Leptin modulation of locomotor and emotional behaviors : the role of STAT3 signaling in dopamine neurons

La leptine circule en proportion de la masse graisseuse du corps et la transduction de son signal à travers la forme longue de son récepteur via un certain nombre de voies neurales , y compris MAPK, PI3-K ,AMPK et JAK2 - STAT3 . Il faut noter que STAT3 constitue une voie clée au récepteur de la leptine par laquelle la leptine module l'expression des gènes impliqués dans la régulation du bilan énergétique. La plupart des recherches ont porté sur la fonction du récepteur de la leptine au sein de l' hypothalamus, en particulier la fonction du récepteur de la leptine dans le noyau arqué. Toutefois, les récepteurs de la leptine sont également exprimés sur les neurones dopaminergiques de l'aire tégmentale ventrale et la leptine agit sur cette région du cerveau pour influencer la prise alimentaire, la motivation, la locomotion, l'anxiété et la transmission de la dopamine. De plus, la leptine active la STAT3 dans les dopaminergiques et GABAergiques populations neuronales. Bien que ces résultats contribuent à notre compréhension des multiples actions de la leptine dans le système nerveux central, il reste à résoudre les cellules et la signalisation du récepteur de la leptine qui sont responsables des effets neurocomportementaux de la leptine dans le mésencéphale. Visant à déterminer la contribution de la voie de signalisation STAT3 dans les neurones dopaminergiques du mésencéphale, nous avons généré une lignée de souris knockout conditionnel dans lequel l'activation du gène de STAT3 sur son résidu tyrosine 705 ( Tyr 705 ) est absent spécifiquement dans les neurones dopaminergiques. Avec l'utilisation de ce modèle de souris génétique, nous avons évalué l'impact de l'ablation de la signalisation STAT3 dans les neurones dopaminergiques sur un certain nombre de fonctions liées à la dopamine, y compris l'alimentation, la locomotion, les comportements liés à la récompense, l'émotion et la libération de dopamine dans le noyau accumbens. Fait intéressant, nous avons observé un dimorphisme sexuel dans le phénotype des souris STAT3DAT-KO. L'activation de la voie de signalisation STAT3 dans les neurones dopaminergiques est responsable de l'action de la leptine dans la réduction de la locomotion, récompense liée à l'activité physique, et de l'augmentation de la libération et de la disponibilité de la dopamine chez les souris mâles. Cependant, il ne module pas le comportement émotionnel. D'autre part, les souris femelles STAT3DAT-KO augmentent les niveaux d'anxiété et les niveaux plasmatiques de corticostérone, sans provoquer de changements de la dépression. Cependant, la perte d'activation de STAT3 dans les neurones dopaminergiques ne module pas le comportement locomoteur chez les souris femelles. Notamment, les actions de la leptine dans le mésencéphale pour influencer le comportement alimentaire ne sont pas médiées par l'activation de STAT3 dans les neurones dopaminergiques, considérant que les souris mâles et femelles ont un comportement alimentaire normal. Nos résultats démontrent que la voie de signalisation STAT3 dans les neurones dopaminergiques est responsable des effets anxiolytiques de la leptine, et soutient l'hypothèse que la leptine communique l'état d'énergie du corps (i.e. la relation entre la dépense et les apports énergétiques) pour les régions mésolimbiques pour atténuer les effets de motivation et de récompense de plusieurs comportements qui servent à réhabiliter ou à épuiser les réserves d'énergie. En outre, ce travail souligne l'importance d'étudier la modulation de la signalisation de la leptine dans différente types de cellules, afin d'identifier les voies de signalisation et les mécanismes cellulaires impliqués dans les différentes fonctions neuro-comportementales de la leptine.

