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Here authors demonstrate how a 2D hybrid perovskite melts and forms glass, uncovering atomic-scale structural and dynamic evolution across the crystal–liquid–glass transition. Local structural motifs are retained, advancing understanding of amorphous hybrid materials.

Spatial cell distribution within a tissue microenvironment is a rapidly advancing field. Here, authors assess three commercially available single-cell resolution spatial transcriptomics approaches (CosMx, MERFISH, and Xenium) to inform which technology outperforms for immune profiling of solid tumors using patient samples.

Researchers revealed a 3.6 Å cryo-EM structure showing how HIV-1 Vif hijacks the host’s CUL5 E3 ligase to degrade APOBEC3H, a viral defense protein. The findings shed light on HIV’s immune evasion and suggest potential antiviral targets.

Collateral-sensitivity-based drug cycling effectively prevents and impedes the evolution of antifungal drug resistance in Candida auris.

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).

Ruggeri et al. find in a study of 61 countries that temporal discounting patterns are globally generalizable. Worse financial environments, greater inequality and high inflation are associated with extreme or inconsistent long-term decisions.

The transcriptional regulation of murine spermatogenesis is not well understood. Here, the authors use single-cell and bulk RNA-Sequencing of juvenile and adult mice to characterise somatic and germ cell development, and chromatin profile the X chromosome to show that spermatid-specific genes are repressed by H3K9me3 during meiosis.

Chromosomal instability occurs frequently in cancer, making it an attractive therapeutic target. Here, the authors identify KIF18A as a targetable vulnerability of cancer cells with chromosomal instability and target this using VLS-1272, a selective KIF18A inhibitor.

Metastasis of urothelial carcinoma remains incurable due to insufficient treatment options for advanced disease. Here, the authors combine whole exome sequencing and RNA-seq from metastatic biopsies, and show temporal evolution when compared with primary tumour.

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.

Genome-wide association studies comprising 1,091 metabolites and 309 metabolite ratios in 8,299 individuals from the Canadian Longitudinal Study on Aging provide insights into the genetic architecture of metabolites and their role in human diseases.

Here, Ejemel et al. report the identification and characterization of a cross-neutralizing human IgA monoclonal antibody, named MAb362, that binds the receptor-binding domain of SARS-CoV-2 Spike, blocking its interaction with the ACE2 host receptor.

Whole genome sequencing (WGS) data on non-European and admixed individuals remains scarce. Here, the authors analyse WGS data from 1,171 admixed elderly Brazilians from a census cohort, characterising population-specific genetic variation and exploring the clinical utility of this expanded dataset.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Complex biochemical systems exhibit traits that appear to be highly adapted. Studies of catalytic RNA demonstrate that adaptive traits, such as increased specificity and error tolerance, could originate as evolutionary by-products.

Sub-cycle phase-resolved attosecond interferometry is developed. The obtained phase information enables us to decouple the multiple quantum paths induced in a light-driven system, isolating their coherent contribution and retrieving their temporal evolution.

Geometry is crucial in spatial reorientation, but the underlying neural mechanisms of spatial reorientation are unclear. Here, the authors show that in a two-context reorientation task, distinct CA1 cells code heading retrieval and context recognition during reorientation.

A variant of the OAS1 gene, which encodes an enzyme that is critical for the innate immune response to viral infections, is associated with decreased risk of death in patients with COVID-19.

Meta-analysis of 36,760 cases and 375,188 controls identifies 54 loci associated with susceptibility to cutaneous melanoma. Further analysis combining nevus count and hair color GWAS results provide insights into the genetic architecture of melanoma.

Low read depth sequencing of whole genomes and high read depth exomes of nearly 10,000 extensively phenotyped individuals are combined to help characterize novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with lipid-related traits; in addition to describing population structure and providing functional annotation of rare and low-frequency variants the authors use the data to estimate the benefits of sequencing for association studies.

Mice deficient in the Polycomb repressor Bmi1 have a shortened lifespan and develop numerous abnormalities including defects in stem cell self-renewal and thymocyte maturation. Here it is demonstrated that cells derived from Bmi1^−/− mice also show a marked elevation in the intracellular levels of reactive oxygen species, corresponding to the derepression of previously identified Polycomb target genes and sufficient to engage the DNA damage response pathway.

Analysis of the development of drug products containing nanomaterials identifies several trends as well as the relative rate of approval of these products.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

For colorectal cancer screening, the issue is no longer whether the fecal immunochemical test (FIT) is preferable to the guaiac fecal occult blood test, but how best to use the FIT. Using the OC-Sensor^™ FIT with a hemoglobin cut-off level of 50 ng/ml could offer the best cost-effectiveness ratio compared with nonscreening settings.

