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991.
Li-Fang Chou Yu-Tin Chen Chia-Wei Lu Yi-Ching Ko Chuan-Yi Tang Ming-Jeng Pan Ya-Chung Tian Cheng-Hsun Chiu Cheng-Chieh Hung Chih-Wei Yang 《Gene》2012
Leptospirosis, a widespread zoonosis, is a re-emerging infectious disease caused by pathogenic Leptospira species. In Taiwan, Leptospira santarosai serovar Shermani is the most frequently isolated serovar, causing both renal and systemic infections. This study aimed to generate a L. santarosai serovar Shermani genome sequence and categorize its hypothetical genes, particularly those associated with virulence. The genome sequence consists of 3,936,333 nucleotides and 4033 predicted genes. Additionally, 2244 coding sequences could be placed into clusters of orthologous groups and the number of genes involving cell wall/membrane/envelope biogenesis and defense mechanisms was higher than that of other Leptospira spp. Comparative genetic analysis based on BLASTX data revealed that about 73% and 68.8% of all coding sequences have matches to pathogenic L. interrogans and L. borgpetersenii, respectively, and about 57.6% to saprophyte L. biflexa. Among the hypothetical proteins, 421 have a transmembrane region, 172 have a signal peptide and 17 possess a lipoprotein signature. According to PFAM prediction, 32 hypothetical proteins have properties of toxins and surface proteins mediated bacterial attachment, suggesting they may have roles associated with virulence. The availability of the genome sequence of L. santarosai serovar Shermani and the bioinformatics re-annotation of leptospiral hypothetical proteins will facilitate further functional genomic studies to elucidate the pathogenesis of leptospirosis and develop leptospiral vaccines. 相似文献
992.
Cobra CTX A3, the major cardiotoxin (CTX) from Naja atra, is a cytotoxic, basic β-sheet polypeptide that is known to induce a transient membrane leakage of cardiomyocytes through a sulfatide-dependent CTX membrane pore formation and internalization mechanism. The molecular specificity of CTX A3-sulfatide interaction at atomic levels has also been shown by both nuclear magnetic resonance (NMR) and X-ray diffraction techniques to reveal a role of CTX-induced sulfatide conformational changes for CTX A3 binding and dimer formation. In this study, we investigate the role of sulfatide lipid domains in CTX pore formation by various biophysical methods, including fluorescence imaging and atomic force microscopy, and suggest an important role of liquid-disordered (ld) and solid-ordered (so) phase boundary in lipid domains to facilitate the process. Fluorescence spectroscopic studies on the kinetics of membrane leakage and CTX oligomerization further reveal that, although most CTXs can oligomerize on membranes, only a small fraction of CTXs oligomerizations form leakage pores. We therefore suggest that CTX binding at the boundary between the so and so/ld phase coexistence sulfatide lipid domains could form effective pores to significantly enhance the CTX-induced membrane leakage of sulfatide-containing phosphatidylcholine vesicles. The model is consistent with our earlier observations that CTX may penetrate and lyse the bilayers into small aggregates at a lipid/protein molar ratio of about 20 in the ripple P(β)' phase of phosphatidylcholine bilayers and suggest a novel mechanism for the synergistic action of cobra secretary phospholipase A2 and CTXs. 相似文献
993.
Cheuk-Lun Lee Eve Y. F. Lam Kevin K. W. Lam Hannu Koistinen Markku Sepp?l? Ernest H. Y. Ng William S. B. Yeung Philip C. N. Chiu 《The Journal of biological chemistry》2012,287(44):36999-37009
Macrophages represent the second major type of decidual leukocytes at the fetomaternal interface. Changes in macrophage number and activity are associated with fetal loss and pregnancy complications. Glycodelin-A (GdA) is an abundant glycoprotein in the first-trimester decidua. It is involved in fetomaternal defense and early placental development through its regulatory activities in various immune cells. The N-glycosylation of GdA mediates the binding and therefore the activities of the molecule. In this study, we studied the biological activities of GdA in the functions of human monocytes/macrophages. GdA was purified from amniotic fluid by affinity chromatography. GdA treatment did not affect the viability, cell death, or phagocytic activity of the monocytes/macrophages. GdA, but not recombinant glycodelin without glycosylation, induced IL-6 production as demonstrated by cytokine array, intracellular staining, and ELISA. GdA also induced phosphorylation of ERK in monocytes/macrophages. The involvement of ERKs in IL-6 induction was confirmed using pharmacological inhibitors. Co-immunoprecipitation showed that L-selectin on the monocytes/macrophages was the binding protein of GdA. Treatment with anti-L-selectin antibody reduced GdA binding and GdA-induced IL-6 production. GdA-treated macrophages suppressed IFN-γ expression by co-cultured T-helper cells in an IL-6-dependent manner. These results show that GdA interacts with L-selectin to induce IL-6 production in monocytes/macrophages by activating the ERK signaling pathway. In turn, the increased IL-6 production suppresses IFN-γ expression in T-helper cells, which may play an important role in inducing a Th-2-polarized cytokine environment that flavors the immunotolerance of the fetoplacental unit. 相似文献
994.
