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At least 55 records · Page 3

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↗

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↗

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↗

Materials Data on H12C4S3(N3Cl2)2 by Materials Project

(CN2H4S)12(CCl4)2(CCl3)2Cl2 crystallizes in the triclinic P1 space group. The structure is zero-dimensional and consists of one carbon tetrachloride molecule, one chloroform molecule, one hydrochloric acid molecule, and six thiouronium molecules.

36 MATERIALS SCIENCE↗

Tetraperchlorate of methane

The preparation of the tetraperchlorate of methane (TPM) was attempted. Displacement of halogen from carbon tetrahalides was accomplished with either CCl4 or CBr4 using the halogen perchlorates, ClOClO3, and BOClO3. Although the displacement process was successful, the generated carbon perchlorate intermediates were not isolated. Instead, these species decomposed to COCl2, CO2, and Cl2O7. The vigorous displacement reaction that often occurred required moderation. Fluorocarbon solvents and chlorine perchlorate were successfully tested for compatibility, permitting their use in these synthetic reactions. While the sought for moderating effect was obtained, the net result of the displacement of halogen from CX sub 4 substrates was the same as before. Thus only CO2, COCl2, and Cl2O7 were isolated.

Schack, C. J.↗

Application of selected methods of remote sensing for detecting carbonaceous water pollution

A reach of the Houston Ship Channel was investigated during three separate overflights correlated with ground truth sampling on the Channel. Samples were analyzed for such conventional parameters as biochemical oxygen demand, chemical oxygen demand, total organic carbon, total inorganic carbon, turbidity, chlorophyll, pH, temperature, dissolved oxygen, and light penetration. Infrared analyses conducted on each sample included reflectance ATR analysis, carbon tetrachloride extraction of organics and subsequent scanning, and KBr evaporate analysis of CCl4 extract concentrate. Imagery which was correlated with field and laboratory data developed from ground truth sampling included that obtained from aerial KA62 hardware, RC-8 metric camera systems, and the RS-14 infrared scanner. The images were subjected to analysis by three film density gradient interpretation units. Data were then analyzed for correlations between imagery interpretation as derived from the three instruments and laboratory infrared signatures and other pertinent field and laboratory analyses.

Davis, E. M.↗

Estimate of late 1974 stratospheric concentration of gaseous chlorine compounds /ClX/

The total concentration (ClX) versus altitude of Cl-containing molecules (principally HCl, Cl, ClO) is estimated. It is shown that the predicted present stratospheric concentrations are due to photolysis near 30 km of man-made CF2Cl2 and CFCl3, and CCl4 from a ground-level source, either man-made or natural. The contribution of CH3Cl to stratospheric ClX is evaluated from preliminary measurements of the compound at ground level. Although ground-level sources of HCl and Cl2 are large, tropospheric processes preclude significant impact on the stratosphere.

Cicerone, R. J.↗

Uncertainty propagation in a stratospheric model. I - Development of a concise stratospheric model. II - Monte Carlo analysis of imprecisions due to reaction rates

The paper discusses the development of a concise stratospheric model which uses iteration to obtain coupling between interacting species. The one-dimensional, steady-state, diurnally-averaged model generates diffusion equations with appropriate sources and sinks for species odd oxygen, H2O, H2, CO, N2O, odd nitrogen, CH4, CH3Cl, CCl4, CF2Cl2, CFCl3, and odd chlorine. The model evaluates steady-state perturbations caused by injections of chlorine and NO(x) and may be used to predict ozone depletion. The model is used in a Monte Carlo study of the propagation of reaction-rate imprecisions by calculating an ozone perturbation caused by the addition of chlorine. Since the model is sensitive to only 10 of the more than 50 reaction rates considered, only about 1000 Monte Carlo cases are required to span the space of possible results.

