| 1. |
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| 2. |
- Chondronikola, M., et al.
(author)
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Brown Adipose Tissue Improves Whole-Body Glucose Homeostasis and Insulin Sensitivity in Humans
- 2014
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 63:12, s. 4089-4099
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Journal article (peer-reviewed)abstract
- Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic tissue owing to its ability to dissipate energy as heat. Despite a plethora of data concerning the role of BAT in glucose metabolism in rodents, the role of BAT (if any) in glucose metabolism in humans remains unclear. To investigate whether BAT activation alters whole-body glucose homeostasis and insulin sensitivity in humans, we studied seven BAT-positive (BAT(+)) men and five BAT-negative (BAT(-)) men under thermoneutral conditions and after prolonged (5-8 h) cold exposure (CE). The two groups were similar in age, BMI, and adiposity. CE significantly increased resting energy expenditure, whole-body glucose disposal, plasma glucose oxidation, and insulin sensitivity in the BAT+ group only. These results demonstrate a physiologically significant role of BAT in whole-body energy expenditure, glucose homeostasis, and insulin sensitivity in humans, and support the notion that BAT may function as an antidiabetic tissue in humans.
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| 3. |
- Gnad, T., et al.
(author)
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Adenosine activates brown adipose tissue and recruits beige adipocytes via A(2A) receptors
- 2014
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 516:7531
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Journal article (peer-reviewed)abstract
- Brown adipose tissue (BAT) is specialized in energy expenditure, making it a potential target for anti-obesity therapies(1-5). Following exposure to cold, BAT is activated by the sympathetic nervous system with concomitant release of catecholamines and activation of beta-adrenergic receptors(1-5). Because BAT therapies based on cold exposureor beta-adrenergic agonists are clinically not feasible, alternative strategies must be explored. Purinergic co-transmission might be involved in sympathetic control of BAT and previous studies reported inhibitory effects of the purinergic transmitter adenosine in BAT from hamster or rat(6-8). However, the role of adenosine in human BAT is unknown. Here we show that adenosine activates human and murine brown adipocytes at low nanomolar concentrations. Adenosine is released in BAT during stimulation of sympathetic nerves as well as from brown adipocytes. The adenosine A(2A) receptor is the most abundant adenosine receptor in human and murine BAT. Pharmacological blockade or genetic loss of A(2A) receptors in mice causes adecrease in BAT-dependent thermogenesis, whereas treatment with A(2A) agonists significantly increases energy expenditure. Moreover, pharmacological stimulation of A(2A) receptors or injection of lentiviral vectors expressing the A(2A) receptor into white fat induces brown-like cells-so-called beige adipocytes. Importantly, mice fed a high-fat diet and treated with an A(2A) agonist are leaner with improved glucose tolerance. Taken together, our results demonstrate that adenosine-A(2A) signalling plays an unexpected physiological role in sympathetic BAT activation and protects mice from diet-induced obesity. Those findings reveal new possibilities for developing novel obesity therapies.
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| 4. |
- Henriksen, Egil, et al.
(author)
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Echocardiographic right and left ventricular measurements in male elite endurance athletes
- 1996
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 17:7, s. 1121-1128
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Journal article (peer-reviewed)abstract
- Echocardiography was used to assess normal values in the right and left ventricular cavity and wall in 127 male elite endurance athletes. M-mode and two dimensional measurements of left ventricle and left and right atria were also obtained. All subjects were high-performance orienteers, cross-country skiers and middle-distance runners. They all had a normal electrocardiogram at rest and no echocardiographic evidence of heart disease. With the use of multiple right ventricular cross-sections and two-dimensional measurements, we found a significantly greater right ventricular inflow tract and right and left atrial measurements in endurance athletes compared with earlier studies of normal, active subjects. The right ventricular free wall was slightly thicker than reported in normal active subjects but the differences were small. Left ventricular diastolic diameter was consistent with previous reports of endurance athletes. Of the 127 subjects, 13% had left ventricular wall thickness above 13 mm but none of the athletes had wall thickness above 15 mm. These data suggest that cardiac enlargement occurs symmetrically in both right and left cavities, probably reflecting increased haemodynamic loading, a mechanism by which athletes sustain a high cardiac output during exercise.
