Fluorescence imaging reveals the nuclear behavior of peroxisome proliferator-activated receptor/retinoid X receptor heterodimers in the absence and presence of ligand.

In a global approach combining fluorescence recovery after photobleaching (FRAP), fluorescence correlation spectroscopy (FCS), and fluorescence resonance energy transfer (FRET), we address the behavior in living cells of the peroxisome proliferator-activated receptors (PPARs), a family of nuclear receptors involved in lipid and glucose metabolism, inflammation control, and wound healing. We first demonstrate that unlike several other nuclear receptors, PPARs do not form speckles upon ligand activation. The subnuclear structures that may be observed under some experimental conditions result from overexpression of the protein and our immunolabeling experiments suggest that these structures are subjected to degradation by the proteasome. Interestingly and in contrast to a general assumption, PPARs readily heterodimerize with retinoid X receptor (RXR) in the absence of ligand in living cells. PPAR diffusion coefficients indicate that all the receptors are engaged in complexes of very high molecular masses and/or interact with relatively immobile nuclear components. PPARs are not immobilized by ligand binding. However, they exhibit a ligand-induced reduction of mobility, probably due to enhanced interactions with cofactors and/or chromatin. Our study draws attention to the limitations and pitfalls of fluorescent chimera imaging and demonstrates the usefulness of the combination of FCS, FRAP, and FRET to assess the behavior of nuclear receptors and their mode of action in living cells.

