在大学系统中实施与LMS的学术管理一体化模式

La calidad de la educación superior de un país es un pilar fundamental para su desarrollo; ello implica reestructurar y autoevaluar programas de estudios, así como sistematizar los procesos académicos. La Universidad Católica Santo Toribio de Mogrovejo, en respuesta a estos retos y a las normativas nacionales de calidad, el Sistema Nacional de Evaluación, Acreditación y Certificación de Calidad Educativa (SINEACE) y la Superintendencia Nacional de Educación Superior Universitaria (SUNEDU), incorporó mejoras en los procesos académicos con el uso de Tecnologías de la Información. La presente investigación muestra resultados de la experiencia de implementación de un modelo integrado de gestión académica con los Learning Management Systems (LMS) en un contexto universitario y se explican las diversas fases que conformaron esta propuesta. El estudio corresponde a una investigación tecnológica aplicada con enfoque cuantitativo, la muestra fue censal complementándose con la técnica focus group y la aplicación de entrevistas semiestructuradas. Los resultados más importantes indican que: La implementación del modelo integrado de las plataformas tecnológicas dentro del Campus Virtual (Sistema de Enseñanza-Aprendizaje, Sistema de Gestión Académica y Sistema de Gestión Curricular) e integración de los LMS permiten evidenciar los niveles de logro de las competencias del perfil de egreso y el despliegue del sistema integrado de gestión académica con LMS y brinda un significativo soporte a las actividades del proceso de enseñanza-aprendizaje en USAT

Metabolic control analysis for drug target selection against human diseases

For identification of suitable therapeutic targets (enzymes/transporters) in intermediary metabolism of pathological and parasitic cells, the capacity of the target to govern the metabolic pathway flux should be considered. Metabolic Control Analysis (MCA) is a biochemical framework that enables to quantitate the degree of control that the activity of a target i (ai) exerts on the pathway flux (J), defined as flux control coefficient (CJai). Different experimental strategies are being used to determine the CJai of individual pathway steps, and consequently, the distribution of control in the metabolic pathway. By applying MCA, the components with the highest control on flux can be identified, which are the targets with the highest therapeutic potential. In this chapter we will review the MCA theoretical principles and experimental approaches to determine the CJai in a range of metabolic pathways such as central carbon and antioxidant metabolism, with potential application to other pathways of diverse human diseases

Inhibition of Non-flux-Controlling Enzymes Deters Cancer Glycolysis by Accumulation of Regulatory Metabolites of Controlling Steps

Glycolysis provides precursors for the synthesis of macromolecules and may contribute to the ATP supply required for the constant and accelerated cellular duplication in cancer cells. In consequence, inhibition of glycolysis has been reiteratively considered as an anti-cancer therapeutic option. In previous studies, kinetic modeling of glycolysis in cancer cells allowed the identification of the main steps that control the glycolytic flux: glucose transporter, hexokinase (HK), hexose phosphate isomerase (HPI) and glycogen degradation in human cervix HeLa cancer cells and rat AS-30D ascites hepatocarcinoma. It was also previously experimentally determined that simultaneous inhibition of the non-controlling enzymes lactate dehydrogenase (LDH), pyruvate kinase (PYK) and enolase (ENO) brings about significant decrease in the glycolytic flux of cancer cells and accumulation of intermediate metabolites, mainly fructose-1,6-bisphosphate (Fru1,6BP) and dihydroxyacetone phosphate (DHAP), which are inhibitors of HK and HPI, respectively. Here it was found by kinetic modeling that inhibition of cancer glycolysis can be attained by blocking downstream non flux-controlling steps as long as Fru1,6BP and DHAP, regulatory metabolites of flux-controlling enzymes, are accumulated. Furthermore, experimental results and further modeling showed that oxamate and iodoacetate inhibitions of PYK, ENO and glyceraldehyde3-phosphate dehydrogenase (GAPDH), but not of LDH and phosphoglycerate kinase, induced accumulation of Fru1,6BP and DHAP in AS-30D hepatoma cells. Indeed, PYK, ENO and GAPDH exerted the highest control on the Fru1,6BP and DHAP concentrations. The high levels of these metabolites inhibited HK and HPI and led to glycolytic flux inhibition, ATP diminution and accumulation of toxic methylglyoxal. Hence, the anticancer effects of downstream glycolytic inhibitors are very likely mediated by this mechanism. In parallel, it was also found that uncompetitive inhibition of the flux-controlling steps is a more potent mechanism than competitive and mixed-type inhibition to efficiently perturb cancer glycolysis

ProVACAT: Practising or viewing art cognitive ability trial: A collaboration between the Ben Uri Gallery and Museum and Hammerson House Care Home (2015/16)

