Peroxisome proliferator activated receptors (PPAR) are members of the nuclear receptor family that act as transcription factors to regulate target gene expression. In addition to their well-known effects in regulation of glucose homeostasis and lipid metabolism, PPAR activators have recently been shown to exert antihypertensive effects, although the underlying mechanism is not clear. Our laboratory has previously demonstrated that oxidative stress of an augmented tissue level of superoxide anion (£R2¡E−) in the rostral ventrolateral medulla (RVLM), where promotor neurons for generation of sympathetic vasomotor outflow reside, contributes to neural mechanism of hypertension. I therefore propose to test in my thesis the hypothesis that protection against oxidative stress after activation of the PPARs in the RVLM may contribute to the antihypertensive effect of these transcription factors. Experiments were performed in the spontaneously hypertensive rats (SHR) or normotensive Wistar-Kyoto (WKY) rats under anesthesia or conscious condition. Compared to WKY rats, microinjection bilaterally into the RVLM of a synthetic activator of PPAR£^, rosiglitazone (1 nmol), evoked significantly greater decreased in mean systemic arterial pressure (MSAP) and heart rate (HR) in SHR. These cardiovascular suppressive effects of rosiglitazone were accompanied by greater decrease in tissue level of O2 - and upregulation of the antioxidant uncoupling proteins (UCPs) in the RVLM of SHR. Rosiglitazone also caused a significant greater increase in PPAR£^ expression in the nuclear extracts from RVLM of SHR than WKY rats. All these cellular events induced by rosiglitazone were antagonized by co-administration into the RVLM of the PPAR£^ inhibitor, GW9662 (5 nmol). This PPAR£^ inhibitor also significantly reversed the cardiovascular depressive effects of rosiglitazone. Together these results suggest that PPAR£^ in the RVLM may participate in central cardiovascular regulation by promoting hypotension and bradycardia via amelioration of O2- production and upregulation of antioxidant UCPs. Moreover, a downregulation of the PPAR£^ in the RVLM may contribute to neural mechanism of hypertension.

Abstract The semi-domesticated reindeer is a northern species of Cervidae that is exposed to extreme seasonal changes in temperature and nutrition in its living environment. The objective of this study was to examine the significance of thermogenic brown adipose tissue (BAT) for the survival of newborn reindeer in the cold during the critical perinatal period. The other main objective was to study the effect of wintertime undernutrition on serum and bone marrow fatty acid composition in yearling reindeer, with particular attention on the proportions of unsaturated and polyunsaturated fatty acids (PUFAs) and their feasibility as indicators of nutritional status. The results showed that the most of the adipose tissues in newborn reindeer were functionally active BAT. The tissue had specific anatomical locations, specialized cell morphological structure, high aerobic capacity, and tissue-specific mitochondrial 32000 Mr-uncoupling protein (UCP1) that is considered a rate-limiting factor for thermogenesis. The most readily mobilized fatty acids from BAT triacylglycerols were arachidonic, linoleic, and α-linolenic acids. BAT was most active at birth and during the close perinatal period but its aerobic capacity declined during the first month of life while UCP1 disappeared and the tissue gradually adopted the histological characteristics of white adipose tissue. The newborn reindeer had very low proportions of the principal C18-PUFAs, linoleic and α-linolenic acids, in serum lipids. However, the proportions of C18-PUFAs increased during the first few days of life by a rate that suggests a selective retention of these fatty acids from milk lipids. A prolonged restricted feeding of reindeer with lichen during winter and spring induced significant reductions in the proportions of linoleic and α-linolenic acids in serum cholesteryl esters and phospholipids, while proportion of arachidonic acid and serum prostaglandin PGF2α metabolite concentration increased. Plasma leptin and insulin levels decreased in parallel with decreases in feed intake and body weight. In freely ranging reindeer, the proportions of oleic acid and principal C18-PUFAs were significantly reduced in femur bone marrow triacylglycerols as a result of a wintertime undernutrition. In conclusion, active BAT is the dominant adipose tissue type in the newborn reindeer and it is likely to have a major significance on the thermoregulatory heat production and cold resistance of reindeer during the perinatal period. The changes in the specific PUFA proportions of serum and bone marrow lipids refleict the changes in the nutritional status and suggest that these fatty acids are preferentially utilized during prolonged wintertime undernutrition.

