31 resultados para Socially responsible investing


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Pseudohypoaldosteronism type 1 (PHA1) is a monogenic disorder of mineralocorticoid resistance characterized by salt wasting, hyperkalemia, high aldosterone levels, and failure to thrive. An autosomal recessive form (AR-PHA1) is caused by mutations in the epithelial sodium channel ENaC with usually severe and persisting multiorgan symptoms. The autosomal dominant form of PHA1 (AD-PHA1) is due to mutations in the mineralocorticoid receptor causing milder and transient symptoms restricted to the kidney. We identified a homozygous missense mutation in the SCNN1A gene (c.727T>C/p.Ser(243)Pro), encoding α-subunit of ENaC (α-ENaC) in a prematurely born boy with a severe salt-losing syndrome. The patient improved rapidly under treatment, and dietary salt supplementation could be stopped after 6 mo. Interestingly, the patient's sibling born at term and harboring the same homozygous Ser(243)Pro mutation showed no symptom of salt-losing nephropathy. In vitro expression of the αSer(243)Pro ENaC mutant revealed a slight but significant decrease in ENaC activity that is exacerbated in the presence of high Na(+) load. Our study provides the first evidence that ENaC activity is critical for the maintenance of salt balance in the immature kidney of preterm babies. Together with previous studies, it shows that, when the kidney is fully mature, the severity of the symptoms of AR-PHA1 is related to the degree of the ENaC loss of function. Finally, this study identifies a novel functional domain in the extracellular loop of ENaC.

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Like many organisms, the cladoceran Simocephalus vetulus (Müller) continues to grow when reproducing, whereas the optimal strategy is to stop growing at maturity, and to invest all available production into reproduction thereafter. It has been proposed that a size constraint is responsible for the observed strategy (Perrin, Ruedi & Saiah, 1987), by preventing organisms from investing more than a given amount of energy into reproduction. This hypothesis is developed here and the two folowing prediction are derived: (1) the onset of reproduction should be independent of age and (2) the reproductive investement should be size-specific, thus independent of the productin rate. Both predictions are tested by rearing a clone of S.vetulus in a gradient of productivity. The results support the first prediction, but not the second one, so that the size-constraint hypothesis is disproved.

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OBJECTIVE: A multidimensional lifestyle intervention performed in 652 preschoolers (72% of migrant, 38% of low educational level (EL) parents) reduced body fat, but not BMI and improved fitness. The objective of this study is to examine whether the intervention was equally effective in children of migrant and/or low EL parents.¦METHODS: Cluster-randomized controlled single blinded trial, conducted in 2008/09 in 40 randomly selected preschools in Switzerland. The culturally tailored intervention consisted of a physical activity program and lessons on nutrition, media use and sleep. Primary outcomes included BMI and aerobic fitness. Secondary outcomes included %body fat, waist circumference and motor agility.¦RESULTS: Children of migrant parents benefitted similarly from the intervention compared to their counterparts (p for interaction≥ 0.09). However, children of low EL parents benefitted less, although these differences did not reach statistical significance (p for interaction≥ 0.06). Average intervention effect sizes for BMI were -0.10, -0.05, -0.11 and 0.04 kg/m(2) and for aerobic fitness were 0.55, 0.20, 0.37 and -0.05 stages for children of non-migrant, migrant, middle/high EL and low EL parents, respectively.¦CONCLUSIONS: This intervention was similarly effective among preschoolers of migrant parents compared to their counterparts, while children of low EL parents benefitted less.

