A Comparative Chemogenomics Strategy to Predict Potential Drug Targets in the Metazoan Pathogen, Schistosoma mansoni

Schistosomiasis is a prevalent and chronic helmintic disease in tropical regions. Treatment and control relies on chemotherapy with just one drug, praziquantel and this reliance is of concern should clinically relevant drug resistance emerge and spread. Therefore, to identify potential target proteins for new avenues of drug discovery we have taken a comparative chemogenomics approach utilizing the putative proteome of Schistosoma mansoni compared to the proteomes of two model organisms, the nematode, Caenorhabditis elegans and the fruitfly, Drosophila melanogaster. Using the genome comparison software Genlight, two separate in silico workflows were implemented to derive a set of parasite proteins for which gene disruption of the orthologs in both the model organisms yielded deleterious phenotypes (e.g., lethal, impairment of motility), i.e., are essential genes/proteins. Of the 67 and 68 sequences generated for each workflow, 63 were identical in both sets, leading to a final set of 72 parasite proteins. All but one of these were expressed in the relevant developmental stages of the parasite infecting humans. Subsequent in depth manual curation of the combined workflow output revealed 57 candidate proteins. Scrutiny of these for ‘druggable’ protein homologs in the literature identified 35 S. mansoni sequences, 18 of which were homologous to proteins with 3D structures including co-crystallized ligands that will allow further structure-based drug design studies. The comparative chemogenomics strategy presented generates a tractable set of S. mansoni proteins for experimental validation as drug targets against this insidious human pathogen

Withanolides and related steroids

Since the isolation of the first withanolides in the mid-1960s, over 600 new members of this group of compounds have been described, with most from genera of the plant family Solanaceae. The basic structure of withaferin A, a C28 ergostane with a modified side chain forming a δ-lactone between carbons 22 and 26, was considered for many years the basic template for the withanolides. Nowadays, a considerable number of related structures are also considered part of the withanolide class; among them are those containing γ-lactones in the side chain that have come to be at least as common as the δ-lactones. The reduced versions (γ and δ-lactols) are also known. Further structural variations include modified skeletons (including C27 compounds), aromatic rings and additional rings, which may coexist in a single plant species. Seasonal and geographical variations have also been described in the concentration levels and types of withanolides that may occur, especially in the Jaborosa and Salpichroa genera, and biogenetic relationships among those withanolides may be inferred from the structural variations detected. Withania is the parent genus of the withanolides and a special section is devoted to the new structures isolated from species in this genus. Following this, all other new structures are grouped by structural types. Many withanolides have shown a variety of interesting biological activities ranging from antitumor, cytotoxic and potential cancer chemopreventive effects, to feeding deterrence for several insects as well as selective phytotoxicity towards monocotyledoneous and dicotyledoneous species. Trypanocidal, leishmanicidal, antibacterial, and antifungal activities have also been reported. A comprehensive description of the different activities and their significance has been included in this chapter. The final section is devoted to chemotaxonomic implications of withanolide distribution within the Solanaceae. Overall, this chapter covers the advances in the chemistry and biology of withanolides over the last 16 years.Fil: Misico, Rosana Isabel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados a la Química Orgánica (i); ArgentinaFil: Nicotra, V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; ArgentinaFil: Oberti, Juan Carlos María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; ArgentinaFil: Barboza, Gloria Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; ArgentinaFil: Gil, Roberto Ricardo. University Of Carnegie Mellon; Estados UnidosFil: Burton, Gerardo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados a la Química Orgánica (i); Argentin

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Diagnóstico molecular del virus de leucosis bovina en una población de vacas holstein, colombia

