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Stroke is a multifactorial disease influenced by genetic and environmental factors. Here, the authors apply exome-wide association analysis to find rare coding variants associated with stroke in a Pakistani cohort, finding a significant association of a variant in NOTCH3 that is highly enriched in South Asians.

Antibody production in plasma cells involves the unfold protein response (UPR), but how this is regulated is not clear. Here the authors show that mTORC1 signalling but not Xbp1-mediated transcription regulation in activated B cells is important for the induction of a UPR-related transcriptome that precedes full plasma cell functions.

Inorganic nitrate and nitrite from endogenous or dietary sources are metabolized in vivo to nitric oxide (NO) and other bioactive nitrogen oxides. The nitrate-nitrite-NO pathway is emerging as an important mediator of blood flow regulation, cell signaling, energetics and tissue responses to hypoxia. The latest advances in our understanding of the biochemistry, physiology and therapeutics of nitrate, nitrite and NO were discussed during a recent 2-day meeting at the Nobel Forum, Karolinska Institutet in Stockholm.

Tailoring the macroscopic properties of deep eutectic solvents requires knowing how these depend on the local structure and microscopic dynamics. The authors, with computational and experimental tools spanning a wide range of space- and timescales, shed light into the relationship between micro and macroscopic properties in glyceline and ethaline.

Over 170 susceptibility loci have been identified by genome-wide association studies in breast cancer. Here, the authors interrogated the role of risk-associated variants from non-breast tissue, and using expression quantitative trait loci, identify potential target genes of known breast cancer susceptibility variants, as well as 11 regions not previously known to be associated with breast cancer risk.

Sequencing and genomic diversification of five allopolyploid cotton species provide insights into polyploid genome evolution and epigenetic landscapes for cotton improvement.

Rearrangements of the Ig loci are essential for generating antibody diversity but abnormal translocations can be a driving event for myeloma. Here Walker et al. perform whole exome sequencing on myeloma patients to capture the diversity of mutational changes.

Germline mutations in the Elongator complex gene ELP1 predispose individuals to the development of childhood medulloblastoma.

STAAR is a powerful rare variant association test that incorporates variant functional categories and complementary functional annotations using a dynamic weighting scheme based on annotation principal components. STAAR accounts for population structure and relatedness and is scalable for analyzing large whole-genome sequencing studies.

A manufacturable platform for quantum computing with photons is introduced and a set of monolithically integrated silicon-photonics-based modules is benchmarked, demonstrating dual-rail photonic qubits with performance close to thresholds required for operation.

An antibody-discovery pipeline integrating single-cell mRNA-sequence analysis, bioinformatics, synthetic biology and high-throughput functional analyses enables the rapid discovery of potent human monoclonal antibodies against viral pathogens.

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.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

The mechanisms underlying the influence of aging on cancer are incompletely understood. Warde et al. establish a new model of age- and sex-dependent adrenal cancer. Their work uncovers a tumor-protective role for myeloid immune cells that is enhanced by androgens.

The nature of the insulator-metal phase transition in VO₂ remains elusive. Using pump-probe spectroscopy and near-field imaging, O’Callahan et al. study the ultrafast dynamics of many micro-crystals and find an inhomogeneous response, highlighting the importance of microscopic perturbations to the transition.

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.

John Perry and colleagues report the results of a large genome-wide association study meta-analysis to identify variants influencing age at natural menopause. They identify 54 independent signals and find enrichment near genes involved in delayed puberty and DNA damage response.

1000 Genomes imputation can increase the power of genome-wide association studies to detect genetic variants associated with human traits and diseases. Here, the authors develop a method to integrate and analyse low-coverage sequence data and SNP array data, and show that it improves imputation performance.

A transcriptome-wide characterization of the molecular pathology of post-traumatic stress disorder (PTSD) postmortem brains provides a comprehensive resource for mechanistic insight and therapeutic development.

Biomphalaria glabrata is a fresh water snail that acts as a host for trematode Schistosoma mansoni that causes intestinal infection in human. This work describes the genome and transcriptome analyses from 12 different tissues of B glabrata, and identify genes for snail behavior and evolution.

Plant pathogens have evolved to evade detection by their hosts. Here, Asai et al. show that virulent isolates of the oomycete Hyaloperonospora arabidopsidis can break resistance conferred by the Arabidopsis RPP4 resistance gene via variation in effector expression or subcellular localization.

This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual.

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.

Biomarkers predictive of response to T cell therapy remain to be better defined. This study identifies potential predictive and pharmacodynamic markers of response to NY-ESO-1 T-cell therapy in a solid tumor that may inform lymphodepletion, cell dose, and strategies to enhance anticancer efficacy.

