Dancing with loneliness in later life: A pilot study mapping seasonal variations

Temporal variations in loneliness at the individual and population level have long been reported in longitudinal studies. Although the evidence is limited due to methodological distinctions among studies, we broadly know that loneliness as one ages is a dynamic experience with people becoming more or less lonely or staying the same over time. There is, however, less evidence to understand individual variations in loneliness over shorter periods of time. This paper reports on one element of a small mixed method pilot study to investigate seasonal variations in loneliness over the course of one year and to test the effectiveness of tools used to collect data at repeated short intervals. Our findings confirm that loneliness is dynamic even over shorter periods of time with participants reporting to be lonelier in the evenings, weekends and spring-summer period. Data measures were at times problematic due to language and/or interpretation and reinforce the relevance of reviewing the more common approaches to studying loneliness to more effectively capture the complex and individual nature of the experience.Brunel University Londo

Z2 topological invariants in two dimensions from quantum Monte Carlo

We employ quantum Monte Carlo techniques to calculate the $Z_2$ topological invariant in a two-dimensional model of interacting electrons that exhibits a quantum spin Hall topological insulator phase. In particular, we consider the parity invariant for inversion-symmetric systems, which can be obtained from the bulk's imaginary-time Green's function after an appropriate continuation to zero frequency. This topological invariant is used here in order to study the trivial-band to topological-insulator transitions in an interacting system with spin-orbit coupling and an explicit bond dimerization. We discuss the accessibility and behavior of this topological invariant within quantum Monte Carlo simulations.Comment: 7 pages, 6 figure

Metabolomic profiles are gender, disease and time specific in the interleukin-10 gene-deficient mouse model of inflammatory bowel disease.

Metabolomic profiling can be used to study disease-induced changes in inflammatory bowel diseases (IBD). The aim of this study was to investigate the difference in the metabolomic profile of males and females as they developed IBD. Using the IL-10 gene-deficient mouse model of IBD and wild-type mice, urine at age 4, 6, 8, 12, 16, and 20 weeks was collected and analyzed by nuclear magnetic resonance (NMR) spectroscopy. Multivariate data analysis was employed to assess differences in metabolomic profiles that occurred as a consequence of IBD development and severity (at week 20). These changes were contrasted to those that occurred as a consequence of gender. Our results demonstrate that both IL-10 gene-deficient and wild-type mice exhibit gender-related changes in urinary metabolomic profile over time. Some male-female separating metabolites are common to both IL-10 gene-deficient and control wild-type mice and, therefore, appear to be related predominantly to gender maturation. In addition, we were able to identify gender-separating metabolites that are unique for IL-10 gene-deficient and wild-type mice and, therefore, may be indicative of a gender-specific involvement in the development and severity of the intestinal inflammation. The comparison of the gender-separating metabolomic profile from IL-10 gene-deficient mice and wild-type mice during the development of IBD allowed us to identify changes in profile patterns that appear to be imperative in the development of intestinal inflammation, but yet central to gender-related differences in IBD development. The knowledge of metabolomic profile differences by gender and by disease severity has potential clinical implications in the design of both biomarkers of disease as well as the development of optimal therapies

Diastereoselective reduction of protein-bound methionine sulfoxide by methionine sulfoxide reductase

AbstractMethionine sulfoxide (MetSO) in calmodulin (CaM) was previously shown to be a substrate for bovine liver peptide methionine sulfoxide reductase (pMSR, EC 1.8.4.6), which can partially recover protein structure and function of oxidized CaM in vitro. Here, we report for the first time that pMSR selectively reduces the D-sulfoxide diastereomer of CaM-bound L-MetSO (L-Met-D-SO). After exhaustive reduction by pMSR, the ratio of L-Met-D-SO to L-Met-L-SO decreased to about 1:25 for hydrogen peroxide-oxidized CaM, and to about 1:10 for free MetSO. The accumulation of MetSO upon oxidative stress and aging in vivo may be related to incomplete, diastereoselective, repair by pMSR

