| 11. |
- Fagman, Johan Bourghardt, 1980, et al.
(författare)
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Androgen receptor-dependent and independent atheroprotection by testosterone in male mice.
- 2010
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Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 151:11, s. 5428-37
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Tidskriftsartikel (refereegranskat)abstract
- The atheroprotective effect of testosterone is thought to require aromatization of testosterone to estradiol, but no study has adequately addressed the role of the androgen receptor (AR), the major pathway for the physiological effects of testosterone. We used AR knockout (ARKO) mice on apolipoprotein E-deficient background to study the role of the AR in testosterone atheroprotection in male mice. Because ARKO mice are testosterone deficient, we sham operated or orchiectomized (Orx) the mice before puberty, and Orx mice were supplemented with placebo or a physiological testosterone dose. From 8 to 16 wk of age, the mice consumed a high-fat diet. In the aortic root, ARKO mice showed increased atherosclerotic lesion area (+80%, P < 0.05). Compared with placebo, testosterone reduced lesion area both in Orx wild-type (WT) mice (by 50%, P < 0.001) and ARKO mice (by 24%, P < 0.05). However, lesion area was larger in testosterone-supplemented ARKO compared with testosterone-supplemented WT mice (+57%, P < 0.05). In WT mice, testosterone reduced the presence of a necrotic core in the plaque (80% among placebo-treated vs. 12% among testosterone-treated mice; P < 0.05), whereas there was no significant effect in ARKO mice (P = 0.20). In conclusion, ARKO mice on apolipoprotein E-deficient background display accelerated atherosclerosis. Testosterone treatment reduced atherosclerosis in both WT and ARKO mice. However, the effect on lesion area and complexity was more pronounced in WT than in ARKO mice, and lesion area was larger in ARKO mice even after testosterone supplementation. These results are consistent with an AR-dependent as well as an AR-independent component of testosterone atheroprotection in male mice.
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| 12. |
- Fagman, Johan Bourghardt, 1980, et al.
(författare)
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The androgen receptor confers protection against diet-induced atherosclerosis, obesity, and dyslipidemia in female mice.
- 2015
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Ingår i: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - : Wiley. - 1530-6860 .- 0892-6638. ; 29:4, s. 1540-1550
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Tidskriftsartikel (refereegranskat)abstract
- Androgens have important cardiometabolic actions in males, but their metabolic role in females is unclear. To determine the physiologic androgen receptor (AR)-dependent actions of androgens on atherogenesis in female mice, we generated female AR-knockout (ARKO) mice on an atherosclerosis-prone apolipoprotein E (apoE)-deficient background. After 8 weeks on a high-fat diet, but not on a normal chow diet, atherosclerosis in aorta was increased in ARKO females (+59% vs. control apoE-deficient mice with intact AR gene). They also displayed increased body weight (+18%), body fat percentage (+62%), and hepatic triglyceride levels, reduced insulin sensitivity, and a marked atherogenic dyslipidemia (serum cholesterol, +52%). Differences in atherosclerosis, body weight, and lipid levels between ARKO and control mice were abolished in mice that were ovariectomized before puberty, consistent with a protective action of ovarian androgens mediated via the AR. Furthermore, the AR agonist dihydrotestosterone reduced atherosclerosis (-41%; thoracic aorta), subcutaneous fat mass (-44%), and cholesterol levels (-35%) in ovariectomized mice, reduced hepatocyte lipid accumulation in hepatoma cells in vitro, and regulated mRNA expression of hepatic genes pivotal for lipid homeostasis. In conclusion, we demonstrate that the AR protects against diet-induced atherosclerosis in female mice and propose that this is mediated by modulation of body composition and lipid metabolism.-Fagman, J. B., Wilhelmson, A. S., Motta, B. M., Pirazzi, C., Alexanderson, C., De Gendt, K., Verhoeven, G., Holmäng, A., Anesten, F., Jansson, J. -O., Levin, M., Borén, J., Ohlsson, C., Krettek, A., Romeo, S., Tivesten, A. The androgen receptor confers protection against diet-induced atherosclerosis, obesity, and dyslipidemia in female mice.
