L’hydrogène en tant que vecteur énergétique reste tributaire, pour un développement à grande échelle, de son stockage et de la facilité de dégagement du combustible stocké. Pour les applications embarquées, portables et stationnaires, aucune technologie de stockage (H2 comprimé, H2 liquide, hydrures métalliques ou chimiques) ne répond aujourd’hui au cahier des charges d’un système de stockage. De nombreuses études se penchent donc à la fois sur l'optimisation des composants et le développement de sources d'énergie miniatures. Dans cette optique, la production d'hydrogène par l'hydrolyse des borohydrures est une technologie prometteuse pour les piles à combustible portables. En particulier, le borohydrure de sodium (NaBH4) présente de multiples avantages. Par exemple, les solutions aqueuses de NaBH4 sont non inflammables assurant ainsi la sécurité des procédés, le taux de génération d’hydrogène est facilement contrôlé par un catalyseur, les produits de réaction sont respectueux de l'environnement et peuvent être recyclés. La réaction d’hydrolyse du borohydrure alcalin peut être décrite de la façon suivante : MBH4 + (2+x) H2O → 4 H2 + MBO2.xH2O L’optimisation de la réaction d’hydrolyse et plus globalement l’optimisation du fonctionnement de la cartouche et de ces performances nécessite d’améliorer les connaissances sur les propriétés physico-chimiques du borohydrure et des métaborates en milieu aqueux plus ou moins complexe. L’un des principaux défis consiste à augmenter la concentration en NaBH4 de la solution de la cartouche, tout en évitant les inconvénients induits par la cristallisation des sous-produits (NaBO2.xH2O). Mais il est alors nécessaire de contrôler la stabillité de cette solution, par ajout d'hydroxyde de sodium qui limitera l'auto–décomposition NaBH4. Ce travail montre les deux aspects de l'analyse de la durée de vie de la cartouche génératrice d’hydrogène : – La cinétique d'hydrolyse spontanée des solutions alcalines aqueuses NaBH4 en fonction de la concentration de NaOH (élément stabilisant) et de la plage de température de fonctionnement de la cartouche,– La compréhension sans équivoque de l'opération de cristallisation NaBO2 et plus particulièrement la délimitation du domaine de la phase liquide homogène dans le système quaternaire NaBH4–NaBO2–NaOH–H2O, qui représente l’évolution du mélange lors du fonctionnement de la cartouche d'hydrogène / Numerous investigations are addressing both component optimization and development of miniature energy sources. The rise of portable eletronic devices, brings to the fore the crucial issues of power supply. The foresceable evolution in functionalities and utilizations, as regards portable eletronic devices, together with the introduction of novel electronic components, entail considerable changes in requirements, in terms of power consumption and autonomy. Hydrogen generation by means of the hydrolysis of borohydrides is a promising technology for portable fuel cells. Particularly, sodium borohydride (NaBH4) presents many advantages for that purpose. For example, NaBH4 solutions are non–flammable thus yielding safe processes; the rate of H2 generation is easily controlled by a catalyst; reaction products are environmentally benign and finally the reaction by–product can be recycled. The hydrolysis of NaBH4 in water to produce H2 gives by–products, NaBO2.yH2O, hydrated sodium borate according to MBH4 + (2+x) H2O → 4 H2 + MBO2.xH2O The interesting point of this work is to increase the amount of produced H2 in order to improve the energy density of the H2 generator system. For this, one of the main challenges is to increase the NaBH4 concentration of the cartridge solution thus avoiding the drawbacks induced by NaBO2 crystallization, but also to control the stabillity of this solution, it means add sodium hydroxyde to limit the NaBH4 self–decomposition, thus stabilizing the system. This work shows the two aspects of the analysis of the cartridge timelife : – The kinetic of spontaneous hydrolysis of alkaline aqueous NaBH4 solutions as function of NaOH concentration and the operation temperature range of the cartridge, – An unequivocal understanding of the NaBO2 crystallization process and more specifically the delimitation of the homogeneous liquid phase domain in the quaternary system NaBH4– NaBO2–NaOH–H2O, which represents the mixture present during the hydrogen cartridge operation

No description available.