The impact of early intra-articular corticosteroid injections on the outcome of oligoarticular juvenile idiopathic arthritis

Contexte Un objectif important de la prise en charge de l'arthrite juvénile oligoarticulaire serait d'altérer le cours de la maladie à l'aide d'une thérapie hâtive. Nous avons étudié l'effet des injections intra-articulaires de corticostéroïdes hâtives sur les chances d'atteindre un décompte d'articulation active de zéro et une maladie inactive. Méthode Les données démographiques, cliniques et thérapeutiques des patients avec oligoarthrite juvénile enrôlés dans une étude prospective longitudinale pancanadienne ont été collectées pendant 2 ans. Une injection hâtive était définie comme étant reçue dans les 3 premiers mois suivant le diagnostic. Les équations d'estimation généralisées ont été utilisées pour l'analyse statistique. Résultats Trois cent dix patients ont été inclus. Cent onze (35.8%) ont reçu une injection hâtive. Ces derniers avaient une maladie plus active lors de l'entrée dans l'étude. Les patients exposés à une injection hâtive avaient une chance similaire d'obtenir un décompte d'articulation active de zéro, OR 1.52 (IC95% 0.68-3.37), p=0.306 mais étaient significativement moins à risque d'avoir une maladie inactive, OR 0.35 (IC95% 0.14-0.88), p=0.026. Interprétation Dans cette cohorte de 310 patients avec oligoarthrite juvénile, les injections hâtives de corticostéroïdes n'ont pas mené à une probabilité plus élevée d'atteindre un décompte d'articulation active de zéro ou une maladie inactive. Des problématiques méthodologiques intrinsèques à l'utilisation de données observationnelles pour fins d'estimation d'effets thérapeutiques auraient pu biaiser les résultats. Nous ne pouvons affirmer avec certitude que les injections hâtives n'améliorent pas le décours de la maladie. Des études prospectives adressant les limitations soulevées seront requises pour clarifier la question.

Early-onset and late-onset Alzheimer’s disease are associated with distinct patterns of memory impairment

The goal of this study was to investigate the specific patterns of memory breakdown in patients suffering from early-onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease (LOAD). Twenty EOAD patients, twenty LOAD patients, twenty matched younger controls, and twenty matched older controls participated in this study. All participants underwent a detailed neuropsychological assessment, an MRI scan, an FDG-PET scan, and AD patients had biomarkers as supporting evidence of both amyloïdopathy and neuronal injury. Results of the neuropsychological assessment showed that both EOAD and LOAD groups were impaired in the domains of memory, executive functions, language, praxis, and visuoconstructional abilities, when compared to their respective control groups. EOAD and LOAD groups, however, showed distinct patterns of memory impairment. Even though both groups were similarly affected on measures of episodic, short term and working memory, in contrast semantic memory was significantly more impaired in LOAD than in EOAD patients. The EOAD group was not more affected than the LOAD group in any memory domain. EOAD patients, however, showed significantly poorer performance in other cognitive domains including executive functions and visuoconstructional abilities. A more detailed analysis of the pattern of semantic memory performance among patient groups revealed that the LOAD was more profoundly impaired, in tasks of both spontaneous recall and semantic recognition. Voxel-Based Morphometry (VBM) analyses showed that impaired semantic performance in patients was associated with reduced gray matter volume in the anterior temporal lobe region, while PET-FDG analyses revealed that poorer semantic performance was associated with greater hypometabolism in the left temporoparietal region, both areas reflecting key regions of the semantic network. Results of this study indicate that EOAD and LOAD patients present with distinct patterns of memory impairment, and that a genuine semantic impairment may represent one of the clinical hallmarks of LOAD.

Investigation of Offences against National Security

The study is a close scrutiny of the process of investigation of offences in India along with an analysis of powers and functions of the investigating agency. The offences, which are prejudicial to sovereignty, integrity and security of the nation or to its friendly relations with foreign states, are generally called the offences against national security. Offences against national security being prejudicial to the very existence of the nation and its legal system, is a heinous and terrible one. As early as 1971 the Law Commission of India had pointed out the need of treating the offences relating to national security and their perpetrators on a totally different procedural footing. The recommendation that, all the offences coming under the said category ought to be brought under the purview of a single enactment so as to confront such offences effectively. The discrepancies in and inadequacies of the criminal justice system in India as much as they are related to the investigations of the offences against national security are examined and the reforms are also suggested. The quality of criminal justice is closely linked with the caliber of the prosecution system and many of the acquittals in courts can be ascribed not only to poor investigations but also to poor quality of prosecution.

