67 research outputs found

    Orphan G protein-coupled receptor GPRC5A modulates integrin β1-mediated epithelial cell adhesion

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    G-Protein Coupled Receptor (GPCR), Class C, Group 5, Member A (GPRC5A) has been implicated in several malignancies. The underlying mechanisms, however, remain poorly understood. Using a panel of human cell lines, we demonstrate that CRISPR/Cas9-mediated knockout and RNAi-mediated depletion of GPRC5A impairs cell adhesion to integrin substrates: collagens I and IV, fibronectin, as well as to extracellular matrix proteins derived from the Engelbreth-Holm-Swarm (EHS) mouse sarcoma (Matrigel). Consistent with the phenotype, knock-out of GPRC5A correlated with a reduced integrin β1 (ITGB1) protein expression, impaired phosphorylation of the focal adhesion kinase (FAK), and lower activity of small GTPases RhoA and Rac1. Furthermore, we provide the first evidence for a direct interaction between GPRC5A and a receptor tyrosine kinase EphA2, an upstream regulator of FAK, although its contribution to the observed adhesion phenotype is unclear. Our findings reveal an unprecedented role for GPRC5A in regulation of the ITGB1-mediated cell adhesion and it's downstream signaling, thus indicating a potential novel role for GPRC5A in human epithelial cancers.</p

    A systematic review of correlates of sedentary behaviour in adults aged 18–65 years: a socio-ecological approach

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    Background: Recent research shows that sedentary behaviour is associated with adverse cardio-metabolic consequences even among those considered sufficiently physically active. In order to successfully develop interventions to address this unhealthy behaviour, factors that influence sedentariness need to be identified and fully understood. The aim of this review is to identify individual, social, environmental, and policy-related determinants or correlates of sedentary behaviours among adults aged 18-65 years. Methods: PubMed, Embase, CINAHL, PsycINFO and Web of Science were searched for articles published between January 2000 and September 2015. The search strategy was based on four key elements and their synonyms: (a) sedentary behaviour (b) correlates (c) types of sedentary behaviours (d) types of correlates. Articles were included if information relating to sedentary behaviour in adults (18-65 years) was reported. Studies on samples selected by disease were excluded. The full protocol is available from PROSPERO (PROSPERO 2014:CRD42014009823). Results: 74 original studies were identified out of 4041: 71 observational, two qualitative and one experimental study. Sedentary behaviour was primarily measured as self-reported screen leisure time and total sitting time. In 15 studies, objectively measured total sedentary time was reported: accelerometry (n = 14) and heart rate (n = 1). Individual level factors such as age, physical activity levels, body mass index, socio-economic status and mood were all significantly correlated with sedentariness. A trend towards increased amounts of leisure screen time was identified in those married or cohabiting while having children resulted in less total sitting time. Several environmental correlates were identified including proximity of green space, neighbourhood walkability and safety and weather. Conclusions: Results provide further evidence relating to several already recognised individual level factors and preliminary evidence relating to social and environmental factors that should be further investigated. Most studies relied upon cross-sectional design limiting causal inference and the heterogeneity of the sedentary measures prevented direct comparison of findings. Future research necessitates longitudinal study designs, exploration of policy-related factors, further exploration of environmental factors, analysis of inter-relationships between identified factors and better classification of sedentary behaviour domains

