Search

For many neurodevelopmental disorder (NDD) risk genes, the significance for mutational burden is unestablished. Here, the authors sequence 125 candidate NDD genes in over 16,000 NDD cases; case-control mutational burden analysis identifies 48 genes with a significant burden of severe ultra-rare mutations.

Massively parallel DNA sequencing allows entire genomes to be screened for genetic changes associated with tumour progression. Here, the genomes of four DNA samples from a 44-year-old African-American patient with basal-like breast cancer were analysed. The samples came from peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The findings indicate that cells with a distinct subset of the primary tumour mutation might be selected during metastasis and xenografting.

An exciting genome-wide association study in the British population for seven common diseases. This analysis confirms previously identified loci and provides strong evidence for many novel disease susceptibility loci.

Chromosome 8q24 is known to be a major susceptibility region for prostate cancer risk. Here the authors analyze genetic data across the 8q24 region from 71,535 prostate cancer patients identifying 12 risk loci, three previously unreported, highlighting the contribution of germline variation at this locus.

Genome-wide analysis identifies 30 loci associated with bipolar disorder, allowing for comparisons of shared genes and pathways with other psychiatric disorders, including schizophrenia and depression.

Right-sided colorectal cancer (rCRC) has a different mutational spectrum to the left-sided counterpart. Here the authors develop a mouse model of rCRC that recapitulates human BRAF-mutant rCRC and show that loss of TGFβ-receptor signalling and inflammation induce the development of colonic tumours with a foetal-like phenotype.

The degree to which species tolerate human disturbance contributes to shape human-wildlife coexistence. Here, the authors identify key predictors of avian tolerance of humans across 842 bird species from open tropical ecosystems.

Analysis of plastic debris found in surface waters shows that lakes and reservoirs in densely populated and urbanized regions, as well as those with elevated deposition areas, are particularly vulnerable to plastic contamination.

The de novo design of a pair of complementary peptides, one basic for cell penetration and target binding and one acidic that can be fused to proteins of interest, provides an approach for delivery into mammalian cells and subcellular targeting.

Rational design has endowed self-assembling peptides with structural similarities to natural materials, but recreating the dynamic functional properties inherent to natural systems remains challenging. Here the authors report the discovery of a short peptide based on the tryptophan zipper motif, that shows multiscale hierarchical ordering into hydrogels that display emergent dynamic properties.

A method to control the polarization of a Compton gamma-ray beam is developed. By using a free-electron laser oscillator with two helical undulator magnets of opposite helicities, Compton gamma-ray beams with a polarizability of 0.97 are generated.

As phase 1 of the Earth Microbiome Project, analysis of 16S ribosomal RNA sequences from more than 27,000 environmental samples delivers a global picture of the basic structure and drivers of microbial distribution.

In a large, partially prospective cohort of patients with molecularly profiled and clinically annotated meningioma, the extent of surgical resection and radiotherapy (RT) response correlate with molecular classification, which can be used in a molecular model to predict clinical outcomes in response to RT.

Gestational duration depends on both maternal and fetal genetic influences. Here, the authors perform a fetal genome-wide association meta-analysis and find that a locus on 2q13 is associated with pregnancy duration and further show that the lead SNP rs7594852 changes the binding properties of transcriptional repressor HIC1.

A characteristic of costal-pelagic fishes is their large population size fluctuations, yet the drivers remain elusive. Here, the authors analyze a 45-year timeseries of nitrogen stable isotopes measured in larvae of Northern Anchovy and find that high energy transfer efficiency from the base of the food web up to young larvae confers high survival and recruitment to the adult population.

GPC2 and GD2 have been described as immunotherapeutic targets in neuroblastoma. Here the authors engineer T cells to simultaneously express a GPC2-directed CAR and a bispecific innate immune cell engager targeting GD2 and CD16a, showing antitumor activity in neuroblastoma preclinical models.

Male-pattern baldness (MPB) is related to dysregulation of androgens. Here, authors show that MPB (but not androgens) is associated with skin cancer risk, particularly in the scalp region, suggesting that sun exposure, rather than androgens, is the main driver.

Changes in brain structure asymmetry have been reported in autism spectrum disorder. Here the authors investigate this issue using a large-scale sample consisting of 54 data sets.

Marginal zone lymphoma (MZL) is a common subtype of B-cell non-Hodgkin lymphoma. Here the authors carry out a two-stage genome-wide association study in over 8,000 Europeans and identify two new MZL risk loci at chromosome 6p, implicating the major histocompatibility complex in the disease for the first time.

