| 1. |
- Buchanan, E. M., et al.
(författare)
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The Psychological Science Accelerator's COVID-19 rapid-response dataset
- 2023
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data.
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| 2. |
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| 5. |
- Kivimäki, M., et al.
(författare)
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Job strain as a risk factor for coronary heart disease : A collaborative meta-analysis of individual participant data
- 2012
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 380:9852, s. 1491-1497
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Tidskriftsartikel (refereegranskat)abstract
- Background Published work assessing psychosocial stress (job strain) as a risk factor for coronary heart disease is inconsistent and subject to publication bias and reverse causation bias. We analysed the relation between job strain and coronary heart disease with a meta-analysis of published and unpublished studies. Methods We used individual records from 13 European cohort studies (1985-2006) of men and women without coronary heart disease who were employed at time of baseline assessment. We measured job strain with questions from validated job-content and demand-control questionnaires. We extracted data in two stages such that acquisition and harmonisation of job strain measure and covariables occurred before linkage to records for coronary heart disease. We defined incident coronary heart disease as the first non-fatal myocardial infarction or coronary death. Findings 30 214 (15%) of 197 473 participants reported job strain. In 1•49 million person-years at risk (mean follow-up 7•5 years [SD 1•7]), we recorded 2358 events of incident coronary heart disease. After adjustment for sex and age, the hazard ratio for job strain versus no job strain was 1•23 (95% CI 1•10-1•37). This effect estimate was higher in published (1•43, 1•15-1•77) than unpublished (1•16, 1•02-1•32) studies. Hazard ratios were likewise raised in analyses addressing reverse causality by exclusion of events of coronary heart disease that occurred in the first 3 years (1•31, 1•15-1•48) and 5 years (1•30, 1•13-1•50) of follow-up. We noted an association between job strain and coronary heart disease for sex, age groups, socioeconomic strata, and region, and after adjustments for socioeconomic status, and lifestyle and conventional risk factors. The population attributable risk for job strain was 3•4%. Interpretation Our findings suggest that prevention of workplace stress might decrease disease incidence; however, this strategy would have a much smaller effect than would tackling of standard risk factors, such as smoking. Funding Finnish Work Environment Fund, the Academy of Finland, the Swedish Research Council for Working Life and Social Research, the German Social Accident Insurance, the Danish National Research Centre for the Working Environment, the BUPA Foundation, the Ministry of Social Affairs and Employment, the Medical Research Council, the Wellcome Trust, and the US National Institutes of Health.
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| 6. |
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| 8. |
- Heikkila, K., et al.
(författare)
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Job strain and the risk of severe asthma exacerbations : a meta-analysis of individual-participant data from 100 000 European men and women
- 2014
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 69:6, s. 775-783
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMany patients and healthcare professionals believe that work-related psychosocial stress, such as job strain, can make asthma worse, but this is not corroborated by empirical evidence. We investigated the associations between job strain and the incidence of severe asthma exacerbations in working-age European men and women. MethodsWe analysed individual-level data, collected between 1985 and 2010, from 102 175 working-age men and women in 11 prospective European studies. Job strain (a combination of high demands and low control at work) was self-reported at baseline. Incident severe asthma exacerbations were ascertained from national hospitalization and death registries. Associations between job strain and asthma exacerbations were modelled using Cox regression and the study-specific findings combined using random-effects meta-analyses. ResultsDuring a median follow-up of 10years, 1 109 individuals experienced a severe asthma exacerbation (430 with asthma as the primary diagnostic code). In the age- and sex-adjusted analyses, job strain was associated with an increased risk of severe asthma exacerbations defined using the primary diagnostic code (hazard ratio, HR: 1.27, 95% confidence interval, CI: 1.00, 1.61). This association attenuated towards the null after adjustment for potential confounders (HR: 1.22, 95% CI: 0.96, 1.55). No association was observed in the analyses with asthma defined using any diagnostic code (HR: 1.01, 95% CI: 0.86, 1.19). ConclusionsOur findings suggest that job strain is probably not an important risk factor for severe asthma exacerbations leading to hospitalization or death.
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| 9. |
- Theorell, Töres, et al.
(författare)
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Job strain in relation to body mass index : pooled analysis of 160 000 adults from 13 cohort studies
- 2012
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 272:1, s. 65-73
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Tidskriftsartikel (refereegranskat)abstract
- Job strain in relation to body mass index: pooled analysis of 160 000 adults from 13 cohort studies. J Intern Med 2012; 272: 6573. Background. Evidence of an association between job strain and obesity is inconsistent, mostly limited to small-scale studies, and does not distinguish between categories of underweight or obesity subclasses. Objectives. To examine the association between job strain and body mass index (BMI) in a large adult population. Methods. We performed a pooled cross-sectional analysis based on individual-level data from 13 European studies resulting in a total of 161 746 participants (49% men, mean age, 43.7 years). Longitudinal analysis with a median follow-up of 4 years was possible for four cohort studies (n = 42 222). Results. A total of 86 429 participants were of normal weight (BMI 18.524.9 kg m-2), 2149 were underweight (BMI < 18.5 kg m-2), 56 572 overweight (BMI 25.029.9 kg m-2) and 13 523 class I (BMI 3034.9 kg m-2) and 3073 classes II/III (BMI = 35 kg m-2) obese. In addition, 27 010 (17%) participants reported job strain. In cross-sectional analyses, we found increased odds of job strain amongst underweight [odds ratio 1.12, 95% confidence interval (CI) 1.001.25], obese class I (odds ratio 1.07, 95% CI 1.021.12) and obese classes II/III participants (odds ratio 1.14, 95% CI 1.011.28) as compared with participants of normal weight. In longitudinal analysis, both weight gain and weight loss were related to the onset of job strain during follow-up. Conclusions. In an analysis of European data, we found both weight gain and weight loss to be associated with the onset of job strain, consistent with a U-shaped cross-sectional association between job strain and BMI. These associations were relatively modest; therefore, it is unlikely that intervention to reduce job strain would be effective in combating obesity at a population level.
