Sex and clock to discover new PPARα functions

Summary : PPARα is a ligand-activated transcription factor that is a member of the nuclear receptor superfamily. In rodents, PPARα is highly expressed in liver, especially in parenchymal cells, where it has an impact on several hepatic functions such as nutrient metabolism, inflammation and metabolic stress. Ligands for PPARα comprise long chain unsaturated fatty acids, eicosanoids and lipid lowering fibrate drugs. In liver, many metabolic processes are orchestrated by the hepatic circadian clock. The aim of the hepatic clock is to synchronize cellular pathways allowing animals to adapt their metabolism to predictable daily changes in the environment. Indeed, similar to PPARα, the hepatic clock influences nutrient metabolism and detoxification through circadian output regulators :the PAR-domain basic leucine zipper proteins called PAR blip proteins. In this report, we showed that through a positive feedback loop mechanism, PAR. blip, proteins participate to the availability of PPARα endogenous ligands that contribute to the circadian expression and functions of PPARα. Interestingly, we also discovered some unexpected hepatic sexual dimorphic functions of PPARα. These functions are determined b PPARα sumoylation, interaction with DNA methylation mechanism and with unexpected proteins with gender specificity. The connection between circadian clock and hepatic sexual dimorphism opens new perspectives regarding the chronobiology of PPARα activity and the beneficial effects of PPARα agonist in the treatment of diseases related to steroid hormones metabolism characterized by inflammation and hepatotoxicity. Résumé : PPARα est un facteur de transcription activé par un ligand, membre de la superfamille des récepteurs nucléaires. Chez les rongeurs, PPARα est fortement exprimé dans le foie, spécialement dans les cellules du parenchyme dans lesquelles il joue un role important dans les fonctions hépatiques tels que le métabolisme des nutriments, l'inflammation et les stress métaboliques. Les ligands pour PPARα comprennent les acides gras à longues chaînes, les eicosanoides et les médicaments hypolipidémiques (fibrates). Dans le foie, beaucoup de processus métaboliques sont orchestrés par l'horloge circadienne hépatique. Le but de cette horloge est de synchroniser les voies métaboliqués permettant aux animaux d'adapter leurs métabolismes aux changements journaliers. Ainsi, l'horloge hépatique influence le métabolisme des nutriments tels que l'utilisation des lipides à travers certains régulateurs circadians appelés facteurs de transcription PAR bZips. Dans ce mémoire, nous avons montré qu'à travers une boucle de régulation, les protéines PAR bZip contrôlent la production des ligands endogènes à PPARα, jouant un rôle dans l'expression circadienne et les fonctions de PPARα. Nous avons également découvert des aspects méconnus des fonctions liées au dimorphisme sexuel de PPARα. Nous avons montré que PPARα est différemment sumoylisé entre les sexes et interagit avec la méthylation de l'ADN ainsi qu'avec des protéines insoupçonnées comme partenaires de PPARα. De part leur lien avec l'horloge circadienne et le dimorphisme sexuel, nos découvertes ouvrent de nouvelles perspectives concernant la chronobiologie de l'activité de PPARα et les effets bénéfiques des ses activateurs dans le traitement des maladies liées au métabolisme des hormones stéroides.

The functions of sleep.

Here we report on The Satellite Symposium on Sleep Function that was held in Lausanne during 6(th) FENS forum and brought together neuroscientists from basic and clinical sleep research. We illustrate the principal questions that arose during this interdisciplinary gathering and introduce the contents of nine review articles on aspects of sleep that are contained in this Special Issue of the European Journal of Neuroscience.

