Metabolomics analysis in rats with thiamine deficiency identifies key metabolites in vulnerable brain regions and suggests neural stem progenitor cells play a role in ameliorating metabolic dysfunction

La documentation scientifique fait état de la présence, chez l’adulte, de cellules souches et progénitrices neurales (CSPN) endogènes dans les zones sous-ventriculaire et sous-granulaire du cerveau ainsi que dans le gyrus denté de l’hippocampe. De plus, un postulat selon lequel il serait également possible de retrouver ce type de cellules dans la moelle épinière et le néocortex des mammifères adultes a été énoncé. L’encéphalopathie de Wernicke, un trouble neurologique grave toutefois réversible qui entraîne un dysfonctionnement, voire une défaillance du cerveau, est causée principalement par une carence importante en thiamine (CT). Des observations récentes laissent envisager que les facteurs en cause dans la prolifération et la différenciation des CSPN pourraient également jouer un rôle important lors d’un épisode de CT. L’hypothèse, selon laquelle l’identification de nouveaux métabolites entrant dans le mécanisme ou la séquence de réactions se soldant en une CT pourraient en faciliter la compréhension, a été émise au moyen d'une démarche en cours permettant d’établir le profil des modifications métaboliques qui surviennent en de telles situations. Cette approche a été utilisée pour constater les changements métaboliques survenus au niveau du foyer cérébral dans un modèle de rats déficients en thiamine (rats DT), particulièrement au niveau du thalamus et du colliculus inférieur (CI). La greffe de CSPN a quant à elle été envisagée afin d’apporter de nouvelles informations sur la participation des CSPN lors d’un épisode de CT et de déterminer les bénéfices thérapeutiques potentiels offerts par cette intervention. Les sujets de l’étude étaient répartis en quatre groupes expérimentaux : un premier groupe constitué de rats dont la CT était induite par la pyrithiamine (rats DTiP), un deuxième groupe constitué de rats-contrôles nourris ensemble (« pair-fed control rats » ou rats PFC) ainsi que deux groupes de rats ayant subi une greffe de CSPN, soit un groupe de rats DTiP greffés et un dernier groupe constitué de rats-contrôles (rats PFC) greffés. Les échantillons de foyers cérébraux (thalamus et CI) des quatre groupes de rats ont été prélevés et soumis à des analyses métabolomiques non ciblées ainsi qu’à une analyse visuelle par microscopie à balayage électronique (SEM). Une variété de métabolites-clés a été observée chez les groupes de rats déficients en thiamine (rats DTiP) en plus de plusieurs métabolites dont la documentation ne faisait pas mention. On a notamment constaté la présence d’acides biliaires, d’acide cynurénique et d’acide 1,9— diméthylurique dans le thalamus, alors que la présence de taurine et de carnosine a été observée dans le colliculus inférieur. L’étude a de plus démontré une possible implication des CSPN endogènes dans les foyers cérébraux du thalamus et du colliculus inférieur en identifiant les métabolites-clés ciblant les CSPN. Enfin, les analyses par SEM ont montré une amélioration notable des tissus à la suite de la greffe de CSPN. Ces constatations suggèrent que l’utilisation de CSPN pourrait s’avérer une avenue thérapeutique intéressante pour soulager la dégénérescence symptomatique liée à une grave carence en thiamine chez l’humain.

INVESTIGATIONS ON THE RECOVERY OF TITANIUM VANADIUM AND IRON VALUES FROM THE WASTE CHILORIDE LIQUORS OF TITANIA INDUSTRY

The thesis entitled INVESTIDGATIONS ON THE RECOVERY OF TITANIUM VANADIUM AND IRON VALUES FROM THE WASTE CHILORIDE LIQUORS OF TITANIA INDUSTRY embodies the results of the investigations carried out on the solvent extraction separation of iron (III) vanadium(V) and titanium (IV) chlorides from the waste chloride liquors of titanium minerals processing industry by employing tributylphosphate (TBT) as an extractant. The objective of this study is to generate the knowledge base to achieve the recovery of iron, vanadium and titanium cvalues from multi- metal waste chloride liquors originating from ilmenite mineral beneficiation industries through selective separation and value added material development

Production of Alkaline Protease by Free and Immobilised Cells of VIBRIO sp. Under Different Fermentation Systems and Its Application on Deproteinisation of Prawn Shell Waste for Chitin Recovery

