Angiopoietin like-2: a pro-inflammatory and pro-oxidative protein that contributes to endothelial dysfunction

Le vieillissement vasculaire est caractérisé par une dysfonction de l’endothélium. De nombreux facteurs de risque cardiovasculaire tels que l’obésité et l’hypertension prédisposent l’endothélium à un stress oxydant élevé aboutissant à une dysfonction endothéliale, celle-ci étant communément accompagnée d’une diminution de la biodisponibilité du monoxyde d’azote. Bien que la fonction endothéliale soit un déterminant majeur de la prédiction du risque cardiovasculaire des patients, son évaluation individuelle reste très limitée. En conséquence, il existe un intérêt scientifique grandissant pour la recherche de meilleurs biomarqueurs. L’Angiopoiétine like-2 (angptl2), une protéine identifiée récemment, joue un rôle pro-inflammatoire et pro-oxydant dans plusieurs désordres causés par une inflammation chronique allant de l’obésité à l’athérosclérose. L’inflammation et un stress oxydant accru ont été établis comme des mécanismes sous-jacents à l’apparition d’une dysfonction endothéliale, c’est pourquoi ce travail met l’accent sur le rôle de l’angptl2 dans la dysfonction endothéliale. Plus précisément, ce travail vise à: 1) déterminer les effets aigus de l’angptl2 sur la fonction endothéliale, 2) caractériser la fonction endothéliale et la contribution des différents facteurs relaxants dérivés de l'endothélium (EDRF) dans plusieurs lits vasculaires, et ce, dans un modèle de souris réprimant l’expression de l’angptl2 (knock-down, KD), et 3) examiner si l'absence d'expression angptl2 protège contre la dysfonction endothéliale induite par un régime riche en graisses (HFD) ou par perfusion d'angiotensine II (angII) chez la souris. Dans la première étude, l’incubation aigue avec de l’angptl2 recombinante induit une dysfonction endothéliale dans les artères fémorales isolées de souris de type sauvage (WT), probablement en raison d’une production accrue d'espèces réactives oxygénées. Les artères fémorales de souris angptl2 KD présentent une meilleure fonction endothéliale en comparaison aux souris WT, vraisemblablement par une plus grande contribution de la prostacycline dans la vasodilatation. Après 3 mois d’une diète HFD, les principaux EDRF respectifs des artères fémorales et mésentériques sont conservés uniquement dans les souris angptl2 KD. Cette préservation est associée à un meilleur profil métabolique, une moindre accumulation de triglycérides dans le foie et des adipocytes de plus petite taille. De plus, l’expression de gènes inflammatoires dans ces tissus adipeux n’est augmentée que chez les souris WT. Dans la seconde étude, l’absence d’angptl2 résulte en une production accrue de monoxyde d’azote dans les artères cérébrales isolées par rapport à celles des souris WT. La perfusion chronique d’angII provoque, seulement chez les souris WT, une dysfonction endothéliale cérébrale probablement par le biais d’une augmentation de la production d’espèces réactives oxygénées, probablement dérivé des NADPH oxydase 1 et 2, ainsi que l'augmentation des facteurs constricteurs dérivés de l’endothélium issus de la cyclo-oxygénase. En revanche, l’apocynine réduit la dilatation cérébrale chez les souris KD traitées à l’angII, ce qui suggère le recrutement potentiel d’une voie de signalisation compensatoire impliquant les NADPH oxydases et qui aurait un effet vaso-dilatateur. Ces études suggèrent fortement que l’angptl2 peut avoir un impact direct sur la fonction endothéliale par ses propriétés pro-inflammatoire et pro-oxydante. Dans une optique d’application à la pratique clinique, les niveaux sanguins d’angptl2 pourraient être un bon indicateur de la fonction endothéliale.

Les discours de Pierre Plaoul au Parlement de Paris (1406) : un exemple des rhétoriques française et latine au Moyen Âge tardif

