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HTLV-1 type-C causes more severe disease than type-A, but the underlying reason is unclear. Here the authors show in a macaque model how type-C orf-I affects lung pathogenesis and the immune response to HTLV-1, providing a model to test viral targets for disease prevention.

Here, the authors report that combining Army Liposome Formulation with QS21 saponin (ALFQ) and Alum to formulate the ΔV1gp120 boost decreases the risk of simian immunodeficiency virus (SIV) mac251 acquisition in female macaques.

Using globally consistent measurements and high-resolution modelling, this study finds that black carbon emissions are generally underestimated in the Global South.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Analysis of soundscape data from 139 globally distributed sites reveals that sounds of biological origin exhibit predictable rhythms depending on location and season, whereas sounds of anthropogenic origin are less predictable. Comparisons between paired urban–rural sites show that urban green spaces are noisier and dominated by sounds of technological origin.

Calmodulin (CaM) modulates the sarcoplasmic reticulum Ca²⁺ release channel, the ryanodine receptor (RyR), to facilitate Ca²⁺ cycling in muscle contraction and release. Using fluorescence lifetime FRET with native sarcoplasmic reticulum from skeletal and cardiac muscle, the authors resolve calcium-driven structural states and kinetics of CaM binding to RyR isoforms one and two.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.

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.

Murcy et al. show that increasing the plasma glutamine-to-glutamate ratio in atherosclerosis can distally reprogram transcriptional and post-transcriptional remodeling of the aorta by GLS2-dependent hepatic glutaminolysis.

This study explores apelin receptor’s role in cardiovascular function, identifying residues critical for binding through genetic variants, AlphaFold2 modelling and base editing in cardiomyocytes. Co-crystallization with biased agonist CMF-019 shows a unique binding mode versus endogenous peptides.

Experiments in mice show that the perineural net has a key role in metabolic disease by controlling insulin access to neurons in the arcuate nucleus of the hypothalamus.

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.

Here authors show that machine learning derives the degree of background retinal pigmentation with more nuance than self-described ethnicity. Retinal pigment scores are associated with genes linked to melanin and may improve algorithmic fairness.

Human populations in the southern Africa interior were collecting non-utilitarian objects at around 105,000 years ago, suggesting that the development of this innovative behaviour did not depend on exploiting coastal resources.

Self-related cognitions are central to identity and wellbeing. Using 7-Tesla MRI, Kung et al map a dynamic network centred on the habenula demonstrating its role in encoding self-directed thinking and adaptive responses to negative self-cognitions.

Binge drinking is a rising issue in women, yet the underlying neurobiology remains underexplored. Here authors show the Edinger-Westphal (EWcp) peptidergic neurons as a critical regulator of binge drinking in female mice via actions at the ghrelin receptor (GHSR).

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.

It is thought that the hospital environment may contribute to infant microbiome development. Here, Brooks et al. present a genome-resolved metagenomic study of microbial genotypes from the infant gut and from neonatal intensive care unit rooms, showing that some strains are found in both infants and rooms.

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.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

ABCB6 has been implicated in dyschromatosis universalis hereditaria, a condition that can present with hearing loss. Here, the authors use zebrafish and mice to perform experiments suggesting that ABCB6 plays a role in inner ear development.

HIV-1 vaccine design aims to induce broadly neutralizing antibodies such as IOMA, the only described antibody in its class. Here, the authors present the isolation, characterisation and structure of three additional antibodies within the IOMA class

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.

In a phase 1 dose-escalation trial in patients with nine different types of solid tumors, MAGE-A4-specific T cells had an acceptable safety profile and exhibited an encouraging overall response rate in patients with synovial sarcoma.

Hofmann and colleagues describe the mechanism underlying the therapeutic benefit of combinatorial use of SOS1 and KRAS-G12C inhibitors in the context of KRAS-G12C mutant-driven lung and colorectal cancer.

