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991.
Rangappa S. Keri Catarina Quintanova Sérgio M. Marques A. Raquel Esteves Sandra M. Cardoso M. Amélia Santos 《Bioorganic & medicinal chemistry》2013,21(15):4559-4569
Alzheimer’s disease (AD) is a multifactorial disorder with several target proteins contributing to its etiology. In search for multifunctional anti-AD drug candidates, taking into account that the acetylcholinesterase (AChE) and beta-amyloid (Aβ) aggregation are particularly important targets for inhibition, the tacrine and benzothiazole (BTA) moieties were conjugated with suitable linkers in a novel series of hybrids. The designed compounds (7a–7e) were synthesized and in vitro as well as in ex vivo evaluated for their capacity for the inhibition of acetylcholinesterase (AChE) and Aβ self-induced aggregation, and also for the protection of neuronal cells death (SHSY-5Y cells, AD and MCI cybrids). All the tacrine–BTA hybrids displayed high in vitro activities, namely with IC50 values in the low micromolar to sub-micromolar concentration range towards the inhibition of AChE, and high percentages of inhibition of the self-induced Aβ aggregation. Among them, compound 7a, with the shortest linker, presented the best inhibitory activity of AChE (IC50 = 0.34 μM), while the highest activity as anti-Aβ42 self-aggregation, was evidenced for compound 7b (61.3%, at 50 μM. The docking studies demonstrated that all compounds are able to interact with both catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. Our results show that compounds 7d and 7e improved cell viability in cells treated with Aβ42 peptide. Overall, these multi-targeted hybrid compounds appear as promising lead compounds for the treatment of Alzheimer’s disease. 相似文献
992.
Amélie Ducret Maurice Bouity-Voubou Frédérique Duthoit Erin Norton Pierre Pepin Denis Groleau 《Biocatalysis and Biotransformation》2013,31(1):84-91
The synthesis of inosine from nonactivated and nonprotected ribose and hypoxanthine was performed by enzyme-catalyzed condensation, using a nucleoside hydrolase from Crithidia fasciculata expressed in Escherichia coli with a synthetic gene. One round of directed evolution was performed in the presence of dimethylformamide, used to lower the water activity in the reaction media, leading to a double mutant (Asp54Asn, Arg137Gly). It afforded a doubling of the specificity constant for the hydrolysis of p-nitrophenol-β-d-riboside in the presence of 40% acetonitrile. In aqueous conditions, concentrations of 0.1 and 0.2 mM inosine were obtained, starting from 25 mM hypoxanthine and 2 or 3 M ribose, respectively. With 20% acetonitrile increases of 95% and 60% were observed. These conversions are very low, and the work exemplifies the difficulties encountered when trying to define conditions for hydrolase-catalyzed condensation and at the same time evolve an enzyme to perform well in these a priori unknown conditions. 相似文献
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Aims
To contribute new evidence to the controversy about the factor structure of the Eating Disorder Examination Questionnaire (EDE-Q) and to provide, for the first time, norms based on a large adolescent Mexican community sample, regarding sex and area of residence (urban/rural).Methods
A total of 2928 schoolchildren (1544 females and 1384 males) aged 11-18 were assessed with the EDE-Q and other disordered eating questionnaire measures.Results
Confirmatory factor analysis of the attitudinal items of the EDE-Q did not support the four theorized subscales, and a two-factor solution, Restraint and Eating-Shape-Weight concern, showed better fit than the other models examined (RMSEA = .054); measurement invariance for this two-factor model across sex and area of residence was found. Satisfactory internal consistency (ω ≥ .80) and two-week test-retest reliability (ICCa ≥ .84; κ ≥ .56), and evidence for convergent validity with external measures was obtained. The highest attitudinal EDE-Q scores were found for urban females and the lowest scores were found for rural males, whereas the occurrence of key eating disorder behavioural features and compensatory behaviours was similar in both areas of residence.Conclusions
This study reveals satisfactory psychometric properties and provides population norms of the EDE-Q, which may help clinicians and researchers to interpret the EDE-Q scores of adolescents from urban and rural areas in Mexico. 相似文献996.
Gregory Simon Céline Lano? Nicolas Poirel Sandrine Rossi Amélie Lubin Arlette Pineau Olivier Houdé 《PloS one》2013,8(12)
Although the functional brain network involved in reading for adults and children is now well documented, a critical lack of knowledge still exists about the structural development of these brain areas. To provide a better overview of the structural dynamics of the brain that sustain reading acquisition, we acquired anatomical MRI brain images from 55 children that were divided into two groups: one prior to the formal learning of reading (n = 33, 5–6 years old) and the second a few years after formal learning (n = 22, 9–10 years old). Reading performances were collected based on the “Alouette-R” test, a standardized test for reading text in French. Voxel-based morphometry analysis of gray matter showed that only the right insula volume was different between the two groups. Moreover, the reading group showed that the volumes of the left fusiform gyrus (corresponding to the well-known visual word form area, VWFA), the anterior part of the left inferior occipital gyrus and the left thalamus were significantly modulated by reading performance. This study reinforces the crucial role of the Visual Word Form Area in reading and correlation analyses performed between ROIs volumes suggesting that the VWFA is fully connected with the traditional left-hemispheric language brain network. 相似文献
997.