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| 10. |
- Balazs, J, et al.
(författare)
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INTRODUCING THE SUPREME PROJECT
- 2012
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Ingår i: INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE. - 1070-5503. ; 19, s. S148-S148
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 11. |
- Ferrie, J E, et al.
(författare)
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Diagnosis-specific sickness absence and all-cause mortality in the GAZEL study.
- 2009
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Ingår i: Journal of epidemiology and community health. - : BMJ. - 1470-2738 .- 0143-005X. ; 63:1, s. 50-5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This study aims to examine diagnosis-specific sickness absence as a risk marker for all-cause mortality. METHODS: Prospective occupational cohort (the GAZEL study). Medically certified sickness absence spells >7 days for 15 diagnostic categories, 1990-1992, were examined in relation to all-cause mortality, January 1993-February 2007. The reference group for each diagnostic category was participants with no spell >7 days for that diagnosis. The participants were French public utility workers (5271 women and 13 964 men) aged 37-51 years in 1990, forming the GAZEL study. Over the follow-up period, there were 144 deaths in women and 758 in men. RESULTS: 7875 employees (41.0%) had at least one spell of sickness absence >7 days over the 3-year period. The commonest diagnoses were mental disorders, musculoskeletal diseases, respiratory diseases and external causes in both sexes; genitourinary diseases in women, and digestive and circulatory diseases in men. Of these common diagnoses, mental disorders in women, hazard ratio (95% confidence intervals) 1.24 (1.1 to 1.4), and mental disorders 1.35 (1.3 to 1.5), digestive diseases 1.29 (1.1 to 1.6) and circulatory diseases 1.35 (1.2 to 1.6) in men were associated with mortality after adjustment for age, employment grade and sickness absence in all other diagnostic categories. CONCLUSIONS: Employees with medically certified absence spells of 1 week or more over a 3-year period had a 60% excess risk of early death. In women and men this excess risk was associated with some of the commonest diagnoses of sickness absence, in particular mental disorders. Sickness absence for mental disorders may be a useful early indicator of groups at increased risk of fatal disease.
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| 12. |
- Heikkilä, K., et al.
(författare)
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Job strain and health-related lifestyle : Findings from an individual-participant meta-analysis of 118 000 working adults
- 2013
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Ingår i: American Journal of Public Health. - 0090-0036 .- 1541-0048. ; 103:11, s. 2090-2097
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. We examined the associations of job strain, an indicator of work-related stress, with overall unhealthy and healthy lifestyles. Methods. We conducted a meta-analysis of individual-level data from 11 European studies (cross-sectional data: n = 118 701; longitudinal data: n = 43 971). We analyzed job strain as a set of binary (job strain vs no job strain) and categorical (high job strain, active job, passive job, and low job strain) variables. Factors used to define healthy and unhealthy lifestyles were body mass index, smoking, alcohol intake, and leisure-time physical activity. Results. Individuals with job strain were more likely than those with no job strain to have 4 unhealthy lifestyle factors (odds ratio [OR] = 1.25; 95% confidence interval [CI] = 1.12, 1.39) and less likely to have 4 healthy lifestyle factors (OR = 0.89; 95% CI = 0.80, 0.99). The odds of adopting a healthy lifestyle during study follow-up were lower among individuals with high job strain than among those with low job strain (OR = 0.88; 95% CI = 0.81, 0.96). Conclusions. Work-related stress is associated with unhealthy lifestyles and the absence of stress is associated with healthy lifestyles, but longitudinal analyses suggest no straightforward cause-effect relationship between workrelated stress and lifestyle. Copyright © 2013 by the American Public Health Association®.
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| 13. |
- Kivimäki, M, et al.
(författare)
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Sickness absence as a prognostic marker for common chronic conditions : analysis of mortality in the GAZEL study.
