Rapid and Accurate Assessment of GPCR-Ligand Interactions Using the Fragment Molecular Orbital-Based Density-Functional Tight-Binding Method

The reliable and precise evaluation of receptor–ligand interactions and pair-interaction energy is an essential element of rational drug design. While quantum mechanical (QM) methods have been a promising means by which to achieve this, traditional QM is not applicable for large biological systems due to its high computational cost. Here, the fragment molecular orbital (FMO) method has been used to accelerate QM calculations, and by combining FMO with the density-functional tight-binding (DFTB) method we are able to decrease computational cost 1000 times, achieving results in seconds, instead of hours. We have applied FMO-DFTB to three different GPCR–ligand systems. Our results correlate well with site directed mutagenesis data and findings presented in the published literature, demonstrating that FMO-DFTB is a rapid and accurate means of GPCR–ligand interactions

GeoNode per la gestione di dati aziendali e territoriali nella Precision Farming in Veneto

A giugno 2017 l\u2019Universit\ue0 degli Studi di Padova, attraverso il sostegno della Regione Veneto nell\u2019ambito di un bando POR-FSE, ha dato avvio al progetto \u201cDroni in viticoltura e frutticoltura: geo-informazione per agroecosistemi 4.0 in Veneto e Trentino\u201d della durata di un anno. L\u2019obiettivo di tale progetto era di introdurre l\u2019impiego delle nuove tecnologie quali SAPR, immagini satellitari e sistemi informativi geografici all\u2019interno delle aziende agricole in modo tale da consentire lo sviluppo della cosiddetta \u201cagricoltura di precisione\u201d. Nell\u2019ambito di questo progetto si inserisce la creazione di un webGIS articolato su diverse scale di inquadramento: una scala territoriale ed una aziendale. I dati necessari alla costruzione del progetto sono stati perlopi\uf9 ricercati nel web in database gratuiti offerti da Enti pubblici regionali e nazionali. Nell\u2019ambito dei webGIS territoriali sono stati inoltre inseriti dati provenienti da rilievi APR eseguiti per il monitoraggio dello stato di salute delle colture delle aziende partner del progetto. L\u2019analisi dei dati raccolti e la costruzione del progetto \ue8 avvenuta in ambiente GIS utilizzando software open-source quali QGIS 2.18 per l\u2019elaborazione dei dati raccolti e personali ed uDig 2.0 per la vestizione dei diversi tematismi in modo tale da consentire il caricamento di dati gi\ue0 stilizzati all\u2019interno del webGIS. I servizi erogati dal webGIS territoriale offrono, attraverso carte tematiche, una panoramica del territorio veneto nella sua complessit\ue0, comprendendo sia gli aspetti naturali/ambientali, sia quelli legati all\u2019attivit\ue0 dell\u2019uomo. A questa panoramica si affiancano i webGIS aziendali, nei quali ciascuna azienda pu\uf2 consultare i propri dati, confrontandosi tra l\u2019altro con le realt\ue0 circostanti

Cellular and molecular evidence for a role of tumor necrosis factor alpha in the ovulatory mechanism of trout

Background: The relevance of immune-endocrine interactions to the regulation of ovarian function in teleosts is virtually unexplored. As part of the innate immune response during infection, a number of cytokines such as tumor necrosis factor alpha (TNF alpha) and other immune factors, are produced and act on the reproductive system. However, TNF alpha is also an important physiological player in the ovulatory process in mammals. In the present study, we have examined for the first time the effects of TNF alpha in vitro in preovulatory ovarian follicles of a teleost fish, the brown trout (Salmo trutta). Methods: To determine the in vivo regulation of TNF alpha expression in the ovary, preovulatory brook trout (Salvelinus fontinalis) were injected intraperitoneally with either saline or bacterial lipopolysaccharide (LPS). In control and recombinant trout TNF alpha (rtTNF alpha)-treated brown trout granulosa cells, we examined the percentage of apoptosis by flow cytometry analysis and cell viability by propidium iodide (PI) staining. Furthermore, we determined the in vitro effects of rtTNF alpha on follicle contraction and testosterone production in preovulatory brown trout ovarian follicles. In addition, we analyzed the gene expression profiles of control and rtTNF alpha-treated ovarian tissue by microarray and real-time PCR (qPCR) analyses. Results: LPS administration in vivo causes a significant induction of the ovarian expression of TNF alpha. Treatment with rtTNF alpha induces granulosa cell apoptosis, decreases granulosa cell viability and stimulates the expression of genes known to be involved in the normal ovulatory process in trout. In addition, rtTNF alpha causes a significant increase in follicle contraction and testosterone production. Also, using a salmonid-specific microarray platform (SFA2.0 immunochip) we observed that rtTNF alpha induces the expression of genes known to be involved in inflammation, proteolysis and tissue remodeling. Furthermore, the expression of kallikrein, TOP-2, serine protease 23 and ADAM 22, genes that have been postulated to be involved in proteolytic and tissue remodeling processes during ovulation in trout, increases in follicles incubated in the presence of rtTNF alpha. Conclusions In view of these results, we propose that TNF alpha could have an important role in the biomechanics of follicle weakening, ovarian rupture and oocyte expulsion during ovulation in trout, primarily through its stimulation of follicular cell apoptosis and the expression of genes involved in follicle wall proteolysis and contraction

