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CARMIL2 (Rltpr) is involved in T-cell function. Here, the authors identify human CARMIL2-deficiency as an autosomal recessive primary immunodeficiency disorder characterized by EBV⁺smooth muscle tumours, CD28 co-signalling deficiency and impaired cytoskeletal dynamics.

Here, the authors present an update to a widely used curatedMetagenomicData (cMD) database and use it to create a catalog of microbiome-phenotype associations (age, sex, body mass index), and develop an oral enrichment score in the gut microbiome independently of age.

Forced expression of C-X-C chemokine receptor type 6 in antigen-specific T cells enhanced the recognition and lysis of pancreatic cancer cells and the efficacy of adoptive cell therapy for pancreatic cancer.

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.

Nucleation control of self-assembled quantum dots is challenging. Here, the authors employ conventional molecular beam epitaxy to achieve wafer-scale density modulation of high-quality quantum dots with tunable periodicity on unpatterned substrates.

Small cell lung cancer cells form functional synapses with glutamatergic neurons, receiving synaptic transmissions and deriving a proliferative advantage from these interactions.

A dictionary of human-to-mouse variants aids the design of mouse models of disease.

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.

Multiomic factor analysis of blood multiomic data, including single-cell transcriptomics, for individuals with either acute or chronic coronary syndrome identifies immune cell signatures that correlate with treatment outcomes.

A post hoc analysis of a multicentre, randomised trial showed that prediabetes remission is possible without total weight loss—providing weight is distributed to subcutaneous deposits as opposed to visceral ones.

Functional neuroimaging during a face processing task sheds light on the role of brain default mode network connectivity as a key mediator when considering the association between early life stress and cognitive impairment.

Human mammary tissue remodelling that takes place during pregnancy and lactation remains poorly understood. Here the authors characterize cells in human milk, identifying epithelial cells resembling luminal progenitors and immune cells, contributing insights into this process.

The composition of extracellular vesicles (EVs) is central to their function, yet the field lacks systematic characterization. Here Rai et al. perform proteomic and lipidomic analyses of circulating human plasma EVs and create a web tool for data exploration.

Here the authors engineer a bispecific antibody (Ab) for HIV-1 by combining a gp41 N-heptad repeat targeting Ab with a CD4 binding Ab. Prepositioning via CD4 binding results in high neutralization breadth and potency, and experiments in HIV infected humanized male mice show reduction of viral load.

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

Silencing of endogenous retroviral elements (ERVs) is mediated by KAP1. Here, the authors describe the molecular mechanism by which KAP1 induces structural reorganization and multimerization of HP1α and maintains inaccessible chromatin at ERVs in mouse embryonic stem cells.

The mechanism of currently prescribed antidepressants is incompletely understood. Here, the study identifies associations between antidepressant use and DNA methylation, highlighting shared signals across datasets, and tissue enrichment in the amygdala.

Previous studies have shown that the CD40L-CD40 signaling axis plays a role in atherosclerosis. Here the authors investigate the cell-specific functions of the most relevant CD40L-expressing cell types in atherosclerosis. Deficiency of T cell-derived CD40L reduces and stabilizes plaques through impaired Th1 polarization while platelet-derived CD40L ameliorates atherothrombosis.

Through genome-wide and focused CRISPR screens, Zhang et al. discover that loss of PRC2 or KMT2D-COMPASS enables distinct EMT trajectories, which exert differential effects on the metastatic capability of carcinoma cells.

Three studies identify a transcription-coupled DNA–protein crosslink repair pathway that depends on the Cockayne syndrome proteins and the proteasome.

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.

A design pipeline is presented whereby binding proteins can be designed de novo without the need for prior information on binding hotspots or fragments from structures of complexes with binding partners.

An NNMT inhibitor reduces tumour burden and metastasis in multiple mouse cancer models and restores immune checkpoint blockade efficacy by decreasing cancer-associated-fibroblast-mediated recruitment of myeloid-derived suppressor cells and reinvigorating CD8⁺ T cell activation.

Many protein–protein interactions are mediated by compact amino acid stretches known as short linear motifs (SLiMs) that lack a stable tertiary structure. A study now uses high-throughput precision genome editing to decode the function of over 7,000 SLiMs across the human proteome, providing insights into their roles in cellular homeostasis.

Tumour acidosis is known to drive metabolic adaptations in cancer cells, contributing to their survival and resistance to therapies. A study now identifies a chondroitin sulfate-enriched glycocalyx as a key feature of the acidic tumour microenvironment in glioblastoma that limits lipid uptake and protects cells against death by ferroptosis.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Photons emitted from a quantum dot typically have slightly different frequencies owing to various sources of noise. Here, the authors suppress the noise, notably the noise arising from the nuclear spins, and demonstrate single-photon emission with a transform-limited optical linewidth.

Zhang et al. identify and characterize supermeres as extracellular nanoparticles that exhibit unique biological and functional properties with potential prognostic and therapeutic value across distinct diseases.

Olfactory neuroblastoma (ONB) is a rare malignant tumor whose genetic basis is poorly understood. Here the authors identify recurrent deletions involving dystrophin in the majority of ONB patient tumors examined.

Hypothalamus participates in systemic metabolic processes, while high calorie intake increases immune activation in the central nervous system. Here the authors show that reduced regulatory T cells in the hypothalamus contribute to elevated immune activation in a high calorie environment, thereby prompting a potential therapy target for metabolic diseases.

Current methods for acquiring dissemination kinetics of rare circulating tumor cells (CTCs) that form metastases have several limitations. Here, the authors show an approach for measuring endogenous CTC kinetics by continuously exchanging CTC-containing blood between un-anesthetized, tumor-bearing mice and healthy, tumor-free counterparts.

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.

Understanding the structure of the Kondo cloud formed by conduction electrons screening the impurity spin is a long-standing problem in many-body physics. Shim et al. propose the spatial and energy structure of the multichannel Kondo cloud, by studying quantum entanglement between the impurity and the channels.

An extensive RNA binding protein atlas (RBPome) for primary T cells would be a useful resource. Here the authors use two different methods to characterise the mouse and human T cell RBPome and show regulation of Roquin-1/2 dependent and independent pathways.

CRISPR-Cas9-based screens have allowed the study of gene-drug interactions. Here, the authors develop CRISPR-Cas9 knock-out, activation and repression screens in human gastric 3D organoids, also integrating single-cell CRISPR screens, to identify genes involved in the response to cisplatin in gastric cancer.

Enhanced polyamine depletion in neuroblastoma models decreases translation of mRNA codons with adenosine in the third position, reprogramming the tumour proteome away from cell cycle progression and towards differentiation.

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.

Hegazy and colleagues demonstrate that epithelial oncostatin M receptor expression drives gut inflammation and tumor formation.

Somatic mutations in blood cells (CHIP) are linked to diseases like heart disease, but the mechanisms are unclear. Here, the authors show that different CHIP driver genes alter unique sets of plasma proteins, some of which are validated in mouse models.