- 2008
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Ingår i: Occup Environ Med. - : BMJ. - 1470-7926 .- 1351-0711. ; 65:12, s. 820-6
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Tidskriftsartikel (refereegranskat)abstract
- Sickness absence as a prognostic marker for common chronic conditions: analysis of mortality in the GAZEL study.Kivimäki M, Head J, Ferrie JE, Singh-Manoux A, Westerlund H, Vahtera J, Leclerc A, Melchior M, Chevalier A, Alexanderson K, Zins M, Goldberg M.Department of Epidemiology and Public Health, University College London, London, UK. m.kivimaki@ucl.ac.ukOBJECTIVES: To determine whether sickness absence is a prognostic marker in terms of mortality among people with common chronic conditions. METHODS: Prospective occupational cohort study of 13,077 men and 4871 women aged 37-51 from the National Gas and Electricity Company, France. Records of physician-certified sickness absences over a 3-year period were obtained from employers' registers. Chronic conditions were assessed in annual surveys over the same period. The main outcome measure was all-cause mortality (803 deaths, mean follow-up after assessment of sickness absence: 13.9 years). RESULTS: In Cox proportional hazard models adjusted for age, sex, socioeconomic position and co-morbidity, >28 annual sickness-absence days versus no absence days was associated with an excess mortality risk among those with cancer (hazard ratio 5.4, 95% CI 2.2 to 13.1), depression (1.7, 1.1 to 2.8), chronic bronchitis or asthma (2.7, 1.6 to 4.6) and hypertension (1.6, 1.0 to 2.6). The corresponding hazard ratios for more than five long (>14 days) sickness-absence episodes per 10 person-years versus no such episodes were 5.4 (2.2 to 13.1), 1.8 (1.3 to 2.7), 2.0 (1.3 to 3.2) and 1.8 (1.2 to 2.7), respectively. Areas under receiver operating characteristics curves for these absence measures varied between 0.56 and 0.73, indicating the potential of these measures to distinguish groups at high risk of mortality. The findings were consistent across sex, age and socioeconomic groups and in those with and without co-morbid conditions. CONCLUSION: Data on sickness absence may provide useful prognostic information for common chronic conditions at the population level.
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| 14. |
- Madsen, I. E. H., et al.
(författare)
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Job strain as a risk factor for clinical depression : systematic review and meta-analysis with additional individual participant data
- 2017
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Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 47:8, s. 1342-1356
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Forskningsöversikt (refereegranskat)abstract
- Background. Adverse psychosocial working environments characterized by job strain (the combination of high demands and low control at work) are associated with an increased risk of depressive symptoms among employees, but evidence on clinically diagnosed depression is scarce. We examined job strain as a risk factor for clinical depression. Method. We identified published cohort studies from a systematic literature search in PubMed and PsycNET and obtained 14 cohort studies with unpublished individual-level data from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium. Summary estimates of the association were obtained using random-effects models. Individual-level data analyses were based on a pre-published study protocol. Results. We included six published studies with a total of 27 461 individuals and 914 incident cases of clinical depression. From unpublished datasets we included 120 221 individuals and 982 first episodes of hospital-treated clinical depression. Job strain was associated with an increased risk of clinical depression in both published [relative risk (RR) = 1.77, 95% confidence interval (CI) 1.47-2.13] and unpublished datasets (RR = 1.27, 95% CI 1.04-1.55). Further individual participant analyses showed a similar association across sociodemographic subgroups and after excluding individuals with baseline somatic disease. The association was unchanged when excluding individuals with baseline depressive symptoms (RR = 1.25, 95% CI 0.94-1.65), but attenuated on adjustment for a continuous depressive symptoms score (RR = 1.03, 95% CI 0.81-1.32). Conclusions. Job strain may precipitate clinical depression among employees. Future intervention studies should test whether job strain is a modifiable risk factor for depression.
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| 15. |
- Mogren, A., et al.
(författare)
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Children and adolescents with speech sound disorders are more likely to have orofacial dysfunction and malocclusion
- 2022
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Ingår i: Clinical and Experimental Dental Research. - : Wiley. - 2057-4347. ; 8:5, s. 1130-1141
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Tidskriftsartikel (refereegranskat)abstract
- Background: Children with speech sound disorders (SSD) form a heterogeneous group that differs in terms of underlying cause and severity of speech difficulties. Orofacial dysfunction and malocclusions have been reported in children with SSD. However, the association is not fully explored. Objectives: Our aims were to describe differences in orofacial function and malocclusion between a group of children and adolescents with compared to without SSD and to explore associations between those parameters among the group with SSD. Methods: A total of 105 participants were included, 61 children with SSD (6.0-16.7 years, mean age 8.5 +/- 2.8, 14 girls and 47 boys) and 44 children with typical speech development (TSD) (6.0-12.2 years, mean age 8.8 +/- 1.6, 19 girls and 25 boys). Assessments of orofacial function included an orofacial screening test and assessment of bite force, jaw stability, chewing efficiency, and intraoral sensory-motor function. Possible malocclusions were also assessed. Result: Children with SSD had both poorer orofacial function and a greater prevalence of malocclusion than children with TSD. Furthermore, children with SSD and poorer orofacial function had a greater risk of malocclusion. Conclusion: Our result suggests that children with SSD are more prone to having poorer orofacial function and malocclusion than children with TSD. This illustrates the importance of assessing coexisting orofacial characteristics in children with SSD, especially since orofacial dysfunction may be linked to an increased risk of malocclusion. This result highlights the need for a multiprofessional approach.
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| 16. |
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| 18. |
- Ahmadi, Ahmad, et al.
