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Hydrologic data collected from river gauges inform critical decisions for allocating water resources, conserving ecosystems and predicting the occurrence of droughts and floods. The current global river gauge network is biased towards large, perennial rivers, and strategic adaptations are needed to capture the full scope of rivers on Earth.

Circadian activity modulation in the suprachiasmatic nucleus (SCN) is a network-level emergent property that requires neuropeptide VIP signaling, yet the precise cellular mechanisms are unknown. Patton et al. show that cells expressing VIP or its receptor VPAC2 together determine these emergent properties of the SCN.

A multi-ancestry genome-wide association meta-analysis of kidney cancer identifies 63 regions associated with disease susceptibility including one locus that was associated with increased risk in individuals with African ancestry.

A high-resolution gene expression atlas of prenatal and postnatal brain development of rhesus monkey charts global transcriptional dynamics in relation to brain maturation, while comparative analysis reveals human-specific gene trajectories; candidate risk genes associated with human neurodevelopmental disorders tend to be co-expressed in disease-specific patterns in the developing monkey neocortex.

Chou et al. generate transdifferentiated human neurons from fibroblasts from young or aged individuals and patients with Alzheimer’s disease. Studies of endolysosomes and proteostasis suggest a role for lysosomal quality control in Alzheimer’s disease pathology.

Analysis of ancient human DNA from the Swahili coast reveals that predominantly African female ancestors and Asian male ancestors formed families after around ad 1000 and lived in elite communities in coastal stone towns.

A method called vessel isolation and nuclei extraction for sequencing (VINE-seq) produces a molecular map of vascular and perivascular cell types in the human brain and reveals their contributions to Alzheimer’s disease risk.

Rodin and Dou et al. characterized genome-wide somatic mutation in autistic and control brains, revealing that even unaffected individuals may possess dozens of brain somatic mutations and providing insight into the role of somatic mutation in autism.

Tagging and tracking the blood plasma proteome as a discovery tool reveals widespread endogenous transport of proteins into the healthy brain and the pharmacologically modifiable mechanisms by which the brain endothelium regulates this process with age.

The delivery of CRISPR RNPs has potential advantages over other genome editing approaches, including reduced off-target editing and reduced immunogenicity. Here the authors report self-deliverable Cas9 RNPs capable of robustly editing cultured cells in vitro and the mouse brain upon direct injections.

Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here, the authors present the largest FL study to-date to generate an automatic tumor boundary detector for glioblastoma.

The role of synaptogenesis during the acquisition of goal-directed behaviors is unknown. Here, the authors show that learning-induced synaptogenesis in the adult mouse cortex is required to excite a specific circuit to adjust effort exertion.

Enhancers for endodermal organs are primed at the chromatin level prior to lineage induction by FOXA pioneer transcription factors; how pervasive this is, is not well known. Here the authors show that only a small subset of organ-specific enhancers are bound and primed by FOXA prior to lineage induction, whereas the majority do not undergo chromatin priming and engage FOXA upon lineage induction.

Lung cancer is the leading cause of cancer mortality, despite declining smoking rates. Gorman et al. report multi-ancestry GWAS meta-analyses of lung cancer providing insights into smoking-independent genetic predisposition to the disease.

Interfaces between two dissimilar transition metal oxides can exhibit emergent strongly correlated electronic and magnetic states due to charge transfer and electronic reconfiguration. Here, the authors synthesize and investigate an exotic Mott ground state in LaTiO_3+δ/LaNiO₃heterostructures.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Paint server and homology optimization pipeline (PaintSHOP), an interactive platform for the design of oligo fluorescence in situ hybridization (FISH) experiments, democratizes and standardizes the process of designing complex probe sets for the oligo FISH community.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

The hypothalamic neuropeptide oxytocin exerts analgesic effects, but the underlying pathways remain largely elusive. Here, the authors describe an analgesic pathway formed by oxytocin neurons projecting to the periaqueductal grey, where axonally released oxytocin activates oxytocin-receptor expressing GABA neurons and subsequently reduces pain-like behaviors in both female and male rats.

A national prospective study of patients requiring hospitalization for COVID-19 demonstrates global cognitive deficits at 1 year, associated with elevated brain injury markers and reduced gray matter volume.

A survey of sharks and rays on coral reefs within 66 marine protected areas across 36 countries showcases that the conservation benefits of full MPA protection to sharks almost double when accompanied by effective fisheries management.

Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance.

The atmospheric terminator region of WASP-39 b, a hot gas giant exoplanet, is inhomogeneous, despite past assumptions, with the evening terminator being hotter and thus probably clearer, and the morning terminator probably being cloudy and consequently cooler.

