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Ancient valleys suggest a warm early Mars where liquid water flowed, but a greenhouse effect strong enough to offset a dim early Sun has been difficult to explain. Climate simulations suggest that sufficient concentrations of the greenhouse gases CO₂ and H₂ — outgassed during volcanic eruptions — could have warmed Mars above water’s freezing point.

Electrical excitability in neuroendocrine SCLC cells promotes tumour progression through action potential firing, increasing ATP demand and oxidative phosphorylation dependency, whereas non-neuroendocrine cells provide metabolic support, driving a tumour-autonomous cycle that enhances tumorigenesis and metastasis.

Chemical disequilibrium is a known biosignature, and it is important to determine the conditions for its remote detection. A thermodynamical model coupled with atmospheric retrieval shows that a disequilibrium can be inferred for a Proterozoic Earth-like exoplanet in reflected light at a high O₂/CH₄ abundance case and signal-to-noise ratio of 50.

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).

Auxilliary Activity Family 5 (AA5) comprises mononuclear copper radical oxidases with catalytic diversity that is not well characterised. Here, structural, phylogenetic and biochemical analyses advance our understanding of the potential biological and biotechnology functions of these proteins.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Engineered live bacteria could represent a new class of therapeutic treatment for human disease. Here, the authors use a human gut-on-a-chip microfluidics system to characterize an engineered live bacterial therapeutic, designed for the treatment of phenylketonuria, and to construct mathematical models that predict therapeutic strain function in non-human primates.

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.

Neoantigen prediction from clinical samples is improved using a neural network model trained on a large HLA peptide and genomic tumor dataset.

Upper tract urothelial carcinoma (UTUC) is an aggressive cancer and largely uncharacterised cancer. Here, Faltas and colleagues report its distinctive molecular and immune landscape compared to urothelial carcinoma of the bladder and explore the role of FGFR3 signaling in UTUC biology.

In this immunological ancillary study of the PREVAC trial, the authors show that approved Ebola virus vaccines induce memory T-cell responses that persist during the five year follow-up after initial vaccination.

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.

A comparative analysis of Cryptosporidium genome sequences elucidates the evolutionary history of these parasites and highlights changes associated with its human adaptation.

Characterizing fission products in uranium dioxide nuclear fuel is important for predicting its long-term properties. Here, machine learning is used to mine microscopy images of precipitates and nanoscale gas bubbles in high-burn-up fuels, providing detailed structural insight of nanoscale fission products.

Cancer genetics has benefited from the advent of next generation sequencing, yet a comparison of sequencing and analysis techniques is lacking. Here, the authors sequence a normal-tumour pair and perform data analysis at multiple institutes and highlight some of the pitfalls associated with the different methods.

Comprehensive factor analysis of core diagnostic features provides insights into the complex genetic architecture underlying phenotypic heterogeneity in autism.

Here, using clinical samples and autopsy tissues, the authors combine fast-colorimetric test (LAMP) for SARS-CoV-2 infection and large-scale shotgun metatranscriptomics for host, viral, and microbial profiling and provide a map of the viral genetic features of the New York City outbreak and associate specific host responses and gene expression perturbations with SARS-CoV-2 infection.

As a moist atmosphere warms, it will reach a limit after which it is unable to radiate incoming solar radiation back to space, and a runaway greenhouse will occur. Calculations suggest that this limit is lower than previously thought and, for a water-saturated atmosphere, a runaway greenhouse can occur under present-day solar radiation.

The genome of a western lowland gorilla has been sequenced and analysed, completing the genome sequences of all great ape genera, and providing evidence for parallel accelerated evolution in chimpanzee, gorilla and human lineages at a number of loci.

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.

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

In many planetary atmospheres, including that of Earth, the base of the stratosphere—the tropopause—occurs at an atmospheric pressure of 0.1 bar. A physically based model demonstrates that the pressure-dependence of transparency to infrared radiation leads to a common tropopause pressure that is probably applicable to many planetary bodies with thick atmospheres.

One reason for the high failure rate of experimental cancer therapies is that mouse tumor models do not accurately predict the behavior of human cancers. Zhou et al. provide more realistic models by generating chimeric mice bearing drug-inducible, tissue-specific oncogenes.

Previous work has identified several genes where mutations lead to breast cancer, but other genetic and environmental factors must still be accounted for. A large study of genetic association with breast cancer points to four novel genes and many more genetic markers that should be pursued for their link to cancer susceptibility.

People infected with West Nile virus often experience cognitive side effects including memory loss through unknown mechanisms; mice and humans infected with the virus experience a loss in hippocampal presynaptic terminals, which can be reversed by disrupting complement or microglia in mice.

Two drugs, miconazole and clobetasol, have functions that modulate differentiation of oligodendrocyte progenitor cells directly, enhance remyelination, and significantly reduce disease severity in mouse models of multiple sclerosis.

A new ice core from West Antarctica shows that, during the last ice age, abrupt Northern Hemisphere climate variations were followed two centuries later by a response in Antarctica, suggesting an oceanic propagation of the climate signal to the Southern Hemisphere high latitudes.

This study uses chromatin marks in four mouse cell types to identify ∼1,600 large multi-exonic transcriptional units that do not overlap known protein-coding loci and are highly conserved. Putative functions are assigned to each of these large intervening non-coding RNAs, which range from ES pluripotency to cell proliferation.

The Habitable Exoplanet Observatory (HabEx) is a conceptual space-based 4-m telescope with the means to image and characterize potentially habitable planets orbiting Sun-like stars, and with ultraviolet to near-infrared imaging and spectroscopic capabilities suited to general observatory science.