Search

Crystal structures of BAK core domain dimers suggest a mechanism by which lipids contribute to the oligomerization of BAK, which is essential for BAK-mediated permeabilization of the mitochondrial outer membrane.

The lipid transporter FATP2 reprograms neutrophils to polymorphonuclear myeloid-derived suppressor cells by mediating the uptake of arachidonic acid and promoting the synthesis of prostaglandin E₂.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

Estrogen controls female fertility in part via restraining or promoting kisspeptin (Kiss1)-neuron activity in the arcuate hypothalamic nucleus and the AVPV hypothalamic nucleus, respectively. Here the authors report that estrogen receptor alpha (ERα) interacts with the genome and the nuclear receptor co-repressor NR0B1 (DAX1) to manifest region-specific actions on Kiss1 expression.

Two doses of the coronavirus disease 2019 vaccine ChAdOx1 nCoV-19 boost antibody responses and functions in phase 1/2 trial participants.

Markovic et al. demonstrate in rodents that anhedonia-like states in inflammatory pain are mediated through increased inhibitory control and subsequent diminished activity of mesolimbic dopamine neurons.

Anterior face patches in the macaque have been assumed to represent face identity in a holistic manner. Here the authors show that the neural encoding of face identity in the anterior medial and anterior fundus face patches are instead driven principally by local features.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

Mineralization of platinum-group elements in mafic intrusions occurs due to repeated self-intrusion of magma, according to strontium isotope heterogeneities preserved in the Rum layered intrusion, Scotland.

The CNV analysis group of the Psychiatric Genomic Consortium analyzes a large schizophrenia cohort to examine genomic copy number variants (CNVs) and disease risk. They find an enrichment of CNV burden in cases versus controls and identify 8 genome-wide significant loci as well as novel suggestive loci conferring either risk or protection to schizophrenia.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

Multi-ancestry genome-wide association analyses identify new risk loci for Parkinson’s disease, and fine-mapping and co-localization analyses implicate candidate genes whose expression is associated with disease susceptibility.

Over one hundred loci have been identified to be associated with the familial risk of prostate cancer but the functional effects are poorly understood. Here the authors use single-nucleotide variant and epigentic data to show an underlying genetic architecture marked by histone modification.

Prostate cancer often does not progress to invasive disease and thus markers predicting the course of the disease progression are critical for optimal treatment choices. Here the authors show that variants at two genetic loci correlate with the aggressiveness of prostate cancer.

Fidler et al. show that anti-IL-1β treatment of atherosclerotic Ldlr-null mice with clonal expansion of Tet2-null or Jak2^VF hematopoietic stem cells promotes the recruitment of fibroblast-like cells to the plaque fibrous cap, leading to cap thickening and increased plaque stability. Conversely, the removal of fibroblast-like cells during atherosclerosis progression results in reduced fibrous cap formation in mice receiving anti-IL-1β antibody treatment.

The influence of contaminants is one of the factors hindering self-sustained thermonuclear burn in inertial confinement fusion. Here, the authors present evidence, through simulations and experiments, that contaminants do not fully reach thermal equilibrium, and thus their amount is usually underestimated.

The rapidly evolving Y chromosome accumulates male-benefit genes but is often poorly characterized in many mammals. Here, the authors assemble the male specific region of the horse Y chromosome and investigate its evolution and function.

A single-center, observational cohort study assessing the mitochondrial bioenergetics of left ventricular tissue from patients undergoing coronary artery bypass grafting surgery suggests that viable myocardium has global alterations in bioenergetics and transcriptome without large regional differences between areas with or without inducible ischemia.

RIPK3-mediated phosphorylation of the mixed lineage kinase domain-like (MLKL) pseudokinase is thought to be the trigger for MLKL activation during necroptotic signaling. Here the authors provide evidence that the transition of human MLKL from a monomeric state to a tetramer is essential for necroptosis signalling.

It is hoped that quantum computers may be faster than classical ones at solving optimization problems. Here the authors implement a quantum optimization algorithm over 23 qubits but find more limited performance when an optimization problem structure does not match the underlying hardware.

Cyclic peptides are of particular interest due to their pharmacological properties, but their design for binding to a target protein is challenging. Here, the authors present a computational “anchor extension” methodology for de novo design of cyclic peptides that bind to the target protein with high affinity, and validate the approach by developing cyclic peptides that inhibit histone deacetylases 2 and 6.

Quantum supremacy is demonstrated using a programmable superconducting processor known as Sycamore, taking approximately 200 seconds to sample one instance of a quantum circuit a million times, which would take a state-of-the-art supercomputer around ten thousand years to compute.

Using a database of doubly labelled water energy expenditure measurements spanning more than 30 years, Speakman and colleagues show that total energy expenditure in humans has declined over time, while adjusted physical activity energy expenditure has increased over time.

L-Myc, a paralogue of the proto-oncogene c-Myc, is shown to regulate dendritic cell homeostasis and functionality; unlike c-Myc, L-Myc is not repressed by interferons and its expression allows for optimal dendritic cell proliferation and T-cell priming in the presence of inflammation.

Helper T cell subsets are characterized functionally by the cytokines they produce. Benoist and colleagues demonstrate that in vivo helper T cells do not manifest as discrete helper subsets but rather form a continuum shaped by microbial exposure.

Neural systems adapt to changes in stimulus statistics. The authors find that neocortical pyramidal neurons adapt with a time scale that depends on the time scale of changes in stimulus statistics, and that for individual neurons the firing is a fractional derivative of slowly varying stimulus parameters.

A study demonstrating increasing error suppression with larger surface code logical qubits, implemented on a superconducting quantum processor.

Winter sea ice is thought to provide critical grazing habitat for overwintering Antarctic krill. In contrast, here the authors show that the pack-ice zone is a food-poor habitat, but does serve as an important sheltering ground for developing larvae.

The BIN1 SNP rs744373 is associated with higher CSF tau and phosphorylated tau levels. Here the authors show, using PET imaging, that this SNP is associated with tau accumulation in the brain as well as impaired memory in older individuals without dementia.

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.

GNPS is an open-access community-curated analysis platform for sharing natural product mass spectrometry data that enables continuous, automatic reanalysis of deposited 'living' data sets.

Calcium signalling in glial cells couples neuronal activity to regional changes in cerebral blood flow, but the polarity of its effect on the diameter of neighbouring arterioles has remained controversial. This paper reveals that when the glycolytic state of the brain is enhanced by lower tissue oxygenation, glia-mediated vasoconstrictions convert to vasodilations.

Rosalind Eeles, Christopher Haiman and colleagues report genome-wide association and meta-analyses of prostate cancer in populations of European, African, Japanese and Latino ancestry. They identify 23 new susceptibility loci, including one associated with early-onset prostate cancer.

A quantitative high-throughput screen identified an inhibitor of phosphoglycerate dehydrogenase (PHGDH), a key enzyme for serine synthesis. This inhibitor limits one-carbon unit availability for nucleotide synthesis.