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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).

Translation initiation and elongation factors can be targets for cancer treatment. Here, the authors show that inhibiting translation elongation through eIF5A impairs mitochondrial function, slowing the proliferation of tumour cells.

Via high-throughput imaging and tracking over 140 million single mycobacteria, the authors show that drug- and strain-specific killing predict treatment outcomes, with potential to improve drug development and personalized therapy.

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.

The posterolateral cortical amygdala and other connected brain regions have a key role in mediating the transition from investigative to aggressive behaviour in male mice.

PARP inhibitors, either alone or in combination with bevacizumab, have regulatory approval as maintenance therapy following response to first-line platinum-based chemotherapy. Here this group reports SOLACE2 trial investigating whether combining olaparib with low dose cyclophosphamide treatment improves progression-free survival, comparing to olaparib monotherapy alone, in platinum-sensitive recurrent ovarian cancer.

Questioning of necessary responses to climate change is now the dominant form of skepticism on mainstream television, but skepticism of the science behind climate change persists, suggests an analysis of television news programmes in five countries

Lipid particles loaded with RNA coding for tumour-unspecific antigens can enhance early responses of type-I interferons, mediating the success of immune checkpoint inhibitors as well as epitope spreading.

A gene therapy method using AAV can help deliver HIV-fighting antibodies long-term, but the body often rejects them. Here the authors show that a short course of the drug rapamycin helps prevent host anti-drug antibody responses, showing successful antibody delivery in mice and monkeys.

The Tasmanian tiger is an extinct carnivorous marsupial. By sequencing the genome of a preserved specimen the authors show long-term population decline and reveal the genetic basis of the phenotypic convergence between Tasmanian tigers and canids.

PTB is a repressive splicing regulator. The effect of PTB knockdown in HeLa cells is now examined, indicating that similar to other recently examined factors, PTB variably affects splicing in a predictable fashion depending on where its binding site is relative to the target exon.

Analyses of samples from patients with acute myeloid leukaemia reveal that drug response is associated with mutational status and gene expression; the generated dataset provides a basis for future clinical and functional studies of this disease.

Mitochondria play roles in sensing environmental and physiological stress, but their response can become maladaptive during chronic stress. Here they identify a protective miRNA response in C. elegans that maintains tissue health by attenuating mitochondrial stress signaling.

Over the past 25 years, Kristine Ulvund has helped to increase the species’ population size from 50 or so individuals to more than 500.

Deep permafrost soils produce comparable amounts of greenhouse gases as shallow soils in response to warming, according to incubation experiments of deep Arctic lake sediments.

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.

Engineering a mutant-specific customized base editor precisely corrects a mutation while minimizing bystander edits, leading to substantial phenotypic recovery in mouse models of multisystemic smooth muscle dysfunction syndrome.

Genome-wide ancient DNA data from individuals from the Middle Bronze Age to Iron Age documents large-scale movement of people from the European continent between 1300 and 800 bc that was probably responsible for spreading early Celtic languages to Britain.

Preclinical studies indicate that myeloproliferative neoplasms (MPN) may be sensitive to the estrogen receptor modulator, tamoxifen. Here, the authors present a phase II clinical trial reporting the efficacy of tamoxifen in MPN and analysis of peripheral haematopoietic stem cells to identify potential predictive signatures of responders.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

The role of opioids in the neural systems of maladaptive behavioral suppression is unclear. Here, authors identify a thalamoaccumbal brain circuit that is required for the suppression of reward seeking and is rapidly disengaged by opioids leading to unrestricted behavioral actions.

Studies with patient derived xenografts are hampered by factors such as genetic variability and sample availability. Here, the authors generate a leukemia mouse model by lentiviral transduction of normal human cord blood and show an oncogenic role of HOXB genes.

Sulfolobus islandicus is a model organism within the TACK superphylum of the Archaea. Here, the authors perform a genome-wide analysis of essential genes in this organism, show that the proteinaceous S-layer is not essential, and explore potential stages of evolution of the essential gene repertoire in Archaea.

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.

De novo variants altering a conserved region in an intron of HK1 cause congenital hyperinsulinism by perturbing the activity of a putative cell type-specific regulatory element.

USP30 has been proposed to regulate mitophagy, a relevant Parkinson’s disease mechanism. Here, the authors show that Usp30 knockout mice and USP30 inhibitors like MTX115325 demonstrate neuroprotective responses in an alpha-synuclein mouse model of Parkinson’s disease.

 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. 

The ligandability of the human proteome can be expanded using covalent chemistry. A multi-tiered chemical proteomic strategy now provides in-depth maps of tryptoline acrylamide–protein interactions in cancer cells. This platform afforded the discovery of stereoselective covalent ligands for hundreds of human proteins, including compounds that disrupt protein–protein interactions regulating the cell cycle.

An analysis identifies human monoclonal antibodies that potently neutralize wild-type SARS-CoV-2 and protect animals from disease, including two that synergize in a cocktail, suggesting that these could be candidates for use as therapeutic agents for the treatment of COVID-19 in humans.

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.

Tumour recurrence is a common cause of death for patients with cancer. Here Fox et al. show how the antioxidant transcription factor Nrf2 is activated in dormant residual tumour cells and promotes their proliferation and tumour growth by inducing a metabolic reprogramming aimed to maintain redox homeostasis and nucleotide synthesis.

Glioblastoma is resistant to immune-checkpoint inhibitors. In this study, the authors report the results of an expansion cohort (n = 25) of a randomized testing neoadjuvant plus adjuvant pembrolizumab versus adjuvant pembrolizumab alone in patients with recurrent glioblastoma with resectable tumors.

Patients with Parkinson’s disease treated with fetal tissue are assessed 3 years after surgery.

Proteins continuously undergo non-enzymatic modifications such as glycation, which accumulate under physiological conditions but can be enhanced in disease. Here the authors characterise histone glycation, provide evidence that it affects chromatin, particularly in breast cancer, and identify DJ-1 as a deglycase.

Field studies of the bat-to-bat transfer and ingestion of fluorescent biomarkers as a proxy for an oral vaccine are combined with mathematical models to predict the efficacy of oral vaccines for reducing bat rabies outbreaks.