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| 13. |
- Gustafsson, Susanne, et al.
(författare)
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Long-term outcome for ADL following the health-promoting RCT-Elderly persons in the risk zone
- 2013
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Ingår i: The Gerontologist. - : Oxford University Press. - 0016-9013 .- 1758-5341. ; 53:4, s. 654-663
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To examine independence in activities of daily living (ADL) at the 1- and 2-year followups of the health-promoting study Elderly Persons in the Risk Zone. Design and Method: A randomized, three-armed, single-blind, and controlled study. A representative sample of 459 independent and community-dwelling older adults, 80 years and older, were included. A preventive home visit was compared with four weekly multiprofessional senior group meetings including a follow-up home visit. Results: Analysis showed a significant difference in favor of the senior meetings in postponing dependence in ADL at the 1-year follow-up (odds ratio [OR] = 1.92, 95% confidence interval [CI] = 1.19-3.10) and also in reducing dependence in three (OR = 0.52, 95% CI = 0.31-0.86) and four or more ADL (OR = 0.40, 95% CI = 0.22-0.72) at the 2-year follow-up. A preventive home visit reduced dependence in two (OR = 0.40, 95% CI = 0.24-0.68) and three or more ADL (OR = 0.37, 95% CI = 0.17-0.80) after 1 year. Implications: A long-term evaluation of Elderly Persons in the Risk Zone showed that both senior meetings and a preventive home visit reduced the extent of dependence in ADL after 1 year. The senior meetings were superior to a preventive home visit since additional significant effects were seen after 2 years. To further enhance the long-term effects of the senior meetings and support the process of self-change in health behavior, it is suggested that booster sessions might be a good way of reinforcing the intervention.
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| 14. |
- Johansson, K, et al.
(författare)
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Selection for egg shell strength in laying hens using shell membrane characteristics
- 1996
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Ingår i: BRITISH POULTRY SCIENCE. - : CARFAX PUBL CO. - 0007-1668. ; 37:4, s. 757-763
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- 1. Divergent selection for attachment strength between the shell membrane and the calcium shell was performed in a white Leghorn strain. Multivariate analysis was used to estimate genetic parameters for shell membrane measurements and shell thickness. The
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| 15. |
- Lee, Po-Shun, et al.
(författare)
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mTORC1-S6K activation by endotoxin contributes to cytokine up-regulation and early lethality in animals.
- 2010
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- mTORC1 (mammalian target of rapamycin complex 1) activation has been demonstrated in response to endotoxin challenge, but the mechanism and significance are unclear. We investigated the effect of mTORC1 suppression in an animal model of endotoxemia and in a cellular model of endotoxin signaling.Mice were treated with the mTORC1 inhibitor rapamycin or vehicle prior to lethal endotoxin challenge. Mortality and cytokine levels were assessed. Cultured macrophage-like cells were challenged with endotoxin with or without inhibitors of various pathways known to be upstream of mTORC1. Activated pathways, including downstream S6K pathway, were assessed by immunoblots. We found that mTORC1-S6K suppression by rapamycin delayed mortality of mice challenged with lethal endotoxin, and was associated with dampened circulating levels of VEGF, IL-1β, IFN-γ and IL-5. Furthermore, in vitro cellular studies demonstrated that LPS (lipopolysaccharide) activation of mTORC1-S6K still occurs in the presence of PI3K-Akt inhibition alone, but can be suppressed by concurrent inhibition of PI3K-Akt and MEK-ERK pathways.We conclude that cellular activation of mTORC1-S6K contributes to cytokine up-regulation and mortality in response to endotoxin, and may occur via multiple pathways.
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| 16. |
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| 17. |
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| 18. |
- Sondergaard, E., et al.
