| 1. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 2. |
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| 3. |
- Wåhlén, Erik, et al.
(författare)
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Activated EGFR and PDGFR internalize in separate vesicles and downstream AKT and ERK1/2 signaling are differentially impacted by cholesterol depletion
- 2023
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier. - 0006-291X .- 1090-2104. ; 665, s. 195-201
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Tidskriftsartikel (refereegranskat)abstract
- The interplay between membrane subregions and receptor tyrosine kinases (RTK) will influence signaling in both normal and pathological RTK conditions. In this study, epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor β (PDGFR-β) internalizations were investigated by immunofluorescent microscopy following simultaneous treatment with EGF and PDGF-BB. We found that the two receptors utilize separate routes of internalization, which merges in a common perinuclear endosomal compartment after 45 min of stimulation. This is further strengthened when contrasting the recruitment of either EGFR or PDGFR-β to either clathrin or caveolin-1: PDGFR-β dissociates from caveolin-1 upon stimulation, and engages clathrin, whilst an increased recruitment of EGFR, to both clathrin and caveolin-1, was observed upon EGF stimulation. The association between EGFR and caveolin-1 is supported by the observation that EGFR was localized in lipid raft associated fractions, whereas PDGFR-β was not. We also found that disruption of lipid rafts using MβCD led to an increased EGFR dimerization and phosphorylation in response to ligand, as well as a dramatic decrease in AKT- and a smaller but robust decrease in ERK1/2 phosphorylation. This suggest that lipid rafts may be important to effectively connect the EGFR with downstream proteins to facilitate signaling. Our data implies that cholesterol depletion of the plasma membrane affect the signaling of EGFR and PDGFRβ differently.
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| 4. |
- Wåhlén, Erik, et al.
(författare)
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Differential impact of lipid raft depletion on platelet-derived growth factor (PDGF)-induced ERK1/2 MAP-kinase, SRC and AKT signaling
- 2022
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Ingår i: Cellular Signalling. - : Elsevier. - 0898-6568 .- 1873-3913. ; 96
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Tidskriftsartikel (refereegranskat)abstract
- It has become clear that lipid rafts functions as signaling hotspots connecting cell surface receptors to intracellular signaling pathways. However, the exact involvement of lipid rafts in receptor tyrosine kinase signaling is still poorly understood. In this study, we have analyzed platelet-derived growth factor (PDGF) receptor β (PDGFR-β) signaling in two different cell lines depleted of cholesterol, and as a consequence, disruption of lipid rafts. Cholesterol depletion of BJ-hTERT fibroblasts using methyl-β-cyclodextrin (MβCD) did not affect PDGFR-β activation as measured by its tyrosine phosphorylation. However, we did observe a small reduction in AKT phosphorylation and a more robust decrease of ERK1/2 activation. In contrast, in the osteosarcoma cell line U2OS, we noticed a deficient receptor activation. Interestingly, in U2OS cells, the ERK1/2 pathway was unaffected, but instead AKT and SRC signaling was reduced. These results suggest that cell type specific wiring of signaling pathways can lead to differential sensitivity to cholesterol depletion. Furthermore, MβCD treatment had a much more pronounced morphological effect on U2OS compared to BJ-hTERT cells. This is consistent with a previous report claiming that cancer cells are more sensitive to cholesterol depletion than normal cells. Our data supports the possibility that cholesterol lowering drugs may impede tumor growth.
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| 5. |
- Bergman, Frida, 1984-
(författare)
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Active workstations : a NEAT way to prevent and treat overweight and obesity?
