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

Oat is an important food crop, but the genetic diversity within the gene pool remains unclear. Here, the authors report the analyses of worldwide diversity and population structure of hexaploid oat, and identify signatures of structural rearrangements within the germplasm collection.

In a prospective, regulatory-grade study of assistance to pathologists in MASH histology scoring, AIM-MASH-assisted reads by expert MASH pathologists were superior to unassisted reads and decreased inter-reader variability.

This study shows that CRISPRi mediates precise transcriptional pausing, which can be followed by transcription termination. The pausing effect is asymmetric, only being induced when dCas9-bound guide RNA anneals to the non-template DNA strand.

Brown adipose tissue (BAT) is key for metabolic balance. Here, the authors show that RAP250 deficiency enhances BAT activity. Under these conditions, BAT-derived neuritin-1 regulates thermogenesis and fat metabolism, showing therapeutic promise for obesity and metabolic disorders.

Puddu et al. investigate the role of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) as biomarkers for early-stage colorectal cancer (CRC) detection in cell-free DNA (cfDNA). 6-base genome sequencing, using both 5mC and 5hmC biomarkers, increases the detection of stage I CRC.

High-dose oral vitamin D₃ supplements have previously been shown to be beneficial in children receiving standard therapy for uncomplicated severe acute malnutrition. This randomised controlled trial shows that the same intervention, given in addition to standard therapy, did not improve anthropometric or neurodevelopmental outcomes in children with complicated severe acute malnutrition in Pakistan.

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.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

A mass spectrometry-based approach globally identifies protein regulators of metabolism and reveals the role of LRRC58 in controlling cysteine catabolism.

Genome-wide analyses of vaccine antibody responses in 2,499 infants from Uganda, South Africa and Burkina Faso identify associations between specific HLA genes and response to eight vaccines, providing insights that could be considered for population-adjusted vaccine design strategies.

The authors analyzed the whole-exome sequences of over 16,000 individuals and found that very rare variants predicted to disrupt the SETD1A gene confer substantial risk for schizophrenia. Damaging variants in SETD1A were also associated with diverse, severe developmental disorders, providing an important genetic link between schizophrenia and other neurodevelopmental disorders.

Ancient DNA reveals how the explosive expansion of Yamnaya steppe pastoralists began with a small community north of the Black Sea speaking ancestral Indo-European, and detects genetic links with Anatolian speakers, stemming from a common Indo-Anatolian homeland in the North Caucasus–lower Volga region.

Available wheat genomes are annotated by projecting Chinese Spring gene models across the new assemblies. Here, the authors generate de novo gene annotations for the 9 wheat genomes, identify core and dispensable transcriptome, and reveal conservation and divergence of gene expression balance across homoeologous subgenomes.

The negatively charged boron vacancy in hBN shows promise as a quantum sensor, but, until recently, the focus has been on its ground-state properties. Here, the authors report temperature-dependent spin-resonance optical spectroscopy of the orbital excited state.

Alterations of therapeutic pressures have been shown to affect clonal evolution of resistance. Here, the authors conducted a single arm, phase 2 trial consisting of alternating osimertinib and gefitinib in non-small cell lung cancer, and found ctDNA dynamics were predictive of response.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A wireless ingestible sensor that is equipped with an oxidation–reduction potential sensor, electrochemical reference electrode, and pH and temperature sensors can be used to measure redox balance along the human gut.

Analyses of whole-exome sequencing data identify rare loss-of-function variants in BSN associated with adult-onset obesity, type 2 diabetes and fatty liver disease, with stronger effect sizes than those observed for variants in known obesity risk genes such as MC4R.

An efficient and scalable strategy with robust error correction is reported for encoding a record amount of information (including images, text and audio files) in DNA strands; a ‘DNA archive’ has been synthesized, shipped from the USA to Germany, sequenced and the information read.

Advanced fabrication techniques enable a wide range of quantum devices, such as the realization of a topological qubit. Here, the authors introduce an on-chip fabrication technique based on shadow walls to implement topological qubits in an InSb nanowire without fabrication steps such as lithography and etching.

An ultra-high-throughput multiplex protein–DNA binding assay is used to assess binding of 270 human transcription factors to 95,886 noncoding variants in the human genome, providing data to improve prediction of the effects of noncoding variants on transcription factor binding and thereby increase understanding of molecular pathways involved in diverse human traits and genetic diseases.

