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Brown et al. show that mouse islet progenitors with different transcriptomes produce distinct β-cell subtypes and maternal diet alter the subtype proportions. Similar β-cell subsets exist in humans, with a subset enriched in genes related to β cell function reduced in diabetes.

Mendelian randomization (MR) identifies causal relationships from observational data but has increased error rates when the genetic variants used as instruments come from a single region, a typical scenario when assessing molecular traits like protein or metabolite levels as risk factors. Here the authors introduce a single-region pleiotropy-robust MR method, validating the method on three ground truth sources, showing its capability to identify disease-causing molecular traits.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

NatD is an acetyltransferase responsible for N-α-terminal acetylation of the histone H4 and H2A and has been linked to cell growth. Here the authors show that NatD-mediated acetylation of histone H4 serine 1 competes with the phosphorylation by CK2α at the same residue thus leading to the upregulation of Slug and tumor progression.

Analysis combining multiple global tree databases reveals that whether a ___location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

Nonlinear optical phonons often exhibit rapid decay. Here, the authors demonstrate long-lived nonlinear optical phonons through the spontaneous formation of phonon frequency combs in CrXTe₃ (X=Ge,Si).

Song et al. developed a computational tool to profile binding pairs between tumor-derived antigens and antibodies from high-throughput B cell receptor sequencing data, predicting response to immune-checkpoint inhibitor therapy and risk of adverse events.

Therapeutic T cells engineered to recognize tumour antigens are frequently short-lived and acquire unfavourable phenotypes in tumours. Here authors show that a tandem approach using autologous T cells targeted against the tumour antigen NY-ESO-1, followed by transfer of hematopoietic stem cells with the same specificity in the clinical trial NCT03240861, provides a safe and promising therapeutic option.

Using degron approaches, the authors show that cancer cells experiencing prolonged DNA methylation loss—without substantial DNA damage—undergo non-canonical senescence. This has important potential implications for cancer treatment.

A stereotaxic atlas of the whole mouse brain, based on a Nissl-stained cytoarchitecture dataset with isotropic 1-μm resolution, achieved through continuous micro-optical sectioning tomography, promises to be a versatile brainsmatics tool for studying the whole brain at single-cell level.

Living biophotovoltaics generate bioelectricity by harnessing photosynthetic microorganisms, but barriers to electron transfer across the abiotic/biotic interface hinder solar-to-electricity conversion. Here, the authors report a method for boosting photocurrent by integrating the photosynthetic cyanobacteria with a conductive conjugated polyelectrolyte to form 3D living biocomposites.

Genome-wide sequencing of 180 ancient individuals shows a continuous gradient of ancestry in Early-to-Mid-Holocene hunter-gatherers from the Baltic to the Transbaikal region and distinct contemporaneous groups in Northeast Siberia, and provides insights into the origins of modern Uralic and Yeniseian speakers.

Antibodies against SARS-CoV-2 provide protection against infection, but the virus has evolved to evade them. Here, the authors characterize a human antibody with incomplete neutralization of SARS-CoV-2 variants and engineer it to enhance potency and expand coverage to all tested variants by increasing conformational flexibility.

A parallel experimental and computational approach was used to predict and prepare intercalated, layered hybrid perovskites, highlighting the breadth and flexibility of intercalation.

Inactivating PPP2R1A mutations correlate with better survival after immune checkpoint blockade in patients with ovarian clear cell carcinoma, suggesting that targeting the phosphatase 2A (PP2A) pathway may represent an effective startegy for improving responses to immunotherapy.

Currently, the biological and clinical implications of copy number alteration (CNA) size heterogeneity and co-occurrence are incompletely understood. Here, the authors use 691 meningiomas and 29 cancer types from The Cancer Genome Atlas to develop size-dependent CNA and CNA co-occurrence models to optimize individualized pan-cancer risk stratification.

Single-cell analysis of patient brains and cortical organoids links disrupted developmental metabolic reprogramming to postnatal synaptic dysfunction in dup15q syndrome, revealing shared neuronal changes with idiopathic autism.

In this work, authors report a mechanism for how phage can promote the spread of costly antibiotic resistance. They show that faster-growing sensitive cells dominate the biomass periphery where they encounter more phage, allowing for slower growing resistant cells to persist.

Species’ traits and environmental conditions determine the abundance of tree species across the globe. Here, the authors find that dominant tree species are taller and have softer wood compared to rare species and that these trait differences are more strongly associated with temperature than water availability.