Revisiting Field Capacity (FC): variation of definition of FC and its estimation from pedotransfer functions

Taking into account the nature of the hydrological processes involved in in situ measurement of Field Capacity (FC), this study proposes a variation of the definition of FC aiming not only at minimizing the inadequacies of its determination, but also at maintaining its original, practical meaning. Analysis of FC data for 22 Brazilian soils and additional FC data from the literature, all measured according to the proposed definition, which is based on a 48-h drainage time after infiltration by shallow ponding, indicates a weak dependency on the amount of infiltrated water, antecedent moisture level, soil morphology, and the level of the groundwater table, but a strong dependency on basic soil properties. The dependence on basic soil properties allowed determination of FC of the 22 soil profiles by pedotransfer functions (PTFs) using the input variables usually adopted in prediction of soil water retention. Among the input variables, soil moisture content θ (6 kPa) had the greatest impact. Indeed, a linear PTF based only on it resulted in an FC with a root mean squared residue less than 0.04 m³ m-3 for most soils individually. Such a PTF proved to be a better FC predictor than the traditional method of using moisture content at an arbitrary suction. Our FC data were compatible with an equivalent and broader USA database found in the literature, mainly for medium-texture soil samples. One reason for differences between FCs of the two data sets of fine-textured soils is due to their different drainage times. Thus, a standardized procedure for in situ determination of FC is recommended.

International union of basic and clinical pharmacology. XCI. structure, function, and pharmacology of acid-sensing ion channels and the epithelial Na+ channel.

The epithelial Na(+) channel (ENaC) and the acid-sensing ion channels (ASICs) form subfamilies within the ENaC/degenerin family of Na(+) channels. ENaC mediates transepithelial Na(+) transport, thereby contributing to Na(+) homeostasis and the maintenance of blood pressure and the airway surface liquid level. ASICs are H(+)-activated channels found in central and peripheral neurons, where their activation induces neuronal depolarization. ASICs are involved in pain sensation, the expression of fear, and neurodegeneration after ischemia, making them potentially interesting drug targets. This review summarizes the biophysical properties, cellular functions, and physiologic and pathologic roles of the ASIC and ENaC subfamilies. The analysis of the homologies between ENaC and ASICs and the relation between functional and structural information shows many parallels between these channels, suggesting that some mechanisms that control channel activity are shared between ASICs and ENaC. The available crystal structures and the discovery of animal toxins acting on ASICs provide a unique opportunity to address the molecular mechanisms of ENaC and ASIC function to identify novel strategies for the modulation of these channels by pharmacologic ligands.

Competence in intensive and critical care nursing - development of a basic assessment scale for graduating nursing students

