| 1. |
- Synnergren, Jane, 1967, et al.
(författare)
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Expression of microRNAs and their target mRNAs in human stem cell-derived cardiomyocyte clusters and in heart tissue.
- 2011
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Ingår i: Physiological genomics. - : American Physiological Society. - 1531-2267 .- 1094-8341. ; 43:10, s. 581-94
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have shown that microRNAs (miRNAs) act as posttranscriptional regulators and that they play important roles during heart development and in cardiac function. Thus, they may provide new means of altering stem cell fate and differentiation processes. However, information about the correlation between global miRNA and mRNA expression in cardiomyocyte clusters (CMCs) derived from human embryonic stem cells (hESC) and in fetal and adult heart tissue is lacking. In the present study the global miRNA and mRNA expression in hESC-derived CMCs and in fetal and adult heart tissue was investigated in parallel using microarrays. Target genes for the differentially expressed miRNAs were predicted using computational methods, and the concordance in miRNA expression and mRNA levels of potential target genes was determined across the experimental samples. The biology of the predicted target genes was further explored regarding their molecular functions and involvement in known regulatory pathways. A clear correlation between the global miRNA expression and corresponding target mRNA expression was observed. Using three different sources of cardiac tissue-like samples, we defined the similarities between in vitro hESC-derived CMCs and their in vivo counterparts. The results are in line with previously reported observations that miRNAs repress mRNA expression and additionally identify a number of novel miRNAs with potential important roles in human cardiac tissue. The concordant miRNA expression pattern observed among all the cardiac tissue-like samples analyzed here provide a starting point for future ambitious studies aiming towards assessment of the functional roles of specific miRNAs during cardiomyocyte differentiation.
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| 2. |
- Bauzá-Thorbrügge, Marco, et al.
(författare)
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NRF2 is essential for adaptative browning of white adipocytes.
- 2023
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Ingår i: Redox biology. - : Elsevier. - 2213-2317. ; 68
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Tidskriftsartikel (refereegranskat)abstract
- White adipose tissue browning, defined by accelerated mitochondrial metabolism and biogenesis, is considered a promising mean to treat or prevent obesity-associated metabolic disturbances. We hypothesize that redox stress acutely leads to increased production of reactive oxygen species (ROS), which activate electrophile sensor nuclear factor erythroid 2-Related Factor 2 (NRF2) that over time results in an adaptive adipose tissue browning process. To test this, we have exploited adipocyte-specific NRF2 knockout mice and cultured adipocytes and analyzed time- and dose-dependent effect of NAC and lactate treatment on antioxidant expression and browning-like processes. We found that short-term antioxidant treatment with N-acetylcysteine (NAC) induced reductive stress as evident from increased intracellular NADH levels, increased ROS-production, reduced oxygen consumption rate (OCR), and increased NRF2 levels in white adipocytes. In contrast, and in line with our hypothesis, longer-term NAC treatment led to a NRF2-dependent browning response. Lactate treatment elicited similar effects as NAC, and mechanistically, these NRF2-dependent adipocyte browning responses in vitro were mediated by increased heme oxygenase-1 (HMOX1) activity. Moreover, this NRF2-HMOX1 axis was also important for β3-adrenergic receptor activation-induced adipose tissue browning in vivo. In conclusion, our findings show that administration of exogenous antioxidants can affect biological function not solely through ROS neutralization, but also through reductive stress. We also demonstrate that NRF2 is essential for white adipose tissue browning processes.
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| 3. |
- Sina, E., et al.
