| 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. |
- Lindfors, Petra, et al.
(författare)
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Stress in paid and unpaid work as related to salivary cortisol measures and subjective health complaints in women working in the public sector
- 2017
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Konferensbidrag (refereegranskat)abstract
- Purpose: From a biopsychosocial approach, moderate intensity and variation between demands of different life domains are central to health. Focusing on different aspects of work and non-work demands, we investigated how total workload (TWL) and work-family conflict (WFC) related to the stress marker cortisol and to subjective health complaints (SHC) among women working in the public sector. Overall, we hypothesized that more TWL and WFC would be reflected in poorer health.Design/methodology: Data came from a study of 250 women working within the health care sector. All provided self-reports in questionnaires on time spent on TWL and associated stress perceptions, WFC and SHC. A subsample of 68 women provided salivary samples during one workday. These samples were analyzed for cortisol and used to compute aggregate cortisol measures. Hierarchical regression analyses were performed to investigate how TWL and WFC were related to cortisol and SHC respectively.Results: TWL stress from unpaid work was associated with cortisol. Also, stress from both paid and unpaid work, and TWL-stress, were related to SHC. Importantly, number of hours spent on paid and unpaid work were not linked to any health-related measure. Instead, stress perceptions were associated with both cortisol and SHC. This underscores the importance of individuals’ experiences of demands from different life domains for different health-related measures.Limitations: We included only women.Research/practical implications: Time use data are insufficient meaning that self-reports of individual experiences are needed.Originality/value: Combining biomarker data with self-reports is an obvious strength.
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| 6. |
- 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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| 7. |
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| 8. |
- 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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| 9. |
- 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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| 10. |
- Svedberg, Pia, et al.
(författare)
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A twin study of work-home interference and the risk of future sickness absence with mental diagnoses
- 2016
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Ingår i: European Journal of Public Health, Volume 26 Issue suppl_1. - : Oxford University Press (OUP).
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundWork-home interference has been proposed as an important explanation for sickness absence (SA). Previous studies show mixed results, and have not accounted for genetics and shared everyday environment (familial factors), or investigated diagnosis specific SA. The aim was to study if work-home interference predicts SA due to stress-related mental diagnoses, or SA due to other mental diagnoses, among women and men, when adjusting for various confounders and familial factors.MethodsThis prospective cohort study included 11,916 twins, 19-47 years (49% women).Data on work-to-home and home-to-work conflicts and relevant confounders were derived from a 2005 survey, and national register data on SA spells until 2013 were obtained. Odds Ratios (ORs) with 95% Confidence Intervals (CIs) were calculated. Discordant twin pair design was applied to adjust for familial factors.ResultsFor women, each one unit increase in work-to-home and home-to-work conflicts was associated with SA due to stress-related mental diagnoses and to SA due to other mental diagnoses, when adjusting for sociodemographic factors (ORs 1.15-1.31). With further adjustments for work, health-related or familial factors, none of the associations remained. For men, each one unit increase in work-to-home conflicts was associated with SA due to stress-related diagnoses (ORs 1.23-1.35), independently of confounders.ConclusionsWork-to-home conflict was independently associated with future SA due to stress-related diagnoses among men only. Health and familial factors are important confounders to consider when researching work-home interference and SA, especially among women. Not including such confounders involves risking drawing incorrect conclusions.
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