A method is described for the preparation of an everted rectal sac of the desert locust. Water and solute absorption by the rectum was determined by measuring changes in hemocoel fluid and rectal tissue. Initial absorption rates of Na, K, Cl, water and trans-rectal potential are comparable to those in vivo under similar conditions. After an initial transient period (1 hour), transport activity of the in vitro rectum remained in a steady state for at least 4- hours. The relationship between osmotic gradient and steady state rate of net water movement across the rectal wall was determined. Absorption of water is partially inhibited by anoxia, malonate (10־² M), dinitrophenol (10־³M), potassium cyanide (10־³ M) plus iodoacetate (10־³ M) and ouabain (10־³ M). Tissue ions and water are secreted into the hemocoel compartment when the rectal sac is incubated in isosmotic pure sucrose solution. Dependence of water movement on solute transport is indicated by the requirement of lumen ions for prolonged maintenance of water absorption. Effects of different ions (Na, K and Cl) in bathing media on absorption rate of water and ions, absorbate concentrations, trans-epithelial electro-potential differences, and tissue compositions were determined. Observed properties of water and solute movement in vitro are discussed and evaluated in relation to possible mechanisms for active absorption of water. Possible locations of transport sites are suggested in a hypothetical scheme based on the ultrastructure of rectal epithelium. / Science, Faculty of / Zoology, Department of / Graduate

The epithelial sodium channel, ENaC, forms the rate-limiting step for sodium reabsorption in the cortical collecting duct of the kidney. It is known that ENaC is important in maintaining fluid homeostasis and ultimately blood pressure as mutations in ENaC result in inherited forms of hyper- and hypotension (Liddle's syndrome and Pseudohypoaldosteronism (PHA type I), respectively). Clinically, ENaC activity can be blocked by treatment with the potassium sparing diuretic amiloride. However, due to difficulties in dosing and the transient nature of channel block, treatment goals are seldom achieved. It is, therefore, necessary to better understand the function and regulation of ENaC activity. ENaC is a member of the DEG/ENaC family of ion channels. Each family member is composed of multiple subunits - each subunit contains two transmembrane domains, short cytoplasmic amino and carboxy termini, and a relatively large extracellular domain. ENaC is a heterotrimer of homologous subunits Α-,Β-, and ΓENaC. ENaC is a constitutively active ion channel. It is not ligand gated or voltage activated. However, channel activity can be modulated by a variety of stimuli. I hypothesize that the extracellular domain functions as a sensor, allowing the channel to detect and respond to changes in extracellular conditions. To test this, we expressed human ΑΒΓENaC in Xenopus oocytes and used the two-electrode voltage clamp technique to measure changes in ENaC activity in response to changing extracellular conditions. Using this technique, I identified several novel means of regulating ENaC activity. I found that ENaC activity can be rapidly and reversibly stimulated or suppressed in response to extracellular acidification depending on the balance of extracellular sodium and chloride concentrations and have identified several key residues involved. I found that extracellular chloride inhibits ENaC activity through putative binding sites in the extracellular domain located between the Α- and Β- and Β- and ΓENaC subunits. This allowed us to determine that ENaC adopts an ΑΓΒ channel architecture. Additionally, I have made progress in understanding channel movement by identifying length dependent intersubunit interactions that alter channel gating. Based on our data we conclude that the extracellular domain is integral to modulation of channel activity. The work described herein has significantly advanced the field by improving our understanding of ENaC structure and function.

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

No description available.

No description available.

