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At least 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Planarizing Spalled GaAs(100) Surfaces by MOVPE Growth

III-V photovoltaic devices have demonstrated remarkable performance in many applications, and spalling is a promising technique for reducing device costs by recovering the substrate for reuse. In this study, we investigate the in situ planarization of A-directionally spalled GaAs(100) substrates using metal-organic vapor phase epitaxy (MOVPE) grown C:GaAs with CCl4 as the carbon source. We have characterized the (100)-oriented growth for various CCl4 flow rates and observed that the CCl4 or its by-products promote material diffusion from the facet tops to the underlying valleys. For facets with a height of 5 ..mu..m on a substrate with an A-spall and 6 degreesB -offcut, it took 7 ..mu..m of C:GaAs to planarize the substrate. For a similar sample, with a 6 degreesA -offcut, it required 2 ..mu..m of growth to fill the valleys but there were remnant facets.

III-V↗
NASA NTRS1977

Photodecomposition of chloromethanes adsorbed on silica surfaces

Irradiation of CCl4, CFCl3, and CF2Cl2 in the presence of C2H6 in vessels containing silica sand or fused quartz tubing results in the formation of chlorine-containing products. The formation of these compounds occurs at wavelengths extending up to approximately 400 nm, that is, at wavelengths well beyond the absorption threshold of the chloromethanes in the gas phase. It is suggested that CCl4 adsorbed on silica surfaces photodissociates to yield CCl3 and CCl2 species. The poor material balance obtained in these experiments indicates that several of the chlorine-containing fragments are strongly adsorbed on the surface. At a CCl4 pressure of 13 Pa (0.1 torr), photolysis with 366 nm light in the presence of sand results in the decomposition of one molecule for every 10,000 photons striking the surface. Under otherwise identical conditions, the photon-induced breadkdown of CFCl3 and CF2Cl2 is respectively only 10% or 3% as efficient.

Ausloos, P.↗
DOE OSTI2017

Caffeic acid phenethyl ester attenuates liver fibrosis via inhibition of TGF-β1/Smad3 pathway and induction of autophagy pathway

Caffeic acid phenethyl ester (CAPE) has been reported to possess the hepatoprotective effect. This study was to investigate the mechanism underlying CAPE against liver fibrosis in a liver fibrosis model induced by toxic carbon tetrachloride (CCl4) in male Sprague-Dawley rats and in vitro in CAPE (5 μM, 10 μM, 15 μM) treated hepatic stellate cells (HSC-T6). We found that CAPE treatment remarkably attenuated CCl4-induced liver fibrosis by blocking the activation of HSCs as determined by the expression alternation of transforming growth factor (TGF)-β1, phosphorylated Smad3 (p-Smad3), collage I, α-smooth muscle actin (α-SMA), matrix metalloproteinases (MMPs) 2, tissue inhibitor of matrix metalloproteinases (TIMPs) 1. The hepatoprotective effects of CAPE were also associated with upregulation of autophasomes in HSCs as determined by transmission electron microscopy (TEM) detection. The in vitro study further confrimed that CAPE attenuated liver fibrogenesis via inducing authophagic markers including LC3, ATG5, Beclin 1 expressions, while inhibiting AKT/mTOR signaling in HSC-T6 cells. Thus, the protective effects of CAPE against liver fibrosis might due to the inhibition of TGF-β1/Smad3 signaling and induction of authophagy in HSCs. - Highlights: • CAPE inhibited liver fibrosis through blocking HSCs activation. • CAPE repressed the TGF-β1/Smad3 signaling pathway in liver fibrosis. • CAPE induced autophagy activities in HSCs through accumulating autophagosomes. • CAPE attenuated live fibrosis through inhibing AKT/mTOR signaling in HSCs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Role of histone deacetylases(HDACs) in progression and reversal of liver fibrosis