Modulation of fructose metabolism by dietary factors

High fructose consumption is associated with obesity and characteristics of metabolic syndrome. This includes insulin resistance, dyslipidemia, type II diabetes and hepatic steatosis, the hepatic component of metabolic syndrome. Short term high fructose consumption in healthy humans is considered as a study model to increase intrahepatocellular lipids (IHCL). Protein supplementation added to a short term high fructose diet exerts a protective role on hepatic fat accumulation. Fructose disposal after an acute fructose load is well established. However, fructose disposal is usually studied when a high intake of fructose is ingested. Interaction of fructose with other macronutrients on fructose disposal is not clearly established. We wanted to assess how fructose disposal is modulated with nutritional factors. For the first study, we addressed the question of how would essential amino acid (EAA) supplemented to a high fructose diet have an impact on hepatic fat accumulation? We tried to distinguish which metabolic pathways were responsible for the increase in IHCL induced by high fructose intake and how those pathways would be modulated by EAA. After 6 days of hypercaloric high fructose diet, we observed, as expected an increase in IHCL modulated by an increase in VLDL-triglycerides and an increase in VLDL-13C-palmitate production. When adding a supplementation in EAA, we observed a decrease in IHCL but we could not define which mechanism was responsible for this process. With the second study, we were interested to observe fructose disposal after a test meal that contained lipid, protein and a physiologic dose of fructose co-ingested or not with glucose. When ingested with other macronutrients, hepatic fructose disposal is similar as when ingested as pure fructose. It induced oxidation, gluconeogenesis followed by glycogen synthesis, conversion into lactate and to a minor extent by de novo lipogenesis. When co- ingested with glucose decreased fructose oxidation as well as gluconeogenesis and an increased glycogen synthesis without affecting de novo lipogenesis or lactate. We were also able to observe induction of intestinal de novo lipogenesis with both fructose and fructose co- ingested with glucose. In summary, essential amino acids supplementation blunted increase in hepatic fat content induced by a short term chronic fructose overfeeding. However, EAA failed to improve other cardiovascular risk factors. Under isocaloric condition and in the frame of an acute test meal, physiologic dose of fructose associated with other macronutrients led to the same fructose disposal as when fructose is ingested alone. When co-ingested with glucose, we observed a decrease in fructose oxidation and gluconeogenesis as well as an increased in glycogen storage without affecting other metabolic pathways. - Une consommation élevée en fructose est associée à l'obésité et aux caractéristiques du syndrome métabolique. Ces dernières incluent une résistance à l'insuline, une dyslipidémie, un diabète de type II et la stéatose hépatique, composant hépatique du syndrome métabolique. À court terme une forte consommation en fructose chez l'homme sain est considérée comme un modèle d'étude pour augmenter la teneur en graisse hépatique. Une supplémentation en protéines ajoutée à une alimentation riche en fructose de courte durée a un effet protecteur sur l'accumulation des graisses au niveau du foie. Le métabolisme du fructose après une charge de fructose aiguë est bien établi. Toutefois, ce dernier est généralement étudié quand une consommation élevée de fructose est donnée. L'interaction du fructose avec d'autres macronutriments sur le métabolisme du fructose n'est pas connue. Nous voulions évaluer la modulation du métabolisme du fructose par des facteurs nutritionnels. Pour la première étude, nous avons abordé la question de savoir quel impact aurait une supplémentation en acides aminés essentiels (AEE) associé à une alimentation riche en fructose sur l'accumulation des graisses hépatiques. Nous avons essayé de distinguer les voies métaboliques responsables de l'augmentation des graisses hépatiques induite par l'alimentation riche en fructose et comment ces voies étaient modulées par les AEE. Après 6 jours d'une alimentation hypercalorique riche en fructose, nous avons observé, comme attendu, une augmentation des graisses hépatiques modulée par une augmentation des triglycérides-VLDL et une augmentation de la production de VLDL-13C-palmitate. Lors de la supplémentation en AEE, nous avons observé une diminution des graisses hépatiques mais les mécanismes responsables de ce processus n'ont pas pu être mis en évidence. Avec la seconde étude, nous nous sommes intéressés à observer le métabolisme du fructose après un repas test contenant des lipides, des protéines et une dose physiologique de fructose co-ingéré ou non avec du glucose. Lorsque le fructose était ingéré avec les autres macronutriments, le devenir hépatique du fructose était similaire à celui induit par du fructose pur. Il a induit une oxydation, suivie d'une néoglucogenèses, une synthèse de glycogène, une conversion en lactate et dans une moindre mesure une lipogenèse de novo. Lors de la co-ngestion avec du glucose, nous avons observé une diminution de l'oxydation du fructose et de la néoglucogenèse et une augmentation de la synthèse du glycogène, sans effet sur la lipogenèse de novo ni sur le lactate. Nous avons également pu mettre en évidence que le fructose et le fructose ingéré de façon conjointe avec du glucose ont induit une lipogenèse de novo au niveau de l'intestin. En résumé, la supplémentation en acides aminés essentiels a contrecarré l'augmentation de la teneur en graisse hépatique induite par une suralimentation en fructose sur le court terme. Cependant, la supplémentation en AEE a échoué à améliorer d'autres facteurs de risque cardiovasculaires. Dans la condition isocalorique et dans le cadre d'un repas test aiguë, la dose physiologique de fructose associée à d'autres macronutriments a conduit aux mêmes aboutissants du métabolisme du fructose que lorsque le fructose est ingéré seul. Lors de la co-ngestion avec le glucose, une diminution de l'oxydation du fructose est de la néoglucogenèse est observée en parallèle à une augmentation de la synthèse de glycogène sans affecter les autres voies métaboliques.

The Peroxisomal Enzyme L-PBE Is Required to Prevent the Dietary Toxicity of Medium-Chain Fatty Acids.

Specific metabolic pathways are activated by different nutrients to adapt the organism to available resources. Although essential, these mechanisms are incompletely defined. Here, we report that medium-chain fatty acids contained in coconut oil, a major source of dietary fat, induce the liver ω-oxidation genes Cyp4a10 and Cyp4a14 to increase the production of dicarboxylic fatty acids. Furthermore, these activate all ω- and β-oxidation pathways through peroxisome proliferator activated receptor (PPAR) α and PPARγ, an activation loop normally kept under control by dicarboxylic fatty acid degradation by the peroxisomal enzyme L-PBE. Indeed, L-pbe(-/-) mice fed coconut oil overaccumulate dicarboxylic fatty acids, which activate all fatty acid oxidation pathways and lead to liver inflammation, fibrosis, and death. Thus, the correct homeostasis of dicarboxylic fatty acids is a means to regulate the efficient utilization of ingested medium-chain fatty acids, and its deregulation exemplifies the intricate relationship between impaired metabolism and inflammation.