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Animal societies vary in the number of breeders per group, which affects many socially and ecologically relevant traits. In several social insect species, including our study species Formica selysi, the presence of either one or multiple reproducing females per colony is generally associated with differences in a suite of traits such as the body size of individuals. However, the proximate mechanisms and ontogenetic processes generating such differences between social structures are poorly known. Here, we cross-fostered eggs originating from single-queen (= monogynous) or multiple-queen (= polygynous) colonies into experimental groups of workers from each social structure to investigate whether differences in offspring survival, development time and body size are shaped by the genotype and/or prefoster maternal effects present in the eggs, or by the social origin of the rearing workers. Eggs produced by polygynous queens were more likely to survive to adulthood than eggs from monogynous queens, regardless of the social origin of the rearing workers. However, brood from monogynous queens grew faster than brood from polygynous queens. The social origin of the rearing workers influenced the probability of brood survival, with workers from monogynous colonies rearing more brood to adulthood than workers from polygynous colonies. The social origin of eggs or rearing workers had no significant effect on the head size of the resulting workers in our standardized laboratory conditions. Overall, the social backgrounds of the parents and of the rearing workers appear to shape distinct survival and developmental traits of ant brood.

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In social animals, body size can be shaped by multiple factors, such as direct genetic effects, maternal effects, or the social environment. In ants, the body size of queens correlates with the social structure of the colony: colonies headed by a single queen (monogyne) generally produce larger queens that are able to found colonies independently, whereas colonies headed by multiple queens (polygyne) tend to produce smaller queens that stay in their natal colony or disperse with workers. We performed a cross-fostering experiment to investigate the proximate causes of queen size variation in the socially polymorphic ant Formica selysi. As expected if genetic or maternal effects influence queen size, eggs originating from monogyne colonies developed into larger queens than eggs collected from polygyne colonies, be they raised by monogyne or polygyne workers. In contrast, eggs sampled in monogyne colonies were smaller than eggs sampled in polygyne colonies. Hence, eggs from monogyne colonies are smaller but develop into larger queens than eggs from polygyne colonies, independently of the social structure of the workers caring for the brood. These results demonstrate that a genetic polymorphism or maternal effect transmitted to the eggs influences queen size, which probably affects the social structure of new colonies.

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Introduction: Une élévation de l'activité des facteurs de transcription CREBs dans le tissu adipeux est en partie responsable de l'insulino-résistance systémique dans l'obésité. Le facteur «Inducible cAMP early repressor» (ICER) est un répresseur transcriptionnel passif dont le niveau d'expression antagonise l'activité des CREBs. L'objectif de ce travail adipocytaire des CREBs dans l'obésité chez l'Homme et la souris. Matériels et méthodes: Du tissu adipeux blanc (TAB) a été prélevé chez des souris obèses nourries sous une diète normale et des souris obèses nourries sous un régime riche en graisses pendant 12 semaines. Des biopsies de tissu adipeux viscéral (TAV) ont été prélevées chez les sujets humains minces (BMI = 24 ± 0,5 kg/m2) et obèses (BMI > 35 kg/m2). L'expression des gènes est quantifiée par RT-PCR quantitative. L'activité des CREBs et d'ICER est mesurée par des expériences de retard sur gel. L'activité des histones déacétylases est quantifiée par dosage colorimétrique. Résultats: L'expression et l'activité d'ICER sont diminuées dans le TAB des souris obèses, hyper-glycémiques et insulino-résistantes. De même, l'activité d'ICER est réduite dans le TAV des sujets humains obèses. Cette réduction corrèle avec une augmentation de l'activité des CREBs, une réduction de l'expression de Glut4 et de l'adiponectine, à la fois chez l'Homme et la souris. La diminution de l'expression d'ICER n'est observée que dans la fraction adipocytaire du tissu adipeux. L'expression d'ICER est contrôlée par l'activité des HDACs. L'inhibition des HDACs inhibe l'expression d'ICER dans les adipocytes. L'activité totale des HDACs est réduite dans les tissus adipeux chez les souris et chez les sujets humains obèses. Conclusion: La diminution de l'activité d'ICER dans les adipocytes par une modification de l'activité des HDACs serait responsable de l'augmentation de l'activité des CREBs dans l'obésité.

