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

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.

Duncan and colleagues link specific human brain cell types to schizophrenia and other complex brain phenotypes, providing mechanistic insights and a cellular taxonomy for psychiatric disorders.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

FlyWire presents a neuronal wiring diagram of the whole fly brain with annotations for cell types, classes, nerves, hemilineages and predicted neurotransmitters, with data products and an open ecosystem to facilitate exploration and browsing.

Designed novel protein nanoparticle technology integrates antibody targeting and responds to changes in environmental conditions to release protected molecular cargoes, opening new applications for precision medicine.

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.

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.

Responsible carbon dioxide removal governance requires engagement with stakeholders, who have various agendas, positions and interactions in the socio-technical landscape. This Perspective discusses stakeholder heterogeneity and recommends approaches to characterize and navigate their relationships.

Surface two-photon imaging of the brain cannot access somatic calcium signals of neurons from deep layers of the macaque cortex. Here, the authors present an implant and imaging system for chronic motion-stabilized two-photon imaging of dendritic calcium signals to drive an optical brain-computer interface in macaques.

Specific RNAs are detected in live cells by harnessing endogenous ADAR enzymes.

The magic of the written word.

This study uses epi-retro-seq to link single-cell epigenomes and cell types to long-distance projections for neurons dissected from different regions projecting to different targets across the whole mouse brain.

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.

Hydroxyglutarate synthase (HglS) converts 2-oxoadipate to D-2- hydroxyglutarate during lysine catabolism in bacteria. Here the authors use structural and biochemical approaches to show that HglS acts via successive decarboxylation and intramolecular hydroxylation and that homologous enzymes catalyze the final step of lysine catabolism in plants.

A planetary transit search carried out in a rich stellar field towards the Galactic bulge discovered 16 candidates with orbital periods between 0.4 and 4.2 days, five of which orbit stars of masses with 0.44–0.75 times that of the Sun.

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.

The flagella of mammalian sperm display non-planar, asymmetric beating, but the molecular basis is unclear. Chen et al. performed in situ cryo-ET of mouse and human sperm and discovered asymmetric distributions of regulatory complexes that could generate asymmetric bending force.

This paper examines eight individual genomes using a clone-based sequencing approach, for structural variants of 8,000 nucleotides or more. One of the first high-quality inversion maps for the human genome is generated, and it is demonstrated that previous estimates of variation of this sort have been too high.

CD4⁺ T helper cells producing IL-17A (T_H17 cells) can take on pathogenic or anti-inflammatory functions in context-specific manners. Here the authors show that the anti-inflammatory fate of T_H17 cells contributes, via TGF-β signaling and induction of IL-10, to host immune tolerance, but also simultaneously dampens protective immunity against S. aureus.

The oceans are becoming more acidic as they absorb anthropogenic carbon dioxide—this may limit the ability of marine organisms to secrete carbonate. A sediment-trap study shows that in the Southern Ocean the shell weights of a surface-dwelling single-celled organism with a calcite shell are lower than pre-industrial values, probably as a result of increasing ocean acidity.

ASLPrep is a software suite for reproducible processing of arterial spin labeled magnetic resonance imaging data.

The covalent insertion of fluorophore-labeled DNA adaptors by Tn5 transposase into open chromatin allows its imaging and subsequent analysis by sequencing from exactly the same samples.

Two chronicles of quantum mechanics tell a good tale but don't reflect the conflicts between the physicists who struggled to reconcile theory and fact, explains Don Howard.

An international consortium reports the genomic sequence for ten Drosophila species, and compares them to two other previously published Drosophila species. These data are invaluable for drawing evolutionary conclusions across an entire phylogeny of species at once.

The authors assess the role of N⁶-methyladenosine in T cell development and function, and show that RNA methylation controls T cell homeostasis by regulating IL-7-mediated STAT5 activation.

Facemap is a data analysis framework for tracking keypoints on mouse faces and relating them to large-scale neural activity. Both of these steps use state-of-the-art convolutional neural networks to achieve high precision and fast processing speeds.

The results of a series of genetic experiments indicate that Foxo1 has a pivotal, Foxp3-independent role controlling regulatory T-cell function.

In studies using mouse models of psoriasis, a spectrum of innate lymphoid cell types is reconfigured and converges via multiple trajectories on a type 3-like state, demonstrating the range and flexibility of innate lymphoid cell responses in the skin.

A whole-genome alignment of 240 phylogenetically diverse species of eutherian mammal—including 131 previously uncharacterized species—from the Zoonomia Project provides data that support biological discovery, medical research and conservation.

The identification of modifiable risk factors that are associated with declining renal function is required to stem the increasing incidence of chronic kidney disease worldwide. In this Review, Howard Trachtman and colleagues discuss the impact of environmental chemicals on cardiorenal function. They highlight the ubiquity of exposure to environmental chemicals in the general public, the main sources of contamination, and the predominant adverse effects that might affect renal function.

In order to limit warming and the most severe consequences of climate change, net global carbon emissions must reach zero by 2050. Many ecosystems contain carbon that would be irrecoverable on this timescale if lost and must be protected to meet climate goals.

In mouse macrophages, a range of short and non-ATG-initiated open reading frames that can generate proteins are identified, one of which is shown to be essential for host immunity to enteric mucosal infection and inflammation.

The myeloproliferative disorders (MPD) polycythaemia vera (PV), essential thombocythaemia (ET), and primary myelofibrosis (PMF) are clonal disorders of multipotent haematopoietic progenitors, and most patients with these diseases acquire a single point mutation in the cytoplasmic tyrosine kinase JAK2 (JAK2V617F). What are the implications of these findings for MPD?

The SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme provides a real-time risk assessment of SARS-CoV-2 variants with the potential to affect transmission, virulence and resistance to infection- and vaccine-induced immunity.

Here, the authors discuss issues relating to the co-development of targeted cancer therapies and companion diagnostics that were not covered in depth in the draft guidance released by the US Food and Drug Administration in 2011. They propose potential strategies that will be useful to mitigate challenges and to help guide the future co-development of drugs and diagnostics.

Genetic, pharmacological and metabolomics experiments reveal that the malate–aspartate shuttle and mitochondrial citrate export support the differentiation of mouse T helper 1 cells, whereas succinate dehydrogenase enforces their terminal effector function.

A community of researchers report the lessons learned from applying 44 algorithms to predict drug sensitivity in cancer cell lines using genomic, epigenetic and proteomic datasets

SOS mutagenesis is the 'mutation-prone' cellular replication mechanism that is responsible for UV-induced mutations. More than 50 years of SOS mutagenesis research has exposed the underlying mechanisms of DNA-damage-induced mutagenesis that combine the overlapping functions of replication, repair and recombination.

Large-scale, next-generation sequencing collaborations have identified drivers and vulnerabilities of urothelial carcinoma. In this Review, the authors discuss the mutational landscape of urothelial carcinoma, including specific mutations in pathways and driver genes and describe how the next generation of therapies will be based on patient-specific targetable mutations observed in individual tumours.

Uncovering the genetic determinants of individual variation in gene expression in humans can improve our understanding of gene regulation and help to identify disease risk alleles. Further advances might be achieved by testing under different conditions, by using larger sample sizes or through network analysis.

First responders to the World Trade Center disaster, who were exposed to particulate matter containing potential carcinogens, have a high burden of somatic mutations in blood cells, raising their risk for cancer and other diseases and highlighting the need for enhanced health screening of these individuals.