Search

Analyses of consummatory reproductive behaviours in male mice uncover a brain mechanism whereby an internal state can attribute a social quality to a generic touch to initiate purposeful reproductive actions.

Adaptive optical vision Fourier transformer (AOViFT) is a machine learning-based framework for accurately inferring aberrations and restoring diffraction-limited performance in diverse biological specimens.

Here the authors develop a genetic priority score to predict side effects by integrating multiple lines of genetic evidence. By applying this score, they provide evidence of known side effects and suggest ones with no clinical trial evidence.

Multiancestry fine-mapping of brain protein quantitative trait loci coupled with Mendelian randomization analyses identifies protein–trait pairs consistent with causal effects across neurological and psychiatric conditions.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

In this study, the authors present optimization and efficacy testing of apolipoprotein-based lipid nanoparticles for delivering various nucleic acid therapeutics in vivo to immune cells and their progenitors in the bone marrow.

Systematic comparison of genome-wide association results for disease risk and disease-specific mortality for nine common diseases across seven biobanks finds limited overlap between genetic effects on disease susceptibility and survival.

Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

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.

A tree-like arrangement of dichroic mirrors and multiple cameras coupled with an iterative spectral unmixing algorithm enables multispectral imaging of live cells in up to eight spectral channels with diffraction-limited spatial resolution and temporal resolution of 0.3 s for imaging a full cell volume.

CAR-T cells engineered with αPD-L1–IL-12 fusion proteins show antitumour activity in mouse models of prostate and ovarian cancer.

The molecular mechanisms that regulate postnatal termination of neurogenesis remain poorly described. Here authors report Prdm16 deletion leads to the retention of radial glia in adulthood and prolonged postnatal neuroblast production.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

The identification of cellular targets for natural products that potently inhibit the growth of cancer cell lines implicates oxysterol-binding proteins in the growth of cancer cells. These natural products, termed ORPphilins, also affect sphingomyelin biosynthesis.

Lupu, Grainger, Kirschnick et al. show that, contrary to prevailing belief, the initial specification of mammalian lymphatic endothelial cells primarily occurs from previously unidentified mesenchymal angioblasts rather than from venous endothelium.

A modelling study suggests that Mars had a desert-like climate with intermittent liquid-water oases regulated by a negative feedback among solar luminosity, liquid water and carbonate formation.

Ultrasonic vocalizations of male mice distinguish aggressive, male-directed mounting from reproductive, female-directed mounting behaviours, which are represented by distinct ESR1-expressing populations of neurons in the ventromedial hypothalamus and medial preoptic area, respectively.

BNSTpr^Esr1 activity is required to gate the transition from appetitive to consummatory male social behaviours towards both sexes, by controlling sex- and behaviour-specific representations in VMHvl and MPOA, respectively.

The emergence of resistant subpopulations often underlies the development of resistance to cancer therapy. Here, using a DNA barcoding approach, the authors demonstrate EGFR TKI treatment in non-small cell lung cancer enriches for resistant subpopulation which can be prevented by treatment with the multikinase inhibitor sorafenib via inhibition of MKNK, STAT3 and MCL1.

The RNA methyltransferase activity of SPOUT1/CENP-32 is crucial for accurate mitotic spindle organization. Here, the authors describe a neurodevelopmental disorder caused by bi-allelic pathogenic SPOUT1 variants with reduced activity and compromised function in spindle organization.

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.

Errors in oocyte division can cause infertility and birth defects. Here, authors combine a genetic strategy with a novel optochemical tool to show that spindle pole-localized F-actin is essential for proper meiotic spindle assembly and chromosome segregation.

A protocol detailing the assembly of an adaptive optics two-photon microscope setup and the guidestar-assisted shaping of the wavefront for imaging throughout the mouse neocortex at synaptic resolution.

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.

CRISPR-Cas9-based screens have allowed the study of gene-drug interactions. Here, the authors develop CRISPR-Cas9 knock-out, activation and repression screens in human gastric 3D organoids, also integrating single-cell CRISPR screens, to identify genes involved in the response to cisplatin in gastric cancer.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

There is limited understanding of SARS-CoV-2 intra-host evolution and subsequent transmission and adaptations in the context of persistent infection. Here, the authors describe sequential persistent SARS-CoV-2 infections that led to the emergence, transmission and further evolution of a novel Omicron BA.1.23 lineage.

Embryonic stem cells for chicken and seven other avian species are derived.

Immunoengineering-based cancer therapies have huge potential. Here the authors report on the lipid nanoparticle delivery, to cancer cells, of self-amplifying RNA encoding SARS-CoV-2 spike epitope-loaded MHC I molecules to take advantage of anti-SARS-CoV-2 immunity from a vaccinated population to treat cancer.

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.

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.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Haematopoietic stem cell numbers are restricted at both systemic and local levels.

Armfield X-linked disability (XLID) disorder has previously been linked to a locus in Xq28. Here, the authors report rare missense variants in FAM50A at Xq28, show that FAM50A interacts with the spliceosome, and that mis-splicing is enriched in knockout zebrafish suggesting it is a spliceosomopathy.

Here the authors investigate the underlying genetic mechanisms for pathogenic variant carrier phenotype heterogeneity using exomes and clinical phenotypes from the UK and Mt. Sinai BioMe Biobanks and observed translational potential for all three mechanisms.

A lipid-nanoparticle-based formulation incorporating engineered lipids containing a blood–brain-barrier-crossing moiety effectively delivers mRNA to neurons and astrocytes following systemic administration in mice.

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

In this 4-year unblinded follow-up study, the authors evaluate 63% of the participants of a double-blind randomised control trial that assessed the effects of faecal microbiota transplantation (FMT) on adolescents with obesity.

A distinct population of CD4 T cells resides in specific regions of the steady-state brain, and these T cells are programmed in the periphery by the microbiome to coordinate adaptive behaviour.

Lv et al. discover that homologous disordered regions of proteins linked to ALS/FTD and Parkinson’s, CHCHD10 and CHCHD2, form amyloid fibrils in vitro and that the structures of these fibrils are consistent with potential roles for them in disease.

Immunofluorescence imaging and computational modelling are used to study the spatial distribution of different cell types within the haematopoietic stem cell (HSC) niche; findings show that quiescent HSCs associate specifically with small arterioles that are preferentially found in the endosteal bone marrow and are essential in maintaining this quiescence.

Zhang et al. show that Egr1 regulates transient senescence during neonatal heart regeneration and upon agrin-mediated cardiac repair in adult mice, acting downstream of the integrin–FAK–ERK–Akt1 axis in cardiac fibroblasts.