(författare)
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Media use trajectories and risk of metabolic syndrome in European children and adolescents: the IDEFICS/I.Family cohort
- 2021
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Ingår i: International Journal of Behavioral Nutrition and Physical Activity. - : Springer Science and Business Media LLC. - 1479-5868. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Media use may influence metabolic syndrome (MetS) in children. Yet, longitudinal studies are scarce. This study aims to evaluate the longitudinal association of childhood digital media (DM) use trajectories with MetS and its components. Methods: Children from Belgium, Cyprus, Estonia, Germany, Hungary, Italy, Spain and Sweden participating in the IDEFICS/I.Family cohort were examined at baseline (W1: 2007/2008) and then followed-up at two examination waves (W2: 2009/2010 and W3: 2013/2014). DM use (hours/day) was calculated as sum of television viewing, computer/game console and internet use. MetS z-score was calculated as sum of age- and sex-specific z-scores of four components: waist circumference, blood pressure, dyslipidemia (mean of triglycerides and HDL-cholesterol(-1)) and homeostasis model assessment for insulin resistance (HOMA-IR). Unfavorable monitoring levels of MetS and its components were identified (cut-off: >= 90(th) percentile of each score). Children aged 2-16 years with >= 2 observations (W1/W2; W1/W3; W2/W3; W1/W2/W3) were eligible for the analysis. A two-step procedure was conducted: first, individual age-dependent DM trajectories were calculated using linear mixed regressions based on random intercept (hours/day) and linear slopes (hours/day/year) and used as exposure measures in association with MetS at a second step. Trajectories were further dichotomized if children increased their DM duration over time above or below the mean. Results: 10,359 children and adolescents (20,075 total observations, 50.3% females, mean age = 7.9, SD = 2.7) were included. DM exposure increased as children grew older (from 2.2 h/day at 2 years to 4.2 h/day at 16 years). Estonian children showed the steepest DM increase; Spanish children the lowest. The prevalence of MetS at last follow-up was 5.5%. Increasing media use trajectories were positively associated with z-scores of MetS (slope: beta = 0.54, 95%CI = 0.20-0.88; intercept: beta = 0.07, 95%CI = 0.02-0.13), and its components after adjustment for puberty, diet and other confounders. Children with increasing DM trajectories above mean had a 30% higher risk of developing MetS (slope: OR = 1.30, 95%CI = 1.04-1.62). Boys developed steeper DM use trajectories and higher risk for MetS compared to girls. Conclusions: Digital media use appears to be a risk factor for the development of MetS in children and adolescents. These results are of utmost importance for pediatricians and the development of health policies to prevent cardio-metabolic disorders later in life.
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| 4. |
- Stener-Victorin, Elisabet, et al.
(författare)
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Proteomic analysis shows decreased Type I fibers and ectopic fat accumulation in skeletal muscle from women with PCOS
- 2024
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Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Polycystic ovary syndrome’s (PCOS) main feature is hyperandrogenism, which is linked to a higher risk of metabolic disorders in women. Gene expression analyses in adipose tissue and skeletal muscle reveal dysregulated metabolic pathways in women with PCOS, but these differences do not necessarily lead tochanges in protein levels and biological function. Methods: To advance our understanding of the molecular alterations in PCOS, we performed global proteomic and phosphorylation site analysis using tandem mass spectrometry. Adipose tissue and skeletal muscle were collected at baseline from 10 women with and without PCOS, and in women with PCOS after 5 weeks of treatment with electrical stimulation. Results: Perilipin-1, a protein that typically coats the surface of lipid droplets in adipocytes, was increased whereas proteins involved in muscle contraction and type I muscle fiber function were downregulated in PCOS muscle. Proteins in the thick and thin filaments had many altered phosphorylation sites, indicating differences in protein activity and function. The upregulated proteins in muscle post treatment were enriched in pathways involved in extracellular matrix organization and wound healing, which may reflect a protective adaptation to repeated contractions and tissue damage due to needling. A similar, albeit less pronounced, upregulation in extracellular matrix organization pathways was also seen in adipose tissue. Conclusions: Our results suggest that hyperandrogenic women with PCOS have higher levels of extramyocellular lipids and fewer oxidative insulin-sensitive type I muscle fibers. These could be key factors leading insulin resistance in PCOS muscle while electric stimulation-induced tissue remodeling may be protective.
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| 5. |
- Breau, B., et al.