Whole-genome sequencing of chronic lymphocytic leukemia from 485 patients identifies putative coding and noncoding drivers of disease. Genomically defined subgroups show distinct clinical and biological characteristics.

The Cancer Genome Atlas Research Network reports an integrative analysis of more than 400 samples of clear cell renal cell carcinoma based on genomic, DNA methylation, RNA and proteomic characterisation; frequent mutations were identified in the PI(3)K/AKT pathway, suggesting this pathway might be a potential therapeutic target, among the findings is also a demonstration of metabolic remodelling which correlates with tumour stage and severity.

Panos Deloukas, Nilesh Samani and colleagues report a large-scale association analysis using the Metabochip array in 63,746 coronary artery disease cases and 130,681 controls. They identify 15 susceptibility loci, refine previous associations and use network analysis to highlight biological pathways.

It has been suggested that the outer domains of bacterial flagellins are not needed for motility. Here, the authors show that flagellar filament outer domains from some bacteria have unique structures which can alter the motility of the bacteria.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

The authors found that the key elements of plant form and function, analysed at global scale, are largely concentrated into a two-dimensional plane indexed by the size of whole plants and organs on the one hand, and the construction costs for photosynthetic leaf area, on the other.

Mammographic density is a strong risk factor for breast cancer. Here, the authors identify several new loci associated dense area, non-dense area and percent density, and highlight a shared genetic basis for mammographic density and breast cancer.

Genetic associations with particular patterns of brain folding may provide insight into brain development and function. Here, the authors identify and replicate 388 genetic associations with brain sulcal morphology across 40,169 UK Biobank MRI scans, revealing insights into the processes guiding cortical development and genetic correlations with neuropsychiatric phenotypes.

Injectable biomaterial vaccines designed to magnetically capture pathogen-associated molecular patterns protect mice and pigs against septic shock from lethal bacterial infections.

The millimetre image of the Centaurus A nucleus by the Event Horizon Telescope reveals a highly collimated, asymmetrically edge-brightened jet. The source’s event horizon shadow should be visible at terahertz frequencies, consistent with the universal scale invariance of black holes.

Regulatory B cells have been shown to play critical roles in the modulation of the immune system. Here, the authors implicate TIGIT expression in B cells with the process of immuno-regulation.

The dayside thermal emission spectrum and brightness temperature map of the ultra-hot Jupiter WASP-18b obtained from the NIRISS instrument on the JWST showed water emission features, an atmosphere consistent with solar metallicity, as well as a steep and symmetrical decrease in temperature towards the nightside.

A graph-theoretical programmable quantum photonic device composed of about 2,500 components is fabricated on a silicon substrate within a 12 mm × 15 mm footprint. It shows the generation, manipulation and certification of genuine multiphoton multidimensional entanglement, as well as the implementations of scattershot and Gaussian boson sampling.

Endometrial cancer is the most common invasive gynaecological cancer in developed countries. Here a meta-analysis identifies an additional nine novel endometrial cancer risk loci and eQTL analysis reveals risk variants associate with reduced expression of negative regulators of oncogenic signal transduction proteins.

Kang et al. find that vitamin B₁₂ from gut bacteria modulates host neural function and behaviour in Caenorhabditis elegans: vitamin B₁₂ rewires the methionine/S-adenosylmethionine cycle and choline metabolism, impacting free choline levels for neuronal acetylcholine synthesis.

Oncolytic viruses, such as vesicular stomatitis virus (VSV), are a promising class of cancer therapeutics. Here the authors report that a mutation in the CSDE1 gene renders cancer cells resistant to VSV replication and oncolysis, but a mutation-derived escape-associated neoantigen could be exploited for immunotherapy against treatment-resistant tumors.

Genome-wide association studies are used to identify common genetic variants that affect the structure of selected subcortical regions of the human brain; their identification provides insight into the causes of variability in brain development and may help to determine mechanisms of neuropsychiatric dysfunction.

High-tide flooding (HTF) is more likely with sea-level rise. Projections along the United States coastline, considering likely sea-level rise and tidal amplitude cycles, suggest increased HTF event clustering in time and rapid increases in annual HTF frequency as early as the mid-2030s.

Vaccari et al. report that SIV vaccines formulated with two different adjuvants elicit distinct immune responses and effects on SIV acquisition in rhesus macaques.

A photonic anomalous Floquet insulator is emulated in a silicon photonic chip. Up to four-photon topologically protected entangled states are generated in a monolithically integrated emitter in ambient conditions through four-wave mixing on top of the edge modes of the insulator.

The One Thousand Plant Transcriptomes Initiative provides a robust phylogenomic framework for examining green plant evolution that comprises the transcriptomes and genomes of diverse species of green plants.