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| 5. |
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| 6. |
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| 7. |
- Godl, Klaus, et al.
(author)
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The N terminus of the MUC2 mucin forms trimers that are held together within a trypsin-resistant core fragment.
- 2002
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In: The Journal of biological chemistry. - 0021-9258 .- 1083-351X. ; 277:49, s. 47248-56
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Journal article (peer-reviewed)abstract
- The N terminus of the human MUC2 mucin (amino acids 1-1397) has been expressed as a recombinant tagged protein in Chinese hamster ovary cells. The intracellular form was found to be an endoglycosidase H-sensitive monomer, whereas the secreted form was an oligomer that gave monomers upon disulfide bond reduction. The secreted MUC2 N terminus contained a trypsin-resistant core fragment. Edman sequencing and mass spectrometry of the peptides obtained localized this core fragment to the C-terminal end of the recombinant protein. This core retained its oligomeric nature with an apparent mass of approximately 240 kDa. Upon reduction, peptides of approximately 85 kDa were found, suggesting that the N terminus forms trimers. This interpretation was also supported by gel electrophoresis and gel filtration of the intact MUC2 N terminus. Electron microscopy revealed three globular domains each linked via an extended and flexible region to a central part in a trefoil-like manner. Immunostaining with gold-labeled antibodies localized the N-terminal end to the three globular structures, and the antibodies directed against the Myc and green fluorescent protein tags attached at the C terminus localized these to the stalk side of the central trefoil. The N terminus of the MUC2 mucin is thus assembled into trimers that contain proteolytically stable parts, suggesting that MUC2 can only be partly degraded by intestinal proteases and thus is able to maintain a mucin network protecting the intestine.
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| 8. |
- Hansson, Gunnar C., 1951, et al.
(author)
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Biosynthesis and Secretion of Mucins, Especially the MUC2 Mucin, in Relation to Cystic Fibrosis
- 2005
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In: Advances in Experimental Medicine and Biology. - Göteborg : Springer US. - 9780387230764 ; , s. 169-178
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Book chapter (other academic/artistic)abstract
- The typical CF symptoms with viscous and trapped mucus are still lacking a full explanation. Here we suggest that the CF mucus become sticky and adherent to the epithelial cells by a covalent attachment of MUC2 and MUC5AC. We also suggest that the expression of MUC2 in the lungs could contribute to the CF phenotype. However, there are several unanswered questions before these suggestions can be proved. Among the most urgent ones are to show to what molecules the generated anhydride can attach or if the anhydride only has been hydrolyzed. Once this and other questions have been answered, one can start to address potential therapeutic approaches using recent advances in mucin knowledge.
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| 9. |
- Henriksen, Egil, et al.
(author)
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An echocardiographic study comparing male Swedish elite orienteers with other elite endurance athletes
- 1997
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In: American Journal of Cardiology. - 0002-9149 .- 1879-1913. ; 79:4, s. 521-524
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Journal article (peer-reviewed)abstract
- Between 1979 and 1992, there were 16 known cases of sudden unexpected cardiac death among young Swedish orienteers, whose autopsies showed myocarditis to be a common finding. Therefore, 96 elite orienteers and 47 controls underwent echocardiography, showing left ventricular wall motion abnormalities in 9% of the orienteers compared with 4% in the controls.
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| 10. |
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| 11. |
- Jonsson, Maria, et al.
