The evolution of gene expression levels in mammalian organs.

Changes in gene expression are thought to underlie many of the phenotypic differences between species. However, large-scale analyses of gene expression evolution were until recently prevented by technological limitations. Here we report the sequencing of polyadenylated RNA from six organs across ten species that represent all major mammalian lineages (placentals, marsupials and monotremes) and birds (the evolutionary outgroup), with the goal of understanding the dynamics of mammalian transcriptome evolution. We show that the rate of gene expression evolution varies among organs, lineages and chromosomes, owing to differences in selective pressures: transcriptome change was slow in nervous tissues and rapid in testes, slower in rodents than in apes and monotremes, and rapid for the X chromosome right after its formation. Although gene expression evolution in mammals was strongly shaped by purifying selection, we identify numerous potentially selectively driven expression switches, which occurred at different rates across lineages and tissues and which probably contributed to the specific organ biology of various mammals.

Contribution of PaTrin-2 in Radiotherapy with Temozolomide for the Treatment of Glioblastoma Expressing MGMT

Purpose/Objective(s): Current standard treatment of glioblastoma is radiotherapy (RT) concomitant with temozolomide (TMZ), an alkylating agent. O6-methylguanine-DNA methyltransferase (MGMT) expression is a major mechanism of resistance to Proceedings of the alkylating agent chemotherapy, and MGMT gene promoter methylation (present in 30-45 % of tumors) has been shown to be predictive for tumor response to TMZ therapy. MGMT, an exhaustible repair protein can be depleted by specific inhibitors such as O6- benzylguanine or the non-toxic O6-(4-bromothenyl)guanine (PaTrin-2). Here we have studied the efficacy of the combination of TMZ, RT, and PaTrin-2 to improve the treatment outcome in glioblastoma expressing MGMT. Materials/Methods: 3 glioblastoma lines were chosen: LN18 and T98G expressing MGMT and U251 lacking MGMT expression. A shRNA approach was used to selectively and permanently knockdown level of MGMT in LN18 line. Cells were treated with 10 mM PaTrin-2. After 2 h, various concentrations of TMZ were added, cells were incubated for 24 h, and clonogenic assays were performed. After the same PaTrin-2 pretreatment and 100 mM TMZ exposure, cells were plated 4 h before irradiation with increasing RT doses of up to 6 Gy. Clonogenic survival was assessed after 14 days. Results: Western blot analysis confirmed that reduction of MGMT expression was achieved in LN18A1 expressing MGMT-targeting shRNA. The shRNA non-targeting control sequence did not influenceMGMTprotein level (LN18NT). PaTrin-2 showed no toxicity at 10 mMon the 5 cell lines. TMZ induced up to 70 and 97%of cell death on LN18A1 and U251, respectively, but was not toxic up to 50 mMfor T98G, LN18, and LN18NT. Up to 53%increased TMZ toxicity was observed on the 5 cell lines when treated with the 2 drugs. Irradiation of the 5 lines treated or not with PaTrin-2 showed no survival difference at any irradiation dose. When LN18A1 and U251 cells were irradiated post TMZ treatment, an up to 2.5 and 139.4 fold increase in toxicity, respectively, was observed compared to un-pretreated controls. By contrast, TMZ pretreatment did not increase irradiation toxicity on T98G, LN18, and LN18NT. When cells were incubated with PaTrin-2 and TMZ before the irradiation, up to 3.7, 3.9, 5.8, 6.6 and 348.5 fold increase in toxicity was observed compared to controls on LN18, LN18NT, LN18A1, T98G and U251, respectively. Conclusions: We present here results of TMZ and PaTrin-2 combination ± RT on glioblastoma lines. U251 and LN18A1 cells were much more sensitive to TMZ than LN18, LN18NT, and T98G. PaTrin-2 enhanced the toxicity of TMZ on the MGMT expressing glioblastoma lines. RT further increased TMZ and PaTrin-2 efficacy. These results are encouraging for the treatment of patients with glioblastoma expressing MGMT who have the worst prognosis and respond poorly to RT combined with TMZ.

Reliure de : Pensées chrétiennes tirées de l'Écriture sainte et des saints Pères pour tous les jours du mois, par M. É.-F. Vernage,...