Le 27 mai 1406, le théologien parisien Pierre Plaoul comparaît devant la cour du Parlement de Paris en tant que représentant de l’Université de Paris dans une affaire qui l’oppose à l’Université de Toulouse. Il y prononce un sermon en latin, ce que la cour lui reproche instantanément, lui demandant de parler en français pour la prochaine séance. Le 7 juin, lors de sa deuxième comparution, il parle cette fois en langue vernaculaire et prononce un discours extrêmement différent du premier, autant dans son genre que dans son registre de citations. Les deux discours sont conservés dans le registre X1a4787 des Archives nationales de France. L’édition des discours permet de comprendre le raisonnement derrière leurs différences, mais il permet surtout de constater que le discours français fait état d’une érudition encore plus grande que son homologue latin et que son orateur n’était nullement gêné par l’usage de la langue vernaculaire. Remis dans le contexte historiographique actuel, il en ressort que l’utilisation du français par Plaoul concorde parfaitement avec l’abandon du modèle de rapport diglossique entre latin et français pour la fin du Moyen Âge, lui préférant plutôt un rapport de langues en contacts. Ce postulat est soutenu par les nombreuses occurrences d’universitaires médiévaux démontrant une excellente maîtrise d’un registre savant de la langue vulgaire, des poètes, aux prédicateurs en passant par les practiciens du droit. Un examen plus attentif de l’utilisation de la langue française par les docteurs en théologie du règne de Charles VI vient aussi appuyer l’hypothèse selon laquelle les universitaires du bas Moyen Âge considéraient la langue vernaculaire comme un instrument approprié à la transmission de la culture savante.

Changes in cortical and sub-cortical patterns of activity associated with aging during the performance of a lexical set-shifting task

Bien que le passage du temps altère le cerveau, la cognition ne suit pas nécessairement le même destin. En effet, il existe des mécanismes compensatoires qui permettent de préserver la cognition (réserve cognitive) malgré le vieillissement. Les personnes âgées peuvent utiliser de nouveaux circuits neuronaux (compensation neuronale) ou des circuits existants moins susceptibles aux effets du vieillissement (réserve neuronale) pour maintenir un haut niveau de performance cognitive. Toutefois, la façon dont ces mécanismes affectent l’activité corticale et striatale lors de tâches impliquant des changements de règles (set-shifting) et durant le traitement sémantique et phonologique n’a pas été extensivement explorée. Le but de cette thèse est d’explorer comment le vieillissement affecte les patrons d’activité cérébrale dans les processus exécutifs d’une part et dans l’utilisation de règles lexicales d’autre part. Pour cela nous avons utilisé l’imagerie par résonance magnétique fonctionnelle (IRMf) lors de la performance d’une tâche lexicale analogue à celle du Wisconsin. Cette tâche a été fortement liée à de l’activité fronto-stritale lors des changements de règles, ainsi qu’à la mobilisation de régions associées au traitement sémantique et phonologique lors de décisions sémantiques et phonologiques, respectivement. Par conséquent, nous avons comparé l’activité cérébrale de jeunes individus (18 à 35 ans) à celle d’individus âgés (55 à 75 ans) lors de l’exécution de cette tâche. Les deux groupes ont montré l’implication de boucles fronto-striatales associées à la planification et à l’exécution de changements de règle. Toutefois, alors que les jeunes semblaient activer une « boucle cognitive » (cortex préfrontal ventrolatéral, noyau caudé et thalamus) lorsqu’ils se voyaient indiquer qu’un changement de règle était requis, et une « boucle motrice » (cortex postérieur préfrontal et putamen) lorsqu’ils devaient effectuer le changement, les participants âgés montraient une activation des deux boucles lors de l’exécution des changements de règle seulement. Les jeunes adultes tendaient à présenter une augmentation de l’activité du cortex préfrontal ventrolatéral, du gyrus fusiforme, du lobe ventral temporale et du noyau caudé lors des décisions sémantiques, ainsi que de l’activité au niveau de l’aire de Broca postérieur, de la junction temporopariétale et du cortex moteur lors de décisions phonologiques. Les participants âgés ont montré de l’activité au niveau du cortex préfrontal latéral et moteur durant les deux types de décisions lexicales. De plus, lorsque les décisions sémantiques et phonologiques ont été comparées entre elles, les jeunes ont montré des différences significatives au niveau de plusieurs régions cérébrales, mais pas les âgés. En conclusion, notre première étude a montré, lors du set-shifting, un délai de l’activité cérébrale chez les personnes âgées. Cela nous a permis de conceptualiser l’Hypothèse Temporelle de Compensation (troisième manuscrit) qui consiste en l’existence d’un mécanisme compensatoire caractérisé par un délai d’activité cérébrale lié au vieillissement permettant de préserver la cognition au détriment de la vitesse d’exécution. En ce qui concerne les processus langagiers (deuxième étude), les circuits sémantiques et phonologiques semblent se fusionner dans un seul circuit chez les individus âgés, cela représente vraisemblablement des mécanismes de réserve et de compensation neuronales qui permettent de préserver les habilités langagières.

