Search

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).

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.

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.

Muscularis macrophages, housekeepers of enteric nervous system integrity and intestinal homeostasis, modulate α-synuclein pathology and neurodegeneration in models of Parkinson’s disease, and understanding the accompanying mechanisms could pave the way for early-stage biomarkers.

In a trial involving 45 clinics and 15,596 visits, the use of an AI-based screening tool applied to ECG for opportunistic detection of advanced chronic liver disease led to a significant increase in new diagnoses compared to the standard workflow.

Matthew Meyerson and colleagues report whole-exome and whole-genome sequencing of 55 small intestine neuroendocrine tumors. They identify recurrent somatic mutations in CDKN1B, implicating cell cycle dysregulation in the pathogenesis of these tumors.

A combination of gnotobiotic mouse models, transcriptomics, circuit tracing and chemogenetic manipulations identifies neuronal circuits that integrate microbial signals in the gut with regulation of the sympathetic nervous system.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Aquatic methane originates in anoxic sediments and bottom waters, but some studies suggest it may also come from the oxic water column. Here, the authors experimentally confirm this hypothesis, and explore the rates, controls and biochemical pathways of oxic water methanogenesis.

The Human Microbiome Project Consortium has established a population-scale framework to study a variety of microbial communities that exist throughout the human body, enabling the generation of a range of quality-controlled data as well as community resources.

Multi-modal analysis of genomically unstable ovarian tumours characterizes the contribution of anatomical sites and mutational processes to evolutionary phenotypic divergence and immune resistance mechanisms.

Cell migration through micrometric constraints is limited by low deformability of the nucleus. Here the authors show that in dendritic cells a perinuclear actin network nucleated by Arp2/3 increases nuclear deformation and allows the cells to pass through narrow constrictions, likely by rupturing the nuclear lamina.

The Human Microbiome Project Consortium reports the first results of their analysis of microbial communities from distinct, clinically relevant body habitats in a human cohort; the insights into the microbial communities of a healthy population lay foundations for future exploration of the epidemiology, ecology and translational applications of the human microbiome.

Enantioselective supramolecular recognition allows for the asymmetric synthesis of nitrogen stereocentres, providing chiral ammonium cations in a dynamic crystallization process.

Vargas et al. report that innate immune signalling activation controls dendritic cell migration mode and function by regulating distinct F-actin networks at the cell front and rear.

IUHCT has the ability to deliver cells to the CNS with a window for maximum delivery of cells in mid-gestation. This study provides compelling evidence of IUHCT’s potential for treatment of neurogenetic diseases

The genome of the grey short-tailed opossum Monodelphis domestica has been sequenced and analyzed, giving a first peek at a marsupial's genetic code. Of particular interest are the genetics of the immune system, which has been studied as a model for humans, and of the X chromosome for historical reasons.

Vignali and colleagues show that a full complement of ITAMs is required in the TCR-CD3 complex for TCR-driven T cell proliferation, whereas a low number of functional ITAMs is sufficient for cytokine secretion.

Medulloblastoma is the most common brain tumour in children; using exome sequencing of tumour samples the authors show that these cancers have low mutation rates and identify 12 significantly mutated genes, among them the gene encoding RNA helicase DDX3X.

An international consortium reports the genomic sequence for ten Drosophila species, and compares them to two other previously published Drosophila species. These data are invaluable for drawing evolutionary conclusions across an entire phylogeny of species at once.

Lymphocytes must rapidly scan lymph nodes for cognate antigens. Krummel and colleagues show that myosin IIA acts to optimize cell motility by regulating cell contacts through lymph node stromal environments.

A study describes the release of clinical-grade whole-genome sequence data for 245,388 diverse participants by the All of Us Research Program and characterizes the properties of the dataset.

As phase 1 of the Earth Microbiome Project, analysis of 16S ribosomal RNA sequences from more than 27,000 environmental samples delivers a global picture of the basic structure and drivers of microbial distribution.

Viral infection of the respiratory system induces exuberant fibroblast activity, resulting in extensive remodelling of the extracellular matrix and cytokine release, which promote immune cell infiltration of the affected area at the expense of respiratory function.

The ability of cancer cells to migrate through small, constricted areas is limited by nuclear stiffness. Here the authors show that in turn nuclear stiffness stimulates the delivery of enzymes important for the degradation of the extracellular matrix and the formation of invadopodia in association with fibers thus opposing nuclear movement.

The catalogue of genetic factors that have been implicated in kidney disease continues to grow. In this guide to gene–disease relationships, the authors discuss the crucial process whereby genetic and experimental data are critically evaluated to determine whether a genetic variant has a role in kidney disease, which can affect patient diagnosis, prognosis and management.

This Review Article discusses the importance of considering known microbial processes to inform our understanding of the role of microbial communities in ecosystem processes, and a move away from approaches based solely on correlation analyses.

Neuropilin-1 (Nrp1) on regulatory T (T_reg) cells is shown to interact with semaphorin-4a (Sema4a) to promote a program of T_reg-cell stability and survival, in part through PTEN-mediated modulation of Akt signalling; Nrp1-deficient T_reg cells can maintain immune homeostasis but fail to suppress in inflammatory sites, such as tumours, providing an attractive immunotherapeutic target for the treatment of cancers.

Despite advances in cell and gene therapy for the treatment of disease, no such interventions currently target the kidney. Here, the authors review the potential for cell and gene therapies to be applied to kidney disease, highlighting recent genetic studies, key technical advances and considerations, and areas for further investigation.

Mutation is the source of genetic diversity on which natural selection acts, therefore understanding the rates of mutations is crucial for understanding evolutionary trajectories. In this Opinion article, the authors discuss how emerging experimental mutation-rate data from genome-wide sequencing studies, combined with population-genetic theory, can provide unifying explanations for the diversity in mutation rates between species and across genomic locations.

Microbiome science is fast advancing and its careful integration into public health is detailed in this Perspective.

A comparison of the frequency of pathogenic mutations in 73 genes in the All of Us cohort highlights the differences in pathogenic variation attributed to ancestry.