934 research outputs found

    Change of glaciers in Spitsbergen Island since 1933 observed with surface photographs

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    Change of several glaciers in Spitsbergen Island was investigated using surface photographs taken in 1933 and afterward. All glaciers investigated decreased their thickness and area at their terminal parts in the period from 1933 to 2004

    siRNA-dependent and -independent post-transcriptional cosuppression of the LTR-retrotransposon MAGGY in the phytopathogenic fungus Magnaporthe oryzae

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    The LTR-retrotransposon MAGGY was introduced into naive genomes of Magnaporthe oryzae with different genetic backgrounds (wild-type, and MoDcl1 [mdl1] and MoDcl2 [mdl2] dicer mutants). The MoDcl2 mutants deficient in MAGGY siRNA biogenesis generally showed greater MAGGY mRNA accumulation and more rapid increase in MAGGY copy number than did the wild-type and MoDcl1 mutants exhibiting normal MAGGY siRNA accumulation, indicating that RNA silencing functioned as an effective defense against the invading element. Interestingly, however, regardless of genetic background, the rate of MAGGY transposition drastically decreased as its copy number in the genome increased. Notably, in the MoDcl2 mutant, copy-number-dependent MAGGY suppression occurred without a reduction in its mRNA accumulation, and therefore by a silencing mechanism distinct from both transcriptional gene silencing and siRNA-mediated RNA silencing. This might imply that some mechanism possibly similar to post-transcriptional cosuppression of Ty1 retrotransposition in Saccharomyces cerevisiae, which operates regardless of the abundance of target transcript and independent of RNA silencing, would also function in M. oryzae that possesses the RNA silencing machinery

    Smad3 Phospho-Isoform Signaling in Nonalcoholic Steatohepatitis

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    Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis with insulin resistance, oxidative stress, lipotoxicity, adipokine secretion by fat cells, endotoxins (lipopolysaccharides) released by gut microbiota, and endoplasmic reticulum stress. Together, these factors promote NAFLD progression from steatosis to nonalcoholic steatohepatitis (NASH), fibrosis, and eventually end-stage liver diseases in a proportion of cases. Hepatic fibrosis and carcinogenesis often progress together, sharing inflammatory pathways. However, NASH can lead to hepatocarcinogenesis with minimal inflammation or fibrosis. In such instances, insulin resistance, oxidative stress, and lipotoxicity can directly lead to liver carcinogenesis through genetic and epigenetic alterations. Transforming growth factor (TGF)-β signaling is implicated in hepatic fibrogenesis and carcinogenesis. TGF-β type I receptor (TβRI) and activated-Ras/c-Jun-N-terminal kinase (JNK) differentially phosphorylate the mediator Smad3 to create two phospho-isoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). TβRI/pSmad3C signaling terminates cell proliferation, while constitutive Ras activation and JNK-mediated pSmad3L promote hepatocyte proliferation and carcinogenesis. The pSmad3L signaling pathway also antagonizes cytostatic pSmad3C signaling. This review addresses TGF-β/Smad signaling in hepatic carcinogenesis complicating NASH. We also discuss Smad phospho-isoforms as biomarkers predicting HCC in NASH patients with or without cirrhosis

    Smad Phospho-Isoforms for Hepatocellular Carcinoma Risk Assessment in Patients with Nonalcoholic Steatohepatitis

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    Nonalcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) sometimes occurs in mildly fibrotic livers, while HCC incidence in NASH-related cirrhosis is lower than and less predictable than in hepatitis C virus (HCV)-related cirrhosis. Transforming growth factor (TGF)-β signaling in hepatocytic nuclei is implicated in fibrosis and carcinogenesis. TGF-βtype I receptor (TβRI) and c-Jun N-terminal kinase (JNK) differentially phosphorylate the mediator Smad3, resulting in 2 distinct phospho-isoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). In mature hepatocytes, oncogenic signaling via the JNK/pSmad3L pathway antagonizes signaling via the tumor-suppressive TβRI/pSmad3C pathway. We immunohistochemically examined domain-specific Smad3 phosphorylation in liver biopsy specimens from 30 NASH patients representing different fibrotic stages and 20 chronically infected hepatitis C patients as controls, correlating Smad3 phosphorylation with clinical course. HCC occurred during follow-up in 11 of 12 NASH patients with abundant pSmad3L and limited pSmad3C but in only 2 of 18 with limited pSmad3L. In contrast, HCC developed in 12 of 15 NASH patients with limited pSmad3C but only 1 of 15 with abundant pSmad3C. Two of fourteen NASH patients with mild fibrosis developed HCC, their hepatocytic nuclei showed abundant pSmad3L and limited pSmad3C. Five of sixteen patients with severe fibrosis did not develop HCC, their hepatocytic nuclei showed limited pSmad3L and abundant pSmad3C. Smad phospho-isoforms may represent important biomarkers predicting HCC in NASH and potential therapeutic targets for preventing NASH-related HCC

    The effect of celecoxib for treatment of preterm labor on fetuses during the second trimester of pregnancy: A pilot case series

