Influence of experimental illumination and seasonal variation on crossbreending mating in the snail Biomphalaria Glabrata

The crossbreeding activities of the Schistosoma mansoni vector snail Biomphalaria glabrata were counted in a laboratory aquarium throughout the year under two regimes of 12h light: 12h dark from 7 A., M. to 10 P. M. Mating increased significantly in Authmn and Winter and just missed a significant inverse correlation with temperature and a direct one with locomotion. Other similar experiments were carried out to compare mating under various ilumination conditions in complete daily cycle measurements. Mating counts decreased under the regimes which submited snail to a total exposure of 12h light and 12 dark during a daily cycle in the following sequence: 12h light: 12h dark alternating hourly with light gradient, 12h light: 12h dark, 1h light: 1h dark and 12h dark: 12h light. Under two constant illuminations, the mating scored less than under the previous conditions, except under 12h light. Under darkeness the mating count was lower than light conditions. There was no way to differentiate the night and day rhythms of mating on different days in each regime, except for mating under 12h light: 12 dark alternating with light gradient, constant dark and 12h dark: 12h light conditions. Mating increased in certain light and temperature conditions, in wich the intensities, should have an optimum value.

Setting boundaries: brain dynamics of modal and amodal illusory shape completion in humans.

Normal visual perception requires differentiating foreground from background objects. Differences in physical attributes sometimes determine this relationship. Often such differences must instead be inferred, as when two objects or their parts have the same luminance. Modal completion refers to such perceptual "filling-in" of object borders that are accompanied by concurrent brightness enhancement, in turn termed illusory contours (ICs). Amodal completion is filling-in without concurrent brightness enhancement. Presently there are controversies regarding whether both completion processes use a common neural mechanism and whether perceptual filling-in is a bottom-up, feedforward process initiating at the lowest levels of the cortical visual pathway or commences at higher-tier regions. We previously examined modal completion (Murray et al., 2002) and provided evidence that the earliest modal IC sensitivity occurs within higher-tier object recognition areas of the lateral occipital complex (LOC). We further proposed that previous observations of IC sensitivity in lower-tier regions likely reflect feedback modulation from the LOC. The present study tested these proposals, examining the commonality between modal and amodal completion mechanisms with high-density electrical mapping, spatiotemporal topographic analyses, and the local autoregressive average distributed linear inverse source estimation. A common initial mechanism for both types of completion processes (140 msec) that manifested as a modulation in response strength within higher-tier visual areas, including the LOC and parietal structures, is demonstrated, whereas differential mechanisms were evident only at a subsequent time period (240 msec), with amodal completion relying on continued strong responses in these structures.

Psychiatric comorbidity and additional abuse of drugs in maintenance treatment with l- and d,l-methadone.

Sixty d,l- or l-methadone treated patients in maintenance therapy were interviewed for additional drug abuse and psychiatric comorbidity; 51.7% of the entire population had a comorbid Axis-I disorder, with a higher prevalence in females (P=0.05). Comorbid patients tended to have higher abuse of benzodiazepines, alcohol, cannabis, and cocaine, but not of heroin. They had received a significantly lower d,l- (P<0.05) and l-methadone dose than non-comorbid subjects. The duration of maintenance treatment showed an inverse relationship to frequency of additional heroin intake (P<0.01). Patients with additional heroin intake over the past 30 days had been treated with a significantly lower l-methadone dosage (P<0.05) than patients without. Axis-I comorbidity appears to be decreased when relatively higher dosages of d,l- (and l-methadone) are administered; comorbid individuals, however, were on significantly lower dosages. Finally, l-, but not d,l-methadone seems to be more effective in reducing additional heroin abuse.