Apprentissage d'espaces sémantiques

Dans cette dissertation, nous présentons plusieurs techniques d’apprentissage d’espaces sémantiques pour plusieurs domaines, par exemple des mots et des images, mais aussi à l’intersection de différents domaines. Un espace de représentation est appelé sémantique si des entités jugées similaires par un être humain, ont leur similarité préservée dans cet espace. La première publication présente un enchaînement de méthodes d’apprentissage incluant plusieurs techniques d’apprentissage non supervisé qui nous a permis de remporter la compétition “Unsupervised and Transfer Learning Challenge” en 2011. Le deuxième article présente une manière d’extraire de l’information à partir d’un contexte structuré (177 détecteurs d’objets à différentes positions et échelles). On montrera que l’utilisation de la structure des données combinée à un apprentissage non supervisé permet de réduire la dimensionnalité de 97% tout en améliorant les performances de reconnaissance de scènes de +5% à +11% selon l’ensemble de données. Dans le troisième travail, on s’intéresse à la structure apprise par les réseaux de neurones profonds utilisés dans les deux précédentes publications. Plusieurs hypothèses sont présentées et testées expérimentalement montrant que l’espace appris a de meilleures propriétés de mixage (facilitant l’exploration de différentes classes durant le processus d’échantillonnage). Pour la quatrième publication, on s’intéresse à résoudre un problème d’analyse syntaxique et sémantique avec des réseaux de neurones récurrents appris sur des fenêtres de contexte de mots. Dans notre cinquième travail, nous proposons une façon d’effectuer de la recherche d’image ”augmentée” en apprenant un espace sémantique joint où une recherche d’image contenant un objet retournerait aussi des images des parties de l’objet, par exemple une recherche retournant des images de ”voiture” retournerait aussi des images de ”pare-brises”, ”coffres”, ”roues” en plus des images initiales.

Les substrats neuronaux sous-tendant le binding automatique et contrôlé en mémoire de travail dans la schizophrénie : une étude en IRMf.

Le déficit de mémoire de travail est une des caractéristiques centrales de la schizophrénie et est associé aux problèmes de fonctionnement quotidien des patients. Parmi les différents processus sous-tendus par la mémoire de travail, nous nous intéressons au binding. Le binding est un processus qui permet d’associer plusieurs informations (par exemple, associer le nom d’une personne avec son adresse). En mémoire de travail, les patients schizophrènes ne présentent pas de déficit de binding lorsque les informations sont associées involontairement. Ce type de binding est appelé binding automatique. Cependant, les informations peuvent aussi être associées sous le contrôle volontaire et attentionnel des participants, nous parlons alors de binding contrôlé. À l’heure actuelle, aucune étude n’a été effectuée sur le binding contrôlé en schizophrénie. Notre objectif est de déterminer s'il existe un déficit spécifique de binding contrôlé dans la schizophrénie, et de décrire les substrats neuronaux qui le sous-tendent. Dix-neuf patients schizophrènes et 18 sujets témoins ont effectué une tâche de binding en mémoire de travail dans un scanner IRM. Celle-ci consistait à mémoriser des mots et des positions spatiales dont l’association variait selon deux conditions. Dans la condition de binding contrôlé, les mots et les positions spatiales étaient présentés séparément et les participants devaient faire l’association entre les deux informations eux-mêmes. Dans la condition de binding automatique, les mots étaient d’emblée associés aux positions spatiales. Nos résultats suggèrent que les patients schizophrènes n’auraient pas de déficit de binding automatique alors qu’ils auraient un déficit de binding contrôlé par rapport aux sujets témoins. Le déficit de binding contrôlé serait sous-tendu par des niveaux d’activation plus faibles du cortex préfrontal dorsolatéral. Les processus contrôlés seraient altérés alors que les processus automatiques seraient préservés dans la schizophrénie.

