Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, P?

CBASS and Pycsar are anti-phage defense systems in diverse bacteria that use cyclic nucleotide signals to induce cell death and prevent viral propagation1,2. Phages use multiple strategies to defeat host CRISPR and restriction-modification systems3-10, but no mechanisms are known to evade CBASS and Pycsar immunity. Here we show that phages encode anti-CBASS (Acb) and anti-Pycsar (Apyc) proteins that

SignificanceIt is of fundamental importance to establish the microscopic picture of crystal nucleation for both academic and industrial research. Here, we report an in situ time-resolved Raman spectroscopy to study crystallization from solution, one crystal nucleation at a time. The observed dynamics of α-glycine crystallization from water without any additive supports the nonclassical nucleation pathway

SignificanceCHARGE syndrome is a complex developmental disorder caused by mutations in CHD7 (chromodomain helicase DNA-binding protein-7). We identified Caenorhabditis elegans chd-7 in a screen for suppressors of dauer formation, an alternative larval stage that develops under harsh environmental conditions. We found chd-7 regulates tumor growth factor-β (TGF-β) signaling pathways both for dauer diapause

SignificanceThe connecting cilium (CC) of the photoreceptor provides the only route for the trafficking of the outer segment (OS) proteins. Failure of OS protein transport causes degenerative photoreceptor diseases, including retinitis pigmentosa. We demonstrate that Tmem138, a protein linked to ciliopathy, is localized to the photoreceptor CC. Germline deletion of Tmem138 abolished OS morphogenesis

SignificanceMultiple human genetic diseases are caused by mutations in the maternally transmitted DNA of mitochondria, the powerhouses of the cell. It is important to study how these mutations arise and accumulate with age, especially because humans in many societies now choose to have children at an older age. However, this is difficult to accomplish in humans, particularly for female germline cells

SignificanceIt is increasingly recognized that chronic neuroinflammation is causally relevant to neurodegeneration. In Parkinson's disease (PD), α-synuclein pathology activates inflammatory signaling that disturbs parenchymal homeostasis and disrupts neuron-glia interactions. Herein, we report that the innate immune cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) DNA-sensing pathway

SignificanceLand plants produce numerous terpenoids that regulate development and mediate environmental interactions. Thus, how typical plant terpene synthase (TPS) genes originated and evolved to create terpenoid diversity is of fundamental interest. By investigating TPSs from the genomes and transcriptomes of diverse taxa of green plants, it was demonstrated here that the ancestral TPS gene originated

SignificanceNovel approaches to promote killing of HIV-1-infected cells are necessary for elimination of the latent reservoir, the main barrier to a cure. Here, we utilized a diverse phage-display library to construct T cell receptor (TCR)-mimic antibodies to HIV-1 peptide-major histocompatibility complexes (pMHC). We show that single-chain diabody forms of these antibodies recognize distinct epitopes

SignificanceThe optic nerve conveys information from retinal ganglion cells (RGCs) to visual processing areas of the brain. Although this pathway normally cannot regenerate when injured nor in degenerative diseases such as glaucoma, this failure can be partially reversed by eliciting a controlled immune reaction in the eye. We show here that the chemokine SDF1 (stromal cell-derived factor 1) is an

SignificanceGenes encoding ribosomal RNA (rDNA) are organized into a repetitive array in eukaryotic genomes. The copy number of these genes often varies and is responsive to genetics and environment. Here, we show that variation in copy number at the rDNA locus is capable of altering replicative lifespan in yeast. These results indicate that considering rDNA copy number, and conditions that could potentially

SignificancePhosphatase and tensin homolog protein (PTEN) and fragile X mental retardation protein (FMRP) play a vital role in neuronal development and function. This work provides new evidence for the genetic interaction of Pten and Fmr1 in postnatal development of granule neurons and conserved mechanisms across evolution. The observed cellular phenotypic defects in Pten and Fmr1 knockout (KO) could

SignificanceCarotenoid pigments accumulate in specific patterns in vertebrate tissues and play important roles as colorants, chromophores, and hormone precursors. However, proteins that facilitate transportation of these lipophilic pigments within cells have not been identified. We provide evidence that Aster proteins are key components for this process and show that they bind the pigments with high

SignificanceUnderstanding how humans process time series data is more pressing now than ever amid a progressing pandemic. Current research draws on some fifty years of empirical evidence on laypeople's (in-)ability to extrapolate exponential growth. Yet even canonized evidence ought not to be trusted blindly. As a case in point, I review a seminal study that is still highly (even increasingly) cited

SignificanceAntibiotic exposure stands among the most used interventions to drive microbial communities away from undesired states. How the ecology of microbial communities shapes their recovery-e.g., posttreatment shifts toward Clostridioides difficile infections in the gut-after antibiotic exposure is poorly understood. We study community response to antibiotics using a model community that can reach