(författare)
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ERG Controls B Cell Development by Promoting Igh V-to-DJ Recombination
- 2019
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 29:9
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Tidskriftsartikel (refereegranskat)abstract
- B cell development depends on the coordinated expression and cooperation of several transcription factors. Here we show that the transcription factor ETS-related gene (ERG) is crucial for normal B cell development and that its deletion results in a substantial loss of bone marrow B cell progenitors and peripheral B cells, as well as a skewing of splenic B cell populations. We find that ERG-deficient B lineage cells exhibit an early developmental block at the pre-B cell stage and proliferate less. The cells fail to express the immunoglobulin heavy chain due to inefficient V-to-DJ recombination, and cells that undergo recombination display a strong bias against incorporation of distal V gene segments. Furthermore, antisense transcription at PAX5-activated intergenic repeat (PAIR) elements, located in the distal region of the Igh locus, depends on ERG. These findings show that ERG serves as a critical regulator of B cell development by ensuring efficient and balanced V-to-DJ recombination.
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| 19. |
- Stubelius, Alexandra, 1983, et al.
(författare)
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Sexual dimorphisms in the immune system of catechol-O-methyltransferase knockout mice
- 2012
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Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985. ; 217:8, s. 751-760
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Tidskriftsartikel (refereegranskat)abstract
- The enzyme catechol-O-methyltransferase (COMT) is part of the metabolic pathway of 17 beta-estradiol, converting 2-hydroxyestradiol to 2-methoxyestradiol. We recently showed that administration of the COMT product 2-methoxyestradiol has anti-inflammatory and anti-osteoporotic effects. We have now investigated whether COMT affects the immune system, by immunologically phenotyping COMT deficient (COMT-/-) mice. Immunoglobulin production, T lymphocyte proliferation, NK cell cytotoxicity and oxygen radical production were assessed. In male COMT-/--mice, the total number of T-, and B-lymphocytes from spleen increased but the T-cell proliferative response decreased. The NK cell population shifted toward less mature cells, leaving cytotoxic capacity unaffected. In COMT-/--females, a higher frequency of neutrophils was found but the oxygen radical production was unaltered. In conclusion, only minor changes of the immune system were seen in COMT deficient mice, and the changes were usually seen in males. This study provides clues into how COMT activity, and hence gender differences, affects the immune system. (c) 2012 Elsevier GmbH. All rights reserved.
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| 20. |
- Tufvesson, M., et al.
(författare)
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Selection for sexual male characters and their effects on other fitness related traits in white leghorn chickens
- 1999
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Ingår i: Journal of Animal Breeding and Genetics. - : Wiley. - 0931-2668. ; 116:2, s. 127-138
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Tidskriftsartikel (refereegranskat)abstract
- The size and shape of the cockerel comb, ran be regarded as secondary sexual characters or sexual ornaments. Sexual characters are assumed to be costly to express and the expression of a secondary sexual character is suggested to be favourably correlated with the bearer's condition or fitness. The aim of this study was to clarify the effects of selection for male sexual characters, the correlated responses in other male traits and whether selection for sexual characters affects viability. Two selection lines (lines S and H) and a control line was used for 10 generations. Line S was selected for male comb size at 29 weeks of age and from generation six onwards, comb shape (the way the cockerel bear his comb) was added. Line H was selected for high concentration of hyaluronic acid (HA) in the comb at 28 weeks of age. The average number of animals of each sex and;election line was 560 and the randomly mated control line comprised an average of 150 animals of each sex per generation. Traits recorded an analysed were comb size (CS) and body weight (BW) at 29 weeks of age, comb shape (SH) at 32 weeks of age, comb weight (CW) after slaughter and mortality (M). In line S, the genetic and phenotypic trends increased for CS, CW and BW. Both CS and SH are traits involved in the impression of comb size as visualized by females during male choice and by males during male-male competition. With artificial upward selection for the male character CS (line S), CS, CW, BW and M also increased but SH was impaired. When adding SH to the selection criteria in line S, the negative generic trend for SH was changed to positive. As CS approaches its environmental limit, the heritability and genetic progress can be expected to decline. It seems that 10 generations of selection for increased CS is not enough to reach the environmental limit at which CS is expected to stabilize at an optimum size determined by natural selection.
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