Search

Uracil was identified in the sample returned from the asteroid Ryugu. Having been provided to the early Earth as a component in such asteroidal materials, these molecules might have played a role for prebiotic chemical evolution on the early Earth

Organic cation transporters are important drug transporters that influence therapeutic outcomes. Here, the authors find that these transporters are regulated by tyrosine phosphorylation and propose that tyrosine kinase inhibitors can influence drug transporter function through post-translational mechanisms.

Adverum Biotechnologies is developing one-time gene therapies aimed at revolutionizing the treatment of patients with wet age-related macular degeneration and other serious ocular disorders.

PELP1 is a large scaffolding protein implicated in many cellular activities, including ribosome assembly as part of the Rix1 complex, comprising PELP1, WDR18, TEX10 and other components. Here, authors present the cryo-EM structure of PELP1 in complex with its binding partner WDR18, revealing the architecture of PELP1's numerous signaling motifs.

Using deep sequencing of human carotid plaque cells from male and female patients with carotid stenosis, Sukhavasi et al. identify sex-biased cell-type-specific gene-regulatory networks and different phenotypes in smooth muscle cells, including an osteogenic phenotype in females and a chondrocytic phenotype in males.

Examining drivers of the latitudinal biodiversity gradient in a global database of local tree species richness, the authors show that co-limitation by multiple environmental and anthropogenic factors causes steeper increases in richness with latitude in tropical versus temperate and boreal zones.

The connection between expression variation and phenotypic diversity in the populations of polyploid crops remains elusive. Here, the authors reveal the impact of genetic variants leading to biased expression of homoeologous genes in hexaploid wheat on agronomic traits.

Tumor-associated macrophages support an immunosuppressive tumor microenvironment. Di Conza et al. uncover how IRE1–XBP1 and IRE1−STAT3 endoplasmic reticulum stress responses pathways are engaged by tumor-derived lipids to orchestrate pro-tumorigenic features and survival in tumor-associated macrophages.

The innate immune response in epithelial cells after SARS-CoV-2 infection is not fully understood. Here the authors use human air-liquid interface culture and show single cell transcription changes and delayed type I Interferon responses after SARS-CoV-2 infection compared with other respiratory viruses.

The authors present a public collection of 117 bacterial isolates from the pig gut, including the description of 38 novel taxa. Interesting functions discovered in these organisms include a new fucosyltransferease and sactipeptide-like molecules encoded by biosynthetic gene clusters.

As a consequence of high chemical resistance and low solubility in conventional solvents, deconstructing biomass into fuels and other useful chemical building blocks remains a challenge. Now, through enzyme modification and ionic liquid solvents, it is possible to homogeneously biocatalytically convert cellulose to sugars at a rate 30 times greater than is achievable in water.

Combining 32 genome-wide association studies with high-density imputation provides a comprehensive view of the genetic contribution to type 2 diabetes in individuals of European ancestry with respect to locus discovery, causal-variant resolution, and mechanistic insight.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

After infection with SARS-CoV-2 a diverse set of symptoms remain or develop longer term in a condition termed long-CoVID, yet an accurate and tractable model has remained elusive. Here the authors present a non-human primate model of long-CoVID and show persistent hyperglycemia following acute infection.

Analysis of genomic data from 25 distantly related plant species shows signatures of selection on the same gene families and functions that repeatedly contributed to local adaptation to climate.

A solution-processed electronic device that uses colloidal quantum dots of lead sulphide outperforms the state-of-the-art crystalline alternatives, with ease of fabrication, physical flexibility, large device areas and low cost among its benefits.

The transits of two Sun-like stars by small planets in an open star cluster are reported; such a stellar environment is unlike that of most planet-hosting field stars, and suggests that the occurrence of planets is unaffected by the stellar environment in open clusters.

Basolateral recycling and transcytotic pathways in epithelial cells are defined by specific markers, however the apical recycling pathway is poorly understood. Perez Bay et al. show that Megalin is a marker for this pathway, which intersects with the other routes in shared perinuclear recycling endosomes.

Mutations in proteins that localize to primary cilia cause devastating diseases, yet the primary cilium is a poorly understood organelle. Here the authors use interaction proteomics to identify a network of human ciliary proteins that provides new insights into several biological processes and diseases.

Previous studies identified an association between the 2q35 locus and breast cancer. Here, the authors show that a SNP at 2q35, rs4442975, is associated with oestrogen receptor positive disease and suggest that this effect is mediated through the downregulation of a known breast cancer gene, IGFBP5.

