Search

Spatial CRISPR screens probe the functional impact of mutations within intact tissues. Here, authors present Spatial Perturb-Seq, a technology that localizes CRISPR perturbations and cell identities in situ, uncovers communication between cells, and shows how genes act beyond their cellular borders.

Gestational exposure of mice to the obesogen tributyltin alters 3-D chromatin interactions in primordial germ cells leading to stable reduction of hepatic Ide expression and predisposing male descendants to insulin dysregulation and obesity.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

The roles of orbitofrontal and cingulate cortex in emotional decisions remain unclear. Here the authors show distinct timing between caudal orbitofrontal and cingulate signals, that orbitofrontal stimulation increases avoidance, and that physiological responses mirror behavior.

A technique called condense-seq has been developed to measure nucleosome condensability and used to show that mononucleosomes contain sufficient information to condense into large-scale compartments without requiring any external factors.

KRAS is an oncogene that switches between a GDP-bound inactive state and a GTP-bound active state. Recently developed KRAS G12C inhibitors are specific to the GDP-bound inactive state. Here, the authors develop a class of covalent KRAS G12C inhibitors capable of targeting both states for the treatment of KRAS-driven cancer.

Thermal imaging lenses are typically made from expensive materials such as germanium and silicon. Here, the authors synthesise a sulfur-based polymer with high mid-wave infrared and long-wave infrared transparencies, presenting a high-performing, low-cost alternative to traditional thermal imaging lens materials.

A single intravenous dose of the psychedelic dimethyltryptamine, combined with psychological support, produces rapid and lasting reductions in depressive symptoms in adults with major depressive disorder.

The authors show how Vγ1⁺ γδ T cells produce IL-4 to drive early CD8⁺ T cell and dendritic cell responses to malaria infection in mice.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

It is unclear whether the harsh abiotic conditions of drylands hinder biological invasions. This global analysis shows that drylands are vulnerable to non-native plants and are likely to become more so as native plant diversity declines and grazing pressure intensifies.

Using 63 globally distributed grassland and shrubland sites from the International Drought Experiment, this study identified plant traits linked to drought resistance after 1 year of extreme drought across growth forms, lifespans and climate.

Genome-wide association meta-analysis identifies 58 independent risk loci for major anxiety disorders among individuals of European ancestry and implicates GABAergic signaling as a potential mechanism underlying genetic risk for these disorders.

T cells contribute to protection and pathogenesis in tuberculosis. Here the authors sequence T cell receptor repertoires in human skin biopsies from the site of the tuberculin skin test and show enrichment of clonotypes reactive to Mycobacterium tuberculosis using a computational pipeline metaclonotypist to identify distinct TCRs predicted to share peptide-MHC reactivity across participants, as an approach to explore T cell correlates of tuberculosis disease-risk stratification and vaccine efficacy.

A new platform comprising large-scale 2D arrays of quantum dots patterned with sub-nanometre precision, with each quantum dot defined by tens of phosphorus atoms doped into silicon, allows for analogue simulation of quantum materials on arbitrary lattices.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Non-invasive strategies to detect and track activated myeloid cells will facilitate disease diagnosis and monitoring in patients affected by neuroinflammatory disorders. Here, the authors present 18F-FMD, a dendrimer-based PET tracer that detects and monitors activated myeloid cells at different stages (presymptomatic and symptomatic) of Experimental Autoimmune Encephalomyelitis (EAE) in mice and in response to disease-modifying therapies.

Hepatic glycogenolysis is essential for protein glycosylation and rhythmic secretion by the liver. Disruptions to hepatic glycogenolysis, caused by congenital diseases or physiological factors such as obesity, caloric restriction and changes to meal timing, alter hepatic protein secretion.

Genome-wide association analyses using data from 19 biobanks identify variants influencing risk of thyroid diseases and yield polygenic risk scores associated with features of aggressive thyroid cancer.

Protein motion in crowded environments governs cellular transport and reaction rates. Here, the authors use megahertz X-ray Photon Correlation Spectroscopy to reveal anomalous diffusion of ferritin, linking hydrodynamic and direct interactions to cage-trapping at microsecond time scales.

Catalytic breakdown of highly persistent fluorinated pollutants is hindered by limited proton availability and catalyst degradation. This study shows that in situ proton-supplying sites enable low-temperature, long-lasting decomposition of stubborn PFAS gas.

An 11-qubit atom processor comprising two precision-placed nuclear spin registers of phosphorus in silicon is shown to achieve state-of-the-art Bell-state fidelities of up to 99.5%.