Alveolar echinococcosis of the liver: Diffusion-weighted MRI findings and potential role in lesion characterisation

PURPOSE: To report the diffusion-weighted MRI findings in alveolar echinococcosis (AE) of the liver and evaluate the potential role of apparent diffusion coefficients (ADCs) in the characterisation of lesions. MATERIALS AND METHODS: We retrospectively included 22 patients with 63 AE liver lesions (≥1cm), examined with 3-T liver MRI, including a free-breathing diffusion-weighted single-shot echo-planar imaging sequence (b-values=50, 300 and 600s/mm(2)). Two radiologists jointly assessed the following lesion features: size, location, presence of cystic and/or solid components (according to Kodama's classification system), relative contrast enhancement, and calcifications (on CT). The ADCtotal, ADCmin and ADCmax were measured in each lesion and the surrounding liver parenchyma. RESULTS: Three type 1, 19 type 2, 17 type 3, three type 4 and 21 type 5 lesions were identified. The mean (±SD) ADCtotal, ADCmin and ADCmax for all lesions were 1.73±0.50, 0.76±0.38 and 2.63±0.76×10(-3)mm(2)/s, respectively. The mean ADCtotal for type 1, type 2, type 3, type 4 and type 5 lesions were 1.97±1.01, 1.76±0.53, 1.73±0.41, 1.15±0.42 and 1.76±0.44×10(-3)mm(2)/s, respectively. No significant differences were found between the five lesion types, except for type 4 (p=0.0363). There was a significant correlation between the presence of a solid component and low ADCmin (r=0.39, p=0.0016), whereas an inverse correlation was found between the relative contrast enhancement and ADCtotal (r=-0.34, p=0.0072). CONCLUSION: The ADCs of AE lesions are relatively low compared to other cystic liver lesions, which may help in the differential diagnosis. Although ADCs are of little use to distinguish between the five lesion types, their low value reflects the underlying solid component.