Effects of Wnt3A and mechanical load on cartilage chondrocyte homeostasis

Introduction Articular cartilage functions in withstanding mechanical loads and provides a lubricating surface for frictionless movement of joints. Osteoarthritis, characterised by cartilage degeneration, develops due to the progressive erosion of structural integrity and eventual loss of functional performance. Osteoarthritis is a multi-factorial disorder; two important risk factors are abnormal mechanical load and genetic predisposition. A single nucleotide polymorphism analysis demonstrated an association of hip osteoarthritis with an Arg324Gly substitution mutation in FrzB, a Wnt antagonist. The purpose of this study was two-fold: to assess whether mechanical stimulation modulates β-catenin signalling and catabolic gene expression in articular chondrocytes, and further to investigate whether there is an interplay of mechanical load and Wnt signalling in mediating a catabolic response. Methods Chondrocytes were pre-stimulated with recombinant Wnt3A for 24 hours prior to the application of tensile strain (7.5%, 1 Hz) for 30 minutes. Activation of Wnt signalling, via β-catenin nuclear translocation and downstream effects including the transcriptional activation of c-jun, c-fos and Lef1, markers of chondrocyte phenotype (type II collagen (col2a1), aggrecan (acan), SOX9) and catabolic genes (MMP3, MMP13, ADAMTS-4, ADAMTS-5) were assessed. Results Physiological tensile strain induced col2a1, acan and SOX9 transcription. Load-induced acan and SOX9 expression were repressed in the presence of Wnt3A. Load induced partial β-catenin nuclear translocation; there was an additive effect of load and Wnt3A on β-catenin distribution, with both extensive localisation in the nucleus and cytoplasm. Immediate early response (c-jun) and catabolic genes (MMP3, ADAMTS-4) were up-regulated in Wnt3A stimulated chondrocytes. With load and Wnt3A there was an additive up-regulation of c-fos, MMP3 and ADAMTS-4 transcription, whereas there was a synergistic interplay on c-jun, Lef1 and ADAMTS-5 transcription. Conclusion Our data suggest that load and Wnt, in combination, can repress transcription of chondrocyte matrix genes, whilst enhancing expression of catabolic mediators. Future studies will investigate the respective roles of abnormal loading and genetic predisposition in mediating cartilage degeneration

Deforming tachyon kinks and tachyon potentials

In this paper we investigate deformation of tachyon potentials and tachyon kink solutions. We consider the deformation of a DBI type action with gauge and tachyon fields living on D1-brane and D3-brane world-volume. We deform tachyon potentials to get other consistent tachyon potentials by using properly a deformation function depending on the gauge field components. Resolutions of singular tachyon kinks via deformation and applications of deformed tachyon potentials to scalar cosmology scenario are discussed.Comment: To appear in JHEP, 19 pages, 5 eps figures, minor changes and one reference adde

Epidemiology of influenza-like illness in the Amazon Basin of Peru, 2008-2009.

BackgroundData addressing the incidence and epidemiology of influenza and influenza-like illness (ILI) in tropical regions of the world is scarce, particularly for the neotropics of South America.MethodsWe conducted active, population-based surveillance for ILI across 45 city blocks within the Amazon Basin city of Iquitos, Peru. Demographic data and household characteristics were collected for all participants, and participating households were visited three times weekly to inquire about ILI (fever plus cough or sore throat) among household residents. Nasal and oropharyngeal swabs were collected from participants with ILI and tested for influenza virus infection.ResultsBetween May 1, 2008 and July 8, 2009, we monitored 10,341 participants for ILI for a total of 11,569.5 person-years. We detected 459 ILI episodes, with 252 (54.9%) of the participants providing specimens. Age-adjusted incidence of ILI was estimated to be 46.7 episodes/1000 person-years. Influenza A and B viruses were detected in 25 (9.9%) and 62 (24.6%) specimens of ILI patients, respectively, for an estimated age-adjusted incidence rate of 16.5 symptomatic influenza virus infections/1000 person-years. Risk factors for ILI included age, household crowding, and use of wood as cooking fuel. For influenza virus infection specifically, age and use of wood as a cooking fuel were also identified as risk factors, but no effect of household crowding was observed.ConclusionsOur results represent the initial population-based description of the epidemiology of ILI in the Amazon region of Peru, which will be useful for developing region-specific strategies for reducing the burden of respiratory disease

