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Antimony selenide is a promising photovoltaic material, but the presence of point defects degrades performance. Here, the authors use positron annihilation spectroscopy combined with theory to detect and identify vacancy-type point defects.

The plant general non-self response system is triggered by leaf microbiota members and, in turn, impacts their colonization.

Acute systemic immune activation may affect gut-luminal colonisation dynamics. Here, the authors show that LPS exposure in mice elevates gut-luminal oxygen species levels, inhibiting the microbiota and enabling pathogen growth through aerobic respiration.

Point defects compromise the electronic performance of hybrid perovskites, yet no experimental identifications have been reported. Here, the authors, for the first time, identify lead monovacancy defect in MAPbI3 using positron annihilation lifetime spectroscopy with the aid of density functional theory.

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.

A genome-wide association meta-analysis of individuals with clinically assessed or self-reported depression identifies 44 independent risk loci. Comparisons with other psychiatric disorders and candidate gene analyses provide new insights into major depressive disorder.

The discovery that DNA methylation of different CpG sites can serve as digital barcodes of clonal identity led to the development of EPI-Clone, an algorithm that enables single-cell lineage tracing through cellular differentiation at scale.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

cAMP is a second messenger that acts in distinct intracellular locations regulating diverse cellular functions. Here the authors design a FRET-based cAMP biosensor and use it to measure in vivodynamics of cAMP concentration changes in the sarcoplasmatic reticulum of mouse cardiomyocytes in health and disease.

Steve Brown and colleagues report an analysis of 20 phenotyping tests, including 413 data parameters, across 449 mutant mouse alleles. They identify widespread pleiotropy and assign putative functions to genes that lacked previous phenotypic annotation.

Whether and how slow wave activity (SWA) and the underlying membrane potential UP and DOWN states initiate mechanisms that augment memory functions in humans are not fully understood. Here authors used multineuron patch-clamp in alive human brain tissue, resected during neurosurgeries, to show that membrane potential UP/DOWN states, which mimic neural sleep activity, modulate axonal action potentials to boost synaptic strength and plasticity.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

How accurate are social scientists in predicting societal change, and what processes underlie their predictions? Grossmann et al. report the findings of two forecasting tournaments. Social scientists’ forecasts were on average no more accurate than those of simple statistical models.

The authors investigate microbiota properties for plant protection using synthetic communities and machine learning approaches. They identify strains that reduce pathogen colonization despite variation in microbiota composition.

Beta-adrenergic stimulation of brown adipose tissue leads to thermogenesis via the activating transcription factor 2 (ATF2) mediated expression of the thermogenic genes Ucp1 and Pgc-1α. Here, the authors show that the scaffold protein p62 regulates brown adipose tissue function through modifying ATF2 genomic binding and subsequent Ucp1 and Pgc-1α induction.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

In this study, the concept of dynamic character displacement among interacting bacterial species from leaf-colonizing families was empirically tested using a proteomics approach. A phenotypic shift towards the utilization of alternative carbon sources was observed during coexistence, thereby minimizing niche overlap.

Plant-parasitic nematodes are a threat to crop production. Combining bioinformatics, genetic and biochemical approaches, the authors show that the plant pathogen beet cyst nematode possesses an incomplete vitamin B5 synthesis pathway, of potential prokaryotic origin, complemented by its plant host.

Cyclic five-membered disulfides (1,2-dithiolanes) have been reported either as nonspecific redox motifs, or as highly specific cellular probes for thioredoxin reductase (TrxR). Here the authors show that 1,2-dithiolane probes are nonspecifically reduced by a range of thiol reductants and are not sensitive to TrxR modulation, thus they are unsuitable as cellular probes for TrxR.

Single-cell analysis of COVID-19 patient samples identifies activated immune pathways that correlate with severe disease.

Activation of brown adipose tissue can ameliorate obesity and diabetes. Here the authors show that chemical inhibition of hyaluronan synthesis by 4‐methylumbelliferone or genetic deletion of hyaluronan synthases 2 and 3 decreases body-weight gain and improves glucose homeostasis by inducing the thermogenic capacity of brown adipose tissue in mice.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

A PROTAC termed P4B targeting BRAF V600E mutant has been developed, which displays enhanced inhibitory function in cell lines carrying BRAF mutations that impart resistance to conventional BRAF inhibitors.

Sequencing the nuclear genomes of Guillardia theta and Bigelowiella natans, transitional forms in the endosymbiotic acquisition of photosynthesis by engulfment of certain eukaryotic algae, reveals unprecedented alternative splicing for a single-celled organism (B. natans) and extensive genetic and biochemical mosaicism, shedding light on why nucleomorphs persist in these species but not other algae.