Sydnor et al. developed a new tractography atlas of thalamocortical structural connections and applied it to three youth samples. They uncovered coordinated development between thalamic connectivity and hierarchical cortical plasticity in humans.

How higher-order thalamic feedback modulates sensory-evoked cortical activity is not fully understood. This study reveals that synaptic feedback from the thalamus selectively increases the excitability of distinct cortical neurons through NMDARs and mGluR-mediated modulation of potassium channels, thereby enhancing sensory processing.

Study shows PTSD predisposition shares distinct genes and genomic regions with several cardiovascular conditions. Here the findings reveal neuronal, immune, and metabolic pathways, and repurposed drug targets that further the understanding of the comorbidity.

Fifty years of plankton and water samples show that the proportion of carbon, nitrogen and phosphorus in the ocean now substantially differs from the Redfield ratio, probably reflecting a reduction in phosphorus limitation.

Phytochrome photoreceptors are master regulators of plant development. This paper describes 3D structures of soybean phytochrome A in both Pr (inactive) and Pfr (signalling) states, revealing changes that might transmit the light signal to the cell.

Monomethylation of histone H4 lysine 20 (H4K20me1) contributes to DNA replication but the mechanism is not well understood. Here, the authors identify a conserved tandem Tudor ___domain of BAHCC1 as a H4K20me1-specific reader, which promotes the recruitment of MCM complex to chromatin for efficient DNA replication.

Low formate dehydrogenase (FDH) activity limits formate assimilation via the synthetic reductive glycine pathway. In this study, the authors introduce a faster FDH in synthetic formatotrophic E. coli, which boosts growth rates and bioproduction titers from formate as sole carbon source.

Olfactory perception shows marked sexual dimorphism, yet its genetic basis remains underexplored. Here, the authors show sex-specific and shared genetic loci for odour identification, implicating olfactory receptor clusters and links to Alzheimer’s disease risk.

Certain antimetabolites used to treat cancer are more neurotoxic than others, and it is now shown that this is due to their greater tendency to generate DNA double-stranded breaks, whereas less neurotoxic agents induce single-stranded breaks.

Every spring, Bogong moths use the starry night sky as a compass to navigate up to 1,000 km towards their alpine migratory goal.

Spatially segregated rRNA processing dictates nucleolar morphology and drives outward progression of pre-ribosomal RNA through nucleolar phases.

Neural networks fundamentally dictate function. Here, the authors show thirteen uniquely connected neuron populations within the anterior thalamic nuclei, suggesting multiple parallel subnetworks support its emotional and cognitive functions.

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.

The Somatic Mosaicism across Human Tissues Network aims to create a reference catalogue of somatic mosaicism across different tissues and cells within individuals.

This study uncovered genetic associations with environmental sensitivity in psychiatric and neurodevelopmental traits in an international collaboration using data from more than 21,000 monozygotic twins—the largest genetic study of monozygotic twin differences to date.

P-selectin has been considered as a biomarker of hematopoietic stem cell (HSC) aging. Here, Yang et al. uncovered a new functional role of P-selectin engagement in regulating HSC regeneration and driving stem cell aging when perturbed.

BRCA1 and BRCA2 are well known breast cancer predisposition genes, however, many variants have not yet been classified for their pathogenicity. Here, the authors analyse a large combined cohort to provide evidence of variant pathogenicity.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

DeepRETStroke is a deep learning system using retinal photographs to detect silent brain infarction and predict future stroke events.

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.

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.

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.

In preclinical studies, the FDA approved TSP-1 antagonist gabapentin has been shown to disrupt neuronal-glioma interactions, slowing glioblastoma progression. Here, authors report a retrospective cohort study demonstrating a survival benefit associated with gabapentin in patients with newly diagnosed glioblastoma.

Preliminary results from a phase 2a trial involving 71 patients suggest that a new agent, discovered and designed with artificial intelligence assistance, is safe and effective for the treatment of idiopathic pulmonary fibrosis.

The transcription factor CREM is a pivotal regulator of NK cell function, making CREM a valuable target to increase the efficacy of anticancer immunotherapies based on this cell population and chimeric antigen receptors.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Heo, Xu et al. used comprehensive plasma proteomics to identify 416 plasma proteins (294 new) associated with Alzheimer’s disease and applied machine learning to select 7 proteins that were highly predictive of Alzheimer’s disease across multiple cohorts.