Insufficient coping behavior under chronic stress and vulnerability to psychiatric disorders

Epidemiological data indicate that 75% of subjects with major psychiatric disorders have their onset in the age range of 17-24 years. An estimated 35-50% of college and university students drop out prematurely due to insufficient coping skills under chronic stress, while 85% of students receiving a psychiatric diagnosis withdraw from college/university prior to the completion of their education. In this study we aimed at developing standardized means for identifying students with insufficient coping skills under chronic stress and at risk for mental health problems. A sample of 1,217 college students from 3 different sites in the U.S. and Switzerland completed 2 self-report questionnaires: the Coping Strategies Inventory "COPE" and the Zurich Health Questionnaire "ZHQ" which assesses "regular exercises", "consumption behavior", "impaired physical health", "psychosomatic disturbances", and "impaired mental health". The data were subjected to structure analyses by means of a Neural Network approach. We found 2 highly stable and reproducible COPE scales that explained the observed inter-individual variation in coping behavior sufficiently well and in a socio-culturally independent way. The scales reflected basic coping behavior in terms of "activity-passivity" and "defeatism-resilience", and in the sense of stable, socio-culturally independent personality traits. Correlation analyses carried out for external validation revealed a close relationship between high scores on the defeatism scale and impaired physical and mental health. This underlined the role of insufficient coping behavior as a risk factor for physical and mental health problems. The combined COPE and ZHQ instruments appear to constitute powerful screening tools for insufficient coping skills under chronic stress and for risks of mental health problems.

Is accurate perception of body image associated with appropriate weight-control behavior among adolescents of the Seychelles

BACKGROUND: We examined body image perception and its association with reported weight-control behavior among adolescents in the Seychelles.METHODS: We conducted a school-based survey of 1432 students aging 11-17 years in the Seychelles. Perception of body image was assessed using both a closed-ended question (CEQ) and Stunkard's pictorial silhouettes (SPS). Voluntary attempts to change weight were also assessed.RESULTS: A substantial proportion of the overweight students did not consider themselves as overweight (SPS: 24%, CEQ: 34%), and a substantial proportion of the normal-weight students considered themselves as too thin (SPS: 29%, CEQ: 15%). Logistic regression analysis showed that students with an accurate weight perception were more likely to have appropriate weight-control behavior.CONCLUSIONS: We found that substantial proportions of students had an inaccurate perception of their weight and that weight perception was associated with weight-control behavior. These findings point to forces that can drive the upwards overweight trends.

Emotional behavior in acute stroke : the Lausanne emotion in stroke study

Résumé : Objectif: Etudier les comportements émotionnels chez les patients ayant souffert d'un accident vasculaire cérébral (AVC) Contexte: Les modifications du comportement émotionnel après un AVC sont actuellement bien reconnues mais ont été très peu étudiées dans la phase aigüe de l'AVC. Méthode: Tous les patients présentant un AVC datant de moins de 24 heures ont été inclus prospectivement. Nous avons validé une échelle (the Emotional Behavior Index (EBI)), comprenant 38 qualificatifs, représentant la tristesse, l'agressivité, la désinhibition, l'adaptation, la passivité, l'indifférence et le déni. Les informations cliniques et radiologiques (CT et IRM) ont été obtenues par le biais de notre Registre des AVC. L'analyse statistique a été faite au moyen de tests uni- et multi-variés Résultats: Des 254 patients inclus, 40% présentaient de la tristesse, 49% de la passivité, 17% de l'agressivité, 53% de l'indifférence, 76% de la désinhibition, 18% un manque d'adaptation et 44% une réaction de déni. Plusieurs interactions statistiquement significatives ont été mises en évidence. En effet, la tristesse semble corréler à des antécédents d'alcoolisme (r = p< 0.037), au sexe féminin (r = p<0.028) et à la nature hémorragique de l'AVC (r = p<0.063). L'agressivité corrèle à des antécédents de troubles dépressifs (r = p<0.046) et à la nature hémorragique de l'AVC (r = p<0.06). Le déni corrèle plutôt au sexe masculin (r = p<0.035) et aux lésions hémorragiques (r = p<0.05). Le comportement émotionnel ne corrèle ni au degré et type d'atteinte neurologique, ni à la localisation de l'AVC mais une association entre Les lésions hémorragiques et un comportement agressif a été mis en évidence (p<0.001) de même qu'avec un manque d'adaptation (r = p<0.015), une certaine indifférence (r = p<0.018) et une réaction de déni (r = p<0.045). Conclusion: L'observation systématique des modifications du comportement émotionnel après un AVC suggère que les altérations émotionnelles sont indépendantes de la thymie et de l'atteinte physique et représentent donc probablement des séquelles à part entière de l'AVC. Abstract: Objective: To study emotional behaviors in an acute stroke population. Background: Alterations in emotional behavior after stroke have been recently recognized, but little attention has been paid to these changes in the very acute phase of stroke. Methods: Adult patients presenting with acute stroke were prospectively recruited and studied. We validated the Emotional Behavior Index (EBI), a 38-item scale designed to evaluate behavioral aspects of sadness, aggressiveness, disinhibition, adaptation, passivity, indifference, and denial. Clinical, historical, and imaging (computed tomography/magnetic resonance imaging) data were obtained on each subject through our Stroke Registry. Statistical analysis was performed with both univariate and multivariate tests. Results: Of the 254 patients, 40% showed sadness, 49% passivity, 17% aggressiveness, 53% indifference, 76% disinhibition, 18% lack of adaptation, and 44% denial reactions. Several significant correlations were identified. Sadness was correlated with a personal history of alcohol abuse (r = P < 0.037), female gender (r = P < 0.028), and hemorrhagic nature of the stroke (r = P < 0.063). Aggressiveness was correlated with a personal history of depression (r = P < 0.046) and hemorrhage (r = P < 0.06). Denial was correlated with male gender (r= P < 0.035) and hemorrhagic lesions (r = P < 0.05). Emotional behavior did not correlate with either neurologic impairment or lesion localization, but there was an association between hemorrhage and aggressive behavior (P < 0.001), lack of adaptation (r = P < 0.015), indifference (r = P < 0.018), and denial (r = P < 0.045). Conclusions: Systematic observations of acute emotional behaviors after stroke suggest that emotional alterations are independent of mood and physical status and should be considered as a separate consequence of stroke.

