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).

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

Mexico's genomic researchers believe a mestizo “hapmap” might reveal a genetic basis for some of the nation's health problems, although they are mindful of the potential for the misuse of personal genetic information.

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.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Marine plants reproduce by hydrophilly, that is, the movement of pollen by water. Here, the authors show that invertebrates can also carry pollen from male to female Thalassia testudinum plants.

Jiménez-Blasco et al. show that neurons exhibit moderately low glycolytic rates despite their activity being mainly supported by glucose to preserve redox balance.

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.

Multiancestry genome-wide association analyses identify new risk loci for stroke and stroke subtypes. Fine mapping and bioinformatics analyses of these risk loci point to mechanisms not previously implicated in stroke pathophysiology.

Analysis of 2,170 SARS-CoV-2 sequences from the first wave of the COVID-19 epidemic in Spain provides insights into transmission patterns and the effects of lockdown on the emergence of new variants.

Torrano et al. use bioinformatics analyses to identify PGC1α as a transcriptional regulator of a metabolic program downstream of ERRα that opposes metastatic dissemination in prostate cancer.

The authors previously identified a family of viral insulin-like peptides (VILPs) with high homology to human insulin/IGF−1. Here, they report that one of these VILPs exhibits antagonist properties associated with a unique conformation of the IGF1R.

This paper reports one of the largest breast cancer whole-exome and whole-genome sequencing efforts so far, identifying previously unknown recurrent mutations in CBFB, deletions of RUNX1 and recurrent MAGI1–AKT3 fusion; the fusion suggests that the use of ATP-competitive AKT inhibitors should be evaluated in clinical trials.

Mucopolysaccharidosis type IVA (MPSIVA) is a lysosomal storage disorder causing severe skeletal and non-skeletal alterations in patients. Here, the authors generate a MPSIVA rat model that mimics the disabling human pathology and develop an AAV9-Galns gene therapy to treat the disease.

Primary and metastatic tumours have different metabolic phenotypes due to changes in nutrient availability. Here the authors perform multi-omic analyses of primary and metastatic renal cancer cells grown in a physiological medium and show that the reprogramming of the branched-chain amino acid catabolism and urea cycle through re-expression of ASS1 allows metabolic flexibility during renal cancer progression.

Targeting PML in acute promyelocytic leukaemia has changed the outcome of patients with this disease. Here, the authors demonstrated that PML is also a potential therapeutic target in breast cancer where it specifically regulates cancer initiating cells and tumour progression through the transcriptional regulation of SOX9.

The expression of specific genes can be controlled by the combination of DNA-binding proteins, which determines their binding site selectivity. Here, simplified synthetic basic region leucine zipper-based peptides are induced to dimerize either through their C- or N-terminus, and thus are targeted to different DNA sequences.

Glutathione's key role as a modulator of reactive oxygen species levels has recently been challenged. Quintana-Cabreraet al. now provide in vivoevidence supporting an antioxidant and neuroprotective function for γ-glutamylcysteine, which replaces glutathione by acting as glutathione peroxidase-1 cofactor.

Stegouros elengassen, an ankylosaur from the late Cretaceous of Chile, has a large tail weapon, named a macuahuitl after the Aztec club, with a frond-like structure formed by seven pairs of laterally projecting osteoderms encasing the distal half of the tail.

The mechanisms associated with fatty acid synthase (FASN) upregulation during transformation are unclear. Here, the authors report that FASN promotes anaplerotic shift of the Krebs cycle in cancer cells expressing various oncogenes, and that its inhibition before transformation prevents tumour development and invasion.

The InSight lander has expanded our knowledge of the atmosphere of Mars by observing various phenomena, including airglow, bores, infrasound and Earth-like turbulence.

Short telomeres are risk factors for age-associated diseases such as cardiopathies. Here the authors show that cardiac reactivation of telomerase, the telomere-elongating enzyme whose expression is normally silenced postnatally, mitigates the consequences of myocardial infarction in adult mice.

The extent to which the ocean acts as a sink and source of airborne particles to the atmosphere is unresolved. Here, the authors report high microbial loads over the tropical Atlantic, Pacific and Indian oceans and propose islands as stepping stones for the transoceanic transport of terrestrial microbes..

Neurons and astrocytes cooperate metabolically but differ in key aspects of their metabolism, including the production of mitochondrial reactive oxygen species (ROS). Here, the authors show that mitochondrial ROS produced in astrocytes affect neuronal metabolism and mouse memory and behaviour.

Triple-negative breast cancer (TNBC) lacks prognostic and predictive markers. Here, the authors use phosphoproteomics to define kinases with distinct activity profiles in TNBC, demonstrating their prognostic value as well as their utility for simplifying TNBC classification and designing drug regimens.

mTOR complex 1 signalling regulates polyamine metabolism and thereby promotes tumorigenesis, through regulation of the stability of a key enzyme, AMD1.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.