(författare)
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Association of a protective paraoxonase 1 (PON1) polymorphism in Parkinson's disease
- 2012
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 522:1, s. 30-35
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Tidskriftsartikel (refereegranskat)abstract
- Pesticide exposure has been suggested to increase the risk to develop Parkinson's disease (PD). The arylesterase paraoxonase 1 (PON1) is mainly expressed in the liver and hydrolyzes organophosphates such as pesticides. The polymorphism Leu54Met (rs854560) in PON1, impairing enzyme activity and leading to decreased PON1 expression levels, has been reported to be associated with Parkinson's disease (PD). PON1 is part of a cluster on chromosome 7q21.3 together with PON2 and PON3. We investigated the occurrence of four additional polymorphisms in PON1 and two in PON2 in a Swedish PD case-control material. We found a significant association (p = 0.007) with a PON1 promoter polymorphism, rs854571. The minor allele was more common among controls than PD cases which suggest a protective effect. This is strengthened by the fact that rs854571 is in strong linkage disequilibrium with another PON1 promoter polymorphism, rs854572, reported to increase PON1 gene expression. Our findings support the hypothesis that PON1 is involved in the etiology of PD and that higher PON1 levels are reducing the risk for PD. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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| 19. |
- Almaqwashi, A. A., et al.
(författare)
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Dissecting the Dynamic Pathways of Stereoselective DNA Threading Intercalation
- 2016
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 110:6, s. 1255-1263
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Tidskriftsartikel (refereegranskat)abstract
- DNA intercalators that have high affinity and slow kinetics are developed for potential DNA-targeted therapeutics. Although many natural intercalators contain multiple chiral subunits, only intercalators with a single chiral unit have been quantitatively probed. Dumbbell-shaped DNA threading intercalators represent the next order of structural complexity relative to simple intercalators, and can provide significant insights into the stereoselectivity of DNA-ligand intercalation. We investigated DNA threading intercalation by binuclear ruthenium complex [mu-dppzip(phen)(4)Ru-2](4+) (Piz). Four Piz stereoisomers are defined by the chirality of the intercalating subunit (Ru(phen)(2)dppz) and the distal subunit (Ru(phen)(2)ip), respectively, each of which can be either right-handed (Delta) or left-handed (Lambda). We used optical tweezers to measure single DNA molecule elongation due to threading intercalation, revealing force-dependent DNA intercalation rates and equilibrium dissociation constants. The force spectroscopy analysis provided the zero-force DNA binding affinity, the equilibrium DNA-ligand elongation Delta x(eq), and the dynamic DNA structural deformations during ligand association x(on) and dissociation x(off). We found that Piz stereoisomers exhibit over 20-fold differences in DNA binding affinity, from a K-d of 27 +/- 3 nM for (Delta,Lambda)-Piz to a K-d of 622 +/- 55 nM for (Lambda,Delta)-Piz. The striking affinity decrease is correlated with increasing Delta x(eq) from 0.30 +/- 0.02 to 0.48 +/- 0.02 nm and x(on) from 0.25 +/- 0.01 to 0.46 +/- 0.02 nm, but limited x(off) changes. Notably, the affinity and threading kinetics is 10-fold enhanced for right-handed intercalating subunits, and 2- to 5-fold enhanced for left-handed distal subunits. These findings demonstrate sterically dispersed transition pathways and robust DNA structural recognition of chiral intercalators, which are critical for optimizing DNA binding affinity and kinetics.
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| 20. |
- Almaqwashi, A. A., et al.
(författare)
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DNA intercalation optimized by two-step molecular lock mechanism
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 6, s. 37993-
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Tidskriftsartikel (refereegranskat)abstract
- The diverse properties of DNA intercalators, varying in affinity and kinetics over several orders of magnitude, provide a wide range of applications for DNA-ligand assemblies. Unconventional intercalation mechanisms may exhibit high affinity and slow kinetics, properties desired for potential therapeutics. We used single-molecule force spectroscopy to probe the free energy landscape for an unconventional intercalator that binds DNA through a novel two-step mechanism in which the intermediate and final states bind DNA through the same mono-intercalating moiety. During this process, DNA undergoes significant structural rearrangements, first lengthening before relaxing to a shorter DNA-ligand complex in the intermediate state to form a molecular lock. To reach the final bound state, the molecular length must increase again as the ligand threads between disrupted DNA base pairs. This unusual binding mechanism results in an unprecedented optimized combination of high DNA binding affinity and slow kinetics, suggesting a new paradigm for rational design of DNA intercalators.
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| 21. |
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| 22. |
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| 23. |
- Almaqwashi, A. A., et al.
(författare)
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Strong DNA deformation required for extremely slow DNA threading intercalation by a binuclear ruthenium complex
- 2014
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 42:18, s. 11634-11641
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Tidskriftsartikel (refereegranskat)abstract
- DNA intercalation by threading is expected to yield high affinity and slow dissociation, properties desirable for DNA-targeted therapeutics. To measure these properties, we utilize single molecule DNA stretching to quantify both the binding affinity and the force-dependent threading intercalation kinetics of the binuclear ruthenium complex Delta, Delta-[mu-bidppz-(phen)(4)Ru-2]4(+) (Delta, Delta-P). We measure the DNA elongation at a range of constant stretching forces using optical tweezers, allowing direct characterization of the intercalation kinetics as well as the amount intercalated at equilibrium. Higher forces exponentially facilitate the intercalative binding, leading to a profound decrease in the binding site size that results in one ligand intercalated at almost every DNA base stack. The zero force Delta, Delta-P intercalation K-d is 44 nM, 25-fold stronger than the analogous mono-nuclear ligand (Delta-P). The force-dependent kinetics analysis reveals a mechanism that requires DNA elongation of 0.33 nm for association, relaxation to an equilibrium elongation of 0.19 nm, and an additional elongation of 0.14 nm from the equilibrium state for dissociation. In cells, a molecule with binding properties similar to Delta, Delta-P may rapidly bind DNA destabilized by enzymes during replication or transcription, but upon enzyme dissociation it is predicted to remain intercalated for several hours, thereby interfering with essential biological processes.