Mario A. Rodríguez-Pérez Monsuru A. Adeleke Nathan D. Burkett-Cadena Javier A. Garza-Hernández Filiberto Reyes-Villanueva Eddie W. Cupp Laurent Toé Mario C. Salinas-Carmona Américo D. Rodríguez-Ramírez Charles R. Katholi Thomas R. Unnasch 《PloS one》2013,8(10)
Background
Human landing collections are currently the standard method for collecting onchocerciasis vectors in Africa and Latin America. As part of the efforts to develop a trap to replace human landing collections for the monitoring and surveillance of onchocerciasis transmission, comprehensive evaluations of several trap types were conducted to assess their ability to collect Simulium ochraceum sensu lato, one of the principal vectors of Onchocerca volvulus in Latin America.Methodology/Principal Findings
Diverse trap designs with numerous modifications and bait variations were evaluated for their abilities to collect S. Ochraceum s.l. females. These traps targeted mostly host seeking flies. A novel trap dubbed the “Esperanza window trap” showed particular promise over other designs. When baited with CO2 and BG-lure (a synthetic blend of human odor components) a pair of Esperanza window traps collected numbers of S. Ochraceum s.l. females similar to those collected by a team of vector collectors.Conclusions/Significance
The Esperanza window trap, when baited with chemical lures and CO2 can be used to collect epidemiologically significant numbers of Simulium ochraceum s.l., potentially serving as a replacement for human landing collections for evaluation of the transmission of O. volvulus. 相似文献998.
Marilia Freitas Calmon Manlio Tasso de Oliveira Mota érica Babeto Natália Maria Candido Ana Paula Girol Carlos Fabian Mendiburu Jane Lopes Bonilha Rodrigo Vellasco Duarte Silvestre Bruno Miziara Rosa Jorge Alberto Thomé Gustavo Hernandez Américo Medeiros Fernando Augusto Soares Gustavo Cardoso Guimar?es José Germano Ferraz de Arruda Sonia Maria Oliani Luisa Lina Villa José Vassallo Paula Rahal 《PloS one》2013,8(1)
The incidence of penile cancer varies between populations but is rare in developed nations. Penile cancer is associated with a number of established risk factors and associated diseases including phimosis with chronic inflammation, human papillomavirus (HPV) infection, poor hygiene and smoking. The objective of this study was to identify genes related to this type of cancer. The detection of HPV was analyzed in 47 penile squamous cell carcinoma samples. HPV DNA was detected in 48.9% of penile squamous cell carcinoma cases. High-risk HPV were present in 42.5% of cases and low-risk HPV were detected in 10.6% of penile squamous cell carcinomas. The RaSH approach identified differential expression of Annexin A1 (ANXA1), p16, RPL6, PBEF1 and KIAA1033 in high-risk HPV positive penile carcinoma; ANXA1 and p16 were overexpressed in penile squamous cells positive for high-risk HPVs compared to normal penile samples by qPCR. ANXA1 and p16 proteins were significantly more expressed in the cells from high-risk HPV-positive penile carcinoma as compared to HPV-negative tumors (p<0.0001) independently of the subtype of the carcinoma. Overexpression of ANXA1 might be mediated by HPV E6 in penile squamous cell carcinoma of patients with high-risk HPVs, suggesting that this gene plays an important role in penile cancer. 相似文献
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Estimation of microbial contamination of food from prevalence and concentration data: application to Listeria monocytogenes in fresh vegetables 总被引:1,自引:0,他引:1
A normal distribution and a mixture model of two normal distributions in a Bayesian approach using prevalence and concentration data were used to establish the distribution of contamination of the food-borne pathogenic bacteria Listeria monocytogenes in unprocessed and minimally processed fresh vegetables. A total of 165 prevalence studies, including 15 studies with concentration data, were taken from the scientific literature and from technical reports and used for statistical analysis. The predicted mean of the normal distribution of the logarithms of viable L. monocytogenes per gram of fresh vegetables was -2.63 log viable L. monocytogenes organisms/g, and its standard deviation was 1.48 log viable L. monocytogenes organisms/g. These values were determined by considering one contaminated sample in prevalence studies in which samples are in fact negative. This deliberate overestimation is necessary to complete calculations. With the mixture model, the predicted mean of the distribution of the logarithm of viable L. monocytogenes per gram of fresh vegetables was -3.38 log viable L. monocytogenes organisms/g and its standard deviation was 1.46 log viable L. monocytogenes organisms/g. The probabilities of fresh unprocessed and minimally processed vegetables being contaminated with concentrations higher than 1, 2, and 3 log viable L. monocytogenes organisms/g were 1.44, 0.63, and 0.17%, respectively. Introducing a sensitivity rate of 80 or 95% in the mixture model had a small effect on the estimation of the contamination. In contrast, introducing a low sensitivity rate (40%) resulted in marked differences, especially for high percentiles. There was a significantly lower estimation of contamination in the papers and reports of 2000 to 2005 than in those of 1988 to 1999 and a lower estimation of contamination of leafy salads than that of sprouts and other vegetables. The interest of the mixture model for the estimation of microbial contamination is discussed. 相似文献