| 1. |
- Agholme, Lotta, et al.
(författare)
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Low-dose γ-secretase inhibition increases secretion of Aβ peptides and intracellular oligomeric Aβ.
- 2017
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Ingår i: Molecular and cellular neurosciences. - : Elsevier BV. - 1095-9327 .- 1044-7431. ; 85, s. 211-219
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Tidskriftsartikel (refereegranskat)abstract
- γ-Secretase inhibitors have been considered promising drug candidates against Alzheimer's disease (AD) due to their ability to reduce amyloid-β (Aβ) production. However, clinical trials have been halted due to lack of clinical efficacy and/or side effects. Recent in vitro studies suggest that low doses of γ-secretase inhibitors may instead increase Aβ production. Using a stem cell-derived human model of cortical neurons and low doses of the γ-secretase inhibitor DAPT, the effects on a variety of Aβ peptides were studied using mass spectrometry. One major focus was to develop a novel method for specific detection of oligomeric Aβ (oAβ), and this was used to study the effects of low-dose γ-secretase inhibitor treatment on intracellular oAβ accumulation. Low-dose treatment (2 and 20nM) with DAPT increased the secretion of several Aβ peptides, especially Aβx-42. Furthermore, using the novel method for oAβ detection, we found that 2nM DAPT treatment of cortical neurons resulted in increased oAβ accumulation. Thus, low dose-treatment with DAPT causes both increased production of long, aggregation-prone Aβ peptides and accumulation of intracellular Aβ oligomers, both believed to contribute to AD pathology.
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| 2. |
- Bergström, Petra, et al.
(författare)
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Amyloid precursor protein expression and processing are differentially regulated during cortical neuron differentiation
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid precursor protein (APP) and its cleavage product amyloid beta (A beta) have been thoroughly studied in Alzheimer's disease. However, APP also appears to be important for neuronal development. Differentiation of induced pluripotent stem cells (iPSCs) towards cortical neurons enables in vitro mechanistic studies on human neuronal development. Here, we investigated expression and proteolytic processing of APP during differentiation of human iPSCs towards cortical neurons over a 100-day period. APP expression remained stable during neuronal differentiation, whereas APP processing changed. alpha-Cleaved soluble APP (sAPP alpha) was secreted early during differentiation, from neuronal progenitors, while beta-cleaved soluble APP (sAPP beta) was first secreted after deep-layer neurons had formed. Short A beta peptides, including A beta 1-15/16, peaked during the progenitor stage, while processing shifted towards longer peptides, such as A beta 1-40/42, when post-mitotic neurons appeared. This indicates that APP processing is regulated throughout differentiation of cortical neurons and that amyloidogenic APP processing, as reflected by A beta 1-40/42, is associated with mature neuronal phenotypes.
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| 3. |
- Blom, Victoria, 1975-, et al.
(författare)
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Stress in paid and unpaid work as related to cortisol and subjective health complaints in women working in the public health care sector
- 2017
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Ingår i: International Journal of Workplace Health Management. - 1753-8351 .- 1753-836X. ; 10:4, s. 286-299
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Focusing on 420 women employed within the woman-dominated health care sector, the purpose of this paper is to investigate how any variation in their total workload (TWL) in terms of paid and unpaid work relate to various subjective health complaints (SHC) (n=420) and the neuroendocrine stress marker cortisol (n=68).Design/methodology/approach: The authors explored how any variation in their TWL in terms of paid and unpaid work related cross-sectionally to SHC (n=420), and the neuroendocrine stress marker cortisol (n=68).Findings: Hierarchical regression analyses showed that stress of unpaid work was most strongly related to diurnal variations in cortisol. Both stress of paid and unpaid work as well as TWL stress, but not hours spent on TWL, were related to SHC.Practical implications: Taken together, objective measures of hours spent on various TWL domains were unrelated to outcome measures while perceptions of having too much TWL and TWL stress were linked to both cortisol and SHC, i.e. how individuals perceive a situation seem to be more important for health than the actual situation, which has implications for research and efforts to reduce individual TWL.Originality/value: This study is unique in showing that unpaid work and perceptions having too much TWL relate to stress markers in women working in the public health care sector.
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| 4. |
- Helgadóttir, Björg, et al.
