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Integrated single mode lasers capable of extremely narrow linewidths and high output power will enable precision portable quantum, microwave, and sensing applications. Here we demonstrate a simultaneous record low fundamental linewidth and high output power using an integrated Brillouin laser in a meter-scale silicon nitride coil resonator.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

A new phylogenomic tree for butterflies is constructed using 391 genes from 2,300 species, representing 92% of genera. It suggests that butterflies originated around 100 million years ago in what is now the Americas and originally fed on Fabaceae.

EGF-induced recruitment of UPF1 adjacent to HNRNPC induces splicing surveillance of cell proliferation mRNAs.

In this genomic analysis of peripheral blood samples of the phase 3 CheckMate-067 trial of ipilimumab (IPI) versus nivolumab (NIVO) versus ipilimumab and nivolumab (IPI-NIVO) in melanoma, the status of certain mitochondrial haplogroups in patients was associated therapeutic resistance to NIVO or IPI-NIVO, a finding validated in an independent cohort.

Here, the authors leverage whole-genome sequencing from >88,000 diverse individuals to uncover 18 BMI-related genetic signals, including novel variants in participants of African genetic ancestry, highlighting the value of diversity in genetic discovery.

Moore et al. find that fewer Americans visited misinformation websites during the 2020 election compared with the 2016 election. However, demographic groups more likely to be exposed to misinformation in 2016 remained more likely to be exposed in 2020.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

End-of-life nonhuman primates can be used to screen pools of lipid nanoparticles for clinical safety studies.

Single-cell RNA sequencing with parallel tagging of progenitor cells is used to track clonal relationships and transcriptomic signatures during development of the mouse forebrain.

Integration of genome-wide association analysis of 406,504 individuals in the UK Biobank and scATAC–seq data reveals that variants in tubule epithelial regulatory elements mediate most heritable differences in human kidney function.

 A transcriptomic cell-type atlas of the whole adult mouse brain with ~5,300 clusters built from single-cell and spatial transcriptomic datasets with more than eight million cells reveals remarkable cell type diversity across the brain and unique cell type characteristics of different brain regions. 

Chimeric antigen receptor (CAR)-T cells may become exhausted, non-functional or deplete their target cells of antigen, limiting their efficacy. Chen and colleagues fuse the CTLA-4 cytoplasmic tail to a CAR, which compromises trogocytosis and increases the functional capacity of CAR-T cells.

A generalizable framework to prospectively engineer cis-regulatory elements from massively parallel reporter assay models can be used to write fit-for-purpose regulatory code.

Ryan and colleagues analyze genomic features in tumors from African Americans and European Americans and find that homologous recombination deficiency is more prevalent in African Americans.

Frogs are an ancient and ecologically diverse group of amphibians that include important model systems. This paper reports genome sequences of multiple frog species, revealing remarkable stability of frog chromosomes and centromeres, along with highly recombinogenic extended subtelomeres.

The homeostasis of myelin in the central nervous system is highly regulated, but the underlying mechanisms are unclear. Here, the authors show that the FBXW7 protein has a role in constraining myelin growth in the developing and adult central nervous system, preventing the accumulation of myelin abnormalities. FBXW7 acts in part through targeting the MYRF transcription factor for degradation.

Surgical nerve injuries can cause significant morbidity, yet no approved fluorescent agents exist for visualization. Here, the authors show in a Phase I multi-site trial that bevonescein was safe, established optimal dosing and timing, and provided a fluorescence signal for intraoperative nerve identification.

Chronic myelomonocytic leukaemia is classified as proliferative (pCMML) or dysplastic based on the white blood cell counts but biological differences are unclear. Here, the authors show genetic, transcriptomic and epigenomic differences between these two subtypes establishing that pCMML is RAS-pathway driven and that inhibiting RAS-driven PLK1 expression is a viable therapeutic target.

In a phase 1 trial, patients with pancreatic ductal adenocarcinoma who were treated with surgery and bespoke neoantigen mRNA vaccines combined with anti-PD-L1 and chemotherapy exhibited marked long-lived persistence of neoantigen-specific CD8⁺ T cell clones, which correlated with prolonged recurrence-free survival at a 3.2-year follow-up.

Unbiased selection of CAR-T cells is achieved by massively parallel knock-in engineering.

Scientists disagree about area-based conservation’s role in addressing biodiversity loss. This Perspective examines how conservation scientists, land systems scientists and political ecologists approach these debates differently and argues that environmental data justice frameworks can bridge epistemic divides, helping researchers to develop more effective and equitable conservation interventions.

