934 resultados para Retail stores
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Les laves torrentielles sont l'un des vecteurs majeurs de sédiments en milieu montagneux. Leur comportement hydrogéomorphologique est contrôlé par des facteurs géologique, géomorphologique, topographique, hydrologique, climatique et anthropique. Si, en Europe, la recherche s'est plus focalisée sur les aspects hydrologiques que géomorphologiques de ces phénomènes, l'identification des volumes de sédiments potentiellement mobilisables au sein de petits systèmes torrentiels et des processus responsables de leur transfert est d'une importance très grande en termes d'aménagement du territoire et de gestion des dangers naturels. De plus, une corrélation entre des événements pluviométriques et l'occurrence de laves torrentielles n'est pas toujours établie et de nombreux événements torrentiels semblent se déclencher lorsqu'un seuil géomorphologique intrinsèque (degré de remplissage du chenal) au cours d'eau est atteint.Une méthodologie pragmatique a été développée pour cartographier les stocks sédimentaires constituant une source de matériaux pour les laves torrentielles, comme outil préliminaire à la quantification des volumes transportés par ces phénomènes. La méthode s'appuie sur des données dérivées directement d'analyses en environnement SIG réalisées sur des modèles numériques d'altitude de haute précision, de mesures de terrain et d'interprétation de photographies aériennes. La méthode a été conçue pour évaluer la dynamique des transferts sédimentaires, en prenant en compte le rôle des différents réservoirs sédimentaires, par l'application du concept de cascade sédimentaire sous un angle cartographique.Les processus de transferts sédimentaires ont été étudiés dans deux bassins versants des Alpes suisses (torrent du Bruchi, à Blatten beiNaters et torrent du Meretschibach, à Agarn). La cartographie géomorphologique a été couplée avec des mesures complémentaires permettant d'estimer les flux sédimentaires et les taux d'érosion (traçages de peinture, piquets de dénudation et utilisation du LiDAR terrestre). La méthode proposée se révèle innovatrice en comparaison avec la plupart des systèmes de légendes géomorphologiques existants, qui ne sont souvent pas adaptés pour cartographier de manière satisfaisante les systèmes géomorphologiques complexes et actifs que sont les bassins torrentiels. L'intérêt de cette méthode est qu'elle permet l'établissement d'une cascade sédimentaire, mais uniquement pour des systèmes où l'occurrence d'une lave torrentielle est contrôlé par le degré de remplissage en matériaux du chenal. Par ailleurs, le produit cartographique ne peut être directement utilisé pour la création de cartes de dangers - axées sur les zones de dépôt - mais revêt un intérêt pour la mise en place de mesures de correction et pour l'installation de systèmes de monitoring ou d'alerte.La deuxième partie de ce travail de recherche est consacrée à la cartographie géomorphologique. Une analyse a porté sur un échantillon de 146 cartes ou systèmes de légende datant des années 1950 à 2009 et réalisés dans plus de 40 pays. Cette analyse a permis de mettre en évidence la diversité des applications et des techniques d'élaboration des cartes géomorphologiques. - Debris flows are one of the most important vectors of sediment transfer in mountainous areas. Their hydro-geomorphological behaviour is conditioned by geological, geomorphological, topographical, hydrological, climatic and anthropic factors. European research in torrential systems has focused more on hydrological processes than on geomorphological processes acting as debris flow triggers. Nevertheless, the identification of sediment volumes that have the potential to be mobilised in small torrential systems, as well as the recognition of processes responsible for their mobilisation and transfer within the torrential system, are important in terms of land-use planning and natural hazard management. Moreover, a correlation between rainfall and debris flow occurrence is not always established and a number of debris flows seems to occur when a poorly understood geomorphological threshold is reached.A pragmatic methodology has been developed for mapping sediment storages that may constitute source zone of bed load transport and debris flows as a preliminary tool before quantifying their volumes. It is based on data directly derived from GIS analysis using high resolution DEM's, field measurements and aerial photograph interpretations. It has been conceived to estimate sediment transfer dynamics, taking into account the role of different sediment stores in the torrential system applying the concept of "sediment cascade" in a cartographic point of view.Sediment transfer processes were investigated in two