Thermogenic brown adipose tissue generates heat via mitochondrial uncoupling protein-1 (UCP-1), increases whole-body energy expenditure and may protects against obesity and metabolic disorders. White adipocytes store excess energy in the form of triglycerides. UCP-1 positive adipocytes develop within white adipose tissue (beige or brite adipocytes) in response to cold exposure or β3 adrenergic agonists. It was known that beige adipocytes arise from a distinct lineage compared with brown adipocytes, but the developmental origin of the beige adipocytes is still unclear. Signaling pathways that control beige adipocyte determination and formation are essentially unknown. Here, we identified a novel signaling pathway that regulates the lineage specification of beige adipocytes. Bone morphogenetic protein 7 (BMP7), a known brown adipogenesis inducer, suppresses Rho-GTPase kinase (ROCK) and depolymerizes F-actin (filamentous actin) into G-actin (globular actin) in mesenchymal stem cells. G-actin regulates myocardin-related transcription factor A (MRTFA) that co-transactivates serum response factor (SRF) and promotes smooth muscle cell differentiation in various organs. Subcutaneous white adipose tissue from MRTFA-/- mice had enhanced accumulation of UCP-1+ adipocytes and elevated levels of brown-selective proteins. Compared with wild type (WT) controls, MRTFA-/- mice exhibited improved metabolic profiles and were protected from diet-induced obesity and insulin resistance, suggesting that the beige adipocytes are physiologically functional. Compared to WT mice, stromal vascular cells from MRTFA-/- mice expressed higher levels of distinct beige progenitor markers and reduced levels of smooth muscle markers. Our studies demonstrate a novel ROCK-actin-MRTFA/SRF pathway that contributes to the development of beige adipocytes.

The documentary letters of credit transaction is the most common method of payment for goods in international trade. Its use has been considered so important that it is referred to as the �lifeblood� of international commerce. The purpose of this thesis is, through analysing the present regime of documentary credit established under the The Uniform Customs and Practice for Documentary Credits, 1993 Revision (�UCP�), to identify the rights and duties of all parties in such transactions and the reasons for the frequent occurrence of fraudulent activities associated with the documents required under the credits. It identifies that the present system fails to either encourage or implement substantial realisation of �reasonable care� or �good faith� on the part of the banks, or realisation of the requirement of �good faith� from beneficiaries. As a result, the independence principle has been left without substance, with resulting huge opportunities for fraudsters to cheat on the documents and obtain payment without the need to actually perform their duties to banks and buyers. Such issues have become more acute against the background of an underlying shift in the allocation of risk between the respective parties to letters of credit. There has been a depreciation in the value of the primary document of title and security held by the issue, the bill of lading, with the advent of container shipping. As the letter of credit system is wholly dependent on the integrity of the documents, it is being undermined by these developments. This has represented a shift in the traditional scheme of risk allocation from the seller to the bank. In practice, banks have taken countermeasures by insisting that applicants provide other types of collateral, and by subjecting applicants to rigorous credit checks. Thus, applicants ultimately have had to bear the brunt of costs associated with this reallocation of risk. It will be demonstrated that the UCP does not incorporate adequate or clear enough duties to be exercised on the part of issuers toward applicants, and severely restricts the applicant�s right to sue if the issuer has wrongfully honoured. Ultimately, a balance must be struck between the desirability of protecting the applicant from the beneficiary�s fraud against the benefits gained by maintaining the letter of credit as a commercial instrument and business device. Obviously, there is public interest in protecting both of these commercial values. This thesis advocates that a mechanism in addition to the fraud exception must be introduced to safeguard the system against the ramifications of these changes � increased fraud. The thesis is structured into five chapters. Chapter 1 sets out to demonstrate the circumstances under which the respective risks are borne by each participant in the letter of credit transaction, and how developments in trade practice have caused the burden of certain of these risks among the parties to a letter of credit transaction to shift. Chapter 2, after briefly visiting the historical origins of the letter of credit and the birth of the UCP, explores the implications of the dominance of banking interests over the drafting and interpretation of the UCP, how the UCP has in practice excluded the intrusion of other sources of law and the general reluctance of courts to intervene by applying non-letter of credit principles, the implication of the UCP�s assumption of the law in practice, the resulting marginalisation of local laws, and the inequality in bargaining power between banks and applicants that precludes a choice of law other than the UCP. Chapter 3 explores the independence principle and question of documentary compliance, why the system is ridden with non-compliant documents and the lack of incentive and meaningful duty for the banks to check for �red flags� that may indicate fraud on the documents or in the transaction. It will be emphasised that documentary validity, rather than mere documentary compliance, should be the focus under the letter of credit. Chapter 4 examines the fraud exception to the independence principle, the typical high thresholds of proof that applicants had to overcome to estopp payment, and explores recent trends towards the gradual lowering of such thresholds. Finally, Chapter 5 considers practical measures and proposals for reform that would help to redress the imbalance in the allocation of risk identified in the thesis.