Liver fibrosis refers to a reversible wound healing process response to chronic liver injuries. Activation of hepatic stellate cells (HSCs) is closely correlated with the development of liver fibrosis. Histone deacetylases(HDACs) determine the acetylation levels of core histones to modulate expression of genes. To demonstrate the link between HDACs and liver fibrosis, CCl4-induced mouse liver fibrosis model and its spontaneous reversal model were established. Results of the current study demonstrated that deregulation of liver HDACs may involved in the development of liver fibrosis. Among 11 HDACs tested in our study (Class I, II, and IV HDACs), expression of HDAC2 was maximally increased in CCl4-induced fibrotic livers but decreased after spontaneous recovery. Moreover, expression of HDAC2 was elevated in human liver fibrotic tissues. In this regard, the potential role of HDAC2 in liver fibrosis was further evaluated. Our results showed that administration of HSC-T6 cells with transforming growth factor-beta1 (TGF-β1) resulted in an increase of HDAC2 protein expression in dose- and time-dependent manners. Moreover, HDAC2 deficiency inhibited HSC-T6 cell proliferation and activation induced by TGF-β1. More importantly, the present study showed HDAC2 may regulate HSCs activation by suppressing expression of Smad7, which is a negative modulator in HSCs activation and liver fibrosis. Collectively, these observations revealed that HDAC2 may play a pivotal role in HSCs activation and liver fibrosis while deregulation of HDACs may serve as a novel mechanism underlying liver fibrosis. - Highlights: • This is the first report to systematically examine expressions of HDACs during liver fibrosis and fibrosis reversal. • Aberrant expression of HDAC2 contributes to the development of liver fibrosis. • Provided important foundation for further liver fibrosis conversion studies.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Structural basis for oligomerization and glycosaminoglycan binding of CCL5 and CCL3

CC chemokine ligand 5 (CCL5) and CCL3 are critical for immune surveillance and inflammation. Consequently, they are linked to the pathogenesis of many inflammatory conditions and are therapeutic targets. Oligomerization and glycosaminoglycan (GAG) binding of CCL5 and CCL3 are vital for the functions of these chemokines. Our structural and biophysical analyses of human CCL5 reveal that CCL5 oligomerization is a polymerization process in which CCL5 forms rod-shaped, double-helical oligomers. This CCL5 structure explains mutational data and offers a unified mechanism for CCL3, CCL4, and CCL5 assembly into high-molecular-weight, polydisperse oligomers. Here, a conserved, positively charged BBXB motif is key for the binding of CC chemokines to GAG. However, this motif is partially buried when CCL3, CCL4, and CCL5 are oligomerized; thus, the mechanism by which GAG binds these chemokine oligomers has been elusive. Our structures of GAG-bound CCL5 and CCL3 oligomers reveal that these chemokine oligomers have distinct GAG-binding mechanisms. The CCL5 oligomer uses another positively charged and fully exposed motif, KKWVR, in GAG binding. However, residues from two partially buried BBXB motifs along with other residues combine to form a GAG-binding groove in the CCL3 oligomer. The N termini of CC chemokines are shown to be involved in receptor binding and oligomerization. We also report an alternative CCL3 oligomer structure that reveals how conformational changes in CCL3 N termini profoundly alter its surface properties and dimer–dimer interactions to affect GAG binding and oligomerization. Such complexity in oligomerization and GAG binding enables intricate, physiologically relevant regulation of CC chemokine functions.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
NASA NTRS1975

A search for chemical laser action in low pressure metal vapor flames

Optical emissions were studied from low pressure (approximately 1 torr) dilute diffusion flames of Ca and Mg vapor with O2, N2O and mixtures of CCl4 and O2. The Ca flames with O2 and N2O revealed high vibrational excitation of the product CaO molecule (up to v=30). The flames with CCl4 revealed extreme nonequilibrium metal atom electronic excitation, up to the metal atom ionization limit (6.1 eV for Ca, 7.6 eV for Mg). The metal atom excited electronic state populations did not follow a Boltzmann distribution, but the excitation rates ('pumping rate') were found to obey an Arrhenius-type expression, with the electronic excitation energy playing the role of activation energy and a temperature of about 5000 K for triplet excited states and 2500 K for singlets (vs. approximately 500 K translational temperature).