small catchments in the Swiss Alps (Bruchi torrent, Blatten bei Naters and Meretschibach torrent, Agarn). Thorough field geomorphological mapping coupled with complementary measurements were conducted to estimate sediment fluxes and denudation rates, using various methods (reference coloured lines, wooden markers and terrestrial LiDAR). The proposed geomorphological mapping methodology is quite innovative in comparison with most legend systems that are not adequate for mapping active and complex geomorphological systems such as debris flow catchments. The interest of this mapping method is that it allows the concept of sediment cascade to be spatially implemented but only for supply-limited systems. The map cannot be used directly for the creation of hazard maps, focused on the deposition areas, but for the design of correction measures and the implementation of monitoring and warning systems.The second part of this work focuses on geomorphological mapping. An analysis of a sample of 146 (extracts of) maps or legend systems dating from the middle of the 20th century to 2009 - realised in more than 40 different countries - was carried out. Even if this study is not exhaustive, it shows a clear renewed interest for the discipline worldwide. It highlights the diversity of applications, techniques (scale, colours and symbology) used for their conception.
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Peatlands form in areas where net primary of organic matter production exceeds losses due to the decomposition, leaching or disturbance. Due to their chemical and physical characteristics, bogs can influence water dynamics because they can store large volumes of water in the rainy season and gradually release this water during the other months of the year. In Diamantina, Minas Gerais, Brazil, a peatland in the environmental protection area of Pau-de-Fruta ensures the water supply of 40,000 inhabitants. The hypothesis of this study is that the peat bogs in Pau-de-Fruta act as an environment for carbon storage and a regulator of water flow in the Córrego das Pedras basin. The objective of this study was to estimate the water volume and organic matter mass in this peatland and to study the influence of this environment on the water flow in the Córrego das Pedras basin. The peatland was mapped using 57 transects, at intervals of 100 m. Along all transects, the depth of the peat bog, the Universal Transverse Mercator (UTM) coordinates and altitude were recorded every 20 m and used to calculate the area and volume of the peatland. The water volume was estimated, using a method developed in this study, and the mass of organic matter based on samples from 106 profiles. The peatland covered 81.7 hectares (ha), and stored 497,767 m³ of water, representing 83.7 % of the total volume of the peat bog. The total amount of organic matter (OM) was 45,148 t, corresponding to 552 t ha-1 of OM. The peat bog occupies 11.9 % of the area covered by the Córrego das Pedras basin and stores 77.6 % of the annual water surplus, thus controlling the water flow in the basin and consequently regulating the water course.
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The concept of tripartite synapse suggests that astrocytes make up a functional synapse with pre- and postsynaptic neuronal elements to modulate synaptic transmission through the regulated release of neuromodulators called gliotransmitters. Release of gliotransmitters such as glutamate or D-serine has been shown to depend on Ca21-dependent exocytosis. However, the origin (cytosolic versus vesicular) of the released gliotransmitter is still a matter of debate. The existence of Ca21-regulated exocytosis in astrocytes has been questioned mostly because the nature of secretory organelles which are loaded with gliotransmitters is unknown. Here we show the existence of a population of vesicles that uptakes and stores glutamate and D-serine in astrocytes which are present in situ. Immunoisolated glial organelles expressing synaptobrevin 2 (Sb2) display morphological and biochemical features very similar to synaptic vesicles. We demonstrate that these organelles not only contain and uptake glutamate but also display a glia-specific transport activity for D-serine. Furthermore, we report that the uptake of D-serine is energized by a H1-ATPase present on the immunoisolated vesicles and that cytosolic chloride ions modulate the uptake of D-serine. Finally, we show that serine racemase (SR), the synthesizing enzyme for D-serine, is anchored to the membrane of glial organelles allowing a local and efficient concentration of the gliotransmitter to be transported. We conclude that vesicles in astrocytes do exist with the goal to store and release D-serine, glutamate and most likely other neuromodulators.