The first report from the prospective GenoVA Study provides preliminary insights into the development of a polygenic risk score assay in a clinical setting and discusses the challenges of generating, interpreting and reporting results.

Although progress in the coverage of routine measles vaccination in children in low- and middle-income countries was made during 2000–2019, many countries remain far from the goal of 80% coverage in all districts by 2019.

CCR5 is a co-receptor for many transmitted HIV strains. Here, the authors show that biweekly injection of the CCR5-specific antibody Leronlimab protects rhesus macaques against infection following repeated intrarectal challenges of a CCR5-tropic SHIV.

Interactions between cyclic AMP and calcium signalling pathways mediated by the inositol 1,4,5-trisphosphate receptor are shown to regulate hepatic gluconeogenesis in fasting and diabetes.

Stellar data from the Kepler spacecraft are used to infer the existence of a sub-Mercury-sized exoplanet, the smallest yet discovered, in orbit around a Sun-like star.

Sequencing of the bonobo genome shows that more than three per cent of the human genome is more closely related to either the bonobo genome or the chimpanzee genome than those genomes are to each other.

In an interim analysis of a phase 1 trial of concurrent intrathecal and intravenous anti-PD1 delivery in patients with leptomeningeal disease and melanoma, treatment was feasible and well-tolerated with no dose-limiting toxicities.

While micro-RNAs are known regulators of haematopoiesis and leukemogenesis, the role of long non-coding RNAs is less clear. Here the authors provide a non-coding RNA expression landscape of the human hematopoietic system, highlighting their role in the formation and maintenance of the human blood hierarchy.

Animals’ response to acute stress is known to be influenced by sex and genetics. Here the authors performed RNA-seq on actively translated mRNAs in hippocampal CA3 neurons in mice, and document the effects of sex and genotype (i.e., BDNF Val66Met) on acute stress-induced gene expression.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Hepatitis B virus (HBV) has a limited host range and current animal models can only recapitulate certain aspects of HBV replication. Here, the authors show that expression of the HBV receptor NTCP in macaques supports HBV replication in vivo, suggesting this as animal model for future HBV studies.

Prioritizing candidate biomarkers for verification remains a formidable obstacle to the translation of protein diagnostics to clinical applications. Whiteaker et al. assemble a multistage, targeted proteomics pipeline to relieve this bottleneck and use a mouse cancer model to demonstrate its analytical performance.

ESR1 mutations occur in endocrine-resistant patients but have not yet been reported in in vitro models of breast cancer. Here, the authors report the discovery of naturally occurring ESR1 ^Y537Cand ESR1 ^Y537S mutations in two breast cancer cell lines after acquisition of resistance to long-term-estrogen-deprivation.

Trans-ethnic analyses of exome array data identify new risk loci for type 2 diabetes. Fine-mapping analyses using genome-wide association data show that the index coding variants represent the likely causal variants at only a subset of these loci.

Evolutionarily conserved gene modules mediate neurodegenerative dementia in a variety of mouse models and in postmortem brain tissue from patients.

Analyses of the proportions of individuals who have completed key levels of schooling across all low- and middle-income countries from 2000 to 2017 reveal inequalities across countries as well as within populations.

High-resolution subnational mapping of child growth failure indicators for 105 low- and middle-income countries between 2000 and 2017 shows that, despite considerable progress, substantial geographical inequalities still exist in some countries.

Chapeau et al. develop a nonallosteric inhibitor of the interaction between YAP and all four TEAD proteins. Treatment with the inhibitor, either as monotherapy or in combination with other treatment modalities, leads to induction of cell death in several in vivo cancer models.

Multi-modal profiling reveals major alterations in colonic B cells in patients with ulcerative colitis, including reduced clonal diversity of plasma cells, and suggests that circulating gut-homing plasmablasts could serve as a biomarker for disease activity.

The Great Oxygenation Event (GOE) 2.4 billion years ago is believed to have been critical for the evolution of complex life. Here, Olejarz et al. propose a model suggesting that competition between major bacterial groups could have triggered the GOE in a feedback loop with geophysical processes.

Visual input is often noisy and discontinuous, even though the physical environment is generally stable. The authors show that the visual system trades off change sensitivity to capitalize on physical continuity via serial dependence: present perception is biased toward past visual input. This bias is modulated by attention and governed by a spatiotemporally-tuned operator, a continuity field.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.