Search

\({\rm{Micro}}{\mathbb{S}}{\rm{plit}}\) is a computational unmixing method for multiplexed fluorescence imaging of up to four structures per imaging channel.

Biallelic variants in RNU4-2 cause a recessive neurodevelopmental disorder that is phenotypically and molecularly distinct from dominant ReNU syndrome and associated with reduced RNU4-2 transcript levels, consistent with a loss-of-function mechanism.

Analyses of epidemiological, clinical and molecular data from a prospective cohort of 3,100 patients with esophageal carcinoma suggest intestinal metaplasia as a single precancer pathway preceding the disease.

Analysis of sequencing data from rare disease cohorts identifies biallelic variants in RNU2-2 underlying a developmental and epileptic encephalopathy associated with reduced U2-2 abundance and clinically distinct from the dominant RNU2-2 disorder.

Analyses of snRNA genes in a French cohort of people with rare disorders, with validation through international collaboration, identify monoallelic and biallelic variants in RNU2-2 as frequent causes of neurodevelopmental disorders with epilepsy.

Genome-wide selective sweeps commonly occur in the human gut microbiome and can spread across the world within decades to produce epidemic-like population structures.

Constraining projections using best-performing climate models, uncertainties in future temperature variability can be narrowed, yet remain large over poorly modelled regions, highlighting the need for multiple model ensembles to assess future risks.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

Prinz and colleagues examine the distinct functions and repopulation properties of leptomeningeal and perivascular macrophages that mediate immune responses at brain boundaries.

Single-variant and ultrarare variant burden analyses leveraging exome sequencing data from 22 cohorts identify new risk genes for amyotrophic lateral sclerosis and show cumulative effects of several rare variants on disease risk.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Saturation genome editing of RNU4-2 identifies the functional and clinical impact of variants across the entire gene and delineates variants that cause a new recessive neurodevelopmental disorder distinct from ReNU syndrome.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer due to late detection and rapid progression. Here, the authors integrate multi-regional whole genome and RNA sequencing to characterize intratumoural heterogeneity and evolutionary trajectories underlying the malignant transformation of intraductal papillary mucinous neoplasms into invasive PDAC.

An analysis of 18 metagenomic datasets of individuals with colorectal cancer, adenomas and healthy controls yields improved cancer prediction accuracy based solely on gut metagenomics, as well as the identification of new species associated with the development of cancer.

Neurotransmitter receptor distributions help explain structural and functional brain alterations in Parkinson’s disease. Distinct multi-receptor profiles are associated with the severity of motor, and visuospatial, psychiatric and memory symptoms.

Organ-specific aging clocks for multiple brain and body systems show that the biological age of one organ system selectively influences the aging of multiple other systems via characteristic aging pathways.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Targeting neurons that regulate energy balance may offer new approaches for obesity treatment. Here, authors show that chemogenetic and pharmacological manipulation of GABAergic neurons in the DRN/vlPAG increases adaptive thermogenesis and reduces weight gain in mice fed a highfat diet.

Aging is associated with the formation of focal white matter lesions and atrophy. The authors discovered a role for CD8⁺ T cells in driving white matter-specific interferon responses in microglia and oligodendrocytes, leading to oligodendrocyte loss.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Tools to segment cellular and sub-cellular neuronal structures can be hindered by high neuronal density and low signal-to-noise in thick samples. Here, the authors present SENPAI, a framework for imaging and segmenting neurons from conventional and super-resolution microscopy of clarified brain tissues.

Here, the authors present an update to a widely used curatedMetagenomicData (cMD) database and use it to create a catalog of microbiome-phenotype associations (age, sex, body mass index), and develop an oral enrichment score in the gut microbiome independently of age.

Active nematics are complex systems that exhibit unique collective behaviors due to energy injection at the microscale, which can be harnessed for applications in material design and self-assembly. This study reveals a rich phase diagram of passive soft inclusions suspended in active nematics, demonstrating how varying activity levels and inclusion deformability can lead to dynamic clustering, gelation, and a novel phase separation regime.