SignificanceScholars have identified that inequality is a notable detriment to well-being. Status-signaling luxury expenditure is taken as a symptom of the reduced well-being associated with income inequality. Despite evidence that status-signaling luxury expenditure is higher in unequal regions, it remains unclear who is affected by inequality. We use payroll and daily spending data from 683,677 individuals

SignificanceCancers and chronic infectious pathogens often evade immune-mediated elimination by suppressing T cell function via engaging inhibitory receptors expressed on T cells. The phospholipid lysophosphatidic acid (LPA) is often increased systemically from basal concentrations upon development of cancer and chronic infections. We previously showed that, at these elevated concentrations, LPA suppresses

SignificanceThe steroid hormone progesterone is highly involved in different physiological-pathophysiological processes, including bone formation and cancer progression. Understanding the working mechanisms, especially identifying the receptors of progesterone hormones, is of great value. In the present study, we identified GPR126 as a membrane receptor for both progesterone and 17-hydroxyprogesterone

SignificanceEstrogen receptor α (ERα) is a transcription factor that induces cell proliferation and exhibits increased expression in a large subset of breast cancers. We comprehensively searched for indicators of poor prognosis in ERα-positive breast cancer through the multiple databases, including interactome, transcriptome, and survival analysis, and identified FKBP52. We found that two immunophilins

SignificanceA variety of mechanisms safeguard the body from autoimmune reactions, yet how these processes cooperate is largely unclear. Using a range of mouse genetic models, we uncover a critical tolerogenic axis between the autoimmune regulator, AIRE, and the immune checkpoint molecule, PD-1. Their combined loss induced an early-onset lethal autoimmune syndrome driven by autoreactive CD4+ T cells

Salinity severely affects the yield of chickpea. Understanding the role of lncRNAs can shed light on chickpea salt tolerance mechanisms. However, because lncRNAs are encoded by multiple sites within the genome, their classification to reveal functional versatility at the transcriptional and the post-transcriptional levels is challenging. To address this, we deep-sequenced 24 salt-challenged flower

In year-round horticultural fruit production, the leaf area index (LAI; L) is a useful indicator for proper crop management. In this study, wide-angle time-lapse digital cameras were applied to estimate the L of a row-planted eggplant canopy throughout an entire growth period. Six wide-angle time-lapse cameras were placed above the canopy; three cameras pointed to the nadir, and the other three pointed

Three experts explain how to use design principles to better communicate scientific data.

Nature highlights three key graphics from the week in science and research.

Climate change poses a great challenge to global food security. Recently the combination of crop models (CMs), global climate models (GCMs), and species distribution models (SDMs) has been applied to assess the impacts of climate change on crop production with consideration of changes of crop climate-suitable regions. However, little is known about the uncertainty sources in the wheat production projections

Land surfaces dissipate energy through latent (LE) and sensible (H) heat fluxes that modulate atmospheric temperature and humidity, which in return affect land surface vegetation and soil processes. Within this two-way land-atmosphere coupling, surface energy partitioning (LE versus H) plays a central role in connecting the land and atmosphere states and fluxes. However, considerably large uncertainties

Stimulator of interferon genes (STING) is an adaptor protein in innate immunity against DNA viruses or bacteria1-5. STING-mediated immunity could be exploited in the development of vaccines or cancer immunotherapies. STING is a transmembrane dimeric protein that is located in the endoplasmic reticulum or in the Golgi apparatus. STING is activated by the binding of its cytoplasmic ligand-binding domain

Mammalian embryogenesis requires rapid growth and proper metabolic regulation1. Midgestation features increasing oxygen and nutrient availability concomitant with fetal organ development2,3. Understanding how metabolism supports development requires approaches to observe metabolism directly in model organisms in utero. Here we used isotope tracing and metabolomics to identify evolving metabolic programmes

Horizontal gene transfer can trigger rapid shifts in bacterial evolution. Driven by a variety of mobile genetic elements-in particular bacteriophages and plasmids-the ability to share genes within and across species underpins the exceptional adaptability of bacteria. Nevertheless, invasive mobile genetic elements can also present grave risks to the host; bacteria have therefore evolved a vast array

The outer membrane of Gram-negative bacteria has an external leaflet that is largely composed of lipopolysaccharide, which provides a selective permeation barrier, particularly against antimicrobials1. The final and crucial step in the biosynthesis of lipopolysaccharide is the addition of a species-dependent O-antigen to the lipid A core oligosaccharide, which is catalysed by the O-antigen ligase WaaL2

G protein-coupled receptors (GPCRs) are cell-surface receptors that respond to various stimuli to induce signalling pathways across cell membranes. Recent progress has yielded atomic structures of key intermediates1,2 and roles for lipids in signalling3,4. However, capturing signalling events of a wild-type receptor in real time, across a native membrane to its downstream effectors, has remained elusive