Ariel - Volume 4 Number 6

Editors David A. Jacoby Eugenia Miller Tom Williams Associate Editors Paul Bialas Terry Burt Michael Leo Gail Tenikat Editor Emeritus and Business Manager Richard J. Bonnano Movie Editor Robert Breckenridge Staff Richard Blutstein Mary F. Buechler J.D. Kanofsky Rocket Weber David Maye

Hepatocyte apoptosis is tumor promoting in murine nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease is the most common chronic liver disease and may progress to nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). The molecular determinants of this pathogenic progression, however, remain largely undefined. Since liver tumorigenesis is driven by apoptosis, we examined the effect of overt hepatocyte apoptosis in a mouse model of NASH using mice lacking myeloid cell leukemia 1 (Mcl1), a pro-survival member of the BCL-2 protein family. Hepatocyte-specific Mcl1 knockout (Mcl1$^{∆hep}$) mice and control littermates were fed chow or FFC (high saturated fat, fructose, and cholesterol) diet, which induces NASH, for 4 and 10 months. Thereafter, liver injury, inflammation, fibrosis, and tumor development were evaluated biochemically and histologically. Mcl1$^{∆hep}$ mice fed with the FFC diet for 4 months displayed a marked increase in liver injury, hepatocyte apoptosis, hepatocyte proliferation, macrophage-associated liver inflammation, and pericellular fibrosis in contrast to chow-fed Mcl1$^{∆hep}$ and FFC diet-fed Mcl1-expressing littermates. After 10 months of feeding, 78% of FFC diet-fed Mcl1$^{∆hep}$ mice developed liver tumors compared to 38% of chow-fed mice of the same genotype. Tumors in FFC diet-fed Mcl1$^{∆hep}$ mice were characterized by cytologic atypia, altered liver architecture, immunopositivity for glutamine synthetase, and histologically qualified as HCC. In conclusion, this study provides evidence that excessive hepatocyte apoptosis exacerbates the NASH phenotype with enhancement of tumorigenesis in mice

Effects of short-chain fatty acids on intestinal function in an enteroid model of hypoxia

The healthy GI tract is physiologically hypoxic, but this may be perturbed by certain acute and chronic stressors that reduce oxygen availability systemically. Short-chain fatty acids have been shown to have beneficial effects on intestinal barrier function and inflammation. Therefore, our objective was to see whether short-chain fatty acids (SCFA) would improve GI barrier function, reduce production of pro-inflammatory cytokines, and increase the expression of genes regulating GI barrier function in enteroids exposed to hypoxia. Human duodenal enteroid monolayers were placed under hypoxia (1.0% O2) for 72 h with either 24, or 48 h pre-treatment with a high acetate ratio of SCFA’s or high butyrate ratio or placed under hypoxia concurrently. Transepithelial electrical resistance (TEER) increased with SCFA pre-treatment, especially 48 h of pre-treatment and this was maintained through the first 48 h of hypoxia while cells saw barrier function dramatically decrease by 72 h of hypoxia exposure. Inflammatory protein secretion largely decreased with exposure to hypoxia, regardless of SCFA pre-treatment. Gene expression of several genes related to barrier function were decreased with exposure to hypoxia, and with concurrent and 24 h SCFA pre-treatment. However, 48 h SCFA pre-treatment with a high butyrate ratio increased expression of several metabolic and differentiation related genes. Overall, pre-treatment or concurrent treatment with SCFA mixtures were not able to overcome the negative impacts of hypoxia on intestinal function and cells ultimately still cannot be sustained under hypoxia for 72 h. However, 48 h pre-treatment maintains TEER for up to 48 h of hypoxia while upregulating several metabolic genes

Structural characterization of nanofiber silk produced by embiopterans (webspinners)

