Publications by authors named "Timothy C Stone"

Background: In the United Kingdom, onsite religious services were halted during COVID-19 lockdowns, which were followed by various levels of restrictions on communal worship including social distancing, mandatory wearing of face masks, adequate ventilation and a ban on congregational singing and chanting. The aim of our study was to evaluate the impact of closures and changes within places of worship in response to the first lockdown in 2020, to assess the effect of the pandemic on religious practice and worshippers' wellbeing and religious coping.

Methods: Participants were regular worshippers in the UK, recruited through an online survey using convenience sampling.

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Salivary epigenetic biomarkers may detect esophageal cancer. A total of 256 saliva samples from esophageal adenocarcinoma patients and matched volunteers were analyzed with Illumina EPIC methylation arrays. Three datasets were created, using 64% for discovery, 16% for testing and 20% for validation.

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The COVID-19 pandemic has led to restrictions such as social distancing and mandatory wearing of face masks. Singing and religious gatherings have been linked to infection clusters, and between 2020 and 2021 indoor congregational singing and chanting were prohibited in the United Kingdom. We evaluated attitudes to face mask use and their acceptability as well as changes within places of worship since their reopening in July up to autumn 2020.

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Article Synopsis
  • Early detection of esophageal cancer (EAC) is important for improving survival rates, and researchers are working to find reliable markers to help with this.
  • The study discovered 12 important gene-modules that change in EAC and found that these changes can also be seen in different patient groups, linking them to early signs of the disease.
  • They also identified a special pattern in DNA from saliva that can indicate EAC, suggesting that testing saliva might help spot this cancer sooner and that two specific gene modules (CTNND2 and CCL20) should be studied more.
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Background And Aims: Despite recent advances in advanced prostate cancer treatments, clinical biomarkers or treatments for men with such cancers are imperfect. Targeted therapies have shown promise, but there remain fewer actionable targets in prostate cancer than in other cancers. This work aims to characterise , currently understudied in prostate cancer, and investigate its co-expression with other genes to assess its potential as a biomarker and therapeutic target in human prostate cancer.

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Saliva and buccal samples are popular for epigenome wide association studies (EWAS) due to their ease of collection compared and their ability to sample a different cell lineage compared to blood. As these samples contain a mix of white blood cells and buccal epithelial cells that can vary within a population, this cellular heterogeneity may confound EWAS. This has been addressed by including cellular heterogeneity obtained through cytology at the time of collection or by using cellular deconvolution algorithms built on epigenetic data from specific cell types.

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There is widespread transcriptional dysregulation in Huntington's disease (HD) brain, but analysis is inevitably limited by advanced disease and postmortem changes. However, mutant HTT is ubiquitously expressed and acts systemically, meaning blood, which is readily available and contains cells that are dysfunctional in HD, could act as a surrogate for brain tissue. We conducted an RNA-Seq transcriptomic analysis using whole blood from two HD cohorts, and performed gene set enrichment analysis using public databases and weighted correlation network analysis modules from HD and control brain datasets.

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Article Synopsis
  • Innate immune activation beyond the central nervous system is increasingly recognized as important in neurodegenerative diseases, specifically in Huntington's disease (HD), which is caused by a mutation in the huntingtin gene.
  • A study using RNA-sequencing analyzed blood cells (monocytes) from HD patients and controls, revealing significant transcriptional differences in the resting state of HD monocytes, particularly related to proinflammatory cytokines.
  • These findings suggest that mutant huntingtin leads to a permanent proinflammatory state in myeloid cells, which could contribute to the progression of HD and highlight the potential role of systemic immunity in treating this and other neurodegenerative conditions.
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Background: The YAC128 model of Huntington's disease (HD) shows substantial deficits in motor, learning and memory tasks and alterations in its transcriptional profile. We examined the changes in the transcriptional profile in the YAC128 mouse model of HD at 6, 12 and 18 months and compared these with those seen in other models and human HD caudate.

Results: Differential gene expression by genotype showed that genes related to neuronal function, projection outgrowth and cell adhesion were altered in expression.

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Essential bacterial genes located within operons are particularly challenging to study independently because of coordinated gene expression and the nonviability of knockout mutants. Essentiality scores for many operon genes remain uncertain. Antisense RNA (asRNA) silencing or in-frame gene disruption of genes may help establish essentiality but can lead to polar effects on genes downstream or upstream of the target gene.

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Tissue-resident macrophages are heterogeneous as a consequence of anatomical niche-specific functions. Many populations self-renew independently of bone marrow in the adult, but the molecular mechanisms of this are poorly understood. We determined a transcriptional profile for the major self-renewing population of peritoneal macrophages in mice.

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We have used a novel affinity-based proteomics technology to examine the protein signature of small secreted extracellular vesicles called exosomes. The technology uses a new class of protein binding reagents called SOMAmers® (slow off-rate modified aptamers) and allows the simultaneous precise measurement of over 1000 proteins. Exosomes were highly purified from the Du145 prostate cancer cell line, by pooling selected fractions from a continuous sucrose gradient (within the density range of 1.

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Objective: Chronological age is a powerful epidemiologic risk factor for osteoarthritis (OA), a multifactorial disease that is characterized by articular cartilage (AC) degradation. It is unclear from a molecular perspective how aging interacts with OA to produce this risk to AC integrity. To address this key question, we used in vivo time-course analysis of OA development and murine interstrain variability in natural susceptibility to OA to examine changes in non-OA-prone CBA mice versus OA-prone STR/Ort mice, which develop disease that bears significant histologic resemblance to human OA.

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