A clinical and molecular project on gonadoblastoma needs international collaboration

<p>No abstract available.</p

Evidence for Link Between Mental Disorders and in Utero Exposure to Synthetic Hormones: A Long and Crucial History

Somatic effects of diethylstilbestrol on children exposed in utero have long been recognized. This is not the case for psychiatric disorders, although animal studies provide evidence of somatic and behavioral disorders. Recent studies have reported psychiatric effects of synthetic estrogens on the brain of children exposed in utero as schizophrenia, bipolar disorders, depression, eating disorders, suicides, suicide attempts. Recently, a team of St. Anne’s Hospital, Paris (Prof. Krebs, Dr. Kebir) demonstrated the epigenetic mechanism of DES effect on the brain, a specific methylation of two genes playing important roles in neurodevelopment: the ADAM TS9 (control of the formation of reproductive organs and of the fetus’s CNS) and the ZFP 57 gene suggested to be associated with psychosis. Progestins used in contraception and in hormone replacement therapy are known to affect the adult brain, but no data on children existed before our recent paper on their effects after in utero exposure. Clinical data were collected from 1934 children of the Association of Patients HHORAGES cohort. Our data show the presence of somatic disorders and a drastic increase of psychiatric disorders among children in utero exposed to progestins. These mental disorders are the same as pathologies provoked by exposure to synthetic estrogens

Usinage de métaux durs par Jet d'Eau Abrasif

The aviation industry requires the use of hard and light metals such as Titanium and Inconel, but different machining problems in milling process or by chemical machining complicate their implementation. The aim of this thesis is to develop a controlled depth milling on these hard metals with abrasive water jet (AWJ) technology for pockets machining. Currently, this process is limited to cutting operation but by controlling the input parameters and the geometric characteristics it allows the realization of pockets with constant or variable depth. This work shows the study of elementary passages and their superposition to generate a necessary path for the realization of a pocket in AWJ. It also introduces a variety of strategies for machining rectangular pockets and provides a correction of the operating parameters to obtain a controlled depth.L’industrie aéronautique nécessite l’utilisation de métaux durs et légers, comme le Titane et l’Inconel mais différentes problématiques d’usinage en fraisage ou par usinage chimique compliquent leur mise en oeuvre. L’objectif du travail de thèse est de développer une méthode d’usinage non débouchant de ces métaux durs par jet d’eau abrasif (JEA) pour la réalisation de poches. Actuellement, ce procédé est limité à la découpe mais en contrôlant les paramètres d’usinage il permet la réalisation de poches à profondeurs constante ou variable en maitrisant les caractéristiques géométriques imposées. Ce travail présente l’étude de passages élémentaires et leur superposition afin de générer un parcours nécessaire à la réalisation d’une poche. Il introduit également diverses stratégies pour l’usinage de poches rectangulaires et propose une correction des paramètres opératoires afin d’obtenir un fond à profondeur contrôlée

Hematopoietic-Prostaglandin D2 synthase through PGD2 production is involved in the adult ovarian physiology

<p>Abstract</p> <p>Background</p> <p>The prostaglandin D2 (PGD2) pathway is involved in numerous biological processes and while it has been identified as a partner of the embryonic sex determining male cascade, the roles it plays in ovarian function remain largely unknown. PGD2 is secreted by two prostaglandin D synthases (Pgds); the male-specific lipocalin (L)-Pgds and the hematopoietic (H)-Pgds.</p> <p>Methods</p> <p>To study the expression of the Pgds in the adult ovary, <it>in situ </it>hybridization were performed. Then, to evaluate the role of H-Pgds produced PGD2 in the ovarian physiology, adult female mice were treated with HQL-79, a specific inhibitor of H-Pgds enzymatic activity. The effects on expression of the gonadotrophin receptors <it>FshR </it>and <it>LhR</it>, steroidogenic genes <it>Cyp11A1</it>, <it>StAR </it>and on circulating progesterone and estradiol, were observed.</p> <p>Results</p> <p>We report the localization of <it>H-Pgds </it>mRNA in the granulosa cells from the primary to pre-ovulatory follicles. We provide evidence of the role of H-Pgds-produced PGD2 signaling in the FSH signaling through increased <it>FshR </it>and <it>LhR </it>receptor expression. This leads to the activation of steroidogenic <it>Cyp11A1 </it>and <it>StAR </it>gene expression leading to progesterone secretion, independently on other prostanoid-synthetizing mechanisms. We also identify a role whereby H-Pgds-produced PGD2 is involved in the regulation of follicular growth through inhibition of granulosa cell proliferation in the growing follicles.</p> <p>Conclusions</p> <p>Together, these results show PGD2 signaling to interfere with FSH action within granulosa cells, thus identifying an important and unappreciated role for PGD2 signaling in modulating the balance of proliferation, differentiation and steroidogenic activity of granulosa cells.</p

Association between fetal DES-exposure and psychiatric disorders in adolescence/adulthood: evidence from a French cohort of 1002 prenatally exposed children

