Earthquake-Induced Stress Amplification and Rock Fragmentation within a Deep-Seated Bedding Fault: Case Study of the Daguangbao Landslide Triggered by the 2008 Wenchuan Earthquake (Ms=8.0)

AbstractThe 2008 Wenchuan Ms 8.0 earthquake triggered the Daguangbao (DGB) landslide, of which the shear surface belongs to a thrust bedding fault 400 m below the carbonate slope. After the landslide, a 1.8 km-long inclined sliding face (0.3 km2) was exposed in the south source area. By using shaking table test, the contributions of the fault to the landslide sliding have been studied in this paper. The bedding fault in the test model is simplified as a weak layer with small elasticity and the carbonate layers as a hard layer with high elastic modulus, which is 296 times the weak one. The test records larger displacement amplitude in the upper hard layer than that in the lower one and larger pressure amplitude in the weak layer than that in the hard ones. We ascribed the stress amplification in the weak layer to time delay of shaking wave as wave velocity in the weak layer is only 1/15 of that in the hard layers. Such time delay gives rise to phase differences between the hard layers during shaking. The compressive stress amplification occurs in the weak layer when the upper hard layer moves downwards relative to the lower one; otherwise, tensile stress amplification occurs. It is suggested that this kind of stress amplification triggered an extensive fragmentation of the bedding fault rock mass during the Wenchuan earthquake, which can be verified by a good deal of gentle-dip and steep-dip cracks observed on site. It is proposed that stress amplification had caused a fast dropping of shear strength in the bedding fault to enhance the suddenness of DGB landslide initiation

Interleukin-22 Inhibits Bleomycin-Induced Pulmonary Fibrosis

Pulmonary fibrosis is a progressive and fatal fibrotic disease of the lungs with unclear etiology. Recent insight has suggested that early injury/inflammation of alveolar epithelial cells could lead to dysregulation of tissue repair driven by multiple cytokines. Although dysregulation of interleukin- (IL-) 22 is involved in various pulmonary pathophysiological processes, the role of IL-22 in fibrotic lung diseases is still unclear and needs to be further addressed. Here we investigated the effect of IL-22 on alveolar epithelial cells in the bleomycin- (BLM-) induced pulmonary fibrosis. BLM-treated mice showed significantly decreased level of IL-22 in the lung. IL-22 produced γδT cells were also decreased significantly both in the tissues of lungs and spleens. Administration of recombinant human IL-22 to alveolar epithelial cell line A549 cells ameliorated epithelial to mesenchymal transition (EMT) and partially reversed the impaired cell viability induced by BLM. Furthermore, blockage of IL-22 deteriorated pulmonary fibrosis, with elevated EMT marker (α-smooth muscle actin (α-SMA)) and overactivated Smad2. Our results indicate that IL-22 may play a protective role in the development of BLM-induced pulmonary fibrosis and may suggest IL-22 as a novel immunotherapy tool in treating pulmonary fibrosis

MicroRNA-7 inhibits epithelial-to-mesenchymal transition and metastasis of breast cancer cells via targeting FAK expression

10.1371/journal.pone.0041523PLoS ONE78

Determination of tolbutamide and hydroxytolbutamide by LC–MS/MS in rat and its application to assessment of CYP2C9 activity

A sensitive and selective liquid chromatography–tandem mass spectrometry method (LC–MS/MS) for the determination of tolbutamide (TB) and its metabolite hydroxytolbutamide (HTB) in rat plasma was developed using carbamazepine as an internal standard. Chromatographic separation was performed by an Agilent Zorbax SB-C18 column (150 mmx2.1 mm, 3.5 μm), using the gradient elution of 0.1 % formic acid in water and acetonitrile. Calibration plots were linear over range of 5–1000 ng/mL for TB and 10–2000 ng/mL for HTB in rat plasma. The intra- and inter-day relative standard deviations of the assay were less than 10 % for both TB and HTB. The validated method is successfully used to analyze the influence of bupropion on cytochrome P450-mediated metabolism of TB. The biotransformation rates of TB administered either separately or both simultaneously were compared in this study. The results revealed that bupropion had no significant effect on TB hydroxylation.Colegio de Farmacéuticos de la Provincia de Buenos Aire

The critical role of intracellular zinc in adenosine A2 receptor activation induced cardioprotection against reperfusion injury