Characterisation of Transparent Conducting Thin Films Grown by Pulsed Laser Deposition and RF Magnetron Sputtering

Materials exhibiting transparency and electrical conductivity simultaneously, transparent conductors, Transparent conducting oxides (TCOs), which have high transparency through the visible spectrum and high electrical conductivity are already being used in numerous applications. Low-emission windows that allow visible light through while reflecting the infrared, this keeps the heat out in summer, or the heat in, in winter. A thin conducting layer on or in between the glass panes achieves this. Low-emission windows use mostly F-doped SnO2. Most of these TCO’s are n type semiconductors and are utilized in a variety of commercial applications, such as flat-panel displays, photovoltaic devices, and electrochromic windows, in which they serve as transparent electrodes. Novel functions may be integrated into the materials since oxides have a variety of elements and crystal structures, providing great potential for realizing a diverse range of active functions. However, the application of TCOs has been restricted to transparent electrodes, notwithstanding the fact that TCOs are n-type semiconductors. The primary reason is the lack of p-type TCOs, because many of the active functions in semiconductors originate from the nature of the pn-junction. In 1997, H. Kawazoe et al.[2] reported CuAlO2 thin films as a first p-type TCO along with a chemical design concept for the exploration of other p-type TCOs.

Growth and Characterization of ZnO based Heterojunction diodes and ZnO Nanostructuresby Pulsed Laser Ablation

Transparent conducting oxides (TCO’s) have been known and used for technologically important applications for more than 50 years. The oxide materials such as In2O3, SnO2 and impurity doped SnO2: Sb, SnO2: F and In2O3: Sn (indium tin oxide) were primarily used as TCO’s. Indium based oxides had been widely used as TCO’s for the past few decades. But the current increase in the cost of indium and scarcity of this material created the difficulty in obtaining low cost TCO’s. Hence the search for alternative TCO material has been a topic of active research for the last few decades. This resulted in the development of various binary and ternary compounds. But the advantages of using binary oxides are the easiness to control the composition and deposition parameters. ZnO has been identified as the one of the promising candidate for transparent electronic applications owing to its exciting optoelectronic properties. Some optoelectronics applications of ZnO overlap with that of GaN, another wide band gap semiconductor which is widely used for the production of green, blue-violet and white light emitting devices. However ZnO has some advantages over GaN among which are the availability of fairly high quality ZnO bulk single crystals and large excitonic binding energy. ZnO also has much simpler crystal-growth technology, resulting in a potentially lower cost for ZnO based devices. Most of the TCO’s are n-type semiconductors and are utilized as transparent electrodes in variety of commercial applications such as photovoltaics, electrochromic windows, flat panel displays. TCO’s provide a great potential for realizing diverse range of active functions, novel functions can be integrated into the materials according to the requirement. However the application of TCO’s has been restricted to transparent electrodes, ii notwithstanding the fact that TCO’s are n-type semiconductors. The basic reason is the lack of p-type TCO, many of the active functions in semiconductor originate from the nature of pn-junction. In 1997, H. Kawazoe et al reported the CuAlO2 as the first p-type TCO along with the chemical design concept for the exploration of other p-type TCO’s. This has led to the fabrication of all transparent diode and transistors. Fabrication of nanostructures of TCO has been a focus of an ever-increasing number of researchers world wide, mainly due to their unique optical and electronic properties which makes them ideal for a wide spectrum of applications ranging from flexible displays, quantum well lasers to in vivo biological imaging and therapeutic agents. ZnO is a highly multifunctional material system with highly promising application potential for UV light emitting diodes, diode lasers, sensors, etc. ZnO nanocrystals and nanorods doped with transition metal impurities have also attracted great interest, recently, for their spin-electronic applications This thesis summarizes the results on the growth and characterization of ZnO based diodes and nanostructures by pulsed laser ablation. Various ZnO based heterojunction diodes have been fabricated using pulsed laser deposition (PLD) and their electrical characteristics were interpreted using existing models. Pulsed laser ablation has been employed to fabricate ZnO quantum dots, ZnO nanorods and ZnMgO/ZnO multiple quantum well structures with the aim of studying the luminescent properties.

