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Search Results: 1 - 10 of 75080 matches for " Marie José Goumans "
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Smad7 and protein phosphatase 1α are critical determinants in the duration of TGF-β/ALK1 signaling in endothelial cells
Gudrun Valdimarsdottir, Marie-José Goumans, Fumiko Itoh, Susumu Itoh, Carl-Henrik Heldin, Peter Dijke
BMC Cell Biology , 2006, DOI: 10.1186/1471-2121-7-16
Abstract: The temporal activation of TGF-β-induced Smad1/5 phosphorylation in ECs was found to be affected by de novo protein synthesis, and ALK1 and Smad5 expression levels determined signal strength of TGF-β/ALK1 signaling pathway. Smad7 and protein phosphatase 1α (PP1α) mRNA expression levels were found to be specifically upregulated by TGF-β/ALK1. Ectopic expression of Smad7 or PP1α potently inhibited TGF-β/ALK1-induced Smad1/5 phosphorylation in ECs. Conversely, siRNA-mediated knockdown of Smad7 or PP1α enhanced TGF-β/ALK1-induced signaling responses. PP1α interacted with ALK1 and this association was further potentiated by Smad7. Dephosphorylation of the ALK1, immunoprecipitated from cell lysates, was attenuated by a specific PP1 inhibitor.Our results suggest that upon its induction by the TGF-β/ALK1 pathway, Smad7 may recruit PP1α to ALK1, and thereby control TGF-β/ALK1-induced Smad1/5 phosphorylation.Transforming growth factor-β (TGF-β) elicits its cellular effects through activation of type I and type II serine/threonine kinase receptors [1,2]. The constitutively active type II receptor phosphorylates specific serine and threonine residues in the juxtamembrane region (so-called GS domain) of the type I receptor. Type I receptor acts downstream of type II receptor (Tβ R-II) and has been shown to determine signaling specificity within the heteromeric receptor complex. In most cell types, TGF-β signals via TGF-β type I receptor (Tβ R-I), also termed activin receptor-like kinase 5 (ALK5). In endothelial cells (ECs), however, TGF-β can signal via Tβ R-II and two different type I receptors, i.e. the broadly expressed ALK5 and the EC-restricted ALK1. Whereas ALK5 inhibits EC migration and proliferation, ALK1 stimulates both these processes [3]. The activated type I receptor propagates the signal through phosphorylation of specific receptor-regulated Smads (R-Smads). Whereas ALK5 induces the phosphorylation of Smad2 and Smad3, ALK1 mediates the activation of Smad1 and Smad5
Bone Marrow Alterations and Lower Endothelial Progenitor Cell Numbers in Critical Limb Ischemia Patients
Martin Teraa, Ralf W. Sprengers, Peter E. Westerweel, Hendrik Gremmels, Marie-José T. H. Goumans, Tom Teerlink, Frans L. Moll, Marianne C. Verhaar
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0055592
Abstract: Background Critical limb ischemia (CLI) is characterized by lower extremity artery obstruction and a largely unexplained impaired ischemic neovascularization response. Bone marrow (BM) derived endothelial progenitor cells (EPC) contribute to neovascularization. We hypothesize that reduced levels and function of circulating progenitor cells and alterations in the BM contribute to impaired neovascularization in CLI. Methods Levels of primitive (CD34+ and CD133+) progenitors and CD34+KDR+ EPC were analyzed using flow cytometry in blood and BM from 101 CLI patients in the JUVENTAS-trial (NCT00371371) and healthy controls. Blood levels of markers for endothelial injury (sE-selectin, sICAM-1, sVCAM-1, and thrombomodulin), and progenitor cell mobilizing and inflammatory factors were assessed by conventional and multiplex ELISA. BM levels and activity of the EPC mobilizing protease MMP-9 were assessed by ELISA and zymography. Circulating angiogenic cells (CAC) were cultured and their paracrine function was assessed. Results Endothelial injury markers were higher in CLI (P<0.01). CLI patients had higher levels of VEGF, SDF-1α, SCF, G-CSF (P<0.05) and of IL-6, IL-8 and IP-10 (P<0.05). Circulating EPC and BM CD34+ cells (P<0.05), lymphocytic expression of CXCR4 and CD26 in BM (P<0.05), and BM levels and activity of MMP-9 (P<0.01) were lower in CLI. Multivariate regression analysis showed an inverse association between IL-6 and BM CD34+ cell levels (P = 0.007). CAC from CLI patients had reduced paracrine function (P<0.0001). Conclusion CLI patients have reduced levels of circulating EPC, despite profound endothelial injury and an EPC mobilizing response. Moreover, CLI patients have lower BM CD34+-cell levels, which were inversely associated with the inflammatory marker IL-6, and lower BM MMP-9 levels and activity. The results of this study suggest that inflammation-induced BM exhaustion and a disturbed progenitor cell mobilization response due to reduced levels and activity of MMP-9 in the BM and alterations in the SDF-1α/CXCR4 interaction contribute to the attenuated neovascularization in CLI patients.
