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Neurons that respond emergently to illusory contours drive pattern completion in V1. Pattern completion in lower cortical areas may therefore mediate perceptual inference by selectively reinforcing activity patterns that match prior expectations.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

This Pediatric Cell Atlas study analyzes temporal cortex single-nucleus RNA sequencing datasets from eight diverse donors from 4 to 50 years of age, describing gene expression dynamics over the course of brain maturation.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

Epstein–Barr virus (EBV) infection has a key aetiological role in endemic nasopharyngeal carcinoma (NPC). The authors of this Review discuss advances in NPC screening, which leverage the detection of either plasma EBV DNA or serum antibodies targeting EBV antigens, as well as in prevention, which relies on prophylactic and therapeutic vaccines for NPC.

Transferrin receptor (TfR) and CD98hc are increasingly used to enable more effective drug delivery to the central nervous system. Here, the authors reveal comprehensive and distinct brain cellular and whole body biodistribution patterns of TfR- and CD98hc-binding molecules.

Internucleosomal linker length alters the stability and dynamics of chromatin condensates by shifting the balance between inter- and intramolecular interactions. Further, by changing the linker lengths, a remodeler can induce or suppress chromatin phase separation.

Functional materials that act as bio-sensing media when interfaced with complex bio-matter are attractive for health sciences and bio-engineering. Here, the authors report room temperature enzyme-mediated spontaneous hydrogen transfer between a perovskite quantum material and glucose reactions.

Inflammatory monocytes in the brain meninges promote stress-induced fear behaviour, and the pathways involved can be modulated using psychedelic compounds.

The affected cellular populations during Alzheimer’s disease progression remain understudied. Here the authors use a cohort of 84 donors, quantitative neuropathology and multimodal datasets from the BRAIN Initiative. Their pseudoprogression analysis revealed two disease phases.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

An examination of motor cortex in humans, marmosets and mice reveals a generally conserved cellular makeup that is likely to extend to many mammalian species, but also differences in gene expression, DNA methylation and chromatin state that lead to species-dependent specializations.

The authors seek to understand the precise roles of microglia in the early human brain by coculturing brain organoids with primitive-like macrophages generated from the same human induced pluripotent stem cells (iMac).

Immune receptors regulate immune responses and are key cancer immunotherapy targets. Here, the authors designed helical concave scaffolds to bind convex sites in immune receptors, creating high-affinity protein binders for TGFβRII, CTLA-4, and PD-L1. Co-crystal structures confirmed their therapeutic potential.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Human brain morphodynamics are explored using organoids.

Serum MMP8 is increased in stress-susceptible mice following chronic stress and leads to brain structure and behavioural changes in mice.

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

A multi-cohort genome-wide association study of tau PET, a brain imaging-based marker of Alzheimer’s disease, identifies a CYP1B1-RMDN2 locus as associated with higher tau and faster cognitive decline. These results suggest a new genetic contribution to cerebral tau and target for Alzheimer’s disease research.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

A genome-wide association study meta-analysis combined with multiomics data of osteoarthritis identifies 700 effector genes as well as biological processes with a convergent involvement of multiple effector genes; 10% of these genes express the target of approved drugs.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A study reports single-cell RNA-sequencing profiles for more than 1.6 million cell nuclei from 101 whole mouse embryos including 22 mutant and 4 wild-type genotypes, from one experiment.

The contribution of genetic factors to the tumour immune microenvironment (TIME) remains to be investigated. Here, the authors suggest the role of TIME eQTLs for target genes involved in reversing immune suppressive features.

Studying RNA dynamics in vivo often relies on fluorogenic approaches, but these can be hampered by factors such as limited sensitivity and sample autofluorescence. Here, the authors describe an ultrasensitive platform for RNA imaging, which features RNA tags that recruit light-emitting luciferase fragments.

A study uses single-molecule footprinting to measure protein occupancy at regulatory elements on individual molecules in human cells and describes how different properties of transcription factor binding contribute to gene expression.

A generalizable framework to prospectively engineer cis-regulatory elements from massively parallel reporter assay models can be used to write fit-for-purpose regulatory code.

Altering cellular responses to double-strand breaks in DNA could rebalance CRISPRediting outcomes. Here, the authors use a pooled CRISPR screen to identify inhibition of CDC7 as a strategy to improve HDR outcomes.

Blood–brain barrier dysfunction occurs in ageing and in neurodegenerative diseases. Here, the authors use scRNA-seq to identify transcriptomic changes in endothelial cell subtypes in the aged mouse brain, some of which may generalize to human and can be reversed by treatment with a GLP-1R agonist.

Entanglement was observed in top–antitop quark events by the ATLAS experiment produced at the Large Hadron Collider at CERN using a proton–proton collision dataset with a centre-of-mass energy of √s  = 13 TeV and an integrated luminosity of 140 fb⁻¹.

Genetically engineered mouse models representing the spectrum of human cutaneous melanoma provide a platform for studying clinical responses to immunotherapy.

Epstein-Barr virus (EBV) is associated with different malignant diseases and circulating EBV DNA is a biomarker for nasopharyngeal carcinoma (NPC). Here, the authors report that plasma EBV DNA methylation profiles show disease-associated patterns and can help to distinguish NPC and non-NPC subjects.

Combining microfluidics with combinatorial indexing enables rapid mapping of genome accessibility in hundreds of thousands of single cells.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

Analyses of in vivo models, cell lines and patient-derived samples show that apolipoprotein B mRNA-editing catalytic subunit 3B (APOBEC3B) not only restrains lung tumor initiation but also that its upregulation is associated with resistance to targeted therapies. This study highlights the complex and context-dependent role of APOBEC3B in lung cancer.

Until today effective antivirals for COVID-19 treatment are not widely available. Here, Zhao et al. characterize a dual-functional cross-linking peptide, 8P9R, that can inhibit SARS-CoV-2 virus entry in vitro and suppresses viral replication in vivo in golden Syrian hamster.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

The ATLAS Collaboration reports the observation of the electroweak production of two jets and a Z-boson pair. This process is related to vector-boson scattering and allows the nature of electroweak symmetry breaking to be probed.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Alterations in the tumour suppressor genes STK11 and/or KEAP1 can identify patients with advanced non-small-cell lung cancer who are likely to benefit from combinations of PD-(L)1 and CTLA4 immune checkpoint inhibitors added to chemotherapy.

Here, the authors computationally designed and produced small protein antagonists to target IL-6 and IL-1β signaling to develop modulators of CRS.

Surface proteins are shown to be routed to the outer Gram-positive cell-wall surface by entropy.

The ATLAS Collaboration reports a measurement of the ratio of the decay rates of W bosons to τ leptons and muons, in agreement with universal lepton couplings as postulated in the standard model of particle physics.

The shift in fluorescence lifetime of tumour tissue with respect to normal tissue after systemic injection of the near-infrared dye indocyanine green can be used to distinguish tumour tissue from normal tissue with high accuracy.