Rundel, R. D.↗

Temperature dependence of the rate constants for reactions of O/1D/ atoms with a number of halocarbons

Results are reported for an experimental study of the reactions of O(1D) with CCl4, CFCl3, CF2Cl2, CHFCl2, CHF2Cl, and CF2ClCFCl2 over the temperature range from 173 to 343 K, based on the time-resolved emission of O(1D) at 630 nm. The experiments involved photolysis of O3 by Nd-YAG laser pulses and measurements of 630-nm emission intensity in mixtures with He and the various halocarbons. Pseudo-first-order rate constants are derived from plots of the logarithms of the 630-nm emission intensities as a function of time for particular He/O3/halocarbon mixtures, and second-order rate constants are then obtained from plots of these pseudo-first-order rate constants as a function of halocarbon concentration at constant He and O3 concentrations. No temperature dependence of the second-order rate constants is observed over the range studied, within the precision of the measurements. It is found that the rate constants decrease as H is substituted for Cl in a halocarbon molecule and as F is substituted for H or Cl.

Davidson, J. A.↗

Configurations of base-pair complexes in solutions

A theoretical search for the most stable conformations (i.e., stacked or hydrogen bonded) of the base pairs A-U and G-C in water, CCl4, and CHCl3 solutions is presented. The calculations of free energies indicate a significant role of the solvent in determining the conformations of the base-pair complexes. The application of the continuum method yields preferred conformations in good agreement with experiment. Results of the calculations with this method emphasize the importance of both the electrostatic interactions between the two bases in a complex, and the dipolar interaction of the complex with the entire medium. In calculations with the solvation shell method, the last term, i.e., dipolar interaction of the complex with the entire medium, was added. With this modification the prediction of the solvation shell model agrees both with the continuum model and with experiment, i.e., in water the stacked conformation of the bases is preferred.

Egan, J. T.↗

The hollow-cathode helium-fluorine laser

It is possible to obtain uniform stable long-pulse excitation (in excess of 100 microsec) in gas mixtures involving highly electronegative constituents (SF6, CCl4, NF3, and I2). Such a system was used to investigate the atomic fluorine laser. In the hollow cathode, lasing on fluorine transitions in the doublet system lasted for up to 80 microsec with no signs of the self-termination as reported previously in positive-column devices. The excitation process of the laser appears to depend heavily upon the fluorine donor utilized. For instance, a single-step process is involved when NF3 is used whereas a two-step process is evident for SF6. The details are discussed.

Crane, J. K.↗

Natural and anthropogenic trace gases in the southern hemisphere

The complexity of the global environment makes it necessary that many important trace gases in the earth's atmosphere be measured on a global scale before predictions can be made regarding the effects of human activities on the environment. A description is presented of measurements of 14 atmospheric trace gases in the lower atmosphere (0-4 km) of the southern hemisphere. Concentrations are considered of CCl3F, CCl2F2, CHClF2, C2.Cl3.F3, CH3CCl3, CCl4, C2.Cl4, CH3I, CHCl3, CO, CH3Cl, CH4, N2O, and OCS. The obtained data are analyzed and interpreted to statistically quantify the possible differences of concentrations in and above the boundary layer, to model the vertical profile of CH3I, and to use the data in support of previous findings that CH4 is increasing in the atmosphere.

Rasmussen, R. A.↗

Differences in the concentrations of atmospheric trace gases in and above the tropical boundary layer

Weekly air samples were collected at Cape Kumakahi (0 km) and at nearby Mauna Loa Observatory (3.4 km) which is above the boundary layer. EC/GC and GC/FID techniques were used to measure CH3I, CHCl3, CO and CH4 which are largely natural in origin, and C2Cl4, CCl4, CH3CCl3, (F-11), CCl2F2, (F-12), CHClF, (F-22) and C2F3Cl3 (F-113), which are due to anthropogenic (CCl3F) etc. activities. It was found that all these gases are significantly (alpha is equal to or less than 0.05) more abundant in the boundary layer than above it.

