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The immune response to SARS-CoV-2 infection is variable but has been linked to prognosis and the development of severe immunopathology. Here the authors assess a range of immune parameters in both peripheral blood and respiratory samples, providing a comparative assessment of the immune response between these compartments and their potential impact on immune-pathogenesis.

Here, the authors investigate how cis-regulatory elements (CRE) function in diverse genomic locations. They develop a high-throughput method to assay CRE activity across the genome and apply it to reveal the context dependencies of insulator activity.

Soft electronic patches worn on the skin of infants or children in intensive-care units have a wide range of capabilities in aiding critical care, including monitoring of hemodynamic parameters, cardiac activity, movement and crying.

Uninterrupted monitoring of pressure and temperature at skin interfaces can help to minimize the potential for pressure injuries in hospitalized or bedridden patients. Here, the authors introduce a soft, skin-mountable sensor that can continuously provide readings via antennas mounted under bedding, and demonstrate the functionality and robustness of the devices on patients.

Evaluating the immune status of newborns helps recognition of those who are at higher risk for serious infectious diseases. Here authors identify lower, epigenetically inferred,

neutrophil-to-lymphocyte ratios during the first week of life as risk factor for sepsis and provide insight into the underpinning epigenetic and transcriptional patterns.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

A strategy for inferring phase for rare variant pairs is applied to exome sequencing data for 125,748 individuals from the Genome Aggregation Database (gnomAD). This resource will aid interpretation of rare co-occurring variants in the context of recessive disease.

De novo designed interleukin-4 mimetics were engineered that induce biased signaling activation and exhibit high thermal stability. These mimetics offer insight into cytokine signaling and can be directly incorporated into 3D-printed biomaterials

African Americans have an elevated risk of developing chronic kidney disease, yet only a fraction of those with high-risk genotypes develop the disease. Here, the authors show that a missense variant in APOL1 has a strong protective effect when co-inherited with the high-risk G2 allele of APOL1, with important implications for clinical practice and translational research.

Analysis of data from 33 longitudinal cohorts from low- and middle-income countries indicates that conditions during pre-conception, pregnancy and the first few months of life are crucial in determining the risk of growth faltering in young children.

MicroRNAs regulate gene expression as part of the RNA-induced silencing complex. An analysis of miRNA in Chlamydomonas reinhardtiishows that algal miRNAs target sites predominantly within coding regions to destabilize mRNA and repress translation.

In this work, Bryant and Lastovka et al. utilise advanced ribosome profiling and transcriptomics techniques, to reveal distinct translation control mechanisms in Salmonella and Listeria, two highly divergent bacterial species.

Haloscopes aim at detecting axions by converting them into photons using high-quality resonant cavities, where the cavity resonance should be tuned with the unknown axion mass. Here, the authors improve exclusion limits using four phase-matched resonant cavities and a fast frequency scanning technique.

Predicting recurrence risk in non small cell lung cancer can help to guide treatment decisions. Here, the authors use CT and PET imaging to develop predictive imaging subtypes, which can be integrated with existing ctDNA methods to predict recurrence.

Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Here, the authors carry out a two-stage genome-wide association study for AMD and identify three new AMD risk loci, highlighting the shared and distinct genetic basis of the disease in East Asians and Europeans.

The authors seek to understand the precise roles of microglia in the early human brain by coculturing brain organoids with primitive-like macrophages generated from the same human induced pluripotent stem cells (iMac).

Antibody responses to SARS-CoV-2 are critical in the immune response to infection, but the potential cross-reactivity to other human corona viruses is poorly appreciated. Here the authors apply a systems based approach to characterise the antibody response in pre-pandemic cohorts and assess heterotypic reactivity to SARS-CoV-2.

The human reference genome does not fully reflect human genetic diversity. Here, the authors analyse 338 human genome assemblies from diverse populations to identify missing sequences, define non-reference unique insertions and construct a Human Diversity Reference.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

The complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome IV has been determined. Apart from chromosome XII, which contains the 1–2 Mb rDNA cluster, chromosome IV is the longest S. cerevisiae chromosome. It was split into three parts, which were sequenced by a consortium from the European Community, the Sanger Centre, and groups from St Louis and Stanford in the United States. The sequence of 1,531,974 base pairs contains 796 predicted or known genes, 318 (39.9%) of which have been previously identified. Of the 478 new genes, 225 (28.3%) are homologous to previously identified genes and 253 (32%) have unknown functions or correspond to spurious open reading frames (ORFs). On average there is one gene approximately every two kilobases. Superimposed on alternating regional variations in G+C composition, there is a large central domain with a lower G+C content that contains all the yeast transposon (Ty) elements and most of the tRNA genes. Chromosome IV shares with chromosomes II, V, XII, XIII and XV some long clustered duplications which partly explain its origin.

The lack of appropriate models restricts pre-clinical research for nasopharyngeal carcinoma (NPC). Here the authors report the development and characterization of NPC patient-derived xenografts (PDXs), and EBV positive NPC cell line from patient tumor, and suggest their potential use in future NPC research.

