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Almonacid-Urrego C.C.,University of Leon | Almonacid-Urrego C.C.,University College of Cundinamarca | Sanchez-Campos S.,University of Leon | Tunon M.J.,University of Leon | Gonzalez-Gallego J.,University of Leon
Current Medicinal Chemistry | Year: 2012

Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of abnormal liver function and correlates with central adiposity, obesity, insulin resistance, the metabolic syndrome and type 2 diabetes mellitus. The pathological spectrum of NAFLD ranges from fatty liver to non-alcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and even hepatocellular carcinoma. Though NAFLD and NASH are becoming a major public health problem, ethical constraints on obtaining human liver tissue limit the interpretability of the data and the ability to delineate cause and effect from complex, interactive disease pathogenic pathways. Animal models of NASH can provide critical information leading to identify potential drug targets and to understand their molecular mechanisms, and are platforms for compound screening in drug development and for the assessment of novel therapeutic strategies. This review is aimed to offer an updated overview of the nutritional, genetic and pharmacologic animal models of NASH. Though the information derived from these models has clear relevance for the comprehension of the molecular basis of human disease, most of them fail to reproduce the full spectrum of liver pathology and the metabolic context that characterizes human NASH. Consequently, it is necessary to establish animal models that can best mimic the actual etiology, progression, and pathogenesis of the disease, and prove effectiveness for examining and selecting compounds with potential therapeutic benefit in NASH. © 2012 Bentham Science Publishers.

Gomez J.E.C.,National University of Colombia | Lopez-Pazos S.A.,National University of Colombia | Lopez-Pazos S.A.,University College of Cundinamarca | Ceron J.,National University of Colombia
Journal of Invertebrate Pathology | Year: 2012

An emergent pest is the weevil Asymmathetes vulcanorum, an insect that attacks Colombian potato areas. Here, some Cry proteins from the entomopathogenic bacteria Bacillus thuringiensis were evaluated as biological control strategy. It was found that Cry1B protoxin caused a mortality of 40% with a dose of 8000ng/cm2. Also in this research, it was identified a full length cDNA of an aminopeptidase N, a possible Cry protein receptor located in the insect midgut. This is the first report about B. thuringiensis as an alternative method for control of A. vulcanorum in Colombia. © 2012 Elsevier Inc.

Scott K.M.,University of Otago | Von Korff M.,Group Health Research Institute | Angermeyer M.C.,Center for Public Mental Health | Benjet C.,National Institute of Psychiatry | And 8 more authors.
Archives of General Psychiatry | Year: 2011

Context: The physical health consequences of childhood psychosocial adversities may be as substantial as the mental health consequences, but whether this is the case remains unclear because much prior research has involved unrepresentative samples and a selective focus on particular adversities or physical outcomes. The association between early-onset mental disorders and subsequent poor physical health in adulthood has not been investigated. Objective: To investigate whether childhood adversities and early-onset mental disorders are independently associated with increased risk of a range of adult-onset chronic physical conditions in culturally diverse samples spanning the full adult age range. Design: Cross-sectional community surveys of adults in 10 countries. Setting: General population. Participants: Adults (ie, aged ≥18 years; N=18 303), with diagnostic assessment and determination of age at onset of DSM-IV mental disorders, assessment of childhood familial adversities, and age of diagnosis or onset of chronic physical conditions. Main Outcome Measures: Risk (ie, hazard ratios) of adult-onset (ie, at age >20 years) heart disease, asthma, diabetes mellitus, arthritis, chronic spinal pain, and chronic headache as a function of specific childhood adversities and early-onset (ie, at age >21 years) DSM-IV depressive and anxiety disorders, with mutual adjustment. Results: A history of 3 or more childhood adversities was independently associated with onset of all 6 physical conditions (hazard ratios, 1.44 to 2.19). Controlling for current mental disorder made little difference to these associations. Early-onset mental disorders were independently associated with onset of 5 physical conditions (hazard ratios, 1.43 to 1.66). Conclusions: These results are consistent with the hypothesis that childhood adversities and early-onset mental disorders have independent, broad-spectrum effects that increase the risk of diverse chronic physical conditions in later life. They require confirmation in a prospectively designed study. The long course of these associations has theoretical and research implications. ©2011 American Medical Association. All rights reserved.

