285 research outputs found

    Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

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    Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection

    A new species of Argyromys (Rodentia, Mammalia) from the oligocene of the valley of lakes (Mongolia): its importance for palaeobiogeographical homogeneity across Mongolia, China and Kazakhstan

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    We describe a new species of Rodentia (Mammalia), Argyromys cicigei sp. nov. from Toglorhoi (fossil bed TGW-A/2a) in Mongolia and Ulantatal (fossil beds UTL 1 and UTL 7) in China. Its tooth morphology differs from the type species Argyromys aralensis from Akespe in Kazakhstan by smaller size and simpler structures. Argyromys has been assigned in different families of Muroidea, such as Tachyoryctoididae and Spalacidae. However, the presence of common characters indicates a closer relationship of Argyromys with the genera of Cricetidae s.l. (subfamilies Eucricetodontinae; Cricetopinae; Cricetodontinae and Gobicricetodontinae among others) from Asia than with the earliest representatives of Spalacidae or the endemic Tachyoryctoididae. Argyromys cicigei sp. nov. possesses a simple anterocone and anteroconid in the upper and lower first molars, respectively, which is characteristic for Cricetidae s.l. It has a flat occlusal surface in worn specimens; weakly-developed posterolophs; an oblique protolophule and metaloph on the upper molars and it lacks a labial anterolophid on the m1. These traits are also typical of the Oligocene genera Aralocricetodon and Plesiodipus, included in the subfamilies Cricetodontinae and Gobicricetodontinae respectively. The cladistic analysis performed here supports this hypothesis. The clade formed by Argyromys species is grouped with other cricetid taxa (s.l). Spalacids, however, form a different clade, as do the tachyoryctoids. Previous authors state that the Aral Formation (Kazakhstan) should be dated to the Oligocene instead of the Miocene, based on the presence of several taxa. The finds of Argyromys in both regions supports the statement that they are closer in age than previously thought. The occurrence of Argyromys in Kazakhstan, Mongolia and China evidences the biogeographic unity of the Central Asian bioprovince during the Oligocene

    Thermal Properties of Graphene, Carbon Nanotubes and Nanostructured Carbon Materials

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    Recent years witnessed a rapid growth of interest of scientific and engineering communities to thermal properties of materials. Carbon allotropes and derivatives occupy a unique place in terms of their ability to conduct heat. The room-temperature thermal conductivity of carbon materials span an extraordinary large range - of over five orders of magnitude - from the lowest in amorphous carbons to the highest in graphene and carbon nanotubes. I review thermal and thermoelectric properties of carbon materials focusing on recent results for graphene, carbon nanotubes and nanostructured carbon materials with different degrees of disorder. A special attention is given to the unusual size dependence of heat conduction in two-dimensional crystals and, specifically, in graphene. I also describe prospects of applications of graphene and carbon materials for thermal management of electronics.Comment: Review Paper; 37 manuscript pages; 4 figures and 2 boxe

    Cricetidae (Rodentia, Mammalia) from the oligocene of the valley of Lakes (Mongolia): the genera Aralocricetodon, Eocricetodon, Bagacricetodon, Witenia and Paracricetodon

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    We describe the remains of Aralocricetodon Bendukidze, 1993; Bagacricetodon Gomes Rodrigues et al., 2012; Eocricetodon Wang, 2007; Witenia de Bruijn et al., 2003 and Paracricetodon Schaub, 1925 (Cricetidae, Rodentia, Mammalia) from the Taatsiin Gol and Taatsiin Tsagaan Nuur areas (Mongolia). The studied material (comprising 128 teeth) stems from 9 localities and 23 fossil layers spanning a time interval from ∼33 to ∼24 Ma (early to late Oligocene) and covering the biozones from A to C1. The general dental pattern between the species from the early and late Oligocene differed. The occlusal pattern of the molars was more complicated and the crowns were lower during the early versus late Oligocene. This indicates a change in diet towards more abrasive plants. Several of the studied species were common in both Europe and Asia Minor during the early Oligocene. The species collected from the late Oligocene have also been recorded in Kazakhstan and China. This indicates an interesting biogeographical pattern that merits future study

    Evolution of the genus Eucricetodon (Rodentia, Mammalia) from the Valley of Lakes (Mongolia): a taxonomical description and update on the stratigraphical distribution

