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Cells can regulate their mass density. Here, the authors demonstrate how eukaryotes establish and maintain a lower density in the nucleus than in the cytoplasm via pressure balance, and how deviations emerge during pathophysiological states like senescence.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

The kidney is vascularized with highly specialized and zonated endothelial cells that are essential for its filtration function. Here, Barry et al. provide a single-cell RNA sequencing analysis of the kidney vasculature that highlights its transcriptional heterogeneity and uncovers pathways important for its development and function.

In this work, the authors report a sophisticated combination of genetic, biophysical, and biochemical analyses to identifies the cycling conformational states of PPM1D. The findings reveal how an allosteric inhibitor locks the protein into a conformationally inactive state, and explain the distribution of PPM1D activating mutations in cancer.

The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.

An analysis involving the shotgun sequencing of more than 300 ancient genomes from Eurasia reveals a deep east–west genetic divide from the Black Sea to the Baltic, and provides insight into the distinct effects of the Neolithic transition on either side of this boundary.

Structure of human nuclear pore complex in its cellular environment reveals a substantially dilated central channel and shows that its nucleoplasmic and cytoplasmic rings restrict channel dimensions and create membrane asymmetry at the inner ring.

The tumour microenvironment can be modulated to sensitize tumours to the effects of therapy. Here the authors show that radiation induced miR-103 downregulates TREX1 in endothelial cells, decreases angiogenesis and leads to the secretion of proinflammatory mediators that reduce tumour growth.

Exome-wide analysis identifies rare and low-frequency coding variants associated with body mass index. Gene-based meta-analysis and functional studies implicate 13 genes, eight of which are novel, and neuronal pathways as factors in human obesity.

X-ray crystal structures of the M1 and M4 muscarinic acetylcholine receptors, revealing differences in the orthosteric and allosteric binding sites that help to explain the subtype selectivity of drugs targeting this family of receptors.

A transancestral exome-wide association study for body-fat distribution identifies protein-coding variants that are significantly associated with waist-to-hip ratio adjusted for body mass index.

Data from over 700,000 individuals reveal the identity of 83 sequence variants that affect human height, implicating new candidate genes and pathways as being involved in growth.

Wu et al. identify a mechanistic role for LPAR4 in promoting a fibronectin-rich extracellular matrix via AKT, CREB and integrins, thereby generating a niche that facilitates initiation of pancreatic cancer.

People who experience optic neuritis, a cause of potentially serious sudden vision loss, have up to a 50% chance of ultimately being diagnosed with multiple sclerosis. Here, the authors find that genetic information combined with age and sex helps predict risk of future diagnosis of multiple sclerosis.

A search for transient dark matter in the form of domain walls of axion-like particles finds no statistically significant signal. This places constraints on our theoretical understanding of such scenarios.

During eukaryotic ribosome biogenesis, the nascent 60S subunit is activated by SBDS and GTPase EFL1. Cryo-EM and mutational analyses reveal how SBDS–EFL1 evicts antiassociation factor eIF6 from 60S and explain the effects of disease-related SBDS mutations.

Raf kinase activity is deregulated in cancers and is thought to promote tumor growth by inducing proliferation signaling through MEK/Erk. This report identifies a new role for c-Raf independent of MEK/Erk and relying on phosphorylation of Ser338. Phospho–C-Raf interacts with the mitotic kinases Aurora-A and Plk1, activating the latter to promote mitotic progression and increase cell division, and this pathway is a crucial mediator for the protumorigenic effect of c-Raf in vivo.

Neurofibromatosis type 2 (NF2) is caused by inactivation of the NF2 gene, which encodes merlin. NF2 patients develop peripheral neuropathies. The authors show that NF2 inactivation decreases axonal integrity in mice and NF2 patient tissue. Their data suggest that merlin activates RhoA and promotes neurofilament heavy chain phosphorylation to maintain axonal integrity.

Studies of mouse and human IgA responses against Candida albicans and other common fungal species show that host adaptive immunity selects for fungal effectors that promote commensalism and prevent intestinal disease.

Tumors hijack cellular pathways to evade the effects of cancer therapy. Here, Advaniet al. show that DNA damage-induced phosphorylation of CRAF Serine 338 triggers DNA repair by recruiting CHK2, highlighting a role for CRAF independent from its canonical function as a kinase.

The active-state structure of a GPCR occupied by a partial agonist, β₂AR with salmeterol, together with mutagenesis and biophysical studies, explains this ligand's unusual pharmacological profile.

Clinical insights from patients with a rare genetic skeletal disorder led to the discovery of the first case of a pathogenic gain-of-function miRNA mutation.

Osteogenesis imperfecta (OI) is genetically linked to autosomal dominant or autosomal recessive mutations. Here, Marini et al. describe two families with X-chromosome-linked OI with mutations in MBTPS2 that alter regulated intramembrane proteolysis and subsequent defects in collagen crosslinking and osteoblast function.

The X-ray crystal structure of the human G-protein-coupled receptor protease-activated receptor 1 (PAR1) bound to the antagonist vorapaxar is solved, revealing an unusual method of drug binding that should facilitate the development of improved PAR1-selective antagonists.

Cheresh and colleagues delineate a pathway that regulates tumour cell stemness and resistance to therapy. They find that the unliganded integrin α_vβ₃ is able to promote cancer cell self-renewal, tumour initiation and resistance to EGFR inhibitors by binding KRAS and RalB to activate the NF-κB pathway.

Penguin colonies emit gaseous ammonia that enhances new particle formation processes in Antarctica, according to online observations of gaseous ammonia and aerosol particles from a coastal site in Antarctica.