Art Engagement to Slow Cognitive Impairment and Improve Wellbeing. As the UK National Health Service strives to support an ageing population with increased life expectancy we see a rise in social prescribing. Our ambition is to conduct a randomised, long-term intervention assessing the potential for arts engagement to slow expected cognitive decline and improve wellbeing. We identified a residential care home with the appropriate facilities and support for a feasibility study. Our intervention sees Group A receive practical art sessions exploring new materials and techniques. Group B receive seminars responding to replica artworks with open discussion. Participant wellbeing was measured immediately following each session using the UCL Museum Wellbeing Measures Toolkit. Over twelve weeks, two groups of four participants, each with an average age of 93 attended one hour creative sessions and seminars respectively. The results demonstrate a positive variability of outcomes with different wellbeing responses between the two groups at this early stage. They mark the potential for more ambitious projects, addressing a larger group of participants with greater measurement of cognitive function under a randomised controlled trial. The project seeks to achieve a generalisablity applicable to varying demographics

Genetic analysis of 17 Y-STRs in a Mestizo population from the Central Valley of Mexico

This study aims to portray the complex diversity of the Mexican Mestizo population, which represents 98.8% of the entire population of Mexico. We compiled extended haplotype data of the Y chromosome from populations in the Central Valley of Mexico (CVM), which were compared to other Mestizo and parental (Amerindian, European and African) populations. A complex ancestral relationship was found in the CVM population, suggesting cosmopolitan origins. Nevertheless, the most preeminent lineages point towards a European ancestry, where the R1b was the most frequent. In addition, important frequencies of Amerindian linages were also found in the Mestizo sample studied. Interestingly, the Amerindian ancestry showed a remarkable substructure, which was represented by the two main founding lineages: QL54 (x M3) and M3. However, even within each lineage a high diversity was found despite the small number of samples bearers of these lineages. Further, we detected important genetic differences between the CVM populations and the Mexican Mestizo populations from the north and south. This result points to the fact that Mestizo populations present different ancestral proportions, which are related to the demographic events that gave origin to each population. Finally, we provide additional forensic statistical parameters that are useful in the interpretation of genetic analysis where autosomal loci are limited. Our findings illustrate the complex genetic background of the Mexican Mestizo population and reinforce the need to encompass more geographic regions to generate more robust data for forensic applications

Endoplasmic Reticulum Stress-Sensing Mechanism Is Activated in Entamoeba histolytica upon Treatment with Nitric Oxide

The Endoplasmic Reticulum stores calcium and is a site of protein synthesis and modification. Changes in ER homeostasis lead to stress responses with an activation of the unfolded protein response (UPR). The Entamoeba histolytica endomembrane system is simple compared to those of higher eukaryotes, as a canonical ER is not observed. During amoebiasis, an infection of the human intestine and liver by E. histolytica, nitric oxide (NO) triggers an apoptotic-like event preceded by an impairment of energy production and a loss of important parasite pathogenic features. We address the question of how this ancient eukaryote responds to stress induced by immune components (i.e. NO) and whether stress leads to ER changes and subsequently to an UPR. Gene expression analysis suggested that NO triggers stress responses marked by (i) dramatic up-regulation of hsp genes although a bona fide UPR is absent; (ii) induction of DNA repair and redox gene expression and iii) up-regulation of glycolysis-related gene expression. Enzymology approaches demonstrate that NO directly inhibits glycolysis and enhance cysteine synthase activity. Using live imaging and confocal microscopy we found that NO dramatically provokes extensive ER fragmentation. ER fission in E. histolytica appears as a protective response against stress, as it has been recently proposed for neuron self-defense during neurologic disorders. Chronic ER stress is also involved in metabolic diseases including diabetes, where NO production reduces ER calcium levels and activates cell death. Our data highlighted unique cellular responses of interest to understand the mechanisms of parasite death during amoebiasis

In Vitro and In Silico Analysis of New n-Butyl and Isobutyl Quinoxaline-7-carboxylate 1,4-di-N-oxide Derivatives against Trypanosoma cruzi as Trypanothione Reductase Inhibitors

American trypanosomiasis is a worldwide health problem that requires attention due to ineffective treatment options. We evaluated n-butyl and isobutyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives against trypomastigotes of the Trypanosoma cruzi strains NINOA and INC-5. An in silico analysis of the interactions of 1,4-di-N-oxide on the active site of trypanothione reductase (TR) and an enzyme inhibition study was carried out. The n-butyl series compound identified as T-150 had the best trypanocidal activity against T. cruzi trypomastigotes, with a 13% TR inhibition at 44 μM. The derivative T-147 behaved as a mixed inhibitor with Ki and Ki' inhibition constants of 11.4 and 60.8 µM, respectively. This finding is comparable to the TR inhibitor mepacrine (Ki = 19 µM)