How molybdenum species cleave the phosphoester bond.

217 p.Metal species have a great impact on the biochemistry of living systems. It has been reported that polyoxomolybdates exhibit anti-tumor activity similar to that of commercial drugs. However, the mechanism by which these species are effective against cancer has been an elusive topic. It is believed that their activity is related to their interaction with phosphoester' containing biomolecules.Experimental studies have demonstrated that molybdenum species can cause cleavage in different model phosphoester molecules.However, the complex chemistry of molybdates has made these experimental studies difficult to interpret. We used computational methodologies to shed light on the phosphoesterase activity of molybdenum species in different reaction models. The study employed density functional theory to explore the mechanistic details of hydrolysis reactions of phosphate monoesters and diestersin the presence of different molybdenum species.The study results on the speciation of MoO2Cl2(DMF)2 supported the experimental findings that reported DMF release and Mo¿Clbond breakage. Two different NPP hydrolysis pathways were proposed depending on the complex concentration. Lower concentrations disfavoured the formation of polynuclear species, and the hydrolysis proceeded through less favourable mononuclear intermediates. With enough complex concentration, a nucleation process was favoured over the phosphate interaction. After theformation of dinuclear species, the incorporation of NPP and its consequent hydrolysis showed lower energetic barriers than theuncatalysed reaction. We also examined heptamolybdate as it was reported to hydrolyse NPP while its nuclearity decreased.Pentanuclear active species proposed by experimentals showed a higher activation barrier for its hydrolysis and cannot beconsidered as a catalyst. The study proposed a dinuclear compound resulting from heptamolybdate fragmentation as the catalytic species, which decreased the energetic barrier compared to the non¿catalysed reaction. With DNA and RNA models BNPP andHPNP, the calculations supported the experimental findings that heptamolybdate can hydrolyse phosphodiester molecules without fragmentation. With phosphate diesters, the hydrolysis proceeded through more compact mechanisms than with phosphatemonoesters, in which phosphorane structures are formed.The study revealed that the dinuclear species and the heptamolybdate cluster provide a structural motif that catalyses the hydrolysisof these phosphates. The molybdate structure generally augments the electrophilia of the phosphorous atom and can deprotonateand activate the nucleophile, favouring associative mechanisms. This information can aid in designing effective and non¿toxicphosphoesterases.DIP

Can aluminum, a non-redox metal, alter the thermodynamics of key biological redox processes? The DPPH-QH2 radical scavenging reaction as a test case

[EN] The increased bioavailability of aluminum has led to a concern about its toxicity on living systems. Among the most important toxic effects, it has been proven that aluminum increases oxidative stress in biological systems, a controversial fact, however, due to its non-redox nature. In the present work, we characterize in detail how aluminum can alter redox equilibriums by analyzing its effects on the thermodynamics of the redox scavenging reaction between DPPH., a radical compound often used as a reactive oxygen species model, and hydroquinones, a potent natural antioxidant. For the first time, theoretical and experimental redox potentials within aluminum biochemistry are directly compared. Our results fully agree with experimental reduction and oxidation potentials, unequivocally revealing how aluminum alters the spontaneity of the reaction by stabilizing the reduction of DPPH to DPPH- and promoting a proton transfer to the diazine moiety, leading to the production of a DPPH-H species. The capability of aluminum to modify redox potentials shown here confirms previous experimental findings on the role of aluminum to interfere with free radical scavenging reactions, affecting the natural redox processes of living organisms.This research was financially supported by Eusko Jaurlaritza (the Basque Government), through Consolidated Group Project No. IT1254-19, and the Spanish MINECO/FEDER Project No. PGC2018- 097 529-B-100. JL thanks Donostia International Physics center (DIPC) for his Ph.D. grant. VP also thanks Euskal Herriko Unibertsitatea (UPV/EHU) for the PIC 216/18 contract and the ESPDOC18/85 post-doctoral grant. Technical and human support provided by IZO-SGI, SGIker (UPV/EHU, MICINN, GV/EJ and DIPC) is gratefully acknowledged

