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61.
Anticancer Ruthenium(III) Complex KP1019 Interferes with ATP‐Dependent Ca2+ Translocation by Sarco‐Endoplasmic Reticulum Ca2+‐ATPase (SERCA) 下载免费PDF全文
Fabrizio‐Zagros Sadafi Lara Massai Dr. Gianluca Bartolommei Prof. Maria Rosa Moncelli Prof. Luigi Messori Dr. Francesco Tadini‐Buoninsegni 《ChemMedChem》2014,9(8):1660-1664
Sarco‐endoplasmic reticulum Ca2+‐ATPase (SERCA), a P‐type ATPase that sustains Ca2+ transport and plays a major role in intracellular Ca2+ homeostasis, represents a therapeutic target for cancer therapy. Here, we investigated whether ruthenium‐based anticancer drugs, namely KP1019 (indazolium [trans‐tetrachlorobis(1H‐indazole)ruthenate(III)]), NAMI‐A (imidazolium [trans‐tetrachloro(1H‐imidazole)(S‐dimethylsulfoxide)ruthenate(III)]) and RAPTA‐C ([Ru(η6‐p‐cymene)dichloro(1,3,5‐triaza‐7‐phosphaadamantane)]), and cisplatin (cis‐diammineplatinum(II) dichloride) might act as inhibitors of SERCA. Charge displacement by SERCA adsorbed on a solid‐supported membrane was measured after ATP or Ca2+ concentration jumps. Our results show that KP1019, in contrast to the other metal compounds, is able to interfere with ATP‐dependent translocation of Ca2+ ions. An IC50 value of 1 μM was determined for inhibition of calcium translocation by KP1019. Conversely, it appears that KP1019 does not significantly affect Ca2+ binding to the ATPase from the cytoplasmic side. Inhibition of SERCA at pharmacologically relevant concentrations may represent a crucial aspect in the overall pharmacological and toxicological profile of KP1019. 相似文献
62.
Defined Conjugation of Glycans to the Lysines of CRM197 Guided by their Reactivity Mapping 下载免费PDF全文
Dr. Stefano Crotti Dr. Huili Zhai Dr. Jing Zhou Martin Allan Dr. Daniela Proietti Dr. Werner Pansegrau Dr. Qi‐Ying Hu Dr. Francesco Berti Dr. Roberto Adamo 《Chembiochem : a European journal of chemical biology》2014,15(6):836-843
Systematic characterisation of the reactivity of the lysine moieties in CRM197 towards N‐hydroxysuccinimide linkers bearing alkynes or azides is described. This involves two‐step conjugation of various glycans to CRM197 by click chemistry in a well‐defined manner. By semiquantitative LC‐MS/MS analysis of proteolytic digests of the conjugates formed, the reactivity of lysine residues in the protein was mapped and ranked. Computational analysis of the solvent accessibility of each lysine residue (based on the CRM197 crystal structure) established a correlation between reactivity and surface exposure. By this approach, conjugation involving lysine residues (normally a random process) can be controlled. It enables the preparation of lysine‐mediated glycoconjugates with improved batch‐to‐batch reproducibility, thereby producing neo‐glycoconjugates with more‐consistent biological activity. 相似文献
63.
Roberta D’Ambrosio Alessio Aghemo Raffaele De Francesco Maria Grazia Rumi Enrico Galmozzi Stella De Nicola Cristina Cheroni Paul J. Clark Guido Ronchi Pietro Lampertico Massimo Colombo 《International journal of molecular sciences》2014,15(5):7213-7224
The interleukin 28B (IL28B) rs12979860 polymorphism is associated with treatment outcome in hepatitis C virus (HCV) genotype 1 and 4 patients. Its association with the histological features of chronic hepatitis C and disease severity needs further clarifications. To assess the correlation between IL28B genotype, HCV genotype and liver biopsy findings in untreated patients.
Materials and Methods
Pre-treatment liver biopsies from 335 HCV Caucasian patients (59% males, age 50 years) enrolled in the MIST study were staged for fibrosis and inflammation according to the METAVIR and the Ishak scoring systems; steatosis was dichotomized as <5% or ≥5%. IL28B was typed by Taqman Single Nucleotide Polymorphism (SNP) genotyping assay. HCV genotype was 1 in 151 (45%), 2 in 99 (30%), 3 in 50 (15%) and 4 in 35 (10%) patients. IL28B genotype was CC in 117 (34%), CT in 166 (49%) and TT in 52 (15%). At univariate analysis, the IL28B CC genotype was associated with severe portal inflammation in HCV-1 patients (CC vs. CT/TT: 86% vs. 63%, p = 0.005), severe lobular inflammation in HCV-2 patients (CC vs. CT/TT: 44% vs. 23%, p = 0.03), and less fatty infiltration in HCV-1 patients (CC vs. CT/TT: 72% vs. 51%, p = 0.02). Despite the lack of any association between IL28B and fibrosis stage, in HCV-3 patients IL28B CC correlated with METAVIR F3–F4 (CC vs. CT/TT: 74% vs. 26%, p = 0.05). At multivariate analysis, the genotype CC remained associated with severe portal inflammation in HCV-1, only (Odds Ratio (OR): 95% Confidence Interval (CI): 3.24 (1.23–8.51)). IL28B genotype is associated with the histological features of chronic hepatitis C in a HCV genotype dependent manner, with CC genotype being independently associated with severe portal inflammation. 相似文献64.