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Modern society is triggering sedentary behaviours in different domains. Different strategies can be used to reduce the time spent sitting and increase physical activity in the office environment, which is one domain where sedentary time is often high. One such strategy could be to install treadmill workstations. With these, the office workers can walk on a treadmill while performing their usual work tasks at the computer. However, the long-term effects of these workstations are not known. Aim: The overall aim of this thesis was to investigate the long-term effects on sedentary behaviour, physical activity and associated health factors of installing treadmill workstations in offices compared to regular office work.Method: In this randomized controlled trial, 80 sedentary, middle-aged, healthy office workers with overweight or obesity were individually randomized into either an intervention or a control group. Those in the intervention group had a treadmill workstation installed at their sit-stand desk, to use for at least one hour per day for 13 months. They further received boosting e-mails at four time-points during the study. Participants in the control group continued to work as normal at their sit-stand office desk. All participants also received a health consultation at the beginning of the study, where they got to discuss physical activity and diet recommendations. Measurements reported include physical activity and sedentary behaviour, anthropometric measurements, body composition, metabolic outcomes, stress, depression and anxiety, cognitive function, structural brain images and interview data. Linear mixed models were used for the main statistical analyses of the quantitative data. An exploratory approach was also undertaken, using orthogonal partial least squares regression on the baseline data. Finally, interview data from participants in the intervention group were analysed using a modified Grounded Theory approach.Results: The intervention group increased their daily walking time and their number of steps at all follow-ups compared to the control group. Concomitantly, a decrease in moderate-to-vigorous intensity physical activity (MVPA) was observed within both groups, mainly during weekends. No intervention effects were observed on any of the body, cognitive or brain volume measurements. Our exploratory analyses revealed a significant association between smaller hippocampal volume and percentage sitting time among participants over 51 years of age. From the interview data, we discovered a core category, “The Capacity to Benefit”. The categories were described as the ideal types the Convinced, the Competitive, the Responsible and the Vacillating, based on the principal characteristics of the participants representing their different motivational status and strategies to reach the goal of benefitting from the intervention. Conclusion: It is possible to increase daily physical activity in office environments by introducing treadmill workstations. Future interventions should adapt strategies for the individuals based on their motivational level, but should also workwith the social and physical environment and with factors within the organization to gain the best effects of these interventions.
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| 6. |
- Bergman, Frida, Medicine doktor, 1984-, et al.
(författare)
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Increasing Physical Activity In Office Workers - An RCT Of Treadmill Workstations
- 2018
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Ingår i: Medicine & Science in Sports & Exercise. - : Lippincott Williams & Wilkins. - 0195-9131 .- 1530-0315. ; 50:5, s. 47-47
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- PURPOSE: Our primary hypothesis was that an intervention with treadmill workstations would increase time spent walking. Secondary hypotheses were a decrease in time spent sitting with a concomitant increase in time spent standing and in light intensity physical activity (LPA) leading to positive effects on body measurements and body composition.METHODS: The intervention group received a treadmill workstation at their office desk during 13 months. Daily time spent sitting, standing and walking and number of steps was measured with activPAL®. Daily time in LPA and MVPA was measured with Actigraph®. Body weight, BMI and waist circumference were measured according to standardized protocols. Dual X-ray Absorptiometry was used to estimate body composition. Mixed models was used for the statistical analysis, with group, day of week (weekday/ weekend), time point and gender as fixed effects and age as a covariate. p<0.05 was considered significant.RESULTS: Eighty participants were included. The intervention group significantly increased their time spent walking at all follow-ups, with a difference at 13 months of 22 minutes (p<0.01) and 1645 steps per day (p<0.05), respectively, versus controls. Concomitantly, they decreased their MVPA with 13 minutes per day (p<0.001) at weekdays at 13 months versus baseline. We also found a decrease in LPA with 19 minutes per day (p<0.05), and of 17 minutes per day for MVPA (p<0.001) at 13 months versus baseline at weekends. The control group increased their time spent sitting with 25 minutes per day (p<0.05) and decreased the time spent standing with 35 minutes per day at weekdays (p<0.001) compared to baseline. There was also a decrease in LPA with 14 minutes per day (p<0.01) and in MVPA with 6 minutes per day (p<0.01) versus baseline during weekdays, with a decrease in sitting time with 36 minutes (p<0.05) at weekends. There were no significant changes in body measurements or body composition.CONCLUSION: It is possible to increase daily walking time by introducing treadmill workstations at offices. A decreased MVPA within the intervention group may contribute to lack of effects on body measurements and body composition. It is therefore important that future interventions aim at both reducing sedentary time as well as increasing, or at least remaining, MVPA levels.
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| 7. |
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| 8. |
- Bergman, Frida, 1984-, et al.
