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Turajlic and colleagues assess longitudinal antibody and cellular immune responses against SARS-CoV-2 variants of concern in patients with cancer, following either recovery from SARS-CoV-2 infection or vaccination, in two back-to-back reports from the CAPTURE study.

In a clinical trial in pregnant women with gestational diabetes, a dietary intervention for energy restriction was safe and did not result in any difference in maternal weight or offspring standardized birth weight outcomes compared to the control arm.

AcrB is a prototypical resistance–nodulation–division (RND) bacterial transporter, conferring resistance to a variety of antibiotics. HDX-MS and other, complementary approaches offer insight into AcrB structural dynamics and suggest the molecular mechanisms underlying drug export and inhibition of this multidrug-resistance conferring pump.

This study shows how Escherichia coli ApaH hydrolyzes enigmatic Np₄N alarmones and decaps Np₄-capped RNAs, thereby impacting their lifetimes. Key features enable ApaH to bind RNA substrates in two orientations, depending on the cap and the first RNA nucleotide.

This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual.

A multi-ancestry genome-wide association study for age at menarche followed by fine mapping and downstream analysis implicates 665 pubertal timing genes, such as the G-protein-coupled receptor 83 (GPR83) and other genes expressed in the ovaries involved in the DNA damage response.

Fanconi Anemia (FA) is caused by deficiencies in DNA repair, making it hard to correct. Here the authors report a therapeutic base editing strategy to address two of the most prevalent FANCA mutations in patient hematopoietic stem and progenitor cells.

Inherited mutations in MUTYH have been shown to predispose patients to colorectal cancers. Here, the authors show that MUTYH mutations lead to an increased somatic base substitution mutation rate in normal intestinal epithelial cells, which is the likely cause for the increased cancer risk.

Here, integrating ribosome profiling, RNA-seq and proteomics to reveal transcriptional and post-translational regulation in HIV-infected T cells, the authors show that non-AUG translation of viral upstream ORFs elicits distinct immune responses and regulates viral gene expression in a DDX3-dependent manner.

Engineering cell factories that support the production of large quantities of protein therapeutics remains a significant biomanufacturing challenge. Here the authors engineered cells to sense an early marker of the Unfolded Protein Response (UPR) and, in response, modulate specific UPR signaling pathways mediating stress attenuation and/or apoptosis.

The SARS-CoV-2 spike glycoprotein is flexible, and its receptor-binding domain (RBD) fluctuates between open and closed conformations. Disulfide bonds are engineered into the spike ectodomain to lock the RBD in the closed state, leading to a construct with high thermostability.

Genomic, single-cell transcriptomic and epigenetic analyses show that chaetognaths, following extensive gene loss in the gnathiferan lineage, relied on newly evolved genes and lineage-specific tandem duplications, not caused by a whole-genome duplication event, to shape their distinctive body plan.

This study explores how G3BP proteins influence SARS-CoV-2 infection, revealing their interaction with the viral nucleocapsid protein to enhance the translation of viral RNAs produced by membrane bound replication organelles.

Di Domenico et al. develop a method to reconstruct contact matrices fully stratified by age, education level and socioeconomic position. Results show that accounting for contact assortativity with socioeconomic factors has limited effect on the basic reproduction number, but substantially influences the effectiveness of control strategies.

Abdellaoui et al. examine the geographic distribution of human DNA differences in Great Britain, finding that the geographic distribution of polygenic scores for educational attainment and other complex traits resembles the geographic distribution of economic differences.

Identification of cancer genes altered by non-genetic mechanisms in B-cell lymphoma is challenging. Here, the authors report the development of transposon tools to perform genome-wide recessive screens in vivo and validate identified putative tumor suppressor genes using a CRISPR/Cas9 validation platform.

DNA methylation is an epigenetic modification that control genetic programs. Here, the authors found that the methylation landscape influences the physicochemical properties of DNA and that it can serve as a universal cancer biomarker, and developed a one-step assay for the detection of cancer DNA.

The role of circular RNAs (circRNAs) in modulating gene expression in cancer remains to be investigated. Here, the authors perform whole transcriptome sequencing in 104 primary neuroblastomas and reveal the involvement of MYCN in regulating circRNAs.

Individuals over eighty years of age are less likely to mount a good immune response against SARS-CoV-2 (measured by neutralization titres) after the first dose of the BNT162b2 mRNA vaccine, but achieve good neutralization after the second dose.

Alan Cooper and colleagues investigated the prokaryotic flora of dental calculus from 34 human skeletons spanning several thousand years of European populations, from Mesolithic hunter-gatherers, via Neolithic and medieval agriculturalists, to modern industrial individuals. Cariogenic bacteria became more abundant relatively recently with the Industrial Revolution.

A prospective analysis reveals that emergence of SARS-CoV-2 has had only a marginal impact on the immune response to spike protein of other endemic human coronaviruses and predicts limited cross protection against infection.

A new version of nanorate DNA sequencing, with an error rate lower than five errors per billion base pairs and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection and the generation of high-resolution selection maps across coding and non-coding sites for many genes.

Metformin may serve as a non-toxic intervention to inhibit mitochondrial metabolism and slow DNMT3A-R882 clonal haematopoiesis expansion, thus delaying or averting progression to acute myeloid leukaemia.

