found for over 200 associations, such as a role for human cytomegalovirus in ulcerative colitis.

CRISPR-Cas12a is a programmable endonuclease used for genetic engineering. Here, the authors use real-time single-molecule measurements to show that Cas12a unwinds the target DNA site in dynamic and reversible steps to test for matches with its guide RNA molecule.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Neurons receive their input in three dimensions via their dendrites, but how electrical activity in dendrites is organized is unknown. Here, the authors work out the distinct rules that govern activity across this 3D structure in different brain states.

The hippocampus contributes to path integration, but the firing patterns supporting this function are unknown. Here, the authors found that the activity of hippocampal neurons during a path integration task predicted the animal’s homing direction.