The documentary letters of credit transaction is the most common method of payment for goods in international trade. Its use has been considered so important that it is referred to as the �lifeblood� of international commerce. The purpose of this thesis is, through analysing the present regime of documentary credit established under the The Uniform Customs and Practice for Documentary Credits, 1993 Revision (�UCP�), to identify the rights and duties of all parties in such transactions and the reasons for the frequent occurrence of fraudulent activities associated with the documents required under the credits. It identifies that the present system fails to either encourage or implement substantial realisation of �reasonable care� or �good faith� on the part of the banks, or realisation of the requirement of �good faith� from beneficiaries. As a result, the independence principle has been left without substance, with resulting huge opportunities for fraudsters to cheat on the documents and obtain payment without the need to actually perform their duties to banks and buyers. Such issues have become more acute against the background of an underlying shift in the allocation of risk between the respective parties to letters of credit. There has been a depreciation in the value of the primary document of title and security held by the issue, the bill of lading, with the advent of container shipping. As the letter of credit system is wholly dependent on the integrity of the documents, it is being undermined by these developments. This has represented a shift in the traditional scheme of risk allocation from the seller to the bank. In practice, banks have taken countermeasures by insisting that applicants provide other types of collateral, and by subjecting applicants to rigorous credit checks. Thus, applicants ultimately have had to bear the brunt of costs associated with this reallocation of risk. It will be demonstrated that the UCP does not incorporate adequate or clear enough duties to be exercised on the part of issuers toward applicants, and severely restricts the applicant�s right to sue if the issuer has wrongfully honoured. Ultimately, a balance must be struck between the desirability of protecting the applicant from the beneficiary�s fraud against the benefits gained by maintaining the letter of credit as a commercial instrument and business device. Obviously, there is public interest in protecting both of these commercial values. This thesis advocates that a mechanism in addition to the fraud exception must be introduced to safeguard the system against the ramifications of these changes � increased fraud. The thesis is structured into five chapters. Chapter 1 sets out to demonstrate the circumstances under which the respective risks are borne by each participant in the letter of credit transaction, and how developments in trade practice have caused the burden of certain of these risks among the parties to a letter of credit transaction to shift. Chapter 2, after briefly visiting the historical origins of the letter of credit and the birth of the UCP, explores the implications of the dominance of banking interests over the drafting and interpretation of the UCP, how the UCP has in practice excluded the intrusion of other sources of law and the general reluctance of courts to intervene by applying non-letter of credit principles, the implication of the UCP�s assumption of the law in practice, the resulting marginalisation of local laws, and the inequality in bargaining power between banks and applicants that precludes a choice of law other than the UCP. Chapter 3 explores the independence principle and question of documentary compliance, why the system is ridden with non-compliant documents and the lack of incentive and meaningful duty for the banks to check for �red flags� that may indicate fraud on the documents or in the transaction. It will be emphasised that documentary validity, rather than mere documentary compliance, should be the focus under the letter of credit. Chapter 4 examines the fraud exception to the independence principle, the typical high thresholds of proof that applicants had to overcome to estopp payment, and explores recent trends towards the gradual lowering of such thresholds. Finally, Chapter 5 considers practical measures and proposals for reform that would help to redress the imbalance in the allocation of risk identified in the thesis.