GLUT2-mediated glucose uptake and availability are required for embryonic brain development in zebrafish

Glucose transporter 2 (GLUT2; gene name SLC2A2) has a key role in the regulation of glucose dynamics in organs central to metabolism. Although GLUT2 has been studied in the context of its participation in peripheral and central glucose sensing, its role in the brain is not well understood. To decipher the role of GLUT2 in brain development, we knocked down slc2a2 (glut2), the functional ortholog of human GLUT2, in zebrafish. Abrogation of glut2 led to defective brain organogenesis, reduced glucose uptake and increased programmed cell death in the brain. Coinciding with the observed localization of glut2 expression in the zebrafish hindbrain, glut2 deficiency affected the development of neural progenitor cells expressing the proneural genes atoh1b and ptf1a but not those expressing neurod. Specificity of the morphant phenotype was demonstrated by the restoration of brain organogenesis, whole-embryo glucose uptake, brain apoptosis, and expression of proneural markers in rescue experiments. These results indicate that glut2 has an essential role during brain development by facilitating the uptake and availability of glucose and support the involvement of glut2 in brain glucose sensing

The Discovery of a Potent, Selective, and Peripherally Restricted Pan-Trk Inhibitor (PF-06273340) for the Treatment of Pain

The neurotrophin family of growth factors, comprised of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4), is implicated in the physiology of chronic pain. Given the clinical efficacy of anti-NGF monoclonal antibody (mAb) therapies, there is significant interest in the development of small molecule modulators of neurotrophin activity. Neurotrophins signal through the tropomyosin related kinase (Trk) family of tyrosine kinase receptors, hence Trk kinase inhibition represents a potentially “druggable” point of intervention. To deliver the safety profile required for chronic, nonlife threatening pain indications, highly kinase-selective Trk inhibitors with minimal brain availability are sought. Herein we describe how the use of SBDD, 2D QSAR models, and matched molecular pair data in compound design enabled the delivery of the highly potent, kinase-selective, and peripherally restricted clinical candidate PF-06273340

Luteinizing hormone induces ovulation via tumor necrosis factor α-dependent increases in prostaglandin F2α in a nonmammalian vertebrate

Ovulation is induced by the preovulatory surge of luteinizing hormone (LH) that acts on the ovary and triggers the rupture of the preovulatory ovarian follicle by stimulating proteolysis and apoptosis in the follicle wall, causing the release of the mature oocyte. The pro-inflammatory cytokine tumor necrosis factor α (TNFα) and prostaglandin (PG) F2α (PGF2α) are involved in the control of ovulation but their role mediating the pro-ovulatory actions of LH is not well established. Here we show that Lh induces PGF2α synthesis through its stimulation of Tnfα production in trout, a primitive teleost fish. Recombinant trout Tnfα (rTnfα) and PGF2α recapitulate the stimulatory in vitro effects of salmon Lh (sLh) on contraction, proteolysis and loss of cell viability in the preovulatory follicle wall and, finally, ovulation. Furthermore, all pro-ovulatory actions of sLh are blocked by inhibition of Tnfα secretion or PG synthesis and all actions of rTnfα are blocked by PG synthesis inhibitors. Therefore, we provide evidence that the Tnfα-dependent increase in PGF2α production is necessary for the pro-ovulatory actions of Lh. The results from this study shed light onto the mechanisms underlying the pro-ovulatory actions of LH in vertebrates and may prove important in clinical assessments of female infertility

Creencias sobre la relación familia-escuela de docentes y futuros docentes

[Abstract] Teachers’ and trainee teachers’ beliefs have been capturing the attention of researchers for the last few decades but beliefs about family-school relationships are not often addressed. Our aim was to compare teachers and trainee teachers’ beliefs about familyschool relationships and their self-efficacy to relate with families. Participants were 133 teachers and 194 trainee teachers. We used the Beliefs about Family-School Relationships questionnaire comprised of 22 items that explore beliefs about collaboration, subordination (families should accept the teacher’s authority), delegation (families leaving education to the professionals), and self-efficacy to relate with families. Participants felt highly able to relate with families and support collaboration beliefs, but trainee teachers believed more in collaboration than qualified teachers did. Preschool teachers and trainee teachers believed more in collaboration and less in subordination and delegation compared to primary teachers and trainee teachers. These results have implications for teachers’ undergraduate training and lifelong learning about family-school collaboration.[Resumen] En las últimas décadas, los investigadores han estudiado las creencias de los docentes en ejercicio y en formación, pero se han ocupado menos de las creencias sobre la relación familia-escuela. El objetivo de este trabajo era comparar las creencias sobre la relación familiaescuela y la auto-eficacia para relacionarse. Participaron 133 profesores y 194 futuros docentes. Se usó el Cuestionario de Creencias sobre las Relaciones Familia-Escuela, que consta de 22 ítems que exploran las creencias sobre colaboración, subordinación (las familias deberían aceptar la autoridad del docente), delegación (las familias se despreocupan de la educación), y la auto-eficacia para relacionarse con las familias. Los participantes se sentían altamente capaces y apoyaban la colaboración, pero los futuros docentes creían más en la colaboración que los docentes en ejercicio. Los profesores y los futuros docentes de educación infantil creían más en la colaboración y menos en la subordinación y la delegación, comparados con los profesores y futuros docentes de educación primaria. Estos resultados tienen implicaciones para la formación inicial y continua de los docentes con respecto a la colaboración familia-escuela

