Kinetics of formic acid dehydration on Pt electrodes by time-resolved ATR-SEIRAS

ACKNOWLEDGMENT L.P.-M. acknowledges a doctoral scholarship within the Leverhulme Centre for Doctoral Training in Sustainable Production of Chemicals and Materials (Grant DS-2017-073).Peer reviewedPublisher PD

Reactive and inhibiting species in the electrocatalytic oxidation of glycerol on gold : A study combining in-situ visible reflectance and ATR-SEIRAS

Acknowledgements: The support of the Leverhulme Trust through the Doctoral Scholarship Scheme [DS-2017-073] is gratefully acknowledged.Peer reviewedPostprin

The Central role of KNG1 gene as a genetic determinant of coagulation pathway-related traits: Exploring metaphenotypes

Traditional genetic studies of single traits may be unable to detect the pleiotropic effects involved in complex diseases. To detect the correlation that exists between several phenotypes involved in the same biological process, we introduce an original methodology to analyze sets of correlated phenotypes involved in the coagulation cascade in genome-wide association studies. The methodology consists of a two-stage process. First, we define new phenotypic meta-variables (linear combinations of the original phenotypes), named metaphenotypes, by applying Independent Component Analysis for the multivariate analysis of correlated phenotypes (i.e. the levels of coagulation pathway–related proteins). The resulting metaphenotypes integrate the information regarding the underlying biological process (i.e. thrombus/clot formation). Secondly, we take advantage of a family based Genome Wide Association Study to identify genetic elements influencing these metaphenotypes and consequently thrombosis risk. Our study utilized data from the GAIT Project (Genetic Analysis of Idiopathic Thrombophilia). We obtained 15 metaphenotypes, which showed significant heritabilities, ranging from 0.2 to 0.7. These results indicate the importance of genetic factors in the variability of these traits. We found 4 metaphenotypes that showed significant associations with SNPs. The most relevant were those mapped in a region near the HRG, FETUB and KNG1 genes. Our results are provocative since they show that the KNG1 locus plays a central role as a genetic determinant of the entire coagulation pathway and thrombus/clot formation. Integrating data from multiple correlated measurements through metaphenotypes is a promising approach to elucidate the hidden genetic mechanisms underlying complex diseases.Postprint (published version

Fibronectin modulates the endocannabinoid system through the cAMP/PKA pathway during human sperm capacitation

Fibronectin (Fn) enhances human sperm capacitation via the cAMP/PKA pathway, and the endocannabinoid system participates in this process. Moreover, Fn has been linked to endocannabinoid system components in different cellular models, even though no evidence of such interactions in human sperm is available. Normal semen samples were evaluated over a 4-year period. Our findings suggest that (a) the capacitating effects of Fn were reversed by preincubating the sperm with a cannabinoid receptor 1 (CB1) or transient receptor potential cation channel subfamily V member 1 (TRPV1) antagonist (p < 0.001 and p < 0.05, respectively); (b) cooperation between CB1 and TRPV1 may exist (p < 0.01); (c) the activity of specific fatty acid amide hydroxylase (FAAH) decreased after 1 min (p < 0.01) and increased after 60 min (p < 0.01) of capacitation in the presence of Fn; (d) the effects of Fn on FAAH activity were prevented by preincubating spermatozoa with a protein kinase A (PKA) inhibitor (p < 0.01); (e) Fn modulated both the cyclic adenosine monophosphate concentration and PKA activity (p < 0.05) during early capacitation; and (f) FAAH was a PKA substrate modulated by phosphorylation. These findings indicate that Fn stimulates human sperm capacitation via the cAMP/PKA pathway through modulation of the endocannabinoid system. Understanding the functional competence of human spermatozoa is essential for facilitating clinical advances in infertility treatment and for developing novel contraceptive strategies.Fil: Martínez León, Eduardo Antonio. Universidad de Antofagasta; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Osycka Salut, Claudia Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Signorelli, Janetti. Universidad de Antofagasta; ChileFil: Kong, Milene. Universidad de Antofagasta; ChileFil: Morales, Patricio. Universidad de Antofagasta; ChileFil: Perez Martinez, Silvina Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Díaz, Emilce Silvina. Universidad de Antofagasta; Chil