(författare)
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Longitudinal association of childhood physical activity and physical fitness with physical activity in adolescence: insights from the IDEFICS/I.Family study
- 2022
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Ingår i: International Journal of Behavioral Nutrition and Physical Activity. - : Springer Science and Business Media LLC. - 1479-5868. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study aimed to examine associations of early childhood physical fitness and physical activity (PA) with PA during later childhood/early adolescence while accounting for gender differences. Methods: We selected data of N = 4329 children from the IDEFICS/I. Family cohort (age 2.4-11.7 years) with data on baseline fitness and accelerometer measurements. At baseline, physical fitness tests were conducted including Flamingo balance, Backsaver sit and reach, Handgrip strength, Standing Long Jump, 40-m sprint and 20-m Shuttle run (to estimate cardio-respiratory fitness levels). PA was measured with Actigraph accelerometers over 3 days at baseline (ActiTrainer or GT1M) and 7 days at follow-up (GT3X). Evenson cutpoints were used to determine moderate-to-vigorous PA (MVPA) time, and children with >= 60mins/day of average MVPA were deemed as having met WHO guidelines at baseline and follow-up. Linear and logistic regressions were performed to examine longitudinal associations between meeting WHO guidelines, MVPA, and physical fitness tests at baseline with meeting WHO guidelines and MVPA at follow-up. Models were conducted on the entire sample, the sex-stratified sample, and stratified by sex and pubertal status at follow-up. Results: Results showed that meeting WHO guidelines for MVPA at baseline was positively associated with MVPA (Standardized Beta (B) = 0.13, 95%CI:(5.6;11.1)) and meeting WHO guidelines at follow-up for the entire sample (OR = 2.1, 95%CI:(1.5; 3.14), and stratified by males (OR = 2.5, 95%CI:(1.5; 4.1)) and females (OR = 1.8, 95%CI:(1.0; 3.2)). This was also found for both male pre/early pubertal and pubertal groups but only in the female pre/early pubertal group, and not the female pubertal group (MVPA: B = .00, 95%CI:(- 6.1; 5.6), WHO: OR = 0.61, 95%CI:(0.23;1.6)). Models indicated that Standing Long jump, 40-m sprint, Shuttle run and Flamingo balance at baseline were associated with MVPA and meeting the guidelines at follow-up. Conclusions: Meeting WHO guidelines and certain fitness tests at baseline were strongly associated with MVPA and meeting WHO guidelines at follow-up, but this association varied with sex and pubertal status. Consequently, these findings underline the importance of ensuring sufficient physical activity in terms of quality and quantity for children at the earliest stages of life.
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| 6. |
- Synnergren, Jane, et al.
(författare)
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Transcriptional sex and regional differences in paired human atrial and ventricular cardiac biopsies collected in vivo
- 2020
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Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 52:2, s. 110-120
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Tidskriftsartikel (refereegranskat)abstract
- Transcriptional studies of the human heart provide insight into physiological and pathophysiological mechanisms, essential for understanding the fundamental mechanisms of normal cardiac function and how they are altered by disease. To improve the understanding of why men and women may respond differently to the same therapeutic treatment it is crucial to learn more about sex-specific transcriptional differences. In this study the transcriptome of right atrium and left ventricle was compared across sex and regional location. Paired biopsies from five male and five female patients undergoing aortic valve replacement or coronary artery bypass grafting were included. Gene expression analysis identified 620 differentially expressed transcripts in atrial and ventricular tissue in men and 471 differentially expressed transcripts in women. In total 339 of these transcripts overlapped across sex but notably, 281 were unique in the male tissue and 162 in the female tissue, displaying marked sex differences in the transcriptional machinery. The transcriptional activity was significantly higher in atrias than in ventricles as 70% of the differentially expressed genes were upregulated in the atrial tissue. Furthermore, pathway- and functional annotation analyses performed on the differentially expressed genes showed enrichment for a more heterogeneous composition of biological processes in atrial compared with the ventricular tissue, and a dominance of differentially expressed genes associated with infection disease was observed. The results reported here provide increased insights about transcriptional differences between the cardiac atrium and ventricle but also reveal transcriptional differences in the human heart that can be attributed to sex.
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| 7. |
- Warrén Stomberg, Margareta, et al.
(författare)
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Routine intra-operative assessment of pain and/or depth of anaesthesia by nurse anaesthetists in clinical practice.
