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How the brain supports speaking and listening during conversation of its natural form remains poorly understood. Here, by combining intracranial EEG recordings with Natural Language Processing, the authors show broadly distributed frontotemporal neural signals that encode context-dependent linguistic information during both speaking and listening..

Distal gene regulation is increasingly recognised as a major contributor to complex trait variability. Here, the authors show that a heritable, biologically interpretable transcriptome signature driven by distal regulation predicts metabolic traits across mice and humans.

Most metabolic studies using traditional procedures fail to reveal the spatial patterning associated with metabolic flux and cellular metabolism within tissue microenvironments. Here, the authors show the application of multi-scale microscopy, machine learning-based image segmentation and spatial analysis to map the fate of nutrient-derived ¹³C across spatiotemporal scales.

Iacobucci et al. present the single-cell transcriptomic profile of patients with B cell acute lymphoblastic leukemia, report enriched multipotency and develop a multipotency score that is associated with worse survival in pediatric patients.

The authors use data on the entire Finnish population to develop a machine learning model for predicting COVID-19 vaccination uptake. Important predictors are proxies of socio-economic status, and those at high risk for COVID-19 consequences are less likely to get vaccinated.

Sosa et al. find that hippocampal neural activity in mice encodes both environmental ___location and experience relative to rewards, spanning distances far from reward, through parallel and flexible population-level codes.

Following spinal cord injury, gamified physical therapy that incorporates closed-loop vagus nerve stimulation can aid restoration of arm and hand function.

While learning a typing task, epilepsy patients show higher hippocampal ripple rates during brief rest breaks than while typing. These ‘offline’ ripples predict gains in speed, suggesting that ripples contribute to motor learning during wakeful rest.

Guetter et al. identify a melanoma-associated chondroitin sulfate proteoglycan-positive subpopulation of metastasis founder cells from lymph node biopsies of patients with melanoma and observe that they mediate immune evasion and predict systemic metastasis and poor outcomes.

PCSK9 regulates low density lipoprotein-cholesterol import and determines organ preference of metastatic pancreatic ductal adenocarcinoma, with PCSK9-low cells metastasizing to the liver and PCSK9-high cells preferring the lung.

Functional roles of natural acetylcholine (ACh) dynamics are not fully understood. This study reveals dynamic changes in ACh release across the mouse striatum during learning and extinction, identifying how and where release dynamics shape brain plasticity to gate learning and promote extinction of cue-reward associations.

Compiling data on floral introductions and European colonial history of regions worldwide, the authors find that compositional similarity of floras is higher than expected among regions once occupied by the same empire and similarity increases with the length of time the region was occupied by that empire.

A platform for profiling single-cell density reveals insights into the regulation of cell density homeostasis and patient drug responses.

Watmuff et al. show that drug treatments like carbamazepine reduce hyperactivity and improve goal-directed performance in a neural microphysiological system (DishBrain), suggesting its potential for studying drug effects on information processing.

This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.

Using a spatial reasoning task in mice, the authors show that retrosplenial cortex encodes spatial hypotheses with well-behaved recurrent dynamics, which can combine these hypotheses with incoming information to resolve ambiguities.

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

Literature produced inconsistent findings regarding the links between extreme weather events and climate policy support across regions, populations and events. This global study offers a holistic assessment of these relationships and highlights the role of subjective attribution.

The authors performed phylogenetically controlled behavioural assays and analysed brain transcriptomes across five avian families, identifying convergent patterns of gene expression associated with aggression and nesting behaviour in obligate cavity-nesting birds.

A study reports the development and validation of a wrist-worn, consumer wearable-based system that identifies sudden loss of pulse events with a performance profile suitable for societal-scale use.

Although individual genes that distinguish tumor-reactive CD8+ T cells from bystander T cells in tumors have been described, a functionally meaningful integrative signature has not been established. Here authors show that mutation-associated neoantigen-specific CD8+ tumor-infiltrating lymphocytes can be recognized by MANAscore, an algorithm that uses weighted expression levels of CXCL13, ENTPD1 and IL7R in single-cell RNAseq datasets of lung cancer and melanoma patients as input.

Multiomic analysis of blast-phase myeloproliferative neoplasms identifies a chromosome 21 amplicon harboring DYRK1A as a clonal and therapeutically targetable event in around a quarter of cases.

Stadler et al. evaluate the diagnostic value of urinary tract infection biomarker, nitrite, in predicting disease progression and treatment efficacy. The longitudinal measurement of nitrite in an in-vitro UTI distinguishes between amoxicillin-resistant and susceptible E. coli strains and correlates with bacterial colony-forming unit counts in-vitro and in clinical UTI.

Fillingim et al. show that biological and psychosocial factors jointly predict conditions associated with chronic pain.

Closed-loop brain stimulation of the human hippocampal theta rhythm produces lasting enhancement of network communication. This implicates theta rhythms in human hippocampal network communication and provides a possible route to memory modulation.

Trees come in all shapes and size, but what drives this incredible variation in tree form remains poorly understood. Using a global dataset, the authors show that a combination of climate, competition, disturbance and evolutionary history shape the crown architecture of the world’s trees and thereby constrain the 3D structure of woody ecosystems.

