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- Sandin, Linnea, et al.
(författare)
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Beneficial effects of increased lysozyme levels in Alzheimer’s disease modelled in Drosophila melanogaster
- 2016
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Ingår i: The FEBS Journal. - : John Wiley & Sons. - 1742-464X .- 1742-4658. ; 283:19, s. 3508-3522
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Tidskriftsartikel (refereegranskat)abstract
- Genetic polymorphisms of immune genes that associate with higher risk to develop Alzheimer’s disease (AD) have led to an increased research interest on the involvement of the immune system in AD pathogenesis. A link between amyloid pathology and immune gene expression was suggested in a genome-wide gene expression study of transgenic amyloid mouse models. In this study, the gene expression of lysozyme, a major player in the innate immune system, was found to be increased in a comparable pattern as the amyloid pathology developed in transgenic mouse models of AD. A similar pattern was seen at protein levels of lysozyme in human AD brain and CSF, but this lysozyme pattern was not seen in a tau transgenic mouse model. Lysozyme was demonstrated to be beneficial for different Drosophila melanogaster models of AD. In flies that expressed Aβ1-42 or AβPP together with BACE1 in the eyes, the rough eye phenotype indicative of toxicity was completely rescued by coexpression of lysozyme. In Drosophila flies bearing the Aβ1-42 variant with the Arctic gene mutation, lysozyme increased the fly survival and decreased locomotor dysfunction dose dependently. An interaction between lysozyme and Aβ1-42 in the Drosophila eye was discovered. We propose that the increased levels of lysozyme, seen in mouse models of AD and in human AD cases, were triggered by Aβ1-42 and caused a beneficial effect by binding of lysozyme to toxic species of Aβ1-42, which prevented these from exerting their toxic effects. These results emphasize the possibility of lysozyme as biomarker and therapeutic target for AD.
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| 2. |
- Armstrong, Andrea, et al.
(författare)
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Lysosomal Network Proteins as Potential Novel CSF Biomarkers for Alzheimers Disease
- 2014
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Ingår i: Neuromolecular medicine. - : Humana Press. - 1535-1084 .- 1559-1174. ; 16:1, s. 150-160
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Tidskriftsartikel (refereegranskat)abstract
- The success of future intervention strategies for Alzheimers disease (AD) will likely rely on the development of treatments starting early in the disease course, before irreversible brain damage occurs. The pre-symptomatic stage of AD occurs at least one decade before the clinical onset, highlighting the need for validated biomarkers that reflect this early period. Reliable biomarkers for AD are also needed in research and clinics for diagnosis, patient stratification, clinical trials, monitoring of disease progression and the development of new treatments. Changes in the lysosomal network, i.e., the endosomal, lysosomal and autophagy systems, are among the first alterations observed in an AD brain. In this study, we performed a targeted search for lysosomal network proteins in human cerebrospinal fluid (CSF). Thirty-four proteins were investigated, and six of them, early endosomal antigen 1 (EEA1), lysosomal-associated membrane proteins 1 and 2 (LAMP-1, LAMP-2), microtubule-associated protein 1 light chain 3 (LC3), Rab3 and Rab7, were significantly increased in the CSF from AD patients compared with neurological controls. These results were confirmed in a validation cohort of CSF samples, and patients with no neurochemical evidence of AD, apart from increased total-tau, were found to have EEA1 levels corresponding to the increased total-tau levels. These findings indicate that increased levels of LAMP-1, LAMP-2, LC3, Rab3 and Rab7 in the CSF might be specific for AD, and increased EEA1 levels may be a sign of general neurodegeneration. These six lysosomal network proteins are potential AD biomarkers and may be used to investigate lysosomal involvement in AD pathogenesis.
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| 7. |
- Bjärntoft, Sofie, et al.
(författare)
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A participatory approach to identify key areas for sustainable work environment and health in employees with flexible work arrangements
- 2021
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Ingår i: Sustainability. - : MDPI. - 2071-1050. ; 13:24
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Tidskriftsartikel (refereegranskat)abstract
- Flexible work arrangements are common worldwide, but knowledge on how to achieve a sustainable work environment is sparse. The aim of this study was to use a participatory approach to identify concrete suggestions and key areas for improvement that were considered relevant, effective, and feasible for promoting good work environment and health at organizational, work group and individual level (O-G-I), among office employees with flexible work arrangements. Eight focus group interviews (including 45 employees) were conducted in a large Swedish government agency in 2017. By using a Tree diagram approach, employees made a total of 279 suggestions for improvements, which were sorted into O-G-I levels and mapped into 18 key areas. We found that 13 key areas addressed organizational level (e.g., improving leadership, policy, job demands, and work efficiency), two key areas addressed group level (create common rules of availability and activity-based working), and three key areas addressed individual level (e.g., individuals’ responsibility to clearly communicate their availability). The participatory process was effective in obtaining concrete suggestions and key areas in need of improvement, which may provide an action plan that can guide organizations in developing interventions to promote good work environment and health in flexible work.
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| 8. |
- Boman, Andrea, et al.