International audienceIn utero diethylstilbestrol (DES) exposure has been demonstrated to be associated with somatic abnormalities in adult men and women. Conversely, the data are contradictory regarding the association with psychological or psychiatric disorders during adolescence and adulthood. This work was designed to determine whether prenatal exposure to DES affects brain development and whether it is associated with psychiatric disorders in male and female adolescents and young adults. HHORAGES Association, a national patient support group, has assembled a cohort of 1280 women who took DES during pregnancy. We obtained questionnaire responses from 529 families, corresponding to 1182 children divided into three groups: Group 1 (n = 180): firstborn children without DES treatment, Group 2 (n = 740): exposed children, and Group 3 (n = 262): children born after a previous pregnancy treated by DES. No psychiatric disorders were reported in Group 1. In Group 2, the incidence of disorders was drastically elevated (83.8%), and in Group 3, the incidence was still elevated (6.1%) compared with the general population. This work demonstrates that prenatal exposure to DES is associated with a high risk of psychiatric disorders in adolescence and adulthood

The new molecular biology of granulosa cell tumors of the ovary

Granulosa cell tumors (GCTs) of the ovary belong to the group of ovarian sex-cord stromal tumors and represent 5 to 10% of ovarian malignancies. GCTs exhibit several morphological, biochemical and hormonal features of normal proliferating pre-ovulatory granulosa cells, such as estrogen biosynthesis. Prognostic factors of this condition are lacking, and alternative treatment options to preserve future fertility are needed. Several groups have shown that two genetic factors implicated in GCTs are of particular interest. The gsp oncogene is a constitutive activating mutation of the prognosis of the tumor. FOXL2 is a transcription factor gene involved in ovarian development and function, whose expression is reduced and which is mutated in the majority of GCTs. FOXL2 appears to play a major role in cell cycle regulation. These recent findings open new pathophysiological insights into GCT development as well as revisitation of granulosa cell and ovarian function

Is hypospadias a genetic, endocrine or environmental disease, or still an unexplained malformation?

Q1Artículo de revisión187-197Hypospadias is one of the most frequent genital malformations in the male newborn and results from an abnormal penile and urethral development. This process requires a correct genetic programme, time- and space-adapted cellular differentiation, complex tissue interactions, and hormonal mediation through enzymatic activities and hormonal transduction signals. Any disturbance in these regulations may induce a defect in the virilization of the external genitalia and hypospadias. This malformation thus appears to be at the crossroads of various mechanisms implicating genetic and environmental factors. The genes of penile development (HOX, FGF, Shh) and testicular determination (WT1, SRY) and those regulating the synthesis [luteinizing hormone (LH) receptor] and action of androgen (5a reductase, androgen receptor) can cause hypospadias if altered. Several chromosomal abnormalities and malformative syndromes include hypospadias, from anterior to penoscrotal forms. More recently, CXorf6 and ATF3 have been reported to be involved. Besides these genomic and hormonal factors, multiple substances found in the environment can also potentially interfere with male genital development because of their similarity to hormones. The proportion of hypospadias cases for which an aetiology is detected varies with the authors but it nevertheless remains low, especially for less severe cases. An interaction between genetic background and environment is likely

Long-term survival of olfactory sensory neurons after target depletion.

Life-long addition and elimination of neurons within the adult olfactory epithelium and olfactory bulb allows for adaptive structural responses to sensory experience, learning, and recovery after injury. The interdependence of the two structures is highlighted by the shortened life span of sensory neurons deprived of bulb contact, and has prompted the hypothesis that trophic cues from the bulb contribute to their survival. The specific identity and source of these signals remain unknown. To investigate the potential role of target neurons in this support, we employed a neurotoxic lesion to selectively remove them while preserving the remaining nerve projection pathway, and examined the dynamics of sensory neuron proliferation and survival. Pulse-labeling of progenitors with bromodeoxyuridine showed that, as with surgical bulb removal, increased apoptosis in the epithelium triggered accelerated production of new neurons after chemical depletion of target cells. Rather than undergoing premature death, a large subpopulation of these neurons survived long term. The combination of increased proliferation and extended survival resulted in essentially normal numbers of new sensory neurons surviving for as long as 5 weeks, with an accompanying restoration of olfactory marker protein expression. Changes in neurotrophic factor expression levels as measured by quantitative polymerase chain reaction (Q-PCR), and in bulb cell populations, including the addition of new neurons generated in the subventricular zone, were observed in the injured bulb. These data indicate that olfactory sensory neurons can adapt to reductions in their normal target field by obtaining sufficient support from remaining or alternative cell sources to survive and maintain their projections

Project management case analysis in technology companies

Este artículo tiene como objetivo identificar y analizar tres empresas tecnológicas como Google, Globant y Zemoga, a través del reconocimiento de unas variables comunes de la metodología de Gestión de Proyectos evidenciadas en cada empresa. Entre las variables a destacar están: la innovación, la metodología de gestión de proyectos, la estructura organizacional, el trabajo en equipo, la complejidad y la cultura organizacional. Este análisis de las variables muestra como el ambiente de trabajo y los incentivos a la innovación dentro de la organización, pueden generar una relación simbiótica entre los empleados y la empresa lo que aumenta las probabilidades de tener éxito en la ejecución de proyectos.This article attempts to identify and analyze success technological companies like Google, Globant and Zemoga by recognizing some common variables of the Project Management model of each one. The variables to stand out are: innovation, methodology for project management, organizational structure, teamwork, complexity and organizational culture. This analysis recognizes common strengths in project management and highlight what elements can lead to successful management in technology companies