Marketing de servicios: Atención al cliente

La atención del cliente es una de las principales característica que una empresa de servicio o consumo, debe tomar como primordial dentro de sus funciones. Mantener un cliente es de gran importancia y es un poco complicado, El triunfo de una Empresa depende fundamentalmente de la demanda de sus clientes. Ellos son los protagonistas principales y el factor más importante que interviene en el juego de los negocios. En este trabajo se presenta una caracterización general para brindar un servicio de atención al cliente de calidad, una herramienta para analizar el mejoramiento del valor de los productos y servicios, además de una profunda reflexión sobre la conveniencia de aprovechar los conocimientos y utilizarlos en problemas de la empresa de tal forma que permita conformar una idea más clara de la importancia y necesidad de contar con un diseño del servicio de atención al cliente. El trabajo que presentamos contiene tres capitulo cada uno con temas muy importantes en donde realizamos una explicación clara y concreta de cada uno de ellos. En la actualidad las empresas dan más interés en la administración de cómo debemos dirigir, administrar los recursos económicos, humanos y materiales; dejando inadvertido el servicio de atención al cliente y que cada día nos preocupamos en crecer pero no tomamos importancia de cómo nuestra competencia está creciendo y que está incrementando sus carteras de clientes; debido al buen servicio y la atención que se brinda. Es por tanto que las empresas pequeñas y grandes deben prestar un servicio de Calidad, para lograr posicionarse en el mercado y marcar la diferencia

Villancicos que se han de cantar la noche de Navidad en la Santa Iglesia de Huesca,

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Lifespan Changes of the Human Brain In Alzheimer's Disease

[EN] Brain imaging studies have shown that slow and progressive cerebral atrophy characterized the development of Alzheimer's Disease (AD). Despite a large number of studies dedicated to AD, key questions about the lifespan evolution of AD biomarkers remain open. When does the AD model diverge from the normal aging model? What is the lifespan trajectory of imaging biomarkers for AD? How do the trajectories of biomarkers in AD differ from normal aging? To answer these questions, we proposed an innovative way by inferring brain structure model across the entire lifespan using a massive number of MRI (N = 4329). We compared the normal model based on 2944 control subjects with the pathological model based on 3262 patients (AD + Mild cognitive Impaired subjects) older than 55 years and controls younger than 55 years. Our study provides evidences of early divergence of the AD models from the normal aging trajectory before 40 years for the hippocampus, followed by the lateral ventricles and the amygdala around 40 years. Moreover, our lifespan model reveals the evolution of these biomarkers and suggests close abnormality evolution for the hippocampus and the amygdala, whereas trajectory of ventricular enlargement appears to follow an inverted U-shape. Finally, our models indicate that medial temporal lobe atrophy and ventricular enlargement are two mid-life physiopathological events characterizing AD brain.This work benefited from the support of the project DeepVolBrain of the French National Research Agency (ANR-18-CE45-0013). This study was achieved within the context of the Laboratory of Excellence TRAIL ANR-10-LABX-57 for the BigDataBrain project. Moreover, we thank the Investments for the future Program IdEx Bordeaux (ANR-10-IDEX- 03-02, HL-MRI Project), Cluster of excellence CPU and the CNRS. This study has been also supported by the DPI2017-87743-R grant from the Spanish Ministerio de Economia, Industria y Competitividad. Moreover, this work is based on multiple samples. We wish to thank all investigators of these projects who collected these datasets and made them freely accessible. The C-MIND data used in the preparation of this article were obtained from the C-MIND Data Repository (accessed in Feb 2015) created by the C-MIND study of Normal Brain Development. This is a multisite, longitudinal study of typically developing children from ages newborn through young adulthood conducted by Cincinnati Children's Hospital Medical Center and UCLA and supported by the National Institute of Child Health and Human Development (Contract #s HHSN275200900018C). A listing of the participating sites and a complete listing of the study investigators can be found at https://research.cchmc.org/c-mind. The NDAR data used in the preparation of this manuscript were obtained from the NIH-supported National Database for Autism Research (NDAR). NDAR is a collaborative informatics system created by the National Institutes of Health to provide a national resource to support and accelerate research in autism. The NDAR dataset includes data from the NIH Pediatric MRI Data Repository created by the NIH MRI Study of Normal Brain Development. This is a multisite, longitudinal study of typically developing children from ages newborn through young adulthood conducted by the Brain Development Cooperative Group and supported by the National Institute of Child Health and Human Development, the National Institute on Drug Abuse, the National Institute of Mental Health, and the National Institute of Neurological Disorders and Stroke (Contract #s N01- HD02-3343, N01-MH9-0002, and N01-NS-9-2314, -2315, -2316, -2317, -2319 and -2320). A listing of the participating sites and a complete listing of the study investigators can be found at http://pediatricmri.nih.gov/nihpd/info/participating_centers.html. The ADNI data used in the preparation of this manuscript were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). The ADNI is funded by the National Institute on Aging and the National Institute of Biomedical Imaging and Bioengineering and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics NV, Johnson & Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc., F. Hoffmann-La Roche, Schering-Plough, Synarc Inc., as well as nonprofit partners, the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the U.S. Food and Drug Administration. Private sector contributions to the ADNI are facilitated by the Foundation for the National Institutes of Health (www.fnih.org).Coupé, P.; Manjón Herrera, JV.; Lanuza, E.; Catheline, G. (2019). Lifespan Changes of the Human Brain In Alzheimer's Disease. Scientific Reports. 9:1-12. https://doi.org/10.1038/s41598-019-39809-8S1129Lobo, A. et al. Prevalence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurology 54, S4 (2000).Barnes, J. et al. Alzheimer’s disease first symptoms are age dependent: evidence from the NACC dataset. Alzheimer’s & dementia 11, 1349–1357 (2015).Jack, C. R. et al. Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. 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The EADC-ADNI Harmonized Protocol for manual hippocampal segmentation on magnetic resonance: evidence of validity. Alzheimer’s & Dementia 11, 111–125 (2015).Solow, R. M. A contribution to the theory of economic growth. The quarterly journal of economics 70, 65–94 %@1531–4650 (1956).Coupe, P. et al. Scoring by nonlocal image patch estimator for early detection of Alzheimer’s disease. Neuroimage Clin 1, 141–152, https://doi.org/10.1016/j.nicl.2012.10.002 (2012).Cuingnet, R. et al. Automatic classification of patients with Alzheimer’s disease from structural MRI: a comparison of ten methods using the ADNI database. Neuroimage 56, 766–781, https://doi.org/10.1016/j.neuroimage.2010.06.013 (2011).Eskildsen, S. F. et al. Prediction of Alzheimer’s disease in subjects with mild cognitive impairment from the ADNI cohort using patterns of cortical thinning. Neuroimage 65, 511–521 (2013).Eskildsen, S. F. et al. Structural imaging biomarkers of Alzheimer’s disease: predicting disease progression. 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Percepciones socioculturales de los pobladores de la comunidad el Limón ante un riesgo climático