STAAR is a powerful rare variant association test that incorporates variant functional categories and complementary functional annotations using a dynamic weighting scheme based on annotation principal components. STAAR accounts for population structure and relatedness and is scalable for analyzing large whole-genome sequencing studies.

The cellular composition of recurrent tumors can provide insight into resistance to therapy and inform on second line therapies. Here, using a genetically modified mouse, the authors perform barcoding experiments of the primary tumors to allow them to study the clonal dynamics of tumor recurrence.

This study reports a dense, late summer phytoplankton bloom in the Southern Ocean that accumulated unusually high levels of organic matter and supported feeding hot spots for birds and whales. The authors show that this recurring open ocean bloom is driven by anomalies in easterly winds that push sea ice southwards and favour the upwelling of deep waters enriched in hydrothermal iron.

Nano et al. introduce a pipeline to generate meta-atlases of the human brain from existing single-cell datasets and extract gene modules linked to cell fate specification. Perturbing these programs in human cortical chimeroids validated their roles in cell type specification.

A modeling study using case and mortality data from the first 8 months of the COVID-19 pandemic in the United States explores five potential future scenarios of social distancing mandates and mask use at the state level, with projections of the course of the epidemic through winter 2021.

Available wheat genomes are annotated by projecting Chinese Spring gene models across the new assemblies. Here, the authors generate de novo gene annotations for the 9 wheat genomes, identify core and dispensable transcriptome, and reveal conservation and divergence of gene expression balance across homoeologous subgenomes.

An integrated data and sample repository for clinical, cellular and multi-omics research from diverse spaceflight missions known as Space Omics and Medical Atlas (SOMA) is presented.

Transcription Factor 4 (TCF4) has been associated with autism and schizophrenia. Here, the authors demonstrate aberrant proliferation and differentiation in neural cells and organoids carrying mutations in TCF4.

High-resolution contact maps of active enhancers and target genes generated by H3K27ac HiChIP in primary human cells provide rational guides to link noncoding disease-associated risk variants to candidate causal genes. Genes are validated by CRISPR activation and interference at connected enhancers and eQTL analysis, leading to a fourfold increase in the number of potential target genes for autoimmune and cardiovascular diseases.

The approximately 5-Gb tuatara (Sphenodon punctatus) genome assembly provides a resource for analysing amniote evolution, and highlights the imperative for meaningful cultural engagement with Indigenous communities in genome-sequencing endeavours.

The Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) aims to better understand population genetics of the African diaspora. Here, it uses deeply sequenced whole-genomes to describe the impact of admixture and potential disease burden of deleterious variants.

Fossils of small dinosaurs are less common than their large-bodied counterparts, but whether this relates to preservational biases remains unclear. Evans et al.describe a new pachycephalosaur and provide the first evidence that small-bodied dinosaur diversity is strongly underestimated.

Gao and Wang develop a measurement framework that demonstrates the widespread use and benefits of AI in science. Nonetheless, there is a substantial gap between AI education and application across disciplines.

Transcriptomic analyses of acute phase whole blood from a large cohort of patients with COVID-19 identify molecular determinants of post-infection long-term sequelae.

Benchmarking of scATAC-seq protocols demonstrates the effects of data quality on downstream analyses.

Dhanasekaran and colleagues study minimal residual disease in hepatocellular carcinoma using single-cell spatial transcriptomic and proteomic analysis and find a targetable role for immunosuppressive macrophages.

High-affinity antibodies are often identified through directed evolution but deep leaning methods hold great promise. Here the authors report RESP, a pipeline for efficient identification of high affinity antibodies, and apply this to the PD-L1 antibody Atezolizumab.

A catalogue of predicted loss-of-function variants in 125,748 whole-exome and 15,708 whole-genome sequencing datasets from the Genome Aggregation Database (gnomAD) reveals the spectrum of mutational constraints that affect these human protein-coding genes.

The authors show that the transcription factors NANOG and GATA6 co-bind the same enhancers in common progenitors before divergent epiblast and primitive endoderm lineages emerge. This may help maintain plasticity at early stages and facilitate bifurcation into distinct lineages

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

SciSciGPT is an open-source prototype AI collaborator that explores the use of LLM research tools to automate workflows, support diverse analytical approaches and enhance reproducibility in the domain of science of science.

Senescent melanocytes of skin nevi drive hyperactivation of hair growth through the signalling factor SPP1.

This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual.

Caloric restriction improves Alzheimer’s Disease outcomes in mice, but this diet not only reduces calories, but imposes a prolonged fast between meals. Here, the authors show this fast is essential to improve Alzheimer’s pathology and cognition.