This thesis presents a detailed account of a cost - effective approach towards enhanced production of alkaline protease at profitable levels using different fermentation designs employing cheap agro-industrial residues. It involves the optimisation of process parameters for the production of a thermostable alkaline protease by Vibrio sp. V26 under solid state, submerged and biphasic fermentations, production of the enzyme using cell immobilisation technology and the application of the crude enzyme on the deproteinisation of crustacean waste.The present investigation suggests an economic move towards Improved production of alkaline protease at gainful altitudes employing different fermentation designs utilising inexpensive agro-industrial residues. Moreover, the use of agro-industrial and other solid waste substrates for fermentation helps to provide a substitute in conserving the already dwindling global energy resources. Another alternative for accomplishing economically feasible production is by the use of immobilisation technique. This method avoids the wasteful expense of continually growing microorganisms. The high protease producing potential of the organism under study ascertains their exploitation in the utilisation and management of wastes. However, strain improvement studies for the production of high yielding variants using mutagens or by gene transfer are required before recommending them to Industries.Industries, all over the world, have made several attempts to exploit the microbial diversity of this planet. For sustainable development, it is essential to discover, develop and defend this natural prosperity. The Industrial development of any country is critically dependent on the intellectual and financial investment in this area. The need of the hour is to harness the beneficial uses of microbes for maximum utilisation of natural resources and technological yields. Owing to the multitude of applications in a variety of industrial sectors, there has always been an increasing demand for novel producers and resources of alkaline proteases as well as for innovative methods of production at a commercial altitude. This investigation forms a humble endeavour towards this perspective and bequeaths hope and inspiration for inventions to follow.

Dopamine Receptor Subtypes,IP3, cAMP and cGMP Functional Regulation in Parkinsonism Induced by Unilateral Infusion of Rotenone in Rats: Recovery with Bone Marrow Cells,Serotonin and GABA Supplementation

In the present study, the effects of 5-HT, GABA and Bone Marrow Cells infused intranigrally to substantia nigra individually and in combinations on unilateral rotenone infused Parkinsonism induced rats. Scatchard analysis of DA, DA D1 and D2 receptors in the corpus striatum, cerebral cortex, cerebellum, brain stem and hippocampus showed a significant increase in the Brain regions of rotenone infused rat compared to control. Real Time PCR amplification of DA D1, D2, Bax and ubiquitin carboxy-terminal hydrolase were up regulated in the brain regions of rotenone infused rats compared to control. Gene expression studies of -Synuclien, cGMP and Cyclic AMP response element-binding protein showed a significant down regulation in Rotenone infused rats compared to control. Behavioural studies were carried out to confirm the biochemical and molecular studies.Our study demonstrated that BMC administration alone cannot reverse the above said molecular changes occurring in PD rat. 5-HT and GABA acting through their specific receptors in combination with bone marrow cells play a crucial role in the functional recovery of PD rats. 5-HT, GABA and Bone marrow cells treated PD rats showed significant reversal to control in DA receptor binding and gene expression. 5-HT and GABA have co-mitogenic property. Proliferation and differentiation of cells re-establishing the connections in Parkinson's disease facilitates the functional recovery. Thus, it is evident that 5-HT and GABA along with BMC to rotenone infused rats renders protection against oxidative, related motor and cognitive deficits which makes them clinically significant for cellbased therapy. The BMC transformed to neurons when co-transplanted with 5-HT and GABA which was confirmed with PKH2GL and nestin. These newly formed neurons have functional significance in the therapeutic recovery of Parkinson’s disease.

Role of social pressure as a key contributor of materialism and related status consumption

“At resale stores I have seen brand new clothes with original price tag still hanging from the sleeve. Some children have so many toys that they stay frustrated, not knowing which one to pick up for their next amusement. Presumably sensible adults trade in perfectly good cars just to have something shinier and newer. Didn’t us once live productive normal lives, without all these gadgets” [Cunningham (2005)]. During late eighties, nearly forty four percent of the participants, who took part in a consumer survey conducted in the US, responded positively to the question “My closets are filled with still 2 unopened items” [Faber and O’Guinn (1988)]. Reading such excerpts does not greatly surprise us anymore; as such reports have become common now. For many people shopping has moved beyond something that caters to their needs and wants and has become a hobby [Cunningham (2005)], an activity that they engage in to satisfy their hedonistic or pleasure-seeking goals [Ramnathan and Menon(2006), O’Cass and McEween (2004), Faber and O’Guinn (1989)]. Others look at their new possession as something that fills a void in their lives [Belk (1985), Diener et al. (1993)].

