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Guida et al. assess seven measures of biological age in SJLIFE Cohort and reveal that survivors of cancer age faster than healthy controls and have increased risk of frailty and death. The aging trajectory is further affected by cancer type and therapy.

Analysis of data from 33 longitudinal cohorts from low- and middle-income countries indicates that conditions during pre-conception, pregnancy and the first few months of life are crucial in determining the risk of growth faltering in young children.

In this largest whole-exome sequencing study of epilepsies to date, the Epi25 Collaborative identified extremely rare variants that confer risk for diverse epilepsy subtypes, highlighting roles in synaptic transmission and neuronal excitability.

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.

Quality, quantity and timing of sleep are important factors for overall human health. Here, the authors perform GWAS for sleep traits estimated using wearable accelerometers and identify 47 genetic associations, including 26 novel associations for measures of sleep quality and 10 for nocturnal sleep duration.

The largest whole-exome sequencing study of sporadic congenital hydrocephalus identities mutations associated with disrupted fetal neuro-gliogenesis as the primary pathophysiological event in a significant number of cases.

Transmission spectroscopy observations from the James Webb Space Telescope show the detection of carbon dioxide in the atmosphere of the gas giant exoplanet WASP-39b.

An analysis of longitudinal cohort data across diverse populations suggests that the incidence of wasting between birth and 24 months is higher than previously thought, and highlights the role of seasonal factors that affect child growth.

Nitric oxide is a volatile free radical second messenger with a large number of biological effects. Here Eroglu et al. develop genetically encoded fluorescent biosensors for nitric oxide and use them to visualise subcellular nitric oxide dynamics in single cells.

Mycobacterium tuberculosis disrupts glycolysis in infected myeloid cells. Here, Pacl et al. show that maximal glycolytic capacity in myeloid cells is essential for host protection from tuberculosis and that NAD(H) homeostasis underlies glycolysis-mediated protection of the host.

The inflammasome is normally activated by pathogens to induce tissue inflammation. Here the authors show that, in mouse experimental colitis models, Nlrp1 inflammasome sensor activates IL-18 to reduce beneficial colonic Clostridiales species, thereby decreasing microbial butyrate and its protective effects on colitis.

Here, the authors perform a meta-analysis in 26,699 people with seizures and 492,324 controls to identify 25 genome-wide significant copy-number variants. The discovered loci point to known disease genes and associations with clinical annotations.

Reported COVID-19 mortality rates have been relatively low in Syria, but there has been concern about overwhelmed health systems. Here, the authors use community mortality indicators and estimate that <3% of COVID-19 deaths in Damascus were reported as of 2 September 2020.

Somatic mutational loads in cancer genomes change with chromatin domain boundaries. Different mutational processes lead to distinct somatic mutation distributions in active versus inactive domains, including during tumor evolution.

Toothpaste, mayonnaise and other systems are soft particle glasses. In these, the soft particles are jammed so that the glasses behave like weak solids at rest but at sufficient stress flow like liquids. This has made their theoretical understanding difficult. A new micromechanical model is now able to predict the rheology of these soft particle glasses.

l-cysteine is required for the growth of Lactobacillus iners, a vaginal microbiome species typically associated with adverse outcomes that lacks cysteine biosynthesis pathways and key uptake mechanisms present in other lactobacilli. Cystine uptake inhibitors can be used to suppress L. iners abundance in vitro in favour of L. crispatus, a species associated with favourable outcomes.

Laser microdissection and microarrays are used to assess 900 precise subdivisions of the brains from three healthy men with 60,000 gene expression probes; the resulting atlas allows comparisons between humans and other animals, and will facilitate studies of human neurological and psychiatric diseases.

This study reports a global analysis of binding sites for over 200 RNA-binding proteins (RBPs) from 24 species; conserved RNA-binding motifs are identified, and their analysis allows prediction of interaction sites based on the sequence of the RNA-binding domain alone.

HK022 put is an RNA element that inhibits transcription termination without aids from protein factors. Here, authors solved cryo-EM structures of put-associated RNA polymerase and showed the structure of putRNA and its binding to the RNA polymerase.

William Evans and colleagues find that the proinflammatory genes CASP1 and NLRP3 are expressed at higher levels in primary acute lymphoblastic leukemia cells that are resistant than in those that are sensitive to glucocorticoid treatment. They find that CASP1 mediates glucocorticoid resistance through cleavage of the glucocorticoid receptor.

