Search

The MYST acetyltransferase HBO1 is a critical regulator in maintaining leukaemia stem cells, and a small-molecule inhibitor of HBO1 is developed that shows efficacy against a range of acute myeloid leukaemia cells.

Genomic analyses in large cohorts of patients with cancer identify a new measure of tumor mutational burden, based on genomic regions that are unlikely to undergo loss, that is associated with therapeutic response to immunotherapy.

Oil palm production in Indonesia has expanded by converting more natural ecosystems to agricultural ones. This study finds large yield gaps among large and smallholder farms there, suggesting improved management could increase production while sparing fragile ecosystems.

Activation of integrin αIIbβ3 at the surface of platelets is required for their aggregation and for thrombus formation. Here Xu et al. identify apolipoprotein A-IV as a novel ligand for platelet αIIbβ3 integrin, and find it inhibits platelet aggregation and thrombosis.

Applying metagenomics, the authors identify 13 viruses in febrile Nigerians, including a new dicistrovirus. Real-time phylogenetics spurred national vaccination campaigns, while retrospective analysis linked pegivirus C co-infections to favorable Lassa Fever outcomes.

A longitudinal evolutionary analysis of 126 lung cancer patients with metastatic disease reveals the timing of metastatic divergence, modes of dissemination and the genomic events subject to selection during the metastatic transition.

First-in-human trial of a self-assembling, ferritin nanoparticle-based influenza vaccine shows evidence that this new platform can elicit neutralizing and cross-reactive antibodies and has potential for further vaccine development.

The common bedbug is a pest for humans, yet its molecular biology is poorly understood. Here, the authors sequence the common bedbug genome and profile gene expression across all life stages to show major changes in gene expression after feeding on human blood.

There is increasing evidence that epigenetic mechanisms contribute to therapeutic resistance in cancer. Here the authors study AML patient samples and a mouse model of non-genetic resistance and find that transcriptional plasticity drives stable epigenetic resistance, and identify regulators of enhancer function as important modulators of resistance.

Expression of transposable elements is mapped to unique genomic loci with CELLO-seq.

Conventional epitaxy is of limited application, but by placing a monolayer of graphene between the substrate and the so-called epilayer grown on top, its scope can be substantially extended.

Determining progress in adaptation to climate change is challenging, yet critical as climate change impacts increase. A stocktake of the scientific literature on implemented adaptation now shows that adaptation is mostly fragmented and incremental, with evidence lacking for its impact on reducing risk.

A cross-ancestry genome-wide association meta-analysis of lung cancer including 61,047 cases and 947,237 controls identifies five new cross-ancestry susceptibility loci and highlights ancestry-specific effects of common and rare variants on lung cancer risk.

The nutritional, economic and livelihood contributions provided by aquatic food systems are threatened by climate change. Building climate resilience requires systemic interventions that reduce social vulnerabilities.

Analysis of SARS-CoV-2 genomes from around the world show that following initial importation largely from India, Delta spread in England was driven first by inter-regional travel and then by local population mixing.

Genome-wide analyses identify eight independent loci associated with anorexia nervosa. Genetic correlations implicate both psychiatric and metabolic components in the etiology of this disorder, even after adjusting for the effects of common variants associated with body mass index.

The Structural Variation Analysis Group of The 1000 Genomes Project reports an integrated structural variation map based on discovery and genotyping of eight major structural variation classes in 2,504 unrelated individuals from across 26 populations; structural variation is compared within and between populations and its functional impact is quantified.

The histone methyltransferase DOT1L and the chromatin reader BRD4 together facilitate transcription of genes critical to the molecular pathogenesis of MLL leukemia.

A massively parallel computational and experimental approach for de novo designing and screening small hyperstable proteins targeting influenza haemagglutinin and botulinum neurotoxin B identifies new therapeutic candidates more robust than traditional antibody therapies.

The nuclear receptors REV-ERB-α and REV-ERB-β are indispensible for the coordination of circadian rhythm and metabolism; mice without these nuclear receptors show disrupted circadian expression of core circadian clock and lipid homeostatic gene networks.

In an interim analysis of a phase 1/2 trial, a heterologous prime boost vaccine comprised of a chimpanzee adenovirus and self-amplifying mRNA that encodes neoantigens derived from common oncogenic driver mutations in combination with immune checkpoint blockade was safe and elicited neoantigen-specific T cell responses in patients with advanced solid tumors.