Zwillenberg, M. L.↗
NASA NTRS1982

Carbon, hydrogen and nitrogen isotopes in solvent-extractable organic matter from carbonaceous chondrites

CCl4 and CH3OH solvent extractions were performed on the Murray, Murchison, Orgueil and Renazzo carbonaceous chondrites. Delta-D values of +300-+500% are found in the case of the CH3OH-soluble organic matter. The combined C, H and N isotope data makes it unlikely that the CH3OH-soluble components are derivable from, or simply related to, the insoluble organic polymer found in the same meteorites. A relation between the event that formed hydrous minerals in CI1 and CM2 meteorites and the introduction of water- and methanol-soluble organic compounds is suggested. Organic matter soluble in CCl4 has no N, and delta-C-13 values are lower than for CH3OH-soluble phases. It is concluded that there either are large isotopic fractionations for carbon and hydrogen between different soluble organic phases, or the less polar components are partially of terrestrial origin.

Becker, R. H.↗
NASA NTRS1985

Continental sources of halocarbons and nitrous oxide

Estimates of continental sources of CFC-11, CFC-12, CCl4, CH3CCl3 and N2O are derived from the atmospheric lifetime experiment in Adrigole, Ireland, and anthropogenic emissions of CCl4 and N2O from Europe have been identified. Relative source strengths are consistent with global budgets for the halocarbons and N2O. Different industrial release patterns for halocarbons are observed for Europe, the western United States and Australia.

Prather, M. J.↗
NASA NTRS1988

European sources of halocarbons and nitrous oxide - Update 1986

New information on seasonal and secular trends in the releases of CFCl3, CF2Cl2, CCl4, CH3CCl3, and N20 from Europe was obtained as part of the Atmospheric Lifetime Experiment. Semicontinuous measurements of these pollutants were made at Adrigole, Ireland, using lean air from the Atlantic Ocean as a baseline. The results obtained include unambiguous evidence for elevated levels of N2O occurring concurrent with halocarbon pollution events; the detection of trends in the relative emission of different halocarbons; the discovery of seasonal variations in emission of CF2Cl2, CCl4, and CH3Cl3; the characterization of typical summer and winter pollution episodes; and the identification of weather patterns over Europe that are associated with high concentrations of chlorofluorocarbons at Adrigole. It was estimated that the European source of N2O represents 25 percent of the global emissions associated with combustion and 10 percent of the integrated stratospheric losses.

Prather, Michael↗
NASA NTRS1990

Thermal emission spectroscopy of the middle atmosphere

The general objective of this research is to obtain, via remote sensing, simultaneous measurements of the vertical distributions of stratospheric temperature, ozone, and trace constituents that participate in the catalytic destruction of ozone (NO(sub y): NO, NO2, NO3, HNO3, ClONO2, N2O5, HNO4; Cl(sub x): HOCl), and the source gases for the catalytic cycles (H2O, CH4, N2O, CF2Cl2, CFCl3, CCl4, CH3Cl, CHF2Cl, etc.). Data are collected during a complete diurnal cycle in order to test our present understanding of ozone chemistry and its associate catalytic cycles. The instrumentation employed is an emission-mode, balloon-borne, liquid-nitrogen-cooled Michelson interferometer-spectrometer (SIRIS), covering the mid-infrared range with a spectral resolution of 0.020 cm(exp -1). Cryogenic cooling combined with the use of extrinsic silicon photoconductor detectors allows the detection of weak emission features of stratospheric gaseous species. Vertical distributions of these species are inferred from scans of the thermal emission of the limb in a sequence of elevation angles. The fourth SIRIS balloon flight was carried out from Palestine, Texas on September 15-16, 1986 with 9 hours of nighttime data (40 km). High quality data with spectral resolution 0.022 cm(exp -1), were obtained for numerous limb sequences. Fifteen stratospheric species have been identified to date from this flight: five species from the NO(sub y) family (HNO3, NO2, NO, ClONO2, N2O5), plus CO2, O3, H2O, N2O, CH4, CCl3F, CCl2F2, CHF2Cl, CF4, and CCl4. The nighttime values of N2O5, ClONO2, and total odd nitrogen have been measured for the first time, and compared to model results. Analysis of the diurnal variation of N2O5 within the 1984 and 1986 data sets, and of the 1984 ClONO2 measurements, were presented in the literature. The demonstrated ability of SIRIS to measure all the major NO(sub y) species, and therefore to determine the partitioning of the nitrogen family over a continuous diurnal cycle, is a powerful tool in the verification and improvement of photochemical modeling.

