Differential signalling through ALK-1 and ALK-5 regulates leptin expression in Mesenchymal Stem Cells

Leptin plays a central role in maintaining energy balance, with multiple other systemic effects. Despite leptin importance in peripheral regulation of mesenchymal stem cells (MSC) differentiation, little is known on its expression mechanism. Leptin is often described as adipokine, while it is expressed by other cell types. We have recently shown an in vitro leptin expression, enhanced by glucocorticoids in synovial fibroblasts. Here, we investigated leptin expression in MSC from bone marrow (BM-MSC), cord matrix (UMSC), and primary and dedifferentiated chondrocytes (DCH). Results showed that BM-MSC, but not UMSC, expressed leptin that was strongly enhanced by glucocorticoids. Interestingly, chondrocytes gained leptin expression progressively with dedifferentiation. This dedifferentiation was correlated with downregulation of ALK-5 expression, Smad2 phosphorylation (p-Smad2), and gain of ALK-1 expression and Smad1/5 phosphorylation (p-Smad1/5). TGF-β1 was shown to signal via ALK-5-Smad2/3 and/or ALK-1-Smad1/5 pathways. In BM-MSC, TGF-β1 increased p-Smad2 expression and markedly inhibited endogenous- and glucocorticoidinduced leptin expression, while ALK-5 inhibitor (SB431542) induced and restored this expression. In addition, both prednisolone and SB431542 increased p-Smad1/5 expression. These results suggested ALK-5-Smad2 pathway as inhibitor of leptin expression, while ALK-1-Smad1/5 as activator. Indeed, Smad1 expression silencing induced leptin expression inhibition. Furthermore, prednisolone enhanced the expression of TGF-βRII while decreasing p-Smad2 in BM-MSC and SVF but not in UMSC. In vitro differentiation revealed differential osteogenic potential in SVF, BM-MSC and UMSC that correlates to their leptin expression potential. Our results suggest that ALK-1/ALK-5 balance regulates leptin expression in MSC. It also underlines UMSC as leptin non-producer MSC for cell therapy protocols where leptin expression is not suitable

Overproduced Brucella abortus PdhS-mCherry forms soluble aggregates in Escherichia coli, partially associating with mobile foci of IbpA-YFP

<p>Abstract</p> <p>Background</p> <p>When heterologous recombinant proteins are produced in <it>Escherichia coli</it>, they often precipitate to form insoluble aggregates of unfolded polypeptides called inclusion bodies. These structures are associated with chaperones like IbpA. However, there are reported cases of "non-classical" inclusion bodies in which proteins are soluble, folded and active.</p> <p>Results</p> <p>We report that the <it>Brucella abortus </it>PdhS histidine kinase fused to the mCherry fluorescent protein forms intermediate aggregates resembling "non-classical" inclusion bodies when overproduced in <it>E. coli</it>, before forming "classical" inclusion bodies. The intermediate aggregates of PdhS-mCherry are characterized by the solubility of PdhS-mCherry, its ability to specifically recruit known partners fused to YFP, suggesting that PdhS is folded in these conditions, and the quick elimination (in less than 10 min) of these structures when bacterial cells are placed on fresh rich medium. Moreover, soluble PdhS-mCherry foci do not systematically colocalize with IpbA-YFP, a marker of inclusion bodies. Instead, time-lapse experiments show that IbpA-YFP exhibits rapid pole-to-pole shuttling, until it partially colocalizes with PdhS-mCherry aggregates.</p> <p>Conclusion</p> <p>The data reported here suggest that, in <it>E. coli</it>, recombinant proteins like PdhS-mCherry may transit through a soluble and folded state, resembling previously reported "non-classical" inclusion bodies, before forming "classical" inclusion bodies. The dynamic localization of IbpA-YFP foci suggests that the IbpA chaperone could scan the <it>E. coli </it>cell to find its substrates.</p

Determinants of Non-Vaccination against Pandemic 2009 H1N1 Influenza in Pregnant Women: A Prospective Cohort Study

