P-glycoprotein of blood brain barrier: cross-reactivity of MAb C219 with a 190 kDa protein in bovine and rat isolated brain capillaries

AbstractP-glycoprotein (P-gp), an active efflux pump of antitumor drugs, is strongly expressed in endothelial cells of the blood brain barrier (BBB). Two proteins (155 and 190 kDa) were detected by Western blot analysis of beef and rat capillaries with the monoclonal antibody (MAb) C219. In order to characterize the nature of these proteins, their profile of solubilization by different detergents was established and compared with that of P-gp from the CHRC5 tumoral cell line. The 155 kDa protein (p155) of capillaries and the P-gp of CHRC5 cells were well solubilized by deoxycholate and Elugent, whereas the 190 kDa protein (p190) was only solubilized by sodium dodecylsulfate (SDS). Both proteins have different patterns of extraction by Triton X-114, p155 partitioning as a membrane protein, while p190 was insoluble. Deglycosylation of capillary proteins resulted in a 27–28 kDa decrease in the apparent molecular weight of p155, similar to that observed for the P-gp of CHRC5 cells, but a decrease of only 7–8 for p190. Only p155 was immunoprecipitated by MAb C219. These results suggest that only p155 is the P-gp in BBB and that MAb C219 cross-reacts with a 190 kDa MDR-unrelated glycosylated protein. Consequently, the use of this antibody, which is frequently used to detect P-gp in tumors, could be a pitfall of immunohistochemistry screening for cancer tissues and lead to false positive in the diagnosis of MDR

Enseigner des valeurs à l'ordre collégial

Dans le contexte social et scolaire actuel, il existe une volonté de plus en plus grande des cégeps de donner un sens à la formation technique en enseignant les valeurs rattachées au métier, tout en faisant de la réussite des études une entreprise personnelle. À cet égard, un partenariat entre le Cégep Limoilou et l’Université Laval a permis de développer des activités pédagogiques concrètes pour l’enseignement de valeurs entrepreneuriales dans la formation technique. Cet article présente Ça me tient à cœur !, une activité élaborée en vue de l’acquisition de valeurs entrepreneuriales dans une perspective de développement durable. On y expose les visées de l’activité, les modalités de son déroulement et les résultats de son expérimentation en classe. Réalisée dans un programme technique spécifique, à savoir le programme de Technologie de la mécanique du bâtiment, l’activité présentée est néanmoins transférable à tout programme collégial dont les buts recouvrent le développement de valeurs ou la formation citoyenne. L’article évoque enfin trois autres activités visant le développement d’un système de valeur par les étudiants

A Hexagonal Theory of Flavor

We construct a supersymmetric theory of flavor based on the discrete gauge group (D_6)^2, where D_6 describes the symmetry of a regular hexagon under proper rotations in three dimensions. The representation structure of the group allows one to distinguish the third from the lighter two generations of matter fields, so that in the symmetry limit only the top quark Yukawa coupling is allowed and scalar superpartners of the first two generations are degenerate. Light fermion Yukawa couplings arise from a sequential breaking of the flavor symmetry, and supersymmetric flavor-changing processes remain adequately suppressed. We contrast our model with others based on non-Abelian discrete gauge symmetries described in the literature, and discuss the challenges in constructing more minimal flavor models based on this approach.Comment: 19 pages, ReVTeX, 1 eps figur

Teaching values at the college level

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Cut-points for waist circumference in Europids and South Asians

There is little strong evidence that currently recommended higher waist circumference cut-points for Europids compared with South Asians are associated with similar risk for type 2 diabetes. This study was designed to provide such evidence. Longitudinal studies over 5 years were conducted among 5,515 Europid and 2,214 ethnically South Asian participants. Age-standardized diabetes incidence at different levels of waist circumference and incidence difference relative to a reference value were calculated. The Youden Index was used to determine waist circumference cut-points. At currently recommended cut-points, estimated annual diabetes incidence for a 50-year-old Europid was &lt;0.6% for both sexes, and for a 50-year-old South Asian, 5.8% for men and 2.1% for women. Annual diabetes incidence of 1% was observed for a 50 year old at a waist circumference 35&ndash;40 cm greater in Europid compared to South Asian men and women. Incidence difference between recommended cut-points and a reference value (80 cm in men, 70 cm in women) was 0.3 and 4.4% per year for Europid and South Asian men, and 0.2 and 0.8% per year for Europid and South Asian women, respectively. Waist circumference cut-points chosen using the Youden Index were shown to be dependent on obesity levels in the population. The much higher observed risk of diabetes in South Asians compared to Europids at the respective recommended waist circumference cut-points suggests that differences between them should be greater. Approaches that use the Youden Index to select waist circumference cut-points are inappropriate and should not be used for this purpose.<br /

