Search

Analysis of age of onset and disease duration in a large, international cohort of people with SOD1-ALS shows that there is a distinct phenotype and that onset and progression are decoupled.

In this immunological ancillary study of the PREVAC trial, the authors show that approved Ebola virus vaccines induce memory T-cell responses that persist during the five year follow-up after initial vaccination.

A trait-based approach harnesses the vast amount of microbial genomic data and enables integration with biogeochemical models, predicting soil microbial ecology and physiology without the need for cultures.

Metal–organic framework capture materials could reduce the environmental impact of SO₂ emissions but can have limited stability and poor reversibility. Here, a metal–organic framework with open Cu(ii) sites with fully reversible SO₂ uptake of 17.5 mmol g⁻¹ under ambient conditions is reported.

Bagley et al. conduct a phase 1 trial to study safety and tolerability of CAR T-EGFRvIII cells administered concomitantly with PD-1 inhibition via pembrolizumab in patients with glioblastoma and show tolerability, but without signs of efficacy.

White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.

Hu et al. describe how histone H1.0 regulates myofibroblast activation, linking force generation to nuclear organization and gene transcription.

Reliable detection of mutations below 0.5% variant allele frequency remains a key challenge for circulating tumor DNA sequencing assays.

The relationship of mycorrhizal associations with latitudinal gradients in tree beta-diversity is unexplored. Using a global dataset approach, this study examines how trees with arbuscular mycorrhizal and ectomycorrhizal associations contribute to latitudinal beta-diversity patterns and the environmental controls of these patterns.

Disentangling the various pathways by which climate change may drive community shifts in real-world ecosystems is challenging. Here the authors apply a trend attribution approach to a large dataset from the MASTIF database to assess the contribution of direct and indirect effects of climate on tree fecundity in North America, finding that the latter dominate trends by affecting tree growth and size and thereby fecundity.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

A diverse, multidisciplinary panel of 386 experts in COVID-19 response from 112 countries provides health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

Sequencing of haploid sugarcane, Saccharum spontaneum, allows assembly of a prototypical version of the sugarcane chromosome set. This new reference genome will serve as a resource to accelerate sugarcane improvement.

Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization. Here, the authors isolate a human monoclonal antibody that binds to a highly conserved epitope on the RSV fusion protein, neutralizes RSV A and B subtypes equipotently and is protective in the cotton rat model.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

Lung cancer etiology has largely been studied in homogenous populations of European descent. Here, targeted sequencing in African American lung adenocarcinomas finds significantly higher prevalence of PTPRTand JAK2 mutations, validated independently by whole exome sequencing, highlighting potentially clinically actionable mutations in this population.

Food allergy is triggered by IgE, but some individuals are not allergic to peanuts despite making peanut-specific IgE, and are considered peanut-tolerant. Here, the authors identify differences in blood immune cell composition of peanut-allergic and tolerant infants using mass cytometry, which may help uncover the mechanism of allergic tolerance.

Incidence of food allergy in westernized populations is associated with low abundance of Prevotella. Here, the authors analyse the microbiome of a mother-infant prebirth cohort and find that maternal carriage, but not infant carriage, of P. copri during pregnancy predicts the absence of food allergy in the offspring.

It is not yet clear how ubiquitously-expressed proteins can cause the selective degeneration of particular populations of neurons, such as in spinocerebellar ataxia type 17, SCA17, which results from a CAG trinucleotide repeat expansion in the ubiquitously expressed transcription factor TBP. Here, the authors show that mutant TBP suppresses the cerebellum-enriched transcription of Inpp5a and link altered levels of INPP5A to the selective degeneration of cerebellar neurons.

EZH2 phosphorylation by CDK2 promotes progression of triple-negative breast cancer (TNBC). Here, the authors show that this signaling axis downregulates ERα, and thus combinatorial blockade of CDK2 and EZH2 sensitizes TNBC cells to tamoxifen.

Centriole duplication requires the loading of centriolar proteins to the daughter centriole during mitosis. Fu and colleagues analyse by 3D-structural illumination microscopy the sequential recruitment of centriolar proteins Cep135, Cep295 and Cep152.

TEMPOmap combines pulse-chase metabolic labeling with multiplexed three-dimensional in situ sequencing to simultaneously profile the age and subcellular location of individual RNA molecules from thousands of genes to reveal RNA kinetic landscapes.

The Northern Hemisphere has seen record declines in the summer sea-ice and snow cover at high latitudes, as well as a recent increase in extreme summer events at mid latitudes. The connection between these has been unclear; however, changes in atmospheric circulation attributable to the reduced cryosphere are now shown to be linked to the summer extremes.

A phase I clinical trial of an adjuvant personalized mRNA neoantigen vaccine, autogene cevumeran, in patients with pancreatic ductal carcinoma demonstrates that the vaccine can induce T cell activity that may correlate with delayed recurrence of disease.

A large-scale analysis of variation in human protein levels between individuals is performed using mass-spectrometry-based proteomic technology, and a number of protein quantitative trait loci are identified; over 5% of proteins vary by more than 1.5-fold in their expression levels between individuals, and this variation is not always linked to RNA level.