A Study on the Reversed Lack of Memory Property and its Generalizations

In this thesis, the concept of reversed lack of memory property and its generalizations is studied.We we generalize this property which involves operations different than the ”addition”. In particular an associative, binary operator ” * ” is considered. The univariate reversed lack of memory property is generalized using the binary operator and a class of probability distributions which include Type 3 extreme value, power function, reflected Weibull and negative Pareto distributions are characterized (Asha and Rejeesh (2009)). We also define the almost reversed lack of memory property and considered the distributions with reversed periodic hazard rate under the binary operation. Further, we give a bivariate extension of the generalized reversed lack of memory property and characterize a class of bivariate distributions which include the characterized extension (CE) model of Roy (2002a) apart from the bivariate reflected Weibull and power function distributions. We proved the equality of local proportionality of the reversed hazard rate and generalized reversed lack of memory property. Study of uncertainty is a subject of interest common to reliability, survival analysis, actuary, economics, business and many other fields. However, in many realistic situations, uncertainty is not necessarily related to the future but can also refer to the past. Recently, Di Crescenzo and Longobardi (2009) introduced a new measure of information called dynamic cumulative entropy. Dynamic cumulative entropy is suitable to measure information when uncertainty is related to the past, a dual concept of the cumulative residual entropy which relates to uncertainty of the future lifetime of a system. We redefine this measure in the whole real line and study its properties. We also discuss the implications of generalized reversed lack of memory property on dynamic cumulative entropy and past entropy.In this study, we extend the idea of reversed lack of memory property to the discrete set up. Here we investigate the discrete class of distributions characterized by the discrete reversed lack of memory property. The concept is extended to the bivariate case and bivariate distributions characterized by this property are also presented. The implication of this property on discrete reversed hazard rate, mean past life, and discrete past entropy are also investigated.

Isolation, purification and characterization of Protease Inhibitor from Moringa oleifera Lam.

Protease inhibitors are one of the most important tools of nature for regulating the proteolytic activity of their target proteases. They are synthesized in biological systems and they play a critical role in controlling a number of diverse physiological functions. The current investigation focused on the isolation, purification and characterization of a novel protease inhibitor from Moringa oleifera. The results obtained during the course of study opens new perspectives for the utilization of protease inhibitor from Moringa oleifera for various pharmaceutical, agricultural and food industries. The biological and physicochemical properties exhibited by the novel protease inhibitor from Moringa oleifera clearly testify its suitability for the development as a drug for application in pharmaceutical industries such as anticoagulant agent or biocontrol agent in agriculture and even as a food preservant. There is a scope for further research on the structure elucidation and protein engineering towards a wide range of further applications. Detailed structure/function analysis of these proteins is important to facilitate their use in genetic engineering for various applications.

Modeling and Analysis of Some Heavy Tailed Time Series

The thesis has covered various aspects of modeling and analysis of finite mean time series with symmetric stable distributed innovations. Time series analysis based on Box and Jenkins methods are the most popular approaches where the models are linear and errors are Gaussian. We highlighted the limitations of classical time series analysis tools and explored some generalized tools and organized the approach parallel to the classical set up. In the present thesis we mainly studied the estimation and prediction of signal plus noise model. Here we assumed the signal and noise follow some models with symmetric stable innovations.We start the thesis with some motivating examples and application areas of alpha stable time series models. Classical time series analysis and corresponding theories based on finite variance models are extensively discussed in second chapter. We also surveyed the existing theories and methods correspond to infinite variance models in the same chapter. We present a linear filtering method for computing the filter weights assigned to the observation for estimating unobserved signal under general noisy environment in third chapter. Here we consider both the signal and the noise as stationary processes with infinite variance innovations. We derived semi infinite, double infinite and asymmetric signal extraction filters based on minimum dispersion criteria. Finite length filters based on Kalman-Levy filters are developed and identified the pattern of the filter weights. Simulation studies show that the proposed methods are competent enough in signal extraction for processes with infinite variance.Parameter estimation of autoregressive signals observed in a symmetric stable noise environment is discussed in fourth chapter. Here we used higher order Yule-Walker type estimation using auto-covariation function and exemplify the methods by simulation and application to Sea surface temperature data. We increased the number of Yule-Walker equations and proposed a ordinary least square estimate to the autoregressive parameters. Singularity problem of the auto-covariation matrix is addressed and derived a modified version of the Generalized Yule-Walker method using singular value decomposition.In fifth chapter of the thesis we introduced partial covariation function as a tool for stable time series analysis where covariance or partial covariance is ill defined. Asymptotic results of the partial auto-covariation is studied and its application in model identification of stable auto-regressive models are discussed. We generalize the Durbin-Levinson algorithm to include infinite variance models in terms of partial auto-covariation function and introduce a new information criteria for consistent order estimation of stable autoregressive model.In chapter six we explore the application of the techniques discussed in the previous chapter in signal processing. Frequency estimation of sinusoidal signal observed in symmetric stable noisy environment is discussed in this context. Here we introduced a parametric spectrum analysis and frequency estimate using power transfer function. Estimate of the power transfer function is obtained using the modified generalized Yule-Walker approach. Another important problem in statistical signal processing is to identify the number of sinusoidal components in an observed signal. We used a modified version of the proposed information criteria for this purpose.

