Data analysis in chemistry and bio-medical sciences

EditorialMinisterio de Economía y Competitividad; CTQ2013-41229-PMinisterio de Economía y Competitividad; CTQ2013-41229-P/BQUMinisterio de Economía y Competitividad; CTQ2016-74881-PPaís Vasco. Gobierno; IT1045-1

IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome

Expansion of the polyglutamine repeat within the protein Huntingtin (Htt) causes Huntington's disease, a neurodegenerative disease associated with aging and the accumulation of mutant Htt in diseased neurons. Understanding the mechanisms that influence Htt cellular degradation may target treatments designed to activate mutant Htt clearance pathways. We find that Htt is phosphorylated by the inflammatory kinase IKK, enhancing its normal clearance by the proteasome and lysosome. Phosphorylation of Htt regulates additional post-translational modifications, including Htt ubiquitination, SUMOylation, and acetylation, and increases Htt nuclear localization, cleavage, and clearance mediated by lysosomal-associated membrane protein 2A and Hsc70. We propose that IKK activates mutant Htt clearance until an age-related loss of proteasome/lysosome function promotes accumulation of toxic post-translationally modified mutant Htt. Thus, IKK activation may modulate mutant Htt neurotoxicity depending on the cell's ability to degrade the modified species

MIANN models in medicinal, physical and organic chemistry

[Abstract] Reducing costs in terms of time, animal sacrifice, and material resources with computational methods has become a promising goal in Medicinal, Biological, Physical and Organic Chemistry. There are many computational techniques that can be used in this sense. In any case, almost all these methods focus on few fundamental aspects including: type (1) methods to quantify the molecular structure, type (2) methods to link the structure with the biological activity, and others. In particular, MARCH-INSIDE (MI), acronym for Markov Chain Invariants for Networks Simulation and Design, is a well-known method for QSAR analysis useful in step (1). In addition, the bio-inspired Artificial-Intelligence (AI) algorithms called Artificial Neural Networks (ANNs) are among the most powerful type (2) methods. We can combine MI with ANNs in order to seek QSAR models, a strategy which is called herein MIANN (MI & ANN models). One of the first applications of the MIANN strategy was in the development of new QSAR models for drug discovery. MIANN strategy has been expanded to the QSAR study of proteins, protein-drug interactions, and protein-protein interaction networks. In this paper, we review for the first time many interesting aspects of the MIANN strategy including theoretical basis, implementation in web servers, and examples of applications in Medicinal and Biological chemistry. We also report new applications of the MIANN strategy in Medicinal chemistry and the first examples in Physical and Organic Chemistry, as well. In so doing, we developed new MIANN models for several self-assembly physicochemical properties of surfactants and large reaction networks in organic synthesis. In some of the new examples we also present experimental results which were not published up to date.Ministerio de Ciencia e Innovación; CTQ2009-07733Universidad del Pais Vasco; UFI11/22Universidad del Pais Vasco; GIU 094

Estados de ánimo y rendimiento deportivo en fútbol : ¿existe la ventaja de jugar en casa?

Los estados de ánimo previos a la competición han sido asociados con la selección de deportistas y el rendimiento deportivo. Recientes investigaciones parecen haber demostrado que la relación entre el estado de ánimo precompetitivo y el rendimiento, podría estar mediado por una serie de variables como son la duración del evento, el tipo de deporte e incluso la localización del partido (Terry, 1997). En el presente estudio, tenemos intención de observar cómo los estados de ánimo, previos a la competición, influyen en el rendimiento de un equipo de fútbol durante toda la temporada, y si esta relación está mediada por la variable localización del partido. Según los resultados obtenidos, la variable localización del partido parece mediar en la relación existente entre estados de ánimo y rendimiento, siendo los partidos jugados fuera de casa donde más se manifiestan los estados de ánimo y su consiguiente influencia en el rendimiento.Emotional states, previous to competition, have been associated to competition outcomes and athletes selection. Recent investigations have demonstrated that some variables could being mediating the relationships between emotional states and competition outcome, such as duration of the event, type of sport and game location (Terry, 1997). The present study's intention is to observe how the emotional states, previous to competition, relate to competition performance, in a soccer team during a season. Also, we are interested in the possible mediating role of game location. The study results, seem to confirm that game location mediate the relationship between emotional states and performance, with home matches having the more positive emotional states and performance

In-device spectroscopy at metal/organic semiconductor interfaces.

145 p.En esta tesis doctoral nos hemos basado en el estudio de las barreras energéticas presentes en lasinterfaces entre el nivel de Fermi de los metales y los niveles orbitales de semiconductores orgánicos.Este estudio se ha realizado mediante dispositivos electrónicos verticales de tres terminales y mediante lainyección y transporte de cargas eléctricas. De esta forma, hemos podido determinar cómo dichasbarreras energéticas afectan en el transporte eléctrico, lo cual influye directamente en el funcionamiento yeficiencia de dispositivos optoelectrónicos. La determinación de los niveles energéticos relativos devarios orbitales moleculares nos ha llevado a poder determinar directamente la banda de energíaprohibida de varios semiconductores orgánicos. El estudio se ha llevado a cabo con semiconductoresmoleculares y poliméricos tanto el ultra alto vacío como en condiciones ambientales respectivamente.Además de esto, hemos investigado cómo afecta la tensión mecánica en las barreras energéticas entremetales y semiconductores orgánicos. Para esto, hemos fabricado nuestros dispositivos en substratosflexibles y medidos doblados con distintos radios de torsión.En los dispositivos estudiados, las cargas se inyectan balísticamente en el semiconductor. Esta formaúnica de inyectar las cargas nos ha permitido observar en semiconductores orgánicos el Régimen deInversión Marcus. Como consecuencia de este régimen, hemos observado un diferencial de resistencianegativo en medida de corriente versus voltaje. Hemos podido manipular este último fenómeno mediantetemperatura, luz y campo eléctrico.CICnanoGUN