    Psychometric evaluation of a short measure of social capital at work

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    BACKGROUND: Prior studies on social capital and health have assessed social capital in residential neighbourhoods and communities, but the question whether the concept should also be applicable in workplaces has been raised. The present study reports on the psychometric properties of an 8-item measure of social capital at work. METHODS: Data were derived from the Finnish Public Sector Study (N = 48,592) collected in 2000–2002. Based on face validity, an expert unfamiliar with the data selected 8 questionnaire items from the available items for a scale of social capital. Reliability analysis included tests of internal consistency, item-total correlations, and within-unit (interrater) agreement by r(wg )index. The associations with theoretically related and unrelated constructs were examined to assess convergent and divergent validity (construct validity). Criterion-related validity was explored with respect to self-rated health using multilevel logistic regression models. The effects of individual level and work unit level social capital were modelled on self-rated health. RESULTS: The internal consistency of the scale was good (Cronbach's alpha = 0.88). The r(wg )index was 0.88, which indicates a significant within-unit agreement. The scale was associated with, but not redundant to, conceptually close constructs such as procedural justice, job control, and effort-reward imbalance. Its associations with conceptually more distant concepts, such as trait anxiety and magnitude of change in work, were weaker. In multilevel models, significantly elevated age adjusted odds ratios (ORs) of poor self-rated health (OR = 2.42, 95% confidence interval (CI): 2.24–2.61 for the women and OR = 2.99, 95% CI: 2.56–3.50 for the men) were observed for the employees in the lowest vs. highest quartile of individual level social capital. In addition, low social capital at the work unit level was associated with a higher likelihood of poor self-rated health. CONCLUSION: Psychometric techniques show our 8-item measure of social capital to be a valid tool reflecting the construct and displaying the postulated links with other variables

    Ethnic Inequalities in Psychological Distress : A Population Data Linkage Study on the Pacific Island of Guåhån/Guam

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    Psychological distress and mental illness has been found to be elevated in migrant groups living in sovereign countries, as well as for indigenous people living under colonial or administrative rule. The north Pacific island of Guam is unusual in its ethnic composition as it has no majority ethnic group, has a large indigenous population and remains a territory of the U.S. This study aimed to identify ethnic differences in self-reported psychological distress between the main ethnic groups on Guam. The study uses a cross sectional design with data linkage methodology, drawing on the Guam Census and the Behavioral Risk Factor Surveillance System health survey for Guam. The results showed that the native Chamorro population had worse self-reported psychological distress (defined as a ‘mental health condition or emotional problem’) than White/Caucasians (OR 2.09, 95% CI 1.52–2.87), particularly for severe distress (OR 3.61, 95% CI 1.33–2.77). This relationship persisted even after adjusting for a wide range of socio-demographic and economic factors (OR 2.58, 95% CI 1.15–5.76). Other Pacific Islanders also had higher psychological distress compared to White/Caucasians, but this association was largely explained by the adjusted factors. The findings are discussed in terms of social and economic disadvantage for Pacific Island peoples on Guam, as well as the impact of colonial administration, disaffection, and lack of autonomy for the Chamorro of Guam. Recommendations are made to improve psychiatric treatment for these groups by considering wider socio-political factors in assessment and treatment, as well as broader implications for the national dialogue on self-determination.Peer reviewe

    Sense of coherence and diabetes: A prospective occupational cohort study

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    <p>Abstract</p> <p>Background</p> <p>Sense of coherence (SOC) is an individual characteristic related to a positive life orientation leading to effective coping. A weak SOC has been associated with indicators of general morbidity and mortality. However, the relationship between SOC and diabetes has not been studied in prospective design. The present study prospectively examined the relationship between a weak SOC and the incidence of diabetes.</p> <p>Methods</p> <p>The relationship between a weak SOC and the incidence of diabetes was investigated among 5827 Finnish male employees aged 18–65 at baseline (1986). SOC was measured by questionnaire survey at baseline. Data on prescription diabetes drugs from 1987 to 2004 were obtained from the Drug Imbursement Register held by the Social Insurance Institution.</p> <p>Results</p> <p>During the follow-up, 313 cases of diabetes were recorded. A weak SOC was associated with a 46% higher risk of diabetes in participants who had been =<50 years of age on entry into the study. This association was independent of age, education, marital status, psychological distress, self-rated health, smoking status, binge drinking and physical activity. No similar association was observed in older employees.</p> <p>Conclusion</p> <p>The results suggest that besides focusing on well-known risk factors for diabetes, strengthening SOC in employees of =<50 years of age can also play a role in attempts to tackle increasing rates of diabetes.</p
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