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BACKGROUND AND AIMS: Sustained adipose activation of the transcriptional activators cAMP response binding proteins (CREB) in obesity leads to impaired expression of the glucose transporter GLUT4 and adiponectin (adipoq) in mice model of obesity. Diminution of GLUT4 and adipoq caused by CREB is indirect and relies on the increased repressive activity of the CREB target gene activating transcription factor 3 (ATF3). Specific inactivation of CREB in adipocytes decreases ATF3 production and improves whole-body insulin sensitivity of mice in the context of diet-induced obesity. Thus, elevation of CREB activity is a key mechanism responsible for adipocyte dysfunction and systemic insulin resistance. The inducible cAMP early repressor (ICER) is a negative regulator of the CREB activity. In fact, ICER antagonizes the CREB factor by competing for the regulation of similar target genes. The goal of the study was to investigate whether loss of ICER expression in adipocytes could be responsible for increased CREB activity in obesity. MATERIALS AND METHODS: Mice C57bl6 were fed with a high fat diet (HFD) for 12 weeks to increase body weight and generate insulin resistance. Biopsies of visceral adipose tissues (VAT) were prepared from human lean (BMI=24}0.5 Kg/m2) or obese subjects (BMI>35 Kg/m2). Total RNA and protein were prepared from white adipose tissues (WAT) of chow- or HFD-fed mice and VAT of lean and obese subjects. Activities of CREBs and ICER were monitored by electromobility shift assays (EMSA). The role of ICER on CREB activity was confirmed in 3T3-L1 adipocytes cells. Briefly after differentiation, the cells were electroporated with the plasmid coding for ICER cDNA. Gene expression was quantified by quantitative real-time PCR and western Blotting experiments. RESULTS: The expression of ICER is reduced in WAT of HFD-induced obese mice when compared to chow mice as measured by real-time PCR and EMSA. Similar result was found in human tissues. Reduction in ICER expression was associated with increased ATF3 expression and decreased adipoq and GLUT4 contents. Diminution in ICER levels was observed in adipocytes fraction whereas its expression was unchanged in stroma vascular fraction of WAT. Overexpression of ICER in 3T3-L1 adipocytes silenced the expression of ATF3, confirming the regulation of the factor by ICER. The expression of ICER is regulated by histone deacetylases activity (HDAC). Inhibition of HDACs in 3T3-L1 adipocytes cells using trichostatin inhibited the production of ICER. The whole activity of HDAC was reduced in WAT and VAT of obese mice and human obese subjects. CONCLUSION: Impaired adipose expression of ICER is responsible of increased CREB activity in adipocytes in obesity. This mechanism relies on reduction of the HDAC activity.

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In social insects the number of queens per nest varies greatly. One of the proximate causes of this variation may be that queens produced by multiple-queen colonies are generally smaller, and might thus be unable to found new colonies independently. We examined whether the social origin of queens and males influenced the colony-founding success of queens in the socially polymorphic ant Formica selysi. Queens originating from single-queen and multiple-queen colonies had similar survival rates and colony-founding success, be they alone or in two-queen associations. During the first 5 months, queens originating from single-queen colonies gave rise to more workers than queens originating from multiple-queen colonies. Pairs of queens were also more productive than single queens. However, these differences in productivity were transient, as all types of colonies had reached a similar size after 15 months. Mating between social forms was possible and did not decrease queen survival or colony productivity, compared to mating within social forms. Overall, these results indicate that queens from each social form are able to found colonies independently, at least under laboratory conditions. Moreover, gene flow between social forms is not restricted by mating or genetic incompatibilities. This flexibility in mating and colony founding helps to explain the maintenance of alternative social structures in sympatry and the absence of genetic differentiation between social forms.

