The Akt-like kinase of Leishmania panamensis: As a new molecular target for drug discovery.

The Akt-like kinase of Leishmania spp. is a cytoplasmic orthologous protein of the serine/threonine kinase B-PKB/human-Akt group, which is involved in the cellular survival of these parasites. By the application of a computational strategy we obtained two specific inhibitors of the Akt-like protein of L. panamensis (UBMC1 and UBMC4), which are predicted to bind specifically to the pleckstrin domain (PH) of the enzyme. We show that the Akt-like of Leishmania panamensis is phospho-activated in parasites under nutritional and thermic stress, this phosphorylation is blocked by the UBMC1 and UMBC2 and such inhibition leads to cell death. Amongst the effects caused by the inhibitors on the parasites we found high percentage of hypodiploidy and loss of mitochondrial membrane potential. Ultrastructural studies showed highly vacuolated cytoplasm, as well as shortening of the flagellum, loss of nuclear membrane integrity and DNA fragmentation. Altogether the presented results suggest that the cell death caused by UMBC1 and UMBC4 may be associated to an apoptosis-like process. The compounds present an inhibitory concentration (IC50) over intracellular amastigotes of L. panamensis of 9.2±0.8µM for UBMC1 and 4.6±1.9µM for UBMC4. The cytotoxic activity for UBMC1 and UBMC4 in human macrophages derived from monocytes (huMDM) was 29±1.2µM and >40µM respectively. Our findings strongly support that the presented compounds can be plausible candidates as a new therapeutic alternative for the inhibition of specific kinases of the parasite.

Mapping of main and epistatic effect QTLs associated to grain protein and gluten strength using a RIL population of durum wheat.

Quality, specifically protein content and gluten strength are among the main objectives of a durum wheat breeding program. The aim of this work was to validate quantitative trait loci (QTLs) associated with grain protein content (GPC) and gluten strength measured by SDS sedimentation volume (SV) and to find additional QTLs expressed in Argentinean environments. Also, epistatic QTL and QTL x environmental interactions were analyzed. A mapping population of 93 RILs derived from the cross UC1113 x Kofa showing extreme values in gluten quality was used. Phenotypic data were collected along six environments (three locations, two years). Main effect QTLs associated with GPC were found in equivalent positions in two environments on chromosomes 3BS (R(2)=21.0-21.6%) and 7BL (R(2)=12.1-13%), and in one environment on chromosomes 1BS, 2AL, 2BS, 3BL, 4AL, 5AS, 5BL and 7AS. The most important and stable QTL affecting SV was located on chromosome 1BL (Glu-B1) consistently detected over the six environments (R(2)=20.9- 54.2%). Additional QTLs were found in three environments on chromosomes 6AL (R(2)=6.4-12.5%), and in two environments on chromosomes 6BL (R(2)=11.5-12.1%), 7AS (R(2)=8.2-10.2%) and 4BS (R(2)=11-16.4%). In addition, pleiotropic effects were found affecting grain yield, test weight, thousand-kernel-weight and days to heading in some of these QTLs. Epistatic QTLs and QTL x environment interactions were found for both quality traits, mostly for GPC. The flanking markers of the QTLs detected in this work could be efficient tools to select superior genotypes for the mentioned traits.

Immunohistochemistry expression of P53, Ki67, CD30, and CD117 and presence of clinical metastasis at diagnosis of testicular seminoma.

INTRODUCTION: We evaluated the immunohistochemical expression of p53, Ki67, CD30, and CD117 and correlated it with histological features and presence of clinical metastasis at diagnosis of testicular seminomas. MATERIALS AND METHODS: A retrospective study of 62 patients was performed in patients with pure seminoma. The retroperitoneum was staged with computed tomography scan and the thorax with simple x-rays and/or computed tomography scan. Pathologists were unaware of the clinical stage of the patients. Manual microarrays were created from a tissue representative of tumor. The expression of p53, Ki67, CD30, and CD117 was evaluated as negative, any degree of expression, and expression in more than 50% of neoplastic cells. Univariate and multivariate analysis were performed. RESULTS: Sixty-two cases were analyzed: 43 cases were in clinical stage I (69.4%), 17 were in clinical stage II (27.4%), and 2 were in clinical stage III (3.2%). Fifty-six cases expressed CD117 (90%), 42 p53 (68%), 8 CD30 (13%), and all cases Ki67. There were no differences in p53, Ki67, CD30, and CD117 expression between testicular seminoma with and without clinical metastasis at diagnosis, regardless of the magnitude of expression. Neither of them found positive association between these marker expressions and morphologic risk factors such as tumor size greater than 6 cm and rete testis invasion. CONCLUSIONS: This study shows that expression of p53, Ki67, and CD30 and loss of CD117 expression fail to predict the presence of clinical metastasis at diagnosis of testicular seminoma and do not correlate with other histopathological risk factors in clinical stage I patients.

