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The authors uncover a direct, BAI1-dependent, role for C1q in the control of neural stem cell proliferation and quiescence via MDM2–p53 and p32, a complement cascade-independent mechanism of C1q action that has implications for central nervous system health and disease.

Solar photovoltaics is entering a multi-terawatt era, driven by decades of cost, performance and reliability gains. In this Perspective Alberi et al. discuss the role of historical and future learning, highlighting the increasing importance of sustainability considerations.

Here the authors show that rehabilitating nuclear speckles, membraneless organelles involved in mRNA processing and gene regulation, can boost protein quality control and reduce toxic protein buildup, as well as ameliorate models of diseases like tauopathy and retinal degeneration.

Here Plikus and colleagues provide a step-by-step protocol for the isolation and characterization of lipocartilage from mouse ear and the purification of its lipochondrocytes.

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.

RuGN single atom catalyst with Ru-O₄ structure can effectively mitigate the self-decay of Fe(VI), eliminate the H₂O₂ byproduct, and activate Fe(VI) through Ru-O-Fe coordination, resulting in excellent degradation performance of the RuGN/Fe(VI) system towards micropollutants in water.

Information on how oxygen ions transport is crucial to understanding field-induced phase transformations in materials. Here, Zhang et al. directly image atomic-scale oxygen migration and the subsequent structural reconstruction in a SrCoO_2.5-σ film in the presence of an electric field.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

How the human visual system leverages the rich structure in object motion for perception remains unclear. Here, Bill et al. propose a theory of how the brain could infer motion relations in real time and offer a unifying explanation for various perceptual phenomena.

Using single-cell and spatial transcriptomics data, FlowSig provides a unified signaling modeling framework by connecting intercellular communication mediated by ligand–receptor interactions and intracellular gene expression modules.

Longitudinal population-based surveillance identifies shifts in HIV transmission patterns related to age and sex, suggesting that HIV programmes to increase HIV suppression in men are crucial to reduce incidence in women.

Initial COVID-19 containment in the United States focused on limiting mobility, including school and workplace closures, with enormous societal and economic costs. Here, the authors demonstrate the feasibility of a test-trace-quarantine strategy using an agent-based model and detailed data on the Seattle region.

Interactions among insects, plants, and microorganisms are fundamental for ecosystem function. This study focuses on the attraction of oriental armyworm moths to yeast-fermented nectar and finds that isoamyl alcohol, a yeast-derived compound, activates specific olfactory neurons in the moths, enhancing yeast dispersal and moth reproduction.

Exosomal PD-L1 (exoPD-L1) is a biomarker predicting immunotherapeutic responses. Here the authors report NanoEPIC, a nanoscale cytometry platform that enables phenotypic sorting and exoPD-L1 profiling from blood plasma by using magnetic-activated ranking to differentiate exosomal subpopulations.

Analysis of HbA1c and FPG levels across 117 population-based studies demonstrates regional variation in prevalence of previously undiagnosed screen-detected diabetes using one or both measures and suggests that use of elevated FPG alone could underestimate diabetes prevalence in low- and middle-income countries.

The serine protease TMPRSS2 primes SARS-CoV-2 glycoprotein for cell entry. Here, the authors perform a screen to identify drugs that reduce TMPRSS2 expression and find that halofuginone modulates proteasome-mediated degradation of TMPRSS2 and reduces entry of SARS-CoV-2.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

Andrew Morris, Mark McCarthy, Michael Boehnke and colleagues report a meta-analysis of genome-wide association studies for type 2 diabetes, including 26,488 cases and 83,964 controls from populations of European, east Asian, south Asian and Mexican and Mexican American ancestry. They identify seven loci newly associated with type 2 diabetes and examine the genetic architecture of disease across populations.

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.

A sequencing chemistry that separates nucleotide identification from nucleotide incorporation achieves high accuracy.

E3 ligase subunit protein Fbxo48 interacts with phosphorylated Ampkα and mediates its proteasomal degradation. Interruption of the pAmpkα/Fbxo48 interaction by a small-molecule BC1618 promoted Ampkα activation and improved insulin sensitivity.

Here, Johnson et al show that bacterial pneumonia induces an interaction between the ubiquitin E3 ligase subunit FBX024 and the mitochondrial protein DARS2 to modulate host immune responses.

Comprehensive genomic and transcriptomics analyses of more than 1,300 cases of childhood T-lineage acute lymphoblastic leukaemia identify 15 distinct subtypes that are associated with specific outcomes.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Characterisation of quantum hardware requires clear indications on what can and cannot be learned about quantum noise. Here, the authors show how to characterise learnable degrees of freedom of a Clifford gate using tools from algebraic graph theory.

Rhythmic trafficking of dendritic cells to the tumour draining lymph node governs a circadian response of tumour-antigen-specific CD8⁺ T cells that is dependent on the circadian expression of the co-stimulatory molecule CD80.

Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

DNA is an attractive digital data storing medium due to high information density and longevity. Here the authors use millions of sequences to investigate inherent biases in DNA synthesis and PCR amplification.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

Brainstem gliomas are heterogenous in terms of clinical outcome and disease etiology. Here, the authors present a genetic and epigenetic landscape of brainstem gliomas, finding distinct epigenetic clusters associated with unique genetic and clinical profiles.

Evidence is provided that quantum random circuit sampling, a near-term quantum computational task, is classically hard but verifiable, making it a leading proposal for achieving quantum supremacy.

Humans lack robust regeneration of hair follicles after skin wounding. George Cotsarelis and colleagues now show that γδ T cells are not present at high levels in human skin, that in mice they are a key initial source of the protein fibroblast growth factor 9 and that this factor modulates hair follicle regeneration during skin wound healing. These results suggest a possible topical clinical treatment to regrow hair after wounding and perhaps for other conditions of hair loss.

Glioblastoma can be classified based on IDH and TERT promoter mutations, but ~20% of glioblastoma do not have these mutations (TERTp^WT-IDH^WT glioblastoma). Here, the authors present a genetic landscape of TERTp^WT-IDH^WT glioblastoma, identifying a telomerase-positive subgroup driven by TERT-structural rearrangements and an ALT-positive subgroup with mutations in ATRX or SMARCAL1.

How NALP7 inflammasome formation is regulated is unclear. Here the authors show that STAMBP prevents lysosomal degradation of NALP7 and present BC-1471 as a potential therapeutic STAMBP inhibitor, showing it can reduce TLR-induced IL-1β production.

Senescent melanocytes of skin nevi drive hyperactivation of hair growth through the signalling factor SPP1.

Genome-wide association studies (GWAS) have become a key tool to discover genetic markers for complex traits; however, environmental factors that interact with genes are rarely considered. Here, the authors conduct a GWAS of obesity traits, and find that smoking may alter genetic susceptibilities.

Silicon probes for electrical recording from neurons usually have fewer wires than recording channels available to carry signals off the probe, which restricts the number of channels that can be recorded simultaneously. The authors propose to pool electrodes, using a single wire to serve many channels through a set of controllable switches.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

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.

This Resource describes data, code and tools developed for the Human Reference Atlas and the Human BioMolecular Atlas Program for building and navigating a multiscale human atlas.

Single-cell methods record molecule expressions of cells in a given tissue, but understanding interactions between cells remains challenging. Here the authors show by applying systems biology and machine learning approaches that they can infer and analyze cell-cell communication networks in an easily interpretable way.

Mark McCarthy, Michael Boehnke, Andrew Morris and colleagues perform large-scale association analyses using the Metabochip to gain insights into the genetic architecture of type 2 diabetes. They report several new susceptibility loci, including two that show sex-differentiated effects on disease risk.