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The slit diaphragm is a key component of the glomerular filter. This study reveals that the slit diaphragm of Drosophila nephrocytes exhibits a fishnet architecture, offering insights into the molecular basis of renal filtration.

Space scientists look back on 30 years of exoplanet discoveries — from rows of massive ‘super-Earths‘ to worlds with perfectly synchronized orbits.

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.

The transcription factors TCF1 and LEF1 promote self-renewal and regulatory functions in B-1a cells.

The authors identify naturally occurring senescent glia in aged Drosophila brains and decipher their origin and influence, determining that they can appear in response to neuronal mitochondrial dysfunction and that they promote lipid accumulation, indicating that these cells link key ageing phenomena.

This Review discusses multiomic approaches for the characterization and biological understanding of cellular senescence, including detailed case studies on skeletal muscle and adipose tissue that highlight current outstanding issues in the field.

Little is known of how the architectural complexity of the neural stem cell niche is achieved. Rujano et al. show that the morphogenesis of a glial niche in Drosophila involves complex proliferative strategies and atypical cell–cell fusion.

Studying RNA dynamics in vivo often relies on fluorogenic approaches, but these can be hampered by factors such as limited sensitivity and sample autofluorescence. Here, the authors describe an ultrasensitive platform for RNA imaging, which features RNA tags that recruit light-emitting luciferase fragments.

Mutations in glucocerebrosidase (GCase) cause the lysosomal storage disorder Gaucher’s disease and are the most common risk factor for Parkinson’s disease. Using a fusion protein comprising GCase and a transferrin receptor antibody fragment, the authors show that the transferrin receptor pathway can be therapeutically exploited to both pass the blood-brain barrier and efficiently target lysosomal GCase deficiency.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

CENP-A is a stable centromere mark, although active transcription poses a potential threat for retaining CENP-A through chromatin remodeling and nucleosome eviction. Here, the authors show that maintenance of the centromeric mark is preserved by Spt6, which recycles CENP-A nucleosomes.

Modeled analyses of 854 European cities show that net temperature-related mortality will increase because of an increase in heat-related mortality exceeding future reductions in cold-related mortality under current climate change projections and even in the presence of high adaptation scenarios.

The brain is vulnerable to stress and disease, with much work focused on defining mechanisms that impact the brain’s resilience. Here the author’s reveal in Drosophila that m⁶A epitranscriptomic modification of RNA dampens the brain’s capacity to mitigate stress by regulating RNA stability and translation.

This study reveals that population aging intensifies heat- and cold-related deaths, more so than climate change, in 50 countries. At 1.53 °C global warming, aging contributes to rising heat-related deaths, offsetting declines in cold related death.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

T cells from narcolepsy patients were recently reported to recognize hypocretin, a wakefulness-promoting neurohormone, suggesting autoimmune origin of the disease. Here the authors show that hypocretin-specific T cells expand both in healthy controls and in narcolepsy patients, and identify preliminary features that may distinguish them.

Dust from Comet Siding Spring pelted Mars, but another distant visitor seems to have no dust tail at all.

This study assessed COVID-19 social science preprints’ replicability using structured groups. Both beginners and more-experienced participants used a elicitation protocol to make better-than-chance predictions about the reliability of research claims under high uncertainty.

Humans with inherited defects in DOCK8 expression are prone to allergic, type 2 CD4⁺ T cell responses. Mandl and colleagues reveal an important role for cell death in driving such type 2 signals during infection.

The Cancer Genome Atlas Research Network report integrated genomic and molecular analyses of 164 squamous cell carcinomas and adenocarcinomas of the oesophagus; they find genomic and molecular features that differentiate squamous and adenocarcinomas of the oesophagus, and strong similarities between oesophageal adenocarcinomas and the chromosomally unstable variant of gastric adenocarcinoma, suggesting that gastroesophageal adenocarcinoma is a single disease entity.