MK-7762 is a new oxazolidinone antitubercular agent that is structurally similar to linezolid, and demonstrated in vivo efficacy, lesion penetration and limited toxicity compared to linezolid, indicating it could be used in broad tuberculosis regimens.

Microbial mutualists could affect plant population persistence under climate change. Here the authors show that fungal endophytes contribute to the population persistence of a grass species by ameliorating drought stress but are more likely to disappear locally under climate variability.

More frequent fires in the North American boreal are causing shifts from conifer to deciduous forests. This study finds that when deciduous forests burn, their carbon losses are driven by weather, but are lower than in conifer forests, potentially dampening climate–fire feedbacks.

A wearable paper-based microfluidic device tracks cortisol in sweat via gold nanoflower colorimetric assays and captures circadian rhythms, stress responses and jet lag disruptions.

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).

Peripartum cardiomyopathy (PPCM) is a potentially fatal heart condition with poorly understood molecular causes. Here, the authors show that loss of the protein PTRH2 in female mice leads to postpartum heart failure, identifying it as a potential therapeutic target.

Variants in the PSMC5 gene impair proteasome function and cellular homeostasis, altering brain development in children. This study reveals underlying molecular mechanisms contributing to this neurodevelopmental phenotype, and suggests therapeutic leads for neurodevelopmental proteasomopathies.

Chan and colleagues report that tumor ecosystem and microbiome features are associated with response to anti-PD-L1 avelumab plus chemoradiotherapy in patients with locally advanced head and neck cancer.

Decentralized natural resource governance is thought to aid conservation and reduce poverty, but its heterogeneous local effects are under-explored. A study in Nepal shows that forest governance decentralization reduces poverty but the benefits are greater for dominant ethnic and caste groups compared with minority ones.

Haines et al. developed an MEK–RAF molecular glue called IK-595 that blocks MAPK pathway activation in RAS-mutant and BRAF-mutant cancer cells. IK-595 exhibited high tolerability and strong antitumor effects in preclinical models across cancer types.

Annunziato, Quan and Donckele et al. identify G3BP2 (Ras–GAP SH3 domain-binding protein 2) as a molecular glue-induced neosubstrate of the CRL4^CRBN E3 ubiquitin ligase. The CRBN–glue neosurface uses a molecular surface mimicry mechanism to recruit and degrade G3BP2 in a compound-dependent manner.

An ultrasmall particle adjuvant therapy reprogrammes the tumour microenvironment of a resistant melanoma to a pro-inflammatory state, enhances antitumour immunity and synergizes with immune checkpoint inhibitors to prolong survival in murine models.

Generalised pustular psoriasis (GPP) is a severe type of psoriasis characterized by epidermal neutrophil infiltration and potentially life-threatening flares. Here the authors use single cell and spatial transcriptomic analysis of skin samples implicating contact between IL36G+ keratinocytes and neutrophils as well as ligand-receptor interactions of fibroblasts with T cells, neutrophils or macrophages.

Two-dimensional polyaramid polymers are synthesized to form nanofilms that exhibit the lowest gas permeability of any polymer by orders of magnitude, despite lacking crystallinity, enabling molecular-scale nanomechanical resonators and barrier materials.

Lung adenocarcinomas bearing the ID2 mutational signature display increased LINE-1 retrotransposon activity, which contributes to their fast evolutionary dynamics and aggressive phenotype.

Here they developed an inflamed human intestinal organoid model and used it to build a scRNA-seq perturbation atlas of microenvironmental cues in the context of inflammatory bowel disease.

Transcription factor osr2 is identified as a specific marker and regulator of mural lymphatic endothelial cell (muLEC) differentiation and maintenance, and muLECs and border-associated macrophages share functional analogies but are not homologous, providing an example of convergent evolution.

Reservoir computing is efficient but sensitive to hyperparameters and often neglects excitatory–inhibitory balance. Here, authors introduce self-adapting mechanisms inspired by neuronal dynamics that improve robustness, reduce fine-tuning needs, and boost performance across memory and prediction tasks.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

It is 100 years since the initial development of quantum mechanics, and not only did it bring with it a greater understanding of the world around us, it also introduced a new lexicon. Now, Michelle Francl wonders how the language of quantum mechanics has been flipped to the dark side and appropriated by pseudoscience.

Asexual-to-sexual switching underpins malaria transmission. Prajapati et al. identify an AP2-G loss-of function mutation and use it as a genetic tool to show that GDV1 is essential for initial ap2-g activation and sexual commitment initiation.