Schief and colleagues show that germline-targeting epitope scaffolds can elicit responses from rare broadly neutralizing antibody precursor B cells with predefined binding specificities and genetic features.

Observations from the Lucy spacecraft of the small main-belt asteroid (152830) Dinkinesh reveals unexpected complexity, with a longitudinal trough and equatorial ridge, as well as the discovery of the first contact binary satellite.

Montserrat Garcia-Closas and colleagues report a genome-wide association study for bladder cancer. They identify three new susceptibility loci on chromosomes 22q13.1, 19q12 and 2q37.1.

Adjuvanting the lipid and the encapsulated messenger RNA-encoded antigen in lipid-nanoparticle mRNA vaccines can enhance the efficiency of mRNA delivery and the activation of the immune responses, as shown for a COVID-19 vaccine in mice.

Time-series observations from the JWST of the transiting exoplanet WASP-39b show gaseous water in the planet’s atmosphere and place an upper limit on the abundance of methane.

The medium-resolution transmission spectrum of the exoplanet WASP-39b, described using observations from the Near Infrared Spectrograph G395H grating aboard JWST, shows significant absorption from CO₂ and H₂O and detection of SO₂.

The transmission spectrum of the exoplanet WASP-39b is obtained using observations from the Single-Object Slitless Spectroscopy mode of the Near Infrared Imager and Slitless Spectrograph instrument aboard the JWST.

Imaging technologies are used throughout the life and biomedical sciences to understand mechanisms in biology and diagnosis and therapy in animal and human medicine. We present criteria for globally applicable guidelines for open image data tools and resources for the rapidly developing fields of biological and biomedical imaging.

The authors show that oxytocin-receptor-expressing neurons in the parabrachial nucleus are key regulators of fluid homeostasis that suppress fluid intake when activated, but do not decrease food intake after fasting or salt intake after salt depletion.

A global gauge-corrected monthly river flow and storage dataset suggests that residence time is a key driver of water storage and variability and indicates substantial freshwater discharge to the ocean from the Maritime Continent.

Limited tumor cell delivery is a major challenge for the efficacious delivery of siRNAs to silence traditionally undruggable oncogenes. Here the authors optimize siRNAs for in situ binding to albumin through C18 lipid modifications and show the application of the lead conjugate structure for targeting MCL1 in orthotopic breast tumors in mice.

Non-human primates are important animal models for studying SARS-CoV-2 infection. Here, Salguero et al. directly compare rhesus and cynomolgus macaques and show that both species represent COVID-19 disease of mild clinical cases, and provide a lung histopathology scoring system.

Using over 600 genetic matches of elephant tusks from the same individual or close relatives, from 49 ivory seizures across Africa, Wasser et al. reveal the scale, connectivity and movements of transnational criminal organizations that trade in ivory.

Fishing has had a profound impact on global reef shark populations, and the absence or presence of sharks is strongly correlated with national socio-economic conditions and reef governance.

Leveraging RNA-targeting CRISPR–Cas13d technology, Morelli et al. engineered a novel therapeutic strategy that safely and effectively eliminates toxic expanded huntingtin RNA in multiple models of Huntington’s disease.

A collaborative study demonstrates that, compared with previous SARS-CoV-2 variants, B.1.1.529 isolates cause less infection and disease in mice and hamsters, in agreement with preliminary data from studies in humans.

How epigenetic regulation affects pancreatic development is unclear. Here, the authors show that the histone demethylase LSD1 regulates the epigenetic state of developmental enhancers during pancreatic specification and controls how these enhancers respond to extracellular signals, namely retinoic acid.

The behaviour of strongly correlated nickelates is well studied in bulk but the corresponding strained thin films are largely unexplored. Here, the authors study strained NdNiO₃thin films with various degrees of strain and, in addition to a metal-to-insulator transition, find quantum critical behaviour.

The genetic basis of tinnitus and how it relates to hearing loss genetics is unknown. In a large GWAS for tinnitus, the authors discover tinnitus’ distinct genetic architecture from hearing loss and its correlation with a spectrum of psychiatric disorders.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Tumor suppressor BRCA2 is known to stabilize and restart stalled DNA replication forks. Here the authors show that BRCA2 is recruited to the replication fork through its interaction with MCM10 and inhibits Primase-Polymerase-mediated repriming, lesion bypass and single strand DNA gap formation after DNA damage.

Integrative analysis in patients with diffuse large B-cell lymphoma uncovers that biallelic mutations on TMEM30A are associated with a favorable outcome and enhanced sensitivity to CD47 blockade.

Genetic association studies have identified loci including the choline transporter SLC44A2 as a potential regulator of thrombosis. Here the authors report that loss of SLC44A2 impairs platelet activation and thrombosis in mice via a reduction of mitochondrial ATP production.