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En s'inspirant de la littérature récente qui a dépeint l'ambivalence comme étant adaptative et en lien avec des comportements stratégiques, cette thèse examine le versant utile des attitudes ambivalentes. Elle met tout d'abord en évidence que son expression peut-être sciemment contrôlée et mise en avant pour des raisons d'auto-présentation. De plus, elle démontre que les individus peuvent présenter une attitude ambivalente afin de gagner l'approbation sociale sur un objet d'attitude controversé alors que l'inverse a été observé sur des objets consensuels (Première ligne de recherche). Cette thèse a également révélé que l'expression d'attitudes ambivalentes pouvait amener à être valorisé socialement. En effet, contrairement à des attitudes plus tranchées (pro-normatives ou contre-normatives), les attitudes ambivalentes ont été évaluées de façon plus importante sur la dimension de l'utilité sociale (une dimension qui indique la compétence d'autrui ou encore la propension à évoluer dans la hiérarchie sociale). La valorisation de l'ambivalence n'est apparue que sur la dimension de l'utilité sociale et non sur la dimension de la désirabilité sociale (une dimension qui indique la sympathie d'autrui ainsi que la propension à être apprécié socialement). De plus, ce résultat a été observé sur des thèmes controversés et non sur des thèmes consensuels (Seconde ligne de recherche). Dans l'ensemble cette thèse soutient une approche de l'ambivalence comme donnant lieu à des bénéfices. Elle peut également ouvrir la voie à l'étude de l'ambivalence en lien avec la pensée critique. - Drawing on the recent literature that portrayed ambivalence as being adaptive and linked with strategic behaviors, this thesis examines the useful side of ambivalent attitudes. It first revealed that the expression of ambivalent attitudes could be controlled and purposely displayed for self-presentational concerns. Furthermore, it demonstrated that people could put ambivalence forward to gain social approval when expressing it on controversial social issues, whereas the opposite was true on consensual social issues (First line of research). The thesis also revealed that the expression of ambivalent attitudes could lead to be socially valued. Indeed, contrary to clear-cut attitudes (either pro-normative or counter-normative attitudes), ambivalent attitudes have been evaluated the highest on the social utility dimension (a dimension indicating people's competence as well as the extent to which they are likely to climb in social hierarchy). The valorization of ambivalent attitudes only appeared on social utility and not on social desirability (a dimension indicating people's niceness as well as the extent to which they are likely to be socially appreciated). This effect was true on controversial social issues but not on consensual ones (Second line of research). Overall, this thesis provides support for an approach that conceives attitudinal ambivalence as leading to benefits. It also may open avenues for the study of ambivalence in relation with critical thinking.