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    OBJECTIVE: Although cyclooxygenase inhibitors effectively suppress uterine contraction, constriction of the fetal ductus arteriosus (DA) and oligohydramnios are major concerns. Celecoxib, a selective cyclooxygenase 2 inhibitor, is a potential potent tocolytic agent, but there are no studies that have evaluated the beneficial or adverse effects of celecoxib use on fetuses for more than 48 hours in pregnant women. We therefore aimed to evaluate the effect of middle-long-term celecoxib administration on the fetus during the second trimester of pregnancy, particularly in terms of fetal DA and amniotic fluid volume. MATERIALS AND METHODS: We retrospectively extracted and reviewed data from patients with preterm labor who received celecoxib for tocolysis for more than 48 hours between 2016 and 2020. Celecoxib was used for tocolysis only when treatment of patients with conventional tocolytic agents was ineffective. Data on the peak systolic velocity in ductus arteriosus (PSV-DA) and the maximum vertical pocket (MVP) were collected. RESULTS: A total of 15 patients were eligible. The median gestational age at celecoxib introduction was 22.6 weeks, and the median period of administration was 9 days (range 3-40 days). The median gestational age at delivery was 27.1 weeks, and the median duration from initial celecoxib administration to delivery was 40 days. The Z scores of PSV-DA and MVP did not change significantly after celecoxib administration. During administration, PSV-DA exceeded the 95th percentile of the corresponding normal reference range in three cases, but the levels returned to normal after reduction or discontinuation of treatment. There was no oligohydramnios during the treatment. CONCLUSION: Celecoxib administration for more than 48 hours in the second trimester of pregnancy might be safe and tolerable in terms of fetal PSV-DA and amniotic fluid volume as long as careful ultrasound monitoring is performed. Celecoxib could be an alternative for preterm labor when conventional tocolysis is not effective

    Development of a Time Projection Chamber Using Gas Electron Multipliers (GEM-TPC)

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    We developed a prototype time projection chamber using gas electron multipliers (GEM-TPC) for high energy heavy ion collision experiments. To investigate its performance, we conducted a beam test with 3 kinds of gases (Ar(90%)-CH4(10%), Ar(70%)-C2H6(30%) and CF4). Detection efficiency of 99%, and spatial resolution of 79 μ\mum in the pad-row direction and 313 μ\mum in the drift direction were achieved. The test results show that the GEM-TPC meets the requirements for high energy heavy ion collision experiments. The configuration and performance of the GEM-TPC are described.Comment: 18 pages, 12 figures, published online in Nucl. Instr. and Meth.

    Hydrothermal Friction Experiments on Simulated Basaltic Fault Gouge and Implications for Megathrust Earthquakes

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    Nucleation of earthquake slip at the plate boundary fault (décollement) in subduction zones has been widely linked to the frictional properties of subducting sedimentary facies. However, recent seismological and geological observations suggest that the décollement develops in the subducting oceanic crust in the depth range of the seismogenic zone, at least in some cases. To understand the frictional properties of oceanic crustal material and their influence on seismogenesis, we performed hydrothermal friction experiments on simulated fault gouges of altered basalt, at temperatures of 100–550°C. The friction coefficient (μ) lies around 0.6 at most temperature conditions but a low μ down to 0.3 was observed at the highest temperature and lowest velocity condition. The velocity dependence of μ, (a−b), changes with increasing temperature from positive to negative at ∼100°C and from negative to positive at ∼450°C. Compared to gouges derived from sedimentary facies, the altered basalt gouge showed potentially unstable velocity weakening over a wider temperature range. Microstructural observations and microphysical interpretation infer that competition between dilatant granular flow and viscous compaction through pressure-solution creep of albite contributed to the observed transition in (a−b). Alteration of oceanic crust during subduction produces fine grains of albite and chlorite through interactions with interstitial water, leading to reduction in its frictional strength and an increase in its seismogenic potential. Therefore, shear deformation possibly localizes within the altered oceanic crust leading to a larger potential for the nucleation of a megathrust earthquake in the depth range of the seismogenic zone

    Effect of Configuration of Micro-/Nanoscale Structure on Sliding Surface on Molecular Gas-Film Lubrication

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    Abstract. Nakamori et al. found experimentally that the friction between a partly polished diamond coating and a metal surface was drastically reduced to zero as relative speed increased to a few m/s [Diamond Relat. Mater. 14, (2005), 2122]. It seems that diamond coating took off the counter surface because sliding was noiseless in their experiment. However, the mechanism of this phenomenon was unknown. In the previous work, we performed the numerical simulation of micro-/nanoscale gas flow between two sliding surfaces, i. e., the slider surface with microscale surface roughness like partly polished diamond coating and the flat counter surface. And then, we successfully reproduced lift force large enough to suspend the slider used in the experiment and found that this effect became notable only for micro-/nanoscale gas flow. In the present paper, we investigate the effect of configuration of micro-/nanoscale structure on sliding surface on molecular gas-film lubrication. Since micro-/nanoscale gas flows between two sliding surfaces cannot be treated as a continuum, we use the direct simulation Monte Carlo (DSMC) method

    Effect of Configuration of Micro-/Nanoscale Structure on Sliding Surface on Molecular Gas-Film Lubrication

    Get PDF
    Abstract. Nakamori et al. found experimentally that the friction between a partly polished diamond coating and a metal surface was drastically reduced to zero as relative speed increased to a few m/s [Diamond Relat. Mater. 14, (2005), 2122]. It seems that diamond coating took off the counter surface because sliding was noiseless in their experiment. However, the mechanism of this phenomenon was unknown. In the previous work, we performed the numerical simulation of micro-/nanoscale gas flow between two sliding surfaces, i. e., the slider surface with microscale surface roughness like partly polished diamond coating and the flat counter surface. And then, we successfully reproduced lift force large enough to suspend the slider used in the experiment and found that this effect became notable only for micro-/nanoscale gas flow. In the present paper, we investigate the effect of configuration of micro-/nanoscale structure on sliding surface on molecular gas-film lubrication. Since micro-/nanoscale gas flows between two sliding surfaces cannot be treated as a continuum, we use the direct simulation Monte Carlo (DSMC) method
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