Automated reconstruction of dense neural networks in the ventral nerve cord of the fruit fly provides a resource for investigating the neural control of movement.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

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.

In a broad cross-tissue analysis, the authors show that a receptor called EDA2R steadily increases with age in both humans and animal models, and becomes even more active in conditions like obesity and diabetes, intensifying inflammation-like processes in muscle cells.

Using data from the MONICA/KORA registry, Chen et al. show that the risk of heat-related non-fatal myocardial infarction was significantly elevated in patients receiving anti-platelet medication and beta-receptor blockers compared with non-users, and the effect of the medications was stronger in younger patients, with lower prevalence of pre-existing cardiovascular disease, compared with older patients.

Extreme rainfall events, amplified by climate change, can stress public health, but efforts to assess health impacts have been fragmented so far. A study now analyses the relation between extreme rainfall and mortality from respiratory diseases across urban environments in East Asia.

Flooding impacts billions globally and indirect health effects are not sufficiently examined, especially for women in developing countries. Here, the authors show that flood exposure during pregnancy correlates with a higher risk of pregnancy loss, particularly for marginalized women, revealing increased health disparities in a changing climate.

The Tabulae Paralytica, a compilation of four molecular atlases of spinal cord injury, provides a window into the pathobiology of spinal cord injury, establishing a framework for integrating multimodal, genome-scale measurements in four dimensions to study biology and medicine.

Hodor, an intestinal zinc-gated chloride channel, controls systemic growth in Drosophila by promoting food intake and by modulating Tor signalling and lysosomal homeostasis within enterocytes.

Jane Lubchenco takes the helm at oceanic and atmospheric agency.

New study investigates heat-induced labor loss in 231 Chinese cities, finding that lower-paid sectors could be disproportionately affected in coming decades, although adaptation measures may mitigate inequality related impacts.

Progressive diseases tend to be heterogeneous in their underlying aetiology mechanism, disease manifestation, and disease time course. Here, Young and colleagues devise a computational method to account for both phenotypic heterogeneity and temporal heterogeneity, and demonstrate it using two neurodegenerative disease cohorts.

Aging is associated with various changes in the brain, including transcription alteration. Here, Bradshaw and colleagues describe the transcriptome of aged human cortical microglia, and show age-related gene expression as related to neurodegeneration.

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.

Imbalance of microglial phenotypes in the aging brain might underlie their involvement in late onset neurodegenerative diseases. Here we report the population structure of microglia in the aged human brain and the reduction of a particular microglia subset in individuals with Alzheimer’s disease .

Organ regeneration by stem cells is required to compensate for tissue damage during aging, although how stem cells are maintained in adulthood is poorly understood. Here, the authors show in Drosophila that Shavenbaby interacts with Yorkie, a mediator of Hippo signalling, to ensure adult stem cell survival.

A study comparing the pattern of single-nucleotide variation between unique and duplicated regions of the human genome shows that mutation rate and interlocus gene conversion are elevated in duplicated regions.

Possible effects of weather conditions on COVID-19 transmission are debated. Here, the authors analyse data from early in the pandemic and show that although temperature and humidity had small effects on transmission, they were far out-weighed by the effects of non-pharmaceutical interventions.

The Tetraconata concept suggests that insects and crustaceans may share evolutionarily conserved pathways. Here, the authors describe the animal tropism and structure-function relationship of nigritoxin, showing that this protein is lethal for insects and crustaceans but harmless to other animals.

Adult cardiac progenitor/stem cells (CPSCs) possess valuable potential for heart repair that is limited by the elusiveness of these cells. Here Noseda et al. refine the definition of murine CPSCs producing stem cell antigen 1 (Sca1), mapping the cardiogenic signature and clonogenicity to the subgroup of Sca1⁺cells expressing PDGFRα.

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.

Comparisons within the human pangenome establish that homologous regions on short arms of heterologous human acrocentric chromosomes actively recombine, leading to the high rate of Robertsonian translocation breakpoints in these regions.