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Conventional models propose multiple fault systems across a diffuse deformation zone absorbing plate convergence in the western Mediterranean. Here the authors show new data supporting the active development of a single plate boundary fault system, representing an underappreciated seismic and tsunami hazard.

The authors present an extensive profile of host transcriptional respones to a diverse group of pathogens and allergens. In doing so, they identify TH1, type I IFN, TH17, and TH2 responses, that underlie each immune response in both the blood and lung, which represents a global profile of host-pathogen immune responses.

The prognosis of castration-resistant prostate cancers remains dismal, but accurate preclinical models can lead to effective therapies. Here the Melbourne Urological Research Alliance establish prostate cancer patient-derived xenografts, use the tumors for organoids and single-cell RNA-seq, and show the efficacy of PARP inhibitor combination treatments.

Most instances of Alzheimer’s disease (AD) are sporadic or not associated with a particular mutation. Here, the authors develop knock-in mice that express wildtype human Aβ under control of the mouse App locus, which may have potential for modelling some aspects of sporadic late onset AD.

A multi-ancestry genome-wide association study of prostate cancer performed in 156,319 cases and 788,443 controls identifies 187 novel risk variants associated with the disease. Genetic risk scores associated with overall risk, and risk of aggressive disease in men of African ancestry.

Reference assemblies of great ape sex chromosomes show that Y chromosomes are more variable in size and sequence than X chromosomes and provide a resource for studies on human evolution and conservation genetics of non-human apes.

The physical properties of devices made of printed nanosheets and nanowires are determined by their intrinsic nanostructured network morphology. Here, the authors use FIB-SEM nanotomography to quantitatively analyze printed nanostructured networks via 3D reconstructions.

Here the authors show that SARS-CoV-2 vaccination and boosting, especially in the setting of previous infection, leads to significant increases in antibody levels and neutralizing activity against omicron BA.1 and BA.5 variants in both pregnant patients and their neonates.

Developmental and epileptic encephalopathies are devastating neurological disorders. Here, the authors establish a cohort of patients with variants in the gene DENND5A and use human stem cells to discover a disease mechanism involving altered cell division.

How the necroptosis executioner, MLKL, converts to a killer form has been mysterious. Here, authors show RIPK3-mediated phosphorylation of human MLKL is the cue for pseudokinase domain dimerization before assembly of pro-necroptotic MLKL tetramers.

Emerging SARS-CoV-2 variants of concern were detected early and multiple cases of virus spread not captured by clinical genomic surveillance were identified using high-resolution wastewater and clinical sequencing.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

The atmospheric terminator region of WASP-39 b, a hot gas giant exoplanet, is inhomogeneous, despite past assumptions, with the evening terminator being hotter and thus probably clearer, and the morning terminator probably being cloudy and consequently cooler.

RAC1 is a downstream target of the Wnt signaling that promotes intestinal stem cell expansion and tumorigenesis. Here, the authors identify the specific splice variant RAC1B as an important mediator of colorectal tumourigenesis and a potential target for enhancing the efficacy of EGFR inhibitor treatment.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

Hyperactivation of inflammasome-induced IL-1β can cause immunopathology and is a feature of autoinflammatory diseases. Here, the authors show how ubiquitination of IL-1β limits its activity by targeting it for proteasomal degradation and preventing its cleavage by caspase-1.

Necroptosis is a form of cell death characterized by membrane rupture via MLKL oligomerization, although mechanistic details remain unclear. Here, the authors show that MLKL ubiquitylation of K219 facilitates high-order membrane assembly and subsequent rupture, promoting cytotoxicity.

A study comparing the Y chromosome across mammalian species reveals that selection to maintain the ancestral dosage of homologous X–Y gene pairs preserved a handful of genes on the Y chromosome while the rest were lost; the survival of broadly expressed dosage-sensitive regulators of gene expression suggest that the human Y chromosome is essential for male viability.

The association between obesity and breast cancer biology remains understudied in humans. Here, using a large retrospective data collection, the authors identify obesity associated changes in the genomic, transcriptomic profile, and the tumor microenvironment of primary untreated breast tumors.

Approaches for temporal analysis and quantitative characterisation of single cell morphology and dynamics remain in high demand. Here authors present CellPhe, a pattern recognition toolkit for the unbiased characterisation of cellular phenotypes within time-lapse videos.

A systematic review of evidence, across the key pillars of prevention, diagnosis, treatment and prognosis, outlines milestones that need to be met to enable the broad clinical implementation of precision medicine in diabetes care.