Ramirez F.,University College of Cundinamarca | Davenport T.L.,Vivafresh Technologies | Fischer G.,National University of Colombia | Pinzon J.C.A.,National University of Education of Colombia | Ulrichs C.,Humboldt University of Berlin
Scientia Horticulturae | Year: 2014

We propose a convenient, easily observable set of landmark developmental stages during vegetative and flowering flushes and fruiting events to characterize the changes through which individual growing mango shoots pass in the tropics and subtropics. Individual non-growing stems are in the Resting stage (R), when the apical bud (following a previous vegetative growth event) or lateral buds (following a previous flowering event) are dormant. A flush event is one in which the resting buds on many stems in a section of tree canopy initiate growth (asynchronous flush) or when the entire canopy initiates bud growth at once (synchronous flush). The stages describing vegetative shoot growth are: Vegetative Bud Emergence and Development stage, Elongating Green Leaf stage, Limp Red Leaf stage (LRL), Immature Green Leaf stage, and Mature Green Leaf stage. Reproductive growth stages in purely flowering, or generative, shoots are: Floral Bud Initiation, Emergence and Development stage, Early Panicle Elongation stage, Mid-size Panicle Early Anthesis stage, and Full-size Panicle Maximum Anthesis stage. Fruiting stages are: Emergent Fruit stage, Small-size Green Fruit stage, Mid-size Green Fruit stage, Near Full-size Immature Fruit stage, and the Full-size Mature Fruit stage. Mixed shoots, bearing both leaves and lateral inflorescences at each node, exhibit characteristics of both vegetative and flowering shoots. Landmark stages for Tommy Atkins and Keitt, two cultivars commercially growing in the Americas, were observed in tropical orchards near the village of La Mesa, Colombia. Tommy Atkins leaves had a more intense red coloration during the LRL than did 'Keitt'. More pedicels were found in 'Tommy Atkins' than in 'Keitt' during panicle development. Young fruits of 'Tommy Atkins' developed their distinctive, dark red coloration, whereas 'Keitt' fruit developed less intense reddish coloration once they were mature. Aside from these minor phenotypic differences in distinctive shoot and stem developmental stages, attempts to ascribe a distinct phenological pattern of mango tree growth and development are impractical. Each stem terminal or groups of stem terminals borne on scaffolding branches act as independent structures influenced by environmental conditions, such as temperature, water relations, and nutrition coupled with their physiological age resulting in widely variable tree responses even in similar environments. © 2014 Elsevier B.V.

Olarte-Avellaneda S.,University College of Cundinamarca | Olarte-Avellaneda S.,Pontifical Xavierian University | Rodriguez-Lopez A.,Pontifical Xavierian University | Almeciga-Diaz C.J.,Pontifical Xavierian University | Barrera L.A.,Pontifical Xavierian University
Molecular Biology Reports | Year: 2014

Mucopolysaccharidosis IV A (MPS IV A) is a lysosomal storage disease produced by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) enzyme. Although genotype–phenotype correlations have been reported, these approaches have not enabled to establish a complete genotype–phenotype correlation, and they have not considered a ligand–enzyme interaction. In this study, we expanded the in silico evaluation of GALNS mutations by using several bioinformatics tools. Tertiary GALNS structure was modeled and used for molecular docking against galactose-6-sulfate, N-acetylgalactosamine-6-sulfate, keratan sulfate, chondroitin-6-sulfate, and the artificial substrate 4-methylumbelliferyl-β-d-galactopyranoside-6-sulfate. Furthermore, we considered the evolutionary residue conservation, change conservativeness, position within GALNS structure, and the impact of amino acid substitution on the structure and function of GALNS. Molecular docking showed that amino acids involved in ligand interaction correlated with those observed in other human sulfatases, and mutations within the active cavity reduced affinity of all evaluated ligands. Combination of several bioinformatics approaches allowed to explaine 90 % of the missense mutations affecting GALNS, and the prediction of the phenotype for another 21 missense mutations. In summary, we have shown for the first time a docking evaluation of natural and artificial ligands for human GALNS, and proposed an update in genotype–phenotype correlation for Morquio A, based on the use of multiple parameters to predict the disease severity. © 2014, Springer Science+Business Media Dordrecht.

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