Práce charakterizuje dokumentární akreditiv jako jeden z významných platebních a zajišťovacích instrumentů v mezinárodním obchodě. V jednotlivých kapitolách jsou uvedené výhody a nevýhody jeho použití, typy dokumentárních akreditivů, použitelnost akreditivu a dokumenty používané při akreditivních operacích. Poslední kapitola je zaměřená na eUCP, elektronický akreditiv a systémy elektronického akreditivu.

We report new studies on the early-time dynamics of ultracold neutral plasmas. We use fluorescence spectroscopy to probe plasma dynamics on the nanosecond time scale. We determine the rms ion velocity during the initial plasma period. The initial ion acceleration is found as the time derivative of the ion velocity. We compare to a theoretical model. The experimental results agree with the model at low plasma densities. However, the ion acceleration is a factor of ten lower than the model at higher densities. The cause of this discrepancy is currently unknown.

No description available.

De par leur importante diversité phénotypique (10000 espèces), les oiseaux ont colonisé la plupart des niches écologiques, aussi « extrêmes » soient-elles. Les zones polaires (Arctique et Antarctiques) et le climat extrêmement froid qui les aractérise, suscitent l’intérêt de nombreuses études. Ce travail de thèse avait pour but d’explorer les différents mécanismes intervenant dans la mise en place de la thermorégulation chez l’oiseau. Nous nous sommes principalement intéressés, par une approche intégrative, de l’animal entier (méthodes de calorimétrie indirecte) à l’expression génique (techniques de RT-PCR), à caractériser les modifications métaboliques et l’implication d’une protéine découplante (avUCP) dans les mécanismes de thermorégulation, et principalement la thermogenèse sans frisson (NST) en réponse à une exposition chronique au froid.Au cours de deux études menées chez le caneton de Barbarie, nous avons démontré l’aspect « adaptatif » de la NST ainsi que l’implication potentielle de l’UCP aviaire dans ce mécanisme en faisant varier tout d’abord la température d’acclimatation puis la durée d’exposition pour caractériser la mise en place de la NST au cours de la croissance. Lors d’une troisième étude, nous nous sommes intéressés à une étape clé de la vie des manchots royaux (passage en mer) caractérisée par un stress thermique important et une activité physique accrue dus aux longs séjours en eau froide. Ce contexte environnemental et physiologique entraine nécessairement des adaptations métaboliques, comme la mise en place d’un métabolisme lipidique efficace soutenant ainsi les dépenses énergétiques accrues lors des voyages en mer. / Because of their huge phenotypic diversity (10,000 species), birds were able to colonize many “extreme” ecological niches. Many studies have been focus on the polar areas (i.e. Arctic and Antarctica) with their typical cold climate. The aim of this work was to explore the onset of thermoregulatory mechanisms in birds. Using an integrative approach, from whole animal (indirect calorimetry) to gene expression (RT-PCR analysis), we investigated metabolic adaptations and avian uncoupling protein implication in non shivering thermogenesis (NST) during chronic cold exposure. In two studies, working on Muscovy ducklings, we have highlighted the “adaptative” aspect of NST and potential implication of avUCP in this mechanism in relation to different ambient temperatures of acclimation and to cold exposure duration.In a third study, we were interested by passage from shore to marine life of King Penguins that represents a key step of their life. This is defined by massive cold stress (cold water) and increase of physical activity (long-time swimming), leading great metabolic adaptations, such as an increase of lipid oxidative capacities which would sustain expensive energetic cost of marine life.