Depression is correlated with many brain-related traits. Here, Shen et al. perform phenome-wide association studies of a depression polygenic risk score (PRS) and find associations with 51 behavioural and 26 neuroimaging traits which are further followed up on using Mendelian randomization and mediation analyses.

Environmental influences during prenatal development may have implications for health and disease later in life. Here, Czamara et al. assess DNA methylation in cord blood from new-born under various models including environmental and genetic effects individually and their additive or interaction effects.

2D crystals of the MloK1 potassium channel diffract to only 10 Å. Here the authors present a method, where they apply cryo-EM single-particle image processing to recorded 2D crystal images, which reveals conformational conformational variability of MloK1 within the crystals and enabled them to determine the structure at 4 Å resolution.

How chromatin structure and gene accessibility changes during monocyte differentiation is not clearly defined. Here the authors characterize the chromatin changes during macrophage or dendritic cell maturation from monocytes and the dependence of this upon cohesin and CTCF.

A mass-spectrometry-based draft of the human proteome and a public database for analysis of proteome data are presented; assembled information is used to estimate the size of the protein-coding genome, to identify organ-specific proteins, proteins predicting drug resistance or sensitivity, and many translated long intergenic non-coding RNAs, and to reveal conserved control of protein abundance.

This study uses gene expression predictors for the dorsolateral prefrontal cortex and other brain regions to perform a transcriptomic imputation analysis of schizophrenia, identifying 413 genic associations across 13 brain regions and 36 significantly enriched pathways.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

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.

Arabidopsis thaliana plants lacking the rbohD gene, which encodes the NADPH oxidase RBOHD, have an altered leaf microbiome including an enrichment of opportunistic pathogens, indicating that RBOHD is essential for maintaining leaf microbiota homeostasis.

A proteolytically derived fragment of the epigenetic regulator HDAC4 protects the heart through transcriptional repression of the hexosamine biosynthetic pathway, thereby inhibiting protein O-GlcNAcylation and maintaining normal calcium handling and contractility of cardiomyocytes.

Nanobodies (Nbs) coupled to organic dyes are increasingly used for super-resolution cell imaging, but producing gene-specific Nbs is time-consuming. Here the authors present a peptide-tag/Nb combination for dSTORM imaging which can be easily adapted to different targets in fixed and live cells.

Knapp and colleagues show that elevated heme levels following hemolysis impair the control of bacterial proliferation by inhibiting phagocytosis and migration of human and mouse phagocytes independently of heme-iron acquisition by bacteria as a source of nutrients.

A genome-wide-association meta-analysis of 18,381 austim spectrum disorder (ASD) cases and 27,969 controls identifies five risk loci. The authors find quantitative and qualitative polygenic heterogeneity across ASD subtypes.

Haploid genetic screening of cells under different types of mitochondrial perturbation shows that a pathway involving OMA1, DELE1 and the eIF2α kinase HRI communicates mitochondrial stress to the cytosol to trigger the integrated stress response.

The genetic basis of metabolic diseases is incompletely understood. Here, by high-throughput phenotyping of 2,016 knockout mouse strains, Rozman and colleagues identify candidate metabolic genes, many of which are associated with unexplored regulatory gene networks and metabolic traits in human GWAS.

Relatives of patients with amyotrophic lateral sclerosis have an unexpectedly high incidence of schizophrenia. Here, the authors show a genetic link between the two conditions, suggesting shared neurobiological mechanisms.

Systemic dissection of sexually dimorphic phenotypes in mice is lacking. Here, Karp and the International Mouse Phenotype Consortium show that approximately 10% of qualitative traits and 56% of quantitative traits in mice as measured in laboratory setting are sexually dimorphic.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

The full extent of the genetic basis for hearing impairment is unknown. Here, as part of the International Mouse Phenotyping Consortium, the authors perform a hearing loss screen in 3006 mouse knockout strains and identify 52 new candidate genes for genetic hearing loss.

Schizophrenia is a highly heritable genetic disorder, however, identification of specific genetic risk variants has proven difficult because of its complex polygenic nature—a large multi-stage genome-wide association study identifies 128 independent associations in over 100 loci (83 of which are new); key findings include identification of genes involved in glutamergic neurotransmission and support for a link between the immune system and schizophrenia.

Microbes induce an immune response in plants that includes transcriptional changes and biosynthesis of defence molecules. Analysis of both transcriptome and metabolome output to multiple bacteria identifies a common non-self response to microorganisms.

Heart failure is a major public health issue but due to our poor disease understanding the current therapies are symptomatic. Here the authors identify Myoscape as a novel cardiac protein regulating membrane localization of the L-type calcium channel and heart's contractile force, thus promising new therapeutic avenues for heart failure.