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CLASSIC is a high-throughput genetic profiling platform that combines long- and short-read next-generation-sequencing modalities to quantitatively assess pools of constructs of arbitrary length containing diverse genetic part compositions.

Enzymes are highly selective and sustainable catalysts for chemical synthesis, but their optimization is often limited by the difficulty of identifying functional starting points. This study shows that using the GenSLM protein language model to design TrpB variants can yield stable, active enzymes with broad substrate promiscuity, outperforming natural and evolved counterparts and demonstrating the potential of generative models to accelerate biocatalyst discovery.

Kyle Gaulton, Mark McCarthy, Andrew Morris and colleagues report fine mapping and genomic annotation of 39 established type 2 diabetes susceptibility loci. They find that the set of potential causal variants is enriched for overlap with FOXA2 binding sites in human islet and liver cells, and they show that a likely causal variant near MTNR1B increases FOXA2-bound enhancer activity, providing a molecular mechanism to explain the effect of this locus on disease risk.

Donahue et al. show that ageing is associated with changes in ER morphology. ER-phagy drives age-associated ER remodelling through tissue-specific factors.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

Combining 32 genome-wide association studies with high-density imputation provides a comprehensive view of the genetic contribution to type 2 diabetes in individuals of European ancestry with respect to locus discovery, causal-variant resolution, and mechanistic insight.

Trans-ethnic analyses of exome array data identify new risk loci for type 2 diabetes. Fine-mapping analyses using genome-wide association data show that the index coding variants represent the likely causal variants at only a subset of these loci.

Saccadic eye movements during free viewing exhibit patterns that reflect a strategy to increase neural responses by matching motor behavior with the statistics of the natural world and with the processing limitations of sensory systems.

Due to the crystal symmetry of single-layer transition metal dichalcogenides and the fact that the conduction and valence band edges are at the zone-edge K points, the 2p exciton states are split. A two-colour pump–probe scheme is used to drive the 1s–2p exciton transition, and then probe the changes in absorption near the spectral position of the 1s line to measure the splitting energy.

Analysing the causal links of gene expression and protein abundance on type 2 diabetes risk in blood and seven tissues related to the disease from individuals of four ancestries, the authors advance our understanding of the genetic architecture of type 2 diabetes

Voltage-gated potassium channels cycle between closed and open states through poorly-defined transitions. Pless and colleagues incorporate artificial amino acids into Shaker potassium channels and find that that the negative electrostatic surface potential of Phe481, destabilizes the channel open state.

Confocal Airy beam integrated with single-photon oblique light-sheet tomography (CAB-OLST) is a high-throughput imaging approach for brain-wide mapping of neurons, as demonstrated in cleared mouse brains.

scooby achieves DNA sequence-based single-cell level modeling of RNA-sequencing coverage and ATAC-sequencing insertion profiles by adapting a deep learning model that predicts bulk RNA-sequencing coverage.

The deactivation of CO₂ reduction electrocatalyst in microbial media remains a key barrier for hybrid bio-electrochemical systems. Here, the authors present a bioadaptive nickel single atom catalyst that resists organic poisoning to enable high-rate CO-mediated isopropanol production from CO₂.

MedHELM, an extensible evaluation framework including a new taxonomy for classifying medical tasks and a benchmark of many datasets across these categories, enables the evaluation of large language models on real-world clinical tasks.

Radiation reaction (RR) on particles in strong fields is the subject of intense experimental research, but previous efforts lacked statistical significance due to the extreme regimes required. Here, the authors report a 5σ observation of RR and obtain strong, quantitative evidence favouring quantum models over classical, using an all-optical setup where electrons are accelerated by a laser in a gas jet before colliding with a second, intense pulse.

Allele-preferential transcription factor binding can influence pancreatic ductal adenocarcinoma risk loci function. Here, the authors show allele-specific JunB and JunD binding at chr1p36.33 and propose a role for KLHL17 in protein homeostasis by mitigating inflammation.

This study applies large language models (LLMs) to analyze language used for the description of psychopathology across clinical questionnaires and uses empirical data from four large-scale datasets. The authors find that the empirical structure of psychopathology is well represented in LLMs.

iGluSnFR4f and iGluSnFR4s are the latest generation of genetically encoded glutamate sensors. They are advantageous for detecting rapid dynamics and large population activity, respectively, as demonstrated in a variety of applications in the mouse brain.

DYNA fine-tunes genomic foundation models with disease specificity using a Siamese network. It generalizes to rare-variant test sets and replicates results in ClinVar, advancing variant effect prediction for cardiovascular diseases and RNA splicing.