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    The Oligocene fossil deposits from Valley of Lakes in Central Mongolia have provided a wealth of rodent fossils. Among these, cricetids are a very important part. To date, only the Miocene genera have been described in detail. Here, we focus on the Oligocene genus Eucricetodon from this region. Eucricetodontinae are the most abundant fossils in the Oligocene Valley of Lakes faunas. The present study consists of the description of five species of cricetid rodents from 43 localities ranging in age from the early Oligocene to the early-late Oligocene. In addition to Eucricetodon asiaticus described in Mongolia in 1923, we have found Eucricetodon bagus and Eucricetodon jilantaiensis that were described from Nei Mongol and Eucricetodon occidentalis discovered in Kazakhstan. This taxonomical study provides new information regarding the evolution of the Cricetidae in Central and Eastern Asia during the Oligocene and, more particularly, regarding their phylogenetic relationships and the evolutionary trends

    The insulin polymorphism -23Hph increases the risk for type 1 diabetes mellitus in the Romanian population

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    The insulin -23Hph and IGF2 Apa polymorphisms were genotyped in Romanian patients with T1DM (n = 204), T2DM (n = 215) or obesity (n = 200) and normoponderal healthy subjects (n = 750). The genotypes of both polymorphisms were distributed in concordance with Hardy-Weinberg equilibrium in all groups. The -23Hph AA genotype increased the risk for T1DM (OR: 3.22, 95%CI: 2.09-4.98, p < 0,0001), especially in patients without macroalbuminuria (OR: 4.32, 95%CI: 2.54-7.45, p < 0,0001). No other significant association between the alleles or genotypes of insulin -23Hph and IGF2 Apa and diabetes or obesity was identified

    New Role, New Country: introducing US physician assistants to Scotland

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    This paper draws from research commissioned by the Scottish Executive Health Department (SEHD). It provides a case study in the introduction of a new health care worker role into an already well established and "mature" workforce configuration It assesses the role of US style physician assistants (PAs), as a precursor to planned "piloting" of the PA role within the National Health Service (NHS) in Scotland

    Increased autophagy in EphrinB2-deficient osteocytes is associated with elevated secondary mineralization and brittle bone

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    Mineralized bone forms when collagen-containing osteoid accrues mineral crystals. This is initiated rapidly (primary mineralization), and continues slowly (secondary mineralization) until bone is remodeled. The interconnected osteocyte network within the bone matrix differentiates from bone-forming osteoblasts; although osteoblast differentiation requires EphrinB2, osteocytes retain its expression. Here we report brittle bones in mice with osteocyte-targeted EphrinB2 deletion. This is not caused by low bone mass, but by defective bone material. While osteoid mineralization is initiated at normal rate, mineral accrual is accelerated, indicating that EphrinB2 in osteocytes limits mineral accumulation. No known regulators of mineralization are modified in the brittle cortical bone but a cluster of autophagy-associated genes are dysregulated. EphrinB2-deficient osteocytes displayed more autophagosomes in vivo and in vitro, and EphrinB2-Fc treatment suppresses autophagy in a RhoA-ROCK dependent manner. We conclude that secondary mineralization involves EphrinB2-RhoA-limited autophagy in osteocytes, and disruption leads to a bone fragility independent of bone mass

    Steroid Hormone Control of Cell Death and Cell Survival: Molecular Insights Using RNAi

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    The insect steroid hormone ecdysone triggers programmed cell death of obsolete larval tissues during metamorphosis and provides a model system for understanding steroid hormone control of cell death and cell survival. Previous genome-wide expression studies of Drosophila larval salivary glands resulted in the identification of many genes associated with ecdysone-induced cell death and cell survival, but functional verification was lacking. In this study, we test functionally 460 of these genes using RNA interference in ecdysone-treated Drosophila l(2)mbn cells. Cell viability, cell morphology, cell proliferation, and apoptosis assays confirmed the effects of known genes and additionally resulted in the identification of six new pro-death related genes, including sorting nexin-like gene SH3PX1 and Sox box protein Sox14, and 18 new pro-survival genes. Identified genes were further characterized to determine their ecdysone dependency and potential function in cell death regulation. We found that the pro-survival function of five genes (Ras85D, Cp1, CG13784, CG32016, and CG33087), was dependent on ecdysone signaling. The TUNEL assay revealed an additional two genes (Kap-α3 and Smr) with an ecdysone-dependent cell survival function that was associated with reduced cell death. In vitro, Sox14 RNAi reduced the percentage of TUNEL-positive l(2)mbn cells (p<0.05) following ecdysone treatment, and Sox14 overexpression was sufficient to induce apoptosis. In vivo analyses of Sox14-RNAi animals revealed multiple phenotypes characteristic of aberrant or reduced ecdysone signaling, including defects in larval midgut and salivary gland destruction. These studies identify Sox14 as a positive regulator of ecdysone-mediated cell death and provide new insights into the molecular mechanisms underlying the ecdysone signaling network governing cell death and cell survival
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