Toxicity, accumulation and depuration of heavy metalsin the brown mussel perna indica

In this thesis certain important aspects of heavy metal toxicity have been worked out. Recent studies have clearly shown that when experimental media contained more than one heavy metals, such metals could conspicuously influence the toxic reaction of the animals both in terms of quantity and nature. The experimental results available on individual metal toxicity show that, in majority of such results, unrealistically high concentrations of dissolved metals are involved. A remarkable number of factors have been shown to influence metal toxicity such as various environmental factors particularly temperature and salinity, the condition of the organism and the ability of some of the marine organisms to adapt to metallic contamination. Further, some of the more sensitive functions like embryonic and larval development, growth and fecundity, oxygen utilization and the function of various enzymes are found to be demonstrably sensitive in the presence of heavy metals. However, some of the above functions could be compensated for by adaptive process. If it is assumed that the presence of a single metal in higher concentrations could affect the life function of marine animals, more than one metal in the experimental media should manifest such effects in a greater scale. Commonly known as synergism or more than additivity, majority of heavy metals bring about synergistic reaction .The work presented in this thesis comprises lethal and sublethal toxicities of different salt forms of copper and silver on the brown mussel Perna indica. during the present investigation sublethal concentrations of copper and silver in their dent effects on survival, oxygen consumption, filtration, accumulation and depuration on Perna indica. The results are presented under different sections to make the presentation meaningful .

Pattern of Executive Remuneration in the Manufacturing Public Enterprises in Kerala

The study is undertaken by the researcher with the object of examining the remuneration pattern of executive personnel in the manufacturing public enterprises in Kerala so as to find out whether there is any rationale or criteria involved in remunerating executives. It is also envisaged to find out the pattern of executive remuneration in the various categories of industries and inter—industry disparities among the public sector enterprises. This is considered to be a very fruitful area for investigation, particularly in view of the generally prevailing notion that public sector executives in Kerala are not remunerated properly and glaring inequalities and disparities are existing among the various categories of industries and within the same industry. Therefore the study is to explore the criteria used for the determination of executive remuneration and the relative weightage of various factors such as size of the firm, rate of return sales volume etc of the organisation and various other factors such as qualification, experience, level of job and functions of executives. Further the study is extended to find out the role of 'pay' towards motivation and efficiency of the executive personnel

Functional genomics of the Drosophila melanogaster X chromosome and the role of DWnt5 during development

The collection of X chromosome insertions (PX) lethal lines, which was isolated from a screen for essential genes on the X chromosome, was characterized by means of cloning the insertion sites, mapping the sites within genomic DNA and determination of the associated reporter gene expresssion patterns. The established STS flanking the P element insertion sites were submitted to EMBL nucleotide databases and their in situ data together with the enhancer trap expression patterns have been deposited in the FlyView database. The characterized lines are now available to be used by the scientific community for a detailed analysis of the newly established lethal gene functions. One of the isolated genes on the X chromosome was the Drosophila gene Wnt5 (DWnt5). From two independent screens, one lethal and three homozygous viable alleles were recovered, allowing the identification of two distinct functions for DWnt5 in the fly. Observations on the developing nervous system of mutant embryos suggest that DWnt5 activity affects axon projection pattern. Elevated levels of DWNT5 activity in the midline cells of the central nervous system causes improper establishment and maintenance of the axonal pathways. Our analysis of the expression and mutant phenotype indicates that DWnt5 function in a process needed for proper organization of the nervous system. A second and novel function of DWnt5 is the control of the body size by regulation of the cell number rather than affecting the size of cells. Moreover, experimentally increased DWnt5 levels in a post-mitotic region of the eye imaginal disc causes abnormal cell cycle progression, resulting in additional ommatidia in the adult eye when compared to wild type. The increased cell number and the effects on the cell cycle after exposure to high DWNT5 levels is the result of a failure to downregulate cyclin B and therefore the unsuccessful establishment of a G1 arrest.