Here the authors show that tissue-resident memory and exhausted T cells in tumors are distinct populations that are shaped by relative presence or absence of TCR signals, suggesting that a tailored therapeutic strategy is needed to target each subset.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

Mapping of multi-omic molecular quantitative trait loci associated with tandem repeat size variation in up to 4,412 human brain samples from 1,597 donors offers insights into how these variants affect gene regulation and mediate disease risk.

JWST’s COSMOS-Web survey is used to create an ultra-high-detail dark matter map, revealing hidden filaments, clusters and distant structures. By tracing features out to z = 2, this map shows how dark and luminous matter build the cosmic web across cosmic time.

Here the authors use UK Biobank data to identify 251 genetic loci associated with serum triglycerides to HDL-cholesterol ratio, a surrogate marker for insulin resistance. Key genes, including PLA2G12A, PLA2G6, and TNFAIP8, offer potential therapeutic targets for metabolic diseases.

Fine-mapping of blood cell traits in the UK Biobank identifies putative causal variants and enrichment of fine-mapped variants in accessible chromatin of hematopoietic progenitor cells. The study provides an analytical framework for single-variant and single-cell analyses of genetic associations.

Here the authors perform a gene knockout screen in myeloid cells, identifying 295 genes regulating interleukin-1β production, of which 57 lie in regions associated with inflammatory disease risk. The study sheds light on genetic control of interleukin-1β in inflammation, beyond previously known factors.

A flexible micro-electrocorticography brain–computer interface that integrates a 256 × 256 array of electrodes, signal processing, data telemetry and wireless powering on a single complementary metal–oxide–semiconductor substrate can provide stable, chronic in vivo recordings.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

This study projects the private costs and monetized climate and health damages of electrifying long-haul heavy-duty diesel trucks. Battery electric trucks yield net positive societal benefits by 2035, contingent on policies that accelerate adoption.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Blood metabolites are influenced by a combination of genetic and environmental factors. Here, Yousri and colleagues perform a whole-exome sequencing study in combination with a metabolomics analysis to identify metabolic quantitative trait loci in a Middle Eastern population.

Here, the authors discover over 15,000 eQTLs in human kidney samples by integrating single-nucleus open chromatin data, resulting in high resolution eQTLs, increased enrichment of GWAS heritability and colocalization, followed by downstream validation.

Mammalian oocytes and embryos undergo major epigenetic changes. Here, genome-wide mapping of the histone variant H2A.Z across mouse oogenesis and early embryogenesis reveals distinct maternal, embryonic and persistent enrichment patterns, linking histone variant dynamics to epigenetic inheritance, repeats and developmental reprogramming.

Microbial decomposition of plant litter initially increases the molecular diversity of dissolved organic matter, but prolonged microbial recycling diminishes this diversity, highlighting how microbial metabolism influences soil carbon turnover.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

Parallel operation of two exchange-only qubits consisting of six quantum dots arranged linearly is shown to be achievable and maintains qubit control quality compared with sequential operation, with potential for use in scaled quantum computing.

Dysregulation of blood vessel size can cause vascular malformations. Here, the authors demonstrate that endothelial cells generate circumferential actomyosin cables to control the size of cells and vessels.

The balance between radial progenitors and intermediate precursors to generate upper-layer neurons during the development and evolution of the cerebral cortex is mediated by members of the tuberous sclerosis complex.

In a 23.4-million-cell atlas of 412 single-cell RNA-sequencing studies, SCimilarity query of macrophage and fibroblast profiles from interstitial lung disease reveals similar cell profiles across other fibrotic diseases and tissues.

Sepsis may progress into lethal septic shock, but the cellular mechanisms are still unclear. Here the authors show that, in septic mice, platelets activate perivascular mast cells to cause systemic hypotension and vascular pathology, while inhibiting platelets or mast cell activation suppresses septic shock induction, thereby implicating potential therapy targets.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

Polyamines produced by gut bacteria have been proposed to contribute to inflammatory bowel diseases. Here, Nauta et al. show that bacteria can produce a noncanonical polyamine intermediate that functions similarly to deoxyhypusine synthase inhibitors, activates mitochondrial stress responses, and inhibits nematode development and mouse macrophage differentiation.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

The feasibility of satellite-assisted quantum communication is demonstrated by a field test on the ground. To supress noise due to sunlight the wavelength of 1,550 nm is chosen, and spectrum and spatial filtering technology developed.

This paper presents TDAC-seq, a targeted chromatin-accessibility-profiling method using cytidine deaminases and long-read sequencing, to resolve the effects of CRISPR edits on single chromatin fibers.