Anthropometry measures and prevalence of obesity in the urban adult population of Cameroon: an update from the Cameroon Burden of Diabetes Baseline Survey

BACKGROUND: The objective of the study was to provide baseline and reference data on the prevalence and distribution of overweight and obesity, using different anthropometric measurements in adult urban populations in Cameroon. METHODS: The Cameroon Burden of Diabetes Baseline Survey was a cross-sectional study, conducted in 4 urban districts (Yaoundé, Douala, Garoua and Bamenda) of Cameroon, using the WHO Step approach for population-based assessment of cardiovascular risk factors. Body mass index, waist circumference and waist-to-hip ratio were measured using standardized methods. Overall, 10,011 individuals, 6,004 women and 4,007 men, from 4,189 households, aged 15 years and above participated. RESULTS: Based on body mass index, more than 25% of urban men and almost half of urban women were either overweight or obese with 6.5% of men and 19.5% of women being obese. The prevalence of obesity showed considerable variation with age in both genders. Using body mass index provided the highest prevalence of obesity in men (6.5%) and waist-to-hip ratio the lowest prevalence (3.2%). Among women, using waist-to-hip ratio and waist circumference yielded the highest prevalence of obesity (28%) and body mass index the lowest (19.5%). There was a trend towards an increase in age-adjusted odd ratios of being overweight or obese with duration of education in both sexes. CONCLUSION: The study provides current data on anthropometric measurements and obesity in urban Cameroonian populations, and found high prevalences of overweight and obesity particularly over 35 years of age, and among women. Prevalence varied according to the measure used. Our findings highlight the need to carry out further studies in Cameroonian and other Sub-Saharan African populations to provide appropriate cut-off points for the identification of people at risk of obesity-related disorders, and indicate the need to implement interventions to reverse increasing levels of obesity

Estrogen receptor alpha drives proliferation in PTEN-deficient prostate carcinoma by stimulating survival signaling, MYC expression and altering glucose sensitivity

While high doses of estrogen, in combination with androgens, can initiate prostate cancer (PCa) via activation of the estrogen receptor α (ERα), the role of ERα in PCa cells within established tumors is largely unknown. Here we show that expression of ERα is increased in high grade human PCa. Similarly, ERα is elevated in mouse models of aggressive PCa driven by MYC overexpression or deletion of PTEN. Within the prostate of PTEN-deficient mice, there is a progressive pattern of ERα expression: low in benign glands, moderate in tumors within the dorsal, lateral and ventral lobes, and high in tumors within the anterior prostate. This expression significantly correlates with the proliferation marker Ki67. Furthermore, in vitro knockdown of ERα in cells derived from PTEN-deficient tumors causes a significant and sustained decrease in proliferation. Depletion of ERα also reduces the activity of the PI3K and MAPK pathways, both downstream targets of non-genomic ERα action. Finally, ERα knockdown reduces the levels of the MYC protein and lowers the sensitivity of cellular proliferation to glucose withdrawal, which correlates with decreased expression of the glucose transporter GLUT1. Collectively, these results demonstrate that ERα orchestrates proliferation and metabolism to promote the neoplastic growth of PCa cells

Storytelling in den Vereinten Nationen: Mahbub ul Haq und menschliche Entwicklung

Ausgehend von der Beobachtung, dass Mitarbeiter der Vereinten Nationen eine wichtige Rolle in Prozessen des ideellen Wandels auf internationaler Ebene spielen können, beschäftigt sich dieser Beitrag mit einer bestimmten Form individuellem Einflusses – dem storytelling. Mein Verständnis von storytelling als Einflusstaktik kombiniert dabei kollektive Elemente der soziologischen Praxistheorie mit den reflexiven, akteursbezogenen Überlegungen von Michel de Certeau. Ich analysiere storytelling anhand von drei analytischen Elementen: einem (chronologischen) Plot, einer Reihe von Charakteren und einem interpretativen Thema – die jeweils ihre Wirkung im Zusammenspiel mit der Subjektivität ihres storytellers entfalten. Ich illustriere diese theoretischen Überlegungen mit dem Fall von Mahbub ul Haq, dem es als Sonderberater des United Nations Development Programme (UNDP)-Administrators zu Beginn der 1990er Jahre gelungen ist, die Idee der menschlichen Entwicklung im System der Vereinten Nationen und der internationalen Entwicklungspolitik zu etablieren