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Single cell genome sequencing approaches have identified somatic copy number variants (CNVs) in human neurons, but small sample sizes (<100 neurons) have limited the power to find recurrent patterns such as CNV hotspots in a single individual. Here, the authors develop an approach to map CNVs in 2097 neurons from a neurotypical individual, finding that >10% neurons contain at least one somatic CNV, and enabling deeper investigation of these events.

Trans-ancestry meta-analysis of estimated glomerular filtration rate (eGFR) from 1,046,070 individuals identifies 264 associated loci, providing a resource of molecular targets for translational research of chronic kidney disease.

Female carriers of BRCA1 mutations possess high breast cancer risk, which may reflect deficient growth control of mammary progenitor cells. Here, the authors study progenitor-enriched fractions from these carriers and describe a loss of PLK1-mediated mitotic spindle positioning and an inability of the progeny to acquire features of mature luminal cells.

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.

Senescent melanocytes of skin nevi drive hyperactivation of hair growth through the signalling factor SPP1.

A 50 microRNA-based dynamic risk score for stratifying individuals with and without type 1 diabetes was developed using samples obtained from multicenter and multiethnic cohorts.

The MAPK pathway is an important therapeutic target in pancreatic ductal adenocarcinoma (PDAC), but success is limited by pathway reactivation, which drives resistance. Here, the authors investigate the mechanism underlying HER2-reactivation post KRAS-MAPK inhibition, identifying combination of MAPK and HER2 inhibition as a therapeutic strategy.

Erythropoiesis can be regulated by transcriptional, epigenetic, and post-transcriptional mechanisms. Here the authors report that N⁶-methyladenosine mRNA methyltransferase complex stimulates erythropoiesis by promoting translation of specific mRNAs.

Tagging and tracking the blood plasma proteome as a discovery tool reveals widespread endogenous transport of proteins into the healthy brain and the pharmacologically modifiable mechanisms by which the brain endothelium regulates this process with age.

Retrotransposons are mobile genetic elements normally repressed by DNA methylation in differentiated cells. Here, the authors show that DNA hypomethylation in mouse induced pluripotent stem cells allows retrotransposons to jump, but this can be blocked with a reverse transcriptase inhibitor.

Memory is hypothesised to depend on different brain regions that interact in a network. Here, the authors use case studies of stroke patients with amnesia from the literature to identify brain regions that are part of this network.

Goekbuget et al. characterize the role of the developmentally essential transcriptional repressor FOXD3 in limiting transcription of highly active genes upon entry into S phase to promote faithful DNA replication and to protect genome integrity.

Siew et al. using multi-omic, physiological & imaging approaches have demonstrated that spaceflight causes kidney remodelling, suggesting a contribution to kidney stone formation, & that space radiation causes kidney damage & early signs of dysfunction.

Patient-derived xenograft models (PDX) have been extensively used to study the molecular and clinical features of cancers. Here the authors present a cohort of 536 PDX models from 25 cancers, as well as their genomic and evolutionary profiles and their suitability for clinical trials.

Analysis of copy number alterations in 1,451 patient-derived xenografts (PDXs) and matched patient tumor samples shows strong conservation from patient tumors through late-passage PDXs and a lack of systematic copy number evolution driven by the mouse host.

Sequencing data from two large-scale studies show that most of the genetic variation influencing the risk of type 2 diabetes involves common alleles and is found in regions previously identified by genome-wide association studies, clarifying the genetic architecture of this disease.

Rodin and Dou et al. characterized genome-wide somatic mutation in autistic and control brains, revealing that even unaffected individuals may possess dozens of brain somatic mutations and providing insight into the role of somatic mutation in autism.

T cell responses can be generated to either pathogen infection or from priming with a vaccine. Here the authors compare T cell generation, phenotype and single cell transcriptome of participants vaccinated with a mpox vaccine or infected with the virus showing that the virus induced T cells showed more effective function and phenotype.

McCarthy, Kaeding et al. identify H3K9me3-heterochromatin proteins that repress heterochromatic genes with implications in hepatic reprogramming and show that ERH is key to global H3K9me3 maintenance in human cells.

Controlling immune cell activation would improve the efficiency of cell-based immunotherapies and reduce its associated risks. Here biodegradable particles are functionalized with DNA scaffolds for precise conjugation of a range of immunomodulating agents and applied ex vivo and in vivo for engineered immune cell modulation.

Understanding the immune response to SARS-CoV-2 is dependent on being able to distinguish COVID-19 immune responses from cross-reactive immune responses to other coronaviruses. Here the authors show that choice of antigens and whether an ICS, ELISPOT or T cell proliferation assay is used has a major effect on this discriminatory ability.

Forecasts of COVID-19 mortality have been critical inputs into a range of policies, and decision-makers need information about their predictive performance. Here, the authors gather a panel of global epidemiological models and assess their predictive performance across time and space.

