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Rising CO₂ levels reduced drought stress on plants on the Qinghai–Tibetan Plateau over the past four decades, but this benefit is largely cancelled out by warming that increases plant water demand, as revealed by ecological modelling and multi-source observations from 1979 to 2018.

Hydrocarbon-contaminated soils disrupt microbiome composition and function alongside severely reduced hydrogen oxidation rates, and higher carbon fixation rates, according to an assessment of a 40-year-old legacy petroleum spill on the soil microbial diversity of Bunger Hills, East Antarctica.

A prospective nationwide genomic screening pilot for ten genes in young adults in Australia detected pathogenic variants in 2% of the population, most of whom were ineligible for government-funded genomic testing.

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.

During SARS-CoV-2 infection caspase-8 fuels harmful inflammation independent of apoptosis. Genetic loss of caspase-8 reduces cytokine levels, lowers viral load and mitigates disease severity, revealing non-apoptotic caspase-8 as a key driver of severe COVID-19.

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.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

TANK-binding kinase-1 (TBK1) and its homologue IκB kinase-ε (IKKε) are critical in the induction of the interferon response and the response to infection by pathogens. Here the authors show that pharmacological targeting of TBK1 AND IKKε reduces the immunopathology seen in a murine model of SARS-COV-2 infection.

Douglas Easton, Per Hall and colleagues report meta-analyses of genome-wide association studies for breast cancer, including 10,052 cases and 12,575 controls, followed by genotyping using the iCOGS array in an additional 52,675 cases and 49,436 controls from studies within the Breast Cancer Association Consortium (BCAC). They identify 41 loci newly associated with susceptibility to breast cancer.

Response to chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC) is often limited. Here, the authors report improved response to chemotherapy in PDAC patients with hyperglycaemia and investigate the underlying mechanism via glucose-mediated disruption of redox metabolism

The International Union for Conservation of Nature’s Global Ecosystem Typology has been developed to provide a systematic framework for data on all of Earth’s ecosystems in a unified theoretical context to support biodiversity conservation and ecosystem services.

Metagenomic and biochemical analyses of soil samples from Antarctic desert regions provides evidence that bacteria in these soils derive carbon and energy from atmospheric CO, H₂ and CO₂.

Here, the authors clarify the architecture of genetic risk on chromosome X in three male-biased psychiatric disorders. Leveraging this information they identify an exome-wide significant autism risk gene, MAGEC3, and provide a path forward for future gene discovery on this chromosome.

Parathyroid hormone (PTH) is an endogenous hormone and osteoporosis therapeutic that suppresses sclerostin activity. Here the authors develop SIK inhibitors as potential therapeutic tools and use them to show that PTH-cAMP signalling in osteocytes inhibits SIK2 from driving Hdac4/5 nuclear shuttling to suppress sclerostin.

A report from the Australian Acute Care Genomics programme shows that the integration of rapid whole-genome sequencing and multi-omic analyses informs diagnoses and treatment decisions in a prospective cohort of 290 critically ill infants and children.

Immune checkpoint blockade (ICB) is partially successful as a cancer therapy. Here using mouse models, the authors transcriptionally monitor responding and non-responding tumours showing that responding tumours were associated with transient IFN-β signalling which could promote the anti-tumour response.

Analysis of the dynamics of chromosome reorganization after exit from mitosis reveals the distinct but mutually influential forces that drive chromatin reconfiguration.

An integrated transcriptome, genome, methylome and proteome analysis of over 200 lung adenocarcinomas reveals high rates of somatic mutations, 18 statistically significantly mutated genes including RIT1 and MGA, splicing changes, and alterations in MAPK and PI(3)K pathway activity.

A transcriptional analysis of kidney organoids reveals batch effects as the key drivers of variation, mainly through differences in maturity, and provides a list of highly variable genes and a method for estimating differentiation stage for improved disease modeling.

The assembly of the genome of the koala provides insights into its adaptive biology and identifies gene expansions that contribute to its ability to detoxify eucalyptus-derived compounds and perceive plant secondary metabolites.