A key based cache replacement policy for cooperative caching in mobile ad hoc networks

Cooperative caching in mobile ad hoc networks aims at improving the efficiency of information access by reducing access latency and bandwidth usage. Cache replacement policy plays a vital role in improving the performance of a cache in a mobile node since it has limited memory. In this paper we propose a new key based cache replacement policy called E-LRU for cooperative caching in ad hoc networks. The proposed scheme for replacement considers the time interval between the recent references, size and consistency as key factors for replacement. Simulation study shows that the proposed replacement policy can significantly improve the cache performance in terms of cache hit ratio and query delay

Lignin recovery, Biochar Production and Decolourisation of Coir pith Black Liquor

Coir pith black liquor obtained as a dark brown filtrate from oxidative delignification needs to be decolourised before releasing to open environment. From this liquor industrially valuable lignin was recovered using acid precipitation method. ‘Biochar’ was produced by slow pyrolysis of coir pith at 500oC and 600oC. Water holding capacity and pH of the biochar were estimated. CHNS analysis was carried out to identify the nutrient profile. Structural characterization was done using FTIR and SEM Studies. Biochar produced at 600oC was found to be more suitable for decolourisation of the coir pith black liquor. FTIR analysis indicated peak changes while SEM analysis indicated surface area and porosity changes. Biochar decolourisation experiments were carried out on crude coir pith black liquor and also on lignin recovered coir pith black liquor.

Prediction of Key Symptoms of Learning Disabilities in School-Age Children Using Rough Sets

This paper highlights the prediction of learning disabilities (LD) in school-age children using rough set theory (RST) with an emphasis on application of data mining. In rough sets, data analysis start from a data table called an information system, which contains data about objects of interest, characterized in terms of attributes. These attributes consist of the properties of learning disabilities. By finding the relationship between these attributes, the redundant attributes can be eliminated and core attributes determined. Also, rule mining is performed in rough sets using the algorithm LEM1. The prediction of LD is accurately done by using Rosetta, the rough set tool kit for analysis of data. The result obtained from this study is compared with the output of a similar study conducted by us using Support Vector Machine (SVM) with Sequential Minimal Optimisation (SMO) algorithm. It is found that, using the concepts of reduct and global covering, we can easily predict the learning disabilities in children

Matrix based Key Generation to Enhance Key Avalanche in Advanced Encryption Standard

In symmetric block ciphers, substitution and diffusion operations are performed in multiple rounds using sub-keys generated from a key generation procedure called key schedule. The key schedule plays a very important role in deciding the security of block ciphers. In this paper we propose a complex key generation procedure, based on matrix manipulations, which could be introduced in symmetric ciphers. The proposed key generation procedure offers two advantages. First, the procedure is simple to implement and has complexity in determining the sub-keys through crypt analysis. Secondly, the procedure produces a strong avalanche effect making many bits in the output block of a cipher to undergo changes with one bit change in the secret key. As a case study, matrix based key generation procedure has been introduced in Advanced Encryption Standard (AES) by replacing the existing key schedule of AES. The key avalanche and differential key propagation produced in AES have been observed. The paper describes the matrix based key generation procedure and the enhanced key avalanche and differential key propagation produced in AES. It has been shown that, the key avalanche effect and differential key propagation characteristics of AES have improved by replacing the AES key schedule with the Matrix based key generation procedure

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.