Contact metamorphism and emplacement of the western Adamello tonalite

The geodynamic forces acting in the Earth's interior manifest themselves in a variety of ways. Volcanoes are amongst the most impressive examples in this respect, but like with an iceberg, they only represent the tip of a more extensive system hidden underground. This system consists of a source region where melt forms and accumulates, feeder connections in which magma is transported towards the surface, and different reservoirs where it is stored before it eventually erupts to form a volcano. A magma represents a mixture of melt and crystals. The latter can be extracted from the source region, or form anywhere along the path towards their final crystallization place. They will retain information of the overall plumbing system. The host rocks of an intrusion, in contrast, provide information at the emplacement level. They record the effects of thermal and mechanical forces imposed by the magma. For a better understanding of the system, both parts - magmatic and metamorphic petrology - have to be integrated. I will demonstrate in my thesis that information from both is complementary. It is an iterative process, using constraints from one field to better constrain the other. Reading the history of the host rocks is not always straightforward. This is shown in chapter two, where a model for the formation of clustered garnets observed in the contact aureole is proposed. Fragments of garnets, older than the intrusive rocks are overgrown by garnet crystallizing due to the reheating during emplacement of the adjacent pluton. The formation of the clusters is therefore not a single event as generally assumed but the result of a two-stage process, namely the alteration of the old grains and the overgrowth and amalgamation of new garnet rims. This makes an important difference when applying petrological methods such as thermobarometry, geochronology or grain size distributions. The thermal conditions in the aureole are a strong function of the emplacement style of the pluton. therefore it is necessary to understand the pluton before drawing conclusions about its aureole. A study investigating the intrusive rocks by means of field, geochemical, geochronologi- cal and structural methods is presented in chapter three. This provided important information about the assembly of the intrusion, but also new insights on the nature of large, homogeneous plutons and the structure of the plumbing system in general. The incremental nature of the emplacement of the Western Adamello tonalité is documented, and the existence of an intermediate reservoir beneath homogeneous plutons is proposed. In chapter four it is demonstrated that information extracted from the host rock provides further constraints on the emplacement process of the intrusion. The temperatures obtain by combining field observations with phase petrology modeling are used together with thermal models to constrain the magmatic activity in the immediate intrusion. Instead of using the thermal models to control the petrology result, the inverse is done. The model parameters were changed until a match with the aureole temperatures was obtained. It is shown, that only a few combinations give a positive match and that temperature estimates from the aureole can constrain the frequency of ancient magmatic systems. In the fifth chapter, the Anisotropy of Magnetic Susceptibility of intrusive rocks is compared to 3D tomography. The obtained signal is a function of the shape and distribution of ferromagnetic grains, and is often used to infer flow directions of magma. It turns out that the signal is dominated by the shape of the magnetic crystals, and where they form tight clusters, also by their distribution. This is in good agreement with the predictions made in the theoretical and experimental literature. In the sixth chapter arguments for partial melting of host rock carbonates are presented. While at first very surprising, this is to be expected when considering the prior results from the intrusive study and experiments from the literature. Partial melting is documented by compelling microstructures, geochemical and structural data. The necessary conditions are far from extreme and this process might be more frequent than previously thought. The carbonate melt is highly mobile and can move along grain boundaries, infiltrating other rocks and ultimately alter the existing mineral assemblage. Finally, a mineralogical curiosity is presented in chapter seven. The mineral assemblage magne§site and calcite is in apparent equilibrium. It is well known that these two carbonates are not stable together in the system Ca0-Mg0-Fe0-C02. Indeed, magnesite and calcite should react to dolomite during metamorphism. The presented explanation for this '"forbidden" assemblage is, that a calcite melt infiltrated the magnesite bearing rock along grain boundaries and caused the peculiar microstructure. This is supported by isotopie disequilibrium between calcite and magnesite. A further implication of partially molten carbonates is, that the host rock drastically looses its strength so that its physical properties may be comparable to the ones of the intrusive rocks. This contrasting behavior of the host rock may ease the emplacement of the intrusion. We see that the circle closes and the iterative process of better constraining the emplacement could start again. - La Terre est en perpétuel mouvement et les forces tectoniques associées à ces mouvements se manifestent sous différentes formes. Les volcans en sont l'un des exemples les plus impressionnants, mais comme les icebergs, les laves émises en surfaces ne représentent que la pointe d'un vaste système caché dans les profondeurs. Ce système est constitué d'une région source, région où la roche source fond et produit le magma ; ce magma peut s'accumuler dans cette région source ou être transporté à travers différents conduits dans des réservoirs où le magma est stocké. Ce magma peut cristalliser in situ et produire des roches plutoniques ou alors être émis en