SARS-CoV-2 has been shown to induce IL-1β-mediated neuroinflammation in humans and rodent models. Klein and colleagues show that low-dose COVID-19 vaccination prevents breakthrough infection-mediated hippocampal dysfunction and cognitive memory decline in mouse models.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

Organic frameworks with well-defined micropore structures are attractive materials for mass transfer and catalytic applications. Here, the authors demonstrate that polymers of intrinsic microporosity can be thermal-oxidatively crosslinked yielding robust materials with high molecular-sieving selectivity.

This Brain Somatic Mosaicism Network analysis of 283 cases of malformations of cortical development identifies 69 candidate and known genes in 76 patients. Single-nucleus RNA sequencing and mouse modeling implicate radial glia and daughter excitatory neurons.

In a large trial of patients with recurrent high-grade gliomas, IL-13Rα2-targeting CAR-T cells were feasible to manufacture and well tolerated when delivered via intratumoral and/or intraventricular routes.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

A high-resolution kidney cellular atlas of 51 main cell types, including rare and previously undescribed cell populations, represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.

The human coronary artery disease gene TCF21 promotes the transformation of smooth muscle cells within atherosclerotic plaques into a newly identified population of fibroblast-like cells that contribute to plaque stability.

Native-like soluble HIV envelope (Env) trimers are potential vaccine immunogens, and elimination of furin-dependence could provide a DNA-based alternative. Here, Sarkar et al. show that a cleavage-independent Env construct recapitulates the architecture and glycosylation of the native cleaved trimer.

Myofibroblasts drive fibrosis in systemic sclerosis (SSc), but the cellular progenitors are unknown. Utilizing single cell RNA-sequencing, the authors show that SSc dermal myofibroblasts arise in a two-step process from SFRP2/DPP4-expressing progenitors and implicate upstream transcription factors.

T cell-derived interferon-γ signaling to microglia underlies spatial-learning deficits associated with West Nile virus and Zika virus via the loss of hippocampal presynaptic termini or neurons with elimination of postsynaptic termini, respectively.

Heat waves can pose a threat to biodiversity as heat stress kills sperm cells across the animal kingdom. Here, honey bee queens are found to be vulnerable to temperature changes and the specific stress-response proteins activated in the spermatheca are discussed as potential indicators of heat stress.

This study reveals the mechanism by which protons gate a CLC-type Cl⁻/H⁺ exchanger. The authors show that pH-dependent concerted structural rearrangements open the H⁺ pathway, which allosterically enables the Cl⁻ pore opening and ion exchange.

Whole genome sequencing is emerging as a first-line test for rare genetic diseases. In this study, authors maximise diagnoses by supplementing existing semiautomated analyses with clinically driven reevaluation of genomic data by a specialist multidisciplinary team.

A significant proportion of patients develop innate or acquired resistance to immune checkpoint inhibitors. Here, the authors show that resistance to anti-PD-1 blockade is associated with TGF-beta driven major histocompatibility complex I (MHCI) down-regulation and a de-differentiated phenotype in melanoma patients.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Turajlic and colleagues assess longitudinal antibody and cellular immune responses against SARS-CoV-2 variants of concern in patients with cancer, following either recovery from SARS-CoV-2 infection or vaccination, in two back-to-back reports from the CAPTURE study.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

Multi-ancestry genome-wide analyses identify new risk loci for age-related macular degeneration. Ancestry-specific analyses identify distinct effects at major risk loci, including smaller effect sizes for CFH risk alleles in haplotypes of African ancestry.

It is widely assumed that D1 and D2 dopamine receptor-expressing striatal neurons code for discrete pathways in the basal ganglia. Combining optogenetics and electrophysiology, the authors show that this output architecture does not apply to nucleus accumbens neurons. Current thinking attributing D1/D2 selectivity to accumbens projections thus should be reconsidered.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease. Here, Wray and colleagues identify association of the GPX3-TNIP1 locus with ALS using cross-ethnic meta-analyses.