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Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

Absorption features in Io's reflectance spectrum suggest that frozen SO₂ molecules are present on the surface of Io as free frost; this may have important implications for Io's atmosphere.

Exome sequencing and copy number analysis are used to define genomic aberrations in early sporadic pancreatic ductal adenocarcinoma; among the findings are mutations in genes involved in chromatin modification and DNA damage repair, and frequent and diverse somatic aberrations in genes known as embryonic regulators of axon guidance.

It remains unclear how rapid antibiotic switching affects the evolution of antibiotic resistance in individual patients. Here, Chung et al. combine short- and long-read sequencing and resistance phenotyping of 420 serial isolates of Pseudomonas aeruginosa collected from the onset of respiratory infection, and show that rare resistance mutations can increase by nearly 40-fold over 5–12 days in response to antibiotic changes, while mutations conferring resistance to antibiotics not administered diminish and even go to extinction.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

Indirect DNA damage to cells cultured below a cellular barrier caused by nanoparticles occurs across barriers containing two or more layers, but not monolayer barriers, suggesting that the thickness of the cell barrier is important in signalling.

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.

John Perry, Ken Ong and colleagues analyze genotype data on ∼370,000 women and identify 389 independent signals that associate with age at menarche, implicating ∼250 genes. Their analyses suggest causal inverse associations, independent of BMI, between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men.

The genomic profile and early transmission dynamics of the Omicron strain of SARS-CoV-2.

The mechanisms for replicating and segregating DNA are highly conserved across eukaryotes. A comparative genomic analysis of a free-living protist finds a surprising lack of protein complexes involved in these processes, suggesting that the organism uses alternative mechanisms to process DNA.

Genome-wide association analyses based on whole-genome sequencing and imputation identify 40 new risk variants for colorectal cancer, including a strongly protective low-frequency variant at CHD1 and loci implicating signaling and immune function in disease etiology.

Lagerpetids, bipedal archosaurs that are thought to be related to dinosaurs, are instead a sister group to pterosaurs, and although they have no obvious flight adaptations they share numerous synapomorphies with pterosaurs across the entire skeleton.

The biogeographic origins of Permian terrestrial vertebrates in high-latitude regions remain poorly understood. Here, the authors report an early Permian continental tetrapod fauna from South America in tropical Western Gondwana that constitutes a new biogeographic province with North American affinities.

Aducanumab, a human monoclonal antibody that selectively targets aggregated Aβ, reduces soluble and insoluble Aβ in the brain, an action accompanied by a dose-dependent slowing of clinical decline in treated patients.

It is known that exercise influences many human traits, but not which tissues and genes are most important. This study connects transcriptome data collected across 15 tissues during exercise training in rats as part of the Molecular Transducers of Physical Activity Consortium with human data to identify traits with similar tissue specific gene expression signatures to exercise.

Machine learning applied on electronic health records can predict mental health crises 28 days in advance and become a clinically valuable tool for managing caseloads and mitigating the risk of crisis.

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

Tarpey et al. carry out a large-scale systematic sequencing of the majority of X-chromosome coding exons from 208 families with multiple individuals with mental retardation and a pattern of transmission compatible with X linkage in order to identify XLMR-causative mutations. They find several mutations that appear to be causative in loci already known to be involved in XLMR, as well as new data about those loci, and make inferences about the role of the different classes of variants in these diseases.

Non-enveloped viruses such as SV40 are transported from the extracellular space into the host cell nucleus through a pathway involving endocytosis, trafficking to the endoplasmic reticulum (ER) lumen, transport across the ER membrane to the cytoplasm, and subsequent nuclear import. Helenius and colleagues provide insight into how SV40 escapes from the ER by showing that viral proteins interact with components of the host ER-associated degradation machinery (ERAD). These interactions are crucial for translocation of SV40 into the cytoplasm and infectivity.

Coupling advances in socioeconomic projections, climate models, damage functions and discounting methods yields an estimate of the social cost of carbon of US$185 per tonne of CO₂—triple the widely used value published by the US government.

The entry receptor for SARS-CoV-2, ACE2, translocates to the nucleus following infection with this virus. Here, the authors demonstrate that a peptide targeting the ACE2 nuclear localization signal promotes its methylation and abrogates viral replication of SARS-CoV-2 in Syrian hamsters.

