Search

Abdominal aortic aneurysms (AAA) are characterized by extensive extracellular matrix degradation. Here Hadi et al. identify a netrin-1/neogenin-based crosstalk between macrophages and vascular smooth muscle cells (VSMCs), leading to the secretion of the matrix metalloproteinase MMP-3 by VSMCs and subsequent matrix degradation in AAA lesions.

Savan and colleagues show that distinct isoforms of the RNA-binding protein ZAP function as an antiviral restriction factor or as an interferon-resolution factor, based on differences in their intracellular localization.

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.

Gasser and colleagues report that H3K9me2 and H3K9me3 repress lineage-specific and germline genes by restricting the activity of a subset of transcription factors in terminally differentiated Caenorhabditis elegans tissues.

Reimer et al. used cryo-EM and cellular assays to reveal the structural and regulatory features that distinguish LRRK1 from LRRK2, and placed these features in the context of the evolution of the LRRK family of proteins.

Generations of microbiologists have relied on traditional genetic screening techniques to isolate mutants. Nowadays, advances in high-throughput technologies mean that fluorescent assays can be exploited for the rapid isolation of mutants with complex phenotypes. These single-cell techniques, which include flow cytometry and microfluidic applications, and their uses in microbiology, are discussed in this Review.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

Sepsis in patients is often accompanied by thrombocytopenia, but the exact role of platelets in the pathogenesis of septicaemia has not been elucidated. Here, Xiang et al. present evidence that platelets may act as anti-inflammatory cells and protect from septic shock.

Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

Nuclear HIV-1 mRNA export is mediated by cooperative Rev protein binding to the Rev response element (RRE) RNA, forming a complex recognized by the Crm1 host export factor. A structure of a Rev dimer now shows that the organization of Rev monomers within a dimer defines the RRE recognition interface, with the other side likely binding Crm1.

Viral infection of the respiratory system induces exuberant fibroblast activity, resulting in extensive remodelling of the extracellular matrix and cytokine release, which promote immune cell infiltration of the affected area at the expense of respiratory function.

Organoids derived from human intestinal cells that are co-cultured with bacteria carrying the genotoxic pks⁺ island develop a distinct mutational signature associated with colorectal cancer.

Fungi of the order Mucorales can cause life-threatening infections. Here, Chibucos et al. present genomic and transcriptomic analyses of a diverse set of Mucorales fungi, shedding light on their evolution and identifying potential therapeutic targets in the pathogens and the host.

Pulmonary arterial hypertension (PAH) is a rare lung disorder characterised by narrowing and obliteration of small pulmonary arteries ultimately leading to right heart failure. Here, the authors sequence whole genomes of over 1000 PAH patients and identify likely causal variants in GDF2, ATP13A3, AQP1 and SOX17.

Recent evidence has questioned the dogma of strict maternal transmission of mitochondrial DNA (mtDNA) in humans. Wei et al. saw no evidence of paternal transmission of mtDNA in 11,035 human trios, and show that nuclear-mitochondrial segments (NUMTs) can give the impression of paternal mtDNA transmission, but are actually inherited through the nuclear genome.

Modelling analysis shows that the current rates of annual rice yields of the Southeast Asia region will not be able to produce a large rice surplus in the future unless the exploitable yield gap is narrowed down substantially within the next 20 years.

Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery.

The focal adhesion kinase has a role in cell adhesion and migration. In this study, a fluorescent resonance energy transfer biosensor is designed to monitor focal adhesion kinase activity at membrane microdomains, revealing that the mechanisms that activate focal adhesion kinase are stimulus dependent.

Water use in river basins is an age-old resource-management question, but it is rare to quantify consumption by specific sectors. The Colorado River is being overused for beef and dairy production, endangering the entire river ecosystem.

Single barium atoms trapped in a solid xenon matrix can be imaged and counted by scanning with a focused laser, providing a possible tagging technique for the neutrinoless-double-β-decay experiment nEXO.

Documented cases of horizontal gene transfer from bacteria to eukaryotes are rare, but now, not only is a new class of transferred genes identified, the function of one representative is also demonstrated in its new setting, where it controls bacterial growth.

Affinity tagging, mass spectroscopy and a tailor-made scoring system are used to identify 497 high-confidence interactions between human proteins and human immunodeficiency virus proteins.

Neutrinos are known to have mass, in contradiction to the predictions of the standard model, and one explanation of this mass is that they are Majorana fermions; this conjecture could be proved by observation of the neutrinoless double-β decay process, but new experiments with ¹³⁶Xe find no statistically significant evidence for this process.

Conformation-specific antibodies and longitudinal tracking of individual neurons in situ identifies a toxic monomer species linked to Huntington's disease.

Biologic epicardial patch induces macrophage mediated pathophysiologic repair in chronically infarcted mice and swine hearts shows an immune cell response that results in an infiltration of M2 macrophages

Analysis of 10,900 whole-exome sequences linked to electronic health care records in the Penn Medicine Biobank enabled an exome-wide study of the phenotypic effects of rare loss-of-function gene variants, identifying new gene–disease associations that replicated across other biobanks.