Root effects on the turnover of grain legume residues in soil

Das Ziel dieser Arbeit war, die Einflüsse von Wurzeln und Rhizodeposition auf den Umsatz von Körnerleguminosenresiduen und damit verknüpfte mikrobielle Prozesse zu untersuchen. In einem integrierten Versuch wurden Ackerbohne (Vicia faba L.), Erbse (Pisum sativum L.) und Weiße Lupine (Lupinus albus L.) untersucht. Der Versuch bestand aus drei Teilen, zwei Gefäß-Experimenten und einem Inkubationsexperiment, in denen ausgehend von einem Gefäß-Experiment derselbe Boden und dasselbe Pflanzenmaterial verwendet wurden. In Experiment I wurde die Stickstoff-Rhizodeposition der Körnerleguminosenarten, definiert als wurzelbürtiger N nach dem Entfernen aller sichtbaren Wurzeln im Boden, gemessen und der Verbleib des Rhizodepositions-N in verschiednenen Bodenpools untersucht. Dazu wurden die Leguminosen in einem Gefäßversuch unter Verwendung einer in situ 15N-Docht-Methode mit einer 15N Harnstofflösung pulsmarkiert. In Experiment II wurde der Umsatz der N-Rhizodeposition der Körnerleguminosen und der Einfluss der Rhizodeposition auf den anschließenden C- und N-Umsatz der Körnerleguminosenresiduen in einem Inkubationsexperiment untersucht. In Experiment III wurde der N-Transfer aus den Körnerleguminosenresiduen einschließlich N-Rhizodeposition in die mikrobielle Biomasse und die Folgefrüchte Weizen (Triticum aestivum L.) und Raps (Brassica napus L.) in einem Gewächshaus-Gefäßversuch ermittelt. Die in situ 15N Docht-Markierungs-Methode wies hohe 15N Wiederfindungsraten von ungefähr 84 Prozent für alle drei Leguminosenarten auf und zeigte eine vergleichsweise homogene 15N Verteilung zwischen verschiedenen Pflanzenteilen zur Reife. Die Wurzeln zeigten deutliche Effekte auf die N-Dynamik nach dem Anbau von Körnerleguminosen. Die Effekte konnten auf die N-Rhizodeposition und deren anschließenden Umsatz, Einflüsse der Rhizodeposition von Körnerleguminosen auf den anschließenden Umsatz ihrer Residuen (Stängel, Blätter, erfassbare Wurzeln) und die Wirkungen nachfolgender Nichtleguminosen auf den Umsatzprozess der Residuen zurückgeführt werden: Die N-Rhizodeposition betrug zur Reife der Pflanzen bezogen auf die Gesamt-N- Aufnahme 13 Prozent bei Ackerbohne und Erbse und 16 Prozent bei Weißer Lupine. Bezogen auf den Residual N nach Ernte der Körner erhöhte sich der relative Anteil auf 35 - 44 Prozent. Die N-Rhizodeposition ist daher ein wesentlicher Pool für die N-Bilanz von Körnerleguminosen und trägt wesentlich zur Erklärung positiver Fruchtfolgeeffekte nach Körnerleguminosen bei. 7 - 21 Prozent des Rhizodepositions-N wurden als Feinwurzeln nach Nasssiebung (200 µm) wiedergefunden. Nur 14 - 18 Prozent des Rhizodepositions-N wurde in der mikrobiellen Biomasse und ein sehr kleiner Anteil von 3 - 7 Prozent in der mineralischen N Fraktion gefunden. 48 bis 72 Prozent der N-Rhizodeposition konnte in keinem der untersuchten Pools nachgewiesen werden. Dieser Teil dürfte als mikrobielle Residualmasse immobilisiert worden sein. Nach 168 Tagen Inkubation wurden 21 bis 27 Prozent des Rhizodepositions-N in den mineralisiert. Der mineralisierte N stammte im wesentlichen aus zwei Pools: Zwischen 30 Prozent und 55 Prozent wurde aus der mikrobiellen Residualmasse mineralisiert und eine kleinere Menge stammte aus der mikrobielle Biomasse. Der Einfluss der Rhizodeposition auf den Umsatz der Residuen war indifferent. Durch Rhizodeposition wurde die C Mineralisierung der Leguminosenresiduen nur in der Lupinenvariante erhöht, wobei der mikrobielle N und die Bildung von mikrobieller Residualmasse aus den Leguminosenresiduen in allen Varianten durch Rhizodepositionseinflüsse erhöht waren. Das Potential des residualen Körnerleguminosen-N für die N Ernährung von Folgefrüchten war gering. Nur 8 - 12 Prozent des residualen N wurden in den Folgenfrüchten Weizen und Raps wiedergefunden. Durch die Berücksichtigung des Rhizodepositions-N war der relative Anteil des Residual-N bezogen auf die Gesamt-N-Aufnahme der Folgefrucht hoch und betrug zwischen 18 und 46 Prozent. Dies lässt auf einen höheren N-Beitrag der Körnerleguminosen schließen als bisher angenommen wurde. Die residuale N-Aufnahme von Weizen von der Blüte bis zur Reife wurde durch den Residual-N gespeist, der zur Blüte in der mikrobiellen Biomasse immobilisiert worden war. Die gesamte Poolgröße, Residual-N in der mikrobiellen Biomasse und in Weizen, veränderte sich von der Blüte bis zur Reife nicht. Jedoch konnte ein Rest von 80 Prozent des Residual-N in keinem der untersuchten Pools nachgewiesen werden und dürfte als mikrobielle Residualmasse immobilisiert worden sein oder ist noch nicht abgebaut worden. Die zwei unterschiedlichen Folgefrüchte - Weizen und Raps - zeigten sehr ähnliche Muster bei der N-Aufnahme, der Residual-N Wiederfindung und bei mikrobiellen Parametern für die Residuen der drei Körnerleguminosenarten. Ein differenzierender Effekt auf den Umsatz der Residuen bzw. auf das Residual-N-Aneignungsvermögen der Folgefrüchte konnte nicht beobachtet werden.

Goal-oriented recovery bei nichtlinearen Scheibenproblemen

Es werden die Grundlagen und wichtigsten Konzepte für zielorientierte Fehlerschätzer bei linearen und nichtlinearen Problemen vorgestellt. Mit ihrer Hilfe lassen sich Aussagen über die Güte einzelner lokaler Werte treffen und es ist möglich, das Netz innerhalb von adaptiven Verfahren derart zu optimieren, dass die betrachtete lokale Größe möglichst genau berechnet werden kann.