El presente artículo, resume una investigación cualitativa con enfoque de Investigación-Acción, realizado con jóvenes y adultos habitantes afectados por los riesgos climáticos. La investigación se llevó a cabo en la comunidad El Limón de la subzona de Santa Cruz, Estelí, en el período entre septiembre y diciembre del año 2014. Con esta se pretendía valorar las percepciones socioculturales de los pobladores ante un riesgo climático. Se realizó desde la metodología de investigación, acción participativa, dentro de las técnicas utilizadas están: la encuesta, entrevista semi-estructurada, guía de observación y grupo focal, además de la revisión documental. Las diferentes técnicas se analizaron de acuerdo a cada objetivo y a su naturaleza de IAP. Dentro de los principales hallazgos se encuentra que los pobladores no poseen suficiente conocimiento sobre riesgo, además de existir una influencia en el desarrollo de sus percepciones con respecto a su posición geográfica, ubicada cerca de urbanizadoras. Referido a los efectos que perciben en las actividades socioambientales únicamente ven evidente la escases de agua, el aumento de plagas y enfermedades. Por ello se elaboró una propuesta de acción, encaminada a fomentar la auto gestión como medida de adaptación al cambio climático

Towards a Unified Analysis of Brain Maturation and Aging across the Entire Lifespan: A MRI Analysis