Bayes quadratic unbiased estimator of spatial covariance parameters

This work presents Bayes invariant quadratic unbiased estimator, for short BAIQUE. Bayesian approach is used here to estimate the covariance functions of the regionalized variables which appear in the spatial covariance structure in mixed linear model. Firstly a brief review of spatial process, variance covariance components structure and Bayesian inference is given, since this project deals with these concepts. Then the linear equations model corresponding to BAIQUE in the general case is formulated. That Bayes estimator of variance components with too many unknown parameters is complicated to be solved analytically. Hence, in order to facilitate the handling with this system, BAIQUE of spatial covariance model with two parameters is considered. Bayesian estimation arises as a solution of a linear equations system which requires the linearity of the covariance functions in the parameters. Here the availability of prior information on the parameters is assumed. This information includes apriori distribution functions which enable to find the first and the second moments matrix. The Bayesian estimation suggested here depends only on the second moment of the prior distribution. The estimation appears as a quadratic form y'Ay , where y is the vector of filtered data observations. This quadratic estimator is used to estimate the linear function of unknown variance components. The matrix A of BAIQUE plays an important role. If such a symmetrical matrix exists, then Bayes risk becomes minimal and the unbiasedness conditions are fulfilled. Therefore, the symmetry of this matrix is elaborated in this work. Through dealing with the infinite series of matrices, a representation of the matrix A is obtained which shows the symmetry of A. In this context, the largest singular value of the decomposed matrix of the infinite series is considered to deal with the convergence condition and also it is connected with Gerschgorin Discs and Poincare theorem. Then the BAIQUE model for some experimental designs is computed and compared. The comparison deals with different aspects, such as the influence of the position of the design points in a fixed interval. The designs that are considered are those with their points distributed in the interval [0, 1]. These experimental structures are compared with respect to the Bayes risk and norms of the matrices corresponding to distances, covariance structures and matrices which have to satisfy the convergence condition. Also different types of the regression functions and distance measurements are handled. The influence of scaling on the design points is studied, moreover, the influence of the covariance structure on the best design is investigated and different covariance structures are considered. Finally, BAIQUE is applied for real data. The corresponding outcomes are compared with the results of other methods for the same data. Thereby, the special BAIQUE, which estimates the general variance of the data, achieves a very close result to the classical empirical variance.

Functions satisfying holonomic q-differential equations

In a similar manner as in some previous papers, where explicit algorithms for finding the differential equations satisfied by holonomic functions were given, in this paper we deal with the space of the q-holonomic functions which are the solutions of linear q-differential equations with polynomial coefficients. The sum, product and the composition with power functions of q-holonomic functions are also q-holonomic and the resulting q-differential equations can be computed algorithmically.

Relativistic effects in physics and chemistry of element 105. [Part] IV.

Results of relativistic (Dirac-Slater and Dirac-Fock) and nonrelativistic (Hartree-Fock-Slater) atomic and molecular calculations have been compared for the group 5 elements Nb, Ta, and Ha and their compounds MCl_5, to elucidate the influence of relativistic effects on their properties especially in going from the 5d element Ta to the 6d element Ha. The analysis of the radial distribution of the valence electrons of the metals for electronic configurations obtained as a result of the molecular calculations and their overlap with ligands show opposite trends in behavior for ns_1/2, np_l/2, and (n -1 )d_5/2 orbitals for Ta and Ha in the relativistic and nonrelativistic cases. Relativistic contraction and energetic stabilization of the ns_1/2 and np_l/2 wave functions and expansion and destabilization of the (n-1)d_5/2 orbitals make hahnium pentahalide more covalent than tantalum pentahalide and increase the bond strength. The nonrelativistic treatment of the wave functions results in an increase in ionicity of the MCl_5 molecules in going from Nb to Ha making element Ha an analog of V. Different trends for the relativistic and nonrelativistic cases are also found for ionization potentials, electronic affinities, and energies of charge-transfer transitions as well as the stability of the maximum oxidation state.