The aggregation of proteins or peptides into amyloid fibrils is a hallmark of protein misfolding diseases (e.g., Alzheimer's disease) and is under intense investigation. Many of the experiments performed are in vitro in nature and the samples under study are ordinarily exposed to diverse interfaces, e.g., the container wall and air. This naturally raises the question of how important interfacial effects are to amyloidogenesis. Indeed, it has already been recognized that many amyloid-forming peptides are surface-active. Moreover, it has recently been demonstrated that the presence of a hydrophobic interface can promote amyloid fibrillization, although the underlying mechanism is still unclear. Here, we combine theory, surface property measurements, and amyloid fibrillogenesis assays on islet amyloid polypeptide and amyloid-β peptide to demonstrate why, at experimentally relevant concentrations, the surface activity of the amyloid-forming peptides leads to enriched fibrillization at an air-water interface. Our findings indicate that the key that links these two seemingly different phenomena is the surface-active nature of the amyloid-forming species, which renders the surface concentration much higher than the corresponding critical fibrillar concentration. This subsequently leads to a substantial increase in fibrillization. 相似文献
995.
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997.
Chuah SK Hsu PI Chang KC Chiu YC Wu KL Chou YP Hu ML Tai WC Chiu KW Chiou SS Wu DC Hu TH 《Helicobacter》2012,17(3):216-223
Background: Classical second‐line anti‐Helicobacter pylori includes proton‐pump inhibitor, tetracycline, metronidazole, and bismuth salts, but alternative therapies are required owing to the restricted availability of the latter. Levofloxacin‐containing triple therapy is recommended but is expensive. Besides, quinolone resistance in an endemic tuberculosis infection area like Taiwan is concerned. The low in vitro antibiotic resistance to amoxicillin and tetracycline in Taiwanese H. pylori strains implies that in vivo esomeprazole/amoxicillin/tetracycline (EAT) second‐line rescue therapy may be effective. This study compared the efficacy of esomeprazole/amoxicillin/levofloxacin (EAL) and EAT second‐line eradication therapies and determines the clinical factors influencing the efficacy of salvage regimens. Materials and methods: One hundred and twenty‐eight patients who failed H. pylori eradication using the standard triple therapy for 7 days are randomly assigned to either EAL group (esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, and levofloxacin 500 mg once daily) for 7 days or EAT group (esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, tetracycline 500 mg four times daily) for 14 days. Follow‐up endoscopy or urea breath test was performed 8 weeks later to assess treatment response. Results: The eradication rates of EAL and EAT groups were 78.1 versus 75.0%, p = .676 (in intention‐to‐treat analysis) and 80.3 versus 80%, p = .0964 (per‐protocol analysis). Both groups exhibited similar drug compliance (95.3 vs 96.9%, p = .952) but more adverse events in the EAT group (6.3 vs 12.5%, p = .225). Conclusions: Despite low in vitro drug resistances to amoxicillin and tetracycline, the efficacy of 14‐day EAT regimens attained an unacceptable report card of 75% eradication rates in intention‐to‐treat analysis and was not even superior to the 7‐day EAL regimen. Drug–drug interaction between combined antibiotics should be considered other than in vivo drug resistances. 相似文献
998.
