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 A transcriptomic cell-type atlas of the whole adult mouse brain with ~5,300 clusters built from single-cell and spatial transcriptomic datasets with more than eight million cells reveals remarkable cell type diversity across the brain and unique cell type characteristics of different brain regions. 

A study finds that a protease called granzyme K can activate the entire complement cascade, explaining how it can drive destructive inflammation in inflammatory diseases such as rheumatoid arthritis.

Glutathione has pleiotropic functions in different organs. Here the authors specifically examine deletion of a glutathione synthetic enzyme in the liver of adult mice and show that lack of glutathione affects lipid abundance through repressing NRF2.

DNA single-strand breaks in neurons accumulate at high levelsin functional enhancers.

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.

A genome-wide meta-analysis of data from six US and European cohorts involving 1.3 million individuals identifies 243 genetic variants associated with risk and pathophysiology of depression, which is used to develop polygenic risk scores for the prediction of depression recurrence and comorbid psychiatric disorders.

An estimated AU$583 billion per year cost of in situ recovery of terrestrial and freshwater species in Australia, including through habitat restoration and retention and management of invasive species, is not an expected conservation budget, but exemplifies the severe cost of nature declines.

Single-cell transcriptomics reveals that the heterogeneity of anti-CD19 CAR T cell infusion products contributes to variability in clinical response, early molecular response and development of immune effector cell-associated neurotoxicity syndrome in patients with large B cell lymphomas.

Using the GTEx data and others, a comprehensive analysis of adenosine-to-inosine RNA editing in mammals is presented; targets of the various ADAR enzymes are identified, as are several potential regulators of editing, such as AIMP2.

Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.

In Alzheimer’s disease (AD) tau and neurodegeneration have complex regional relationships. Here, the authors show neuronal hypometabolism discordant with tau burden defines functional resilience or susceptibility to Alzheimer’s pathology via limbic/cortical axes. Susceptible groups have faster cognitive decline and evidence of non-Alzheimer’s pathologies.

Here, the authors use cryo-EM to solve the structures of seven potent human antibodies, and demonstrate in vivo protection in a liver burden assay, using chimeric Plasmodium berghei sporozoites expressing Plasmodium falciparum circumsporozoite protein.

The authors highlight inconsistencies and divergencies in the literature reporting data on indirect calorimetry for studies on whole-body energy homeostasis, and propose harmonization of standards to facilitate data comparison and interpretation across different datasets.

A broadly neutralizing antibody (bnAb) response is required to combat SARS-CoV-2 variants of concern (VOCs). The authors isolated and characterized a large panel of sarbecovirus bnAbs from vaccinated individuals who had recovered from COVID-19, finding that many of these antibodies were able to neutralize all VOCs, including Omicron, and demonstrate prophylaxis in mice infected with diverse sarbecoviruses.

Safely opening university campuses has been a major challenge during the COVID-19 pandemic. Here, the authors describe a program of public health measures employed at a university in the United States which, combined with other non-pharmaceutical interventions, allowed the university to stay open in fall 2020 with limited evidence of transmission.

Hydrologic data collected from river gauges inform critical decisions for allocating water resources, conserving ecosystems and predicting the occurrence of droughts and floods. The current global river gauge network is biased towards large, perennial rivers, and strategic adaptations are needed to capture the full scope of rivers on Earth.

Many individual genetic risk loci associate with multiple diseases, but the molecular basis of these loci often remains unclear. Here, the authors provide a framework to reveal the genetic cross-disease associations at the PROCR vascular disease locus.

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.

Pre-existing immune responses between antigenically related viruses can influence responses in viral infections or vaccinations. Here the authors assess and characterize the presence of antibody and memory B cell populations specific to SARS-CoV2 and endemic human coronaviruses.

Whether Alzheimer’s disease originates in basal forebrain or entorhinal cortex remains highly debated. Here the authors use structural magnetic resonance data from a longitudinal sample of participants stratified by cerebrospinal biomarker and clinical diagnosis to show that tissue volume changes appear earlier in the basal forebrain than in the entorhinal cortex.

Evidence synthesized from 252 large-herbivore exclusion studies suggests that herbivore-induced change in dominance, independent of site productivity or precipitation, best predicts herbivore effects on biodiversity in grassland and savannah sites.