Insertion of a tissue-invariant chromatin domain boundary into 16 ectopic loci leads to various structural phenotypes, which depend on local chromatin features, CTCF binding and transcriptional status.

The authors identify Irf7 and associated interferon signaling as an important factor suppressing bone metastasis of breast cancers. Irf7 is lost in experimental metastasis and human bone metastastic tissue, and this fosters an immunosuppressive environment that facilitates metastasis. Manipulating this innate immune signaling pathway emerging from tumor cells by interferon administration had beneficial effects in mouse models by reducing bone metastasis and increasing survival time.

The molecular basis of the clinically important MAM blood group antigen present in most humans is unknown. We identify EMP3 as its encoding gene, establishing MAM as a new blood group system, and demonstrate the role of EMP3 in erythropoiesis through its interaction with the signalling molecule CD44.

It is unclear whether CO₂-stimulation of photosynthesis can propagate through slower ecosystem processes and lead to long-term increases in terrestrial carbon. Here the authors show that CO₂-stimulation of photosynthesis leads to a 30% increase in forest regrowth over a decade of CO₂ enrichment.

Biological nitrogen fixation is achieved by nitrogenase, but the mechanism remains enigmatic. Here, the authors report high resolution single particle cryoEM structures of homocitrate-compromised MoFe-proteins and unveil a new binding partner.

The lipocalin protein Scn-Ngal is known to bind iron-chelating siderophores, leading to inhibition of bacterial growth. New results reveal that Scn-Ngal, in the absence of bacterial infection, can form a complex with catechol that binds and transports iron in vivo.

Andrea Superti-Furga, Ron Wevers, Clara van Karnebeek, Luisa Bonafé and colleagues identify mutations in NANS, which encodes the sialic acid synthase, in nine individuals with severe infantile-onset developmental delay and skeletal dysplasia. They describe abnormal metabolites accumulating because of deficient NANS enzyme activity and show that impaired sialic acid synthesis in zebrafish perturbs skeletal development, which can partially be rescued by supplementation with exogenous sialic acid.

Stuart Macregor, Tien Wong and colleagues report meta-analyses that identify 16 new loci associated with central corneal thickness. They also identify two loci associated with risk of developing keratoconus, a common corneal ectasia.

X-linked myotubular myopathy (XLMTM) is a severe muscle disease with no effective treatment. Here, the authors show that tamoxifen, a drug used to treat breast cancer, rescues the pathology in a mouse model of the disease, at least in part by normalizing expression of the disease modifier proteins DNM2 and BIN1

Agriculture is often viewed as a source of problems needing innovative solutions. But agriculture can actually be a source of innovations for the bioeconomy, if researchers embrace the cultural changes needed.

Merlini, Rafalski et al. show that dynamic microglial brain surveillance prevents hyperexcitability and seizures by G_i-dependent microglia–neuron interactions in response to evoked neuronal activity to maintain physiological network synchronization.

The World Health Organization framework for tracking SARS-CoV-2 variants has been updated to reflect the continued evolution of the virus; this framework could be adapted for other emerging respiratory diseases with epidemic and pandemic potential.

The recent FACE model–data synthesis project used data from two FACE experiments to assess land ecosystem models. This Perspective details the 'assumption-centered' approach used to identify and evaluate the causes of model differences.

Global sequencing and surveillance capacity for SARS-CoV-2 must be strengthened and combined with multidisciplinary studies of infectivity, virulence and immune escape, in order to track the unpredictable evolution of the ongoing COVID-19 pandemic.

This Review on the interplay between the immune system and metastasis is part of our wider Series of Reviews on Cancer Immunology and Immunotherapy.

The authors summarize the history of the ENCODE Project, the achievements of ENCODE 1 and ENCODE 2, and how the new data generated and analysed in ENCODE 3 complement the previous phases.

Kyle Walsh and colleagues identify a variant near TERC associated with glioma susceptibility. They further show that glioma risk alleles near TERC and TERT are associated with longer mean telomere length in leukocytes, implicating telomerase activity in gliomagenesis.