Topological Invariants in Hydrodynamics and Hydromagnetics

In this thesis we are studying possible invariants in hydrodynamics and hydromagnetics. The concept of flux preservation and line preservation of vector fields, especially vorticity vector fields, have been studied from the very beginning of the study of fluid mechanics by Helmholtz and others. In ideal magnetohydrodynamic flows the magnetic fields satisfy the same conservation laws as that of vorticity field in ideal hydrodynamic flows. Apart from these there are many other fields also in ideal hydrodynamic and magnetohydrodynamic flows which preserves flux across a surface or whose vector lines are preserved. A general study using this analogy had not been made for a long time. Moreover there are other physical quantities which are also invariant under the flow, such as Ertel invariant. Using the calculus of differential forms Tur and Yanovsky classified the possible invariants in hydrodynamics. This mathematical abstraction of physical quantities to topological objects is needed for an elegant and complete analysis of invariants.Many authors used a four dimensional space-time manifold for analysing fluid flows. We have also used such a space-time manifold in obtaining invariants in the usual three dimensional flows.In chapter one we have discussed the invariants related to vorticity field using vorticity field two form w2 in E4. Corresponding to the invariance of four form w2 ^ w2 we have got the invariance of the quantity E. w. We have shown that in an isentropic flow this quantity is an invariant over an arbitrary volume.In chapter three we have extended this method to any divergence-free frozen-in field. In a four dimensional space-time manifold we have defined a closed differential two form and its potential one from corresponding to such a frozen-in field. Using this potential one form w1 , it is possible to define the forms dw1 , w1 ^ dw1 and dw1 ^ dw1 . Corresponding to the invariance of the four form we have got an additional invariant in the usual hydrodynamic flows, which can not be obtained by considering three dimensional space.In chapter four we have classified the possible integral invariants associated with the physical quantities which can be expressed using one form or two form in a three dimensional flow. After deriving some general results which hold for an arbitrary dimensional manifold we have illustrated them in the context of flows in three dimensional Euclidean space JR3. If the Lie derivative of a differential p-form w is not vanishing,then the surface integral of w over all p-surfaces need not be constant of flow. Even then there exist some special p-surfaces over which the integral is a constant of motion, if the Lie derivative of w satisfies certain conditions. Such surfaces can be utilised for investigating the qualitative properties of a flow in the absence of invariance over all p-surfaces. We have also discussed the conditions for line preservation and surface preservation of vector fields. We see that the surface preservation need not imply the line preservation. We have given some examples which illustrate the above results. The study given in this thesis is a continuation of that started by Vedan et.el. As mentioned earlier, they have used a four dimensional space-time manifold to obtain invariants of flow from variational formulation and application of Noether's theorem. This was from the point of view of hydrodynamic stability studies using Arnold's method. The use of a four dimensional manifold has great significance in the study of knots and links. In the context of hydrodynamics, helicity is a measure of knottedness of vortex lines. We are interested in the use of differential forms in E4 in the study of vortex knots and links. The knowledge of surface invariants given in chapter 4 may also be utilised for the analysis of vortex and magnetic reconnections.

Studies on isolation and molecular characterization of plasmids from Vibrios

While the seriousness of the problem of antibiotic resistance is now recognized, the complex web of resistance linking humans, animals, and the environment is getting realized. More often, antibiotics are used as a preventive measure against diseases. Antibiotic use for agriculture leads to the increased resistance in the environment since antibiotics are inevitable element during agriculture/aquaculture and antibiotic residues are excreted as waste that is frequently spread onto farmland as organic fertilizer. Fecal bacteria survive long periods in the environment and spread through runoff into groundwater, rivers, and marine ecosystems.However, horizontal gene transfer occurs in the animals and guts of humans and in a variety of ecosystems, creating a pool of resistance in the rice fields and open waters. Even if people are not in direct contact with resistant disease through food animals, there are chances of contact with resistant fecal pathogens from the environment. Additionally, pathogens that are autochthonous to the environment can acquire resistance genes from the environment. Our study revealed that autochthonous , bacteria Vibrio spp gained antibiotic resistance in the environment. Further, it was evident that horizontal gene transfer occurs in Vibrio by means of plasmids, which further augments the gravity of the problem. Non-pathogenic bacteria may also acquire resistance genes and serve as a continuing source of resistance for other bacteria, both in the environment, and in the human gut. As the effectiveness of antibiotics for medical applications decline, the indiscriminate use of in aquaculture and in humans can have disastrous conditions in future due to horizontal gene transfer and the spread of resistant organisms: We must recognize and deal with the threat posed by overuse of antibiotics.

Studies on taxonomy and ecology of Mysidacea from the EEZ of India

Members of the order Mysidacea are important component in marine and estuarine plankton inhabiting all regions of the oceans. There are many brackish water species and few species occur in fresh water, some have become adapted to the specialized environments of caves and wells. They are omnivores, responsible for remineralisation of a substantial portion of the detritus in the water column. They form an important link in the food chain (between microbial producers and secondary consumers) and therefore play a major role in the cycling of energy within the aquatic ecosystem. In tropical and subtropical waters, swarms of mysids are exploited commercially and marketed as preserved cooked food. Mysids have been used in fish farming as live feed resource. They are also excellent experimental organism, extremely useful in the studies of potential impact of various pollutants in the aquatic environment. Mysids are also used in wood pulp effluent plants.Considering the significant role of mysids in the productivity of tropical and coastal ecosystems,the present study has been undertaken to extend our knowledge on the systematics, species composition, distribution,abundance and ecology of mysid fauna of the Indian EEZ and adjoining areas. The present study therefore will undoubtedly fumish valuable information on Mysidacea of the Indian waters.

