Coulomb-blockade transport in single-crystal organic thin-film transistors

Coulomb-blockade transport--whereby the Coulomb interaction between electrons can prohibit their transport around a circuit--occurs in systems in which both the tunnel resistance, Rb between neighbouring sites is large (>h/e2) and the charging energy, E(C) (E(C) = e2/2C, where C is the capacitance of the site), of an excess electron on a site is large compared to kT. (Here e is the charge of an electron, k is Boltzmann's constant, and h is Planck's constant.) The nature of the individual sites--metallic, superconducting, semiconducting or quantum dot--is to first order irrelevant for this phenomenon to be observed. Coulomb blockade has also been observed in two-dimensional arrays of normal-metal tunnel junctions, but the relatively large capacitances of these micrometre-sized metal islands results in a small charging energy, and so the effect can be seen only at extremely low temperatures. Here we demonstrate that organic thin-film transistors based on highly ordered molecular materials can, to first order, also be considered as an array of sites separated by tunnel resistances. And as a result of the sub-nanometre sizes of the sites (the individual molecules), and hence their small capacitances, the charging energy dominates at room temperature. Conductivity measurements as a function of both gate bias and temperature reveal the presence of thermally activated transport, consistent with the conventional model of Coulomb blockade.     

AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus

Obesity is an epidemic in Western society, and causes rapidly accelerating rates of type 2 diabetes and cardiovascular disease. The evolutionarily conserved serine/threonine kinase, AMP-activated protein kinase (AMPK), functions as a 'fuel gauge' to monitor cellular energy status. We investigated the potential role of AMPK in the hypothalamus in the regulation of food intake. Here we report that AMPK activity is inhibited in arcuate and paraventricular hypothalamus (PVH) by the anorexigenic hormone leptin, and in multiple hypothalamic regions by insulin, high glucose and refeeding. A melanocortin receptor agonist, a potent anorexigen, decreases AMPK activity in PVH, whereas agouti-related protein, an orexigen, increases AMPK activity. Melanocortin receptor signalling is required for leptin and refeeding effects on AMPK in PVH. Dominant negative AMPK expression in the hypothalamus is sufficient to reduce food intake and body weight, whereas constitutively active AMPK increases both. Alterations of hypothalamic AMPK activity augment changes in arcuate neuropeptide expression induced by fasting and feeding. Furthermore, inhibition of hypothalamic AMPK is necessary for leptin's effects on food intake and body weight, as constitutively active AMPK blocks these effects. Thus, hypothalamic AMPK plays a critical role in hormonal and nutrient-derived anorexigenic and orexigenic signals and in energy balance.     

Structural and functional relationships between photoreceptor tetraspanins and other superfamily members

The two primary photoreceptor-specific tetraspanins are retinal degeneration slow (RDS) and rod outer segment membrane protein-1 (ROM-1). These proteins associate together to form different complexes necessary for the proper structure of the photoreceptor outer segment rim region. Mutations in RDS cause blinding retinal degenerative disease in both rods and cones by mechanisms that remain unknown. Tetraspanins are implicated in a variety of cellular processes and exert their function via the formation of tetraspanin-enriched microdomains. This review focuses on correlations between RDS and other members of the tetraspanin superfamily, particularly emphasizing protein structure, complex assembly, and post-translational modifications, with the goal of furthering our understanding of the structural and functional role of RDS and ROM-1 in outer segment morphogenesis and maintenance, and our understanding of the pathogenesis associated with RDS and ROM-1 mutations.