Intestinal gluconeogenesis is a key factor for early metabolic changes after gastric bypass but not after gastric lap-band in mice

Unlike the adjustable gastric banding procedure (AGB), Roux-en-Y gastric bypass surgery (RYGBP) in humans has an intriguing effect: a rapid and substantial control of type 2 diabetes mellitus (T2DM). We performed gastric lap-band (GLB) and entero-gastro anastomosis (EGA) procedures in C57Bl6 mice that were fed a high-fat diet. The EGA procedure specifically reduced food intake and increased insulin sensitivity as measured by endogenous glucose production. Intestinal gluconeogenesis increased after the EGA procedure, but not after gastric banding. All EGA effects were abolished in GLUT-2 knockout mice and in mice with portal vein denervation. We thus provide mechanistic evidence that the beneficial effects of the EGA procedure on food intake and glucose homeostasis involve intestinal gluconeogenesis and its detection via a GLUT-2 and hepatoportal sensor pathway.     

Do ecologically close species shift their daily activities when in sympatry? A test on chamois in the presence of mouflon

Temporal partitioning of daily activities between species may promote coexistence within animal communities by reducing behavioural interference, particularly when species highly overlap in the use of space and resources. Such a strategy may be used by Alpine chamois (Rupicapra rupicapra rupicapra) when in the presence of mouflon (Ovis gmelini musimon × Ovis sp.), an introduced highly gregarious species with a broader ecological niche, overlapping with that of chamois. Using simultaneous monitoring of 29 Global Positioning System‐collared chamois and 12 mouflon, we assessed the temporal variation in activity patterns of chamois amongst two subpopulations: one without mouflon and one with mouflon, during January and August, which are the two most extreme periods of spatial overlap of mouflon with chamois distribution. Substantial differences in activity patterns between chamois and mouflon were observed (mean 13.8 ± 10.5% in January and 10.6 ± 11.6% in August). More subtle differences appeared between both subpopulations of chamois and persisted, regardless of the spatial overlap with mouflon (3.2 ± 1.8% in January and 2.6 ± 1.5% in August), thus highlighting that there is no behavioural interference from mouflon on chamois. Our findings suggest that the temporal partitioning of daily activities between chamois and mouflon, although probably a result of species‐specific adaptations to environmental conditions, may contribute to their coexistence. © 2014 The Linnean Society of London, Biological Journal of the Linnean Society, 2014, 111 , 621–626.     

The crossroads of neuroinflammation in infectious diseases: endothelial cells and astrocytes

Homeostasis implies constant operational defence mechanisms, against both external and internal threats. Infectious agents are prominent among such threats. During infection, the host elicits the release of a vast array of molecules and numerous cell-cell interactions are triggered. These pleiomorphic mediators and cellular effects are of prime importance in the defence of the host, both in the systemic circulation and at sites of tissue injury, for example, the blood-brain barrier (BBB). Here, we focus on the interactions between the endothelium, astrocytes, and the molecules they release. Our review addresses these interactions during infectious neurological diseases of various origins, especially cerebral malaria (CM). Two novel elements of the interplay between endothelium and astrocytes, microparticles and the kynurenine pathway, will also be discussed.     

Exploration of Natural and Artificial Sequence Spaces: Towards a Functional Remodeling of Membrane-bound Cytochrome P450

Abstract

Two complementary methods are described that associate in vitro and in vivo steps to generate sequence diversity by segment directed saturated mutagenesis and family shuffling. A high-throughput DNA chip-based procedure for the characterization and potentially the equalization of combinatorial libraries is also presented. Using these approaches, two combinatorial libraries of cytochrome P450 variants derived from the CYP1A subfamily were constructed and their sequence diversity characterized. The results of functional screening using high-throughput tools for the characterization of membrane P450-catalyzed activities, suggest that the 204–214 sequence segment of human CYP1A1 is not critical for polycyclic aromatic hydrocarbon recognition, as was hypothesized from previous data. Moreover, mutations in this segment do not alter the discrimination between alkoxyresorufins, which, for all tested mutants, remained similar to that of wild-type CYP1A1. In contrast, the constructed CYP1A1–CYP1A2 mosaic structures, containing multiple crossovers, exhibit a wide range of substrate preference and regioselectivity. These mosaic structures also discriminate between closely related alkoxyresorufin substrates. These results open the way to global high-throughput analysis of structure–function relationships using combinatorial libraries of enzymes together with libraries of structurally related substrates.     

MicroRNAs Act as Cofactors in Bicoid-Mediated Translational Repression

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