Paul Sabatier University

About: Paul Sabatier University is a education organization based out in Toulouse, France. It is known for research contribution in the topics: Population & Catalysis. The organization has 15431 authors who have published 23386 publications receiving 858364 citations.

DNA polymerase θ up-regulation is associated with poor survival in breast cancer, perturbs DNA replication, and promotes genetic instability

Abstract: “Replicative stress” is one of the main factors underlying neoplasia from its early stages. Genes involved in DNA synthesis may therefore represent an underexplored source of potential prognostic markers for cancer. To this aim, we generated gene expression profiles from two independent cohorts (France, n = 206; United Kingdom, n = 117) of patients with previously untreated primary breast cancers. We report here that among the 13 human nuclear DNA polymerase genes, DNA Polymerase θ (POLQ) is the only one significantly up-regulated in breast cancer compared with normal breast tissues. Importantly, POLQ up-regulation significantly correlates with poor clinical outcome (4.3-fold increased risk of death in patients with high POLQ expression), and this correlation is independent of Cyclin E expression or the number of positive nodes, which are currently considered as markers for poor outcome. POLQ expression provides thus an additional indicator for the survival outcome of patients with high Cyclin E tumor expression or high number of positive lymph nodes. Furthermore, to decipher the molecular consequences of POLQ up-regulation in breast cancer, we generated human MRC5-SV cell lines that stably overexpress POLQ. Strong POLQ expression was directly associated with defective DNA replication fork progression and chromosomal damage. Therefore, POLQ overexpression may be a promising genetic instability and prognostic marker for breast cancer.

Acoustic oscillations of rapidly rotating polytropic stars. II. Effects of the Coriolis and centrifugal accelerations

Abstract: Context. With the launch of space missions devoted to asteroseismology (like COROT), the scientific community will soon have accurate measurements of pulsation frequencies in many rapidly rotating stars. Aims. The present work focuses on the effects of rotation on pulsations of rapidly rotating stars when both the Coriolis and centrifugal accelerations require a non-perturbative treatment. Methods. We develop a 2-dimensional spectral numerical approach which allows us to compute acoustic modes in centrifugally distorted polytropes including'the full influence of the Coriolis force. This method is validated through comparisons with previous studies, and the results are shown to be highly accurate. Results. In the frequency range considered and with COROT's accuracy, we establish a domain of validity for perturbative methods, thus showing the need for complete calculations beyond v sin i = 50 km s -1 for a R = 2.3 R ⊙ , M = 1.9 M ⊙ polytropic star. Furthermore, it is shown that the main differences between complete and perturbative calculations come essentially from the centrifugal distortion.

Germline Loss-of-Function Mutations in EPHB4 Cause a Second Form of Capillary Malformation-Arteriovenous Malformation (CM-AVM2) Deregulating RAS-MAPK Signaling

Abstract: BACKGROUND: Most arteriovenous malformations (AVMs) are localized and occur sporadically. However, they also can be multifocal in autosomal-dominant disorders, such as hereditary hemorrhagic telangiectasia and capillary malformation (CM)-AVM. Previously, we identified RASA1 mutations in 50% of patients with CM-AVM. Herein we studied non-RASA1 patients to further elucidate the pathogenicity of CMs and AVMs. METHODS: We conducted a genome-wide linkage study on a CM-AVM family. Whole-exome sequencing was also performed on 9 unrelated CM-AVM families. We identified a candidate gene and screened it in a large series of patients. The influence of several missense variants on protein function was also studied in vitro. RESULTS: We found evidence for linkage in 2 loci. Whole-exome sequencing data unraveled 4 distinct damaging variants in EPHB4 in 5 families that cosegregated with CM-AVM. Overall, screening of EPHB4 detected 47 distinct mutations in 54 index patients: 27 led to a premature stop codon or splice-site alteration, suggesting loss of function. The other 20 are nonsynonymous variants that result in amino acid substitutions. In vitro expression of several mutations confirmed loss of function of EPHB4. The clinical features included multifocal CMs, telangiectasias, and AVMs. CONCLUSIONS: We found EPHB4 mutations in patients with multifocal CMs associated with AVMs. The phenotype, CM-AVM2, mimics RASA1-related CM-AVM1 and also hereditary hemorrhagic telangiectasia. RASA1-encoded p120RASGAP is a direct effector of EPHB4. Our data highlight the pathogenetic importance of this interaction and indicts EPHB4-RAS-ERK signaling pathway as a major cause for AVMs.

On the unicity of dempster rule of combination

Abstract: Dempster has proposed a rule for the combination of uncertain items of information issued from several sources. This note proves the unicity of this rule under an independence assumption. the existence of alternative rules is stressed, some corresponding to different assumptions, others pertaining to different types of combination.