- 2001
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Ingår i: Journal of clinical nursing. - : Wiley Interscience. - 0962-1067 .- 1365-2702. ; 10:4, s. 429-36
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Tidskriftsartikel (refereegranskat)abstract
- Patient safety and comfort during general anaesthesia and surgery are to a considerable extent dependent on the capability of anaesthesia personnel to interpret directly monitored as well as indirect clinical signs of pain and/or depth of anaesthesia. The aim of the present study was to evaluate how nurse anaesthetists in their clinical routine work assess and interpret intra-operative responses evoked by pain stimuli and/or insufficient depth of anaesthesia. A questionnaire was designed to assess the perceived relevance and validity of cardiovascular, respiratory, mucocutaneous, eye-associated, and muscular responses for routine assessment of intra-operative pain and/or insufficient depth of anaesthesia in patients undergoing surgery under general anaesthesia. Data were obtained from 223 nurse anaesthetists working at nine different university anaesthesia departments in Sweden. A number of significant indicators for pain and depth of anaesthesia could be identified for spontaneously breathing as well as for mechanically ventilated patients. No variable was considered entirely specific for either intra-operative pain or depth of anaesthesia. Changes in breathing rate/volume, central haemodynamics (BP, HR), lacrimation, and presence of moist and sticky skin were given higher score values as indicators of pain than as indicators of depth of anaesthesia. Occurrence of grimaces, attempted movements, and presence of non-centred pupils were variables considered more indicative of insufficient depth of anaesthesia than intra-operative pain. In conclusion, it is obvious from the present data that indirect physiological signs of intra-operative pain and depth of anaesthesia are still considered of importance by Swedish anaesthesia nurses in the anaesthetic management of surgical patients.
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| 8. |
- Van Dijk, Willeke, et al.
(författare)
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The Effect of Mechanical Massage and Mental Training on Heart Rate Variability and Cortisol in Swedish Employees : A Randomized Explorative Pilot Study
- 2020
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Ingår i: Frontiers in Public Health. - : Frontiers Media S.A.. - 2296-2565. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Work-related stress is relatively common in modern society and is a major cause of sick-leave. Thus, effective stress reducing interventions are needed. This study examined the effects of mental training and mechanical massage, on employee's heart rate variability (HRV) and plasma cortisol at their workplaces. Moreover, it was investigated whether baseline systolic blood pressure (SBP) can explain differences in effectiveness of the intervention. Ninety-three participants from four workplaces were randomly assigned to one of the five programs: (I) Mechanical massage and mental training combined, II) Mechanical massage, III) Mental training, IV) Pause, or V) Control. HRV and plasma cortisol were measured at baseline and after 4 and 8 weeks. SBP was measured at baseline. On the reduction of cortisol levels, a small effect of the mechanical massage program was found, whereas no effect was found for the other programs. None of the programs showed any effect on HRV. Nonetheless, when the level of systolic blood pressure was taken into account, some small beneficial effects on HRV and cortisol of mental training and the mechanical massage were found. This exploratory pilot-study provides useful information for future studies that aim to reduce stress among employees.
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| 9. |
- Tajsharghi, Homa, 1968, et al.
(författare)
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Embryonic myosin heavy-chain mutations cause distal arthrogryposis and developmental myosin myopathy that persists postnatally.
- 2008
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Ingår i: Archives of neurology. - : American Medical Association (AMA). - 1538-3687 .- 0003-9942. ; 65:8, s. 1083-90
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Myosin is a molecular motor and the essential part of the thick filament of striated muscle. The expression of myosin heavy-chain (MyHC) isoforms is developmentally regulated. The embryonic isoform encoded from MYH3 (OMIM *160720) is expressed during fetal life. Recently, mutations in MYH3 were demonstrated to be associated with congenital joint contractures, that is, Freeman-Sheldon and Sheldon-Hall syndromes, which are both distal arthrogryposis syndromes. Mutations in other MyHC isoforms cause myopathy. It is unknown whether MYH3 mutations cause myopathy because muscle tissue has not been studied. OBJECTIVES: To determine whether novel MYH3 mutations are associated with distal arthrogryposis and to demonstrate myopathic changes in muscle biopsy specimens from 4 patients with distal arthrogryposis and MYH3 mutations. DESIGN: In a cohort of patients with distal arthrogryposis, we analyzed the entire coding sequence of MYH3. Muscle biopsy specimens were obtained, and in addition to morphologic analysis, the expression of MyHC isoforms was investigated at the protein and transcript levels. RESULTS: We identified patients from 3 families with novel MYH3 mutations. These mutations affect developmentally conserved residues that are located in different regions of the adenosine triphosphate-binding pocket of the MyHC head. The embryonic (MYH3) isoform was not detected in any of the muscle biopsy samples, indicating a normal developmental downregulation of MYH3 in these patients. However, morphologic analysis of muscle biopsy specimens from the 4 patients revealed mild and variable myopathic features and a pathologic upregulation of the fetal MyHC isoform (MYH8) in 1 patient. CONCLUSIONS: Distal arthrogryposis associated with MYH3 mutations is secondary to myosin myopathy, and postnatal muscle manifestations are variable.
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| 10. |
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