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Single-cell profiling of human prostate cancer and studies in mouse models show that macrophages expressing SPP1 mediate immunotherapeutic resistance through adenosine pathway activation and represent a potential target for future studies.

Inflammation can reduce food intake. Here the authors show that the GABAergic pathway from bed nucleus of stria terminalis to lateral hypothalamus regulates the inflammation induced reduction in feeding in mice.

How the development of the cochlear epithelium is regulated is unclear. Here, the authors use single cell RNAseq analysis to provide insight into the transcriptional changes arising during development of the murine cochlear inner and outer hair cells.

Sex differences in brain transcriptomics have unknown cell type specificity. Here, authors show concordant cortical transcriptomic patterns in depression within individual cell types between sexes, but distinctly affected top cell types and genes.

Ian Krantz, Katsuhiko Shirahige and colleagues report the genetic characterization of a new clinical syndrome characterized by cognitive impairment, heart and pulmonary defects, and skeletal dysplasia, among other symptoms. They identify gain-of-function mutations in the super elongation complex gene AFF4 as causing the disorder.

A context-aware, attention-based deep learning model pretrained on single-cell transcriptomes enables predictions in settings with limited data in network biology and could accelerate discovery of key network regulators and candidate therapeutic targets.

The Human Microbiome Project Consortium has established a population-scale framework to study a variety of microbial communities that exist throughout the human body, enabling the generation of a range of quality-controlled data as well as community resources.

Epigenetic changes associated with post-natal differentiation have been characterized. Here the authors generate epigenomic and transcriptional profiles from primary human breast cells, providing insights into the transcriptional and epigenetic events that define post-natal cell differentiation in vivo.

Repression of gene transcription using CRISPR-Cas9 has been achieved in vitro but not for delivery into adult animal models. Here, the authors use AAV8 to deliver the transcriptional repressor dSaCas9^KRAB to the cholesterol regulator Pcsk9, and show repression up to 24 weeks and reduced cholesterol levels in mice.

This protocol details the generation and characterization of vestibular inner ear organoids from human pluripotent stem cells. This is an extension of a previous protocol for skin organoid generation, with which it shares foundational methodology and reagents.

Two doses of the coronavirus disease 2019 vaccine ChAdOx1 nCoV-19 boost antibody responses and functions in phase 1/2 trial participants.

Building crystal structures into the electron density is an important step in protein structure solution. Here, the authors recruit online game players, students, and experienced crystallographers to compete in a competition to solve a new structure, and find that crowdsourcing model-building works.

Graphene is a promising material for the next-generation of nanoelectronic devices, but it has been difficult to produce single-layer samples in bulk quantities. A solution-based process for the large-scale production of single-layer, chemically converted graphene has now been demonstrated and used to make field-effect devices with currents that are three orders of magnitude higher than previously reported for chemically produced graphene.

We demonstrate that phages have co-opted cas genes from CRISPR defence systems, which subsequently evolved anti-defence functions.

A double-transgenic mouse model that enables monitoring or manipulation of dopamine and serotonin simultaneously in the brain’s nucleus accumbens shows that these neuromodulators have opponent roles in reward learning.

Biomolecular condensates compartmentalize molecules without membranes. Understanding condensate composition is important given that their function relies on the selective exclusion or enrichment of molecules. Now, investigating small-molecule partitioning reveals variations across compounds, yet correlations indicate physical similarities between disparate condensates. Machine learning accurately predicts partitioning on the basis of physicochemical features, demonstrating the role of a hydrophobic environment in driving enrichment and exclusion.

This study defined spatial gene expression in the human dorsolateral prefrontal cortex. It reveals layer-enriched expression of genes associated with schizophrenia and autism, highlighting the clinical relevance of spatially defined expression.

Virtual memory T cells are CD8 T cells with memory phenotype present in unimmunized mice. Here the authors show that these cells have higher affinity for self-antigen, depend on IL-15 for proliferation and antigen-non-specific cytotoxicity in mice, and that a similar population exists in humans.

Genome-wide data from 400 individuals indicate that the initial spread of the Beaker archaeological complex between Iberia and central Europe was propelled by cultural diffusion, but that its spread into Britain involved a large-scale migration that permanently replaced about ninety per cent of the ancestry in the previously resident population.

Manipulating the flow of heat at the nanoscale is difficult because it requires the ability to tune the thermal properties of tiny structures. Here, the authors locally change the thermal conductivity of an individual silicon nanowire by irradiating it with helium ions.

Systemic inflammation is recognized as a central pathobiologic feature in heart failure with preserved ejection fraction (HFpEF). Here, the authors report 70 pro- and anti-inflammatory eicosanoid and eicosanoid-related metabolites associated with HFpEF status.

