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A single-cell multiomics analysis of over 200,000 cells of the primary motor cortex of human, macaque, marmoset and mouse shows that divergence of transcription factor expression corresponds to species-specific epigenome landscapes, and conserved and divergent gene regulatory features are reflected in the evolution of the three-dimensional genome.

Recombinant adeno-associated virus tools for enhanced microglial transduction in mice are reported. These viruses can be used to express functional reporters or genome editing tools with high microglial specificity, with the help of microglia-specific Cre lines.

In this work, the authors present novel PLpro inhibitors, with lead compound GZNL-P36 showing potent activity against SARS-CoV-2 variants, improving survival and reducing lung viral loads in a mouse model, offering promise for COVID−19 therapies.

Nellie is a comprehensive automated pipeline for studying the structure and intracellular dynamics of diverse organelles that offers accurate segmentation, tracking and feature extraction on both 2D and 3D data.

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.

The hippocampus contributes to path integration, but the firing patterns supporting this function are unknown. Here, the authors found that the activity of hippocampal neurons during a path integration task predicted the animal’s homing direction.

Aviner et al. show that translation and aggregation of Huntingtin (HTT) are regulated by a stress-responsive upstream open reading frame. Mutant HTT depletes translation elongation factor eIF5A, leading to ribosome pausing and collisions.

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 impacts of SARS-CoV-2 infection and COVID-19 vaccination in pregnancy are not fully understood. Here, the authors perform a cohort study using data from Scotland and find that infection was associated with increased risk of preterm birth and some adverse maternal outcomes, but there was no evidence of adverse outcomes associated with vaccination.

Nearly all bird species build nests; however, there is extensive variation in both how and where their nests are built. Here, Fang and colleagues reconstruct the evolution of nest structure, nest site and nest attachment across all extant bird families.

Spatial molecular imaging analysis of human pancreatic adenocarcinomas describes multicellular neighborhoods in the tumor microenvironment. Ligand–receptor analysis using optimal transport-based SCOTIA identifies interleukin-6 as a mediator of chemoresistance.

Patient-derived glioma cell (PDGC) cultures have been poorly characterized on a molecular level. Here, the authors analyze 50 PDGC lines from glioblastoma patients using multi-omics and drug screening; find molecular subtypes that are associated with drug response and prognosis, as well as a MYC/MYCN-amplification associated with serum-free culture.

The spindle matrix proteins, including Chro, are known to regulate mitotic spindle assembly in the cytoplasm. Here the authors show that in Drosophila larval brain, Chro promotes neural stem cell (NSC) reactivation and prevents activated NSCs from entering quiescence, and that Chro carries out such a role by regulating the expression of key transcription factors in the nucleus.

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.

Green technologies foster the use of green energy; however, large investment costs hinder adoption. In a large-scale field experiment, the authors show that message framing can promote a serious commitment to solar panels among the broader public.

HPV’s E6 protein promotes cancer by degrading p53. This study reveals the cryoEM structure of HPV16 E6 in complex with E6AP and p53, highlighting their picomolar affinity and large protein-protein interaction interface.

Genomic, transcriptomic and DNA methylation data from tissue samples from 208 Chinese patients with prostate cancer define the landscape of alterations in this population, and comparison with data from Western cohorts suggests that the disease may stratify into different molecular subtypes.

Developing zebrafish retina and brain tissues undergo a nuclear jamming transition that induces crystalline-like cellular ordering, with the emergent tissue stiffness controlled by nuclear mechanics.

Half of our genome is transposable elements (TEs), often called junk DNA. Using the latest ENCODE data, the authors find TEs to contribute ~25% of human regulatory elements (REs). TEs can be adopted into new REs or replace old ones during evolution.

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

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.

Analyses of expression profiles from whole blood of 31,684 individuals identify cis-expression quantitative trait loci (eQTL) effects for 88% of genes and trans-eQTL effects for 37% of trait-associated variants.

Gluconeogenesis produces glucose from non-carbohydrate carbon substrates, particularly occurs during fasting. Here, the authors show lysine methyltransferase KMT5C promotes gluconeogenesis by decreasing PGC-1α degradation, which is independent of its methyltransferase activity.

Dietary inulin fibre alters the composition and metabolism of gut microbiota, resulting in elevated levels of bile acids that subsequently trigger mucosal type 2 inflammation characterized by eosinophilia, with clinical implications for allergy and anti-helminth defence.

Analyses of summary statistics from GWAS are subject to biases due to errors in the discovery GWAS or linkage disequilibrium reference data set or heterogeneity between data sets. Here, the authors propose a quality control method to be added to analysis of GWAS summary data that can reduce such biases.