11β-Hydroxysteroid Dehydrogenase Type 2 (11βHSD2) catalyses the inactivation of cortisol. In aldosterone target tissues co-expression of 11βHSD2 and mineralocorticoid receptors (MR) protects the receptor from activation by glucocorticoids. In the syndrome of Apparent Mineralocorticoid Excess, mutations in the HSD11B2 gene cause hypertension, which is thought to be driven by volume expansion secondary to sodium retention. 11βHSD2 mice are indeed hypertensive but paradoxically volume contracted, suggestive of a urine-concentrating defect. The current studies were designed to evaluate sodium and water homeostasis in 11βHSD2-/- mice. 11βHSD2-/- mice developed a severe and progressive polyuric-polydipsic phenotype. Despite basal polyuria, at <100 days 11βHSD2-/- mice had a functional concentration response when challenged with 24 hours water deprivation. At >180 days the exacerbated polyuria was associated with severe medullary injury in the null mice. Basal aquaporin 2 (AQP2) abundance was reduced in the 11βHSD2-/- mice at both <100 and >180 days. Moreover, vasopressin 2 receptor (V2R) stimulation failed to normalize the impaired response to water deprivation in >180 day null mice. Consequently, a renal origin to the polyuria was postulated. Indeed, mice in which 11βHSD2 had been selectively targeted in the brain had a normal water turnover. A key finding from these studies is that functional deletion of 11βHSD2 in the brain, specifically the nucleus of the solitary tract (NTS), resulted in an increased salt appetite. Moreover, the mice displayed a preference for 1.5% NaCl over water. Blockade of mineralocorticoid receptors (MR) significantly reduced NaCl intake. This is the first demonstration of an increased salt appetite in a model with normal renal function and in the absence of sodium depletion. These data implicate activation of MR on 11βHSD2 positive neurons in the NTS in the behavioural drive to consume sodium.

The nodes of Ranvier are short, periodical interruptions in the myelin sheath of myelinated axons, at which voltage-gated sodium channels are highly concentrated. The correct targeting of sodium channels to the nodes of Ranvier permits rapid propagation of action potentials in myelinated axons. The nodes of Ranvier contain a unique set of ion channels, cell-adhesion molecules, and cytoplasmic adaptor proteins. Neurofascins are cell adhesion molecules of the immunoglobulin superfamily and previous work has shown they are involved in the assembly of the node of Ranvier. The Neurofascin (Nfasc) gene is subject to extensive alternative splicing. RT-PCR studies have suggested that there were several different Neurofascin (Nfasc) transcripts. Thus far, research on the Neurofascins has concentrated on two isoforms, Nfasc186 and Nfasc155, which are expressed in neurons and glia respectively. A third Neurofascin isoform, Nfasc140, lacking the Mucin domain and two of the fibronectin repeats was originally identified in the laboratory of V. Bennett. However, neither the location nor function of this protein was known. By RT-PCR I successfully cloned the Nfasc140 cDNA and determined its domain composition, which was confirmed by a series of Western blots using domain-specific antibodies. The developmental expression of Nfasc140 revealed that it is the predominate isoform of Neurofascin during the embryonic stage. Using cell-type-specific conditional Neurofascin knock-out mice, I have also found that Nfasc140 is a neuronal isoform, like Nfasc186. I have used transgenic mouse lines to characterize the location and function of Nfasc140. Like Nfasc186, Nfasc140 is targeted to the nodes of Ranvier and axonal initial segment. Also Nfasc140 alone can reconstitute the nodal complex in Neurofascin knock-out mice in CNS and PNS in the absence of Nfasc186 and Nfasc155. It can also partially restore the electrophysiological function of PNS nerves. In order to address the role of the paranodes in sodium channel clustering, I generated a new neuronal-Cre-expressing transgenic line which, when bred with floxed Nfasc mice, generated early neuronal Neurofascin knock-out mice. Using those animals I have shown that after the ablation of all neuronal Neurofascins, when only glial Nfasc155 is presented, sodium channels can still target to the nodes of Ranvier in both PNS and CNS. These conditional knock-out mice have a longer life span than pan-Neurofascin knock-out mice. This indicates the importance of paranodal junctions, in addition to nodal neuronal Neurofascins, in clustering sodium channels at the node.