(författare)
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Treadmill workstations in office workers who are overweight or obese : a randomised controlled trial
- 2018
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Ingår i: The Lancet Public Health. - : The Lancet Publishing Group. - 2468-2667. ; 3:11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Treadmill workstations that enable office workers to walk on a treadmill while working at their computers might increase physical activity in offices, but long-term effects are unknown. We therefore investigated whether treadmill workstations in offices increased daily walking time.Methods: We did a randomised controlled trial of healthy office workers who were either overweight or obese. We recruited participants from 13 different companies, which comprised 17 offices, in Umeå, Sweden. We included people who were aged 40-67 years, had sedentary work tasks, and had a body-mass index (BMI) between 25 kg/m2 and 40 kg/m2. After the baseline measurement, we stratified participants by their BMI (25-30 kg/m2 and >30 to 40 kg/m2); subsequently, an external statistician randomly assigned these participants (1:1) to either the intervention group (who received treadmill workstations for optional use) or the control group (who continued to work at their sit-stand desks as usual). Participants in the intervention group received reminders in boosting emails sent out to them at four occasions during the study period. Researchers were masked to group assignment until after analysis of the primary outcome. After the baseline measurement, participants were not masked to group belongings. The primary outcome was total daily walking time at weekdays and weekends, measured at baseline, 2 months, 6 months, 10 months, and 13 months with the accelerometer activPAL (PAL Technologies, Glasgow, UK), which was worn on the thigh of participants for 24 h a day for 7 consecutive days. We used an intention-to-treat approach for our analyses. This trial is registered with ClinicalTrials.gov, number NCT01997970, and is closed to new participants.Findings: Between Nov 1, 2013, and June 30, 2014, a total of 80 participants were recruited and enrolled (n=40 in both the intervention and control groups). Daily walking time during total time awake at weekdays increased between baseline and 13 months by 18 min (95% CI 9 to 26) in the intervention group and 1 min (-7 to 9) in the control group (difference 22 min [95% CI 7 to 37], pinteraction=0·00045); for weekend walking, the change from baseline to 13 months was 5 min (-8 to 18) in the intervention group and 8 min (-5 to 21) in the control group (difference -1 min [-19 to 17]; pinteraction=0·00045). Neither measure met our predetermined primary outcome of 30 min difference in total walking time between the intervention and control group, so the primary outcome of the trial was not met. One adverse event was reported in a participant who accidently stepped on their Achilles tendon.Interpretation: In a sedentary work environment, treadmill workstations result in a statistically significant but smaller-than-expected increase in daily walking time. Future studies need to investigate how increasing physical activity at work might have potentially compensatory effects on non-work activity.
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| 9. |
- Bergman, Frida, Medicine doktor, 1984-, et al.
(författare)
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Walking Time Is associated With Hippocampal Volume in Overweight and Obese Office Workers
- 2020
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Ingår i: Frontiers in Human Neuroscience. - : Frontiers Media S.A.. - 1662-5161. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the long-term effects on cognition and brain function after installing treadmill workstations in offices for 13 months.Methods: Eighty healthy overweight or obese office workers aged 40–67 years were individually randomized to an intervention group, receiving a treadmill workstation and encouraging emails, or to a control group, continuing to work as usual. Effects on cognitive function, hippocampal volume, prefrontal cortex (PFC) thickness, and circulating brain-derived neurotrophic factor (BDNF) were analyzed. Further, mediation analyses between changes in walking time and light-intensity physical activity (LPA) on changes in BDNF and hippocampal volume between baseline and 13 months, and multivariate analyses of the baseline data with percentage sitting time as the response variable, were performed.Results: No group by time interactions were observed for any of the outcomes. In the mediation analyses, positive associations between changes in walking time and LPA on changes in hippocampal volume were observed, although not mediated by changes in BDNF levels. In the multivariate analyses, a negative association between percentage sitting time and hippocampal volume was observed, however only among those older than 51 years of age.Conclusion: Although no group by time interactions were observed, our analyses suggest that increased walking and LPA may have positive effects on hippocampal volume and that sedentary behavior is associated with brain structures of importance for memory functions.Trial Registration: www.ClinicalTrials.gov as NCT01997970.
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| 10. |
- Bernin, Diana, 1979, et al.
(författare)
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Real time MRI to elucidate the functionality of coating films intended for modified release
- 2019
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 311-312, s. 117-124
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Tidskriftsartikel (refereegranskat)abstract
- Polymer films based on mixtures of ethyl cellulose (EC) and hydroxypropyl cellulose (HPC) have been widely used to coat pellets and tablets to modify the release profile of drugs. For three different EC/HPC films we used 1H and 19F MRI in combination with a designed release cell to monitor the drug, polymer and water in 5 dimensional (5D) datasets; three spatial, one diffusion or relaxation and a temporal dimension, in real time. We observed that the water inflow through the films correlated with the initiation of the dissolution of the drug in the tablet beneath the film. Leaching of the pore forming HPC further accelerated water penetration and resulted in a drug release onset after a hydrostatic pressure was generated below the film indicated by positional changes of the film. For the more permeable film, both water ingress and drug egress showed a large variability of release over the film surface indicating the heterogeneity of the system. Furthermore, the 1H diffusion dataset revealed the formation of a gel layer of HPC at the film surface. We conclude that the setup presented provides a significant level of details, which are not achieved with traditional methods.
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