International audienceBACKGROUND: In October 2009, the French government organized a national-wide, free of charge vaccination campaign against pandemic H1N1 influenza virus, especially targeting pregnant women, a high risk group for severe illness. The study objective was to evaluate pandemic flu vaccine uptake and factors associated with non-vaccination in a population of pregnant women. METHODOLOGY/PRINCIPAL FINDINGS: In a prospective cohort conducted in 3 maternity hospitals in Paris, 882 pregnant women were randomly included between October 12, 2009 and February 3, 2010, with the aim to study characteristics of pandemic influenza during pregnancy. At inclusion, socio-demographic, medical, obstetrical factors and those associated with a higher risk of flu exposition and disease-spreading were systematically collected. Pandemic flu vaccine uptake was checked until delivery. 555 (62.9%) women did not get vaccinated. Determinants associated with non-vaccination in a multivariate logistic regression were: geographic origin (Sub-Saharan African origin, adjusted Odd Ratio aOR = 5.4[2.3-12.7], North African origin, aOR = 2.5[1.3-4.7] and Asian origin, aOR = 2.1[1.7-2.6] compared to French and European origin) and socio-professional categories (farmers, craftsmen and tradesmen, aOR = 2.3[2.0-2.6], intermediate professionals, aOR = 1.3[1.0-1.6], employees and manual workers, aOR = 2.5[1.4-4.4] compared to managers and intellectual professionals). The probability of not receiving pandemic flu vaccine was lower among women vaccinated against seasonal flu in the previous 5 years (aOR = 0.6[0.4-0.8]) and among those who stopped smoking before or early during pregnancy (aOR = 0.6[0.4-0.8]). Number of children less than 18 years old living at home, work in contact with children or in healthcare area, or professional contact with the public, were not associated with a higher vaccine uptake. CONCLUSIONS/SIGNIFICANCE: In this cohort of pregnant women, vaccine coverage against pandemic 2009 A/H1N1 flu was low, particularly in immigrant women and those having a low socio-economic status. To improve its effectiveness, future vaccination campaign for pregnant women should be more specifically tailored for these populations

Cryptococcal Neuroradiological Lesions Correlate with Severity during Cryptococcal Meningoencephalitis in HIV-Positive Patients in the HAART Era

Cryptococcal meningoencephalitis has an overall global mortality rate of 20% in AIDS patients despite antifungals. There is a need for additional means of precise assessment of disease severity. We thus studied the radiological brain images available from 62 HIV-positive patients with cryptococcocal meningoencephalitis to analyse the brain lesions associated with cryptococcosis in relationship with disease severity, and the respective diagnostic contribution of magnetic resonance (MR) versus computed tomography (CT)

Contribution à la synthèse de copolymères séquencés à base de poly(aryléthersulfone)s et de poly(aryléthercétone)s

Doctorat en sciences chimiques -- UCL, 199

Analgésie péridurale obstétricale et lombalgie du post-partum: un lien de cause à effet?

peer reviewedbackache is a common problem in the general population. the prevalence of backpain is increased during pregnancy and after delivery. early studies have suggested that labor epidural analgesia might be associated with an increased incidence of backache in the postpartum period. However, these initial studies were retrospective and their design included several methodological deficiencies. All the prospective studies published afterwards (prospective cohort studies and 3 ran- domized controlled trials) yield the same result : there is no relationship between labor epidural analgesia and long-term postpartum backpain. pregnant women must be aware of this in order to make an informed and appropriate choice about labor epidural analgesia, the most effective technique for intra- partum pain relief.resume : Aujourd’hui, les lombalgies sont un problème fré- quent dans la population générale. leur prévalence est encore plus élevée au cours de la grossesse et après celle-ci. des études anciennes suggèrent que l’analgésie obstétricale pourrait être responsable d’une augmentation de l’incidence des lombalgies au cours du post-partum. il faut cependant remarquer que ces études sont rétrospectives et de piètre qualité méthodologique. toutes les études prospectives réalisées depuis sont de bien meilleure qualité. elles concluent qu’il n’y a pas de lien entre l’analgésie péridurale au cours du travail et les lombalgies pro- longées du post-partum. cette information doit être fournie aux femmes désirant bénéficier d’une analgésie périmédullaire lors de leur accouchement afin de leur permettre de prendre une décision en toute connaissance de cause

[How Reliable Are Allegations of Children Under Age in Matters of Sexual Abuse]

When a child under age states he/she has been sexually abused, there seldom exists an objective certainty to support the allegation. Whereas clinicians know that a child who speaks spontaneously probably speaks the truth, it is nonetheless difficult to exclude the possibility of fabulating, lying or mistaking. The error probability is sharply increased when abuse is referred by a parent, specially in a context of parental separation. This article thus presents a review of criteria which help to better assess the truth or error of allegations. Criteria include analysis of the child's talk, application of projective techniques, observation of his/her behavior, etc. The author also describes some differential diagnoses based on the behaviors and sexual allegations of children under age