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The major processes discussed below are protein turnover (degradation and synthesis), degradation into urea, or conversion into glucose (gluconeogenesis, Figure 1). Daily protein turnover is a dynamic process characterized by a double flux of amino acids: the amino acids released by endogenous (body) protein breakdown can be reutilized and reconverted to protein synthesis, with very little loss. Daily rates of protein turnover in humans (300 to 400 g per day) are largely in excess of the level of protein intake (50 to 80 g per day). A fast growing rate, as in premature babies or in children recovering from malnutrition, leads to a high protein turnover rate and a high protein and energy requirement. Protein metabolism (synthesis and breakdown) is an energy-requiring process, dependent upon endogenous ATP supply. The contribution made by whole-body protein turnover to the resting metabolic rate is important: it represents about 20 % in adults and more in growing children. Metabolism of proteins cannot be disconnected from that of energy since energy balance influences net protein utilization, and since protein intake has an important effect on postprandial thermogenesis - more important than that of fats or carbohydrates. The metabolic need for amino acids is essentially to maintain stores of endogenous tissue proteins within an appropriate range, allowing protein homeostasis to be maintained. Thanks to a dynamic, free amino acid pool, this demand for amino acids can be continuously supplied. The size of the free amino acid pool remains limited and is regulated within narrow limits. The supply of amino acids to cover physiological needs can be derived from 3 sources: 1. Exogenous proteins that release amino acids after digestion and absorption 2. Tissue protein breakdown during protein turnover 3. De novo synthesis, including amino acids (as well as ammonia) derived from the process of urea salvage, following hydrolysis and microflora metabolism in the hind gut. When protein intake surpasses the physiological needs of amino acids, the excess amino acids are disposed of by three major processes: 1. Increased oxidation, with terminal end products such as CO₂ and ammonia 2. Enhanced ureagenesis i. e. synthesis of urea linked to protein oxidation eliminates the nitrogen radical 3. Gluconeogenesis, i. e. de novo synthesis of glucose. Most of the amino groups of the excess amino acids are converted into urea through the urea cycle, whereas their carbon skeletons are transformed into other intermediates, mostly glucose. This is one of the mechanisms, essential for life, developed by the body to maintain blood glucose within a narrow range, (i. e. glucose homeostasis). It includes the process of gluconeogenesis, i. e. de novo synthesis of glucose from non-glycogenic precursors; in particular certain specific amino acids (for example, alanine), as well as glycerol (derived from fat breakdown) and lactate (derived from muscles). The gluconeogenetic pathway progressively takes over when the supply of glucose from exogenous or endogenous sources (glycogenolysis) becomes insufficient. This process becomes vital during periods of metabolic stress, such as starvation.
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The role of astrocytes as structural and metabolic support for neurons is known since the beginning of the last century. Because of their strategic localization between neurons and capillaries they can monitor and control the level of synaptic activity by providing energetic metabolites to neurons and remove excess of neurotransmitters. During the last two decades number of papers further established that the astrocytic plasma-membrane G-protein coupled receptors (GPCR) can sense external inputs (such as the spillover of neurotransmitters) and transduce them as intracellular calcium elevations and release of chemical transmitters such as glutamate. The chemokine CXCR4 receptor is a GPCR widely expressed on glial cells (especially astrocytes and microglia). Activation of the astrocytic CXCR4 by its natural ligand CXCL12 (or SDF1 alpha) results in a long chain of intracellular and extracellular events (including the release of the pro-inflammatory cytokine TNFalpha and prostanglandins) leading to glutamate release. The emerging role of CXCR4-CXCL12 signalling axis in brain physiology came from the recent observation that glutamate in astrocytes is released via a regulated exocytosis process and occurs with a relatively fast time-scale, in the order of few hundred milliseconds. Taking into account that astrocytes are electrically non-excitable and thus exocytosis rely only on a signalling pathway that involves the release Ca(2+) from the internal stores, these results suggested a close relationship between sites of Ca(2+) release and those of fusion events. Indeed, a recent observation describes structural sub-membrane microdomains where fast ER-dependent calcium elevations occur in spatial and temporal correlation with fusion events.
