Search

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Chemical recycling of poly(methyl methacrylate) (PMMA) typically requires high temperatures. Here, the authors report the UV-initiated depolymerisation of PMMA at low temperatures, in non-chlorinated solvents, such as benzonitrile.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

DBiTplus represents an integrated experimental and computational workflow that unifies sequencing-based and imaging-based spatial omics, demonstrated by combining transcriptomic profiling and multiplexed protein imaging on the same tissue section.

In this study, the authors assess changing symptom profiles associated with different SARS-CoV-2 variants from May 2020 to March 2022 in England. Using data from the REACT-1 study, they find that Omicron infection is more often associated with cold and influenza-like symptoms, and less with loss of taste and smell.

The impact of variants of uncertain significance (VUS) on protein function and cancer risk remain unclear. Here, the authors focus on the functional impact of VUS of the PALB2 gene and identify defects in DNA damage repair by homologous recombination associated with increased risk of breast cancer.

This study characterises Long COVID using data from the REACT-2 community-based study in England. It estimates that 38% (in autumn/winter 2020/21) and 22% (in spring 2021) of people reported at least one symptom 12 weeks after symptom onset; identifies risk factors for persistent symptoms; and finds evidence of symptom clustering.

Here they demonstrate a therapeutic intervention elevating levels of CYP450-derived lipids to control the expansion of intermediate monocytes in tissue and peripheral blood, presenting a first in class therapeutic approach for treating chronic inflammatory disease.

Cosgun et al. show that, in B cell leukemia, β-catenin expression is maintained at low levels through glycogen synthase kinase 3B (GSK3β)-mediated phosphorylation. Inhibition of GSK3β results in β-catenin–Ikaros–NuRD complex formation, leading to B-ALL cell death through MYC repression.

The REACT-1 study measures the community prevalence of SARS-CoV-2 in England through repeated cross-sectional surveys. Here, the authors present data from REACT-1 that document the increase in infection prevalence, particularly among children, associated with the Omicron variant in January 2022.

Wastewater surveillance could provide a means of monitoring SARS-CoV-2 prevalence that does not rely on testing individuals. Here, the authors report results from England’s national wastewater surveillance program, use it to estimate prevalence, and compare estimates with those from population-based prevalence surveys.

The risk of intensive care unit admission among children with COVID-19 or its sequelae is affected by age, ethnicity and comorbidities. Understanding these modifiers might help identify at-risk children and guide interventions.

An alternative mating system, termed parasex, produces progeny with high levels of genotypic diversity and is able to fulfil the roles of meiosis when it is absent in the fungal pathobiont Candida albicans.

A clinical review of all pediatric deaths in England from March 2020 to February 2021 attributes 25 deaths to SARS-CoV-2 infection and identifies risk factors to guide interventions.

REACT-2 is a large-scale community study of SARS-CoV-2 seroprevalence in England. Here, the authors estimate that 6% of adults in England had been infected by mid-July 2020, with health and long-term care workers and those of Black or South Asian ethnicity disproportionately affected.

De novo structural variants are an important cause of rare disorders but remain poorly understood. Here, the authors analyse over 12,000 families and reveal the prevalence, diversity, and clinical impact of complex de novo structural variants.

The duration of symptomatic COVID-19 and its impacts on health and quality of life are not well understood. In this study, the authors report results from a survey of ~275,000 adults in England and find that persistent COVID-19 is relatively rare but is associated with poorer mental health and health-related quality of life.

This mathematical modelling study projects the dynamics of SARS-CoV-2 in England until the end of 2022 assuming that the Omicron BA.2 sublineage remains dominant. They show that booster vaccination was highly effective in mitigating severe outcomes and that future dynamics will depend greatly on assumptions about waning immunity.

Many countries have closed schools as part of their COVID-19 response. Here, the authors model SARS-CoV-2 transmission on a network of schools and households in England, and find that risk of transmission between schools is lower if primary schools are open than if secondary schools are open.

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.

