Molecular regulators of glucose and lipid metabolism in skeletal muscle

Skeletal muscle is a primary site of insulin action and insulin-stimulated glucose transport and occupies a center stage in maintaining whole body glucose and lipid homeostasis. Another key feature of a healthy skeletal muscle is its ability to switch between utilization of lipids and glucose as fuel in response to feeding or fasting respectively. This metabolic flexibility is impaired in skeletal muscle from insulin resistant and type 2 diabetic patients. Key molecules such as AMP Kinase [AMPK] and Pyruvate Dehydrogenase Kinase [PDK] play a crucial role in maintaining metabolic flexibility in a healthy skeletal muscle. These molecules have recently emerged as potential drug targets to combat diabetes. One strategy to activate the AMPK pathway is via altering the expression of AMP-metabolizing enzymes, such as 5’-nucleotidases [NT5C]. The role of cytosolic 5´-nucleotidases was determined in metabolic responses linked to the development of insulin resistance in obesity and type 2 diabetes (Study I). NT5C1A and NT5C2 gene silencing led to increase in the AMP/ATP ratio, increase in phosphorylation of AMPK and ACC, and an increase in palmitate oxidation and glucose transport in mouse and human skeletal muscle. Another strategy to activate the AMPK system would be to lower the threshold of AMPK activation by rendering AMPK more sensitive to its activators. This strategy has been undertaken in this thesis by pre-treating skeletal muscle with methotrexate [MTX] and targeting 5-Amino-4-imidazolecarboxamide Ribonucleotide Transformylase [ATIC] (Study II). MTX is an inhibitor of ATIC, an enzyme involved in de-novo nucleotide biosynthesis. ATIC imposes a metabolic block leading to intracellular ZMP accumulation, lowering the threshold for AMPK activation. Increased glucocorticoid action leads to reduced whole body insulin action and may predispose to type 2 diabetes. Local conversion of cortisone to active cortisol by the enzyme 11β-hydroxysteroid dehydrogenase [11β-HSD1] in target tissues may regulate tissue specific roles of glucocortioids in pathophysiological states. Chronic high dose exposure to cortisone or cortisol reduced glucose metabolism and enhanced lipid metabolism, via induction of pyruvate dehydrogenase kinase 4 [PDK4] expression in myotubes. siRNA-mediated reduction or pharmacological inhibition of 11β-HSD1 prevented the effects of cortisone but not cortisol, on metabolic responses (Study III). Type 2 diabetes mellitus is associated with abnormal substrate metabolism, raising the possibility that alterations in the expression of mitochondrial enzymes controlling lipid uptake and metabolism may be altered (Study IV). Evidence that expression of key enzymes regulating mitochondrial function in skeletal muscle is altered in type 2 diabetes mellitus [T2DM] patients is provided. In summary, activation of AMPK can play a central role in overcoming impairments in skeletal muscle glucose and lipid metabolism and this can be achieved by perturbing the enzymes involved in nucleotide metabolism such as 5’-nucleotidases and ATIC. Alterations in molecular regulators of substrate metabolism such as PDK4, reflect pathogenic condition and could be targeted to restore skeletal muscle energy homeostasis

Influence of quantum confinement on the ferromagnetism of (Ga,Mn)As diluted magnetic semiconductor

We investigate the effect of quantum confinement on the ferromagnetism of diluted magnetic semiconductor Ga$_{1-x}$Mn$_x$As using a combination of tight-binding and density functional methods. We observe strong majority-spin Mn $d$-As $p$ hybridization, as well as half metallic behavior, down to sizes as small as 20 \AA in diameter. Below this critical size, the doped holes are self-trapped by the Mn-sites, signalling both valence and electronic transitions. Our results imply that magnetically doped III-V nanoparticles will provide a medium for manipulating the electronic structure of dilute magnetic semiconductors while conserving the ferromagnetic properties and even enhancing it in certain size regime.Comment: 4 pages, 3 figure

