Search

DNA-sequencing data from primary tumours and paired metastases from participants in the TRACERx lung study and PEACE autopsy programme are used to analyse the metastatic diversity of advanced non-small cell lung cancer and the seeding patterns that underpin it.

Intracranial recordings in children revealed neural signals predicting attentional lapses. Closed-loop stimulation rescued performance and scalp EEG enabled noninvasive modulation, identifying a reproducible marker of attentional control.

Babies born by caesarean may miss immune system trigger.

Exposome analyses across 34 countries showed that social exposures were associated with faster functional brain aging and physical exposures with faster structural brain aging.

Ageing impairs strategic re-aiming but enhances implicit recalibration during sensorimotor learning. The strategic deficit probably reflects reduced memory caching, whereas the implicit enhancement is linked to altered multisensory integration.

Autophagic activity has a protective role in Alzheimer’s disease in mice. Here the authors investigate the role of autophagy-initiating protein ULK1 and report that its overexpression stimulates autophagic flux, reduces amyloid and tau pathology and delays cognitive decline.

Chu et al. present a framework for programmable RNA translation, of interest for RNA therapeutics. The method enables large-scale discovery and engineering of internal ribosome entry sites, which are validated by high-throughput functional assays.

The genetically encoded voltage indicators JEDI3sub and JEDI3hyp enhance monitoring of subthreshold neuronal activity in the awake mouse brain using a variety of two-photon microscopy techniques.

Here, the authors examine how people combine facial expressions and context to understand others’ emotions. They find that most people use a Bayesian integration strategy, where cues are weighted based on ambiguity, but others use more simplistic averaging strategies.

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.

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.

Although the number of participants is important for phenotypic prediction accuracy in brain-wide association studies using functional MRI, scanning for at least 30 min offers the greatest cost effectiveness.

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).

It has been proposed that language meaning is represented throughout the cerebral cortex in a distributed ‘semantic system’, but little is known about the details of this network; here, voxel-wise modelling of functional MRI data collected while subjects listened to natural stories is used to create a detailed atlas that maps representations of word meaning in the human brain.

NeAT is a computational framework that facilitates incorporating adaptive optics into custom or commercial two-photon microscopes. This allows correcting aberrations and conjugation errors in real time in the mouse brain during morphological or functional imaging.

Yu et al. develop a platform to model genetic diversity in drug treatment at the single-cell level. Using KRAS-G12C inhibitors as a proof of concept, they identify the pathway driving cell death and potential resistance mechanisms.

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.

He and colleagues develop a METTL3-based RNA base-editing screening strategy to identify functional N⁶-methyladenosine (m⁶A) sites that are important for prostate cancer cells and validate the role of a top m⁶A target, CHD9, in this context.

The authors developed Cheese3D, a hardware–software framework for precise and sensitive measurement of whole-face movements in mice that enables quantitative inference of neural and physiological processes.

Approach and avoidance behavior is disrupted in many psychiatric disorders, but the neural circuits that support this behavior are unknown. Here, the authors identify a theta-mediated limbic circuit that support approach and avoidance decision-making, contributing to a network understanding of psychiatric disorders, especially those characterized by maladaptive avoidance.

Single-cell RNA sequencing and assay for transposase-accessible chromatin using sequencing profiling of human retinal samples from diverse ancestries create an epitranscriptomic atlas characterizing over 130 cell types. Integration with genome-wide association study and expression quantitative trait loci data provides further insights into gene regulation and disease etiology.

Genetically superior sheep to found next-generation flock.

Badkul et al. develop eMOSAIC, a method that improves drug discovery by accurately predicting the interaction mechanics of various compounds with multiple proteins.

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.

Stars who become famous for an illness can have a huge impact on medical research. Helen Pearson talks to physician and historian of medicine Barron Lerner about the good and the bad of celebrity patients

Imaging fluorescent molecules in live cells is revolutionizing cell biology. But a pretty image is not necessarily a good one, and many biologists are learning this the hard way, finds Helen Pearson.

The authors demonstrate that the accuracy of predictions in network biology scales with larger foundation models pretrained with larger, more diverse data and that quantization enables resource-efficient predictions while preserving biological knowledge.

Unpicking the problems of infertility may help guide treatment.

Mice with a hefty dose of a certain gut bacteria are fatter.

Bug-eating bugs destroy life-threatening biofilms.

Better hygiene could squelch transfer of disease to corals.

Turning the ubiquitous shipping container into a mobile clinic.

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.

Pre-existing chronic diseases can delay or accelerate cancer diagnosis. Here the authors report that the duration of analgesic treatment as well as history of anxiety or depression can impact risk of advance stage lung and colon cancer in patients.

The epigenetic mechanisms underlying phenotypic diversity across different metastatic sites in castration-resistant prostate cancer (CRPC) remain to be characterised. Here, multi-omic profiling across metastatic lesions identifies regulatory networks driving tumour lineage programs and potential therapeutic targets.

Face cells in the macaque inferotemporal cortex are initially able to detect faces and then rapidly switch to a face-specific neural code to discriminate between different face identities.

Here the authors suggest that in Atypical Teratoid Rhabdoid Tumors, EZH2 inhibition triggers a viral mimicry response via the activation of genes with intronic IR-Alu elements. This response also involves enhanced LINE-1 expression, leading to activation of cGAS/STING signalling.

Variant-to-gene-to-program is a new approach to building maps of genome function to link risk variants to disease genes and to convergent signalling pathways in an unbiased manner; its strength is demonstrated in coronary artery disease.

Analysis of copy number alterations in 1,451 patient-derived xenografts (PDXs) and matched patient tumor samples shows strong conservation from patient tumors through late-passage PDXs and a lack of systematic copy number evolution driven by the mouse host.

Deposition of tau protein aggregates occurs during aging and Alzheimer disease. Here, the authors show that tau burden in the anterior-temporal memory network is associated with disrupted fMRI connectivity and functional isolation of the hippocampus from other memory network components.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

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.

Doctors are testing the boundaries of medicine in order to help more people have babies. Helen Pearson explores the fertile ground at the American Society of Reproductive Medicine meeting in Philadelphia.

Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

Transcriptome-wide m⁶A RNA methylation profile in 162 primary prostate tumors identifies m⁶A association with prognostic clinical features and disease aggression.

Survey results suggest a rise in questioning of scientific evidence.

The oncoprotein c-Myc is often overexpressed in triple negative breast cancer and has a role in tumor progression and resistance to therapy. Here the authors show that elevated MYC expression is correlated with low immune infiltration, diminished MHC-I pathway expression and that CpG/aOX40 treatment could overcome resistance to PD-L1 blockade in MYC-high breast tumors.