Kunde, V. G.↗
NASA NTRS1996

A Comparison of Measurements from ATMOS and Instruments Aboard the ER-2 Aircraft: Halogenated Gases

We compare volume mixing ratio profiles of N2O, CFC-11, CFC-12, CCl4, SF6, and HCl in the mid-latitude lower stratosphere measured by the ATMOS Fourier transform spectrometer on the ATLAS-3 Space Shuttle Mission with in situ measurements acquired from the NASA ER-2 aircraft during Nov. 1994. Good agreement is found between ATMOS and in situ correlations of [CFC-11], [CFC-12], and [SF6] with [N2O]. ATMOS measurements of [CCl4] are 15% high compared to ER-2 data, but agree within the systematic uncertainties. ATMOS observations of [HCl] vs [N2O] are within approximately 10% of ER-2 data for [HCl] > 1 ppbv, but exceed in situ measurements by larger fractional amounts for smaller [HCl]. ATMOS measurements of [ClONO2] agree well with values inferred from in situ observations of [ClO], [NO], and [O3]. The sum of [HCl] and [ClONO2] observed by ATMOS, supplemented by a minor contribution from [ClO] estimated with a photochemical model, is consistent with the levels of inorganic chlorine inferred from in situ measurements of chlorine source gases.

Chang, A. Y.↗
NASA NTRS2011

A Model Study of the Impact of Source Gas Changes on the Stratosphere for 1850-2100

The long term stratospheric impacts due to emissions of CO2, CH4, N2O, and ozone depleting substances (ODSs) are investigated using an updated version of the Goddard two-dimensional (2D) model. Perturbation simulations with the ODSs, CO2, CH4, and N2O varied individually are performed to isolate the relative roles of these gases in driving stratospheric changes over the 1850-2100 time period. We also show comparisons with observations and the God- 40 dard Earth Observing System chemistry-climate model simulations for the time period 1970-2100 to illustrate that the 2D model captures the basic processes responsible for longterm stratospheric change. The 2D simulations indicate that prior to 1940, the 45 ozone increases due to CO2 and CH4 loading outpace the ozone losses due to increasing N2O and carbon tetrachloride (CCl4) emissions, so that ozone reaches a broad maximum during the 1920s-1930s. This preceeds the significant ozone depletion during approx. 1960-2050 driven by the ODS loading. During the latter half of the 21st century as ODS emissions diminish, CO2, N2O, and CH4 loading will all have significant impacts on global total ozone based on the IPCC AIB (medium) scenario, with CO2 having the largest individual effect. Sensitivity tests illustrate that due to the strong chemical interaction between methane and chlorine, the CH4 impact on total ozone becomes significantly more positive with larger ODS loading. The model simulations also show that changes in stratospheric temperature, Brewer-Dobson circulation (BDC), and age of air during 1850-2100 are controlled mainly by the CO2 and ODS loading. The simulated acceleration of the BDC causes the age of air to decrease by approx. 1 year from 1860-2100. The corresponding photochemical lifetimes of N2O, CFCl3, CF2Cl2, and CCl4 decrease by 11-13% during 1960-2100 due to the acceleration of the BDC, with much smaller lifetime changes 4%) caused by changes in the photochemical loss rates.