Effects of dietary protein type on oxidized cholesterol-induced alteration in age-related modulation of lipid metabolism and indices of immune function in rats.

Exogenous oxidized cholesterol disturbs both lipid metabolism and immune functions. Therefore, it may perturb these modulations with ageing. Effects of the dietary protein type on oxidized cholesterol-induced modulations of age-related changes in lipid metabolism and immune function was examined using differently aged (4 weeks versus 8 months) male Sprague-Dawley rats when casein, soybean protein or milk whey protein isolate (WPI) was the dietary protein source, respectively. The rats were given one of the three proteins in diet containing 0.2% oxidized cholesterols mixture. Soybean protein, as compared with the other two proteins, significantly lowered both the serum thiobarbituric acid reactive substances value and cholesterol, whereas it elevated the ratio of high density lipoprotein-cholesterol/cholesterol in young rats, but not in adult. Moreover, soybean protein, but not casein and WPI, suppressed the elevation of Delta6 desaturation indices of phospholipids in both liver and spleen, particularly in young. On the other hand, WPI, compared to the other two proteins, inhibited the leukotriene B4 production of spleen, irrespective of age. Soybean protein reduced the ratio of CD4(+)/CD8(+) T-cells in splenic lymphocytes. Therefore, the levels of immunoglobulin (Ig)A, IgE and IgG in serum were lowered in rats given soybean protein in both age groups except for IgA in adult, although these observations were not shown in rats given other proteins. Thus, various perturbations of lipid metabolism and immune function caused by oxidized cholesterol were modified depending on the type of dietary protein. The moderation by soybean protein on the change of lipid metabolism seems to be susceptible in young rats whose homeostatic ability is immature. These observations may be exerted through both the promotion of oxidized cholesterol excretion to feces and the change of hormonal release, while WPI may suppress the disturbance of immune function by oxidized cholesterol in both ages. This alleviation may be associated with a large amount of lactoglobulin in WPI. These results thus showed a possibility that oxidized cholesterol-induced perturbations of age-related changes of lipid metabolism and immune function can be moderated by both the selection and combination of dietary protein.

Dietary proteins and atherosclerosis.

