| 1. |
- Agudelo, Leandro Z
(författare)
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Skeletal muscle PGC-1α1 and KAT enzymes at the intersection between depression and metabolic disease
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Depression and metabolic diseases are leading causes of disability and major contributors to socioeconomic burden worldwide. Physical activity exerts many beneficial effects that confer direct health improvement in individuals suffering from these disorders. However, the molecular mechanisms underlying the influence of different components of exercise interventions remain unknown. To isolate the impact of skeletal muscle conditioning on stress-induced depression, we used transgenic models that exhibit many of the chronic adaptations to aerobic exercise in skeletal muscle. Here, we show a mechanism by which skeletal muscle PGC-1α1 modulates kynurenine metabolism and mediates resilience to stress-induced depression. PGC-1α1 acts in concert with PPARα/δ transcription factors to induce the expression of kynurenine aminotransferases in skeletal muscle. The activity of this pathway diverts the metabolism of stress-induced kynurenine to kynurenic acid. Since kynurenic acid is unable to cross the blood brain barrier, this peripheral shift protects the brain from stress-induced accumulation of kynurenines. In addition, we further show that skeletal muscle PGC-1α1 and kynurenine aminotransferases are part of the physiological adaptations to aerobic exercise in both rodents and humans. Given that exercise-mediated activation of this pathway leads to peripheral accumulation of kynurenic acid, we evaluated the physiological role of this metabolite in modulating energy homeostasis. Here, we describe that kynurenic acid plays a role in systemic energy homeostasis through the regulation of adipose tissue function and inflammation. Kynurenic acid induces the expression of lipid metabolism, thermogenic and anti-inflammatory gene networks in the white adipose compartment. This reduces body-weight gain and improves glucose tolerance in animals fed a high-fat diet. Mechanistic studies in primary adipocytes show that kynurenic acid activates the G protein-coupled receptor 35. Downstream signaling of this activation is mediated through Ca2+, ERK, CREB and PGC-1α1 stabilization. Finally, activation of GPR35 by kynurenic acid induces the expression of RGS14, which sensitizes β-adrenergic response to specific agonists. In sum, this work uncovers a previously unknown function of PGC-1α1 in skeletal muscle and kynurenic acid in white adipose tissue. Targeting this metabolic node has great potential for the treatment of depression and metabolic diseases such as type-2 diabetes.
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| 2. |
- Agudo, A, et al.
(författare)
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Consumption of vegetables, fruit and other plant foods in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts from 10 European countries
- 2002
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Ingår i: Public Health Nutrition. - 1475-2727. ; 5:6B, s. 1179-1196
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe and compare the consumption of the main groups and subgroups of vegetables and fruits (V&F) in men and women from the centres participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). Design: Cross-sectional analysis. Dietary intake was assessed by means of a 24-hour dietary recall using computerised interview software and standardised procedures. Crude and adjusted means were computed for the main groups and sub-groups of V&F by centre, separately for men and women. Adjusted means by season, day of the week and age were estimated using weights and covariance analysis. Setting: Twenty-seven centres in 10 European countries participating in the EPIC project. Subjects: In total, 35 955 subjects (13 031 men and 22 924 women), aged 35-74 years, randomly selected from each EPIC cohort. Results: The centres from southern countries had the highest consumption of V&F, while the lowest intake was seen in The Netherlands and Scandinavia for both genders. These differences were more evident for fruits, particularly citrus. However, slightly different patterns arose for some sub-groups of vegetables, such as root vegetables and cabbage. Adjustment for body mass index, physical activity, smoking habits and education did not substantially modify the mean intakes of vegetables and fruits. vegetable and fruit intake follows a south-north gradient in both Conclusions:. Total, genders, whereas for several sub-groups of vegetables a different geographic distribution exists. Differences in mean intake of V&F by centre were not explained by lifestyle factors associated with VF intake.
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| 3. |
- Agudo, Antonio, et al.
(författare)
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Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
- 2013
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Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 34:6, s. 1244-1250
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary hemochromatosis (HH) is a strong risk factor for hepatocellular cancer, and mutations in the HFE gene associated with HH and iron overload may be related to other tumors, but no studies have been reported for gastric cancer (GC). A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), including 365 incident gastric adenocarcinoma and 1284 controls matched by center, sex, age and date of blood collection. Genotype analysis was performed for two functional polymorphisms (C282Y/rs1800562 and H63D/rs1799945) and seven tagSNPs of the HFE genomic region. Association with all gastric adenocarcinoma, and according to anatomical localization and histological subtype, was assessed by means of the odds ratio (OR) and 95% confidence interval (CI) estimated by unconditional logistic regression adjusted for the matching variables. We observed a significant association for H63D with OR (per rare allele) of 1.32 (CI = 1.03-1.69). In subgroup analyses, the association was stronger for non-cardia anatomical subsite (OR = 1.60, CI = 1.16-2.21) and intestinal histological subtype (OR = 1.82, CI = 1.27-2.62). Among intestinal cases, two tagSNPs (rs1572982 and rs6918586) also showed a significant association that disappeared after adjustment for H63D. No association with tumors located in the cardia or with diffuse subtype was found for any of the nine SNPs analyzed. Our results suggest that H63D variant in HFE gene seems to be associated with GC risk of the non-cardia region and intestinal type, possibly due to its association with iron overload although a role for other mechanisms cannot be entirely ruled out.