Intensive and critical care nursing is a speciality in its own right and with its own nature within the nursing profession. This speciality poses its own demands for nursing competencies. Intensive and critical care nursing is focused on severely ill patients and their significant others. The patients are comprehensively cared for, constantly monitored and their vital functions are sustained artificially. The main goal is to win time to cure the cause of the patient’s situation or illness. The purpose of this empirical study was i) to describe and define competence and competence requirements in intensive and critical care nursing, ii) to develop a basic measurement scale for competence assessment in intensive and critical care nursing for graduating nursing students, and iii) to describe and evaluate graduating nursing students’ basic competence in intensive and critical care nursing by seeking the reference basis of self-evaluated basic competence in intensive and critical care nursing from ICU nurses. However, the main focus of this study was on the outcomes of nursing education in this nursing speciality. The study was carried out in different phases: basic exploration of competence (phase 1 and 2), instrumentation of competence (phase 3) and evaluation of competence (phase 4). Phase 1 (n=130) evaluated graduating nursing students’ basic biological and physiological knowledge and skills for working in intensive and critical care with Basic Knowledge Assessment Tool version 5 (BKAT-5, Toth 2012). Phase 2 focused on defining competence in intensive and critical care nursing with the help of literature review (n=45 empirical studies) as well as competence requirements in intensive and critical care nursing with the help of experts (n=45 experts) in a Delphi study. In phase 3 the scale Intensive and Critical Care Nursing Competence Scale (ICCN-CS) was developed and tested twice (pilot test 1: n=18 students and n=12 nurses; pilot test 2: n=56 students and n=54 nurses). Finally, in phase 4, graduating nursing students’ competence was evaluated with ICCN-CS and BKAT version 7 (Toth 2012). In order to develop a valid assessment scale of competence for graduating nursing students and to evaluate and establish the competence of graduating nursing students, empirical data were retrieved at the same time from both graduating nursing students (n=139) and ICU nurses (n=431). Competence can be divided into clinical and general professional competence. It can be defined as a specific knowledge base, skill base, attitude and value base and experience base of nursing and the personal base of an intensive and critical care nurse. Personal base was excluded in this self-evaluation based scale. The ICCN-CS-1 consists of 144 items (6 sum variables). Finally, it became evident that the experience base of competence is not a suitable sum variable in holistic intensive and critical care competence scale for graduating nursing students because of their minor experience in this special nursing area. ICCN-CS-1 is a reliable and tolerably valid scale for use among graduating nursing students and ICU nurses Among students, basic competence of intensive and critical care nursing was self-rated as good by 69%, as excellent by 25% and as moderate by 6%. However, graduating nursing students’ basic biological and physiological knowledge and skills for working in intensive and critical care were poor. The students rated their clinical and professional competence as good, and their knowledge base and skill base as moderate. They gave slightly higher ratings for their knowledge base than skill base. Differences in basic competence emerged between graduating nursing students and ICU nurses. The students’ self-ratings of both their basic competence and clinical and professional competence were significantly lower than the nurses’ ratings. The students’ self-ratings of their knowledge and skill base were also statistically significantly lower than nurses’ ratings. However, both groups reported the same attitude and value base, which was excellent. The strongest factor explaining students’ conception of their competence was their experience of autonomy in nursing. Conclusions: Competence in intensive and critical care nursing is a multidimensional concept. Basic competence in intensive and critical care nursing can be measured with self-evaluation based scale but alongside should be used an objective evaluation method. Graduating nursing students’ basic competence in intensive and critical care nursing is good but their knowledge and skill base are moderate. Especially the biological and physiological knowledge base is poor. Therefore in future in intensive and critical care nursing education should be focused on both strengthening students’ biological and physiological knowledge base and on strengthening their overall skill base. Practical implications are presented for nursing education, practice and administration. In future, research should focus on education methods and contents, mentoring of clinical practice and orientation programmes as well as further development of the scale.

Discrete commutative difference operator theory

The object of this thesis is to formulate a basic commutative difference operator theory for functions defined on a basic sequence, and a bibasic commutative difference operator theory for functions defined on a bibasic sequence of points, which can be applied to the solution of basic and bibasic difference equations. in this thesis a brief survey of the work done in this field in the classical case, as well as a review of the development of q~difference equations, q—analytic function theory, bibasic analytic function theory, bianalytic function theory, discrete pseudoanalytic function theory and finally a summary of results of this thesis

The full infinite dimensional moment problem on semi-algebraic sets of generalized functions

We consider a generic basic semi-algebraic subset S of the space of generalized functions, that is a set given by (not necessarily countably many) polynomial constraints. We derive necessary and sufficient conditions for an infinite sequence of generalized functions to be realizable on S, namely to be the moment sequence of a finite measure concentrated on S. Our approach combines the classical results about the moment problem on nuclear spaces with the techniques recently developed to treat the moment problem on basic semi-algebraic sets of Rd. In this way, we determine realizability conditions that can be more easily verified than the well-known Haviland type conditions. Our result completely characterizes the support of the realizing measure in terms of its moments. As concrete examples of semi-algebraic sets of generalized functions, we consider the set of all Radon measures and the set of all the measures having bounded Radon–Nikodym density w.r.t. the Lebesgue measure.

Regular Derivations in Basic Superposition-Based Calculi

We prove the completeness of the regular strategy of derivations for superposition-based calculi. The regular strategy was pioneered by Kanger in [Kan63], who proposed that all equality inferences take place before all other steps in the proof. We show that the strategy is complete with the elimination of tautologies. The implication of our result is the completeness of non-standard selection functions by which in non-relational clauses only equality literals (and all of them) are selected.

