Biochemical characterization and modulation of LH/CG-receptor during human trophoblast differentiation.: LH/CG-R in human trophoblast differentiation.

Due to the key role of the human chorionic gonadotropin hormone (hCG) in placental development, the aim of this study was to characterize the human trophoblastic luteinizing hormone/chorionic gonadotropin receptor (LH/CG-R) and to investigate its expression using the in vitro model of human cytotrophoblast differentiation into syncytiotrophoblast. We confirmed by in situ immunochemistry and in cultured cells, that LH/CG-R is expressed in both villous cytotrophoblasts and syncytiotrophoblasts. However, LH/CG-R expression decreased during trophoblast fusion and differentiation, while the expression of hCG and hPL (specific markers of syncytiotrophoblast formation) increased. A decrease in LH/CG-R mRNA during trophoblast differentiation was observed by means of semi-quantitative RT-PCR with two sets of primers. A corresponding decrease ( approximately 60%) in LH/CG-R protein content was shown by Western-blot and immunoprecipitation experiments. The amount of the mature form of LH/CG-R, detected as a 90-kDa band specifically binding (125)I-hCG, was lower in syncytiotrophoblasts than in cytotrophoblasts. This was confirmed by Scatchard analysis of binding data on cultured cells. Maximum binding at the cell surface decreased from 3,511 to about 929 molecules/seeded cells with a kDa of 0.4-0.5 nM. Moreover, on stimulation by recombinant hCG, the syncytiotrophoblast produced less cyclic AMP than cytotrophoblasts, indicating that LH/CG-R expression is regulated during human villous trophoblast differentiation. J. Cell. Physiol. 212: 26-35, 2007. (c) 2007 Wiley-Liss, Inc

Association of the PHACTR1/EDN1 genetic locus with spontaneous coronary artery dissection

Background: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene. Objectives: This study sought to test the association between the rs9349379 genotype and SCAD. Methods: Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD. Results: The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence. Conclusions: The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Application of progressive quadratic response surface method for an oscillation problem optimization

International audienceThe paper presents an effective optimization strategy applied in a physical structure optimization of a semiconductor Power MOSFET with expensive constraint computations. In order to deals with inaccuracy due to inevitable numerical errors in the objective function calculation (the power losses of the power MOSFET), the paper proposes to use the Progressive Quadratic Response Surface Method (PQRSM). The paper focuses on three aspects: the inevitable numerical errors in the power losses computation, the PQRSM principle, and finally the comparisons of several optimization methods on this problem

Application of progressive quadratic response surface method for an oscillation problem optimization

International audiencePurpose - The purpose of this paper is to present an effective optimization strategy applied in a physical structure optimization of a semiconductor power metal oxide semiconductor field-effect transistor (MOSFET), with an expensive integration constraint computation. Design/methodology/approach - In order to deal with inaccuracy due to inevitable numerical errors in the objective function calculation (the power losses of the power MOSFET) and in the constraint computation, the paper proposes to use the progressive quadratic response surface method (PQRSM). Findings - The paper focuses on four aspects: the inevitable numerical errors in the power loss and the integration constraint computation; the response surface approximation (RSA) method; the PQRSM principle; and finally the comparisons of several optimization methods applied on this application problem. Originality/value - An original optimization method, PQRSM, is proposed for reducing the oscillation problem of a semi-analytical model. The optimization results of PQRSM have been compared with the evolution strategy (ES) algorithm, with similar results but faster computation

Human Trophoblast in Trisomy 21: A Model for Cell–Cell Fusion Dynamic Investigation

International audienceTrophoblastic cell fusion is one essential step of the human trophoblast differentiation leading to formation of the syncytiotrophoblast, site of the numerous placental functions. This process is multifactorial and finely regulated. Using the physiological model of primary culture of trophoblastic cells isolated from human placenta, we have identified different membrane proteins directly involved in trophoblastic cell fusion: connexin 43, ZO-1 and recently syncytins. These fusogenic membrane retroviral envelop glycoproteins: syncytin-1 (encoded by the HERV-W gene) and syncytin-2 (encoded by the FRD gene) and their receptors are major factors involved in human placental development. Disturbances of syncytiotrophoblast formation are observed in trisomy 21-affected placentas. Overexpression of the copper/zinc superoxide dismutase (SOD-1), encoded by chromosome 21 as well as an abnormal hCG signaling are implicated in the defect of syncytiotrophoblast formation. This abnormal trophoblast fusion and differentiation in trisomy 21-affected placenta is reversible in vitro by different ways

Towards reduced threshold voltages for vertical power Mosfet transistors

International audienceThe threshold voltage of insulated gate power transistors usually is around 3 to 4V and their nominal gate to source voltage between 15 and 20V. These unanimously recognized electrical characteristics are questioned in this paper in order to evaluate which benefits could be drawn from a reduction of the threshold voltage of power transistors. Logic level MOSFETs already exist, but this paper chooses to study theoretically the electrical and physical characteristics of power transistors as a function of the threshold voltage to see if these electrical values of power electronics standards are still appropriate. It appears that the reduction of the threshold voltage of power MOSFET reduces the amount of control power and may improve switching characteristics

Towards reduced threshold voltages for vertical power Mosfet transistors

International audienceThe threshold voltage of insulated gate power transistors usually is around 3 to 4V and their nominal gate to source voltage between 15 and 20V. These unanimously recognized electrical characteristics are questioned in this paper in order to evaluate which benefits could be drawn from a reduction of the threshold voltage of power transistors. Logic level MOSFETs already exist, but this paper chooses to study theoretically the electrical and physical characteristics of power transistors as a function of the threshold voltage to see if these electrical values of power electronics standards are still appropriate. It appears that the reduction of the threshold voltage of power MOSFET reduces the amount of control power and may improve switching characteristics

Impact of Trisomy 21 on Human Trophoblast Behaviour and Hormonal Function

International audienceAlthough trisomy 21 (T21) is the most frequent genetic abnormality and some maternal serum markers for this fetoplacental aneuploidy are of placental origin, little is known of its impact on placental development. We therefore studied the influence of T21 on trophoblast behaviour. Using cultured cells from 46 human T21 pregnancies, we confirmed the defective morphological and functional differentiation of the villous cytotrophoblast in this setting; indeed, villous cytotrophoblast cells aggregate normally but fuse inefficiently to form the syncytiotrophoblast. This is in part related to the abnormal oxidative status of the T21 cytotrophoblast, characterized by a gene dosage-related increase in SOD-1 (copper-zinc superoxide dismutase) expression and activity. This was associated with a significant (P<0.01) increase in catalase activity but no significant change in glutathione peroxidase activity. On the basis of these in vitro findings and studies of large panels of maternal serum, we propose a pathophysiological explanation for trisomy 21 maternal serum markers of placental origin