Exogenous zinc can protect cardiac cells from reperfusion injury, but the exact roles of endogenous zinc in the pathogenesis of reperfusion injury and in adenosine A2 receptor activation-induced cardioprotection against reperfusion injury remain unknown. Adenosine A1/A2 receptor agonist 5′-(N-ethylcarboxamido) adenosine (NECA) given at reperfusion reduced infarct size in isolated rat hearts subjected to 30 min ischemia followed by 2 h of reperfusion. This effect of NECA was partially but significantly blocked by the zinc chelator N,N,N′,N′-tetrakis-(2-pyridylmethyl) ethylenediamine (TPEN), and ZnCl2 given at reperfusion mimicked the effect of NECA by reducing infarct size. Total tissue zinc concentrations measured with inductively coupled plasma optical emission spectroscopy (ICPOES) were decreased upon reperfusion in rat hearts and this was reversed by NECA. NECA increased intracellular free zinc during reperfusion in the heart. Confocal imaging study showed a rapid increase in intracellular free zinc in isolated rat cardiomyocytes treated with NECA. Further experiments revealed that NECA increased total zinc levels upon reperfusion in mitochondria isolated from isolated hearts. NECA attenuated mitochondrial swelling upon reperfusion in isolated hearts and this was inhibited by TPEN. Similarly, NECA prevented the loss of mitochondrial membrane potential (ΔΨm) caused by oxidant stress in cardiomyocytes. Finally, both NECA and ZnCl2 inhibited the mitochondrial metabolic activity. NECA-induced cardioprotection against reperfusion injury is mediated by intracellular zinc. NECA prevents reperfusion-induced zinc loss and relocates zinc to mitochondria. The inhibitory effects of zinc on both the mPTP opening and the mitochondrial metabolic activity may account for the cardioprotective effect of NECA

The R Protein of SARS-CoV: Analyses of Structure and Function Based on Four Complete Genome Sequences of Isolates BJ01-BJ04

The R (replicase) protein is the uniquely defined non-structural protein (NSP) responsible for RNA replication, mutation rate or fidelity, regulation of transcription in coronaviruses and many other ssRNA viruses. Based on our complete genome sequences of four isolates (BJ01-BJ04) of SARS-CoV from Beijing, China, we analyzed the structure and predicted functions of the R protein in comparison with 13 other isolates of SARS-CoV and 6 other coronaviruses. The entire ORF (open-reading frame) encodes for two major enzyme activities, RNA-dependent RNA polymerase (RdRp) and proteinase activities. The R polyprotein undergoes a complex proteolytic process to produce 15 function-related peptides. A hydrophobic domain (HOD) and a hydrophilic domain (HID) are newly identified within NSP1. The substitution rate of the R protein is close to the average of the SARS-CoV genome. The functional domains in all NSPs of the R protein give different phylogenetic results that suggest their different mutation rate under selective pressure. Eleven highly conserved regions in RdRp and twelve cleavage sites by 3CLP (chymotrypsin-like protein) have been identified as potential drug targets. Findings suggest that it is possible to obtain information about the phylogeny of SARS-CoV, as well as potential tools for drug design, genotyping and diagnostics of SARS

A multi-wavelength mid-IR laser based on BaGa4Se7 optical parametric oscillators

A multi-wavelength mid-IR laser consisting of 3.05 μm, 4.25 μm, and 5.47 μm BaGa4Se7(BGSe)optical parametric oscillators (OPOs) switched by DKDP electro-optic switches with one 10 Hz/7.6 ns pumping wave is demonstrated. Maximum energies at 3.05 μm, 4.25 μm, and 5.47 μm are 1.35 mJ, 1.03 mJ, and 0.56 mJ, respectively, corresponding to optical-to-optical conversion efficiencies of 9.4%, 7.6%, and 4.2%. To the best of our knowledge, this study is the first of generation of three mid-IR wavelength lasers using electro-optic switches. Furthermore, this study provides a viable solution for a high-energy or high-power, compact, or even portable multi-wavelength mid-IR laser device that employs a single pumping wave

Rare deleterious germline variants and risk of lung cancer

Recent studies suggest that rare variants exhibit stronger effect sizes and might play a crucial role in the etiology of lung cancers (LC). Whole exome plus targeted sequencing of germline DNA was performed on 1045 LC cases and 885 controls in the discovery set. To unveil the inherited causal variants, we focused on rare and predicted deleterious variants and small indels enriched in cases or controls. Promising candidates were further validated in a series of 26,803 LCs and 555,107 controls. During discovery, we identified 25 rare deleterious variants associated with LC susceptibility, including 13 reported in ClinVar. Of the five validated candidates, we discovered two pathogenic variants in known LC susceptibility loci, ATM p.V2716A (Odds Ratio [OR] 19.55, 95%CI 5.04–75.6) and MPZL2 p.I24M frameshift deletion (OR 3.88, 95%CI 1.71–8.8); and three in novel LC susceptibility genes, POMC c.*28delT at 3′ UTR (OR 4.33, 95%CI 2.03–9.24), STAU2 p.N364M frameshift deletion (OR 4.48, 95%CI 1.73–11.55), and MLNR p.Q334V frameshift deletion (OR 2.69, 95%CI 1.33–5.43). The potential cancer-promoting role of selected candidate genes and variants was further supported by endogenous DNA damage assays. Our analyses led to the identification of new rare deleterious variants with LC susceptibility. However, in-depth mechanistic studies are still needed to evaluate the pathogenic effects of these specific alleles