Expression of transposable elements is mapped to unique genomic loci with CELLO-seq.

The function of rare non-coding variants remains challenging to decipher. Here, the authors developed MapUTR to uncover 10,524 functional rare 3’ UTR variants regulating mRNA abundance, many of which reside in cancer driver genes.

ABC-type heterotrimeric proteins can be designed de novo using coiled coils and helical bundles as starting scaffolds, extended using helical repeat proteins and then used as building blocks for higher-order oligomeric assemblies.

Whole-exome sequencing analyses in a cohort of 1,030 patients with premature ovarian insufficiency identify new likely pathogenic variants and reveal distinct genetic architectures between primary and secondary amenorrhea.

Jellyfish plays an important ecological role in surface waters and the deep sea. Here the authors report genome sequences of two true jellyfish, Sanderia malayensis and Rhopilema esculentum, showing distinct homeobox gene clusters and sesquiterpenoid pathway.

Ancient DNA, stable isotopes and other archaeological methods establish that humans were living at extremely high elevation on the Tibetan Plateau 4,400 years ago, maintaining sedentary lifestyles that combined fishing, hunting and crop exchange.

Dipterocarp trees are iconic but severely threatened species in Asian rainforests. This study assembles high-quality genomes of seven dipterocarp species to reveal the molecular basis of key adaptations and identifies a recent sharp population decline coinciding with local human activity.

Whether Kupffer cells play a role in regulating the pathogenesis of fatty liver disease remains to be completely explored. Here, the authors show GPR3 activation stimulates glycolysis in Kupffer cells through GPR3-β-arrestin2-GAPDHPKM2 pathway and inhibits high-fat diet induced obesity and liver pathogenesis.

High-resolution pulse shaping is highly sought after, but existing systems are impractical outside of laboratory settings. Here, the authors introduce a chip-scale spectral shaper that uses high-Q microresonator filter banks and inline phase control to manipulate lines at GHz-level spacing.

Understanding the emergence, evolution, and transmission of antibiotic resistance genes (ARGs) is essential to combat antimicrobial resistance. Here, Munk et al. analyse ARGs in hundreds of sewage samples from 101 countries and describe regional patterns, diverse genetic environments of common ARGs, and ARG-specific transmission patterns.

Pfs48/45, a surface protein of Plasmodium falciparum, is a promising anti-malarial vaccine candidate whose structure is not entirely resolved. Here, the authors present the structure of the full-length molecule, and characterise the binding and activity of transmission blocking antibodies.

By modelling the radio, optical, UV and X-ray data of the unusually bright cosmological explosion AT 2022cmc, Pasham et al. argue for the presence of a highly collimated jet moving at ≳99.99% the speed of light.

Engineered adeno-associated viruses (AAVs) aim to improve safety and potency for use in gene therapy but mechanisms underlying these features are poorly understood. Here, authors use unbiased screens to identify an interaction with the human immune system and a determinant of enhanced brain potency.

c-MYC is often deregulated in human cancers including lymphomas. Here, the authors show that a member of the pseudokinase family, tribbles homologue 3 (TRIB3), interacts with c-MYC to suppress c-MYC ubiquitination and degradation, leading to increased proliferation and self-renewal of lymphoma cells.

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.

FlyWire presents a neuronal wiring diagram of the whole fly brain with annotations for cell types, classes, nerves, hemilineages and predicted neurotransmitters, with data products and an open ecosystem to facilitate exploration and browsing.

Population genomics uncover multiple independent origins and the importance of gene flow in the spread of target-site resistance mutations in the mite pest Tetranychus urticae.

Antibody design still heavily relies on isolating antigen-specific antibodies from serum. Here the authors report a Pre-trained Antibody generative large Language Model (PALM-H3) for the de novo generation of artificial antibodies heavy chain complementarity-determining region 3 with desired antigen-binding specificity.

Drug nanoaggregates could be used to improve drug pharmacokinetics when developed for drug delivery, however, the structural features of molecules that drive nanoaggregate formation remain elusive. Here, the authors investigate nanoaggregate self-assembly mechanisms using small molecule fragments to identify the critical molecular forces that contribute to self-assembly, namely aromatic groups and hydrogen bond acceptors/donors.

Recent research sheds light on sex-specific molecular changes in the brains of MDD patients, but their association with specific symptoms is still uncertain. Here, the authors revealed the existence of gene signatures underlying the expression of distinct symptom domains in the brain of men and women with depression.

Osmotic pressure is thought to play a key role in many cellular and developmental processes, but remains challenging to measure it in cells and tissues. Here, the authors present a sensor based on double emulsion droplets that allows quantification of osmotic pressure in situ and in vivo.