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Résumé L'objectif de la thèse est de comprendre le mode d'organisation économique spécifique aux petits centres urbains qui composent les espaces frontaliers sahéliens, en s'interrogeant sur leur concurrence ou leur complémentarité éventuelle à l'intérieur d'un régime de spatialité particulier. En s'appuyant sur l'exemple du carrefour économique de Gaya-Malanville-Kamba situé à la frontière entre le Niger, le Bénin et le Nigeria, il questionne le rôle de la ville-frontière ainsi que le jeu des acteurs marchands localement dominants, à partir de quatre grandes interrogations : Quelles sont les spécificités de l'Afrique sahélienne qui obligent à renouveler les approches géographiques de l'espace marchand? Quels sont les facteurs déterminants de l'activité économique frontalière? Les formes d'organisation de l'espace qui concourent à la structuration de l'économie sont-elles concurrentes ou coopératives? Les logiques économiques frontalières sont-elles compatibles avec l'orientation des programmes de développement adoptés par les pays sahéliens et leurs partenaires bi- ou multilatéraux? Dans une première partie, un modèle territorial de l'Afrique sahélienne permet de rendre compte de la prédominance des logiques circulatoires sur les logiques productives, une propriété essentielle de toute organisation économique confrontée à l'instabilité climatique. Dans une seconde partie, l'étude considère les facteurs déterminants de l'activité économique frontalière que sont le degré d'enclavement des territoires, la libre circulation des biens et des personnes, les relations concurrentielles ou coopératives qui lient les marchés ainsi que les liens clientélistes qui unissent patron et obligés. Une troisième partie est consacrée aux productions agricoles de tente organisées sous forme de coopératives paysannes ou d'initiatives privées. Une quatrième partie s'intéresse aux réseaux de l'import-export et du commerce de détail qui bénéficient de l'augmentation des besoins engendrée par l'urbanisation sahélienne. L'économie spatiale qui résulte de ces flux est organisée selon deux logiques distinctes : d'une part, les opportunités relatives à la production agricole conduisent certains investisseurs à intensifier l'irrigation pour satisfaire la demande des marchés urbains, d'autre part, les acteurs du capitalisme marchand, actifs dans l'import-export et la vente de détail, développent des réseaux informels et mobiles qui se jouent des différentiels nationaux. Les activités commerciales des villes-marchés connaissent alors des fluctuations liées aux entreprises productives et circulatoires de ces patrons, lesquelles concourent à l'organisation territoriale générale de l>Afrique sahélienne. Ces logiques évoluent dans un contexte fortement marqué par les politiques des institutions financières internationales, des agences bilatérales de coopération et des ONGs. Celles-ci se donnent pour ambition de transformer les économies, les systèmes politiques et les organisations sociales sahéliennes, en faisant la promotion du libéralisme, de la bonne gouvernance et de la société civile. Ces axes directeurs, qui constituent le champ de bataille contemporain du développement, forment un ensemble dans lequel la spécificité sahélienne notamment frontalière est rarement prise en compte. C'est pourquoi l'étude conclut en faveur d'un renouvellement des politiques de développement appliquées aux espaces frontaliers. Trois grands axes d'intervention peuvent alors être dégagés, lesquels permettent de réconcilier des acteurs et des logiques longtemps dissociés: ceux des espaces séparés par une limite administrative, ceux de la sphère urbaine et rurale et ceux du capitalisme marchand et de l'investissement agricole, en renforçant la coopération économique transfrontalière, en prenant en considération les interactions croissantes entre villes et campagnes et en appuyant les activités marchandes. Abstract: Urbanisation in West Africa is recent and fast. If only 10 % of the total population was living in urban areas in 1950, this proportion reached 40 % in 2000 and will be estimated to 60 % in 2025. Small and intermediate cities, located between the countryside and large metropolis, are particularly concerned with this process. They are nowadays considered