More than one hundred years ago the "protein hypothesis" of the pathogenesis of atherosclerosis and its association with cardiovascular disease was put forward on the basis of animal experiments; however, it has so far never been verified in humans. This theory was soon replaced by the "lipid hypothesis", which was confirmed in humans as of 1994. Epidemiological ecological studies in the 1960 s showed significant associations between dietary animal protein and mortality from cardiovascular disease. However, animal protein intake was also significantly correlated with saturated fatty acid and cholesterol intake. In the last decades two prospective cohort studies demonstrated a decreased cardiovascular risk in women during high- versus low-protein intake when adjusting for other dietary factors (e. g., saturated fats) and other cardiovascular risk factors. A direct cholesterol lowering effect of proteins has not been shown. Despite earlier research indicating that soy protein has cardioprotective effects as compared to other proteins, these observations have not been confirmed by randomized placebo-controlled trials. However, most experts recommend the consumption of foods rich in plant proteins as alternatives to meat and dairy products rich in saturated fat and containing cholesterol. There are no scientific arguments to increase the daily protein intake to more than 20 % of total energy intake as recommended by the guidelines, in order to improve cardiovascular health.

Dietary lipids reduce the expression of carotenoid-based coloration in Lacerta vivipara

1. The importance of dietary lipids for carotenoid-based ornaments has rarely been investigated, although theory predicts that dietary lipids may control the development of these widespread animal signals. Dietary lipids have been suggested to enhance the expression of male carotenoid-based ornaments because they provide carotenoids with a hydrophobic domain that facilitates their absorption and transport. Dietary lipids may also enhance the uptake of tocopherols (vitamin E), which share common absorption and transport routes with carotenoids. Here, we test whether dietary lipids enhance carotenoid availability and male carotenoid-based colorations. We also explore the effects of dietary lipids on plasma tocopherol concentration, which allow disentangling between different pathways that may explain how dietary lipids affect ornamental expression. 2. Following a two-factorial design, we manipulated dietary access of naturally occurring fatty acids (oleic acid) and carotenoids (lutein and zeaxanthin) and measured its effects on the circulating concentrations of carotenoids (lutein and zeaxanthin) and vitamin E (α- and γ-(β-) tocopherols) and on the ventral, carotenoid-based coloration of male common lizards (Lacerta vivipara). 3. Lutein but not zeaxanthin plasma concentrations increased with carotenoid supplementation, which, however, did not affect coloration. Lipid intake negatively affected circulating concentrations of lutein and γ-(β-) tocopherol and led to significantly less orange colorations. The path analysis suggests that a relationship between the observed colour change and the change in plasma concentrations of γ-(β-) tocopherol may exist. 4. Our study shows for the first time that dietary lipids do not enhance but reduce the intensity of male carotenoid-based ornaments. Although dietary lipids affected plasma carotenoid concentration, its negative effect on coloration appeared to be linked to lower vitamin E plasma concentrations. These findings suggest that a conflict between dietary lipids and carotenoid and tocopherol uptake may arise if these nutrients are independently obtained from natural diets and that such conflict may reinforce signal honesty in carotenoid-based ornaments. They also suggest that, at least in the common lizard, sexual selection with respect to carotenoid-based coloration may select for males with low antioxidant capacity and thus for males of superior health.

Alcohol intake and the risk of coronary heart disease in the Spanish EPIC

Background: The association between alcohol consumption and coronary heart disease (CHD) has been widely studied. Most of these studies have concluded that moderate alcohol intake reduces the risk of CHD. There are numerous discussions regarding whether this association is causal or biased. The objective of this paper is to analyse the association between alcohol intake and CHD risk in the Spanish cohort of the European Prospective Investigation into Cancer (EPIC). Methods: Participants from the EPIC Spanish cohort were included (15 630 men and 25 808 women). The median follow-up period was 10 years. Ethanol intake was calculated using a validated dietary history questionnaire. Participants with a definite CHD event were considered cases. A Cox regression model adjusted for relevant co-variables and stratified by age was produced. Separate models were carried out for men and women. Results: The crude CHD incidence rate was 300.6/100 000 person-years for men and 47.9/100 000 person-years for women. Moderate, high and very high consumption was associated with a reduced risk of CHD in men: hazard ratio 0.90 (95% CI 0.56 to 1.44) for former drinkers, 0.65 (95% CI 0.41 to 1.04) for low, 0.49 (95% CI 0.32 to 0.76) for moderate, 0.46 (95% CI 0.30 to 0.71) for high and 0.50 (95% CI 0.29 to 0.85) for very high consumers. A negative association was found in women, with p values above 0.05 in all categories. Conclusions: Alcohol intake in men aged 29–69 years was associated with a more than 30% lower CHD incidence. This study is based on a large prospective cohort study and is free of the abstainer error.