A existência de uma proteína mitocondrial desacopladora em plantas, PUMP, foi demonstrada em 1995. A PUMP, como a proteína desacopladora de mitocôndrias de tecido adiposo marrom, UCP1, e outras proteínas homólogas descobertas posteriormente, aumenta a condutividade de membrana a H+. Nucleotídeos de purina, PN, inibem a atividade das proteínas desacopladoras e o mecanismo de condução de H+ depende da presença de ácidos graxos livres, FFA. A atividade e a expressão da PUMP são estimuladas pela exposição ao frio e mudam durante o amadurecimento de frutos. A expressão do gene da PUMP de Arabidopsis thaliana em E. coli permite a obtenção de AtPUMP. Neste trabalho, analisando a funcionalidade da AtPUMP incorporada em proteolipossomos, demonstramos que esta proteína é funcional. A incorporação de proteínas desacopladoras em proteolipossomos fornece um sistema modelo que permite analisar as suas propriedades funcionais e mecanísticas. A condutância a H+ em proteolipossomos contendo PUMP isolada de batata foi claramente ativada por FFA. Contudo, a inibição por PN não se mostrou reprodutível. A AtPUMP, reconstituída em proteolipossomos, foi ativada por FFA com Km\'s aparentes de: 42 µM (ácido linoleico, LA), 55 µM (ácido láurico) e 70 µM (ácido palmítico), e inibida por PN com Ki\'s aparentes de: 0.8 mM (GDP), 0.85 mM (ATP), 0.98 mM (GTP) e 1.4 mM (ADP). O efluxo de H+ ativado por LA mediado por AtPUMP aumentou exponencialmente em função do potencial transmembrânico (Δψ). O coeficiente de partição (KP) entre a fase aquosa e proteolipossomos contendo AtPUMP para o LA de 64170, foi ~1,6 vezes superior que ao KP obtido para o LA em lipossomos. Em ensaios de ligação obtidos usando microcalorimetria de titulação isotérmica (ITC), determinou-se que a AtPUMP tem, provavelmente, dois sítios de ligação para o LA e que essa interação é exotérmica. Em ensaios de microcalorimetria com suspensão de mitocôndrias de batatas, determinou-se que há uma correlação linear entre o calor produzido e o oxigênio consumido (65,6 kcal/mol O2) quando a PUMP foi ativada por LA. Através dos resultados obtidos até então, concluo que a PUMP (AtPUMP) é um desacoplador mitocondrial presente em plantas. Os estudos apresentados aqui, de reconstituição em lipossomos, foram essenciais para a compreensão da regulação da atividade dessa proteína. Além disso, foram obtidas as primeiras medidas diretas de liberação de calor pela PUMP por microcalorimetria. / In 1995, a plant mitochondrial uncoupling protein, PUMP, was first described. PUMP, like the known uncoupling protein from brown adipose tissue, UCP1, increases the inner mitochondrial membrane permeability to H+. H+ transport is dependent on the presence of free fatty acids, FFA, and it is inhibited by purine nucleotides, PN. PUMP expression and activity are stimulated by cold exposure, which may vary during fruit ripening. By expressing a full length cDNA encoding the Arabidopsis UCP in E. coli, the recombinant AtPUMP was obtained. In this study, AtPUMP was incorporated in proteoliposomes and the functionality of the protein was demonstrated. The incorporation of uncoupling proteins in proteoliposomes constitutes a model that allows the functional and the mechanistic analysis of these proteins. The H+ conductance mediated by reconstituted potato PUMP was, undoubtedly, activated by FFA. However, the inhibition by PN was not reproducible. Reconstituted AtPUMP was activated by FFA and the apparent Km\'s were determined: 42 µM (linoleic acid, LA), 55 µM (lauric acid) and 70 µM (palmitic acid). Reconstituted AtPUMP was inhibited by PN, and the apparent Kis were determined: 0.8 mM (GDP), 0.85 mM (ATP), 0.98 mM (GTP) and 1.4 mM (ADP). AtPUMP mediated H+ efflux rate, activated by LA, was exponentially dependent on membrane potential (Δψ). The partition coefficient (KP) between the aqueous phase and the membrane phase was determined for LA. The KP was 1.6 times higher for AtPUMP proteoliposomes than for liposomes. Using Isothermal Titration Microcalorimetry (ITC), we verified that there is a linear correlation between the heat produced and oxygen depletion (65,2 kcal/mol O2) in a suspension of potato mitochondria, when PUMP was activated by LA. Using ITC we also determined that LA might bind to two different sites in AtPUMP. Based on the results obtained, we concluded that PUMP (or AtPUMP) is a plant mitochondrial uncoupler. The reconstitution assays permitted the study of FFA and PN regulation. In addition, our results represent the first direct confirmation that fatty acids regulate heat release in plant mitochondria, a process that may play a role in cold adaptation, fruit ripening and flower blossoming.