(författare)
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The association between part-time and temporary employment and sickness absence : A prospective Swedish twin study
- 2019
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Ingår i: European Journal of Public Health. - : Oxford University Press (OUP). - 1101-1262 .- 1464-360X. ; 29:1, s. 147-153
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sickness absence (SA) is becoming a major economic problem in many countries. Our aim was to investigate whether type of employment, including temporary employment or part-time employment, is associated with SA while controlling for familial factors (genetic and shared environment). Differences between men and women and across employment sectors were explored.Methods: This is a prospective twin study based on 21 105 twins born in Sweden 1959–85. The participants completed a survey in 2005 with follow-up of SA (≥15 days), using register data, until end of 2013. The data were analyzed with logistic regression, with results presented as odds ratios (OR) with 95% confidence intervals (CI).Results: Temporary employment involved higher odds of SA (OR=1.21 95% CI=1.04–1.40) compared to full-time employment. Both part-time workers (OR=0.84 95% CI=0.74–0.95) and the self-employed (OR=0.77 95%CI=0.62–0.94) had lower odds of SA. Stratifying by sex showed lower odds for part-timers (OR=0.82 95% CI=0.73–0.94) and self-employed women (OR=0.65 95% CI=0.47–0.90), but higher odds for men in temporary employment (OR=1.33 95% CI=1.03–1.72). Temporary employees in county councils (OR=1.73 95% CI=1.01–2.99) and municipalities (OR=1.41 95% CI=1.02–1.96) had higher odds while part-timers employed in the private sector had lower odds (OR=0.77 95% CI=0.64–0.93). Familial factors did not confound the association between employment type and SA.Conclusions: Employment type is associated with SA, with temporary employment involving a higher risk compared to permanent full-time employment while both part-time employment and self-employment involved a lower risk. The associations vary between women and men and across sectors.
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| 5. |
- Nazir, Faisal Hayat, et al.
(författare)
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Expression and secretion of synaptic proteins during stem cell differentiation to cortical neurons.
- 2018
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Ingår i: Neurochemistry international. - : Elsevier BV. - 1872-9754 .- 0197-0186. ; 121, s. 38-49
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Tidskriftsartikel (refereegranskat)abstract
- Synaptic function and neurotransmitter release are regulated by specific proteins. Cortical neuronal differentiation of human induced pluripotent stem cells (hiPSC) provides an experimental model to obtain more information about synaptic development and physiology in vitro. In this study, expression and secretion of the synaptic proteins, neurogranin (NRGN), growth-associated protein-43 (GAP-43), synaptosomal-associated protein-25 (SNAP-25) and synaptotagmin-1 (SYT-1) were analyzed during cortical neuronal differentiation. Protein levels were measured in cells, modeling fetal cortical development and in cell-conditioned media which was used as a model of cerebrospinal fluid (CSF), respectively. Human iPSC-derived cortical neurons were maintained over a period of at least 150 days, which encompasses the different stages of neuronal development. The differentiation was divided into the following stages: hiPSC, neuro-progenitors, immature and mature cortical neurons. We show that NRGN was first expressed and secreted by neuro-progenitors while the maximum was reached in mature cortical neurons. GAP-43 was expressed and secreted first by neuro-progenitors and its expression increased markedly in immature cortical neurons. SYT-1 was expressed and secreted already by hiPSC but its expression and secretion peaked in mature neurons. SNAP-25 was first detected in neuro-progenitors and the expression and secretion increased gradually during neuronal stages reaching a maximum in mature neurons. The sensitive analytical techniques used to monitor the secretion of these synaptic proteins during cortical development make these data unique, since the secretion of these synaptic proteins has not been investigated before in such experimental models. The secretory profile of synaptic proteins, together with low release of intracellular content, implies that mature neurons actively secrete these synaptic proteins that previously have been associated with neurodegenerative disorders, including Alzheimer's disease. These data support further studies of human neuronal and synaptic development in vitro, and would potentially shed light on the mechanisms underlying altered concentrations of the proteins in bio-fluids in neurodegenerative diseases.
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| 6. |
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| 7. |
- Roll Bennet, Petra, 1968-, et al.