Embryonic development produces different cell types in response to a small number of inductive signals. Here, the authors characterise how maternal factors modify chromatin to specify initial competence in Xenopus tropicalis, finding that the pioneering activity of the pluripotency factors Pou5f3 and Sox3 establishes competence for germ layer formation by remodelling chromatin before the onset of signalling.

Oncofetal (OnF) reprogramming, driven by YAP and AP-1, induces phenotypic plasticity and therapy resistance in WNT-dependent colorectal cancer (CRC). Targeting the OnF state in combination with chemotherapy substantially attenuates tumor growth in mouse models and patient-derived CRC tumoroids.

Whole-genome sequencing of tumour and germline DNA samples from 92 patients with high-grade serous ovarian cancer identifies frequent gene breakages that inactivate the tumour suppressors RB1, NF1, RAD51B and PTEN, and contribute to chemotherapy resistance; acquired resistance was associated with diverse mechanisms such as reversions of germline BRCA1/2 mutations and overexpression of the drug efflux pump MDR1.

Microbial communities are responsible for biological wastewater treatment. Here, Dueholm et al. generate more than 5 million high-quality, full-length 16S rRNA gene sequences from wastewater treatment plants across the world to construct a database with a comprehensive taxonomy, providing insights into diversity and function of these microbial communities.

Assembly of the hexaploid oat genome and its diploid and tetraploid relatives clarifies the evolutionary history of oat and allows mapping of genes for agronomic traits.

As holidays beckon, Nature's reviewers and editors offer a selection of reading for researchers away from the bench and lecture hall.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Johnson and Obradovich report that widely used large language models, including the early text-davinci-003 and GPT-4, regularly produce text completions that simulate behaviour reminiscent of altruism.

A whole-genome sequencing analysis of 100 pancreatic ductal adenocarcinomas has discovered known and newly identified genetic drivers of pancreatic cancer; these genetic alterations can be classified into four subtypes, which raises the possibility of improved targeting of clinical treatments.

A succession of storms during the 2013–2014 winter led to record flooding in the UK. Here, the authors use high-resolution climate simulations to show that this event could have been anticipated and that there remains a high chance of exceeding observed record monthly rainfall totals in many parts of the UK.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

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.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Comparison of multiple genome assemblies from wheat reveals extensive diversity that results from the complex breeding history of wheat and provides a basis for further potential improvements to this important food crop.

The intrinsic robustness to perturbations makes antiferromagnets ideal building blocks for spintronic devices, however, it also manipulation and detection of antiferromagnetic ordering difficult. Here, Xu et al demonstrate an anisotropic tunnelling magnetoresistance in an all-antiferromagnetic tunnel junction.

Genome-wide data from 400 individuals indicate that the initial spread of the Beaker archaeological complex between Iberia and central Europe was propelled by cultural diffusion, but that its spread into Britain involved a large-scale migration that permanently replaced about ninety per cent of the ancestry in the previously resident population.

Single-cell whole-genome sequencing shows that 'foreground' cell-to-cell structural variation and alterations in copy number are associated with genomic diversity and evolution in triple-negative breast and high-grade serous ovarian cancers.

The mechanisms underlying the regulation of the skin thermal barrier are poorly understood. Here the authors show that the thermal properties of the skin are reactive to diet and that skin is a target for dietary fat delivery.

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

Transcription factor (TF) networks are essential for the molecular identity of each cell type. Here, the authors show that TF Nanog utilises multiple molecular strategies to enhance embryonic stem cell self-renewal, which include regulation of chromatin accessibility in the presence of LIF or maintenance of H3K27me3 at developmental regulators in its absence.

Pecan is an important specialty crop that has experienced extensive interspecific hybridization and nearly-obligate outcrossing. Here, the authors assemble diploid genomes of four outbred genotypes, identify interspecific introgressions through comparative genomics analyses, and map QTLs associated with pest resistance.

Archaeogenetic study of ancient DNA from medieval northwestern Europeans reveals substantial increase of continental northern European ancestry in Britain, suggesting mass migration across the North Sea during the Early Middle Ages.

Metabolic engineering guided by laboratory evolution enables upcycling of nylon by Pseudomonas putida.

A structure-guided fragment screen identified a compound, which interacts with a ligand-binding site of unknown function in eukaryotic initiation factor 4E (eIF4E). X-ray crystallography was used to characterise binding and target engagment was shown in cells.

At the mucosal interface of the gut and microbiome immune cells play pivotal roles to regulate between commensalism, colonisation and pathogenic invasion. Here, Lo et al. show CTLA-4 expression in innate lymphoid cells is linked to mucosal homeostasis in a microbiome dependent manner.