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Résumé : La majorité des souches de souris de laboratoire sont résistantes à l'infection par le parasite Leishmania major (L. major). A l'opposé, les souris de la souche BALB développent une maladie évolutive. La résistance et la sensibilité sont corrélées avec l'apparition de lymphocytes T CD4+ spécifiques du parasite, Th1 (de l'anglais T helper) ou Th2 respectivement. La réponse aberrante Th2 chez les souris de la souche BALB/c dépend, au moins en partie, de façon critique de la production rapide d'IL-4 suite à l'infection. Ce pic précoce d'IL-4 est produit par une population de lymphocytes T CD4+ restreinte aux molécules du MHC de classe II, exprimant les chaînes du récepteur des cellules T Vß4-Va8. Ces lymphocytes sont spécifiques d'un épitope de l'homologue Leishmania de la molécule RACK1 des mammifères, appelée LACK. Il a été clairement démontré que l'IL-4 rapidement produite par ces cellules T CD4+ Vß4-Va8 induit la maturation Th2 responsable de la sensibilité vis-à-vis de L. major. Des expériences ont été entreprises pour étudier la régulation de cette réponse précoce d'IL-4. Dans ce travail, nous avons documenté, dans les cellules provenant des ganglions de souris sensibles infectées par L. major, une augmentation de la transcription de l'ARNm de l'IL-2 qui précède la réponse précoce d'IL-4. La neutralisation de l'IL-2 durant les premiers jours d'infection induit la maturation des cellules Thl et la résistance vis-à-vis de L. major. Ces effets de l'anticorps anti-IL-2 neutralisant sont liés à sa capacité d'interférer avec la transcription rapide d'IL-4 des cellules CD4+ réactives à l'antigène LACK. Une augmentation similaire d'IL-2 survient chez les souris résistantes C57BL/6 qui sont incapables de générer la réponse précoce d'IL-4. Cependant, la protéiné LACK induit une transcription précoce d'IL-2 uniquement chez les souris sensibles. Des expériences de reconstitution utilisant des souris C.B.-17 SCID et des cellules T CD4+ réactives à LACK provenant de souris BALB/c IL-2-~démontrent un mode d'action autocrine de l'IL-2 sur la régulation de la réponse précoce d'IL4. Par conséquent, chez les souris C57BL/6, l'absence du pic précoce d'ARNm de l'IL-4 important pour la progression de la maladie paraît liée à l'incapacité des cellules T CD4+ réactives à LACK de produire de l'IL-2. Un rôle dans le contrôle de la production précoce d'IL-4 par les cellules T régulatrices CD4+CD25+ a été investigué en déplétant in vivo cette population de cellules. La déplétion induit une élévation du pic précoce de l'ARNm de l'IL-4 dans les ganglions drainant de souris BALB/c, ainsi qu'une exacerbation du cours de la maladie avec des taux augmentés d'IL-4 dans les ganglions. La réponse rapide d'IL-2 vis-à-vis de L. major est aussi significativement augmentée chez les souris BALB/c déplétées en cellules CD4+CD25+. De plus, nous avons démontré que le transfert de 10puissance(7) cellules provenant de la rate de souris BALB/c déplétées en cellules T régulatrices CD4+CD25+ rend les souris SCID sensibles à l'infection et permet la différentiation Th2. Au contraire, les souris SCID reconstituées avec 10' cellules de la rate de souris BALB/c contrôle sont résistantes à infection par L. major et développent une réponse Thl. Chez les souris SCID reconstituées avec des cellules de rate déplétées en cellules exprimant le marqueur CD25, le traitement avec un anticorps neutralisant l'IL-4 au moment de l'infection par L. major prévient le développement de la réponse Th2 et rend ces souris résistantes à l'infection. Ces résultats démontrent que les cellules T régulatrices CD4+CD25+ jouent un rôle dans la régulation du pic précoce d'IL-4 responsable du développement cellulaire Th2 dans ce modèle d'infection. Summary Mice from most strains are resistant to infection with Leishmania major (L. major). In contrast, BALB mice develop progressive disease. Resistance and susceptibility result from parasite-specific CD4+ Thl or Th2 cells, respectively. The aberrant Th2 response in BALB/c mice depends, at least in part, upon the production of IL-4 early after infection. The CD4+ T cells responsible for this early IL-4 response to L. major express a restricted TCR repertoire (Vß4-Va8) and respond to an I-Ad-restricted epitope of the Leishmania homologue of mammalian RACK1, designated LACK. The role of these cells and the IL-4 they produce for subsequent Th2 cell development and disease progression in BALB/c mice was demonstrated. Experiments have been undertaken to study the regulation of the rapid IL-4 production to L. major. In this report, we document an IL-2 mRNA burst, preceding the reported early IL-4 response, in draining lymph nodes of susceptible mice infected with L. major. Neutralization of IL-2 during the first days of infection redirected Thl cell maturation and resistance to L. major, through interference with the rapid IL-4 transcription in LACKreactive CD4+ cells. A burst of IL-2 transcripts also occurred in infected C57BL/6 mice that do not mount an early IL-4 response. However, although the LACK protein induced IL-2 transcripts in susceptible mice, it failed to trigger this response in resistant C57BL/6 mice. Reconstitution experiments using C.B.-17 SCID mice and LACK-reactive CD4+ T cells from IL-2-/- BALB/c mice showed that triggering of the early IL-4 response required autocrine IL2. Thus, in C57BL/6 mice, the inability of LACK-reactive CD4+ T cells to express early IL-4 mRNA transcription, important for disease progression, appears due to an incapacity of these cells to produce IL-2. A role for CD4+CD25+ regulatory T cells in the control of this early IL-4 production was investigated by depleting in vivo this regulatory T cell population. Depletion induced an increase in the early burst of IL-4 mRNA in the draining lymph nodes of BALB/c mice, and exacerbated the course of disease with higher levels of IL-4 mRNA and protein in their lymph nodes. The rapid IL-2 response to L. major is also significantly enhanced in BALB/c mice depleted of CD4+CD25+ cells. We further showed that transfer of 10~ BALB/c spleen cells that were depleted of CD4+CD25+ regulatory T cells rendered SCID mice susceptible to infection and allowed Th2 differentiation while SCID mice reconstituted with 10 control BALB/c spleen cells were resistant to infection with L. major and developed a Thl response. Treatment with a mAb against IL-4 upon infection with L. major in SCID mice reconstituted with CD25-depleted spleen cells prevented the development of Th2 polarization and rendered them resistant to infection. These results demonstrate that CD4+CD25+ regulatory T cells play a role in regulating the early IL-4 mRNA and the subsequent development of a Th2 response in this model of infection.