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| 27. |
- Bahira, M., et al.
(författare)
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A ruthenium dimer complex with a flexible linker slowly threads between DNA bases in two distinct steps
- 2015
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 43:18, s. 8856-8867
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Tidskriftsartikel (refereegranskat)abstract
- Several multi-component DNA intercalating small molecules have been designed around ruthenium-based intercalating monomers to optimize DNA binding properties for therapeutic use. Here we probe the DNA binding ligand [mu-C-4(cpdppz)(2)(phen)(4)Ru-2](4+), which consists of two Ru(phen)(2)dppz(2+) moieties joined by a flexible linker. To quantify ligand binding, double-stranded DNA is stretched with optical tweezers and exposed to ligand under constant applied force. In contrast to other bis-intercalators, we find that ligand association is described by a two-step process, which consists of fast bimolecular intercalation of the first dppz moiety followed by similar to 10-fold slower intercalation of the second dppz moiety. The second step is rate-limited by the requirement for a DNA-ligand conformational change that allows the flexible linker to pass through the DNA duplex. Based on our measured force-dependent binding rates and ligand-induced DNA elongation measurements, we are able to map out the energy landscape and structural dynamics for both ligand binding steps. In addition, we find that at zero force the overall binding process involves fast association (similar to 10 s), slow dissociation (similar to 300 s), and very high affinity (K-d similar to 10 nM). The methodology developed in this work will be useful for studying the mechanism of DNA binding by other multi-step intercalating ligands and proteins.
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| 28. |
- Björkblom, Benny, et al.
(författare)
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c-Jun N-Terminal Kinase Phosphorylation of MARCKSL1 Determines Actin Stability and Migration in Neurons and in Cancer Cells
- 2012
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Ingår i: Molecular and Cellular Biology. - : American Society for Microbiology. - 0270-7306 .- 1098-5549. ; 32:17, s. 3513-3526
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Tidskriftsartikel (refereegranskat)abstract
- Cell migration is a fundamental biological function, critical during development and regeneration, whereas deregulated migration underlies neurological birth defects and cancer metastasis. MARCKS-like protein 1 (MARCKSL1) is widely expressed in nervous tissue, where, like Jun N-terminal protein kinase (JNK), it is required for neural tube formation, though the mechanism is unknown. Here we show that MARCKSL1 is directly phosphorylated by JNK on C-terminal residues (S120, T148, and T183). This phosphorylation enables MARCKSL1 to bundle and stabilize F-actin, increase filopodium numbers and dynamics, and retard migration in neurons. Conversely, when MARCKSL1 phosphorylation is inhibited, actin mobility increases and filopodium formation is compromised whereas lamellipodium formation is enhanced, as is cell migration. We find that MARCKSL1 mRNA is upregulated in a broad range of cancer types and that MARCKSL1 protein is strongly induced in primary prostate carcinomas. Gene knockdown in prostate cancer cells or in neurons reveals a critical role for MARCKSL1 in migration that is dependent on the phosphorylation state; phosphomimetic MARCKSL1 (MARCKSL1S120D,T148D,T183D) inhibits whereas dephospho-MARCKSL1S120A,T148A,T183A induces migration. In summary, these data show that JNK phosphorylation of MARCKSL1 regulates actin homeostasis, filopodium and lamellipodium formation, and neuronal migration under physiological conditions and that, when ectopically expressed in prostate cancer cells, MARCKSL1 again determines cell movement.
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| 29. |
- Brandao, Luiz Eduardo M., et al.
(författare)
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Acute sleep loss alters circulating fibroblast growth factor 21 levels in humans: A randomised crossover trial
- 2022
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Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 31:2
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Tidskriftsartikel (refereegranskat)abstract
- The hormone fibroblast growth factor 21 (FGF21) modulates tissue metabolism and circulates at higher levels in metabolic conditions associated with chronic sleep-wake disruption, such as type 2 diabetes and obesity. In the present study, we investigated whether acute sleep loss impacts circulating levels of FGF21 and tissue-specific production, and response pathways linked to FGF21. A total of 15 healthy normal-weight young men participated in a randomised crossover study with two conditions, sleep loss versus an 8.5-hr sleep window. The evening before each intervention, fasting blood was collected. Fasting, post-intervention morning skeletal muscle and adipose tissue samples underwent quantitative polymerase chain reaction and DNA methylation analyses, and serum FGF21 levels were measured before and after an oral glucose tolerance test. Serum levels of FGF21 were higher after sleep loss compared with sleep, both under fasting conditions and following glucose intake (similar to 27%-30%, p = 0.023). Fasting circulating levels of fibroblast activation protein, a protein which can degrade circulating FGF21, were not altered by sleep loss, whereas DNA methylation in the FGF21 promoter region increased only in adipose tissue. However, even though specifically the muscle exhibited transcriptional changes indicating adverse alterations to redox and metabolic homeostasis, no tissue-based changes were observed in expression of FGF21, its receptors, or selected signalling targets, in response to sleep loss. In summary, we found that acute sleep loss resulted in increased circulating levels of FGF21 in healthy young men, which may occur independent of a tissue-based stress response in metabolic peripheral tissues. Further studies may decipher whether changes in FGF21 signalling after sleep loss modulate metabolic outcomes associated with sleep or circadian disruption.