as efficient vectors of local economic development because of fiscal or monetary disparities between states, which enable businessmen to develop particular skills based on local urban networks. The majority of theses networks are informal and extremely flexible, like in the Gaya - Malanville - Kamba region, located between Niger, Benin and Nigeria. Evidence show that this economic space is characterised by high potentialities (climatic and hydrological conditions, location on main economic West African axis) and few constraints (remoteness of some potentially high productive areas). In this context, this PhD deals with the economic relationships between the three market cities. Focusing on the links that unite the businessmen of the local markets - called patron; - it reveals the extreme flexibility of their strategies as well as the deeply informal nature of their activities. Through the analysis of examples taken from the commerce of agricultural products, import and export flows and detail activities, it studies the changes that have taken place in the city centres of Gaya, Malanville and Kamba. Meanwhile, this research shows how these cities represent a border economical area based on rival and complementary connections. In the first Part, it was necessary to reconsider the usual spatial analysis devoted to the question of economic centrality. As a matter of fact, the organisation of West African economic spaces is very flexible and mobile. Centrality is always precarious because of seasonal or temporary reasons. This is why the first chapters are devoted to the study of the specificity of the Sahelian territoriality. Two main elements are relevant: first the population diversity and second, the urban-rural linkages. In the second part, the study considers three main factors on which the cross-border economic networks are dependent: enclosure that prevents goods to reach the markets, administrative constraints that limit free trade between states and cities and the concurrent or complementary relationships between markets. A third part deals with the clientelist ties engaged between the patrons and their clients with the hypothesis that these relationships are based on reciprocity and inequality. A fourth part is devoted to' the study of the spatial organisation of commercial goods across the borders, as far as the agriculture commercial products, the import-export merchandises and the retail products are concerned. This leads to the conclusion that the economic activity is directly linked to urban growth. However, the study notices that there is a lack of efficient policies dealing with strengthening the business sector and improving the cross-border cooperation. This particularity allows us to favour new local development approaches, which would take into account the important potential of private economical actors. In the same time, the commercial flows should be regulated with the help of public policies, as long as they are specifically adapted to the problems that these areas have to deal with.
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This law is intended to reduce the number of hazardous methamphetamine labs in Iowa, by controlling meth cooks’ access to the key meth-making ingredient: pseudoephedrine. In 2004, Iowa law enforcement agencies responded to a record 1,472 meth lab incidents. Below, please find links to: Senate File 169 (Iowa’s pseudoephedrine control law); an Iowa meth fact sheet; a brief overview of the law; and general compliance guidelines for consumers, pharmacies, retailers and law enforcement. Most provisions of this law, pertaining to pseudoephedrine sales, are effective May 21, 2005. However, two other provisions were effective immediately—March 22, 2005—upon the Governor’s signing of this measure into law: (1) removal of exceptions on the Schedule V Controlled Substance status for ephedrine [all ephedrine products now may only be sold in licensed pharmacies…no retail sales of ephedrine permitted]; and (2) addition of a requirement that bailable defendants charged with manufacture, delivery, possession with the intent to deliver, or distribution of methamphetamine, shall, in addition to a substance abuse evaluation, remain under supervision and be required to undergo random drug tests as a condition of release.
