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How axolotl salamanders know what portion of the limb to regenerate remains a mystery. In this article, the authors show that precise retinoic acid degradation is critical for instructing regeneration of the appropriate limb segment.

Several 17B-HSD13 variants have been identified as protective against NASH/MASH. However the protein’s endogenous function is unknown. Here authors describe sulfonamide-based inhibitors and synthetic substrates, then apply to multiple cellular systems revealing that the most prevalent IsoD variant maintains NAD-dependent catalytic activity.

Microglia and border-associated macrophages play a role in regulating cerebral blood flow (CBF), but the underlying mechanisms are unclear. Here, the authors show a role for microglial CD39 in the regulation of basal CBF and neurovascular coupling.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Safety and efficacy remain important challenges for non-antiretroviral-based microbicides. Here, Derby et al. show that a Griffithsin-Carrageenan fast dissolving vaginal insert provides on-demand protection against SHIV infections in macaques, paving the way for the development of pre-exposure prophylaxis on-demand products.

MaizeCODE maps active regulatory regions tied to maize domestication traits in a diverse panel of tissues and inbreds. It reveals bi-directional enhancer RNAs and the molecular conflicts between activity and silencing of non-coding regions.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Analysing camera-trap data of 163 mammal species before and after the onset of COVID-19 lockdowns, the authors show that responses to human activity are dependent on the degree to which the landscape is modified by humans, with carnivores being especially sensitive.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

Signaling via the mTOR complex 1 (mTORC1) maintains cellular and organismal homeostasis. Here the authors show that the AAA + ATPase Thorase binds mTOR to promote disassembly and inactivation of mTORC1 to fine tune TOR signaling according to amino acid availability.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

The molecular circuitry that drives dendrite formation during osteocytogenesis remains poorly understood. Here the authors show that deletion of Sp7, a gene linked to rare and common skeletal disease, in mature osteoblasts and osteocytes causes severe defects in osteocyte dendrites.

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.

Genome-wide association studies have identified regions which confer risk of high-grade serous epithelial ovarian cancer. Here the authors use expression quantitative train locus analysis to identify candidate genes and functionally characterise them, identifying a role for HOXD9 in ovarian cancer.

Most confirmed susceptibility variants for epithelial ovarian cancer lie in non-protein-coding sequences. Here Permuth-Wey and colleagues investigate variants in 3′ untranslated regions (UTRs) and uncover a new susceptibility locus.

HNF1B is overexpressed in the clear cell subtype and epigenetically silenced in the serous subtype of ovarian cancer. Pearce and colleagues now show that genetic variants in HNF1B are differentially associated with risks of developing these two cancer subtypes, possibly through an epigenetic mechanism.

Could out-of-sync body clocks be contributing to human disease? Melissa Lee Phillips reports.

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.

Temporal multi-omic analysis of tissues from rats undergoing up to eight weeks of endurance exercise training reveals widespread shared, tissue-specific and sex-specific changes, including immune, metabolic, stress response and mitochondrial pathways.

Elisabeth Mangold and colleagues report a genome-wide association study for non-syndromic cleft lip with or without cleft palate.

Elisabeth Mangold and colleagues carried out a genome-wide association study for nonsyndromic cleft lip with or without cleft palate, and report a locus on 8q24.21 that is strongly associated with this phenotype.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

The protein kinase mTOR is known to contribute to cancer development. However, existing drugs targeting mTOR, such as rapamycin, have not been very effective at inhibiting cancer cell survival and also have the unwanted side effect of immunosuppression. Studying preclinical models of leukemia driven by the BCR-ABL oncogene, Matthew Janes et al. now show that a new mTOR inhibitor—which unlike previous ones is an ATP competitive inhibitor that targets the active site of the enzyme—can overcome these drawbacks.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

It is known that exercise influences many human traits, but not which tissues and genes are most important. This study connects transcriptome data collected across 15 tissues during exercise training in rats as part of the Molecular Transducers of Physical Activity Consortium with human data to identify traits with similar tissue specific gene expression signatures to exercise.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

Sequencing of the hexaploid bread wheat genome shows that it is highly dynamic, with significant loss of gene family members on polyploidization and domestication, and an abundance of gene fragments.

Sudipto Roy, Carol Wicking, Carsten Bergmann and colleagues report that mutations in DZIP1L cause autosomal recessive polycystic kidney disease (ARPKD). Through studies of mouse and zebrafish models of DZIP1L loss of function, the authors demonstrate that DZIP1L is required for proper function of the periciliary diffusion barrier.

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.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

Pooling participant-level genetic data into a single analysis can result in variance stratification, reducing statistical performance. Here, the authors develop variant-specific inflation factors to assess variance stratification and apply this to pooled individual-level data from whole genome sequencing.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

Single-cell analysis of lung, heart, kidney and liver autopsy samples shows the molecular and cellular changes and immune response resulting from severe COVID-19 infection.

In this Perspective, the authors discuss the current status of ecological forecasting research, its role in helping to address the climate and biodiversity crises facing society and potential future directions, with a central focus on how to scale up ecological forecasting capabilities.

Xavier Argout and colleagues report the draft genome of Theobroma cacao, the tropical crop that is the source of chocolate. The sequence assembly covers approximately 80% of the genome.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

Organic ligands enhance the stability and the solution processability of semiconductor quantum dots, but they can impede charge transport in films of such nanoparticles. Passivation with atomic ligands now offers an alternative strategy that enables the fabrication of PbS colloidal-quantum-dot solar cells with power-conversion efficiencies of up to 6%.

Bonheur et al. developed a subcellular-distribution-based bidirectional neural activity reporter that operates on the timescale of minutes, and they demonstrate increases and decreases of neural activity associated with social behaviors in Drosophila.

Shorter regulatory review times for high-risk cardiovascular devices correlate with the likelihood of reports of adverse events.