(author)
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St depression at caesarean section and the relation to oxytocin dose : a randomised controlled trial
- 2010
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In: BJOG : an international journal of obstetrics and gynaecology. - : Wiley. - 1470-0328. ; 117:1, s. 76-83
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Journal article (peer-reviewed)abstract
- Objective To investigate whether there is a difference in occurrence of electrocardiogram changes suggestive of myocardial ischaemia between two different doses of oxytocin. Design Double-blind randomised controlled trial Setting University hospital in Sweden. Population A total of 103 healthy women undergoing elective caesarean section under spinal anaesthesia. Methods The participants were randomised to 5 or 10 units of oxytocin, given as an intravenous bolus. A Holter monitor was used to record electrocardiograms and non invasive blood pressure and heart rate (HR) was monitored. A blood sample was obtained 12-hour postoperatively. Main outcome measures Depression of the ST segment. Secondary outcomes: symptoms, Troponon I levels, mean arterial pressure (MAP), HR and blood loss. Results There was a significant difference in occurrence of ST depressions associated with oxytocin administration, 4 (7.7%) with 5 and 11 (21.6%) with 10 units, P < 0.05. The absolute risk reduction was 13.9% (95% confidence interval, 0.5-27.3). Decrease of mean MAP from baseline to 2 minutes differed, being 9 mmHg in the 5 unit group and 17 mmHg in the 10 unit group (P < 0.01). The increase in mean HR did not differ. Troponin I levels were increased in four subjects (3.9%). There were no differences in occurrence of symptoms, Troponin I levels, or estimated blood loss. Conclusion ST depressions were associated with oxytocin administration significantly more often in subjects receiving 10 units compared with 5 units. Interventions to prevent hypotension during caesarean section may reduce the occurrence of ST depressions on electrocardiograms.
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| 12. |
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| 13. |
- Lasar, D., et al.
(author)
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Peroxisome Proliferator Activated Receptor Gamma Controls Mature Brown Adipocyte Inducibility through Glycerol Kinase
- 2018
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 22:3, s. 760-773
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Journal article (peer-reviewed)abstract
- Peroxisome proliferator-activated receptors (PPARs) have been suggested as the master regulators of adipose tissue formation. However, their role in regulating brown fat functionality has not been resolved. To address this question, we generated mice with inducible brown fat-specific deletions of PPAR alpha, beta/delta, and gamma, respectively. We found that both PPARa and beta/delta are dispensable for brown fat function. In contrast, we could show that ablation of PPAR gamma in vitro and in vivo led to a reduced thermogenic capacity accompanied by a loss of inducibility by beta-adrenergic signaling, as well as a shift from oxidative fatty acid metabolism to glucose utilization. We identified glycerol kinase (Gyk) as a partial mediator of PPAR gamma function and could show that Gyk expression correlates with brown fat thermogenic capacity in human brown fat biopsies. Thus, Gyk might constitute the link between PPAR gamma-mediated regulation of brown fat function and activation by b-adrenergic signaling.
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| 14. |
- Lidell, Anton, et al.
(author)
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The Current and Future Challenges for Virtual Commissioning and Digital Twins of Production Lines
- 2022
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In: SPS2022. - Amsterdam; Berlin; Washington, DC : IOS Press. - 9781643682686 - 9781643682693 ; , s. 508-519
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Conference paper (peer-reviewed)abstract
- The use of virtual commissioning has increased in the last decade, but there are still challenges before the software code validation method is widespread in use. One of the extensions to virtual commissioning is the digital twin technology to allow for further improved accuracy. The aim of this paper is to review existing standards and approaches to developing virtual commissioning, through a literature review and interviews with experts in the industry. First, the definitions and classifications related to virtual commissioning and digital twins are reviewed, followed by, the approaches for the development of virtual commissioning and digital twins reported in the literature are explored. Then, in three interviews with experts of varying backgrounds and competencies, the views of the virtual technologies are assessed to provide new insight for the industry. The findings of the literature review and interviews are, among others, the apparent need for standardisation in the field and that a sought-after standard in the form of ISO 23247-1 is underway. The key finding of this paper is that digital twin is a concept with a promising future in combination with other technologies of Industry 4.0. We also outline the challenges and possibilities of virtual commissioning and the digital twin and could be used as a starting point for further research in standardisations and improvements sprung from the new standard.