surface. Un magma représente un mélange entre un liquide et des cristaux. Ces cristaux peuvent être extraits de la source ou se former tout au long du chemin jusqu'à l'endroit final de cristallisation. L'étude de ces cristaux peut ainsi donner des informations sur l'ensemble du système magmatique. Au contraire, les roches encaissantes fournissent des informations sur le niveau d'emplacement de l'intrusion. En effet ces roches enregistrent les effets thermiques et mécaniques imposés par le magma. Pour une meilleure compréhension du système, les deux parties, magmatique et métamorphique, doivent être intégrées. Cette thèse a pour but de montrer que les informations issues de l'étude des roches magmatiques et des roches encaissantes sont complémentaires. C'est un processus itératif qui utilise les contraintes d'un domaine pour améliorer la compréhension de l'autre. Comprendre l'histoire des roches encaissantes n'est pas toujours aisé. Ceci est démontré dans le chapitre deux, où un modèle de formation des grenats observés sous forme d'agrégats dans l'auréole de contact est proposé. Des fragments de grenats plus vieux que les roches intru- sives montrent une zone de surcroissance générée par l'apport thermique produit par la mise en place du pluton adjacent. La formation des agrégats de grenats n'est donc pas le résultat d'un seul événement, comme on le décrit habituellement, mais d'un processus en deux phases, soit l'altération de vieux grains engendrant une fracturation de ces grenats, puis la formation de zone de surcroissance autour de ces différents fragments expliquant la texture en agrégats observée. Cette interprétation en deux phases est importante, car elle engendre des différences notables lorsque l'on applique des méthodes pétrologiques comme la thermobarométrie, la géochronologie ou encore lorsque l'on étudie la distribution relative de la taille des grains. Les conditions thermales dans l'auréole de contact dépendent fortement du mode d'emplacement de l'intrusion et c'est pourquoi il est nécessaire de d'abord comprendre le pluton avant de faire des conclusions sur son auréole de contact. Une étude de terrain des roches intrusives ainsi qu'une étude géochimique, géochronologique et structurale est présente dans le troisième chapitre. Cette étude apporte des informations importantes sur la formation de l'intrusion mais également de nouvelles connaissances sur la nature de grands plutons homogènes et la structure de système magmatique en général. L'emplacement incrémental est mis en évidence et l'existence d'un réservoir intermédiaire en-dessous des plutons homogènes est proposé. Le quatrième chapitre de cette thèse illustre comment utiliser l'information extraite des roches encaissantes pour expliquer la mise en place de l'intrusion. Les températures obtenues par la combinaison des observations de terrain et l'assemblage métamorphique sont utilisées avec des modèles thermiques pour contraindre l'activité magmatique au contact directe de cette auréole. Au lieu d'utiliser le modèle thermique pour vérifier le résultat pétrologique, une approche inverse a été choisie. Les paramètres du modèle ont été changés jusqu'à ce qu'on obtienne une correspondance avec les températures observées dans l'auréole de contact. Ceci montre qu'il y a peu de combinaison qui peuvent expliquer les températures et qu'on peut contraindre la fréquence de l'activité magmatique d'un ancien système magmatique de cette manière. Dans le cinquième chapitre, les processus contrôlant l'anisotropie de la susceptibilité magnétique des roches intrusives sont expliqués à l'aide d'images de la distribution des minéraux dans les roches obtenues par tomographie 3D. Le signal associé à l'anisotropie de la susceptibilité magnétique est une fonction de la forme et de la distribution des grains ferromagnétiques. Ce signal est fréquemment utilisé pour déterminer la direction de mouvement d'un magma. En accord avec d'autres études de la littérature, les résultats montrent que le signal est dominé par la forme des cristaux magnétiques, ainsi que par la distribution des agglomérats de ces minéraux dans la roche. Dans le sixième chapitre, une étude associée à la fusion partielle de carbonates dans les roches encaissantes est présentée. Si la présence de liquides carbonatés dans les auréoles de contact a été proposée sur la base d'expériences de laboratoire, notre étude démontre clairement leur existence dans la nature. La fusion partielle est documentée par des microstructures caractéristiques pour la présence de liquides ainsi que par des données géochimiques et structurales. Les conditions nécessaires sont loin d'être extrêmes et ce processus pourrait être plus fréquent qu'attendu. Les liquides carbonatés sont très mobiles et peuvent circuler le long des limites de grain avant d'infiltrer d'autres roches en produisant une modification de leurs assemblages minéralogiques. Finalement, une curiosité minéralogique est présentée dans le chapitre sept. L'assemblage de minéraux de magnésite et de calcite en équilibre apparent est observé. Il est bien connu que ces deux carbonates ne sont pas stables ensemble dans le système CaO-MgO-FeO-CO.,. En effet, la magnésite et la calcite devraient réagir et produire de la dolomite pendant le métamorphisme. L'explication présentée pour cet assemblage à priori « interdit » est que un liquide carbonaté provenant des roches adjacentes infiltre cette roche et est responsable pour cette microstructure. Une autre implication associée à la présence de carbonates fondus est que la roche encaissante montre une diminution drastique de sa résistance et que les propriétés physiques de cette roche deviennent comparables à celles de la roche intrusive. Cette modification des propriétés rhéologiques des roches encaissantes peut faciliter la mise en place des roches intrusives. Ces différentes études démontrent bien le processus itératif utilisé et l'intérêt d'étudier aussi bien les roches intrusives que les roches encaissantes pour la compréhension des mécanismes de mise en place des magmas au sein de la croûte terrestre.