Older LGBTQ+ People’s Perspectives On Discrimination And Ageing In The UK: Emerging Findings From A Timeline Study

Meeting abstract presented at the Gerontological Society of America (GSA) 2023 Annual Scientific Meeting, Tampa, FL, USA, 8-12 November, 2023.This paper presents emerging findings from a United Kingdom study of socially inclusive ageing, reporting on timeline interviews with a sample of 25 LGBTQ+ people aged forty years and above, carried out during summer and fall of 2023. The research interrogates older LGBTQ+ people’s understanding of the impact of minority sexuality and gender identity on their lived experience and the ways in which this impacts their approach to challenges and opportunities linked to ageing. We draw on an innovative methodological approach, adapting Adriansen’s (2012) timeline interview method to fit the needs of older participants. Timeline interviews provide an approach to life-story research that structures a conversation around a written timeline, produced on paper during unstructured qualitative interviews. During the paper presentation we share anonymised timeline and narrative data highlighting milestones in individual biographies. We focus on moments and periods where sexuality and gender identity may have been a positive factor in individual life stories (romantic relationships, community membership) or have been seen as more problematic (discrimination, stigma and marginalisation). The timelines and associated interview data also provide opportunities to ground the biographies of older LGBTQ+ people in the context of social, cultural, political and policy contexts. The timelines reveal compelling data about ageing and identity, belonging and exclusion. Our emerging findings reflect C. Wright Mills’s concept of the sociological imagination, placing personal troubles and histories in the context of public issues. We gratefully acknowledge the funding this study has received from the United Kingdom Economic and Social Research Council.United Kingdom Economic and Social Research Counci

Programmed Death-1 Expression on Epstein Barr Virus Specific CD8+ T Cells Varies by Stage of Infection, Epitope Specificity, and T-Cell Receptor Usage

BACKGROUND: Programmed Death-1 (PD-1) is an inhibitory member of the CD28 family of molecules expressed on CD8+ T cells in response to antigenic stimulation. To better understand the role of PD-1 in antiviral immunity we examined the expression of PD-1 on Epstein-Barr virus (EBV) epitope-specific CD8+ T cells during acute infectious mononucleosis (AIM) and convalescence. METHODOLOGY/PRINCIPAL FINDINGS: Using flow cytometry, we observed higher frequencies of EBV-specific CD8+ T cells and higher intensity of PD-1 expression on EBV-specific CD8+ T cells during AIM than during convalescence. PD-1 expression during AIM directly correlated with viral load and with the subsequent degree of CD8+ T cell contraction in convalescence. Consistent differences in PD-1 expression were observed between CD8+ T cells with specificity for two different EBV lytic antigen epitopes. Similar differences were observed in the degree to which PD-1 was upregulated on these epitope-specific CD8+ T cells following peptide stimulation in vitro. EBV epitope-specific CD8+ T cell proliferative responses to peptide stimulation were diminished during AIM regardless of PD-1 expression and were unaffected by blocking PD-1 interactions with PD-L1. Significant variability in PD-1 expression was observed on EBV epitope-specific CD8+ T cell subsets defined by V-beta usage. CONCLUSIONS/SIGNIFICANCE: These observations suggest that PD-1 expression is not only dependent on the degree of antigen presentation, but also on undefined characteristics of the responding cell that segregate with epitope specificity and V-beta usage