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| 15. |
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| 16. |
- Lidell, Martin, 1970, et al.
(author)
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An autocatalytic cleavage in the C terminus of the human MUC2 mucin occurs at the low pH of the late secretory pathway.
- 2003
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In: The Journal of biological chemistry. - 0021-9258. ; 278:16, s. 13944-51
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Journal article (peer-reviewed)abstract
- During purification of a recombinant MUC2 C terminus expressed in CHO-K1 cells, the protein was partly cleaved when buffers with a pH of 6.0 were used. When buffers with higher pH values were used, less cleavage was found. Disulfide bonds held the two fragments generated together as these were only observed after reduction. Edman sequencing of the C-terminal 110-kDa fragment revealed that the cleavage had occurred at an Asp-Pro bond, a site described previously to generate the so-called "link peptide" after disulfide bond reduction. In vitro studies on the conditions for cleavage showed that it occurred in a time-dependent manner at a pH below 6.0. Furthermore, the reaction was not enzyme-mediated as it occurred in pure preparations of the MUC2 C terminus and was not inhibited by protease inhibitors. When expressed in the mucin producing cell line LS 174T, the C terminus was cleaved to a higher extent compared with the CHO-K1 cells. Neutralizing the secretory pathway with either NH(4)Cl or bafilomycin A1 inhibited this cleavage. Altogether, our results suggest that the cleavage is an autocatalytic reaction that occurs in the acidic environment of the late secretory pathway. Furthermore, the cleavage produced a new, reactive C terminus that has the potential to attach the mucin to itself or other molecules. Because a pH below 6 can be reached in the late secretory pathway and on mucosal surfaces, the cleavage and possible cross-linking are likely to be of biological importance.
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| 17. |
- Lidell, Martin, 1970, et al.
(author)
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Cleavage in the GDPH sequence of the C-terminal cysteine-rich part of the human MUC5AC mucin.
- 2006
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In: The Biochemical journal. - 1470-8728. ; 399:1, s. 121-9
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Journal article (peer-reviewed)abstract
- MUC5AC is the main gel-forming mucin expressed by goblet cells of the airways and stomach where it protects the underlying epithelia. We expressed the C-terminal cysteine-rich part of the human MUC5AC mucin in CHO-K1 cells (Chinese-hamster ovary K1 cells) where it formed disulfide-linked dimers in the ER (endoplasmic reticulum). After reducing the disulfide bonds of these dimers, not only the expected monomers were found, but also two smaller fragments, indicating that the protein was partially cleaved. The site of cleavage was located at an Asp-Pro bond situated in a GDPH (Gly-Asp-Pro-His) sequence found in the vWD4 (von Willebrand D4) domain. This sequence is also found in the human MUC2 mucin, previously shown to be cleaved at the same site by a slow, non-enzymatic process triggered by a pH below 6 [Lidell, Johansson and Hansson (2003) J. Biol. Chem. 278, 13944-13951]. In contrast with this, the cleavage of MUC5AC started already in the neutral ER. However, it continued and was slightly accelerated at a pH below 6.5, a pH found in the later parts of the secretory pathway. The cleavage generated a reactive group in the new C-terminus that could link the protein to a primary amine. No cleavage of MUC5AC has so far been reported. By using an antibody reacting with the C-terminal cleavage fragment, we could verify that the cleavage occurs in wild-type MUC5AC produced by HT-29 cells. The cleavage of MUC5AC and the generation of the reactive new C-terminus could contribute to the adherent and viscous mucus found at chronic lung diseases such as asthma and cystic fibrosis, characterized by mucus hypersecretion and lowered pH of the airways.