(författare)
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Displaying parental responsibility for childhood obesity : aspects of care and family relationships
- 2015
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Ingår i: Families, Relationships and Societies. - : Bristol University Press. - 2046-7435 .- 2046-7443. ; 4:1, s. 19-33
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Tidskriftsartikel (refereegranskat)abstract
- Childhood obesity is a much-debated health issue in Sweden as well as worldwide. Considerable emphasis is given to the prevention of excessive weight gain and obesity in early childhood, for example by providing lifestyle advice to parents. Based on interviews with Swedish parents of obese children aged between eight and 12, in this article parent narratives of everyday practices in relation to children’s diet and exercise habits are analysed as acts of ‘displaying normality’. The results show that explanations as to why it is difficult to manage the child’s weight appear to be connected to avoiding the risk of the child receiving negative attention and issues relating to the child’s own responsibility. These findings are discussed in terms of ‘displaying family normality’.
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| 8. |
- Stenseke, Marie, et al.
(författare)
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Kris i naturen – vår existens har blivit sårbar
- 2019
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Ingår i: Svenska Dagbladet, Stockholm. - 1101-2412.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Fler arter än någonsin i mänsklighetens historia hotas av utrotning och den biologiska mångfalden lokalt har förändrats kraftigt i en stor del av världens ekosystem. Grundläggande förändringar behövs både i samhället och för individer, för att bromsa den negativa trenden, skriver en rad debattörer.
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| 9. |
- Svedberg, Pia, et al.
(författare)
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Are time pressure and sleep problems due to thoughts about work risk factors for future sick leave?
- 2017
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Ingår i: European Journal of Public Health. - : Oxford University Press (OUP). - 1101-1262 .- 1464-360X. ; 27:S3, s. 252-252
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous research indicates that long working hours, time pressure and overtime work relate to a range of adverse outcomes including poor recovery and health complaints. But, findings are inconclusive and limited, especially regarding the associations to sick leave. The aim was to study if time pressure or sleep problems due to thoughts about work were associated with future sick leave, when adjusting for confounders including familial factors, and stratifying by occupational sector. Methods: The study sample included 23,777 twin individuals (54.5% women), aged 19-47 years who participated in a survey in 2005 including questions on time pressure, sleep, work and health. Register data on sick-leave spells lasting >14 days were obtained from the National Social Insurance Agency. Individuals were followed from date of survey response until 12/31/2013. Associations between time pressure, sleep problems due to thoughts about work and future sick leave were investigated using logistic regression analyses to assess Odds Ratios (OR) with 95% Confidence Intervals (CI). Results: Thirty-five percent of the individuals had an incident sick leave spell during the 8-years of follow-up. Sleep problems due to thoughts about work once a month or more often were associated with sick leave in the fully adjusted model (OR 1.22, CI 1.10-1.36). Stratified by sector, the highest estimate was shown for state employees (OR 1.54, CI 1.11-2.13). Familial factors did not seem to influence the associations. We found no statistically significant associations between time pressure and sick leave. No sex differences were found. Conclusions: Results indicate that sleep problems due to thoughts about work is a risk factor for future sick leave. This follows previous research showing that sleep length and disturbances, regardless of their reasons, are associated with sick leave. But, experiences of work-related time pressure seem not to be associated with sick leave.
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| 10. |
- Svedberg, Pia, et al.
(författare)
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Time pressure and sleep problems due to thoughts about work as risk factors for future sickness absence
- 2018
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 0340-0131 .- 1432-1246. ; 91:8, s. 1051-1059
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: This study investigated whether time pressure or sleep problems due to thoughts about work are associated with future sickness absence (SA) among women and men employed in different sectors, also when adjusting for confounders including familial factors (genetics and shared environment).METHODS: The study sample included 16,127 twin individuals (52% women), aged 19-47 years who in 2005 participated in an online survey including questions regarding time pressure, sleep, work and health. Register data on SA (> 14 days) were obtained from the National Social Insurance Agency and individuals were followed from date of survey response until 12/31/2013. Associations between time pressure, sleep problems due to thoughts about work and future SA were investigated using logistic regression analyses to assess odds ratios (OR) with 95% confidence intervals (CI).RESULTS: In total 5723 (35%) individuals had an incident SA spell during follow-up. Sleep problems due to thoughts about work were associated with SA in the fully adjusted model (OR 1.22, CI 1.10-1.36). Stratified by sector, the highest estimate was found for state employees (OR 1.54, CI 1.11-2.13). Familial factors did not seem to influence the associations. We found no statistically significant associations between time pressure and SA. No sex differences were found.CONCLUSIONS: Results indicated that sleep problems due to thoughts about work is a risk factor for future SA. This follows previous research showing that sleep length and sleep disturbances, regardless of reason, are associated with SA. But, experiences of work-related time pressure seem to have no effect on SA.
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