Methanol Dehydrogenation on Pt Electrodes : Active Sites and Role of Adsorbed Spectators Revealed through Time-Resolved ATR-SEIRAS

ACKNOWLEDGMENT L.P.-M. acknowledges a doctoral scholarship within the Leverhulme Centre for Doctoral Training in Sustainable Production of Chemicals and Materials (Grant DS-2017-073).Peer reviewedPostprin

Theoretical insight into vibrational spectra of metal-water interfaces from density functional theory based molecular dynamics

Acknowledgements J. C. is grateful for funding support from the National Natural Science Foundation of China (Grants No. 21373166 and 21621091), and the Thousand Youth Talents Program of China.Peer reviewedPostprin

Mechanisms of the sperm guidance, an essential aid for meeting the oocyte

In mammals, ejaculated spermatozoa must migrate into the female reproductive tract in order to reach and fertilize the oocyte (Figure 1). The number of spermatozoa that reach the oviductal isthmus (where they attach to oviductal cells and form the sperm reservoir) is small (1,2) and only ~10% of these spermatozoa in humans become capacitated (3) and acquire a state of readiness for fertilizing the oocyte. In addition, the sperm cells have a torturous and long way between the reservoir and the oocyte at the fertilization site (3–5 cm in humans) (2). These facts, together with the tiny dimensions of the gametes in comparison to the tube length make improbable the sperm arrival to the fertilization site and make evident the need for sperm guidance (4). Different guidance mechanisms appear essential for successful sperm arrival to the fertilization site: the short range mechanism such as chemotaxis (swimming up a chemoattractant gradient) (5) and the long range mechanisms such as rheotaxis (swimming against a fluid flow) and thermotaxis (the temperature-oriented cell motility).Fil: Lottero Leconte, Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Alonso, Carlos Agustín Isidro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Castellano, Luciana Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Perez Martinez, Silvina Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentin

Análisis de la motivación y rendimiento académico utilizando el aprendizaje basado en problemas con estudiantes de Ciencias de la salud :Terapia ocupacional

El Aprendizaje basado en Problemas (ABP) se caracteriza por desarrollar una serie de habilidades y competencias indispensables en el entorno profesional. Es un método innovador en el cual el aprendizaje es significativo, ya que se centra en el estudiante y fomenta el aprendizaje autónomo. En las disciplinas de ciencias de la salud, se precisan unas estrategias educativas específicas, ya que los estudios de ciencias de la Salud están fragmentados en diferentes especialidades, es por este motivo que el ABP es una herramienta que puede ser muy útil. El objetivo de este estudio es conocer si la utilización del ABP mejora la motivación de los estudiantes y también si influye en el rendimiento académico de los estudiantes. Para ello, se incorporó en la metodología el uso de actividades que conllevaran ABP en dos asignaturas y dos cursos de la Facultad de Ciencias de la Salud, (Intervención de la Terapia Ocupacional en Salud Mental I y técnicas terapéuticas). Dichas asignaturas fueron impartidas en la titulación de Terapia Ocupacional durante el curso académico 2013/2014. La muestra estuvo compuesta por un total de 106 estudiantes. Para medir la motivación, se administró el cuestionario de motivación y estrategias de aprendizaje (en sus siglas en inglés, MSLQ) al comienzo de las dos asignaturas para conocer el nivel de motivación del que partían. Cuando finalizaron las dos asignaturas se volvió a administrar a los estudiantes que habían participado en la encuesta inicial. Concretamente, se presentan las características de la experiencia, así como un análisis descriptivo sobre la relación entre el uso de la ABP y la nota final de las asignaturas. Se compararon también las calificaciones de asignaturas que no habían implementado el ABP en su metodología. Los resultados mostraron de forma general que los niveles de motivación son parecidos en la fase inicial y final, obteniéndose por lo general puntuaciones de 4 en aproximadamente el 50% de los encuestados. En cambio, cabe señalar que al compararse las notas de de los estudiantes en las asignaturas que habían implementado ABP y en las que no, los resultados mostraron que en las asignaturas con ABP las calificaciones finales fueron más altas que en aquellas asignaturas que no se implementó. Estos resultados indican que el uso de la metodología basada en ABP contribuye a que los estudiantes mantengan un nivel de motivación durante la asignatura, el cual a su vez influye positivamente en el rendimiento académico de los estudiantesUniversidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