Work Hours, Social Value of Leisure and Globalisation

We examine how openness interacts with the coordination of consumption-leisure decisions in determining the equilibrium working hours and wage rate when there are leisure externalities (e.g., due to social interactions). The latter are modelled by allowing a worker’s marginal utility of leisure to be increasing in the leisure time taken by other workers. Coordination takes the form of internalising the leisure externality and other relevant constraints (e.g., labour demand). The extent of openness is measured by the degree of capital mobility. We find that: coordination lowers equilibrium work hours and raises the wage rate; there is a U-shaped (inverse-U-shaped) relationship between work hours (wages) and the degree of coordination; coordination is welfare improving; and, the gap between the coordinated and uncoordinated work hours (and the corresponding wage rates) is affected by the extent and nature of openness.

Oligomerization of the alpha 1a- and alpha 1b-adrenergic receptor subtypes. Potential implications in receptor internalization.

We combined biophysical, biochemical, and pharmacological approaches to investigate the ability of the alpha 1a- and alpha 1b-adrenergic receptor (AR) subtypes to form homo- and hetero-oligomers. Receptors tagged with different epitopes (hemagglutinin and Myc) or fluorescent proteins (cyan and green fluorescent proteins) were transiently expressed in HEK-293 cells either individually or in different combinations. Fluorescence resonance energy transfer measurements provided evidence that both the alpha 1a- and alpha 1b-AR can form homo-oligomers with similar transfer efficiency of approximately 0.10. Hetero-oligomers could also be observed between the alpha 1b- and the alpha 1a-AR subtypes but not between the alpha 1b-AR and the beta2-AR, the NK1 tachykinin, or the CCR5 chemokine receptors. Oligomerization of the alpha 1b-AR did not require the integrity of its C-tail, of two glycophorin motifs, or of the N-linked glycosylation sites at its N terminus. In contrast, helix I and, to a lesser extent, helix VII were found to play a role in the alpha 1b-AR homo-oligomerization. Receptor oligomerization was not influenced by the agonist epinephrine or by the inverse agonist prazosin. A constitutively active (A293E) as well as a signaling-deficient (R143E) mutant displayed oligomerization features similar to those of the wild type alpha 1b-AR. Confocal imaging revealed that oligomerization of the alpha1-AR subtypes correlated with their ability to co-internalize upon exposure to the agonist. The alpha 1a-selective agonist oxymetazoline induced the co-internalization of the alpha 1a- and alpha 1b-AR, whereas the alpha 1b-AR could not co-internalize with the NK1 tachykinin or CCR5 chemokine receptors. Oligomerization might therefore represent an additional mechanism regulating the physiological responses mediated by the alpha 1a- and alpha 1b-AR subtypes.

Accounting for the dead in the longitudinal analysis of income-related health inequalities

This paper develops an accounting framework to consider the effect of deaths on the longitudinal analysis of income-related health inequalities. Ignoring deaths or using inverse probability weights (IPWs) to re-weight the sample for mortality-related attrition can produce misleading results, since to do so would be to disregard the most extreme of all health outcomes. Incorporating deaths into the longitudinal analysis of income-related health inequalities provides a more complete picture in terms of the evaluation of health changes in respect to socioeconomic status. We illustrate our work by investigating health mobility in Quality Adjusted Life Years (QALYs) as measured by the SF6D from 1999 till 2004 using the British Household Panel Survey (BHPS). We show that for Scottish males explicitly accounting for the dead, rather than using IPWs to account for mortality-related attrition, changes the direction of the relationship between relative health changes and initial income position, while for other population groups it increases the strength of this relationship by up to 14 times. When deaths are explicitly incorporated into the analysis it is found that over this five year period for both Scotland and England & Wales the relative health changes were significantly regressive such that the poor experienced a larger share of the health losses relative to their initial share of health and a large amount of this was related to mortality.

Transmission of macro-liquidity shocks to liquidity-sorted stock portfolios’ returns: The role of the financial crisis

This study examines the impact of macro-liquidity shocks on the returns of UK stock portfolios sorted on the basis of a series of micro-liquidity measures. The macro-liquidity shocks are extracted on the meeting days of the Bank of England Monetary Policy Committee relative to market expectations embedded in futures contracts on the 3-month LIBOR during the period June 1999- December 2009. We report definitive evidence that these shocks are transmitted to the cross-section of liquidity-sorted portfolios, with most liquid stocks playing a very active role. Our results emphatically document that the shocks-returns relationship has reversed its sign during the recent financial crisis; the standard inverse relationship between interest rate surprises and portfolios’ returns before the crisis has turned into positive during the crisis. This finding confirms the inability of interest rate cuts to boost returns in the shortrun during the crisis, because these were perceived by market participants as a signal of a deteriorating economic outlook.

A Thomason model structure on the category of small n-fold categories

We construct a cofibrantly generated Thomason model structure on the category of small n-fold categories and prove that it is Quillen equivalent to the standard model structure on the category of simplicial sets. An n-fold functor is a weak equivalence if and only if the diagonal of its n-fold nerve is a weak equivalence of simplicial sets. We introduce an n-fold Grothendieck construction for multisimplicial sets, and prove that it is a homotopy inverse to the n-fold nerve. As a consequence, the unit and counit of the adjunction between simplicial sets and n-fold categories are natural weak equivalences.