Numérisation partielle de reliure

[Illustrations de Histoire de la mission des Pères Capucins en l'Isle de Maragnan et terres circonvoisines...] / L. Gaultier [grav.] ; Le Père Claude d'Abbeville, aut. du texte

Comprend : [Frontispice : Pape, moine, personnification de l'Eglise. Armoiries. XVIè siècle.] [cote : microfilm m 10858/R 15836] ; [pl. en reg. p.90 : élévation d'une croix pour la bénédiction de l'Ile de Maragnan. XVIIè siècle.] [cote : microfilm m 10858/R 15836] ; [pl. en reg. p.348 : indigène de l'Ile de Maragnan, nommé François Carypyra, de la tribu des Tabaiares. XVIIè siècle.] François Carypyra. [cote : microfilm m 10858/R 15836] ; [pl. en reg. p.356 : indigène de l'Ile de Maragnan, nommé Jacques Patova. XVIIè siècle.] Jacques Patova. [cote : microfilm m 10858/R 15836] ; [pl. en reg. p.359 : indigène de l'Ile de Maragnan, nommé Antoine Manen, natif de Renary, originaire de Para de l'Ouest. XVIIè siècle.] Anthoine Manen. [cote : microfilm m 10858/R 15836] ; [pl. en reg. p.362 : indigène de l'Ile de Maragnan, nommé Itapoucou Topinamba et baptisé Louis-Marie. XVIIè siècle.] Louis Marie. [cote : microfilm m 10858/R 15836] ; [pl. en reg. p.364 : indigène de l'Ile de Maragnan, nommé Ouäroyio Topinamba et baptisé Louis-Henry. XVIIè siècle.] Louis Henri. [cote : microfilm m 10858/R 15836] ; [pl. en reg. p.365 : indigène de l'Ile de Maragnan, nommé Iapouäy et baptisé Louis de Saint-Jean. XVIIè siècle.] Louis de St. Iehan. [cote : microfilm m 10858/R 15836]

Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits.

Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5×10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.

Automatic Mapping and Classification of Spatial Environmental Data

The paper deals with the development and application of the generic methodology for automatic processing (mapping and classification) of environmental data. General Regression Neural Network (GRNN) is considered in detail and is proposed as an efficient tool to solve the problem of spatial data mapping (regression). The Probabilistic Neural Network (PNN) is considered as an automatic tool for spatial classifications. The automatic tuning of isotropic and anisotropic GRNN/PNN models using cross-validation procedure is presented. Results are compared with the k-Nearest-Neighbours (k-NN) interpolation algorithm using independent validation data set. Real case studies are based on decision-oriented mapping and classification of radioactively contaminated territories.

S. Pau. I Corintis 12: 12-31: El cos humà i l'Església. Paràmetres clàssics d'un símil útil i veritablement significatiu.

L'objectiu d'aquest article és presentar un seguit de textos clàssics d'autors i escoles filosòfiques diferents que poden estar en la base subconscient de la primera carta de Sant Pau als Corintis. L'apòstol es mostra molt hàbil en l'ús de la imatge del cos humà i de la necessària coordinació de tots els seus membres per fer veure a la comunitat cristiana de Corint la urgència d¿aparcar tota dissensió interna en ares de la unitat. Tanmateix, aquesta imatge no és una creació original stricto sensu de l'apòstol, sinó que ja la medicina, la filosofia i la historiografia gregues l'havien emprada amb finalitats diverses.

S. Pablo. I Corintios 12: 12-31: El cuerpo humano y la Iglesia. Parámetros clásicos de un símil útil y verdaderamente significativo

El objetivo de este artículo es presentar un conjunto de textos clásicos de autores i escuelas filosóficas diferentes que pueden estar en la base subconsciente de la primera carta de San Pablo a los Corintios. El apóstol se muestra muy hábil en el uso de la imagen del cuerpo humano y de la necesaria coordinación de todos sus miembros para convencer a la comunidad cristiana de Corinto de la urgencia de aparcar toda disensión interna en aras de la unidad. Sin embargo, esta imagen no es una creación original stricto sensu del apóstol, sino que ya la medicina, la filosofía y la historiografía griegas la habían usado con finalidades diversas.

Antihelenismo y anticlasicismo en la obra de Oscar Wilde. El polo opuesto de una mente paradójica.

Gracias a una poderosa arma intelectual, la paradoja, Oscar Wilde descubre también los déficits del Clasicismo y del Helenismo. Un análisis riguroso del conjunto de su obra desde la perspectiva de la Tradición Clásica, nos revela también un Oscar Wilde diferente del usual Wilde filohelénico y, sobre todo, platónico. El objetivo de este artículo es abordar un tema muy poco estudiado por los filólogos clásicos cual es el anticlasicismo y el antihelenismo como necesidades intelectuales.