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Abstract : The human body is composed of a huge number of cells acting together in a concerted manner. The current understanding is that proteins perform most of the necessary activities in keeping a cell alive. The DNA, on the other hand, stores the information on how to produce the different proteins in the genome. Regulating gene transcription is the first important step that can thus affect the life of a cell, modify its functions and its responses to the environment. Regulation is a complex operation that involves specialized proteins, the transcription factors. Transcription factors (TFs) can bind to DNA and activate the processes leading to the expression of genes into new proteins. Errors in this process may lead to diseases. In particular, some transcription factors have been associated with a lethal pathological state, commonly known as cancer, associated with uncontrolled cellular proliferation, invasiveness of healthy tissues and abnormal responses to stimuli. Understanding cancer-related regulatory programs is a difficult task, often involving several TFs interacting together and influencing each other's activity. This Thesis presents new computational methodologies to study gene regulation. In addition we present applications of our methods to the understanding of cancer-related regulatory programs. The understanding of transcriptional regulation is a major challenge. We address this difficult question combining computational approaches with large collections of heterogeneous experimental data. In detail, we design signal processing tools to recover transcription factors binding sites on the DNA from genome-wide surveys like chromatin immunoprecipitation assays on tiling arrays (ChIP-chip). We then use the localization about the binding of TFs to explain expression levels of regulated genes. In this way we identify a regulatory synergy between two TFs, the oncogene C-MYC and SP1. C-MYC and SP1 bind preferentially at promoters and when SP1 binds next to C-NIYC on the DNA, the nearby gene is strongly expressed. The association between the two TFs at promoters is reflected by the binding sites conservation across mammals, by the permissive underlying chromatin states 'it represents an important control mechanism involved in cellular proliferation, thereby involved in cancer. Secondly, we identify the characteristics of TF estrogen receptor alpha (hERa) target genes and we study the influence of hERa in regulating transcription. hERa, upon hormone estrogen signaling, binds to DNA to regulate transcription of its targets in concert with its co-factors. To overcome the scarce experimental data about the binding sites of other TFs that may interact with hERa, we conduct in silico analysis of the sequences underlying the ChIP sites using the collection of position weight matrices (PWMs) of hERa partners, TFs FOXA1 and SP1. We combine ChIP-chip and ChIP-paired-end-diTags (ChIP-pet) data about hERa binding on DNA with the sequence information to explain gene expression levels in a large collection of cancer tissue samples and also on studies about the response of cells to estrogen. We confirm that hERa binding sites are distributed anywhere on the genome. However, we distinguish between binding sites near promoters and binding sites along the transcripts. The first group shows weak binding of hERa and high occurrence of SP1 motifs, in particular near estrogen responsive genes. The second group shows strong binding of hERa and significant correlation between the number of binding sites along a gene and the strength of gene induction in presence of estrogen. Some binding sites of the second group also show presence of FOXA1, but the role of this TF still needs to be investigated. Different mechanisms have been proposed to explain hERa-mediated induction of gene expression. Our work supports the model of hERa activating gene expression from distal binding sites by interacting with promoter bound TFs, like SP1. hERa has been associated with survival rates of breast cancer patients, though explanatory models are still incomplete: this result is important to better understand how hERa can control gene expression. Thirdly, we address the difficult question of regulatory network inference. We tackle this problem analyzing time-series of biological measurements such as quantification of mRNA levels or protein concentrations. Our approach uses the well-established penalized linear regression models where we impose sparseness on the connectivity of the regulatory network. We extend this method enforcing the coherence of the regulatory dependencies: a TF must coherently behave as an activator, or a repressor on all its targets. This requirement is implemented as constraints on the signs of the regressed coefficients in the penalized linear regression model. Our approach is better at reconstructing meaningful biological networks than previous methods based on penalized regression. The method is tested on the DREAM2 challenge of reconstructing a five-genes/TFs regulatory network obtaining the best performance in the "undirected signed excitatory" category. Thus, these bioinformatics methods, which are reliable, interpretable and fast enough to cover large biological dataset, have enabled us to better understand gene regulation in humans.
