Protection against fatty liver but normal adipogenesis in mice lacking adipose differentiation-related protein

Adipose differentiation-related protein (ADFP; also known as ADRP or adipophilin), is a lipid droplet (LD) protein found in most cells and tissues. ADFP expression is strongly induced in cells with increased lipid load. We have inactivated the Adfp gene in mice to better understand its role in lipid accumulation. The Adfp-deficient mice have unaltered adipose differentiation or lipolysis in vitro or in vivo. Importantly, they display a 60% reduction in hepatic triglyceride (TG) and are resistant to diet-induced fatty liver. To determine the mechanism for the reduced hepatic TG content, we measured hepatic lipogenesis, very-low-density lipoprotein (VLDL) secretion, and lipid uptake and utilization, all of which parameters were shown to be similar between mutant and wild-type mice. The finding of similar VLDL output in the presence of a reduction in total TG in the Adfp-deficient liver is explained by the retention of TG in the microsomes where VLDL is assembled. Given that lipid droplets are thought to form from the outer leaflet of the microsomal membrane, the reduction of TG in the cytosol with concomitant accumulation of TG in the microsome of Adfp-/- cells suggests that ADFP may facilitate the formation of new LDs. In the absence of ADFP, impairment of LD formation is associated with the accumulation of microsomal TG but a reduction in TG in other subcellular compartments.     

TGF-β-Elicited Induction of Tissue Inhibitor of Metalloproteinases (TIMP)-3 Expression in Fibroblasts Involves Complex Interplay between Smad3, p38α, and ERK1/2

Transforming growth factor-β (TGF-β) promotes extracellular matrix deposition by down-regulating the expression of matrix degrading proteinases and upregulating their inhibitors. Tissue inhibitor of metalloproteinases (TIMP)-3 is an ECM-associated specific inhibitor of matrix degrading metalloproteinases. Here, we have characterized the signaling pathways mediating TGF-β-induced expression of TIMP-3. Basal and TGF-β-induced TIMP-3 mRNA expression was abolished in Smad4-deficient mouse embryonic fibroblasts and restoring Smad4 expression rescued the response. Inhibition of Smad signaling by expression of Smad7 and dominant negative Smad3 completely abolished TGF-β-elicited expression of TIMP-3 in human fibroblasts, whereas overexpression of Smad3 enhanced it. Inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) activation with PD98059 and p38 mitogen-activated protein kinase activity by SB203580 resulted in suppression of TGF-β-induced TIMP-3 expression, indicating that ERK1/2 and p38 MAPK mediate the effect of TGF-β on TIMP-3 expression. Specific activation of p38α and ERK1/2 by constitutively active mutants of MKK3b or MEK1, respectively, and simultaneous co-expression of Smad3 resulted in induction of TIMP-3 expression in the absence of TGF-β indicating that Smad3 co-operates with p38 and ERK1/2 in the induction of TIMP-3 expression. These results demonstrate the complex interplay between Smad3, p38α, and ERK1/2 signaling in the regulation of TIMP-3 gene expression in fibroblasts, which may play a role in inflammation, tissue repair, and fibrosis.     

Xenocylindrocladium guianense andX. subverticillatum, two new species of hyphomycetes from plant debris in the tropics

Two new species of hyphomycetes,Xenocylindrocladium guianense andX. subverticillatum, are described from plant debris collected in French Guiana and Singapore, respectively. The genusXenocylindrocladium has thus far been known from one species,X. serpens, which was described from plant debris collected in Ecuador. The two new taxa are compared with and distinguished fromX. serpens based on morphology, cultural characteristics and phylogenetic analysis of DNA sequence data of the 5.8S rDNA with flanking ITS1 and ITS2 regions and the 5′ end of the β-tubulin gene. These species are also compared with other closely related hypocrealean taxa. Present collection data suggest that species ofXenocylindrocladium could be restricted to the tropics.     

LEFT MAIN CORONARY ARTERY OCCLUSION: SURGICAL MANAGEMENT

Left main coronary occlusion is a rare lesion. A case that was successfully managed by coronary bypass surgery is presented. Occlusion of the left main coronary artery and management of left main coronary artery disease is discussed.     

Inverted distal duplication of the long arm of chromosome 8: borderline intelligence and discrete dysmorphic syndrome.

In this report, we describe an 11-years-old girl with inverted duplication in the distal part of the long arm of chromosome 8 (inv dup(8)(q24.11----q24.3). The most remarkable finding is her borderline intelligence and her nearly normal phenotype.     

Collagen matrix deposition is dramatically enhanced in vitro when crowded with charged macromolecules: the biological relevance of the excluded volume effect

The excluded volume effect (EVE) rules all life processes. It is created by macromolecules that occupy a given volume thereby confining other molecules to the remaining space with large consequences on reaction kinetics and molecular assembly. Implementing EVE in fibroblast culture accelerated conversion of procollagen to collagen by procollagen C-proteinase (PCP/BMP-1) and proteolytic modification of its allosteric regulator, PCOLCE1. This led to a 20-30- and 3-6-fold increased collagen deposition in two- and three-dimensional cultures, respectively, and creation of crosslinked collagen footprints beneath cells. Important parameters correlating with accelerated deposition were hydrodynamic radius of macromolecules and their negative charge density.     

Biodiversity and Biogeography of Chthamalid Barnacles from the North-Eastern Pacific (Crustacea Cirripedia)

The biogeography and ecology of the species of Chthamalus present on the west coast of America are described, using data from 51 localities from Alaska to Panama, together with their zonation on the shore with respect to that of other barnacles. The species present were C. dalli, Pilsbry 1916, C. fissus, Darwin, 1854, C. anisopoma Pilsbry 1916 and four species in the C. panamensis complex. The latter are C. panamensis Pilsbry, 1916, C. hedgecocki, Pitombo & Burton, 2007, C. alani nom. nov. (formerly C. southwardorum Pitombo & Burton, 2007) and C. newmani sp. nov.). These four species were initially separated by enzyme electrophoresis. They could only be partially separated by DNA bar coding but may be separated using morphological characters.     

Spatial and temporal variation in diets of the crabs <Emphasis Type="Italic">Metopograpsus frontalis</Emphasis> (Grapsidae) and <Emphasis Type="Italic">Perisesarma bidens</Emphasis> (Sesarmidae): implications for mangrove food webs

The diets of the mangrove crabs, Metopograpsus frontalis Miers and Perisesarma bidens de Haan, were investigated monthly for 13 months at two Hong Kong mangroves, to examine possible spatial and temporal influences on their feeding ecology. In both species, a higher degree of gut fullness was observed in summer (May–September) than in winter, suggesting a reduction in winter foraging activity. M. frontalis was omnivorous, with animal and plant materials and inorganic sediments being the major food items. P. bidens was detritivorous, with plant materials and inorganic sediment dominating the gut contents. M. frontalis is, therefore, an opportunistic feeder, whilst P. bidens, like many other members of the Sesarmidae, is a detritivore. Some degree of seasonal variation was shown in the diet of M. frontalis (with more algal material in winter) and P. bidens (with more sediments in summer), but diets were similar between sexes in both species. The dietary pattern of M. frontalis also varied between sites. The diets of the crabs, therefore, appear to be a result of the interplay between the seasonal, physical climate and biological factors, especially food availability and the crabs’ ecology. Results suggest that the predatory role of Metopograpsus, which has been poorly studied, is potentially important to estuarine food webs; whilst the trophic importance of sesarmid crabs, such as Perisesarma, especially in mangrove outwelling, should be critically re-evaluated.