String theory and the Kauffman polynomial

We propose a new, precise integrality conjecture for the colored Kauffman polynomial of knots and links inspired by large N dualities and the structure of topological string theory on orientifolds. According to this conjecture, the natural knot invariant in an unoriented theory involves both the colored Kauffman polynomial and the colored HOMFLY polynomial for composite representations, i.e. it involves the full HOMFLY skein of the annulus. The conjecture sheds new light on the relationship between the Kauffman and the HOMFLY polynomials, and it implies for example Rudolph's theorem. We provide various non-trivial tests of the conjecture and we sketch the string theory arguments that lead to it.Comment: 36 pages, many figures; references and examples added, typos corrected, final version to appear in CM

Rothamsted Conference RC No 11 : the making of new grassland experiences of practical farmers

RESP-74

Inhibitory Effects of Leptin on Pancreatic α-Cell Function

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)OBJECTIVE-Leptin released from adipocytes plays a key role in the control of food intake, energy balance, and glucose homeostasis. In addition to its central action, leptin directly affects pancreatic beta-cells, inhibiting insulin secretion, and, thus, modulating glucose homeostasis. However, despite the importance of glucagon secretion in glucose homeostasis, the role of leptin in a-cell function has not been studied in detail. In the present study, we have investigated this functional interaction. RESEARCH DESIGN AND METHODS-The presence of leptin receptors (ObR) was demonstrated by RT-PCR analysis, Western blot, and immunocytochemistry. Electrical activity was analyzed by patch-clamp and Ca(2+) signals by confocal microscopy. Exocytosis and glucagon secretion were assessed using fluorescence methods and radioimmunoassay, respectively. RESULTS-The expression of several ObR isoforms (a-e) was detected in glucagon-secreting alpha TC1-9 cells. ObRb, the main isoform involved in leptin signaling, was identified at the protein level in alpha TC1-9 cells as well as in mouse and human alpha-cells. The application of leptin (6.25 nmol/l) hyperpolarized the alpha-cell membrane potential, suppressing the electrical activity induced by 0.5 mmol/l glucose. Additionally, leptin inhibited Ca(2+) signaling in alpha TC1-9 cells and in mouse and human alpha-cells within intact islets. A similar result occurred with 0.625 nmol/l leptin. These effects were accompanied by a decrease in glucagon secretion from mouse islets and were counteracted by the phosphatidylinositol 3-kinase inhibitor, wortmannin, suggesting the involvement of this pathway in leptin action. CONCLUSIONS-These results demonstrate that leptin inhibits alpha-cell function, and, thus, these cells are involved in the adipo-insular communication. Diabetes 58:1616-1624, 200958716161624Ministerio de Educacion y Ciencia [BFU2007-67607, PCI2005-A7-0131, BFU2008-01492, SAF2006-07382]Ministerio de Ciencia a InnovacionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Ministerio de Educacion y Ciencia [BFU2007-67607, PCI2005-A7-0131, BFU2008-01492, SAF2006-07382]FAPESP [2008/53811-8

Leptin enhances glycogen storage in hepatocytes by inhibition of phosphorylase and exerts an additive effect with insulin

The effects of the adipocyte-derived hormone leptin on glucose metabolism in hepatocytes were investigated. Incubation of hepatocytes from Wistar rats with leptin for 16 h caused a dose-dependent increase in incorporation of [14C]glucose into glycogen, with a maximal effect at 30 nmol/l leptin. This effect of leptin was observed over a range of glucose concentrations (10-25 mmol/l) and was associated with stimulation of net glycogen deposition. It was not counteracted by mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase, indicating that it is not due to increased gluconeogenic flux. Leptin also enhanced the short-term stimulation of glycogen synthesis by insulin. These effects of leptin were associated with inhibition of phosphorylase a, which occurred after 4 h of exposure to leptin. Culture with leptin for 16 h did not affect the activities of glucose-6-phosphatase or glucokinase or the activation state of glycogen synthase. Leptin did not affect glycolysis determined from the detritiation of [3-3H]glucose. The inhibitory effects of leptin on phosphorylase a were counteracted by shortterm incubation with glucagon but were additive with the inhibitory effects of insulin and also with the inhibition caused by resorcinol (25 μmol/l), which inhibits phosphorylase kinase by a mechanism analogous to the antidiabetic drug proglycosyn. These results show that leptin has additive effects with insulin in inhibiting phosphorylase and stimulating glycogen storage in hepatocytes, indicating that these hormones act by separate but convergent mechanisms. It is concluded that the primary action of leptin in hepatocytes is to enhance glycogen storage. This may be an important compensatory mechanism for the inhibition of insulin secretion