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Here the authors map the dynamics of human NK cell residency and recirculation, showing that CD56^bright NK cells transiently occupy tissues and recirculate via lymphatics, whereas CD56^dim NK cells remain vascular except during inflammation.

Over 20 species of geographically and phylogenetically diverse bird species produce convergent whining vocalizations towards their respective brood parasites. Model presentation and playback experiments across multiple continents suggest that these learned calls provoke an innate response even among allopatric species.

Beck et al. develop a model where striosomes create a flexible “decision-space” that adapts to environmental context and internal state. It explains how we make choices and why decision-making varies between people, and in neuropsychiatric disorders.

An efficient quantum thermal simulation algorithm that exhibits detailed balance, respects locality, and serves as a self-contained model for thermalization in open quantum systems.

A combined sequencing technique assesses 18 patients with high-grade serous ovarian cancer over a multi-year period from diagnosis to recurrence and shows drug resistance typically arises from selective expansion of one or a few clones present at diagnosis.

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.

Here, using longitudinal pre- and post-infection samples from the RV217 Early Capture HIV Cohort Study, the authors show that mucosa-associated invariant T (MAIT) cells become activated and expand during the early acute phase of HIV infection, with subsequent reprogramming towards innate-like functionality.

The role of complex spikes in reinforcement learning is still unclear. Here, the authors show that complex spikes carry multiple context based, cell type specific and learning dependent signals that are independent of changes in any motor kinematics and unlikely to instruct the concurrent simple spike activity during reinforcement learning.

Knee osteoarthritis has a sex-specific phenotype with post-menopausal persons experiencing the highest incidence. Here the authors investigate the underlying mechanisms in a mouse model of menopause and find that the loss of 17β-estradiol and progesterone enhanced susceptibility to senescence, extracellular matrix disassembly and cartilage degradation.

Familial adenomatous polyposis (FAP) is an inherited gastrointestinal syndrome associated with duodenal adenoma formation. Here the authors show that IL17A-producing NKp44- group 3 innate lymphoid cells accumulate in FAP duodenal tissue and are associated with duodenal adenoma formation in patients with FAP.

Lynch and colleagues characterize γδ T cells in colorectal and endometrial cancer and identify distinct subsets with opposing cytotoxic and wound healing functions, leading them to develop an expansion method that enhances cytotoxic functions.

By leveraging diverse datasets from brain stimulation therapy for Tourette Syndrome and tic-inducing brain lesions, Baldermann et al. reveal a critical role of action-related functional networks in both the treatment and pathophysiology of tic disorders.

Using juxtacellular recording and labeling of hippocampal interneurons in drug-free and behaving rats, the authors show that parvalbumin-expressing basket interneurons fire in a behavioral state–dependent manner, in contrast with neuropeptide Y– and nitiric oxide synthase–expressing ivy cells.

Paiardini and colleagues describe a subset of lymph node HIV- and SIV-specific TOX^hiTCF1⁺CD39⁺CD8⁺ T cells that coexhibit stem- and effector-like phenotypic and transcriptional profiles and associate with reduced viral burden.

Causal manipulations combined with simultaneous recordings of both interneurons and medium spiny neurons in the striatum reveal dissociable contributions of cholinergic and parvalbumin interneurons in movement initiation and termination.

The authors show that artificially enhancing the temporal coordination between hippocampal sharp wave-ripples and cortical delta waves and spindles leads to the reorganization of cortical networks, an increase in their responsivity during recall, and memory consolidation. The study provides causal evidence for the role of hippocampo-cortical interactions during sleep in memory consolidation.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

By examining neural responses from tree shrews performing hierarchical decision tasks with rule reversals, the authors identify a thalamocortical mechanism for regulating cognitive flexibility.

Sleep in mammals comprises physiologically and functionally distinct stages. Here, the authors report a transitional sleep stage in Drosophila associated with 7–10 Hz oscillatory activity that can be obtained through activation of the sleep-promoting neurons of the dorsal fan-shaped body.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Viral infections and exposure to inhaled allergens are linked to asthma onset, exacerbations and progression. Here, the authors used controlled experimental rhinovirus infection in patients with and without asthma, and further assessed in vitro the role of house dust mite allergen combined with rhinovirus and SARS-CoV-2 infection. They discovered that rhinovirus-induced activation of epithelial RIG-I inflammasome supresses antiviral immunity, promotes inflammation during asthma exacerbations and aggravates subsequent infection with SARS-CoV-2, particularly upon house dust mite exposure.

The absence of an objective way of assessing freezing of gait in Parkinson’s Disease hinders research and care. A machine-learning contest using wearable sensor data delivered detection algorithms with high precision and identified time-of-day effects.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

The dorsal raphe nucleus (DRN) is known to modulate aggressive behaviour in rodents. Here the authors show that glutamatergic projections from the lateral habenula to DRN modulate aggression between male mice.

Perro and colleagues develop a CD3⁺ T cell engager co-targeting BCMA and CD38 to improve immunotherapy for multiple myeloma, demonstrate cytotoxicity in patient-derived samples and murine models and develop a quantitative systems pharmacology model.

Streptococcus pyogenes is a deadly bacteria without a vaccine. Here, researchers measured antibodies in serum and saliva from a strep throat human challenge trial. Baseline antibodies led to variable responses and affected susceptibility to strep throat.

A study reports on the antigenic characterization of SARS-CoV-2 BA.1, BA.1.1 and BA.2 and the neutralizing activity of different monoclonal antibodies and sera against them.

Circulating IgG3 increases in chronic HIV infection. Moir and colleagues describe a negative regulatory role of secreted IgG3 in response to chronic HIV infection through its action on nonconventional CD27^– memory B cells.

Insufficient AHR activation has been suggested in SLE, and augmenting AHR activation therapeutically may prevent CXCL13⁺ T_PH/T_FH differentiation and the subsequent recruitment of B cells and formation of lymphoid aggregates in inflamed tissues.

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.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

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.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.