"This is the peer reviewed version of the following article: Coupé, Pierrick, Gwenaelle Catheline, Enrique Lanuza, and José Vicente Manjón. 2017. Towards a Unified Analysis of Brain Maturation and Aging across the Entire Lifespan: A MRI Analysis. Human Brain Mapping 38 (11). Wiley: 5501 18. doi:10.1002/hbm.23743, which has been published in final form at https://doi.org/10.1002/hbm.23743. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."[EN] There is no consensus in literature about lifespan brain maturation and senescence, mainly because previous lifespan studies have been performed on restricted age periods and/or with a limited number of scans, making results instable and their comparison very difficult. Moreover, the use of nonharmonized tools and different volumetric measurements lead to a great discrepancy in reported results. Thanks to the new paradigm of BigData sharing in neuroimaging and the last advances in image processing enabling to process baby as well as elderly scans with the same tool, new insights on brain maturation and aging can be obtained. This study presents brain volume trajectory over the entire lifespan using the largest age range to date (from few months of life to elderly) and one of the largest number of subjects (N=2,944). First, we found that white matter trajectory based on absolute and normalized volumes follows an inverted U-shape with a maturation peak around middle life. Second, we found that from 1 to 8-10 y there is an absolute gray matter (GM) increase related to body growth followed by a GM decrease. However, when normalized volumes were considered, GM continuously decreases all along the life. Finally, we found that this observation holds for almost all the considered subcortical structures except for amygdala which is rather stable and hippocampus which exhibits an inverted U-shape with a longer maturation period. By revealing the entire brain trajectory picture, a consensus can be drawn since most of the previously discussed discrepancies can be explained. Hum Brain Mapp 38:5501-5518, 2017. (C) 2017 Wiley Periodicals, Inc.French State (French National Research Ageny in the frame of the Investments for the future Program IdEx Bordeaux); Contract grant number: ANR-10-IDEX-03-02, HL-MRI Project; Contract grant sponsor: Cluster of excellence CPU and TRAIL (HR-DTI ANR-10-LABX-57); Contract grant sponsor: CNRS ("Defi imag'In and the dedicated volBrain support); Contract grant sponsor: Ministerio de Economia y competitividad (Spanish); Contract grant number: TIN2013-43457-R; Contract grant sponsor: National Institute of Child Health and Human Development; Contract grant number: HHSN275200900018C; Contract grant sponsors: National Institute of Child Health and Human Development, the National Institute on Drug Abuse, the National Institute of Mental Health, and the National Institute of Neurological Disorders and Stroke; Contract grant numbers: N01- HD02-3343, N01-MH9-0002, and N01-NS-9-2314, -2315, -2316, -2317, -2319 and -2320; Contract grant sponsor: National Institutes of Health; Contract grant number: U01 AG024904; Contract grant sponsor: National Institute on Aging and the National Institute of Biomedical Imaging and Bioengineering (ADNI); Contract grant sponsor: NIH; Contract grant number: P30AG010129, K01 AG030514; Contract grant sponsor: Dana Foundation; Contract grant sponsor: OASIS project (OASIS data); Contract grant numbers: P50 AG05681, P01 AG03991, R01 AG021910, P50 MH071616, U24 RR021382, R01 MH56584; Contract grant sponsor: Common-wealth Scientific Industrial Research Organization (a publicly funded government research organization); Contract grant sponsor: Science Industry Endowment Fund, National Health and Medical Research Council of Australia; Contract grant number: 1011689; Contract grant sponsors: Alzheimer's Association, Alzheimer's Drug Discovery Foundation, and an anonymous foundation; Contract grant sponsor: Human Brain Project; Contract grant number: PO1MHO52176-11 (ICBM, P.I. Dr John Mazziotta); Contract grant sponsor: Canadian Institutes of Health Research; Contract grant number: MOP-34996; Contract grant sponsor: U.K. Engineering and Physical Sciences Research Council (EPSRC); Contract grant number: GR/S21533/02; Contract grant sponsor: ABIDE funding resources; Contract grant sponsor: NIMH; Contract grant number: K23MH087770; Contract grant sponsor: Leon Levy Foundation; Contract grant sponsor: NIMH award to MPM; Contract grant number: R03MH096321Coupé, P.; Catheline, G.; Lanuza, E.; Manjón Herrera, JV. (2017). Towards a Unified Analysis of Brain Maturation and Aging across the Entire Lifespan: A MRI Analysis. Human Brain Mapping. 38(11):5501-5518. https://doi.org/10.1002/hbm.23743S550155183811Ashburner, J., & Friston, K. J. (2005). Unified segmentation. NeuroImage, 26(3), 839-851. doi:10.1016/j.neuroimage.2005.02.018Aubert-Broche, B., Fonov, V. S., García-Lorenzo, D., Mouiha, A., Guizard, N., Coupé, P., … Collins, D. L. (2013). 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