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| 18. |
- Lidell, Martin, 1970, et al.
(author)
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Entamoeba histolytica cysteine proteases cleave the MUC2 mucin in its C-terminal domain and dissolve the protective colonic mucus gel.
- 2006
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 103:24, s. 9298-303
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Journal article (peer-reviewed)abstract
- In order for the protozoan parasite Entamoeba histolytica (E.h.) to cause invasive intestinal and extraintestinal infection, which leads to significant morbidity and mortality, it must disrupt the protective mucus layer by a previously unknown mechanism. We hypothesized that cysteine proteases secreted from the amoeba disrupt the mucin polymeric network, thereby overcoming the protective mucus barrier. The MUC2 mucin is the major structural component of the colonic mucus gel. Heavily O-glycosylated and protease-resistant mucin domains characterize gel-forming mucins. Their N- and C-terminal cysteine-rich domains are involved in mucin polymerization, and these domains are likely to be targeted by proteases because they are less glycosylated, thereby exposing their peptide chains. By treating recombinant cysteine-rich domains of MUC2 with proteases from E.h. trophozoites, we showed that the C-terminal domain was specifically targeted at two sites by cysteine proteases, whereas the N-terminal domain was resistant to proteolysis. The major cleavage site is predicted to depolymerize the MUC2 polymers, thereby disrupting the protective mucus gel. The ability of the cysteine proteases to dissolve mucus gels was confirmed by treating mucins from a MUC2-producing cell line with amoeba proteases. These findings suggest a major role for E.h. cysteine proteases in overcoming the protective mucus barrier in the pathogenesis of invasive amoebiasis. In this report, we identify a specific cleavage mechanism used by an enteric pathogen to disrupt the polymeric nature of the mucin gel.
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| 19. |
- Lidell, Martin, 1970, et al.
(author)
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Mapping of the 45M1 epitope to the C-terminal cysteine-rich part of the human MUC5AC mucin.
- 2008
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In: The FEBS journal. - : Wiley. - 1742-464X. ; 275:3, s. 481-9
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Journal article (peer-reviewed)abstract
- Mucins are large glycoproteins protecting mucosal surfaces throughout the body. Their expressions are tissue-specific, but in disease states such as cystic fibrosis, inflammation and cancer, this specificity can be disturbed. MUC5AC is normally expressed in the mucous cells of the epithelia lining the stomach and the trachea, where it constitutes a major component of the gastric and respiratory mucus. A number of mAbs have been raised against the gastric M1 antigen, an early marker for colonic carcinogenesis. Several of these mAbs recognize epitopes present on MUC5AC, suggesting that MUC5AC is the antigen. However, some of the mAbs raised against the gastric M1 antigen are widely used as antibodies against MUC5AC, despite the fact that their specificity for MUC5AC has not been clearly shown. In this study, we have tested the reactivity of the latter antibodies against a recombinantly expressed C-terminal cysteine-rich part of human MUC5AC. We demonstrate for the first time that the widely used mAb 45M1, as well as 2-12M1 and 166M1, are true antibodies against MUC5AC, with epitopes located in the C-terminal cysteine-rich part of the mucin.
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| 20. |
- Lidell, Martin, 1970, et al.
(author)
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The recombinant C-terminus of the human MUC2 mucin forms dimers in Chinese-hamster ovary cells and heterodimers with full-length MUC2 in LS 174T cells.