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| 30. |
- Bäckhed, Fredrik, 1973, et al.
(författare)
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Identification of target tissue glycosphingolipid receptors for uropathogenic, F1C-fimbriated Escherichia coli and its role in mucosal inflammation
- 2002
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 277:20, s. 18198-205
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial adherence to mucosal cells is a key virulence trait of pathogenic bacteria. The type 1 fimbriae and the P-fimbriae of Escherichia coli have both been described to be important for the establishment of urinary tract infections. While P-fimbriae recognize kidney glycosphingolipids carrying the Galalpha4Gal determinant, type 1 fimbriae bind to the urothelial mannosylated glycoproteins uroplakin Ia and Ib. The F1C fimbriae are one additional type of fimbria correlated with uropathogenicity. Although it was identified 20 years ago its receptor has remained unidentified. Here we report that F1C-fimbriated bacteria selectively interact with two minor glycosphingolipids isolated from rat, canine, and human urinary tract. Binding-active compounds were isolated and characterized as galactosylceramide, and globotriaosylceramide, both with phytosphingosine and hydroxy fatty acids. Comparison with reference glycosphingolipids revealed that the receptor specificity is dependent on the ceramide composition. Galactosylceramide was present in the bladder, urethers, and kidney while globotriaosylceramide was present only in the kidney. Using a functional assay, we demonstrate that binding of F1C-fimbriated Escherichia coli to renal cells induces interleukin-8 production, thus suggesting a role for F1C-mediated attachment in mucosal defense against bacterial infections.
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| 31. |
- Eliasson, Kent, et al.
(författare)
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All in the Family : self Selection and Migration by Couples
- 2014
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Ingår i: Papers in regional science (Print). - : John Wiley & Sons. - 1056-8190 .- 1435-5957. ; 93:1, s. 101-124
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Tidskriftsartikel (refereegranskat)abstract
- This paper examines determinants of couple migration in a model that accounts for self-selection of migrant couples. The study is based on a sample of married couples from the Swedish population. The model incorporates controls for earnings of both spouses preceding the move, and explicitly addresses unmeasured heterogeneity in the family decision to migrate. Two statistical formulations are presented. In the first version, migration is measured as a dichotomous move/stay decision. A second formulation replaces the dichotomous indicator with the distance moved by migrants. Results suggest that family migration is selective of relatively low earning wives with unmeasured potential for strong earnings.
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| 32. |
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| 33. |
- Gibney, A., et al.
(författare)
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A Click Chemistry-Based Artificial Metallo-Nuclease
- 2023
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Ingår i: Angewandte Chemie-International Edition. - 1433-7851 .- 1521-3773. ; 62:38
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Tidskriftsartikel (refereegranskat)abstract
- Artificial metallo-nucleases (AMNs) are promising DNA damaging drug candidates. Here, we demonstrate how the 1,2,3-triazole linker produced by the Cu-catalysed azide-alkyne cycloaddition (CuAAC) reaction can be directed to build Cu-binding AMN scaffolds. We selected biologically inert reaction partners tris(azidomethyl)mesitylene and ethynyl-thiophene to develop TC-Thio, a bioactive C-3-symmetric ligand in which three thiophene-triazole moieties are positioned around a central mesitylene core. The ligand was characterised by X-ray crystallography and forms multinuclear Cu-II and Cu-I complexes identified by mass spectrometry and rationalised by density functional theory (DFT). Upon Cu coordination, Cu-II-TC-Thio becomes a potent DNA binding and cleaving agent. Mechanistic studies reveal DNA recognition occurs exclusively at the minor groove with subsequent oxidative damage promoted through a superoxide- and peroxide-dependent pathway. Single molecule imaging of DNA isolated from peripheral blood mononuclear cells shows that the complex has comparable activity to the clinical drug temozolomide, causing DNA damage that is recognised by a combination of base excision repair (BER) enzymes.
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| 34. |
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| 35. |
- Hughes, Carmel M, et al.