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| 4. |
- Bucken-Knapp, Gregg, et al.
(författare)
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The eye of the beholder: Narrating crisis in the ongoing Swedish labor migration policy debate
- 2015
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Ingår i: Korkut, U., Buchen-Knapp, G., Cox, R.H., Mahndran, K. (Eds.). Discursive Governance in Politics, Policy, and the Public Sphere. - London : Palgrave Macmillan. ; , s. 127-144
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Bokkapitel (refereegranskat)
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| 5. |
- Capek, Miloslav, et al.
(författare)
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Numerical Benchmark based on characteristic modes of a spherical shell
- 2017
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Ingår i: 2017 IEEE Antennas and Propagation Society International Symposium, Proceedings. - 9781538632840 ; 2017-January, s. 965-966
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Konferensbidrag (refereegranskat)abstract
- Characteristic modes of a spherical shell are found analytically and compared with numerical solutions acquired from both in-house and commercial packages. These studies led to a proposal of several independent benchmarks, all with analytically known results. Dependence on mesh size, electrical size and other parameters can easily be incorporated. It is observed that all contemporary implementations have limitations.
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| 6. |
- Carmont, Michael R, 1972, et al.
(författare)
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Free Hamstring Open Augmentation for Delayed Achilles Tendon Rupture
- 2017
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Ingår i: The Achilles Tendon An Atlas of Surgical Procedures. Editors: Thermann, H., Becher, C., Carmont, M.R., Karlsson, J., Maffulli, N., Calder, J., van Dijk, C.N.. - : Springer. - 9783662540749
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Bokkapitel (refereegranskat)
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| 7. |
- Carmont, Michael R, 1972, et al.
(författare)
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Functional Outcomes of Achilles Tendon Minimally Invasive Repair Using 4- and 6-Strand Nonabsorbable Suture: A Cohort Comparison Study
- 2017
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Ingår i: Orthopaedic Journal of Sports Medicine. - : SAGE Publications. - 2325-9671. ; 5:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of management of Achilles tendon rupture is to reduce tendon lengthening and maximize function while reducing the rerupture rate and minimizing other complications. Purpose: To determine changes in Achilles tendon resting angle (ATRA), heel-rise height, patient-reported outcomes, return to play, and occurrence of complications after minimally invasive repair of Achilles tendon ruptures using nonabsorbable sutures. Methods: Between March 2013 and August 2015, a total of 70 patients (58 males, 12 females) with a mean age of 42 8 years were included and evaluated at 6 weeks and 3, 6, 9, and 12 months after repair of an Achilles tendon rupture. Surgical repair was performed using either 4-strand or 6-strand nonabsorbable sutures. After surgery, patients were mobilized, fully weightbearing using a functional brace. Early active movement was permitted starting at 2 weeks. Results: There were no significant differences in the ATRA, Achilles Tendon Total Rupture Score (ATRS), and Heel-Rise Height Index (HRHI) between the 4- and 6-strand repairs. The mean (SD) relative ATRA was -13.1 degrees (6.6 degrees) (dorsiflexion) following injury; this was reduced to 7.6 degrees (4.8 degrees) (plantar flexion) directly after surgery. During initial rehabilitation at 6 weeks, the relative ATRA was 0.6 degrees (7.4 degrees) (neutral) and -7.0 degrees (5.3 degrees) (dorsiflexion) at 3 months, after which ATRA improved significantly with time to 12 months (P = .005). At 12 months, the median ATRS was 93 (range, 35-100), and the mean (SD) HRHI and Heel-Rise Repetition Index were 81% (0.22%) and 82.9% (0.17%), respectively. The relative ATRA at 3 and 12 months correlated with HRHI (r = 0.617, P < .001 and r = 0.535, P < .001, respectively). Conclusion: Increasing the number of suture strands from 4 to 6 does not alter the ATRA or HRHI after minimally invasive Achilles tendon repair. The use of a nonabsorbable suture during minimally invasive repair when used together with accelerated rehabilitation did not prevent the development of an increased relative ATRA. The ATRA at 3 months after surgery correlated with heel-rise height at 12 months.
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