Fleming, E. L.↗
DOE OSTI2013

Th1-skewed tissue responses to a mycolyl glycolipid in mycobacteria-infected rhesus macaques

Highlights: •Glucose monomycolate (GMM) is a marker glycolipid for active tuberculosis. •Tissue responses to GMM involved up-regulation of Th1-attracting chemokines. •Th1-skewed local responses were mounted at the GMM-injected tissue. -- Abstract: Trehalose 6,6′-dimycolate (TDM) is a major glycolipid of the cell wall of mycobacteria with remarkable adjuvant functions. To avoid detection by the host innate immune system, invading mycobacteria down-regulate the expression of TDM by utilizing host-derived glucose as a competitive substrate for their mycolyltransferases; however, this enzymatic reaction results in the concomitant biosynthesis of glucose monomycolate (GMM) which is recognized by the acquired immune system. GMM-specific, CD1-restricted T cell responses have been detected in the peripheral blood of infected human subjects and monkeys as well as in secondary lymphoid organs of small animals, such as guinea pigs and human CD1-transgenic mice. Nevertheless, it remains to be determined how tissues respond at the site where GMM is produced. Here we found that rhesus macaques vaccinated with Mycobacterium bovis bacillus Calmette–Guerin mounted a chemokine response in GMM-challenged skin that was favorable for recruiting T helper (Th)1 T cells. Indeed, the expression of interferon-γ, but not Th2 or Th17 cytokines, was prominent in the GMM-injected tissue. The GMM-elicited tissue response was also associated with the expression of monocyte/macrophage-attracting CC chemokines, such as CCL2, CCL4 and CCL8. Furthermore, the skin response to GMM involved the up-regulated expression of granulysin and perforin. Given that GMM is produced primarily by pathogenic mycobacteria proliferating within the host, the Th1-skewed tissue response to GMM may function efficiently at the site of infection.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

ODC1 inhibits the inflammatory response and ROS-induced apoptosis in macrophages

Highlights: • ODC1 is up-regulated by LPS, BCG and CCl4 stimulation. • ODC1 inhibits inflammatory responses in macrophages. • ODC1 mediates NF-κB and MAPK activation. • ODC1 inhibits ROS-induced macrophage apoptosis. Macrophage activation plays a critical role in the innate immune response. Ornithine decarboxylase (ODC1) metabolizes l-ornithine to polyamines and is the rate-limiting enzyme involved in the metabolism of polyamines, which are reportedly involved in cell differentiation, proliferation, and migration. However, the function of ODC1 in immune cells and especially in macrophages, as well as its underlying molecular mechanism, remains unclear. This study revealed the potential ODC1 function and mechanism associated with the lipopolysaccharide (LPS)-, Bacillus Calmette–Guerin (BCG)-, or carbon tetrachloride (CCl{sub 4})-induced inflammatory response in macrophages. We found significant upregulation of ODC1 in macrophages following LPS simulation and ODC1-specific suppression of proinflammatory cytokine secretion from macrophages upon stimulation with LPS, BCG and CCl{sub 4}, respectively, suggesting a role as a common control element of the inflammatory response. Western blotting for nuclear factor-κB and mitogen-activated protein kinases revealed significant inhibition of phosphorylation of multiple transcription factors following ODC1 overexpression in macrophages. Moreover, ODC1 inhibited reactive oxygen species-induced and caspase-dependent apoptosis highlighted by decreased caspase-3 and -9 expression following ODC1 upregulation. These findings indicated that ODC1 was involved in attenuating the inflammatory response upon stimulation of macrophages, making it a potential therapeutic target for inflammatory diseases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Inhibition of soluble epoxide hydrolase attenuates hepatic fibrosis and endoplasmic reticulum stress induced by carbon tetrachloride in mice