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1. The effects of "cafeteria feeding" on primiparous Wistar rats during lactation have been studied by measuring circulating levels of glucose, amino acids, lactate, urea and ammonia as well as glycogen levels in liver and muscle. 2. No significant changes in glucose levels were observed despite alterations in blood glucose compartmentation. 3. Compared with controls, the dams given the cafeteria diet had higher liver glycogen stores which were more easily mobilized at the peak of lactation. 4. Rats given the cafeteria diet showed a lower amino acid utilization than controls and adequately maintained circulating levels, as determined by the lower circulating levels of ammonia and urea. 5. No significant differences in body-weight were observed in the period studied despite increasing dam weight after weaning in the cafeteria-fed group. 6. The size of pups of cafeteria-fed dams was greater than that of controls, and the differences were marked after weaning, when the metabolic machinery of the cafeteria pup maintained high protein accretion and body build-up using fat as the main energy substrate characteristic of the preweaning stage. The controls, however, changed to greater utilization of amino acids as an energy substrate and adapted to high-protein (lowbiological-quality) diets with a significantly different pattern of circulating nitrogen distribution.
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[cat] Espanya és un dels principals mercats de productes pesquers d’Europa i del món. El consum de productes pesquers ha estat tradicionalment molt important a Espanya, el 2005 es varen consumir 36,7 kg per persona (MAPA, diversos anys). Malgrat això, el mercat i cóm interactuen els diversos nivells de la cadena de comercialització han gaudit de poca atenció. En aquest estudi, utilitzant dades setmanals, s’analitza per als dotze principals productes pesquers, l’elasticitat en la transmissió de preus al llarg de la cadena de comercialització a Espanya (llotja, mercat central i detallista). Finalment s’investiga la presència d’assimetria en la transmissió de preus entre aquests nivells de mercat. Els resultats obtinguts tenen importants implicacions a l’hora d’analitzar la demanda, poder de mercat i marges al llarg del mercat per als productes pesquers.
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BACKGROUND: Guidelines for the management of anaemia in patients with chronic kidney disease (CKD) recommend a minimal haemoglobin (Hb) target of 11 g/dL. Recent surveys indicate that this requirement is not met in many patients in Europe. In most studies, Hb is only assessed over a short-term period. The aim of this study was to examine the control of anaemia over a continuous long-term period in Switzerland. METHODS: A prospective multi-centre observational study was conducted in dialysed patients treated with recombinant human epoetin (EPO) beta, over a one-year follow-up period, with monthly assessments of anaemia parameters. RESULTS: Three hundred and fifty patients from 27 centres, representing 14% of the dialysis population in Switzerland, were included. Mean Hb was 11.9 +/- 1.0 g/dL, and remained stable over time. Eighty-five % of the patients achieved mean Hb >or= 11 g/dL. Mean EPO dose was 155 +/- 118 IU/kg/week, being delivered mostly by subcutaneous route (64-71%). Mean serum ferritin and transferrin saturation were 435 +/- 253 microg/L and 30 +/- 11%, respectively. At month 12, adequate iron stores were found in 72.5% of patients, whereas absolute and functional iron deficiencies were observed in only 5.1% and 17.8%, respectively. Multivariate analysis showed that diabetes unexpectedly influenced Hb towards higher levels (12.1 +/- 0.9 g/dL; p = 0.02). One year survival was significantly higher in patients with Hb >or= 11 g/dL than in those with Hb <11 g/dL (19.7% vs 7.3%, p = 0.006). CONCLUSION: In comparison to European studies of reference, this survey shows a remarkable and continuous control of anaemia in Swiss dialysis centres. These results were reached through moderately high EPO doses, mostly given subcutaneously, and careful iron therapy management.
