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After spinal cord injury, lesion-remote astrocytes acquire heterogeneous, spatially restricted reactivity states that shape neuroinflammation, neural repair and neurological recovery.

This study demonstrates that guanfacine immediate release enhances cognitive control circuit function and behavioral performance in a neurobiologically defined cognitive biotype of depression, achieving a 76.5% clinical response rate and improving life satisfaction, marking a promising advance in precision medicine.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

The photosynthetic production of oxygen in the ocean is thought to have begun at least 2.7 billion years ago. The geochemistry of marine sediments deposited 2.6 billion years ago suggests that ocean margins were oxygenated at least 100 million years before the first significant increase in atmospheric oxygen concentrations.

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).

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.

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.

How atmospheric oxygen concentrations evolved from only small amounts for the early Earth to about 21 per cent today remains uncertain; here our latest understanding of the evolution of Earth’s oxygen levels is discussed.

The authors investigate functional connectivity before and after transcranial magnetic stimulation in veterans with treatment-resistant depression stratified by cognitive biotype, demonstrating associated brain connectivity-mediated improvement in cognitive behavioral task performance.

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.

Earth’s oxygenation history can be reconstructed using machine learning and mafic igneous geochemical data. Agreement with independent proxy predictions for surface conditions implies that interior processes are critical in atmospheric oxygenation.

A 2.5-billion-year record of oxygen isotopes in sedimentary sulfate reveals the transitional oxygenation of the Earth’s surface and provides constraints on the dynamic, lengthy co-oxygenation of Earth’s atmosphere and oceans.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disorder characterised by asthma, eosinophilia and vasculitis. Here, the authors describe a genome-wide association study of EGPA that reveals clinical and genetic differences between subgroups stratified by autoantibody status (ANCA).

Phosphorus is a biolimiting nutrient that is important in regulating the redox state of the ocean–atmosphere system. Here, the ratio of phosphorus to iron in iron-oxide-rich sedimentary rocks through time has been used to evaluate the evolution of the marine phosphate reservoir. Phosphate concentrations have been relatively constant over the past 542 million years of Earth's history, but were high in the aftermath of the 'snowball Earth' glaciations some 750 to 635 million years ago, with implications for the rise of metazoan life.

Loss of the Y chromosome in tumour cells is associated with a poor prognosis for patients with bladder cancer by causing local T cell exhaustion, which also increases the response to immune checkpoint blockade therapy.

In this Review, Lyons, Tino and colleagues explore the evolution of microbial life on Earth and examine the diversity of early microbial metabolic pathways, their associations with biogeochemical cycles and how they shaped and responded to changing surface environments over billions of years.

A global multi-taxon extinction risk assessment of freshwater fauna for The IUCN Red List of Threatened Species finds one-quarter of species to be at high risk of extinction.

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.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

Metabolic disorder significantly contributes to diabetic vascular complications, including diabetic retinopathy (DR). This study reveals that O-GlcNAcylation, a nutrient-sensitive protein modification, drives vascular dysfunction in DR by stabilizing Hippo signaling key components YAP/TAZ. Targeting O-GlcNAc-YAP/TAZ shows therapeutic potential for mitigating DR pathology.

Why did oxygen not appear in Earth's atmosphere until hundreds of millions of years after photosynthesizing organisms first produced it? Perhaps because reducing gases from undersea volcanoes claimed it first.

Chromium isotopes provide an eyebrow-raising history of oxygenation of Earth's atmosphere. Not least, it seems that oxygen might have all but disappeared half a billion years after its initial rise.

Glioma tumours are known to be heterogenous in mutation and gene expression patterns, but sampling limitations can lead to inaccurate detection of evolutionary events. Here, the authors carry out multi-omics analysis of multi-regional biopsies from 68 patients and show differential mutations in non-enhancing regions.

Reconstruction of oceanic phosphorus concentrations during a large negative carbon-isotope excursion co-occurring with global oceanic oxygenation and evolution of some of Earth’s earliest animals suggests that decoupled phosphorus and ocean anoxia cycles during the Ediacaran may have prolonged the rise of atmospheric oxygen.

Would Earth's early ocean have been a frozen wasteland had levels of atmospheric methane not been sky high? Maybe. Or maybe, according to a new view of an old idea, the main warming agent was carbon dioxide.

A dataset of 3D images from more than 200,000 human induced pluripotent stem cells is used to develop a framework to analyse cell shape and the location and organization of major intracellular structures.

Restoring mitochondrial function has emerged as a promising therapeutic strategy for diabetic retinopathy. Here, the authors show that mitochondrial hyperfusion blunts mitophagy during the disease process, and that rescuing this process pharmacologically confers retinal neuroprotection independent of an improved glycaemic status in type-1 diabetic mice.

The disappearance of non-mass-dependent sulphur isotope anomalies from the rock record is thought to indicate the increase in atmospheric oxygen concentration from its initial, persistently low level; however, as a result of long-term surface recycling these anomalies may in fact survive in the sedimentary record for as long as 100 million years after an increase in atmospheric oxygen.

It has been suggested that the Cambrian ocean was oxygen deficient, but physical evidence for widespread anoxia has been lacking. Now, sulphur isotope data from Cambrian rocks at six different locations around the world is presented, with the finding of a positive sulphur isotope excursion in phase with a large excursion in the marine carbon isotope record, which is thought to be indicative of a global carbon cycle perturbation at the time. With the help of a box model, these isotope shifts support the idea of large-scale anoxic and sulphidic conditions in the later Cambrian ocean.

The evolution of oxygenic photosynthesis should have occurred some time before the oxidation of Earth’s atmosphere 2.5 billion years ago. The molybdenum isotopic signature of shallow marine rocks that formed at least 2.95 billion years ago is consistent with deposition in waters that were receiving oxygen from photosynthesis at least half a billion years before the oxidation of the atmosphere.

Data are presented that support the idea of an oxygenation event in the immediate aftermath of the Marinoan glaciation, pre-dating previous estimates for post-Marinoan oxygenation by more than 50 million years.

Clay minerals played a vital role in the delivery of phosphorus (P) to shallow Neoproterozoic post-Snowball glaciation marine waters. The resulting increase in P bioavailability by at least 20-fold coincided with seawater oxygenation.

Global oxygen regulation over Earth history has largely depended on variations in organic carbon burial, which includes the suppression of land vegetation due to fires. Here, the authors show that major evolutionary changes in plant ecosystems could have influenced fire regimes and thus affected atmospheric O₂.

Zinc is a marine nutrient that may have been limited in the early oceans. Estimates of marine zinc availability through time suggest that values were instead near-modern during the Proterozoic eon.

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.

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.

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.

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.