Sequencing data from two large-scale studies show that most of the genetic variation influencing the risk of type 2 diabetes involves common alleles and is found in regions previously identified by genome-wide association studies, clarifying the genetic architecture of this disease.

Artemisinin-resistantPlasmodium is an increasing problem. Here, using a medicinal chemistry programme, the authors identify a tetraoxane-based drug candidate that shows no cross-resistance with an artemisinin-resistant strain (PfK13-C580Y) and is efficient in Plasmodiummouse models.

A tool kit to study bacterial efflux pumps and the movement of compounds across the cell envelope was developed enabling investigation of efflux pump physiological functions, substrate specificities and profiling of efflux pump inhibitors.

The heparan sulfate proteoglycan-binding cytokine APRIL has a protective role against atherosclerotic disease.

The processes that regulate melanoblast migration during development are also thought to be involved in melanoma metastasis. Here, Prex1 null mice are shown to have a melanoblast migration defect and, when crossed to a mouse model of melanoma, are resistant to metastasis, suggesting a role for Prex1 in metastatic melanoma.

Two doses of the coronavirus disease 2019 vaccine ChAdOx1 nCoV-19 boost antibody responses and functions in phase 1/2 trial participants.

What neural computations underlie the human sense of confidence? Geurts et al. show that subjective confidence is based on a probability distribution represented in cortical activity.

Growing evidence suggests that environmental rather than genetic factors are major contributors to asthma development. Here the authors show that high intake of dietary fibre by pregnant mice increases resistance of their progeny to the development of allergic airways disease.

The cellular effects of cold preservation in heart transplantation and how warm ischaemia leads to damage are unclear. Here the authors identify succinate accumulation as a major damaging metabolic change in warm ischaemia.

The CNV analysis group of the Psychiatric Genomic Consortium analyzes a large schizophrenia cohort to examine genomic copy number variants (CNVs) and disease risk. They find an enrichment of CNV burden in cases versus controls and identify 8 genome-wide significant loci as well as novel suggestive loci conferring either risk or protection to schizophrenia.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

Multi-ancestry genome-wide association analyses identify new risk loci for Parkinson’s disease, and fine-mapping and co-localization analyses implicate candidate genes whose expression is associated with disease susceptibility.

Mutations in the gene encoding PC1 cause ADPKD, a common genetic renal disease. Here, the authors show that expression of the C-terminal 200 amino acids of the large PC1 protein in mouse models of ADPKD suppresses cystic disease through an interaction with the mitochondrial enzyme NNT.

The male-specific region of rhesus macaque and human Y chromosome (MSY) are sequenced and compared to the human MSY, showing that during the last 25 million years MSY gene loss in the rhesus and human lineages was limited to the youngest stratum (stratum 5), whereas gene loss in the older strata ceased more than 25 million years ago.

Prostate cancer often does not progress to invasive disease and thus markers predicting the course of the disease progression are critical for optimal treatment choices. Here the authors show that variants at two genetic loci correlate with the aggressiveness of prostate cancer.

The protein OCRL is linked to Lowe syndrome and Dent disease, two related diseases. Mutations in the OCRL Ash-RhoGAP domain abolish its interactions with the F&H motifs in APPL1, Ses1 and Ses2. Structural and biochemical analysis of the OCRL Ash-RhoGAP domain with F&H motifs shows that clinical mutations destabilize the Ash-RhoGAP domain, abolishing the interactions between OCRL- and F&H-motif-containing proteins.

Deep learning was used to map the crown sizes of each tree in the West African Sahara, Sahel and sub-humid zone using submetre-resolution satellite imagery, revealing a relatively high density of trees in arid areas.

An analysis of skeletal stem cells in mice reveals that bone ageing occurs at the level of local niches affecting skeletal and haematopoietic lineage output, which may influence systemic aspects of multi-organ physiological ageing.

GNPS is an open-access community-curated analysis platform for sharing natural product mass spectrometry data that enables continuous, automatic reanalysis of deposited 'living' data sets.

Biosynthesis of peptidoglycan requires carefully orchestrated transpeptidation reactions to maintain the structural integrity of this essential component of the bacterial cell wall. Now, rotor-fluorescent d-amino acids have been shown to enable real-time tracking of these transpeptidation reactions in live bacterial cells. These powerful tools allow visualization of peptidoglycan biosynthesis with high spatiotemporal resolution.

Two below-threshold surface code memories on superconducting processors markedly reduce logical error rates, achieving high efficiency and real-time decoding, indicating potential for practical large-scale fault-tolerant quantum algorithms.