- 2003
-
In: The Biochemical journal. - 0264-6021. ; 372:Pt 2, s. 335-45
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Journal article (peer-reviewed)abstract
- The entire cDNA corresponding to the C-terminal cysteine-rich domain of the human MUC2 apomucin, after the serine- and threonine-rich tandem repeat, was expressed in Chinese-hamster ovary-K1 cells and in the human colon carcinoma cell line, LS 174T. The C-terminus was expressed as a fusion protein with the green fluorescent protein and mycTag sequences and the murine immunoglobulin kappa-chain signal sequence to direct the protein to the secretory pathway. Pulse-chase studies showed a rapid conversion of the C-terminal monomer into a dimer in both Chinese-hamster ovary-K1 and LS 174T cells. Disulphide-bond-stabilized dimers secreted into the media of both cell lines had a higher apparent molecular mass compared with the intracellular forms. The MUC2 C-terminus was purified from the spent culture medium and visualized by molecular electron microscopy. The dimer nature of the molecule was visible clearly and revealed that each monomer was attached to the other by a large globular domain. Gold-labelled antibodies against the mycTag or green fluorescent protein revealed that these were localized to the ends opposite to the parts responsible for the dimerization. The C-terminus expressed in LS 174T cells formed heterodimers with the full-length wild-type MUC2, but not with the MUC5AC mucin, normally expressed in LS 174T cells. The homodimers of the MUC2 C-termini were secreted continuously from the LS 174T cells, but no wild-type MUC2 secretion has been observed from these cells. This suggests that the information for sorting the MUC2 mucin into the regulated secretory pathway in cells having this ability is present in parts other than the C-terminus of MUC2.
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| 21. |
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| 22. |
- Perdikari, A., et al.
(author)
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BATLAS: Deconvoluting Brown Adipose Tissue
- 2018
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 25:3
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Journal article (peer-reviewed)abstract
- Recruitment and activation of thermogenic adipocytes have received increasing attention as a strategy to improve systemic metabolic control. The analysis of brown and brite adipocytes is complicated by the complexity of adipose tissue biopsies. Here, we provide an in-depth analysis of pure brown, brite, and white adipocyte transcriptomes. By combining mouse and human transcriptome data, we identify a gene signature that can classify brown and white adipocytes in mice and men. Using a machine-learning-based cell deconvolution approach, we develop an algorithm proficient in calculating the brown adipocyte content in complex human and mouse biopsies. Applying this algorithm, we can show in a human weight loss study that brown adipose tissue (BAT) content is associated with energy expenditure and the propensity to lose weight. This online available tool can be used for in-depth characterization of complex adipose tissue samples and may support the development of therapeutic strategies to increase energy expenditure in humans.
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| 23. |
- Pham, T. T., et al.
(author)
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Human Bone Marrow Adipose Tissue is a Metabolically Active and Insulin-Sensitive Distinct Fat Depot
- 2020
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In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 105:7, s. 2300-2310
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Journal article (peer-reviewed)abstract
- CONTEXT: Bone marrow (BM) in adult long bones is rich in adipose tissue, but the functions of BM adipocytes are largely unknown. We set out to elucidate the metabolic and molecular characteristics of BM adipose tissue (BMAT) in humans. OBJECTIVE: Our aim was to determine if BMAT is an insulin-sensitive tissue, and whether the insulin sensitivity is altered in obesity or type 2 diabetes (T2DM). DESIGN: This was a cross-sectional and longitudinal study. SETTING: The study was conducted in a clinical research center. PATIENTS OR OTHER PARTICIPANTS: Bone marrow adipose tissue glucose uptake (GU) was assessed in 23 morbidly obese subjects (9 with T2DM) and 9 healthy controls with normal body weight. In addition, GU was assessed in another 11 controls during cold exposure. Bone marrow adipose tissue samples for molecular analyses were collected from non-DM patients undergoing knee arthroplasty. INTERVENTION(S): Obese subjects were assessed before and 6 months after bariatric surgery and controls at 1 time point. MAIN OUTCOME MEASURE: We used positron emission tomography imaging with 2-[18F]fluoro-2-deoxy-D-glucose tracer to characterize GU in femoral and vertebral BMAT. Bone marrow adipose tissue molecular profile was assessed using quantitative RT-PCR. RESULTS: Insulin enhances GU in human BMAT. Femoral BMAT insulin sensitivity was impaired in obese patients with T2DM compared to controls, but it improved after bariatric surgery. Furthermore, gene expression analysis revealed that BMAT was distinct from brown and white adipose tissue. CONCLUSIONS: Bone marrow adipose tissue is a metabolically active, insulin-sensitive and molecularly distinct fat depot that may play a role in whole body energy metabolism. © Endocrine Society 2020.