Prevalencia de hábitos, conductas e intereses de estudiantes de medicina de 5 escuelas del país / Prevalence of habits, behaviors and interests among medical students from 5 medical school in Chile

Los estudiantes de medicina dedican gran parte del tiempo a estudiar las materias necesarias para su preparación profesional. Así, logran un adecuado desarrollo de conocimientos científicos y competencias médicas. Sin embargo, los médicos necesitan desarrollar habilidades humanísticas.Su objetivo es conocer prevalencias de hábitos, conductas e intereses de alumnos de medicina de distintas escuelas del país, públicas y privadas, en áreas culturales, recreativas, deportivas, actividades comunitarias y de ayuda social, religiosas, políticas, y trabajos remunerados. Se realizó una encuesta anónima a 299 alumnos de medicina de 5 Universidades del país de primero, tercero, y séptimo año; elegidos al azar, en aspectos antes mencionados. Los datos se analizaron con el programa EpiInfo 2002. Fuman: 31,1 por ciento. Bebe alcohol: 73,91 por ciento. Leen periódicos: 75,59 por ciento, priorizan noticias nacionalesy culturales. Actividades recreativas no deportivas y deportivas más de una vez al mes: 51,2 por ciento y 51,51 por ciento. Un 27,09 por ciento realiza actividades comunitarias, considerándolas importante un 79,26 por ciento. Un 61,54 por ciento manifiesta interés por política, sólo un 55,85 por ciento está inscrito en el Servicio Electoral. Un 71,57 por ciento adhiere a alguna religión, un 70 por ciento se declara católico. No trabaja un 77,93 por ciento, la mayoría por no tener tiempo. Los que trabajan, 62,5 por ciento lo hacen para tener dinero extra.Casi la mitad de los estudiantes de medicina dedica parte de su tiempo a actividades culturales, y a pesar de que la mayoría considera importante para su formación la práctica de actividades comunitarias, pocos las realizan. En las escuelas de medicina no hay un claro incentivo para el desarrollo de las artes y letras, por lo que creemos debe impulsarse la integración de las humanidades médicas en la malla curricular de la carrera de medicina.

Most of their time, medical students are engaged in studying the courses needed for their professional training. Thus, they develop an adequate scientific knowledge and acquire medical skills. However, physicians also need to develop humanistic abilities. The purpose of the present work is to assess the prevalence of habits, behaviors and interests among medical students from different public and private medical schools across the country, considering the areas of culture, leisure, sports, community and social care, religion, politics and paid jobs. An anonymous survey was carried out among 299 randomly selected medical students from5 Chilean Universities who were in the first, the third and the seventh year of their career. Data analysis was performed with EpiInfo 2002. The results were as follows: 31,11 percent were smokers; 73.91 percent drank alcohol; 75.59 percent read the newspapers, favoring national and culture news; 51.2 percent and 51.51 percent performed non-sport leisureand sport activities more than once a month; 27.09 percent were involved in community aid, and 79.26 percent considered such activities as important; 61.54 percent expressed interest in politics, and only 55.85 percent were listed on the electoral roll; 71.57 percent adhered to any religion, 70 percent declared themselves Catholics; 77.93 percent did not work, most of them due to lack of time; among those who worked, 62.5 percent did it to obtain extra money. Almost half of medical students spend part of their time in cultural activities, and although most of the students consider community care as an important factor for their training, very few put into practice such activities. Medical schools do not encourage clearly enough the development of arts and letters, therefore the integration of medical humanities to the medical curriculum should be encouraged.

Three new furostanol saponins from the leaves of Lycianthes synanthera ("Chomte"), an edible Mesoamerican plant.

Three new furostanol oligoglycosides, 3-O-{alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->4)]-beta-D-glucopyranosyl}-26-O-beta-D-glucopyranosyl-22alpha-methoxy-25R-furost-5-ene-3beta,17alpha,26-triol (1), 3-O-{alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->4)]-beta-D-glucopyranosyl}-26-O-beta-D-glucopyranosylfurost-5-ene-3beta,17alpha,22alpha,25,26-pentol (2), and 3-O-{alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->4)]-beta-D-glucopyranosyl}-26-O-beta-D-glucopyranosylfurost-5-ene-3beta,22alpha,25,26-tetrol (3), named lycianthosides A-C, together with known flavone glycosides were isolated from Lycianthes synanthera leaves, an edible plant of the Solanaceae family that grows naturally in Guatemala. The nutrient composition of the raw leaves was also evaluated.