Diseño e instalación de una planta solar fotovoltaica de 100kW para autoconsumo de una nave industrial

Se estudiara la implantacion de una planta solar fotovoltaica para una nave y un estudio de la estructura de los panelesUniversidad Europea de MadridGrado en Ingeniería en Sistemas IndustrialesPresencia

Generación de biogás a partir de las aguas residuales y residuos orgánicos de una escuela en África

En las últimas décadas se ha intensificado la necesidad del desarrollo de nuevas tecnologías orientadas a la producción de energía de forma limpia y sostenible. Esto se debe principalmente al hecho de que el uso de combustibles fósiles contribuye de forma acentuada para la generación de gases de efecto invernadero. En este aspecto la optimización de metodologías para la producción de biocombustibles destaca por la abundante disponibilidad de materia orgánica, con lo cual presenta elevado potencial energético. Con la utilización de biodigestores en el proceso de fermentación de la materia orgánica, se obtiene el biogás que posee en su composición el gas metano, ampliamente utilizado como combustible. En este trabajo fin de grado se propone el diseño de digestores anaerobios para el tratamiento de las aguas residuales y residuos orgánicos con el objetivo final de la obtención de biocombustible que pueda ser utilizado en las instalaciones donde se producen los desechos orgánicos. Dichas instalaciones se ubican una escuela de primaria en una favela de África, localizada a 45km al norte de Nairobi, capital de Kenia. En dicha escuela no existen infraestructuras relacionadas con la gestión de residuos ni con el tratamiento de aguas residuales, lo que produce problemas de salud pública. Además, la escuela podrá ahorrar hasta 3240 euros al año en combustible. Una vez que se haya instalado el biodigestor, se plantea capacitar profesionalmente a los empleados y familiares en las labores técnicas de implementación y mantenimiento. Para ello, es importante destacar también que se ha adoptado un documento de consenso internacional, la Agenda 2030 para el Desarrollo Sostenible de las Naciones Unidas. Las metas están marcadas en cada uno de los objetivos, con lo cual se han enfocado en los ODS (1) Fin de la pobreza, (4) Educación de calidad, (6) Agua limpia y saneamiento, (7) Energía asequible y no contaminante, (13) Acción por el clima.<br /

Relationship between tissue retention efficiency and production traits in a slow-growing broiler population

An experiment was conducted using 96 individually caged male broilers between 49 and 77 d of age. One objective was to establish phenotypic relationships between some production traits [feed conversion ratio (FCR), feed consumption, residual feed consumption (RFC), relative weight gain (RWG), weight gain (WG) and live weight (LW)] and “tissue retention efficiency” (TRE) traits in a slow-growing broiler population. The other objective was the characterization of Campero-INTA broilers for TRE traits. Weight and feed consumption were recorded weekly. Forty four broilers were slaughtered at 44 d of age to estimate initial body composition while the remaining birds were slaughtered at 79 d of age. Ether extract and crude protein content of the carcasses were used to estimate TRE traits: Energy retained as protein (ERP), energy retained as fat (ERF), ERP/(ERP+ERF), ERF/(ERP+ERF), protein retention efficiency and lipid-protein ratio. Correlation coefficients between traits were obtained and regression analyses were done for the evaluation of the influence of production traits on TRE traits. The independent variable that best explained ERF was WG (R2 = 0.49). Inclusion of final LW and RWG raised the R2 to 0.58 and decreased the error term. The ERP was best explained by RWG (R2 = 0.37); lipid-protein ratio by final LW (R2 = 0.49); protein retention efficiency by FCR (R2 = 0.34) and fraction of retained energy (ERF-ERP/ERP+ERF) by WG (R2 = 0.29). The TRE traits were not well predicted by the measured production traits. The high phenotypic variability observed in some of the TRE traits suggested a need for further studies on these characteristics. Keywords: Broiler; tissue retention; efficiency; slow-growing stock South African Journal of Animal Science Vol. 37 (3) 2007: pp.164-16