Approximate solutions of the Dirac equation for the Rosen-Morse potential including the spin-orbit centrifugal term

We give the approximate analytic solutions of the Dirac equations for the Rosen-Morse potential including the spin-orbit centrifugal term. In the framework of the spin and pseudospin symmetry concept, we obtain the analytic bound state energy spectra and corresponding two-component upper- and lower-spinors of the two Dirac particles, in closed form, by means of the Nikiforov-Uvarov method. The special cases of the s-wave kappa=1,-1 (l=l bar=0) Rosen-Morse potential, the Eckart-type potential, the PT-symmetric Rosen-Morse potential and non-relativistic limits are briefly studied.Comment: 23 page

APPLICATIONS OF RAPD AND ISSR MARKERS IN PLANT GENOME ANALYSIS

AbstractPlant genome analysis requires a good genetic marker for tagging the gene of interest.  PCR–based markers are the preferred techniques available due to their obvious advantages over conventional phenotypic markers. Random amplified polymorphic DNA (RAPD) and inter simple sequence repeat (ISSR) are ideal genetic markers employed for various studies, mostly in studies on genetic diversity, phylogeny, gene tagging, genome mapping and evolutionary biology. These markers are simple and no sequence knowledge is required.  This review reports the usefulness of RAPD and ISSR markers for the assessment of genetic diversity and its application in plant genetics in a wide range of crop plants.Â

ANTINUTRITIONAL FACTORS IN PULSES AND THEIR DIVERSITY

Abstract In India, legume seeds are identified as a major source of proteins after milk. However, these legume seeds are also known to contain factors which hinder the digestibility and thus nutritionally antagonistic. These may reduce the availability of otherwise good proteins in the diet and cause diseases originating from malnutrition.  A comprehensive review on the presence of seed storage proteins and important anti-nutritional factors in food legumes has been carry out. These factors affecting digestibility include proteolytic inhibitors, phytohemagglutinins, phytic acids and tannins etc. These factors are shown to be widely present in leguminous foods which are important constituents of the diet of a large section of the world's population and particularly people in the developing countries.Â

Polymerization of methyl acrylate and as comonomer with ethylene using single-site catalysts

Because of the excellent control over polymerizations provided by single-site catalysts (SSCs), numerous research groups are trying to find such catalysts, which would also be efficient for the polymerization of polar monomers. However, many SSCs are deactivated by undergoing reactions with the electronegative atoms in the polar groups. In the present work, we attempted to copolymerize ethylene with methyl acrylate using three SSCs: (1) a bis(imino)pyridyl iron(II) chloride / methylaluminoxane catalyst, (2) a chiral metallocene / tris(pentafluorophenyl) borane catalyst, and (3) an in situ trifluromethyl substituted nickel (II) enolate catalyst. Only the first two catalysts led to polymer formation. The metallocene had relatively low activities and formed polymethyl acrylate. The most efficient catalyst for the synthesis of the copolymers was the ironbased catalyst 1. The ethylene consumption indicates that its activity reaches a maximum after which it steadily declines. By kinetic measurements, 1H and 13C NMR spectroscopy and the measurement of glass and melting temperatures, we could show that copolymers of ethylene and methyl acrylate were not formed. The products formed were blends, of high density polyethylene and methyl acrylate. Homopolymerizations of methyl acrylate using the three catalyst systems were also studied. Again it was found that the catalyst 1 had the highest activities. Atactic polymers were formed. There was a clear dependence of the activity and molecular weight on the Al/Fe-ratio, which indicates that the polymerization mechanism is coordinative and not initiated by radical species

Basic Treatment of QCD Phase Transition Bubble Nucleation

Starting from the QCD Lagrangian and the surface tension of QCD bubbles we derive the critical size of bubbles, the nucleation probability and the nucleation site separation distance. We find the separation of sites is more than an order of magnitude larger than previous QCD model estimates, which could lead to observable effects.Comment: 8 pages, one figur