Physicochemical and Biochemical Characterization of Enzymes Immobilized on lnorganic Matrices

Biotechnology is currently considered as a useful altemative to conventional process technology in industrial and catalytic fields. The increasing awareness of the need to create green and sustainable production processes in all fields of chemistry has stimulated materials scientists to search for innovative catalysts supports. lmmobilization of enzymes in inorganic matrices is very useful in practical applications due to the preserved stability and catalytic activity of the immobilized enzymes under extreme conditions. Nanostructured inorganic, organic or hybrid organic-inorganic nanocomposites present paramount advantages to facilitate integration and miniaturization of the devices (nanotechnologies), thus affording a direct connection between the inorganic, organic and biological worlds. These properties, combined with good chemical stability, make them competent candidates for designed biocatalysts, protein-separation devices, drug delivery systems, and biosensors Aluininosilicate clays and layered double hydroxides, displaying, respectively, cation and anion exchange properties, were found to be attractive materials for immobilization because of their hydrophilic, swelling and porosity properties, as well as their mechanical and thermal stability.The aim of this study is the replacement of inorganic catalysts by immobilized lipases to obtain purer and healthier products.Mesocellular silica foams were synthesized by oil-in-water microemulsion templating route and were functionalized with silane and glutaraldehyde. " The experimental results from IR spectroscopy and elemental analysis demonstrated the presence of immobilized lipase and also functionalisation with silane and glutaraldehyde on the supports.The present work is a comprehensive study on enzymatic synthesis of butyl isobutyrate through esterification reaction using lipase immobilized onto mesocellular siliceous foams and montmorillonite K-10 via adsorption and covalent binding. Moreover, the irnrnobil-ization does not modify the nature of the kinetic mechanism proposed which is of the Bi-Bi Ping—Pong type with inhibition by n-butanol. The immobilized biocatalyst can be commercially exploited for the synthesis of other short chain flavor esters. Mesocellular silica foams (MCF) were synthesized by microemusion templating method via two different routes (hydrothermal and room temperature). and were functionalized with silane and glutaraldehyde. Candida rugosa lipase was adsorbed onto MCF silica and clay using heptane as the coupling medium for reactions in non-aqueous media. I From XRD results, a slight broadening and lowering of d spacing values after immobilization and modification was observed in the case of MCF 160 and MCF35 but there was no change in the d-spacing in the case of K-10 which showed that the enzymes are adsorbed only on the external surface. This was further confirmed from the nitrogen adsorption measurements

Studies on meroplankton

Plankton community, drawn from a vary wide variety of animal phyla, formed the basic food supply of marine life and indicators of water mass. The term meroplankton generally referred to that portion of the zooplankton which is transient in nature, remaining rest of their lives in the nektonic or benthic environment. This group was selected for intensive studies, considering the role of meroplankton in the economy of the sea and the scarcity of literature on them from the Indian Ocean. The preser .udy besides providing information regarding the fixation and preservation !e _ iniques and biochemical aspects of tropical meroplankton, also consolidates information regarding their zoogeography in the Indian Ocean region, with a view to amplifying the limited information available from this area. The distribution studies are based on the collections made during the International Indian Ocean Expedition (1960-65), whereas the material for preservation and biochemical studies was collected from the coastal waters during 1968-1978. Salient features:- 2% of formaldehyde buffered with 2% borax, added to the plankton in the ratio of 9:1 was found the best fixative. On fixation the plankton underwent shrinkage due to loss of 15 to 87% water. Addition of antioxidants prevented colour fading. Narcotization by different specific reagents prior to fixation reduced distortions due to violent reaction and improved morphological conditions. One percent formaldehyde solution in sea water buffered with borax or neutralised with calcium carbonate perfectly preserved majority of meroplankton. Equally good was one percent propylene phenoxetol buffered with borax. Biochemical compostion of vaioous taxa showed variations according to their age class, size groups metamorphosing stage, feeding mechanism, type of organism fed and time of collection. General distribution studies of 4 meroplankton taxa - Anthozoan larvae, cirripedia larvae, sipunculoid larvae and gastropod larvae stowed abundance in the coastal areas especially during the SW monsoon period. Based on the larval distribution different zoo-geographical areas in the Indian Ocean are differentiated.

