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.

Climate and land-use change are transforming biodiversity, yet national futures remain uncertain. The study projects growing extinction debts, but suggests that sustainable low-emission pathways can limit the worst impacts on British biodiversity.

Robustness checks and reproduction of analyses with existing and updated data based on 110 articles in economics and political science journals with data and code-sharing requirements found high levels of robustness and reproducibility and determined that robustness was not dependent on author characteristics or data availability.

Sepsis is a heterogeneous inflammatory disease and it is believed treatment requires suitable stratification based on the underlying disease pathology and immunology. Here the authors show genetic variation in the regulatory elements of MTOR can impact neutrophil-T cell cross talk in the context of pneumonia associated sepsis, highlighting a genetic framework for targeted patient stratification.

Planet-evolution models explain JWST data for L 98-59 d through a new scenario: while cooling and escape shrank this planet, a permanent magma ocean supplies sulfur to its atmosphere, in which SO₂ is produced by photochemistry.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

JWST has detected \({{\rm{H}}}_{3}^{+}\) and auroral emissions at Neptune—the only giant planet in the Solar System for which they had proved to be elusive up to now. The observations reveal a factor-of-two cooling of Neptune’s upper atmosphere compared with Voyager 2 data, indicative of energy balance processes acting on a shorter timescale than solar forcing.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

Multiple myeloma involves alterations to T cell function, but mechanisms underlying disease evolution remain unclear. Here the authors find that, unlike solid cancers, multiple myeloma lacks exhausted T cells and is instead characterized by antigen-driven terminal memory T cell differentiation, which may be driven by tumour-intrinsic features including tumour burden and antigen-presentation gene expression.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

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.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

In a study of four brain-dead human decedents, extracorporeal liver cross-circulation using genetically modified pig livers provides essential hepatic functions, supporting the feasibility of this approach for temporary liver support as a bridge to organ transplantation.

Proxy records from Lake Baikal show that rapid cooling coincided with Northern Hemisphere ice sheet expansion 2.7 million years ago, a change accompanied by a transition to open steppe ecosystems.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Removing race and ethnicity from clinical algorithms is feasible, but it requires careful evaluation of algorithmic changes and systemic efforts to address underlying disparities.

This work developed an all-fibre-coupled THz reflection single-pixel imaging system capable of real-time, in vivo, and in situ imaging. It achieves a five-fold improvement in throughput over the state of the art, reaching 30,000 pixels per second.

Lipid nanoparticle based mRNA vaccines are known to induce robust CD4 + T cell responses. Here the authors establish a role of endogenously derived antigen processing in the optimal priming of CD4 + T cell responses to mRNA lipid nanoparticle vaccines.

A high-resolution transcriptomic and epigenomic cell-type atlas of the developing mouse visual cortex from embryonic to postnatal development is presented, providing a real-time dynamic molecular map associated with individual cell types and specific developmental events.

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

A study of SARS-CoV-2 variants examining their transmission, infectivity, and potential resistance to therapies provides insights into the biology of the Delta variant and its role in the global pandemic.

Prenatal Zika virus (ZIKV) exposure can lead to a spectrum of developmental issues, but the mechanisms remain unclear. Here the authors show that prenatal ZIKV exposure in macaques disrupts neurodevelopment, causing prolonged maternal attachment and visual deficits at 3 months that normalize by 12 months, independent of sensory function.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

Here they demonstrate a therapeutic intervention elevating levels of CYP450-derived lipids to control the expansion of intermediate monocytes in tissue and peripheral blood, presenting a first in class therapeutic approach for treating chronic inflammatory disease.

α/β-hydrolase domain-containing protein 11 (ABHD11) is a mitochondrial hydrolase, and its expression in CD4 + T-cells has been linked to remission status in rheumatoid arthritis. Here the authors report that pharmacological inhibition of ABHD11 modulates T-cell effector function via increased 24,25-epoxycholesterol biosynthesis and subsequent liver X receptor activation.

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

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

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.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Genome-wide association analyses of two oral glucose tolerance test-derived measures of postprandial insulin resistance discover ten new loci. Functional characterization identifies nine candidate genes implicated in the regulation of GLUT4.

Many premalignant colorectal polyps in familial adenomatous polyposis arise polyclonally rather than from a single mutated cell, showing diverse early evolutionary trajectories that frequently occur without clonal APC or KRAS driver events.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

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.