Embiopterans produce silken galleries and sheets using exceptionally fine silk fibers in which they live and breed. In this study, we use electron microscopy (EM), Fourier-transform infrared (FT-IR) spectroscopy, wide angle X-ray diffraction (WAXD) and solid-state nuclear magnetic resonance (ssNMR) techniques to elucidate the molecular level protein structure of webspinner (embiid) silks. Silks from two species Antipaluria urichi and Aposthonia ceylonica are studied in this work. Electron microscopy images show that the fibers are about 90–100 nm in diameter, making webspinner silks among the finest of all known animal silks. Structural studies reveal that the silk protein core is dominated by β-sheet structures, and that the protein core is coated with a hydrophobic alkane-rich surface coating. FTIR spectra of native embiid silk shows characteristic alkane CH2 stretchings near 2800–2900 cm−1, which decrease approximately 50% after washing the silk with 2 : 1 CHCl3 : MeOH. Furthermore, 13C ssNMR data shows a significant CH2 resonance that is strongly affected by the presence of water, supporting the idea that the silk fibers are coated with a hydrocarbon-rich layer. Such a layer is likely used to protect the colonies from rain. FTIR data also suggests that embiid silks are dominated by β-sheet secondary structures similar to spider and silkworm silk fibers. NMR data confirms the presence of β-sheet nanostructures dominated by serine-rich repetitive regions. A deconvolution of the serine Cβ NMR resonance reveals that approximately 70% of all seryl residues exist in a β-sheet structure. This is consistent with WAXD results that suggest webspinner silks are 70% crystalline, which is the highest crystalline fraction reported for any animal silks. The work presented here provides a molecular level structural picture of silk fibers produced by webspinners

Scintillation of tantalate compounds

A screening of 63 metal-tantalate-oxides was conducted in search of heavy scintillator materials operating at ambient temperature. While tantalates are known to have slow scintillation decay times, the high atomic number of tantalum (73) provides good stopping power for gamma rays. Screened samples were synthesized by solid state reactions. Scintillation properties of these materials were evaluated by X-ray diffraction, X-ray excited luminescence and pulsed X-ray luminescence. Of the 63 synthesized tantalates examined only 12 had luminosity values greater than 1000 ph/MeV at room temperature. From these, ScTaO4, YTa3O9, and Zn3Ta2O8 have greater than 40% of their emission in the first μs. The brightest and fastest compound of those tested was Zn3Ta2O8 with an estimated luminosity of 26,000 ph/MeV and a main decay time of 600 ns from its crystalline powder. Further attention is given to Zn3Ta2O8 and Mg4Ta2O9 scintillation properties, demonstrating their potential for scintillation applications

The use of live attenuated influenza vaccine (LAIV) in healthcare personnel (HCP): Guidance from the society for healthcare epidemiology of America (SHEA)

Because of the live viral backbone of live attenuated influenza vaccine (LAIV), questions have arisen regarding infection control precautions and restrictions surrounding its use in healthcare personnel (HCP). This document provides guidance from the Society for Healthcare Epidemiology of America regarding use of LAIV in HCP and the infection control precautions that are recommended with its use in this population. Infect Control Hosp Epidemiol 2012;33(10):981-98

ACE-ASIA - Regional climatic and atmospheric chemical effects of Asian dust and pollution

Although continental-scale plumes of Asian dust and pollution reduce the amount of solar radiation reaching the earth's surface and perturb the chemistry of the atmosphere, our ability to quantify these effects has been limited by a lack of critical observations, particularly of layers above the surface. Comprehensive surface, airborne, shipboard, and satellite measurements of Asian aerosol chemical composition, size, optical properties, and radiative impacts were performed during the Asian Pacific Regional Aerosol Characterization Experiment (ACE-Asia) study. Measurements within a massive Chinese dust storm at numerous widely spaced sampling locations revealed the highly complex structure of the atmosphere, in which layers of dust, urban pollution, and biomass-burning smoke may be transported long distances as distinct entities or mixed together. The data allow a first-time assessment of the regional climatic and atmospheric chemical effects of a continental-scale mixture of dust and pollution. Our results show that radiative flux reductions during such episodes are sufficient to cause regional climate change