Isolation, Stabilization and Characterization of Xanthophyll from Marigold Flower- Tagetes Erecta-L

The present paper deals with the chemistry, isolation, separation, characterisation and stabilisation of the Marigold oleoresin and its application as a natural food colorant. Marigold (Tagetes Erecta L), an ornamental plant belonging to the composite family, has a rich source of natural antioxidant-Lutein. A natural pigment, xanthophylls offer an alternative to synthetic dyes as a food colorant, due to its non-toxicity. Chromatographic separations of saponified and unsaponified oleoresin were performed and Trans-Lutein identified as the major constituent. Well-preserved flowers exhibit a high yield of Xanthophyll content (105.19 g/Kg) in contrast to the unpreserved flower sample (54.87 g/Kg), emphasizing the significance of flower preservation in the extraction of xanthophyll. The stability and amount of xanthophyll also increased from 105.19 g/Kg to 226.88 g/Kg on saponification and subsequent purification with Ethylene Dichloride

Natural Rubber Latex Filler Masterbatch by Soap Sensitised Coagulation-Preparation, Processing and Evaluation

Sensitisation of natural rubber latex by addition of a small quantity of an anionic surfactant prior to the addition of a coacervant results in quick coagulation. The natural rubber prepared by the novel coagulation method shows improved raw rubber characteristics, better cure characteristics in gum and carbon black filled compounds and improved mechanical properties as compared to the conventionally coagulated natural rubber. Compounds based on dried masterbatches prepared by the incorporation of fluffy carbon black in different forms of soap sensitised natural rubber latices such as fresh latex, preserved field latex, centrifuged latex and a blend of preserved field latex and skim latex show improved cure characteristics and vucanizate properties as compared to an equivalent conventional dry rubber-fluffy carbon black based compound. The latex masterbatch based vulcanizates show higher level of crosslinking and better dispersion of filler. Vulcanizates based on fresh natural rubber latex- dual filler masterbatches containing a blend of carbon black and silica prepared by the modified coagulation process shows very good mechanical and dynamic properties that could be correlated to a low rolling resistance. The carbon black/silica/nanoclay tri-filler - fresh natural rubber latex masterbatch based vulcanizates show improved mechanical properties as the proportion of nanoclay increased up to 5 phr. The fresh natural rubber latex based carbon black-silica masterbatch/ polybutadiene blend vulcanizates show superior mechanical and dynamic properties as compared to the equivalent compound vulcanizates prepared from the dry natural rubber-filler (conventional dry mix)/polybutadiene blends

Investigation on key molecular targets responsible for antidiabetic properties of Symplocos cochinchinensis (Lour.) S. Moore