The activity of several protein kinases is increased upon cellular production of reactive oxygen species, which can cause cysteine oxidation. Here the authors show that sulfenylation of specific cysteine residues within Src induce local structural changes that directly impact its activation.

Developmental disorders (DDs) are more prevalent in males, thought to be due to X-linked genetic variation. Here, the authors investigate the burden of X-linked coding variants in 11,044 DD patients, showing that this contributes to ~6% of both male and female cases and therefore does not solely explain male bias in DDs.

The largest known hydrothermal plume moves dissolved iron halfway across the Pacific. In situ measurements show that dissolved and particulate iron transport is facilitated by reversible exchange of dissolved iron onto organic compounds.

Observations of TOI-849b reveal a radius smaller than Neptune’s but a large mass of about 40 Earth masses, indicating that the planet is the remnant core of a gas giant.

A key obstacle to sequencing DNA as it passes through a nanopore is that the translocation rate is too fast to resolve individual bases. Cherf et al. solve this problem with an improved method for ratcheting DNA forward and backward through the nanopore using a DNA polymerase.

The role of impaired lung function in lung cancer etiology is complex due to the relation of cigarette smoking to both conditions. Here, supported by Mendelian randomization analysis the authors find a link between pulmonary function impairment and lung cancer risk beyond smoking, implicating immune-related pathways

ROR-γ antagonists suppress androgen receptor expression and growth of prostate tumors, but not of androgen-responsive healthy tissue, in preclinical models.

Genome sequences of a deep-sea vent and a shallow-water mussel species are compared. The former has expanded gene families for protein stabilization and removal of toxic substances and has a more complex immune system.

The basis for associations between lung cancer and major histocompatibility complex genes is not completely understood. Here the authors further consider genetic variation within the MHC region in lung cancer patients and identify independent associations within HLA genes that explain MHC lung cancer associations in Europeans and Asian populations.

Programmable addition via site-specific targeting elements (PASTE) combines the specificity, efficiency and cargo size benefits of site-specific integrases with the programmability of prime editing for precise and efficient integration of large DNA sequences into mammalian genomes.

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.

We present James Webb Space Telescope observations that detect the 3.3 μm polycyclic aromatic hydrocarbon feature in a galaxy observed less than 1.5 billion years after the Big Bang.

It is unclear whether bidirectional non-coding RNAs transcribed from enhancer elements (eRNAs) have any functional role; here, eRNA transcription is shown to be functionally important during the activation of genes by the oestrogen receptor in human breast cancer cells.

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.

Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

Richard Trembath and colleagues report a meta-analysis of genome-wide association studies for psoriasis, including 2 cohorts genotyped on the custom Immunochip array, in a total of 10,588 cases and 22,806 controls. They identify 15 new susceptibility loci and refine signals in previously known loci, highlighting a role for innate host defense in susceptibility to psoriasis.

By integrating healthcare and exome-sequencing data from parent–offspring trios of patients with developmental disorders, 28 genes that had not previously been associated with developmental disorders were identified.

Whole-exome analysis of individuals with developmental disorders shows that de novo mutations can equally cause loss or altered protein function, but that most mutations causing altered protein function have not yet been described.

Chromodomain Helicase DNA-binding (CHD) proteins have been implicated in neurodevelopmental processes. Here, the authors identify missense variants in CHD3 that disturb its chromatin remodeling activities and cause a neurodevelopmental disorder with macrocephaly and speech and language impairment.

The current ‘second space age’ has enabled multiple studies on the effects of spaceflight on human physiology and health, which are contributing to the development of measures that will be needed to maintain astronaut health in future space missions.

Subtypes of cancer associated fibroblasts can both promote and suppress tumorigenesis. Here, the authors investigate how p53 status in pancreatic cancer cells affects their interaction with cancer associated fibroblasts, and report perlecan as a mediator of the pro-metastatic environment.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

The application of a potent lactate dehydrogenase (LDHA) inhibitor GNE-140 on pancreatic cancer cells revealed that resistance to GNE-140 is attributable to an AMPK–mTOR–S6K-mediated switch in utilization from glycolysis to oxidative phosphorylation.

A combination of spectroscopy, microscopy and theoretical calculations shows that the reactivity of titanium silicalite-1 as an epoxidation catalyst is due to the presence of dinuclear titanium sites.