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ATP, released by both neurons and glia, is an important mediator of brain intercellular communication. We find that selective activation of purinergic P2Y1 receptors (P2Y1R) in cultured astrocytes triggers glutamate release. By total internal fluorescence reflection imaging of fluorescence-labeled glutamatergic vesicles, we document that such release occurs by regulated exocytosis. The stimulus-secretion coupling mechanism involves Ca2+ release from internal stores and is controlled by additional transductive events mediated by tumor necrosis factor-alpha (TNFalpha) and prostaglandins (PG). P2Y1R activation induces release of both TNFalpha and PGE2 and blocking either one significantly reduces glutamate release. Accordingly, astrocytes from TNFalpha-deficient (TNF(-/-)) or TNF type 1 receptor-deficient (TNFR1(-/-)) mice display altered P2Y1R-dependent Ca2+ signaling and deficient glutamate release. In mixed hippocampal cultures, the P2Y1R-evoked process occurs in astrocytes but not in neurons or microglia. P2Y1R stimulation induces Ca2+ -dependent glutamate release also from acute hippocampal slices. The process in situ displays characteristics resembling those in cultured astrocytes and is distinctly different from synaptic glutamate release evoked by high K+ stimulation as follows: (a) it is sensitive to cyclooxygenase inhibitors; (b) it is deficient in preparations from TNF(-/-) and TNFR1(-/-) mice; and (c) it is inhibited by the exocytosis blocker bafilomycin A1 with a different time course. No glutamate release is evoked by P2Y1R-dependent stimulation of hippocampal synaptosomes. Taken together, our data identify the coupling of purinergic P2Y1R to glutamate exocytosis and its peculiar TNFalpha- and PG-dependent control, and we strongly suggest that this cascade operates selectively in astrocytes. The identified pathway may play physiological roles in glial-glial and glial-neuronal communication.
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Collective evidence indicates that motor neuron degeneration in amyotrophic lateral sclerosis (ALS) is non-cell-autonomous and requires the interaction with the neighboring astrocytes. Recently, we reported that a subpopulation of spinal cord astrocytes degenerates in the microenvironment of motor neurons in the hSOD1(G93A) mouse model of ALS. Mechanistic studies in vitro identified a role for the excitatory amino acid glutamate in the gliodegenerative process via the activation of its inositol 1,4,5-triphosphate (IP(3))-generating metabotropic receptor 5 (mGluR5). Since non-physiological formation of IP(3) can prompt IP(3) receptor (IP(3)R)-mediated Ca(2+) release from the intracellular stores and trigger various forms of cell death, here we investigated the intracellular Ca(2+) signaling that occurs downstream of mGluR5 in hSOD1(G93A)-expressing astrocytes. Contrary to wild-type cells, stimulation of mGluR5 causes aberrant and persistent elevations of intracellular Ca(2+) concentrations ([Ca(2+)](i)) in the absence of spontaneous oscillations. The interaction of IP(3)Rs with the anti-apoptotic protein Bcl-X(L) was previously described to prevent cell death by modulating intracellular Ca(2+) signals. In mutant SOD1-expressing astrocytes, we found that the sole BH4 domain of Bcl-X(L), fused to the protein transduction domain of the HIV-1 TAT protein (TAT-BH4), is sufficient to restore sustained Ca(2+) oscillations and cell death resistance. Furthermore, chronic treatment of hSOD1(G93A) mice with the TAT-BH4 peptide reduces focal degeneration of astrocytes, slightly delays the onset of the disease and improves both motor performance and animal lifespan. Our results point at TAT-BH4 as a novel glioprotective agent with a therapeutic potential for ALS.
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The past fiscal year brought some improvements in the Iowa economy that should position the state for stronger hiring in the year ahead. The housing market is on solid footing, and hiring is broader in scope, including a number of the service-providing industries that had been on hold for some time. State and local government fiscal conditions have also stabilized due to a rise in tax revenues. This means that government cutbacks will be less of a drag on overall job growth. During FY 2013, Iowa’s non-farm jobs advanced by 19,200 (+1.3 percent) compared to 23,000 (+1.6 percent) for the prior fiscal year. Although manufacturing continued to post the largest over the year job gain at close to 5,600, job growth shifted away from manufacturing to the service providing industries by mid-year. Annual job gains of 2,000 or more were reflected in professional and business services, education and health, leisure and hospitality, retail trade and financial activities. Statewide non-farm employment averaged 1,517,700 in FY 2013, the highest level achieved since the record of 1,524,800 in FY 2008.