(författare)
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Provision of pharmaceutical care by community pharmacists : a comparison across Europe
- 2010
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Ingår i: Pharmacy World & Science. - : Springer Science and Business Media LLC. - 0928-1231 .- 1573-739X. ; 32:4, s. 472-487
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate the provision of pharmaceutical care by community pharmacists across Europe and to examine the various factors that could affect its implementation. Methods A questionnaire-based survey of community pharmacies was conducted within 13 European countries. The questionnaire consisted of two sections. The first section focussed on demographic data and services provided in the pharmacy. The second section was a slightly adapted version of the Behavioral Pharmaceutical Care Scale (BPCS) which consists of three main dimensions (direct patient care activities, referral and consultation activities and instrumental activities). Results Response rates ranged from 10–71% between countries. The mean total score achieved by community pharmacists, expressed as a percentage of the total score achievable, ranged from 31.6 (Denmark) to 52.2% (Ireland). Even though different aspects of pharmaceutical care were implemented to different extents across Europe, it was noted that the lowest scores were consistently achieved in the direct patient care dimension (particularly those related to documentation, patient assessment and implementation of therapeutic objectives and monitoring plans) followed by performance evaluation and evaluation of patient satisfaction. Pharmacists who dispensed higher daily numbers of prescriptions in Ireland, Germany and Switzerland had significantly higher total BPCS scores. In addition, pharmacists in England and Ireland who were supported in their place of work by other pharmacists scored significantly higher on referral and consultation and had a higher overall provision of pharmaceutical care. Conclusion The present findings suggest that the provision of pharmaceutical care in community pharmacy is still limited within Europe. Pharmacists were routinely engaged in general activities such as patient record screening but were infrequently involved in patient centred professional activities such as the implementation of therapeutic objectives and monitoring plans, or in self-evaluation of performance.
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| 36. |
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| 37. |
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| 38. |
- Mogren, A., et al.
(författare)
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Malocclusion in children with speech sound disorders and motor speech involvement: a cross-sectional clinical study in Swedish children
- 2022
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Ingår i: European Archives of Paediatric Dentistry. - : Springer Science and Business Media LLC. - 1818-6300 .- 1996-9805. ; 23:4, s. 619-628
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The objectives of this study were to investigate the occurrence, types and severity of malocclusions in children with speech sound disorder (SSD) persisting after 6 years of age, and to compare these findings to a control group of children with typical speech development (TSD). Methods In total, 105 children were included: 61 with SSD and motor speech involvement (mean age 8:5 +/- 2:8 years; range 6:0-16:7 years, 14 girls and 47 boys) and 44 children with TSD (mean age 8:8 +/- 1:6; range 6:0-12:2 years, 19 girls and 25 boys). Extra-oral and intra-oral examinations were performed by an orthodontist. The severity of malocclusion was scored using the IOTN-DHC Index. Results There were differences between the SSD and TSD groups with regard to the prevalence, type, and severity of malocclusions; 61% of the children in the SSD group had a malocclusion, as compared to 29% in the TSD group. In addition, the malocclusions in the SSD group were rated as more severe. Functional posterior crossbite and habitual lateral and/or anterior shift appeared more frequently in the SSD group. Class III malocclusion, anterior open bite and scissors bite were found only in the SSD group. Conclusion Children with SSD and motor speech involvement are more likely to have a higher prevalence of and more severe malocclusions than children with TSD.
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| 39. |
- Nakosteen, Robert A, et al.
(författare)
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Active labor market programs and regional mobility of labor : evidence from the Swedish recession 1994 – 1995
- 2012
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Ingår i: Contemporary economic policy. - : Wiley-Blackwell. - 1074-3529 .- 1465-7287. ; 30:2, s. 178-194
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Tidskriftsartikel (refereegranskat)abstract
- This paper addresses the impact of active labor market programs on interregional migration in Sweden. The purpose of the study is to determine the extent to which the programs, which provide training and labor market assistance to jobless individuals, induce participants to migrate. Analysis is based on data registers compiled in 1994 and 1995 by Statistics Sweden and the Labor Market Board of Sweden. The paper specifies and estimates a two-equation model of participation and subsequent migration. The model, which is estimated by the method of maximum simulated likelihood, accounts for the role of program participation as an endogenous choice variable in the decision to migrate. In an attempt to capture the effect of migrant self-selection, the estimation approach also controls for unobserved heterogeneity in the participation and migration equations. Results of the study indicate a significant positive impact of participation on subsequent mobility for males. This result is robust with respect to alternative specifications of the migration equation and alternative formulations of the model for program participation. For females, the evidence of program impacts is mixed and it appears to be sensitive to the statistical formulation of the model.
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| 40. |
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| 41. |
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| 42. |
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| 43. |
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| 44. |
- Ran, C, et al.
(författare)
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Genetic Variations and mRNA Expression of NRF2 in Parkinson's Disease
- 2017
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Ingår i: Parkinson's disease. - : Hindawi Limited. - 2090-8083 .- 2042-0080. ; 2017, s. 4020198-
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Tidskriftsartikel (refereegranskat)abstract
- Nuclear factor erythroid 2-like 2 (NRF2) encodes a transcription factor regulating mechanisms of cellular protection and is activated by oxidative stress. NRF2 has therefore been hypothesized to confer protection against Parkinson’s disease and so far an NRF2 haplotype has been reported to decrease the risk of developing disease and delay disease onset. Also NRF2 adopts a nuclear localization in Parkinson’s disease, which is indicative of increased NRF2 activity. We have investigated the association between NRF2 and Parkinson’s disease in a Swedish case-control material and whether NRF2 expression levels correlate with NRF2 genetic variants, disease, or disease onset. Using pyrosequencing, we genotyped one intronic and three promoter variants in 504 patients and 509 control subjects from Stockholm. Further, we quantified NRF2 mRNA expression in EBV transfected human lymphocytes from patients and controls using quantitative real-time reverse transcription PCR. We found that one of the promoter variants, rs35652124, was associated with age of disease onset (Χ2 = 14.19, p value = 0.0067). NRF2 mRNA expression levels however did not correlate with the rs35652124 genotype, Parkinson’s disease, or age of onset in our material. More detailed studies on NRF2 are needed in order to elucidate how this gene affects pathophysiology of Parkinson’s disease.