Erwin Gelfand, Andrew Snow, Joshua Milner and colleagues identify heterozygous CARD11 mutations associated with severe atopic disease in eight individuals from four families. They further show that the mutant CARD11 proteins exhibit both loss-of-function and dominant-interfering activity and that the cellular defects in patient T cells can be partially rescued by supplementing with glutamine.

A reference genome sequence for threespine sticklebacks, and re-sequencing of 20 additional world-wide populations, reveals loci used repeatedly during vertebrate evolution; multiple chromosome inversions contribute to marine-freshwater divergence, and regulatory variants predominate over coding variants in this classic example of adaptive evolution in natural environments.

Fat distribution is associated with cardiometabolic disease, although it has been less well studied than overall obesity. In a multiancestry exome-sequencing study, the authors identified predicted loss-of-function mutations in INHBE associated with favorable fat distribution and protection from type 2 diabetes.

Empirically based models of disease progression in familial frontotemporal dementia reveal the relative ordering of clinical, neuroimaging, and fluid biomarker changes and facilitate novel clinical trial designs

Volcanic activity led to ocean acidification at the onset of Oceanic Anoxic Event 2, which then persisted for 600,000 years due to biogeochemical feedbacks, according to marine osmium isotope and carbonate sedimentation records offshore from southwest Australia.

Enhanced Wus2/Bbm expression substantially improves leaf transformation, Cas9-mediated gene dropouts and targeted gene insertion in maize, sorghum and other Poaceae species.

Topologically protected hinge modes could be important for developing quantum devices, but electronic transport through those states has not been demonstrated. Now quantum transport has been shown in gapless topological hinge states.

US population exposure to extreme heat is set to increase four- to sixfold from the late twentieth century. Changes in population are as important as changes in climate in driving this outcome.

Fibrillar deposits of tau protein (neurofibrillary tangles) are thought to cause neuronal death in patients with Alzheimer's disease, and tau-related frontotemporal dementia. Here, however, the opposite has been found: the activation of executioner caspase enzymes occurs first, preceding tangle formation by hours to days. Tangle-bearing neurons seem to be long-lived, indicating that tangles might be 'off pathway' to acute neuronal death.

Accurate transfer RNA (tRNA) aminoacylation is necessary for translational fidelity; however, the accuracy of tRNA aminoacylation in vivo is uncertain. In mammalian cells, approximately 1% of methionine residues used in protein synthesis are now shown to be aminoacylated to non-methionyl-tRNAs. Furthermore, misacylation of methionine increases up to tenfold upon exposing cells to viruses, toll-like receptor ligands or oxidative stress.

An analysis of human chromosome 15 — which is altered in Prader-Willi and Angelman syndromes — reveals that it resembles a hall of mirrors, as it contains a number of sequence duplications throughout its length. The evolutionary events that may have led to the high number of duplications was also reconstructed.

Senile plaques are thought to accumulate over the course of decades in brains of Alzheimer's disease patients. In vivo mutiphoton microscopy is used to follow the birth of such plaques in live Alzheimer's disease model mice. It is found that plaques form extraordinarily quickly, over 24 hours. Within 1–2 days, the microglia move in and noticeable neuritic changes ensue. These data argue that neuritic dysfunction follows, rather than precedes, amyloid deposition.

Bispecifics by orthogonal interfaces To improve correct antibody heavy-light chain pairing during bispecific antibody assembly, Lewis et al. design antibody heavy and light chains with orthogonal interfaces.

The tau protein is theorized to spread transneuronally in Alzheimers disease, though this theory remains unproven in humans. Our simulations of epidemic-like protein spreading across human brain networks support this theory, and suggest the spreading dynamics are modified by β-amyloid

Exploring the diversity of the wild progenitor of the wheat D subgenome allows for rapid trait discovery.

Scientific revolutions have famously inspired scientists and innovation but large-scale analyses of scientific revolutions in modern science are rare. Here, the authors investigate one possible factor connected with a topic’s extraordinary growth—scientific prizes.

Despite the appearance of analytical rigour, IIASA's widely acclaimed global energy projections are highly unstable and based on informal guesswork. This results from inadequate peer review and quality control, raising questions about political bias in scientific analysis.

Droplet interface bilayer measurements have now shown that membranes formed from chiral phospholipid bilayers are enantioselectively permeable to chiral amino acids. The results show that membrane stereochemistry is necessary and sufficient to drive such enantioselective transport, presenting a new potential route to homochirality. These findings could also have implications for pharmacokinetics and drug design.

Aegilops sharonensis is a wild diploid relative of wheat. Here, the authors assemble the genome of Ae. sharonensis and use the assembly as an aid to clone the Ae. sharonensis-derived stem rust resistance gene Sr62 in the allohexaploid genome of wheat.

Chemical experiments on californium are stymied by isotope availability and radioactivity considerations, but are advanced here with synthesis and characterization of an organometallic complex.