Our paper provides several insights on the characteristics of the concept of “Poles d’Excellence Rurale” (PER) through bilateral comparisons with that of Competitive Pole (CP) and cluster. The concept of PER is a French government’ initiative designed for the development of rural areas similar to that of the Competitive Pole. We emphasize important particularities of these concepts by analyzing some of their similarities and major differences.Pole d’Excellence Rurale, Competitive Pole, cluster, rural development

Busche, A.

Dopatka, M.

Dutrannoy, V.

Esquitino, V.

Garshasbi, M.

Gavvovidis, I.

Ghani, M.

Klose, J.

Kuss, A.

Meyer, F.

Mueller, S.

Neitzel, H.

Nowak, J.

Nowak, S.

Poehlmann, C.

Ropers, H.

Schindler, D.

Sperling, K.

Trimborn, M.

Walther, D.

Zabel, C.

PLoS ONE

English

PubMed

Mutations in the human gene MCPH1 cause primary microcephaly associated with a unique cellular phenotype with premature chromosome condensation (PCC) in early G2 phase and delayed decondensation post-mitosis (PCC syndrome). The gene encodes the BRCT-domain containing protein microcephalin/BRIT1. Apart from its role in the regulation of chromosome condensation, the protein is involved in the cellular response to DNA damage. We report here on the first mouse model of impaired Mcph1-function. The model was established based on an embryonic stem cell line from BayGenomics (RR0608) containing a gene trap in intron 12 of the Mcph1 gene deleting the C-terminal BRCT-domain of the protein. Although residual wild type allele can be detected by quantitative real-time PCR cell cultures generated from mouse tissues bearing the homozygous gene trap mutation display the cellular phenotype of misregulated chromosome condensation that is characteristic for the human disorder, confirming defective Mcph1 function due to the gene trap mutation. While surprisingly the DNA damage response (formation of repair foci, chromosomal breakage, and G2/M checkpoint function after irradiation) appears to be largely normal in cell cultures derived from Mcph1gt/gt mice, the overall survival rates of the Mcph1gt/gt animals are significantly reduced compared to wild type and heterozygous mice. However, we could not detect clear signs of premature malignant disease development due to the perturbed Mcph1 function. Moreover, the animals show no obvious physical phenotype and no reduced fertility. Body and brain size are within the range of wild type controls. Gene expression on RNA and protein level did not reveal any specific pattern of differentially regulated genes. To the best of our knowledge this represents the first mammalian transgenic model displaying a defect in mitotic chromosome condensation and is also the first mouse model for impaired Mcph1-function

MPG.PuRe

Ion Lucian Ceapraz

Research Papers in Economics

COMPETITION AMONG HOSPITALS AND ITS MEASUREMENT: THEORY AND A CASE STUDY

Trimborn, Marc

Ghani, Mahdi

Walther, Diego J.

Dopatka, Monika

Dutrannoy, Véronique

Busche, Andreas

Meyer, Franziska

Nowak, Stefanie

Nowak, Jean N

Zabel, Claus

Klose, Joachim

Esquitino, Veronica

Garshasbi, Masoud

Kuss, Andreas W.

Ropers, Hans-Hilger

Mueller, Susanne

Poehlmann, Charlotte

Gavvovidis, Ioannis

Schindler, Detlev

Sperling, Karl

Neitzel, Heidemarie

Max Planck Society eDoc Server

Establishment of a mouse model with misregulated chromosome condensation due to defective Mcph1 function.

Mutations in the human gene MCPH1 cause primary microcephaly associated with a unique cellular phenotype with premature chromosome condensation (PCC) in early G2 phase and delayed decondensation post-mitosis (PCC syndrome). The gene encodes the BRCT-domain containing protein microcephalin/BRIT1. Apart from its role in the regulation of chromosome condensation, the protein is involved in the cellular response to DNA damage. We report here on the first mouse model of impaired Mcph1-function. The model was established based on an embryonic stem cell line from BayGenomics (RR0608) containing a gene trap in intron 12 of the Mcph1 gene deleting the C-terminal BRCT-domain of the protein. Although residual wild type allele can be detected by quantitative real-time PCR cell cultures generated from mouse tissues bearing the homozygous gene trap mutation display the cellular phenotype of misregulated chromosome condensation that is characteristic for the human disorder, confirming defective Mcph1 function due to the gene trap mutation. While surprisingly the DNA damage response (formation of repair foci, chromosomal breakage, and G2/M checkpoint function after irradiation) appears to be largely normal in cell cultures derived from Mcph1(gt/gt) mice, the overall survival rates of the Mcph1(gt/gt) animals are significantly reduced compared to wild type and heterozygous mice. However, we could not detect clear signs of premature malignant disease development due to the perturbed Mcph1 function. Moreover, the animals show no obvious physical phenotype and no reduced fertility. Body and brain size are within the range of wild type controls. Gene expression on RNA and protein level did not reveal any specific pattern of differentially regulated genes. To the best of our knowledge this represents the first mammalian transgenic model displaying a defect in mitotic chromosome condensation and is also the first mouse model for impaired Mcph1-function

Marc Trimborn

Mahdi Ghani

Diego J Walther

Monika Dopatka

Véronique Dutrannoy

Andreas Busche

Franziska Meyer

Stefanie Nowak

Jean Nowak

Claus Zabel

Joachim Klose

Veronica Esquitino

Masoud Garshasbi

Andreas W Kuss

Hans-Hilger Ropers

Susanne Mueller

Charlotte Poehlmann

Ioannis Gavvovidis

Detlev Schindler

Karl Sperling

Heidemarie Neitzel

Directory of Open Access Journals

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COMPETITION AMONG HOSPITALS AND ITS MEASUREMENT: THEORY AND A CASE STUDY

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MPG.PuRe

Research Papers in Economics

MPG.PuRe

Max Planck Society eDoc Server

Directory of Open Access Journals