Chiral Bronsted Acid-Catalyzed Enantioselective alpha-Amidoalkylation Reactions: A Joint Experimental and Predictive Study,

Enamides with a free NH group have been evaluated as nucleophiles in chiral Bronsted acid-catalyzed enantioselective alpha-amidoalkylation reactions of bicyclic hydroxylactams for the generation of quaternary stereocenters. A quantitative structure-reactivity relationship (QSRR) method has been developed to find a useful tool to rationalize the enantioselectivity in this and related processes and to orient the catalyst choice. This correlative perturbation theory (PT)-QSRR approach has been used to predict the effect of the structure of the substrate, nucleophile, and catalyst, as well as the experimental conditions, on the enantioselectivity. In this way, trends to improve the experimental results could be found without engaging in a long-term empirical investigation.Ministerio de Economia y Competitividad (CTQ2013-41229-P), IKERBASQUE foundation, Gobierno Vasco (IT-623-13) and Universidad del Pais Vasco/Euskal Herriko Unibertsitatea UPV/EHU are gratefully acknowledged for their financial support. Technical and human support provided by Servicios Generales de Investigacion SGIker (UPV/EHU, MINECO, GV/EJ, ERDF and ESF) is also acknowledged

Peripheral Inflammatory Parameters in Late-Life Depression: A Systematic Review

Depressive disorders appear relatively frequently in older patients, and therefore represent an important disease burden worldwide. Given the high levels of inflammatory parameters found in depressed elderly patients, the "inflammaging" hypothesis is gaining strength. In this systematic review, we summarize current evidence regarding the relationship between inflammatory parameters and late-life depression, with a unique focus on longitudinal studies to guarantee temporality. According to the data summarized in this review, the levels of some proinflammatory parameters-especially interleukin (IL)-8, IL-6, and tumor necrosis factor (TNF)-α-could serve as biomarkers for the future development of depressive symptoms in elderly patients. Proinflammatory cytokines seem to be associated with the future development of clinically significant depression, irrespective of baseline scores, thus indicating that inflammation temporally precedes and increases depression risk. As insufficient research has been conducted in this field, further prospective studies are clearly warranted.This study was funded by grants from Research Network Center of Mental Health-CIBERSAM (2010-P-02); the Government of Spain “Health Research Fund” FEDER (PI08-1213, PI11-01977, PI14-01900, PI08-0873; PI10-01746; PS09/02002; PI12/02077; PI15-00789; PI13/00451); Ministry of Health and Social Equality (20111064) Policy; Local funding from the Department of Education, Language Policy and Culture of the Basque Government (200911147, 2013111162, 2010111170, SAIO10-PC10BF01); European Comission funds (UE/2012/FI-STAR). We appreciate the support of the University of the Basque Country (GIC10/80, GIC12/84) and the Basque Foundation for Health Innovation and Research-BIOEF. The Psychiatry Research Unit of the University Hospital of Álava-Santiago is supported by the “Stanley Research Foundation” (03-RC-003). John O’Brien is supported by the NIHR Cambridge Biomedical Research Centre awarded to the University of Cambridge, Cambridge University Hospitals NHS Trust and Cambridgeshire and Peterborough NHS Trust

In-device spectroscopy at metal/organic semiconductor interfaces.

145 p.En esta tesis doctoral nos hemos basado en el estudio de las barreras energéticas presentes en lasinterfaces entre el nivel de Fermi de los metales y los niveles orbitales de semiconductores orgánicos.Este estudio se ha realizado mediante dispositivos electrónicos verticales de tres terminales y mediante lainyección y transporte de cargas eléctricas. De esta forma, hemos podido determinar cómo dichasbarreras energéticas afectan en el transporte eléctrico, lo cual influye directamente en el funcionamiento yeficiencia de dispositivos optoelectrónicos. La determinación de los niveles energéticos relativos devarios orbitales moleculares nos ha llevado a poder determinar directamente la banda de energíaprohibida de varios semiconductores orgánicos. El estudio se ha llevado a cabo con semiconductoresmoleculares y poliméricos tanto el ultra alto vacío como en condiciones ambientales respectivamente.Además de esto, hemos investigado cómo afecta la tensión mecánica en las barreras energéticas entremetales y semiconductores orgánicos. Para esto, hemos fabricado nuestros dispositivos en substratosflexibles y medidos doblados con distintos radios de torsión.En los dispositivos estudiados, las cargas se inyectan balísticamente en el semiconductor. Esta formaúnica de inyectar las cargas nos ha permitido observar en semiconductores orgánicos el Régimen deInversión Marcus. Como consecuencia de este régimen, hemos observado un diferencial de resistencianegativo en medida de corriente versus voltaje. Hemos podido manipular este último fenómeno mediantetemperatura, luz y campo eléctrico.CICnanoGUN