Fiancette et al. utilize models of inducible transcription factor deletion in mature tissue-resident ILCs to reveal complementary and competing transcriptional networks that determine ILC3 phenotype and functional capacity.

RNA-binding motifs in eukaryotic proteins are presented in a comprehensive resource.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

Sarcomatoid and rhabdoid tumours are highly aggressive forms of renal cell carcinoma that are also responsive to immunotherapy. In this study, the authors perform a comprehensive molecular characterization of these tumours discovering an enrichment of specific alterations and an inflamed phenotype.

Genome-wide data from 166 East Asian individuals dating to between 6000 bc and ad 1000 and from 46 present-day groups provide insights into the histories of mixture and migration of human populations in East Asia.

Proteomics of small sample sizes using data-independent acquisition methods achieves higher throughput with multiplexing.

DNA analysis of 6 individuals from eastern and south-central Africa spanning the past approximately 18,000 years, and of 28 previously published ancient individuals, provides genetic evidence supporting hypotheses of increasing regionalization at the end of the Pleistocene.

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

Primary tumor presence and progression shape the systemic immune landscape and immune responses to pathogens in multiple murine tumor models.

Detailed insight into how the brain responds to Trypanosoma brucei infection is lacking. Here, single cell and spatial transcriptomics are integrated to characterise this response, identifying a unique crosstalk between microglia and plasma cells.

The hypothalamic neuropeptide oxytocin exerts analgesic effects, but the underlying pathways remain largely elusive. Here, the authors describe an analgesic pathway formed by oxytocin neurons projecting to the periaqueductal grey, where axonally released oxytocin activates oxytocin-receptor expressing GABA neurons and subsequently reduces pain-like behaviors in both female and male rats.

A survey of sharks and rays on coral reefs within 66 marine protected areas across 36 countries showcases that the conservation benefits of full MPA protection to sharks almost double when accompanied by effective fisheries management.

Aaron Gitler, Robert Farese Jr. and colleagues identify the RNA lariat debranching enzyme Dbr1 as a potent suppressor of TDP-43 toxicity in yeast. They further show that Dbr1 knockdown reduces TDP-43 toxicity in mammalian cells, identifying this enzyme as a possible therapeutic target in amyotrophic lateral sclerosis and other diseases marked by TDP-43 accumulation.

The tunability of electronic properties is a central goal of research into topological semimetals. Here, the authors report Weyl nodal ring states in the magnetic semimetal EuGa₄ and link the nodal ring state to the observed large non-saturating magnetoresistance.

Studies using mouse models of lung adenocarcinoma identify an association between age, iron homeostasis and tumour initiation potential that involves NUPR1 and lipocalin-2.

Here authors show that machine learning derives the degree of background retinal pigmentation with more nuance than self-described ethnicity. Retinal pigment scores are associated with genes linked to melanin and may improve algorithmic fairness.

Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance.

Neural networks trained using predictive models generate representations that recover the underlying low-dimensional latent structure in the data. Here, the authors demonstrate that a network trained on a spatial navigation task generates place-related neural activations similar to those observed in the hippocampus and show that these are related to the latent structure.

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

The atmospheric terminator region of WASP-39 b, a hot gas giant exoplanet, is inhomogeneous, despite past assumptions, with the evening terminator being hotter and thus probably clearer, and the morning terminator probably being cloudy and consequently cooler.

The Pharma Proteomics Project generates the largest open-access plasma proteomics dataset to date, offering insights into trans protein quantitative trait loci across multiple biological domains, and highlighting genetic influences on ligand–receptor interactions and pathway perturbations across a diverse collection of cytokines and complement networks.

This Perspective provides a roadmap toward globally federated open data resources for bioimaging data.

Interactions between the immune system and adipose tissue contribute to the regulation of body weight, however, the underlying mechanisms remain incompletely understood. Here the authors dissect the role of two structurally and functionally similar immune mediators, BAFF and APRIL, in modifying diet-induced weight gain and adipocyte lipid handling.

Lipophilic siRNA conjugates exert therapeutic activity in the mouse CNS.

Determining the time evolution of reactions at the quantum mechanical level improves our understanding of molecular dynamics. Here, authors separate the breakup of water, one bond at a time, from other processes leading to the same final products and experimentally identify, separate, and follow step by step two breakup paths of the transient OD⁺ fragment.

Some anesthetics despite being generally associated with sedation, can also increase brain activity—a phenomenon called paradoxical excitation. The authors identified dozens of compounds that generally decrease neuronal activity, but increase activity in the caudal hindbrain of zebrafish.