Schwannomas are regularly treated with radiotherapy, but the molecular effects on these tumours and their microenvironment remain unclear. Here, the authors show that radiotherapy can induce epigenetic reprogramming and immune infiltration in schwannomas, and develop the snARC-seq approach to analyse the epigenomic evolution at the single-cell level.

Three electron microscopy datasets are combined to provide a complete connectomic description of the neural circuitry that makes up the neck connective in Drosophila, including the descending neurons, ascending neurons and sensory ascending neurons.

Genomic analysis of 118 cervical tumors from Ugandan individuals identifies HPV-clade-specific differences in tumor DNA methylation, regulatory-region-associated histone marks, gene expression and pathway dysregulation.

Senescent cells accumulate in tissues with aging and disease but are difficult to detect due to distinct cell-type-specific senescence phenotypes. Here, the authors present the SenePy algorithm to identify senescent cells using single-cell transcriptomic data.

The Nr4a family of nuclear receptors has been implicated in thymocyte central tolerance via clonal deletion and regulatory T cell induction. Here the authors show, using mouse bone marrow chimeras, that Nr4a1 and Nr4a3 are also redundantly required for Bcl211/BIM induction and contribute to an anergy-like transcriptome in auto-reactive thymocytes.

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.

The chromatin-remodelling enzyme ATRX and the transcription factor HNF4A are identified as pivotal regulators of colonic epithelial identity, with roles in metastasis in colorectal cancer.

Using a multipurpose, single-cell CRISPR platform, we demonstrate precise timing of tissue-specific cell expansion during mouse embryonic development, unconventional developmental relationships between cell types, new epithelial progenitor states and insights into precancer initiation by leveraging genetic histories.

Toxicities limit combination of PARP inhibitors (PARPi) and chemotherapy in patients with germline BRCA1 and BRCA2 pathogenic variant (gBRCAm) breast cancer. Here, the authors report a preclinical study followed by a randomised phase II/III clinical trial investigating the addition of a gap between chemotherapy (carboplatin and paclitaxel) and PARPi (olaparib), in patients with early gBRCAm breast cancer.

The ability to physically partition the human brain at a spatial resolution comparable to neuroimaging methods enabled the development of a brain-wide atlas of mitochondrial content, specialization and enzymatic oxidation and phosphorylation activities.

Retromer complex cooperates with Vps5 and Vps17 in yeast to traffic transmembrane proteins. Here, the authors present structural and functional studies that reveal the mechanism of Retromer and Vps5 interaction.

Sznajder et al. identified a molecular link between autism and myotonic dystrophy, showing that a tandem repeat mutation in a single gene can disrupt splicing of multiple autism-related genes during brain development, leading to autism-like traits.

Deconvolution methods reveal individual cell types in complex tissues profiled by bulk methods. Here the authors present a Bayesian deconvolution method that outperforms existing methods when benchmarked on >700 datasets, especially in estimating cell-type-specific gene expression profiles.

The relationship between lipid dyshomeostasis and tau pathology in FTLD and AD remains unclear. Here, the authors demonstrate that GRAMD1B contributes to lipid dyshomeostasis, autophagy impairment, and tau hyperphosphorylation in neurons.

A mathematical framework to estimate the fitness of cancer driver mutations by integrating mutational bias, oncogenicity and immunogenicity finds fundamental trade-offs in cancer evolution.

The lateral hypothalamic area (LHA) mediates reward seeking. Here, the authors show how LHA afferent connections promote reward seeking by shaping synaptic strength according to energy state, processes disrupted by overconsuming palatable food.

In this systematic review and meta-analysis, Chen et al. show how the relationship between emotion regulation and mental health varies across cultures, identifying moderators such as indulgence, individualism and uncertainty avoidance.

Pulendran and colleagues define a molecular signature that can be used to predict the durability of antibody responses to vaccination and reveal important insights into the mechanisms by which vaccines induce durable immunity.

Patients with metastatic cancers of unknown primary (CUP) are currently unable to gain access to drugs through standard of care or clinical trials. Here, the authors perform whole-genome and transcriptome sequencing (WGTS) on 72 patients with CUP and demonstrate the feasibility of using WGTS to determine the specific cancer types of CUP, thereby clinically benefiting patients with CUP.

A systemically administered peptide (CARSKNKDC) that homes to injured tissues, has inherent ability to promote wound healing. Here, the authors show that this peptide binds to syndecan-4 and activates ARF6 to trigger re-epithelialisation and the naturally occurring wound repair pathway.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

The status of immune cells within human pancreatic lymphatic tissues during the onset and progression of type 1 diabetes (T1D) is underexplored. Here, by flow cytometry and CITEseq, the authors profile pancreatic, mesenteric, and splenic lymphatic tissues from individuals with varying clinical statuses and identify tissue-specific immune responses associated with T1D autoimmunity.

The molecular etiology of hypertensive disorders of pregnancy is largely unknown. Here the authors show from a prospective study of diverse pregnancies that the disease can be split into molecular subtypes based on RNA data and validated a classifier for individuals with no preexisting high risk factors.