An hybrid methodology for RL-based behavior coordination in a target following mission with an AUV

Proposes a behavior-based scheme for high-level control of autonomous underwater vehicles (AUVs). Two main characteristics can be highlighted in the control scheme. Behavior coordination is done through a hybrid methodology, which takes in advantages of the robustness and modularity in competitive approaches, as well as optimized trajectories

A behavior-based scheme using reinforcement learning for autonomous underwater vehicles

This paper presents a hybrid behavior-based scheme using reinforcement learning for high-level control of autonomous underwater vehicles (AUVs). Two main features of the presented approach are hybrid behavior coordination and semi on-line neural-Q_learning (SONQL). Hybrid behavior coordination takes advantages of robustness and modularity in the competitive approach as well as efficient trajectories in the cooperative approach. SONQL, a new continuous approach of the Q_learning algorithm with a multilayer neural network is used to learn behavior state/action mapping online. Experimental results show the feasibility of the presented approach for AUVs

Hábitos y estilos de vida modificables en niños con sobrepeso y obesidad.

INTRODUCTION In the prevention for being overweight and for obesity, much attention is given to the influence of dietary factors, making the joint evaluation with other modifiable factors necessary. OBJECTIVES The aim of this project is to study the association between modifiable factors (physical activity, sedentary lifestyle, and dietary habits) with the prevalence of being overweight or obese in the youth population. METHODS Cross-Sectional study of 1283 school children between the ages of 3 and 16 years old, with measurements of the MBI, dietary habits, physical activity, sedentary lifestyle and family history of being overweight. Physical activity measured in MET was classified according to Pate criteria. RESULTS 22.4% of the boys and 32.9% of the girls were overweight. The presence of a BMI>25 in parents multiplied by 2.4 the risk of being overweight in children (OR CI 95% 1.5-3.7). 63.6% of overweight boys meet physical activity recommendations compared with 52.2% of girls, although in their case, it was greater than the average (45%). Sedentary time was 141 minutes for men and 128 minutes for women, with more sedentary behaviors associated with being overweight, especially in girls over 12 years of age (66.7%). Consuming cereal (OR 0.8) and having five meals per day (OR 0.5) act as protective factors. CONCLUSIONS In subjects with overweight, the levels of physical activity are close to those recommended levels, so which the values of a sedentary lifestyle together with dietary habits (if the parents have overweight) acquire a new relevance in intervention strategies of this problem.

A nutritional intervention study with hydrolyzed collagen in pre-pubertal Spanish children: influence on bone modeling biomarkers

Aim: The aim of the study was to investigate the influence of dietary intake of commercial hydrolyzed collagen (Gelatine Royal ®) on bone remodeling in pre-pubertal children. Methods: A randomized double-blind study was carried out in 60 children (9.42 ± 1.31 years) divided into three groups according to the amount of partially hydrolyzed collagen taken daily for 4 months: placebo (G-I, n = 18), collagen (G-II, n = 20) and collagen + calcium (G-III, n = 22) groups. Analyses of the following biochemical markers were carried out: total and bone alkaline phosphatase (tALP and bALP), osteocalcin, tartrate-resistant acid phosphatase (TRAP), type I collagen carboxy terminal telopeptide, lipids, calcium, 25-hydroxyvitamin D, insulin-like growth factor 1 (IGF-1), thyroid-stimulating hormone, free thyroxin and intact parathormone. Results: There was a significantly greater increase in serum IGF-1 in G-III than in G II (p < 0.01) or G-I (p < 0.05) during the study period, and a significantly greater increase in plasma tALP in G-III than in G-I (p < 0.05). Serum bALP behavior significantly (p < 0.05) differed between G-II (increase) and G-I (decrease). Plasma TRAP behavior significantly differed between G-II and G-I (p < 0.01) and between G-III and G-II (p < 0.05). Conclusion: Daily dietary intake of hydrolyzed collagen seems to have a potential role in enhancing bone remodeling at key stages of growth and development.