A modelling analysis shows that an unusually long gamma-ray burst gave rise to a lanthanide-rich kilonova following the merger of a neutron star–neutron star or of a neutron star–black hole.

Recent advancements in the sample quality of infinite-layer nickelates have made systematic comparisons with cuprates increasingly relevant. Hsu et al. report anomalous electronic transport in high-crystallinity (Nd,Sr)NiO₂ at large magnetic fields, map out the transport phase diagram, and discuss similarities and differences with cuprates.

Many low modulus systems, such as sensors, circuits and radios, are in 2D formats that interface with soft human tissue in order to form health monitors or bioelectronic therapeutics. Here the authors produce 3D architectures, which bypass engineering constraints and performance limitations experienced by their 2D counterparts.

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

Luis Pérez-Jurado, Stephen Chanock and colleagues detect clonal chromosomal abnormalities in peripheral blood or buccal samples from individuals in the general population. They show that the frequency of such events increases with age and is associated with elevated risk of developing subsequent hematological cancers.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

Neutron and X-ray scattering measurements provide further insight into the anharmonic behaviour of lead halide perovskites, revealing that rotations of PbBr₆ octahedra in CsPbBr₃ crystals occur in a correlated fashion along two-dimensional planes.

Med-PaLM, a state-of-the-art large language model for medicine, is introduced and evaluated across several medical question answering tasks, demonstrating the promise of these models in this domain.

Analysis of HbA1c and FPG levels across 117 population-based studies demonstrates regional variation in prevalence of previously undiagnosed screen-detected diabetes using one or both measures and suggests that use of elevated FPG alone could underestimate diabetes prevalence in low- and middle-income countries.

Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn’s disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology.

A magnetic confinement regime established at the Korea Superconducting Tokamak Advanced Research device enables the generation of plasmas over 10⁸ kelvin for 20 seconds with the aid of fast ions without plasma edge instabilities or impurity accumulation.

A deep learning model detects low frequency mosaic variants with improved accuracy.

Over 170 susceptibility loci have been identified by genome-wide association studies in breast cancer. Here, the authors interrogated the role of risk-associated variants from non-breast tissue, and using expression quantitative trait loci, identify potential target genes of known breast cancer susceptibility variants, as well as 11 regions not previously known to be associated with breast cancer risk.

Drugs targeting cardiovascular disease (CVD) can have negative consequences for liver function. Here, the authors combine genome wide analyses on 69,479 individuals to identify loss-of-function variants with beneficial effects on CVD-related traits without negative impacts on liver function.

A meta-analysis of exome-wide association studies for blood lipid levels in East Asian populations identifies a novel coding variant. Exome array data from the Global Lipids Genetics Consortium were integrated and led to the discovery of novel and population-specific variants associated with cholesterol and triglycerides.

How accurate are social scientists in predicting societal change, and what processes underlie their predictions? Grossmann et al. report the findings of two forecasting tournaments. Social scientists’ forecasts were on average no more accurate than those of simple statistical models.

Cyclic-di-GMP is a bacterial second messenger that binds to the regulatory domain of ATPases of some bacteria. Here, the authors report the crystal structure of this interaction, identify a cyclic-di-GMP binding mode, and show that this interaction might be important for bacterial biofilm formation.

Damaged DNA is often targeted to nuclear pore complexes for repair. Here, the authors show that kinesin-14 mediates this process ensuring error-prone repair, while perinuclear telomere attachment licenses damaged telomeric loci for this repair and kinesin-14 blocks senescence in the absence of telomerase.

A combination of mass spectrometry, pooled genome screens and STRING analysis identifies key uptake mediating interactions between nanoparticle-adsorbed proteins and cells via the low-density lipoprotein receptor.

Interim analysis of a phase III clinical trial of HER2-positive gastric adenocarinoma shows pembrolizumab plus trastuzumab and chemotherapy improves response rates compared with trastuzumab and chemotherapy alone.

Deep-learning models for the automated measurement of retinal-vessel calibre in retinal photographs perform comparably to or better than expert graders in associations of measurements of retinal-vessel calibre with cardiovascular risk factors.

Interactions of atmospheric neutrinos with quantum-gravity-induced fluctuations of the metric of spacetime would lead to decoherence. The IceCube Collaboration constrains such interactions with atmospheric neutrinos.

How the circadian clock generates rhythms of arousal remains unclear. Here, authors show that a clock-output molecule reduces excitability of an arousal circuit during the active phase. These results suggest a multifaceted role for the clock in arousal.

Genetic variants associated with susceptibility to pancreatic cancer have been identified using genome wide association studies (GWAS). Here, the authors combine data from over 9000 patients and perform a meta-analysis to identify five novel loci linked to pancreatic cancer.

Understanding the emergence, evolution, and transmission of antibiotic resistance genes (ARGs) is essential to combat antimicrobial resistance. Here, Munk et al. analyse ARGs in hundreds of sewage samples from 101 countries and describe regional patterns, diverse genetic environments of common ARGs, and ARG-specific transmission patterns.