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| 45. |
- Ran, C., et al.
(författare)
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Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden
- 2016
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 45
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Tidskriftsartikel (refereegranskat)abstract
- Several genetic studies have demonstrated an association between mutations in glucocerebrosidase (GBA), originally implicated in Gaucher's disease, and an increased risk of Parkinson's disease (PD). We have investigated the possible involvement of genetic GBA variations in PD in the Swedish population. Three GBA variants, E326K, N370S, and L444P were screened in the largest Swedish Parkinson cohort reported to date; 1625 cases and 2025 control individuals. We found a significant association with high effect size of the rare variant L444P with PD (odds ratio 8.17; 95% confidence interval: 2.51-26.23; p-value = 0.0020) and a significant association of the common variant E326K (odds ratio 1.60; 95% confidence interval: 1.16-2.22; p-value = 0.026). The rare variant N370S showed a trend for association. Most L444P carriers (68%) were found to reside in northern Sweden, which is consistent with a higher prevalence of Gaucher's disease in this part of the country. Our findings support the role of GBA mutations as risk factors for PD and point to lysosomal dysfunction as a mechanism contributing to PD etiology. (C) 2016 The Author(s). Published by Elsevier Inc.
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| 46. |
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| 47. |
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| 48. |
- Werner, Erik, et al.
(författare)
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Hairpins in the conformations of a confined polymer
- 2018
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Ingår i: Biomicrofluidics. - : AIP Publishing. - 1932-1058. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- If a semiflexible polymer confined to a narrow channel bends around by 180°, the polymer is said to exhibit a hairpin. The equilibrium extension statistics of the confined polymer are well understood when hairpins are vanishingly rare or when they are plentiful. Here, we analyze the extension statistics in the intermediate situation via experiments with DNA coated by the protein RecA, which enhances the stiffness of the DNA molecule by approximately one order of magnitude. We find that the extension distribution is highly non-Gaussian, in good agreement with Monte-Carlo simulations of confined discrete wormlike chains. We develop a simple model that qualitatively explains the form of the extension distribution. The model shows that the tail of the distribution at short extensions is determined by conformations with one hairpin. © 2018 Author(s).
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| 49. |
- Westerlund, Emma E., et al.
(författare)
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Tuberculosis-related knowledge is associated with patient outcomes in shantytown residents; Results from a cohort study, Peru
- 2015
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Ingår i: Journal of Infection. - : W.B. Saunders Ltd. - 0163-4453. ; 71:3, s. 347-357
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Tuberculosis is frequent among poor and marginalized people whose limited tuberculosis-related knowledge may impair healthcare access. We characterised tuberculosis-related knowledge and associations with delayed treatment and treatment outcome. Methods: Tuberculosis patients (n = 943), people being tested for suspected tuberculosis (n = 2020), and randomly selected healthy controls (n = 476) in 16 periurban shantytowns were interviewed characterizing: socio-demographic factors; tuberculosis risk-factors; and patients' treatment delay. Principle component analysis was used to generate a tuberculosisrelated knowledge score. Patients were followed-up for median 7.7 years. Factors associated with tuberculosis treatment delay, treatment outcome and tuberculosis recurrence were assessed using linear, logistic and Cox regression. Results: Tuberculosis-related knowledge was poor, especially in older people who had not completed schooling and had never been diagnosed with tuberculosis. Tuberculosis treatment delay was median 60 days and was more delayed for patients who were poorer, older, had more severe tuberculosis and in only unadjusted analysis with incomplete schooling and low tuberculosis-related knowledge (all p ≤ 0.03). Lower than median tuberculosis-related knowledge was associated with tuberculosis recurrence (unadjusted hazard ratio = 2.1, p = 0.008), and this association was independent of co-morbidities, disease severity and demographic factors (multiple regression adjusted hazard ratio = 2.6, p = 0.008). Conclusions: Low tuberculosis-related knowledge independently predicted tuberculosis recurrence. Thus health education may improve tuberculosis prognosis. © 2015 The British Infection Association.
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| 50. |
- Åström, Johanna, 1980-, et al.
(författare)
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See the future by looking at the past : predicting divorce with pre-marital earnings
- 2011
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Ingår i: Applied Economics Letters. - : Routledge. - 1350-4851 .- 1466-4291. ; 18:1, s. 997-1000
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Tidskriftsartikel (refereegranskat)abstract
- The effect of spouse's premarital earnings capacity on the probability of divorce is examined. This study is based on longitudinal register data on married and cohabitating couples in Sweden. We use the residuals from estimated earnings equations of men and women based on observations before their marriage in estimation of a logit model of divorce. By using information on individuals as singles, we can identify the impact of relative earnings power on the probability of divorce, per se, without the confounding effect of the marital relationship. The results indicate that differences in spouse's conditional earnings capacities increase the probability of divorce.
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