The bovine leukemia virus (BLV) has a single-stranded RNA genome; it belongs to the Retroviridae family and has eight different genotypes. B lymphocytes are the target cell of BLV, which has a negative impact on the immune system of cattle, making them more susceptible to other diseases of infectious origin; infected dairy cows also have lower production over herd (2.5 to 5 %). The disease is transmitted through consumption of milk and mostly iatrogenic. The aim of this study was to make the diagnosis of BLV by nested PCR technique in 500 samples of blood from Holstein cows, which belonging to several herds located in municipalities with dairyness in the department of Antioquia, it were taken during the months of february to june 2013. It was performed a nested PCR to detect a region of the provirus detecting the viral env gene. A fragment of 444 bp was obtained and the sequence identity was found through BLAST ® application. The BLV prevalence for the department of Antioquia was 44 % (219/500). One of the PCR product was sequenced and classified as genotype 1; finding a 99 % identity with the sequence FJ808575.1. Samples from three regions of Antioquia department (East, North and Aburra Valley) were evaluated; the BLV prevalence was 70 %, 45 %, 31 % respectively. The molecular prevalence of BLV was between 16 and 88 % by the municipality. There was statistically significant difference (p<0.05) between the region of origin and the virus prevalence. The presence of BLV has been confirmed in the majority of the evaluated dairy units, which belong to one most important dairy regions in the department of Antioquia.El virus de la leucosis bovina (BLV) posee un genoma RNA de cadena sencilla, pertenece a la familia Retroviridae y presenta ocho genotipos diferentes. Los linfocitos B son la célula blanco del BLV, lo cual tiene un impacto negativo sobre el sistema inmune de los bovinos ya que los hace más susceptibles a otras enfermedades de origen infeccioso además las vacas lecheras presentan una menor producción respecto al hato (2,5 a 5 %). Esta enfermedad se transmite a través del consumo de leche y principalmente de forma iatrogénica. El objetivo del presente trabajo fue diagnosticar BLV por medio de la técnica PCR anidada, para lo cual se tomaron 500 muestras de sangre de vacas Holstein pertenecientes a varios hatos ubicados en los principales municipios con carácter lechero en el departamento de Antioquía, durante los meses de febrero a junio de 2013. Se realizó una PCR anidada para detectar el provirus amplificando una región del gen env viral. Se obtuvo un fragmento de 444 pb y se comprobó la identidad de la secuencia a través de la aplicación BLAST ®. La prevalencia para el departamento de Antioquía fue del 44 % (219/500). Uno de los productos de PCR fue secuenciado y clasificado como genotipo 1; se encontró un 99 % de identidad con la secuencia FJ808575.1. Se evaluaron tres subregiones lecheras Oriente, Norte y Valle de Aburra. La presencia del virus fue de 70 %, 45 %, 31 % respectivamente. La prevalencia molecular de BLV varió entre 16 y 88 % por municipio. Se encontró diferencia estadísticamente significativa (p<0,05) entre el lugar de origen de la muestra y la presencia del virus. Se ha confirmado la presencia BLV en gran parte de las unidades lecheras evaluadas en una de las regiones lecheras más importantes en el departamento de Antioquía

Journal of Developmental Entrepreneurship : Vol. 20, No. 3, September 2015

1. The Challenge of Being an Entrepreneur: Editor’s Note / P. Koveos 2. Devaluation, Competitiveness, and New Business Formation in Emerging Countries / H. Herrera-Echeverri, et al. 3. Comparing the Development of Entrepreneurial Self-Efficiacy of Female Entrepreneurs in Male- and Female-Dominated Industries / G.L. Sweida, J.A. Woods 4. Chance Non-Control and Entrepreneurship / B. Antoncic, et al. 5. Entrepreneurship Education in the Cotext of Developing Countries: study of the status and the main barriers in Mozambican Higher Education Institutions /D.B. Libombo, A. Dinis 6. Benchmarking Entrepreneurship Education in U.S., Australian, and New Zealand University Agriculture Programs / J.E. Mehlhorn, et al. 7. Social Media Use to Suport Entrepreneurship in the Face of Disruption / H. Ajjan, et al. 8. Are Entrepreneurs’ Networks Dynamic? A replication study testing changes in entrepreneurs’ networks during new venture development / D.M. Sulliva

Foreign Investment, Institutional Quality, Public Expenditure, and Activity of Venture Capital Funds in Emerging Market Countries

This paper empirically analyzes the effects of foreign direct investment (FDI), institutional quality, and the size of a government on venture capital (VC) activity. We conclude that institutional quality, FDI, and public spending have definitive importance as elements for the development of a public policy that increases the quantity and quality of VC fund (VCF) investment. Higher institutional quality, greater FDI, and lower public spending allow the volume of VCF investment to grow. FDI shows a higher level of significance in promoting investment in high-tech companies, and institutional quality increases the productivity of FDI investment in the generation of VCF. Government spending dramatically and (counter-intuitively) adversely affects the activities of VCF. Notably, the higher the institutional quality of a country, the less state intervention is required to promote investment of VCF. The results are consistent with the hypothesis of the FDI spillover and crowding out by public spending