Role of the c-Jun N-terminal Kinase signaling in pancreatic β-cells

L'insuline est une hormone qui diminue la concentration de sucre dans le sang et qui est produite par la cellule β du pancréas. Un défaut de production de cette hormone est une des causes principales du diabète. Cette perte de production d'insuline est la conséquence à la fois, de la réduction du nombre de cellules β et du mauvais fonctionnement des cellules β restantes. L'inflammation, en activant la voie de signalisation «c-Jun N-terminal Kinase» (JNK) contribue au déclin de ces cellules. Cette voie de signalisation est activée par des protéines telles que des kinases qui reçoivent le signal de stress. Dans ce travail de thèse nous nous sommes intéressés à étudier le rôle de «Dual leucine zipper bearing kinase» (DLK) comme protéine capable de relayer le stress inflammatoire vers l'activation de la voie JNK dans les cellules β-pancréatiques. Nous montrons que DLK est présente dans les cellules β-pancréatiques et qu'elle agit effectivement comme un activateur de la voie de signalisation de JNK. En outre, DLK joue un rôle clé dans le contrôle de l'expression de l'insuline, de la sécrétion de l'insuline en réponse au glucose et au maintien de la survie des cellules β. Si l'expression de cette protéine diminue, la cellule produit moins d'insuline et sera plus sensible à la mort en réponse au stress inflammatoire. A l'inverse si l'expression de DLK est augmentée, la cellule β produit et secrète plus d'insuline. Des variations de l'expression de DLK sont par ailleurs, associées à l'état de santé de la cellule β. Chez la ratte en gestation ou la souris obèse, dans lesquelles la cellule β produit plus d'insuline, l'expression de DLK est augmentée. En revanche dans les cellules β des patients diabétiques, l'expression de DLK est diminuée par rapport aux cellules non malades. En résumé, DLK est nécessaire pour le bon fonctionnement de la cellule β-pancréatique et son expression corrèle avec le degré de santé des cellules, faisant que cette protéine pourrait être une cible thérapeutique potentiel. Les cellules β-pancréatiques ont la capacité de réguler la sécrétion d'insuline en s'adaptant précisément au stimulus et à la glycémie. La fonction de la cellule β est cruciale dans l'homéostasie du glucose puisque sa dysfonction et sa mort mènent au développement des diabètes de type 1 et 2. De nombreuses études suggèrent que l'inflammation pourrait avoir un rôle dans la dysfonction et la destruction de ces cellules dans le diabète de type 2. L'excès chronique de cytokines proinflammatoires accélère le dysfonctionnement de la cellule β pancréatique par un mécanisme qui implique la voie de signalisation «c-Jun N-terminal Kinase» (JNK). L'activation de cette voie est organisée par des protéines d'échafaudages. Elle se fait par trois étapes successives de phosphorylation impliquant une «Mitogen Activated Protein Kinase Kinase Kinase» (MAP3K), une MAP2K et JNK. Dans ce travail de thèse nous montrons l'expression abondante et spécifique de la MAP3K «Dual Leucine Zipper Bearing Kinase» (DLK) dans les cellules β pancréatiques. Cela est la conséquence de l'absence du répresseur transcriptionnel «Repressor Element 1 Silencing Transcription». Nous montrons également que DLK régule l'activation de JNK et qu'il s'avère nécessaire pour la fonction et la survie de la cellule β pancréatique par un mécanisme impliquant le facteur de transcription PDX-1. L'invalidation de l'expression de DLK diminue l'expression de l'insuline et potentialise l'apoptose induite par des cytokines proinflammatoires. A l'inverse, la surexpression de DLK augmente l'expression et la sécrétion d'insuline induites par le glucose. Par conséquent des niveaux d'expression appropriés de DLK sont déterminants pour la fonction et la survie de la cellule β pancréatique. L'obésité et la grossesse sont caractérisées par une hyperinsulinémie qui résulte d'une augmentation de la production et de la sécrétion de l'insuline. L'expression de DLK est augmentée dans des îlots de rattes gestantes et des souris obèses comparés à leurs contrôles respectifs. A l'inverse, dans des sujets diabétiques, l'expression de DLK est diminuée. Ensemble ces résultats montrent l'importance de DLK dans l'adaptation des îlots par un mécanisme qui pourrait impliquer la voie de signalisation de JNK. Des défauts dans cette voie régulée par DLK pourraient contribuer au dysfonctionnement et la mort de la cellule β pancréatique et par conséquent au développement du diabète. L'étude détaillée du mécanisme par lequel DLK active la voie de signalisation JNK et régule la fonction de la cellule β pancréatique pourrait ouvrir la voie des nouvelles thérapies ciblant l'amélioration de la fonction de la cellule β dans le diabète. - Pancreatic β-cells are evidently plastic in their ability to regulate insulin secretion. The quantity of insulin released by these cells varies according to the stimulus, and the prevailing glucose concentration, β-cell function is pivotal in glucose homeostasis, as their dysfunction, and death can lead to development of type 1 and type 2 diabetes. There are numerous reports so far underlying the role of inflammation in dysfunction, and destruction of β-cells, in both type 1 and type 2 diabetes. Chronic excess of pro¬inflammatory cytokines promotes a β-cell decline, via induction of the c-Jun N-terminal Kinase (JNK) pathway. The activation of the JNK pathway is organized by a scaffold protein-mediated module in which, a three-step phosphorylation cascade occurs. The latter includes, Mitogen activated protein kinase kinase kinase (MAP3K), MAP2K and JNK. In this thesis, we unveil that the MAP3K Dual Leucine Zipper Bearing Kinase (DLK) is selectively, and highly expressed in pancreatic β-cells, as the result from the absence of the transcriptional repressor named, Repressor Element 1 Silencing Transcription (REST). We show that DLK regulates activation of JNK, and is required for β-cell function and survival by modulating the PDX-1 transcription factor. Silencing of DLK expression diminishes insulin expression, and potentiated cytokine-mediated apoptosis. Conversely, overexpression of DLK increased insulin expression, and glucose-induced insulin secretion. Therefore, an appropriate level of DLK is critical for β-cell function and survival. Obesity and pregnancy are characterized by hyperinsulinemia resulting from an increased production and secretion of insulin. In isolated islets of pregnant rats, and obese mice, the expression of DLK was elevated when compared to their respective controls. However, decreased expression of DLK was observed in islets of individuals with diabetes. Taken together, we highlight the importance of DLK in islet adaptation, and describe a mechanism that may involve the JNK signaling. Deficiency in the JNK pathway regulated by DLK may contribute to β-cell failure and death, and thereby development of diabetes. Unraveling the mechanism whereby DLK activates the JNK pathway, and β-cell function, may pave the way for the design of novel therapies, aiming to improve β-cell function and survival in diabetes in general.