Liver fibrosis is a pathological condition in which chronic inflammation and changes to the extracellular matrix lead to alterations in hepatic tissue architecture and functional degradation of the liver. Inhibitors of the enzyme soluble epoxide hydrolase (sEH) reduce fibrosis in the heart, pancreas and kidney in several disease models. In this study, we assess the effect of sEH inhibition on the development of fibrosis in a carbon tetrachloride (CCl{sub 4})-induced mouse model by monitoring changes in the inflammatory response, matrix remolding and endoplasmic reticulum stress. The sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) was administered in drinking water. Collagen deposition in the liver was increased five-fold in the CCl{sub 4}-treated group, and this was returned to control levels by TPPU treatment. Hepatic expression of Col1a2 and 3a1 mRNA was increased over fifteen-fold in the CCl{sub 4}-treated group relative to the Control group, and this increase was reduced by 50% by TPPU treatment. Endoplasmic reticulum (ER) stress observed in the livers of CCl{sub 4}-treated animals was attenuated by TPPU treatment. In order to support the hypothesis that TPPU is acting to reduce the hepatic fibrosis and ER stress through its action as a sEH inhibitor we used a second sEH inhibitor, trans-4-(4-[3-(4-trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy)-benzoic acid (t-TUCB), and sEH null mice. Taken together, these data indicate that the sEH may play an important role in the development of hepatic fibrosis induced by CCl{sub 4}, presumably by reducing endogenous fatty acid epoxide chemical mediators acting to reduce ER stress. - Highlights: • We administer an inhibitor of sEH in a CCl4 murine model. • sEH inhibition reduces liver collagen deposition and pro-fibrotic gene expression. • sEH inhibition induces MMP-1a activity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Silent information regulator 1 (SIRT1) ameliorates liver fibrosis via promoting activated stellate cell apoptosis and reversion

SIRT1 (silent information regulator 1), a conserved NAD +-dependent histone deacetylase, is closely related with various biological processes. Moreover, the important role of SIRT1 in alcoholic liver disease, nonalcoholic fatty liver and HCC had been widely reported. Recently, a novel role of SIRT1 was uncovered in organ fibrosis diseases. Here, we investigated the inhibitory effect of SIRT1 in liver fibrogenesis. SIRT1 protein was dramatically decreased in CCl4-treated mice livers. Stimulation of LX-2 cells with TGF-β1 also resulted in a significant suppression of SIRT1 protein. Nevertheless, TGF-β1-induced LX-2 cell activation was inhibited by SIRT1 plasmid, and this was accompanied by up-regulation of cell apoptosis-related proteins. Overexpression of SIRT1 also attenuated TGF-β1-induced expression of myofibroblast markers α-SMA and COL1a. However, the important characteristic of the recovery of liver fibrosis is not only the apoptosis of activated stellate cells but also the reversal of the myofibroblast-like phenotype to a quiescent-like phenotype. Restoration of SIRT1 protein was observed in the in vivo spontaneously liver fibrosis reversion model and in vitro MDI (isobutylmethylxanthine, dexamethasone, and insulin)-induced reversed stellate cells, and forced expression of SIRT1 also promoted the reversal of activated stellate cells. Furthermore, lncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) was increased in liver fibrosis. RNAi-mediated suppression of MALAT1 resulted in a decrease of myofibroblast markers and restoration of SIRT1 protein. These observations suggested that SIRT1 contributed to apoptosis and reversion of activated LX-2 cells and SIRT1 might be regulated by MALAT1 in liver fibrosis. Therefore, SIRT1 could be considered as a valuable therapeutic target for translational studies of liver fibrosis. - Highlights: • This is the first report of SIRT1 expression and function in liver fibrogenesis and reversion. • Aberrant expression of SIRT1 might just occur at a post-transcriptional level. • LncRNA MALAT1 might be responsible for the changes of SIRT1 in liver fibrosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Methylation of Septin9 mediated by DNMT3a enhances hepatic stellate cells activation and liver fibrogenesis