This paper describes a framework for classifying small insertions and deletions from genomic data and applies it to a large dataset comprising seven tumor types. The analysis highlights new insertion and deletion signatures and a classifier of postreplicative repair dysfunction.

Mucosal Associated Invariant T cells have been implicated in response to bacterial pathogens. Here the authors show that in human viral infections, these cells are activated by IL-18 in cooperation with other pro-inflammatory cytokines, producing interferon gamma and granzyme B.

In this Consensus Statement, an international panel of experts present an overview of the latest developments in the field of cholangiocarcinoma. A set of consensus recommendations and research priorities is provided.

Older people have suboptimal responses to primary series vaccines, which can place them at risk for adverse coronavirus disease 2019 outcomes. Here the authors show that booster vaccines provide a substantial increase in antibody levels in the short term but that there is significant waning 100 d after booster shots.

Here, Murray-Nerger et al use a genome-wide CRISPR/Cas9 screen to show that the nuclear protein SFPQ suppresses lytic reactivation of Epstein-Barr virus by promoting the expression and accumulation of linker histone H1 on the viral genome.

John et al. show that upon classical activation, macrophages undergo nitric oxide-driven reprogramming of nucleotide metabolism, which affects immune functions and responses.

Parkinson’s disease (PD) involves toxic protein buildup and energy failure in neurons. Continuously breathing low-oxygen air protected mice from PD-like neuronal loss and reversed symptoms, even after they began, suggesting that hypoxia may protect neurons.

Tumor-associated neutrophils exhibit heterogeneity in breast cancer. Here, the authors identify a distinct precursor population (PreNeu) in estrogen receptor-positive tumors. PreNeu suppress homologous recombination in cancer cells, promoting error-prone DNA repair and enhancing sensitivity to PARP inhibitors.

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.

An expert-elicitation process identifies current methodological barriers for monitoring terrestrial biodiversity, and how technological and procedural development of robotic and autonomous systems may contribute to overcoming these challenges.

The complexity of epithelial cell states in the fibrotic niche in the context of chronic kidney disease remains incompletely understood. Here the authors integrate snRNA and ATAC-seq with high-plex single-cell molecular imaging to generate a spatially-revolved multiomic atlas of human kidney disease.

Myelodysplastic syndromes (MDS) are age-related pathologies in which alterations of hematopoietic stem cells lead to abnormal formation of blood cells. Here, the authors study the lesions that these cells undergo in aging and disease, characterizing a factor whose alteration in MDS leads to abnormal blood cell production.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

Age-specific differences upon SARS-CoV-2 infection are marked by emergence of goblet 2 inflammatory cells expressing antiviral interferon stimulating genes in paediatric nasal cultures, and basaloid-like cells with increased viral spread in cultures from older adults.

A somatic niche embraces the female germline in cereal ovules. MADS31 precisely maintains developmental progression of this niche to support the germline by repressing the post-fertilization programme.

In a randomized trial, a remotely delivered weight management intervention for people with long COVID and excess weight improved respective long COVID symptoms and quality of life and resulted in substantial weight loss when compared with a control group, with no serious adverse effects reported.

Cohesin plays a crucial role in both chromosome organization and DNA repair. Here the authors find that cohesin mediated genome architecture prevents interactions between damaged chromatin. In contrast cohesin phosphorylation  appears to primarily impact DNA repair speed.

The RNA methyltransferase activity of SPOUT1/CENP-32 is crucial for accurate mitotic spindle organization. Here, the authors describe a neurodevelopmental disorder caused by bi-allelic pathogenic SPOUT1 variants with reduced activity and compromised function in spindle organization.

Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery.

Acheiropodia is associated with homozygous deletions in the LMBR1 gene around ZRS, an enhancer regulating SHH during limb development, but how these deletions lead to this phenotype is unknown. Here the authors use whole-genome sequencing, ChIP-seq, 4C-seq and DNA FISH to show that alterations in CTCF motifs are responsible via altered enhancer–promoter interactions.

The barrier function of skin epidermis requires polarized secretion of lamellar bodies towards the body surface. Here, Rudd et al. identify Flower (FWE) as a novel regulator of lamellar body trafficking and a determinant of epidermal barrier function.

Here authors present SAMOSA-ChAAT, a method for resolving how chromatin-interacting proteins restructure individual chromatin fibers, in high throughput and at scale. They provide evidence that the imitation switch family remodeling enzymes sense nucleosome density to program internucleosomal spacing on individual molecules.

Development of a dual-fluorescent reporter system allows rapid quantification of diverse genomic copy number changes that arise in Candida albicans during adaptation to antifungal drugs.

Pesticides overuse has led to evolution of resistance but the associated crop yield losses or economic costs at large scale are not known. This study estimates the annual cost of resistance in England for black-grass and calls for national-scale planning to address the problem.

The post-transcriptional 5-methylcytosine (m⁵C) modification occurs in a wide range of nuclear-encoded RNAs. Here the authors identify the mitochondrial tRNA-Met as a target for the m⁵C methyltransferase NSun3—found mutated in a mitochondrial disease patient—and link mitochondrial tRNA modifications with energy metabolism.