(författare)
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The role of LAMP-2 in AβPP processing and Aβ degradation; implications for Alzheimer’s Disease
- 2015
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Dysfunction in the lysosomal network, i.e., the endosomal, lysosomal and autophagy systems, are implicated in the pathways in Alzheimer’s disease brain pathology. This dysfunction is mirrored in the cerebrospinal fluid where a specific subset of lysosomal network proteins are found at elevated levels, lysosomal associated membrane protein-2 (LAMP-2) being one of the identified lysosomal proteins. Here we report that hippocampus and frontal cortex in Alzheimer’s disease cases have increased mRNA and protein expression of LAMP-2, and thus these brain areas are likely involved in the increased LAMP-2 levels seen in cerebrospinal fluid from Alzheimer’s disease patients. The increased LAMP-2 levels correlated with increased levels of β-amyloid1-42 (Aβ1-42). Oligomeric Aβ1-42 caused an upregulation of intracellular LAMP-2 in neuroblastoma cells, but did not trigger the release of LAMP-2 to the extracellular milieu, indicating that other cell types or mechanisms are responsible for the LAMP-2 release seen in cerebrospinal fluid. Overexpression of LAMP-2 in neuroblastoma cells caused a trend of reduction of secreted Aβ1-42 and changed the processing pattern of the Aβ precursor protein. These results indicate that Aβ1-42 mediated increase of LAMP-2 expression can act as a regulator of Aβ generation and secretion. LAMP-2 overexpression did not change the cellular uptake of extracellularly added Aβ1-42, but caused a delayed clearance of Aβ1-42. Whether the prolonged intracellular localization of Aβ1-42 in LAMP-2 overexpressing cells can change the transmission or degradation of Aβ remains to be investigated.
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| 9. |
- Glimne, Susanne, et al.
(författare)
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Headaches in combination with visual ability, eye- and musculoskeletal strain in connection with visually demanding work tasks
- 2022
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Konferensbidrag (refereegranskat)abstract
- Suboptimal visual ergonomics (i.e., the interaction between our vision, the light, the visual object, and the influence of other factors which impairs visibility) in work environment such as glare can cause headache in combination with eyestrain, visual ability, and musculoskeletal strain. Symptoms constituted to the syndrome of eyestrain has been well described among computer workers (see for example Han et al., 2013; Portello et al., 2012; Bhanderi et al., 2008; Mocci et al., 2001; Sanchez-Roman et al., 1996). However, research has not focused on investigating the presence of headaches associated with eye-related and musculoskeletal disorders among employees and visual related environmental factors.The purpose of presented research was to study the presence of headaches in combination with visual ability, eye- and musculoskeletal strain, and work ability in connection with visually demanding work. Trained assessors recruited study participants primarily from their regular clients in the OHS field. Evaluators were instructed to recruit participants with a variety of characteristics to ensure highly variable data, such as different work tasks, age, and gender. The participants mean age was 48.3 years (±10.3); 66% were women.A visual ergonomics risk assessment method (VERAM, Heiden et al. 2019; Zetterberg et al. 2017) was used to compile the participated workers subjective grading of headache, eye- and musculoskeletal strain using a questionnaire (n=430). At the same time, an evaluation of the visual environment was carried out, which established if there was a risk of glare associated with the implementation of work task (e.g., computer work and other related work such as industry, healthcare, and shipping industry). The frequency of headaches was divided into three categories; (1) no headache, (2) headache occasionally, and (3) headache a few times per week/almost every day. The measurements regarding evaluation of the visual environment used a photometer, an instrument which was available and that the assessors could use, usually a Hagner ScreenMaster or Hagner S1 / S2 / S3.About 65% of the workers reported headaches occasionally, a few times/week or almost every day. Among the workers with headaches reported about 29% of them that they experienced the headaches a few times/week or almost every day.Out of the workers with headaches reported 37% a severity of the headaches of more than 3 (on a scale of 1-10) and 5 % reported a severity of more than 6. About 40% of the workers also stated that the headaches affected their working ability. The headaches were mainly located around the eyes, forehead, or temples (70%) and came in the afternoon (69%). About 75% of the workers also reported that the headache disappeared or were reduced when they were off work for one night or over the weekend. The data collection showed that visual- related symptoms increased the higher the estimated headaches was.The musculoskeletal strain increased when the headache increased. When workers reported a high frequency of headaches 95% of them reported neck strain, 86% shoulder strain, 73% upper back strain, and 61% were reported arm strain.Moreover, only 8.2% of the workers rated their visual ability as bad or very bad, but at the same time, about 60% reported dim vision, 14% diplopia, and 59% problems changing focus at some time.Dividing the data into workers with experienced or unexperienced headaches this study has shown that there was a significant presence of headaches in combination with visual related symptoms regarding experienced photophobia (p=0.011), eye pain (p=0.015), diplopia (p=0.029), and arm strain (p=0.006). Further, the statistical analysis showed that there was a tendency of combination regarding headaches and visual ability (p=0.070).Dividing the data into workers with experienced or unexperienced headaches, our study showed that the frequency of headache increased due to high luminance levels within the visual field (p=0.044).This study concludes presence of headaches in combination with eye- and musculoskeletal strain performing work task such as computer work. Further, the presence of headaches is due to visual ability induced by high luminance levels within the visual field.
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| 10. |
- Heiden, Marina, 1974-, et al.
(författare)
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Trunk and upper arm postures in paper mill work
- 2019
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Ingår i: Applied Ergonomics. - : Elsevier. - 0003-6870 .- 1872-9126. ; 70, s. 90-96
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to assess postures andmovements of the trunk and upper arm during paper mill work, and to determinethe extent to which they differ depending on method of assessment. For each oftwenty-eight paper mill workers, postures and movements were assessed duringthree full shifts using inclinometer registration and observation from video. Summary metrics for each shift, e.g.,10th, 50th, and 90th posture percentile, were averagedacross shifts and across workers. In addition, the standard deviation between workers,and the standard deviation between shifts within worker were computed. The resultsshowed that trunk and arm postures during paper mill work were similar to otheroccupations involving manual materials handling, but the velocity of armmovements were lower. While postures determined by inclinometry and observationwere similar on a group level, substantial differences were found betweenresults obtained by the two methods for individual workers, particularly for extremepostures. Thus, measurements by either method on individuals or small groupsshould be interpreted with caution.
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