Liang‐da Chiu Françoise Hullin‐Matsuda Toshihide Kobayashi Hajime Torii Hiro‐o Hamaguchi 《Journal of biophotonics》2012,5(10):724-728
The 1602 cm–1 Raman signature, which we call the “Raman spectroscopic signature of life” in yeasts, is a marker Raman band for cell metabolic activity. Despite the established fact that its intensity sensitively reflects the metabolic status of the cell, its molecular origin remained unclear. In this work, we propose ergosterol as the major contributor of the 1602 cm–1 Raman signature. The theoretical isotope shift calculation for ergosterol agreed with previous observations. Furthermore, experiments showed that the Raman spectrum of ergosterol corresponds very well with the depleting spectral component in yeast that behaves together with the 1602 cm–1 signature when the cells are under stress. This work implies that the 1602 cm–1 Raman signature could serve as an intrinsic ergosterol marker in yeasts for the study of sterol metabolism in vivo and in a label‐free manner, which could not be done by any other techniques at the current stage. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) 相似文献
999.
Wu CK Yang CY Lin JW Hsieh HJ Chiu FC Chen JJ Lee JK Huang SW Li HY Chiang FT Chen JJ Tsai CT 《Obesity (Silver Spring, Md.)》2012,20(4):730-737
The purpose of this study was to investigate the associations among central obesity, inflammation, and left ventricular (LV) diastolic dysfunction by structural equation modeling. Echocardiographic parameters were assessed in 102 otherwise-healthy adults over age 30. The participants were classified as having LV diastolic dysfunction by echocardiographic findings including mitral inflow E/A ratio <1, deceleration time >220 cm/s, or decreased peak annular early diastolic velocity in tissue Doppler imaging or otherwise the control group. Serum C-reactive protein (CRP) and lipid profile were also measured. The homeostasis model of insulin resistance (HOMA) was calculated. Central obesity was assessed by computerized tomography (CT) at the L4 level. In a multivariate regression analysis, the relationship between visceral adipose tissue (VAT) and LV diastolic dysfunction became insignificant when CRP was introduced into the model, although CRP itself was significantly associated with LV diastolic dysfunction (odds ratio (OR): 1.32, 95% confidence interval (CI): 1.01-1.72, P = 0.04). A significant correlation was also found between VAT and CRP (r = 0.70; P < 0.001). We then performed path analysis as illustrated by the structural equation model. This proved our hypotheses that VAT might affect LV diastolic dysfunction through the effect of CRP (total fat load with inflammation (B = 1.133, P < 0.001) and that inflammation might affect LV diastolic dysfunction (B = 0.373. P < 0.001)). Using structural equation modeling, we concluded that higher amounts of VAT were associated with low-grade inflammation and this may lead to subclinical LV diastolic dysfunction in otherwise-healthy subjects. 相似文献
1000.
Sophora flavescens is a Chinese medicinal herb used for the treatment of gastrointestinal hemorrhage, skin diseases, pyretic stranguria and viral hepatitis. In this study the herb-drug interactions between S. flavescens and indinavir, a protease inhibitor for HIV treatment, were evaluated in rats. Concomitant oral administration of Sophora extract (0.158 g/kg or 0.63 g/kg, p.o.) and indinavir (40 mg/kg, p.o.) in rats twice a day for 7 days resulted in a dose-dependent decrease of plasma indinavir concentrations, with 55%-83% decrease in AUC(0-∞) and 38%-78% reduction in C(max). The CL (Clearance)/F (fraction of dose available in the systemic circulation) increased up to 7.4-fold in Sophora-treated rats. Oxymatrine treatment (45 mg/kg, p.o.) also decreased indinavir concentrations, while the ethyl acetate fraction of Sophora extract had no effect. Urinary indinavir (24-h) was reduced, while the fraction of indinavir in faeces was increased after Sophora treatment. Compared to the controls, multiple dosing of Sophora extract elevated both mRNA and protein levels of P-gp in the small intestine and liver. In addition, Sophora treatment increased intestinal and hepatic mRNA expression of CYP3A1, but had less effect on CYP3A2 expression. Although protein levels of CYP3A1 and CYP3A2 were not altered by Sophora treatment, hepatic CYP3A activity increased in the Sophora-treated rats. All available data demonstrated that Sophora flavescens reduced plasma indinavir concentration after multiple concomitant doses, possibly through hepatic CYP3A activity and induction of intestinal and hepatic P-gp. The animal study would be useful for predicting potential interactions between natural products and oral pharmaceutics and understanding the mechanisms prior to human studies. Results in the current study suggest that patients using indinavir might be cautioned in the use of S. flavescens extract or Sophora-derived products. 相似文献