Rasmussen, R. A.↗

The atmospheric lifetime experiment. I - Introduction, instrumentation, and overview

The Atmospheric Lifetime Experiment is designed to determine accurately the atmospheric concentrations of the four halocarbons CFCl3, CF2Cl2, CCl4, and CH3CCl3, and also of N2O with emphasis on measurement of their long-term trends in the atmosphere. Comparison of these concentrations and trends for the four halocarbons with estimates of their industrial emission rates then enables calculations of their global circulation rates and globally averaged atmospheric lifetimes. The experiment utilizes automated dual-column electron-capture gas chromatographs which sample the background air about 4 times daily at the following globally distributed sites: Adrigole, Ireland, Cape Meares, Oregon; Ragged Point, Barbados; Point Matatula, American Samoa, and Cape Grim, Tasmania. The climatology of these 'clean air' sites and their ability to describe the global air mass are reviewed. The instrumentation and methods for data acquisition and processing are then described. An overview of the data obtained and the trends derived during the 3-year period from July 1978 through June 1981 for each of the five species being measured is presented.

Prinn, R. G.↗

The Atmospheric Lifetime Experiment. II - Calibration

The calibration standards used in the Atmospheric Lifetime Experiment (ALE) for CFCl3, CF2Cl2, CH3CCl3, and CCl4 are described. This includes the preparation of the primary standards by static dilution and their propagation and stability for the period 1977-1982. Two independent assessments of the absolute concentrations of the primary standards used to initiate the ALE measurements in 1977-1978 are reported. For consistency in the ALE program the values assigned to the primary standards and subsequent working standards used in the field were not altered during the experiment when results of better estimates of the original concentration values were obtained. Rather, the appropriate factors by which the ALE mixing ratios for a given species should be multiplied to obtain the best estimate of the current concentration of a given species, are provided.

Rasmussen, R. A.↗

The retrieval of atmospheric constituent mixing-ratio profiles from solar absorption spectra

Methods used to determine various atmospheric gas distributions are summarized. The experimentally determined mixing ratio profiles (the mixing ratio of a gas is the ratio of the number of gas molecules to the number of air molecules) of some atmospheric gases are shown. In most in situ experiments stratospheric gas samples are collected at several altitudes by balloon, aircraft, or rocket. These samples are then analyzed by various methods. Mixing ratio profiles of Ci, ClO, and OH were determined by laser induced fluorescence of samples. Others have analyzed gas samples by gas chromatography in order to determine the molecular abundances of CCl2F2, CCl4, CCl3F, CFCl3, CF2Cl2, CHClF2, CH3CCl3, CH4, CO, C2Cl3F3, C2Cl4, C2HCl3, C2H2, C2H4, C2H6, C3H8, C6H6, C7H8, H2, and N2O.

Shaffer, W. A.↗

s-wave threshold in electron attachment - Results in 2-C4F6 and CFCl3 at ultra-low electron energies

Electron attachment lineshapes and cross sections are reported for the processes 2-C4F6(-)/2-C4F6 and Cl(-)/CFCl3 at electron energies of 0-120 and 0-140 meV, and at resolutions of 6 and 7 meV (FWHM), respectively. As in previous measurements in CCl4 and SF6, the results show resolution-limited narrow structure in the cross section at electron energies below 15 meV. This structure arises from the divergence of the s-wave cross section in the limit of zero electron energy. Comparisons are given with swarm-measured results, and with collisional ionization (high-Rydberg attachment) data in this energy range.

Chutjian, A.↗

Atmospheric trace gases - Trends and distributions over the last decade

Concentrations of the halocarbons CCl3F (F-11), CCl2F2 (F-12), CCl4, and CH3CCl3, methane (CH4), and nitrous oxide (N2O) over the decade between 1975 and 1985 are reported, based on measurements taken every January at the South Pole and in the Pacific Northwest. The concentrations of F-11, F-12, and CH3CCl3 in both hemispheres are now more than twice their concentrations 10 years ago. However, the annual rates of increase of F-11, F-12, and CH3CCl3 are now considerably slower than earlier in the decade, reflecting in part the effects of a ban on their nonessential uses. Continued increases in these trace gas concentrations may warm the earth and deplete the stratospheric ozone layer, which may cause widespread climatic changes and affect global habitability.

Rasmussen, R. A.↗