Environmental Kuznets Curves for Carbon Emissions: A Critical Survey

The empirical finding of an inverse U-shaped relationship between per capita income and pollution, the so-called Environmental Kuznets Curve (EKC), suggests that as countries experience economic growth, environmental deterioration decelerates and thus becomes less of an issue. Focusing on the prime example of carbon emissions, the present article provides a critical review of the new econometric techniques that have questioned the baseline polynomial specification in the EKC literature. We discuss issues related to the functional form, heterogeneity, “spurious” regressions and spatial dependence to address whether and to what extent the EKC can be observed. Despite these new approaches, there is still no clear-cut evidence supporting the existence of the EKC for carbon emissions. JEL classifications: C20; Q32; Q50; O13 Keywords: Environmental Kuznets Curve; Carbon emissions; Functional form; Heterogeneity; “Spurious” regressions; Spatial dependence.Residential satisfaction is often used as a barometer to assess the performance of public policy and programmes designed to raise individuals' well-being. However, the fact that responses elicited from residents might be biased by subjective, non-observable factors casts doubt on whether these responses can be taken as trustable indicators of the individuals' housing situation. Emotional factors such as aspirations or expectations might affect individuals' cognitions of their true residential situation. To disentangle this puzzle, we investigated whether identical residential attributes can be perceived differently depending on tenure status. Our results indicate that tenure status is crucial not only in determining the level of housing satisfaction, but also regarding how dwellers perceive their housing characteristics. Keywords: Housing satisfaction, subjective well-being, homeownership. JEL classification: D1, R2.