Understanding the mechanisms underlying the survival of drug tolerant persister cells following chemotherapy remains elusive. Here, multi-omics analysis and experimental approaches show that the germ-cell-specific H3K4 methyltransferase PRDM9 promotes metabolic rewiring in glioblastoma stem cells.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Conventional methods for human motion analysis using sensors tightly attached to the body are often uncomfortable. Here, the authors demonstrate motion recognition and prediction using sensors embedded in garments. The results provide guidance for the development of wearable technology integrated into everyday clothing.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

Polyamines produced by gut bacteria have been proposed to contribute to inflammatory bowel diseases. Here, Nauta et al. show that bacteria can produce a noncanonical polyamine intermediate that functions similarly to deoxyhypusine synthase inhibitors, activates mitochondrial stress responses, and inhibits nematode development and mouse macrophage differentiation.

Pre-existing chronic diseases can delay or accelerate cancer diagnosis. Here the authors report that the duration of analgesic treatment as well as history of anxiety or depression can impact risk of advance stage lung and colon cancer in patients.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Here, using samples from ~1,100 individuals, the authors define the nasal microbiome linked to Staphylococcus aureus colonization, identifying seven communities- either S. aureus-dominated or dominated by other bacteria.

PU.1^low CD28-expressing microglia may act as suppressive cells in Alzheimer’s disease, mitigating its progression by reducing neuroinflammation and amyloid plaque load, indicating potential immunotherapeutic approaches for treatment.

Determinants of WEE1 inhibitor sensitivity in cancer cells are largely undefined. Here, the authors show that WEE1 inhibitors beyond their cell cycle perturbing effects also lead to paradoxical activation of the integrated stress response kinase GCN2.

The authors developed a screen to find compounds that modulate intracellular Staphylococcus aureus metabolism and discovered KL1, which sensitizes persisters to antibiotics by reversing host-induced tolerance.

The authors find that TDP-43 loss of function—the pathology defining the neurodegenerative conditions ALS and FTD—induces novel mRNA polyadenylation events, which have different effects, including an increase in RNA stability, leading to higher protein levels.

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).

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

Benefits on health have been found to vary across different levels of physical activity (PA) for chronic conditions including cancer. Here the authors report that each minute of vigorous intensity PA is equivalent to various minutes of moderate and light PA in terms of all-cause, cardiometabolic disease and cancer mortality outcomes in a device-based population.

How DNA Polymerase Epsilon accomplishes continuous leading strand synthesis during DNA replication is not understood. Here, the authors describe a two tiers mechanism required to sustain Pol Epsilon processivity: CHTF18-dependent loading of PCNA at leading strand and dsDNA binding by its POLE3-POLE4 subunits.

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.

Deaminases of the APOBEC3 family contribute to the mutagenesis of various cancers, including urothelial carcinoma (UC) of the bladder. Here, the authors use functional studies and transcriptomics to demonstrate that APOBEC3 promotes tumour progression and squamous trans-differentiation in UC through IL-1α and downstream activation of the AP-1 transcription factor.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

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.

Testicular germ cell tumours (TGCT) are the most common cancers in young men. Here, the authors analyse the genomic landscape of TGCT using data from the Genomics England 100,000 Genomes Project, revealing divergent evolutionary trajectories and the prevalence of human leukocyte antigen loss.

The existence of phosphatases specialized in regulating the axon initial segment (AIS) was unclear. Here, the authors show that a PP2A-B55 subunit is selectively enriched at the AIS and contributes to its local phospho-regulation.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Focal gene amplification is a common feature of advanced and metastatic cancers. Here, the authors employ CRISPR-Cas9 nickase to target cancer-associated focal gene amplifications to selectively kill cancer cells through the production of DNA replication-associated double-strand breaks.

Determinants of Vibrio cholerae transmission are incompletely understood. Here, the authors use an infant mouse model to show that events in the intestine govern inter-animal transmission and that bacterial motility along with cholera toxin-driven diarrhea are critical for pathogen spread.