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| 24. |
- Romu, Thobias, et al.
(author)
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A randomized trial of cold-exposure on energy expenditure and supraclavicular brown adipose tissue volume in humans
- 2016
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In: Metabolism-Clinical and Experimental. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 65:6, s. 926-934
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Journal article (peer-reviewed)abstract
- Objective. To study if repeated cold-exposure increases metabolic rate and/or brown adipose tissue (BAT) volume in humans when compared with avoiding to freeze. Design. Randomized, open, parallel-group trial. Methods. Healthy non-selected participants were randomized to achieve cold-exposure 1 hour/day, or to avoid any sense of feeling cold, for 6 weeks. Metabolic rate (MR) was measured by indirect calorimetry before and after acute cold-exposure with cold vests and ingestion of cold water. The BAT volumes in the supraclavicular region were measured with magnetic resonance imaging (MRI). Results. Twenty-eight participants were recruited, 12 were allocated to controls and 16 to cold-exposure. Two participants in the cold group dropped out and one was excluded. Both the non-stimulated and the cold-stimulated MR were lowered within the group randomized to avoid cold (MR at room temperature from 1841 +/- 199 kCal/24 h to 1795 +/- 213 kCal/24 h, p = 0.047 cold-activated MR from 1900 +/- 150 kCal/24 h to 1793 +/- 215 kCal/24 h, p = 0.028). There was a trend towards increased MR at room temperature following the intervention in the cold-group (p = 0.052). The difference between MR changes by the interventions between groups was statistically significant (p = 0.008 at room temperature, p = 0.032 after cold-activation). In an on-treatment analysis after exclusion of two participants that reported >= 8 days without cold-exposure, supraclavicular BAT volume had increased in the cold-exposure group (from 0.0175 +/- 0.015 1 to 0.0216 +/- 0.014 1, p = 0.049). Conclusions. We found evidence for plasticity in metabolic rate by avoiding to freeze compared with cold-exposure in a randomized setting in non-selected humans.
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| 25. |
- Sihlbom, Carina, 1973, et al.
(author)
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Localization of O-glycans in MUC1 glycoproteins using electron-capture dissociation fragmentation mass spectrometry.
- 2009
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In: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 19:4, s. 375-81
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Journal article (peer-reviewed)abstract
- MUC1 is a mucin glycoprotein containing multiple tandem repeats of 20 amino acids, with five serines and threonines that can be O-glycosylated. Here, we investigated the O-glycosylation site occupancy in MUC1 glycoproteins produced in two mutant CHO cell lines, Lec3.2.8.1 and ldlD. We found that the average site occupancy was higher in MUC1 from Lec3.2.8.1 than from ldlD and that the occupancy increased with the number of tandem repeats in the protein and also depended on the culture conditions used for production. Moreover, we describe the successful use of electron-capture dissociation (ECD) fragmentation, coupled to online liquid chromatography mass spectrometry, to determine the glycosylation of individual sites in recombinant MUC1 proteins with 16 tandem repeats. We analyzed MUC1 tandem repeat peptides with 1-5 GalNAc residues by ECD fragmentation and found that the first site to be glycosylated was either Ser-5 or Thr-6, with the addition of a second GalNAc at Thr-14. For peptides with three GalNAc residues, several different variants of glycopeptides were found, indicating a heterogeneous order of glycosylation at this stage. In contrast, only one variant was found for peptides with four GalNAc residues, where Thr-19 in the PDTR motif was left unglycosylated, indicating that this site is glycosylated last. The results gave novel insight into the order of GalNAc substitution in MUC1 in vivo.
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