Operational functions for innovative startups in France

Nessa tese, é buscado um maior entendimento sobre a importância das funções operacionais nas startups francesas. Uma grande flexibilidade das tarefas a ser coberta e uma gestão horizontal caracterizam as startups. Desse jeito, não é muito comum para as empresas recentemente criadas como as startups ter uma politica clara de recursos humanos. Na verdade, cada participante na start-up pode ser levado a pensar de forma diferente em termos de vendas desenvolvimento de negócios, comercialização, marketing, tecnologia ou desenvolvimento de produto. Essa tese não vai explorar cada uma dessas tarefas. Mas vai procurar para identifcar a percepção sobre a alocação ótima de recursos para cada função chave da nova empresa. Qualquer seja o setor de mercado em consideração ou o estágio de amadurecimento da startup, funções chaves que são percebidas como sendo a base para start-ups bem sucedidas são pesquisa & desenvolvimento e comercialização. Funções de liderança não são tão importantes. Somente a startup focada na tecnologia tem uma "função de chefe executivo" com maior importância do que as startups médias. Além disso, empreendedores em série, bem sucedidos ou não, focam predominantemente aspectos relacionados ao marketing e à captação de recursos em detrimento de aspectos ligados à gestão do negócio. No final, os empresários, muitas vezes tem um preconceito ao respeito da sua formação acadêmica porque ele sobrestimam funções que eles pensam poder fazer em comparação das funções que eles são capazes de fazer. Nessa tese, intent-se demonstrar a relação entre as funções ocupadas por um sócio e as ações que ele possui na startup. Essa relação depende do número de sócios (conhecido como acionistas), o tipo de sócios (acionistas principais ou acionistas segundarias) e o impacto na administração corporativa a respeito da distribuição do capital próprio.

General massive one-loop off-shell three-point functions

In this work we compute the most general massive one-loop off-shell three-point vertex in D-dimensions, where the masses, external momenta and exponents of propagators are arbitrary. This follows our previous paper in which we have calculated several new hypergeometric series representations for massless and massive (with equal masses) scalar one-loop three-point functions, in the negative dimensional approach.

Massless and massive one-loop three-point functions in negative dimensional approach

In this article we present the complete massless and massive one-loop triangle diagram results using the negative dimensional integration method (NDIM). We consider the following cases: massless internal fields; one massive, two massive with the same mass m and three equal masses for the virtual particles. Our results are given in terms of hypergeometric and hypergeometric-type functions of the external momenta (and masses for the massive cases) where the propagators in the Feynman integrals are raised to arbitrary exponents and the dimension of the space-time is D. Our approach reproduces the known results; it produces other solutions as yet unknown in the literature as well. These new solutions occur naturally in the context of NDIM revealing a promising technique to solve Feynman integrals in quantum field theories.

Semiclassical scaling functions of sine-Gordon model

We present an analytic study of the finite size effects in sine-Gordon model, based on the semi-classical quantization of an appropriate kink background defined on a cylindrical geometry. The quasi-periodic kink is realized as an elliptic function with its real period related to the size of the system. The stability equation for the small quantum fluctuations around this classical background is of Lame type and the corresponding energy eigenvalues are selected inside the allowed bands by imposing periodic boundary conditions. We derive analytical expressions for the ground state and excited states scaling functions, which provide an explicit description of the flow between the IR and UV regimes of the model. Finally, the semiclassical form factors and two-point functions of the basic field and of the energy operator are obtained, completing the semiclassical quantization of the sine-Gordon model on the cylinder. (C) 2004 Elsevier B.V. All rights reserved.

A discrete finite-dimensional phase space approach for the description of Fe8 magnetic clusters: Wigner and Husimi functions

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Generalized squeezing operators, bipartite Wigner functions and entanglement via Wehrl's entropy functionals

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Stieltjes functions and discrete classical orthogonal polynomials

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)