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Geleophysic (GD) and acromicric dysplasia (AD) belong to the acromelic dysplasia group and are both characterized by severe short stature, short extremities, and stiff joints. Although AD has an unknown molecular basis, we have previously identified ADAMTSL2 mutations in a subset of GD patients. After exome sequencing in GD and AD cases, we selected fibrillin 1 (FBN1) as a candidate gene, even though mutations in this gene have been described in Marfan syndrome, which is characterized by tall stature and arachnodactyly. We identified 16 heterozygous FBN1 mutations that are all located in exons 41 and 42 and encode TGFβ-binding protein-like domain 5 (TB5) of FBN1 in 29 GD and AD cases. Microfibrillar network disorganization and enhanced TGFβ signaling were consistent features in GD and AD fibroblasts. Importantly, a direct interaction between ADAMTSL2 and FBN1 was demonstrated, suggesting a disruption of this interaction as the underlying mechanism of GD and AD phenotypes. Although enhanced TGFβ signaling caused by FBN1 mutations can trigger either Marfan syndrome or GD and AD, our findings support the fact that TB5 mutations in FBN1 are responsible for short stature phenotypes.

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The ability to distinguish nestmates from foreign individuals is central to the functioning of insect societies. In ants, workers from multiple-queen colonies are often less aggressive than workers from single-queen ones. In line with this observation, it has been hypothesized that workers from multiple-queen colonies have less precise recognition abilities than workers from single-queen ones because their colonies contain genetically more diverse individuals, which results in a broader template of recognition cues. Here, we assessed the impact of social structure ( queen number) variation on nestmate recognition and aggression in a large population of the socially polymorphic ant Formica selysi. We staged unilateral aggression tests on the nest surface. Workers from single-and multiple-queen colonies had good nestmate recognition ability and did not differ significantly in their level of aggression towards foreign, immobilized workers ( cue-bearers). In particular, workers from multiple-queen colonies efficiently recognized non-nestmates despite the higher genetic diversity in their colony. Cue-bearers from single- and multiple-queen colonies elicited similar reactions. However, the level of aggression was higher between than within social forms, suggesting that workers detect a signal that is specific to the colony social structure. Finally, the level of aggression was not correlated with the genetic distance between colonies. Overall, we found no evidence for the hypothesis that the presence of multiple breeders in the same colony decreases recognition abilities and found no simple relationship between genetic diversity and aggression level. (c) 2007 The Association for the Study of Animal Behaviou

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We empirically contribute to the debate on business education in building on a decision frame perspective of decision making in corporate responsibility settings. Business schools have been accused to teach amoral theories, leading their students to behave less morally and engendering corporate responsibility scandals. Research has also pointed toward self-selection: business students would differ from non-business students before entering business school. We examine the role of socioeconomic status, core self-evaluations in this regard. Further, we investigate the belief in a free market as a distal influence triggering a business frame, and moral intensity as a proximal influence triggering a moral frame on responsible decision making by business and non-business students. Cross-sectional data obtained from 566 students on two decision making scenarios mostly supported our hypotheses. Socioeconomic status but not core self-evaluations explain the belief in a free market, and had indirect effects on the likelihood to make a less responsible decision. Importantly, the relationship between business studies and the belief in a free market remained significant after accounting for these variables. Our study thus contributes to the socialization and self-selection arguments. We discuss theoretical and practical implications for research on decision frames and for business education, respectively.