Diabetes mellitus is a heterogeneous metabolic disorder characterized by hyperglycemia with disturbances in carbohydrate, protein and lipid metabolism resulting from defects in insulin secretion, insulin action or both. Currently there are 387 million people with diabetes worldwide and is expected to affect 592 million people by 2035. Insulin resistance in peripheral tissues and pancreatic beta cell dysfunction are the major challenges in the pathophysiology of diabetes. Diabetic secondary complications (like liver cirrhosis, retinopathy, microvascular and macrovascular complications) arise from persistent hyperglycemia and dyslipidemia can be disabling or even life threatening. Current medications are effective for control and management of hyperglycemia but undesirable effects, inefficiency against secondary complications and high cost are still serious issues in the present prognosis of this disorder. Hence the search for more effective and safer therapeutic agents of natural origin has been found to be highly demanding and attract attention in the present drug discovery research. The data available from Ayurveda on various medicinal plants for treatment of diabetes can efficiently yield potential new lead as antidiabetic agents. For wider acceptability and popularity of herbal remedies available in Ayurveda scientific validation by the elucidation of mechanism of action is very much essential. Modern biological techniques are available now to elucidate the biochemical basis of the effectiveness of these medicinal plants. Keeping this idea the research programme under this thesis has been planned to evaluate the molecular mechanism responsible for the antidiabetic property of Symplocos cochinchinensis, the main ingredient of Nishakathakadi Kashayam, a wellknown Ayurvedic antidiabetic preparation. A general introduction of diabetes, its pathophysiology, secondary complications and current treatment options, innovative solutions based on phytomedicine etc has been described in Chapter 1. The effect of Symplocos cochinchinensis (SC), on various in vitro biochemical targets relevant to diabetes is depicted in Chapter 2 including the preparation of plant extract. Since diabetes is a multifactorial disease, ethanolic extract of the bark of SC (SCE) and its fractions (hexane, dichloromethane, ethyl acetate and 90 % ethanol) were evaluated by in vitro methods against multiple targets such as control of postprandial hyperglycemia, insulin resistance, oxidative stress, pancreatic beta cell proliferation, inhibition of protein glycation, protein tyrosine phosphatase-1B (PTP-1B) and dipeptidyl peptidase-IV (DPPxxi IV). Among the extracts, SCE exhibited comparatively better activity like alpha glucosidase inhibition, insulin dependent glucose uptake (3 fold increase) in L6 myotubes, pancreatic beta cell regeneration in RIN-m5F and reduced triglyceride accumulation in 3T3-L1 cells, protection from hyperglycemia induced generation of reactive oxygen species in HepG2 cells with moderate antiglycation and PTP-1B inhibition. Chemical characterization by HPLC revealed the superiority of SCE over other extracts due to presence of bioactives (beta-sitosterol, phloretin 2’glucoside, oleanolic acid) in addition to minerals like magnesium, calcium, potassium, sodium, zinc and manganese. So SCE has been subjected to oral sucrose tolerance test (OGTT) to evaluate its antihyperglycemic property in mild diabetic and diabetic animal models. SCE showed significant antihyperglycemic activity in in vivo diabetic models. Chapter 3 highlights the beneficial effects of hydroethanol extract of Symplocos cochinchinensis (SCE) against hyperglycemia associated secondary complications in streptozotocin (60 mg/kg body weight) induced diabetic rat model. Proper sanction had been obtained for all the animal experiments from CSIR-CDRI institutional animal ethics committee. The experimental groups consist of normal control (NC), N + SCE 500 mg/kg bwd, diabetic control (DC), D + metformin 100 mg/kg bwd, D + SCE 250 and D + SCE 500. SCEs and metformin were administered daily for 21 days and sacrificed on day 22. Oral glucose tolerance test, plasma insulin, % HbA1c, urea, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, total protein etc. were analysed. Aldose reductase (AR) activity in the eye lens was also checked. On day 21, DC rats showed significantly abnormal glucose response, HOMA-IR, % HbA1c, decreased activity of antioxidant enzymes and GSH, elevated AR activity, hepatic and renal oxidative stress markers compared to NC. DC rats also exhibited increased level of plasma urea and creatinine. Treatment with SCE protected from the deleterious alterations of biochemical parameters in a dose dependent manner including histopathological alterations in pancreas. SCE 500 exhibited significant glucose lowering effect and decreased HOMA-IR, % HbA1c, lens AR activity, and hepatic, renal oxidative stress and function markers compared to DC group. Considerable amount of liver and muscle glycogen was replenished by SCE treatment in diabetic animals. Although metformin showed better effect, the activity of SCE was very much comparable with this drug. xxii The possible molecular mechanism behind the protective property of S. cochinchinensis against the insulin resistance in peripheral tissue as well as dyslipidemia in in vivo high fructose saturated fat diet model is described in Chapter 4. Initially animal were fed a high fructose saturated fat (HFS) diet for a period of 8 weeks to develop insulin resistance and dyslipidemia. The normal diet control (ND), ND + SCE 500 mg/kg bwd, high fructose saturated fat diet control (HFS), HFS + metformin 100 mg/kg bwd, HFS + SCE 250 and HFS + SCE 500 were the experimental groups. SCEs and metformin were administered daily for the next 3 weeks and sacrificed at the end of 11th week. At the end of week 11, HFS rats showed significantly abnormal glucose and insulin tolerance, HOMA-IR, % HbA1c, adiponectin, lipid profile, liver glycolytic and gluconeogenic enzyme activities, liver and muscle triglyceride accumulation compared to ND. HFS rats also exhibited increased level of plasma inflammatory cytokines, upregulated mRNA level of gluconeogenic and lipogenic genes in liver. HFS exhibited the increased expression of GLUT-2 in liver and decreased expression of GLUT-4 in muscle and adipose. SCE treatment also preserved the architecture of pancreas, liver, and kidney tissues. Treatment with SCE reversed the alterations of biochemical parameters, improved insulin sensitivity by modifying gene expression in liver, muscle and adipose tissues. Overall results suggest that SC mediates the antidiabetic activity mainly via alpha glucosidase inhibition, improved insulin sensitivity, with antiglycation and antioxidant activities.