1-(Benzo[d]thiazol-2-yl)-3-phenylureas as dual inhibitors of casein kinase 1 and ABAD enzymes for treatment of neurodegenerative disorders

This work was supported by the Ministry of Health of the Czech Republic [no. NV15-28967 A], Specific Research Project of Faculty of Science, University of Hradec Kralove [no. 2103-2017], National Institute of Mental Health [NIMH CZ; no. ED2.1.00/03.0078] from the European Regional Development Fund, COST CA15135, The Alzheimer’s Society (specifically The Barcopel Foundation), The Rosetrees trust and The Biotechnology and Biological Sciences Research Council (BBSRC) [no. BB/J01446X/1]. Funding from Ministry of Economy and competitiveness, Spain [no. SAF2012-37979-C03-01] is also acknowledged.Several neurodegenerative disorders including Alzheimer’s disease (AD) have been connected with deregulation of casein kinase 1 (CK1) activity. Inhibition of CK1 therefore presents a potential therapeutic strategy against such pathologies. Recently, novel class of CK1-specific inhibitors with N-(benzo[d]thiazol-2-yl)-2-phenylacetamide structural scaffold has been discovered. 1-(benzo[d]thiazol-2-yl)-3-phenylureas, on the other hand, are known inhibitors amyloid-beta binding alcohol dehydrogenase (ABAD), an enzyme also involved in pathophysiology of AD. Based on their tight structural similarity, we decided to evaluate series of previously published benzothiazolylphenylureas, originally designed as ABAD inhibitors, for their inhibitory activity towards CK1. Several compounds were found to be submicromolar CK1 inhibitors. Moreover, two compounds were found to inhibit both, ABAD and CK1. Such dual-activity could be of advantage for AD treatment, as it would simultaneously target two distinct pathological processes involved in disease’s progression. Based on PAMPA testing both compounds were suggested to permeate the blood-brain barrier, which makes them, together with their unique dual activity, interesting lead compounds for further development.Publisher PDFPeer reviewe

Identification of Amino Acid Residues Responsible for Inhibition of Host Gene Expression by Influenza A H9N2 NS1 Targeting of CPSF30

H9N2 influenza A viruses (IAV) are considered low pathogenic avian influenza viruses (LPAIV). These viruses are endemic in poultry in many countries in Asia, the Middle East and parts of Africa. Several cases of H9N2-associated infections in humans as well as in pigs have led the World Health Organization (WHO) to include these viruses among those with pandemic potential. To date, the processes and mechanisms associated with H9N2 IAV adaptation to mammals are poorly understood. The non-structural protein 1 (NS1) from IAV is a virulence factor that counteracts the innate immune responses. Here, we evaluated the ability of the NS1 protein from A/quail/Hong Kong/G1/97 (HK/97) H9N2 to inhibit host immune responses. We found that HK/97 NS1 protein counteracted interferon (IFN) responses but was not able to inhibit host gene expression in human or avian cells. In contrast, the NS1 protein from earlier H9N2 IAV strains, including the first H9N2 A/turkey/Wisconsin/1/1966 (WI/66), were able to inhibit both IFN and host gene expression. Using chimeric constructs between WI/66 and HK/97 NS1 proteins, we identified the region and amino acid residues involved in inhibition of host gene expression. Amino acid substitutions L103F, I106M, P114S, G125D and N139D in HK/97 NS1 resulted in binding to the 30-kDa subunit of the cleavage and polyadenylation specificity factor (CPSF30) and, in consequence, inhibition of host gene expression. Notably, changes in the same amino acid residues resulted in the lack of inhibition of host gene expression by WI/66 NS1. Importantly, our results identified a new combination of amino acids required for NS1 binding to CPSF30 and inhibition of host gene expression. These results also confirm previous studies demonstrating strain specific differences in the ability of NS1 proteins to inhibit host gene expression