The Committee on Climate Change: A policy analysis

Domestic action on climate change is increasingly important in the light of the difficulties with international agreements and requires a combination of solutions, in terms of institutions and policy instruments. One way of achieving government carbon policy goals may be the creation of an independent body to advise, set or monitor policy. This paper critically assesses the Committee on Climate Change (CCC), which was created in 2008 as an independent body to help move the UK towards a low carbon economy. We look at the motivation for its creation in terms of: information provision, advice, monitoring, or policy delegation. In particular we consider its ability to overcome a time inconsistency problem by comparing and contrasting it with another independent body, the Monetary Policy Committee of the Bank of England. In practice the Committee on Climate Change appears to be the ‘inverse’ of the Monetary Policy Committee, in that it advises on what the policy goal should be rather than being responsible for achieving it. The CCC incorporates both advisory and monitoring functions to inform government and achieve a credible carbon policy over a long time frame. This is a similar framework to that adopted by Stern (2006), but the CCC operates on a continuing basis. We therefore believe the CCC is best viewed as a "Rolling Stern plus" body. There are also concerns as to how binding the budgets actually are and how the budgets interact with other energy policy goals and instruments, such as Renewable Obligation Contracts and the EU Emissions Trading Scheme. The CCC could potentially be reformed to include: an explicit information provision role; consumption-based accounting of emissions and control of a policy instrument such as a balanced-budget carbon tax.

Switching between apparently redundant iron-uptake mechanisms benefits bacteria in changeable environments.

Bacteria often possess multiple siderophore-based iron uptake systems for scavenging this vital resource from their environment. However, some siderophores seem redundant, because they have limited iron-binding efficiency and are seldom expressed under iron limitation. Here, we investigate the conundrum of why selection does not eliminate this apparent redundancy. We focus on Pseudomonas aeruginosa, a bacterium that can produce two siderophores-the highly efficient but metabolically expensive pyoverdine, and the inefficient but metabolically cheap pyochelin. We found that the bacteria possess molecular mechanisms to phenotypically switch from mainly producing pyoverdine under severe iron limitation to mainly producing pyochelin when iron is only moderately limited. We further show that strains exclusively producing pyochelin grew significantly better than strains exclusively producing pyoverdine under moderate iron limitation, whereas the inverse was seen under severe iron limitation. This suggests that pyochelin is not redundant, but that switching between siderophore strategies might be beneficial to trade off efficiencies versus costs of siderophores. Indeed, simulations parameterized from our data confirmed that strains retaining the capacity to switch between siderophores significantly outcompeted strains defective for one or the other siderophore under fluctuating iron availabilities. Finally, we discuss how siderophore switching can be viewed as a form of collective decision-making, whereby a coordinated shift in behaviour at the group level emerges as a result of positive and negative feedback loops operating among individuals at the local scale.

Benzodiazepine receptor ligand influences on learning: an endogenous modulatory mechanism mediated by benzodiazepines possibly of alimentary origin

In rats pre-but not post-training ip administration of either flumazenil, a central benzodiazepine (BSD) receptor antagonist, or of n-butyl-B-carboline-carboxylate (BCCB), an inverse agonist, enhanced retention of inhibitory avoidance learning. Flumazenil vlocked the enhancing effect of BCCB, and the inhibitory effect of the BZD agonists clonazepam and diazepam also given pre-training. Post-training administration of these drugs had no effects. The peripheral BZD receptor agonist/chloride channel blocker Ro5-4864 had no effect on the inhibitory avoidance task when given ip prior to training, buth it caused enhancement when given immediately post-training either ip or icv. This effect was blocked by PK11195, a competitive antagonist of Ro5-4864. These results suggest that ther is an endogenous mechanism mediated by BZD agonists, which is sensitive to inverse agonists and that normally down-regulates the formation of memories through a mechanism involving GABA-A receptors and the corresponding chloride channels. The most likely agonists for the endogenous mechanism suggested are the diazepam-like BZDs found in brain whose origin is possibly alimentary. Levels of these BZDs in the cortex were found to sharply decrease after inhibitory acoidance training or mere exposure to the training apparatus.