The transcription factor Ikaros, which is essential for lymphocyte development, contains multiple zinc fingers. Smale and colleagues show that mice lacking different zinc fingers develop distinct lymphocyte-developmental defects and tumor susceptibility.

Analysis of chromatin state and accessibility in mouse tissues from twelve sites and eight developmental stages provides a comprehensive view of chromatin dynamics.

This paper describes molecular subtypes of cervical cancers, including squamous cell carcinoma and adenocarcinoma clusters defined by HPV status and molecular features, and distinct molecular pathways that are activated in cervical carcinomas caused by different somatic alterations and HPV types.

Although epigenome-wide association studies of Alzheimer’s disease have highlighted neuropathology-associated DNA methylation differences, previous studies have been limited in sample size and brain region used. Here, the authors combine data from six DNA methylomic studies of Alzheimer’s disease (N = 1453 unique individuals) to identify differentially methylated loci across cortex.

Simon Harris and colleagues report whole-genome sequencing of 36 Chlamydia trachomatis representative strains from temporally and geographically diverse sources and use this to construct a genome-wide phylogeny of the species. They find that epidemic spread can be driven by clonal expansion from a single source and also report evidence for recombination in recent clinical strains both within and between biovars.

SPAK kinase is a master regulator of cation-Cl⁻ cotransporters. Here the authors describe a new SPAK inhibitor with robust protective effects in rodent hydrocephalous and ischemic stroke models.

Differentiated planetesimals may have delivered iron-rich material to Earth in giant impacts at the end of accretion. Impact experiments suggest that the planetesimals’ iron cores vaporized, aiding dispersal and mixing into Earth’s mantle.

Chlamydia trachomatis isolates causing a blinding disease (trachoma) form a single lineage that is different from the lineages causing urogenital infections. Here, Andersson et al. show however that trachoma isolates from Australia are more closely related to urogenital strains than to other trachoma isolates.

There are increasing questions about emissions from unconventional oil and gas exploration, and the impact of such exploration on health outcomes has not been thoroughly studied. Looking at data from 2.5 million wells and more than 15 million medical beneficiaries, Li et al. find an increased mortality risk for beneficiaries downwind of unconventional plays.

GWAS have previously found 24 genomic loci associated with chronotype, an individual’s preference for early or late sleep timing. Here, the authors identify 327 additional loci in a sample of 697,828 individuals and further explore the relationships of chronotype with metabolic and psychiatric diseases.

Transcription factors compete for superenhancer sites and have antagonist functions. Farrar and colleagues identify regulatory competition between STAT5 and IKAROS or NF-κB in B cells and show that the ratio of STAT5 to IKAROS or to NF-κB can serve as a prognostic marker of disease severity of the leukemia B-ALL.

In the Gale Crater on Mars, organic matter has been detected, but in much lower concentrations than expected. Here, the authors conduct clay mineral synthesis experiments which suggest that clay minerals may rapidly form under oxidized conditions and thus explain the low organic concentrations in Gale Crater.

Monitoring neuronal activity in the rodent in vivobrain is commonly done using micro-electrode arrays but these devices are not normally compatible with optical technologies. Here the authors design a transparent and flexible electrode array based on graphene that allows them to combine electrophysiological recordings with optogenetic and imaging experiments.

Colorectal tumors with mutated KRAS and APC require the amino acid transporter SLC7A5 to drive tumorigenesis. Mechanistically, SLC7A5 drives transcriptional and metabolic reprogramming by maintaining intracellular amino acid levels, leading to enhanced protein synthesis.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

A cross-ancestry meta-analysis identified 126 genetic loci associated with chronic pain intensity, revealing correlations with substance use and psychiatric traits.

Age-related macular degeneration (AMD) leads to dysfunctional retinal pigment epithelium (RPE) and vision loss. Here, the authors perform ATAC-seq to study chromatin accessibility and find that differentially accessible regions are enriched for photoreceptor and RPE-specific transcription factors in AMD

Loss of BAF47 destabilizes the BAF complex on chromatin, and reintroduction of BAF47 leads to enhancer activation and Polycomb opposition at bivalent promoters. BAF47 loss affects BAF and PBAF complexes, which have distinct functions in regulation of enhancers and promoters.