TMEM16F is a transmembrane protein that facilitates passive phospholipid transbilayer movement and ion conduction across membranes. Here, authors reveal a structural heterogeneity which is possibly linked to TMEM16F unique dual function.

Mutations in elongation factor G protect bacteria from aminoglycoside antibiotics through unknown mechanisms. Here, the authors show that the mutations selectively slow the movement of antibiotic-bound ribosomes along mRNA, which prevents error-prone protein synthesis and thus membrane damage and antibiotic uptake.

The microbiota influences the cytotoxicity of chemotherapy in patients with colorectal cancer but the impact on metastatic relapse is less clear. Here, the authors report that chemotherapy-induced intestinal mucositis induces systemic immune changes via production the microbial metabolite, indole-3-propionic acid (IPA), preventing metastases.

Germ layer specification during zygotic genome activation is regulated by chromatin state. Here, the authors use single-cell multiome profiling in Drosophila to show that H3K27me3 and H3K27ac at cis-regulatory elements control cell type-specific gene expression and developmental progression.

How does the hippocampus learn with only a single presentation of a stimulus? Nicola and Clopath show how interneuron networks can dilate pre-existing spike sequences during sharp waves into theta sequences for one-shot learning.

HIV replication has been shown previously to be inhibited by combinations of T cells and NK cells according to HLA and KIR haplotype. Here the authors consider a combination of KIR2DL2+ NK and HLA-C*12:02-restricted T cells and clarify how a specific HIV pol escape mutant facilitates virus control by KIR2DL2+ NK cells.

The spin exchange, which is central to spintronics, has been restricted to devices with long-range magnetic ordering to date. Here, Pei et al. design a single-molecule-magnet and utilize its internal spin exchange to control the current through a single-molecule junction with high spin polarization (>95%).

In a phase 2 trial evaluating healthy donor fecal microbial transplantation plus either anti-PD-1 in patients with non-small cell lung cancer or anti-PD-1 and anti-CTLA-4 in patients with melanoma, encouraging efficacy was seen in both cohorts, with responses linked to significantly greater loss of baseline bacterial species.

Single atom catalysts, comprising minute amounts of transition metals dispersed on inert substrates, have emerged as prominent materials in heterogenous catalysis but their precise arrangement on surfaces is challenging. Here, the authors introduce the on-surface synthesis of a single atom platform wherein atoms are firmly anchored to specific coordination sites evenly distributed along carbon-based polymers.

Melinda Mills, Nicola Barban, Harold Snieder, Marcel den Hoed and colleagues perform a meta-analysis of data from over 300,000 individuals for age at first birth and number of children ever born. They identify 12 significant loci that associate with these traits, providing insights into the genetic basis of human reproductive behavior.

A comprehensive longitudinal analysis of individuals with preclinical Huntington’s disease identifies biomarkers of neurodegeneration and somatic expansion in blood DNA, detectable years before symptom onset.

Here the authors show that endogenous or therapeutically delivered GDF-15 activates brainstem neurons that trigger splenic β-adrenergic signaling. This, in turn, suppresses autoreactive T cells and reduces neuroinflammation, identifying a possible target for multiple sclerosis treatment.

Food and the gut go on show, Angolan ‘sea monsters’ resurface and Alexander von Humboldt pops into focus. Nicola Jones reports.

A metagenomic survey of babies attending the first year of nursery detected extensive baby-to-baby microbial strain transmission, pointing to social interactions in infancy as crucial drivers of infant microbiome development.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

In a post-hoc analysis of circulating tumor DNA (ctDNA) features from patients with metastatic prostate cancer treated with [¹⁷⁷Lu]Lu–PSMA-617 or cabazitaxel in the randomized phase 2 TheraP trial, low ctDNA levels at baseline were predictive of clinical benefit from [¹⁷⁷Lu]Lu–PSMA-617, and PTEN or ATM alterations were identified as potential biomarkers of response.