The authors find that the Avpr1a gene, encoding the vasopressin-1A receptor, is responsible for strain-dependent pain sensitivity of mice to formalin and capsaicin. In humans, a single nucleotide polymorphism in AVPR1A was found to affect capsaicin pain and desmopressin analgesia. In both species, the effects were male specific and dependent on stress levels at the time of testing.

Results from the phase 2/3 clinical trial of gantenerumab or solanezumab in dominantly inherited Alzheimer’s disease reveal no beneficial effects on cognitive measures despite a significant reduction in amyloid plaques and other key biomarkers in those treated with gantenerumab.

Cabozantinib, an inhibitor of multiple receptor tyrosine kinases, has efficacy in a mouse model of neurofibromatosis type I and has clinical activity in reducing plexiform neurofibroma volume in a phase II trial of patients with NF1.

Genetic variants associated with susceptibility to pancreatic cancer have been identified using genome wide association studies (GWAS). Here, the authors combine data from over 9000 patients and perform a meta-analysis to identify five novel loci linked to pancreatic cancer.

The authors use single-nucleus RNA-seq to identify 10 GABAergic interneuron subtypes in human cortex layer 1. Molecular, morphological, and physiological evidence points to an emerging human cell type, the rosehip cell, not found in other species.

Gonzalez et al. use a viral evolutionary approach to generate cross-species compatible AAV (ccAAVs) vectors. They describe a highly potent new variant, AAV.cc47, with enhanced transduction efficiency over AAV serotype 9 and show its efficacy in different mouse models, pigs and non-human primates.

It has long been known that breastfeeding inhibits female fertility and that it is a factor in restricting population growth. But just how important is it?

Ian Blair and colleagues use genome-wide linkage analysis and whole exome sequencing to identify mutations in the CCNF gene in large cohorts of amyotrophic lateral sclerosis and frontotemporal dementia patients. In addition to validating the mutations in international cohorts, the authors also show that mutant CCNFgene product affects ubiquitination and protein degradation in cultured cells.

Integration of GWAS and single-cell transcriptomic data from the entire nervous system systematically identifies cell types underlying brain complex traits and provides insights into the etiology of Parkinson’s disease.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

A 51-minute-orbital-period, fully eclipsing binary system consisting of a star with a comparable temperature to that of the Sun but a 100 times greater density, accreting onto a white dwarf is reported.

Radiation can cause the amorphization of crystalline materials, which needs to be understood if they are to be used in nuclear reactors. Here, the authors show a direct correlation between amorphization resistance and disordering energetics in spinel crystals, the opposite of that observed in pyrochlores.

A new genus and species is described from fragmentary remains of a reptile from the mid–Triassic of Tanzania. The finding clarifies the relationships among the silesaurs. It is among the earliest known ornithodirans (dinosaurs plus pterosaurs), and demonstrates that silesaurs were not two-legged carnivores, as expected, but larger and more herbivorous. Furthermore, the find shows that we still know very little about the earliest stages of dinosaur and pterosaur evolution.

This work describes the identification and characterization of novel small molecule activators of SIRT1, an NAD⁺-dependent deacetylase that mediates the beneficial effects of caloric restriction. These small molecules are structurally unrelated to, and much more potent than, resveratrol, and improve metabolic function in animal models of diabetes and obesity.

Most carbon capture technologies rely on corrosive amine solutions, or high surface area materials. Here, the authors fabricate polymer microcapsules with liquid carbonate cores and permeable silicone shells combining the capacity of liquid sorbents with the surface area and low volatility of solid materials.

This report by the Consortium for Refractive Error and Myopia uses gene-environment-wide interaction study (GEWIS) to identify genetic loci that affect environmental influence in myopia development, and identifies ethnic specific genetic loci that attribute to eye refractive errors.

There is abundant evidence that new species can arise when a population of organisms is split into isolated elements. The occurrence of sympatric speciation — speciation without isolation — is much more contentious but is now set on firmer theoretical ground.

Derailed differentiation of human-specific progenitors of the developing cerebellar rhombic lip is the cause of group 4 medulloblastoma, the most common childhood brain tumour. 

Brain and skull development are intimately related across tetrapods. Here, the authors show a close relationship between brain and skull roof across evolutionary transitions and ontogenetic stages of reptiles.