A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.

A study of 36 massive galaxies at redshifts between 5 and 9 from the JWST FRESCO survey finds that galaxy formation of the most massive galaxies is 2–3 times higher than the most efficient galaxies at later epochs.

Amyotrophic Lateral Sclerosis (ALS) is highly heritable but the mechanisms of sporadic ALS are not fully understood. In this study, the authors identify drivers of variation and disease-relevant changes in the epigenomic profile of iPSC-derived motor neuron lines generated from ALS patients and healthy controls as part of the Answer ALS program.

Metabolomics data from germ-free and specific-pathogen-free mice reveal effects of the microbiome on host chemistry, identifying conjugations of bile acids that are also enriched in patients with inflammatory bowel disease or cystic fibrosis.

Cui et al. find that arginine depletion and inflammation reduces nuclear localization of arginyl-tRNA synthetase, which influences alternative splicing via condensate-like serine/arginine repetitive matrix protein 2, and regulates cellular metabolism and response to inflammation.

A finger-based brain–computer interface was developed for a person with tetraplegia to allow him to fly a virtual quadcopter, an innovation that can lead to improved social connectedness, recreation and a sense of enablement.

Bennu’s surface presents evidence of a variety of particle sizes, from fine regolith to metre-sized boulders. Its moderate thermal inertia suggests that the boulders are very porous or blanketed by thin dust. Bennu’s boulders exhibit high albedo variations, indicating different origins and/or ages.

This paper describes molecular subtypes of cervical cancers, including squamous cell carcinoma and adenocarcinoma clusters defined by HPV status and molecular features, and distinct molecular pathways that are activated in cervical carcinomas caused by different somatic alterations and HPV types.

Doil Choi and colleagues report the genome sequence of the hot pepper, Capsicum annuum, as well as the resequencing of two cultivated peppers and a wild species, Capsicum chinense. Comparative genomic analysis across Solanaceae provides insights into genome expansion, pungency, ripening and disease resistance in hot peppers.

Human fibroblasts are reprogrammed to generate blastocyst-like structures called iBlastoids, which recapitulate aspects of embryo implantation.

This Brain Somatic Mosaicism Network analysis of 283 cases of malformations of cortical development identifies 69 candidate and known genes in 76 patients. Single-nucleus RNA sequencing and mouse modeling implicate radial glia and daughter excitatory neurons.

The fusion of dead Cas9 with KRAB and the transcriptional repressor domain of the chromatin modifier MeCP2 leads to an efficient transcriptional silencer that can be applied to genome-scale screens and genetic circuits.

Global change drivers such as climate and land-use change can impact biodiverse regions and damage the ecosystem services they provide. This study assessed the impact of such global change drivers on tree species distributions across Southeast Asian forests.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Tracing the phylogeny of the molecular components of synapses, Ryan and Grant speculate on the core components of the last common ancestor of all synapses and posit that the diversification of upstream signalling components contributed to increased signalling complexity later in evolution.

The implementation of COVID-19 stay-at-home policies was associated with a considerable drop in urban crime in 27 cities across 23 countries. More stringent restrictions over movement in public space were predictive of larger declines in crime.

Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

The FANTOM4 study identified transcriptional start sites active during proliferation arrest and differentiation of the human monocytic cell line THP-1. Systematic knockdown of 52 transcription factors provide support for their model in which a complex transcriptional network regulates the differentiation process.

Despite the identification of genetic risk loci for late-onset Alzheimer’s disease (LOAD), the genetic architecture and prediction remains unclear. Here, the authors use genetic risk scores for prediction of LOAD across three datasets and show evidence suggesting oligogenic variant architecture for this disease.

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

Genomes and transcriptomes of five distinct lineages of African cichlids, a textbook example of adaptive radiation, have been sequenced and analysed to reveal that many types of molecular changes contributed to rapid evolution, and that standing variation accumulated during periods of relaxed selection may have primed subsequent diversification.

Michael Talkowski and colleagues analyze balanced chromosomal abnormalities in 273 individuals by whole-genome sequencing. Their findings suggest that sequence-level resolution improves prediction of clinical outcomes for balanced rearrangements and provides insight into pathogenic mechanisms such as altered gene regulation due to changes in chromosome topology.

The dissociation mechanism of the heme axial ligand in heme proteins is not yet fully understood. The authors investigate the photodissociation dynamics of the bond between heme Fe and methionine S in ferrous cytochrome c using femtosecond time-resolved X-ray solution scattering and X-ray emission spectroscopy, simultaneously tracking electronic and nuclear structure changes.

Rapid extracellular antigen profiling of a cohort of 194 individuals infected with SARS-CoV-2 uncovers diverse autoantibody responses that affect COVID-19 disease severity, progression and clinical and immunological characteristics.