Focal therapy is an emerging treatment option that involves the focal ablation of prostate cancer with preservation of surrounding healthy tissue, which might result in reduced morbidity. In this Review the authors discuss the controversy surrounding optimal patient selection, preoperative tumour localization strategies and the lack of long-term oncological data for focal therapy modalities.

The chronology and mode of parallel evolution remain unclear. Here, the authors compare mid-Holocene and contemporary bottlenose dolphin adaptations between pelagic and coastal ecosystems with paleogenomics, finding rapid adaptation to newly emerged habitat from standing genetic variation.

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

The presence of earthworms is known to enhance the quality and moisture of soil in cool and wet climates. Evanset al. show that termites and ants can improve soil quality in warmer and drier climates—their presence results in elevated water infiltration and nitrogen content, leading to increased wheat yields.

The MAGIC investigators report results of a large genome-wide association study meta-analysis to identify common variants influencing fasting glucose homeostasis. They further show that several of the newly discovered loci influencing glycemic traits are also associated with risk of type 2 diabetes.

The identity of the enzyme that enables vitamin K to combat the adverse side effects of a drug called warfarin has been long sought. Analysis of a type of cell death called ferroptosis has now unexpectedly solved the mystery.

This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual.

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.

Nutrient availability dictates cell differentiation and transition through the Dictyostelium discoideum life cycle. Kelly et al. reveal that the increase in reactive oxygen species associated with nutrient limitation coincides with a sequestration of available cysteine in glutathione, thus limiting sulfur-dependent mitochondrial respiration and promoting aggregation into the differentiated spore form.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

He et al. develop a network-based metric of amyloid-β burden by integrating individualized brain connectomes with amyloid-PET imaging. This approach improves prediction of future cognitive decline in older adults and may support earlier identification of individuals at risk of dementia.

Multiple transcriptome approaches, including single-cell sequencing, demonstrate that escape from X chromosome inactivation is widespread and occasionally variable between cells, chromosomes, and tissues, resulting in sex-biased expression of at least 60 genes and potentially contributing to sex-specific differences in health and disease.

The authors show that rare genetic variants contribute to large gene expression changes across diverse human tissues and provide an integrative method for interpretation of rare variants in individual genomes.

The genome of the gibbon, a tree-dwelling ape from Asia positioned between Old World monkeys and the great apes, is presented, providing insights into the evolutionary history of gibbon species and their accelerated karyotypes, as well as evidence for selection of genes such as those for forelimb development and connective tissue that may be important for locomotion through trees.

A computational approach to generate reference-free protein families from the sequence space in metagenomes reveals an enormously diverse functional space.

Sub-lethal marine heatwaves is shown experimentally to lead to suppression of reproduction in sea urchins. This effect helps explain historical collapses in larval supply that affect population dynamics and is consistent for populations across the latitudinal range.

Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

Ageing increases the risk of many diseases. Here the authors compare blood cell transcriptomes of over 14,000 individuals and identify a set of about 1,500 genes that are differently expressed with age, shedding light on transcriptional programs linked to the ageing process and age-associated diseases.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

The interplay between amyloid and tau pathology in Alzheimer’s disease is still not well understood. Here, the authors show that amyloid-related increased in soluble p-tau is related to subsequent accumulation of tau aggregates and cognitive decline in early stage of the disease.

Co-production includes diverse aims, terminologies and practices. This study explores such diversity by mapping differences in how 32 initiatives from 6 continents co-produce diverse outcomes for the sustainable development of ecosystems at local to global scales.

The genome sequence of segmental allotetraploid peanut suggests that diversity generated by genetic deletions and homeologous recombination helped to favor the domestication of Arachis hypogaea over its diploid relatives.

Alzheimer’s disease is heterogeneous in its neuroimaging and clinical phenotypes. Here the authors present a semi-supervised deep learning method, Smile-GAN, to show four neurodegenerative patterns and two progression pathways providing prognostic and clinical information.

Systematic characterization of longitudinal tau variability in human Alzheimer’s disease using an unbiased subtyping algorithm reveals four trajectories of tau deposition with distinct clinical features.