Implanted spheres of a broad variety of material classes significantly abrogate foreign body reactions and fibrosis in rodent and non-human primates when the spheres are larger than 1.5 mm in diameter.

This study shows, when analyzing multi-sample metagenomic datasets, the multi-coverage binning approach outperforms the single-coverage binning alternative in generating bins with higher quality and less contamination.

Douglas Easton, Per Hall and colleagues report meta-analyses of genome-wide association studies for breast cancer, including 10,052 cases and 12,575 controls, followed by genotyping using the iCOGS array in an additional 52,675 cases and 49,436 controls from studies within the Breast Cancer Association Consortium (BCAC). They identify 41 loci newly associated with susceptibility to breast cancer.

Stephanie London, Martin Tobin and colleagues report meta-analyses of genome-wide association studies for forced vital capacity (FVC), a spirometric measure of pulmonary function that reflects lung volume. They identify six regions newly associated with FVC and demonstrate that candidate genes at these loci are expressed in lung tissue and primary lung cells.

Paul Pharoah, Joellen Schildkraut, Thomas Sellers and colleagues report a meta-analysis of genome-wide association studies for epithelial ovarian cancer and genotyping using the iCOGS array in 18,174 cases and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. They identify three new ovarian cancer susceptibility loci, including one specific to the serous subtype, and their integrated molecular analysis of genes and regulatory regions at these loci suggests disease mechanisms.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

Alison Dunning, Stacey Edwards and colleagues analyze 3,872 common variants across the ESR1 locus in 118,816 women. They find five independent variants within regulatory regions that associate with different breast cancer–related phenotypes and regulate the expression of ESR1, RMND1 and CCDC170.

Exome-wide genetic analysis on >300,000 individuals identifies associations with plasma lipid traits. Loci significantly associated with cholesterol and triglycerides are examined together to determine the effects of alleles on type 2 diabetes and coronary artery disease risk.

A comprehensive analysis of brain somatic mosaicism across the neocortex demonstrates the origins and distribution patterns of cells within the human brain.

Volumetric additive manufacturing of protein scaffolds has a wide range of possible biomedical applications. Here the authors report on the bioprinting of unmodified silk sericin and silk fibroin inks with shape-memory and tuneable mechanical properties and demonstrate the potential of the inks in different applications.

The Qinghai-Tibet Plateau is as cold as the Arctic, but presents unique hypoxia and high ultraviolet conditions. Here the authors find that gene flow from Arctic gyrfalcons aids plateau saker falcons’ cold adaptation, and independent non-coding genomic changes underlie hypoxic and ultraviolet responses.

Glucocorticoids, such as dexamethasone, are used as anti-inflammatory and immunosuppressive drugs, however patients may exhibit resistance or side effects. Here the authors propose that a dexamethasone related neutrophil-specific DNA methylation index can be used as a marker of glucocorticoid exposure and response and as a prognostic factor in brain tumor survival.

Cerebrospinal fluid (CSF) is essential for brain development. Here, the authors use gold nanoparticle enhanced X-ray microtomography to map CSF distribution in post-natal rodents and describe particle size-dependent CSF pathways that transport CSF into the brain parenchyma of rodents.

The dynamics of SARS-CoV-2 transmission in the Middle East have been relatively under-studied. Here, the authors integrate genomic and travel data and show that introductions to the region were initially driven by intercontinental air travel, after which regional land travel became a more important driver.

We introduce a major scientific endeavour called π-HuB (proteomic navigator of the human body), its aim being to generate and harness multimodality proteomic datasets to enhance our understanding of human biology.

In an inter-laboratory study, the authors compare the accuracy and performance of three optical density calibration protocols (colloidal silica, serial dilution of silica microspheres, and colony-forming unit (CFU) assay). They demonstrate that serial dilution of silica microspheres is the best of these tested protocols, allowing precise and robust calibration that is easily assessed for quality control and can also evaluate the effective linear range of an instrument.

Pierce et al perform genome-wide CRISPR screening and identify LKB1 as a regulator of chromatin accessibility and metastatic progression in lung cancer through a mechanism of SOX17-mediated epigenetic changes.

Ultra-high-frequency radio-frequency acoustic molecular imaging is a safe molecular imaging diagnostic option because it does not require radioactive probes or high magnetic fields, but lack of biocompatible targeted contrast agents has so far limited its in vivo application. In this paper the authors present perfluorocarbon nanodroplets containing hypertonic saline solution for targeted molecular imaging of prostate cancer in animal models.

The cryo-electron microscropy structures of the full-length ectodomain of VAR2CSA in both ligand-binding and ligand-free states reveal the sequestration mechanism of placental malaria.

Here, the authors perform transcriptional profiling on tracheal aspirates of adults requiring mechanical ventilation for SARS-CoV2-induced acute respiratory distress syndrome (ARDS) and identify a dysregulated host response predicted to predicted to be potentially modulated by dexamethasone.

In a single-arm, non-randomized trial, neoadjuvant atezolizumab therapy in a large cohort of patients with resectable non-small cell lung cancer was safe and the study met its primary end point of major pathological response ≥15%.