The interferon regulatory factors (IRFs) are involved in the innate immune response and are activated by phosphorylation. The structure of a pseudophosphorylated IRF5 activation domain now reveals structural changes in the activated form that would turn an autoinhibitory region into a dimerization interface. In vivo analysis supports the relevance of such a dimer to transcriptional activation.

A high-resolution kidney cellular atlas of 51 main cell types, including rare and previously undescribed cell populations, represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.

Human population genomic studies, including whole‐genome sequencing, were undertaken to identify determinants of bone mineral density (BMD), a major predictor of osteoporotic fractures. Non‐coding variants with large effects on BMD and fractures were identified near the EN1 locus and mouse studies confirmed this gene has an important role in skeletal biology.

Central retinal artery occlusion (CRAO) is an acute stroke of the eye that can result in profound visual impairment. Standard noninvasive therapies do not markedly alter the natural history of CRAO, and this has prompted investigations into new treatment strategies. As Chen and Lee discuss in this Review, thrombolytic therapy—especially local intra-arterial fibrinolysis—is showing considerable promise for the acute management of acute CRAO.

Integration of GWAS and single-cell transcriptomic data from the entire nervous system systematically identifies cell types underlying brain complex traits and provides insights into the etiology of Parkinson’s disease.

Levels of circulating thyrotropin and free thyroxine reflect thyroid function, however, their genetic underpinnings remain poorly understood. Taylor et al. take advantage of whole-genome sequence data from cohorts within the UK10K project to identify novel variants associated with these traits.

Contact-dependent growth inhibition (CDI) is an important mechanism of bacterial competition. Here, Bartelli et al. show that proteolytic processing of a CDI toxin induces a conformational switch required for translocation into target bacteria.

Prime editing efficiency is enhanced using a mutated reverse transcriptase and addition of deoxynucleosides.

Population-based genome sequencing provides an increasingly rich resource for the identification of low-frequency, large effect variants associated with clinically important phenotypes. Timpson et al. use UK10K data to identify a variant of the APOC3gene strongly associated with plasma triglyceride levels.

This Registered Report presents evidence from 87 countries and regions showing that brief emotion-regulation interventions consistently reduced negative emotions and increased positive emotions during the COVID-19 pandemic.

In ovarian cancer, metastatic phenotype may impact surgical outcomes. Here, the authors show miR-409-3p regulates FABP4 which can increase metastatic potential of ovarian cancer, and treatment with DOPC nanoliposomes containing either miR-409--3p mimic or FABP4 siRNA inhibits tumor progression in mice.

Evolution- and structure-guided mutagenesis allows elucidation of the solution NMR structure of the N-terminal domain of APOBEC3G. Mapping of HIV-1 Vif binding to the APOBEC3G NTD reveals an interaction interface distinct from those in other APOBEC3 proteins.

Chronic lymphocytic leukaemia cells depend on glutathione to counteract their high reactive oxygen species (ROS) levels. However, their ability to synthesize this antioxidant is compromised by inefficient cystine uptake. Huang and colleagues now show that bone marrow stromal cells promote leukaemia cell survival by metabolizing cystine to cysteine and releasing it into the microenvironment to be taken up by leukaemia cells.

Itaconate is an immunomodulatory macrophage metabolite. Mesaconate, a structurally similar molecule, is shown to be synthesized from itaconate in inflammatory macrophages and shows similar immunomodulatory effects, despite not repressing tricarboxylic acid cycle activity nor inhibiting succinate dehydrogenase activity.

It is desirable to deposit more energy in the dense plasma core to trigger the fusion ignition. Here the authors demonstrate enhanced energy coupling from laser to plasma core by using solid targets and guiding the transport of relativistic electron beam with external magnetic field.

A fluorescent bicolour sensor is proposed as the basis of a barium-tagging technique for the detection of neutrinoless double β decay in xenon gas experiments.

Imputation uses genotype information from SNP arrays to infer the genotypes of missing markers. Here, the authors show that an imputation reference panel derived from whole-genome sequencing of 3,781 samples from the UK10K project improves the imputation accuracy and coverage of low frequency variants compared to existing methods.

Fast-ignition laser fusion involves directing an intense relativistic electron beam onto a fuel target. Experiments and simulations now enable a visualization of the location of fast electrons and the energy-coupling mechanisms at play.