Catalysis by Modified Pillared Clays and Porous Clay Heterostructures

In this venture three distinct class of catalysts such as, pillared clays and transition metal loaded pillared clays , porous clay heterostructures and their transition metal loaded analogues and DTP supported on porous clay heterostructures etc. were prepared and characterized by various physico chemical methods. The catalytic activities of prepared catalysts were comparatively evaluated for the industrially important alkylation, acetalization and oxidation reactions.The general conclusions drawn from the present investigation are  Zirconium, iron - aluminium pillared clays were synthesized by ion exchange method and zirconium-silicon porous heterostructures were Summary and conclusions 259 prepared by intergallery template method. Transition metals were loaded in PILCs and PCHs by wet impregnation method.  Textural and acidic properties of the clays were modified by pillaring and post pillaring modifications.  The shift in 2θ value to lower range and increase in d (001) spacing indicate the success of pillaring process.  Surface area, pore volume, average pore size etc. increased dramatically as a result of pillaring process.  Porous clay heterostructures have higher surface area, pore volume, average pore diameter and narrow pore size distribution than that of pillared clays.  The IR spectrum of PILCs and PCHs are in accordance with literature without much variation compared to parent montmorillonite which indicate that basic clay structure is retained even after modification.  The silicon NMR of PCHs materials have intense peaks corresponding to Q4 environment which indicate that mesoporous silica is incorporated between clay layers.  Thermo gravimetric analysis showed that thermal stability is improved after the pillaring process. PCH materials have higher thermal stability than PILCs.  In metal loaded pillared clays, up to 5% metal species were uniformly dispersed (with the exception of Ni) as evident from XRD and TPR analysis. Chapter 9 260  Impregnation of transition metals in PILCs and PCHs enhanced acidity of catalysts as evident from TPD of ammonia and cumene cracking reactions.  For porous clay heterostructures the acidic sites have major contribution from weak and medium acid sites which can be related to the Bronsted sites as evident from TPD of ammonia.  Pillared clays got more Lewis acidity than PCHs as inferred from α- methyl styrene selectivity in cumene cracking reaction.  SEM images show that layer structure is preserved even after modification. Worm hole like morphology is observed in TEM image of PCHs materials  In ZrSiPCHS, Zr exists as Zr 4+ and is incorporated to silica pillars in the intergallary of clay layers as evident from XPS analysis.  In copper loaded zirconium pillared clays, copper exists as isolated species with +2 oxidation state at lower loading. At higher loading, Cu exists as clusters as evident from reduction peak at higher temperatures in TPR.  In vanadium incorporated PILCs and PCHs, vanadium exist as isolated V5+ in tetrahedral coordination which is confirmed from TPR and UVVis DRS analysis.  In cobalt loaded PCHs, cobalt exists as CoO with 2+ oxidation state as confirmed from XPS.  Cerium incorporated iron aluminium pillared clay was found to be the best catalyst for the hydroxylation of phenol in aqueous media due to the additional surface area provided by ceria mesopores and its redox properties. Summary and conclusions 261  Cobalt loaded zirconium porous clay heterostructures were found to be promising catalyst for the tertiary butylation of phenol due to higher surface area and acidic properties.  Copper loaded pillared clays were found to be good catalyst for the direct hydroxylation of benzene to phenol.  Vanadium loaded PCHs catalysts were found to be efficient catalysts for oxidation of benzyl alcohol.  DTP was firmly fixed on the mesoporous channels of PCHs by Direct method and functionalization method.  DTP supported PCHs catalyst were found to be good catalyst for acetalization of cyclohexanone with more than 90% conversion.

Drainage, salt leaching and physico-chemical properties of irrigated man-made terrace soils in a mountain oasis of northern Oman

Little is known about the sustainability of irrigated oasis agriculture in northern Oman. The objective of this study therefore was to examine which factors allowed agricultural productivity to be apparently maintained during the two millenia of a mountain oasis’ existence. Soil moisture and physico-chemical properties were measured in a typical flood-irrigated field sown to alfalfa (Medicago sativa L.). Particle size, organic (C_org) and inorganic carbon content, pH and electrical conductivity (EC)of the soil profile were analyzed at 0.15, 0.45 and 1.00 m. Saturated hydraulic conductivity and the soil’s apparent bulk density and water potential were determined from undisturbed samples at 0.05, 0.25 and 0.60 m. During irrigation cycles of 6–9 days, volumetric water contents ranged from 30% to 13%. A tracer experiment with potassium bromide revealed that 52–56% of the irrigation water was stored in the upper 0.4 m of the soil. The rest of the water moved further down the profile, thus providing the necessary drainage to avoid the build-up of toxic salt concentrations. Due to differences in pore size, plant-available water in the topsoil amounted to 18.7% compared to 13% and 13.5% at 0.25- and 0.60-m depth, respectively. The aggregate structure in the upper 1.0 m of the profile is likely preserved by concentrations of calcium carbonate (CaCO3) from 379 to 434 mg kg^-1 and C_org from 157 to 368 mg kg^-1 soil. The data indicate that the sustainability of this irrigated landuse system is due to high water quality with low sodium but high CaCO3 concentration, the elaborate terrace structure and water management which allows adequate drainage.