Francesco Di Girolamo Alfonsina D’Amato Isabella Lante Fabrizio Signore Marta Muraca Lorenza Putignani 《International journal of molecular sciences》2014,15(9):15396-15411
Due to the incompleteness of animal genome sequencing, the analysis and characterization of serum proteomes of most farm animals are still in their infancy, compared to the already well-documented human serum proteome. This review focuses on the implications of the farm animal serum proteomics in order to identify novel biomarkers for animal welfare, early diagnosis, prognosis and monitoring of infectious disease treatment, and develop new vaccines, aiming at determining the reciprocal benefits for humans and animals. 相似文献
65.
Maximum likelihood estimation of models based on continuous latent variables generally requires to solve integrals that are not analytically tractable. Numerical approximations represent a possible solution to this problem. We propose to use the adaptive Gaussian–Hermite (AGH) numerical quadrature approximation for a particular class of continuous latent variable models for time-series and longitudinal data. These dynamic models are based on time-varying latent variables that follow an autoregressive process of order 1, AR(1). Two examples are the stochastic volatility models for the analysis of financial time series and the limited dependent variable models for the analysis of panel data. A comparison between the performance of AGH methods and alternative approximation methods proposed in the literature is carried out by simulation. Empirical examples are also used to illustrate the proposed approach. 相似文献
66.
Market competition requires that organisations excel at both operational performance and innovation. Though process orientation is intended to benefit operations in general, the impact of specific elements remains unclear. The purpose of this study is to identify the specific organisational design components of process orientation that simultaneously influence operational performance and innovation. We survey employees in the financial services sector (N = 1069) regarding the influence of six process-oriented organisation design components on operational performance and innovation using PLS-SEM. The results indicate that organisational structure and process improvement encourage both operational performance and innovation. Personal autonomy is partially beneficial, while the others have no joint influence on operational performance and innovation. This study is first in providing evidence regarding the influence of a broad variety of organisational design components of process orientation on operational performance and innovation. The study contributes to theory on how process orientation improves operational performance and innovation. The findings can serve as a guideline for managers and organisations as to which organisational design components should be implemented to improve operations. 相似文献
67.
Giovanni Pulci Jacopo Tirillò Francesco Marra Fabrizio Sarasini Alessandra Bellucci Teodoro Valente Cecilia Bartuli 《Metallurgical and Materials Transactions A》2014,45(3):1401-1408
Thermal sprayed MCrAlY coatings are widely used as a bond coat in thermal barrier systems to protect the substrate from corrosion and high temperature oxidation and to improve the compatibility between the ceramic top coat and metallic substrate. In this paper, the high temperature oxidation resistance of MCrAlY coatings with modified compositions was evaluated; in particular, the effect of the addition of reactive and refractory elements (Ta, Re, Si, and Hf) was investigated. MCrAlY coatings were obtained by high velocity oxygen fuel spray and vacuum plasma spray techniques; samples were exposed to air at 1423 K (1150 °C) and the oxidation kinetics were evaluated by measuring the thickness of the thermally grown oxide (TGO) scale at several exposure times. Experimental data confirmed that the oxidation resistance of MCrAlY coatings is strictly related to the amount of the reactive and refractory elements in the starting powders and that a thorough understanding of the microstructural modifications taking place during oxidation is essential for controlling TGO growth and thermal barriers’ durability. 相似文献
68.
Daniela dell'Oro Francesco Casamassima Giuseppe Gesualdo Marco Iammarino Paolo Mambelli Valeria Nardelli 《International Journal of Food Science & Technology》2014,49(5):1391-1400
The aim of this study was to develop and validate an efficient analytical method based on gas chromatography/tandem mass spectrometry (GC/MS/MS) for detection and quantification of six pyrethroids residues (Phenothrin, Permethrin, Cyfluthrin, Cypermethrin, Deltamethrin and Fenvalerate) in chicken eggs. The method was based on a preliminary liquid–liquid extraction of albumen‐free yolk samples, followed by a clean‐up by solid‐phase extraction. GC/MS/MS analyses were carried out in the selected reaction monitoring mode. Validation parameters such as specificity, detection capability, decision limit, precision, recovery, stability and ruggedness were determined, resulting in compliance with Decision 2002/657/EC. No complicated apparatus are required; moreover, low volumes of organic solvents and a nonintensive manual labour are required. These low costs and simple procedure, based on rapid and safe operations, may represent a useful tool in the routine analysis of pyrethroids pesticides, in the place of the currently used conventional techniques. 相似文献
69.
Lucia Padalino Marcella Mastromatteo Lucia Lecce Sara Spinelli Francesco Contò Matteo Alessandro Del Nobile 《International Journal of Food Science & Technology》2014,49(6):1544-1556
The goal of the study was to obtain spaghetti enriched with pea flour with sensory properties close to conventional pasta. To this aim, the study has been organised in two subsequent trials. In the first, the pea flour amount added to the spaghetti was continuously increased until the overall sensory quality reached its threshold value (pea flour concentration = 15%). In fact, the spaghetti samples supplemented with 15% pea flour (15%S‐P) showed less elasticity, unpleasant colour and higher firmness compared to the control sample (CTRL). The second step was aimed to improve the overall sensory quality of the 15%S‐P spaghetti by means of guar gum (GUAR). The sample with GUAR (15%S‐P/GUAR) showed a pleasant colour, odour and taste. Furthermore, the 15%S‐P/GUAR sample recorded a low starch digestibility value (i.e. 54) and a higher soluble fibre content with respect to the 15%S‐P sample. 相似文献
70.