Liver fibrosis, resulting from chronic and persistent injury to the liver, is a worldwide health problem. Advanced liver fibrosis results in cirrhosis, liver failure and even hepatocellular cancer (HCC), often eventually requiring liver transplantation, poses a huge health burden on the global community. However, the specific pathogenesis of liver fibrosis remains not fully understood. Numerous basic and clinical studies have provided evidence that epigenetic modifications, especially DNA methylation, might contribute to the activation of hepatic stellate cells (HSCs), the pivotal cell type responsible for the fibrous scar in liver. Here, reduced representation bisulfite sequencing (RRBS) and bisulfite pyrosequencing PCR (BSP) analysis identified hypermethylation status of Septin9 (Sept9) gene in liver fibrogenesis. Sept9 protein was dramatically decreased in livers of CCl4-treated mice and immortalized HSC-T6 cells exposed to TGF-β1. Nevertheless, the suppression of Sept9 could be blocked by DNMT3a-siRNA and DNA methyltransferase inhibitor, 5-aza-2′-deoxycytidine (5-azadC). Overexpressed Sept9 attenuated TGF-β1-induced expression of myofibroblast markers α-SMA and Col1a1, accompanied by up-regulation of cell apoptosis-related proteins. Conversely, RNAi-mediated silencing of Sept9 enhanced accumulation of extracellular matrix. These observations suggested that Sept9 contributed to alleviate liver fibrosis might partially through promoting activated HSCs apoptosis and this anti-fibrogenesis effect might be blocked by DNMT-3a mediated methylation of Sept9. Therefore, pharmacological agents that inhibit Sept9 methylation and increase its expression could be considered as valuable treatments for liver fibrosis. - Highlights: • This is the first report of Sept9 methylation and function in liver fibrosis. • Ectopic expression of Sept9 could block the liver fibrogenesis. • DNMT3a might be responsible for the suppression of Sept9 in liver fibrosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Multiplexed Digital mRNA Profiling of the Inflammatory Response in the West Nile Swiss Webster Mouse Model

Background and purpose: The ability to track changes in gene expression following viral infection is paramount to understanding viral pathogenesis. This study was undertaken to evaluate the nCounter, a high throughput digital gene expression system, as a means to better understand West Nile virus (WNV) dissemination and the inflammatory response against WNV in the outbred Swiss Webster (SW) mouse model over the course of infection. Methodology: The nCounter Mouse Inflammation gene expression kit containing 179 inflammation related genes was used to analyze gene expression changes in multiple tissues over a nine day course of infection in SW mice following intraperitoneal injection with WNV. Protein expression levels for a subset of these cytokine/chemokine genes were determined using a multiplex protein detection system (BioPlex) and comparisons of protein/RNA expression levels made. Results: Expression analysis of spleen, lung, liver, kidney and brain of SW mice infected with WNV revealed that Cxcl10 and Il12b are differentially expressed in all tissues tested except kidney. Data stratification of positively confirmed infected (WNV (+)) versus non-infected (WNV (2) tissues allowed differentiation of the systemic inflammatory gene response from tissue specific responses arising from WNV infection. Significant (p,0.05) decrease in C3ar1 was found in WNV (2) spleen. Il23a was significantly upregulated, while Il10rb was down-regulated in WNV (2) lung. Il3 and Mbl2 were down-regulated in WNV (2) liver. In WNV (+) livers, Stat1, Tlr2, chemokines Cxcl1, Cxcl3, Cxcl9, Cxcl10, cytokines Il6, Il18, cytokine-related gene Il1r and cytokine agonist Ilrn were significantly upregulated. In WNV (2) brain tissues, Csf2 and Cxcl10 were significantly upregulated. Similar gene and protein expression kinetics were found for Ccl2, Ccl3, Ccl4 and Ccl5 and correlated with the presence of infectious virus. In summary, the utility of the nCounter platform for rapid identification of gene expression changes in SW mice associated with WNV infection was demonstrated.

54 ENVIRONMENTAL SCIENCES↗