Human Embryonic and Fetal Mesenchymal Stem Cells Differentiate toward Three Different Cardiac Lineages in Contrast to Their Adult Counterparts
Arti A. Ramkisoensing, Dani?l A. Pijnappels, Sa?d F. A. Askar, Robert Passier, Jim Swildens, Marie José Goumans, Cindy I. Schutte, Antoine A. F. de Vries, Sicco Scherjon, Christine L. Mummery, Martin J. Schalij, Douwe E. Atsma
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0024164
Abstract: Mesenchymal stem cells (MSCs) show unexplained differences in differentiation potential. In this study, differentiation of human (h) MSCs derived from embryonic, fetal and adult sources toward cardiomyocytes, endothelial and smooth muscle cells was investigated. Labeled hMSCs derived from embryonic stem cells (hESC-MSCs), fetal umbilical cord, bone marrow, amniotic membrane and adult bone marrow and adipose tissue were co-cultured with neonatal rat cardiomyocytes (nrCMCs) or cardiac fibroblasts (nrCFBs) for 10 days, and also cultured under angiogenic conditions. Cardiomyogenesis was assessed by human-specific immunocytological analysis, whole-cell current-clamp recordings, human-specific qRT-PCR and optical mapping. After co-culture with nrCMCs, significantly more hESC-MSCs than fetal hMSCs stained positive for α-actinin, whereas adult hMSCs stained negative. Furthermore, functional cardiomyogenic differentiation, based on action potential recordings, was shown to occur, but not in adult hMSCs. Of all sources, hESC-MSCs expressed most cardiac-specific genes. hESC-MSCs and fetal hMSCs contained significantly higher basal levels of connexin43 than adult hMSCs and co-culture with nrCMCs increased expression. After co-culture with nrCFBs, hESC-MSCs and fetal hMSCs did not express α-actinin and connexin43 expression was decreased. Conduction velocity (CV) in co-cultures of nrCMCs and hESC-MSCs was significantly higher than in co-cultures with fetal or adult hMSCs. In angiogenesis bioassays, only hESC-MSCs and fetal hMSCs were able to form capillary-like structures, which stained for smooth muscle and endothelial cell markers.Human embryonic and fetal MSCs differentiate toward three different cardiac lineages, in contrast to adult MSCs. Cardiomyogenesis is determined by stimuli from the cellular microenvironment, where connexin43 may play an important role.
ENDOGLIN Is Dispensable for Vasculogenesis, but Required for Vascular Endothelial Growth Factor-Induced Angiogenesis
Zhen Liu, Franck Lebrin, Janita A. Maring, Sander van den Driesche, Stieneke van der Brink, Maarten van Dinther, Midory Thorikay, Sabrina Martin, Kazuki Kobayashi, Lukas J. A. C. Hawinkels, Laurens A. van Meeteren, Evangelia Pardali, Jeroen Korving, Michelle Letarte, Helen M. Arthur, Charles Theuer, Marie-José Goumans, Christine Mummery, Peter ten Dijke
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0086273
Abstract: ENDOGLIN (ENG) is a co-receptor for transforming growth factor-β (TGF-β) family members that is highly expressed in endothelial cells and has a critical function in the development of the vascular system. Mutations in Eng are associated with the vascular disease known as hereditary hemorrhagic telangiectasia type l. Using mouse embryonic stem cells we observed that angiogenic factors, including vascular endothelial growth factor (VEGF), induce vasculogenesis in embryoid bodies even when Eng deficient cells or cells depleted of Eng using shRNA are used. However, ENG is required for the stem cell-derived endothelial cells to organize effectively into tubular structures. Consistent with this finding, fetal metatarsals isolated from E17.5 Eng heterozygous mouse embryos showed reduced VEGF-induced vascular network formation. Moreover, shRNA-mediated depletion and pharmacological inhibition of ENG in human umbilical vein cells mitigated VEGF-induced angiogenesis. In summary, we demonstrate that ENG is required for efficient VEGF-induced angiogenesis.
Modulation of TGF-β/BMP-6 expression and increased levels of circulating smooth muscle progenitor cells in a type I diabetes mouse model
Peter E Westerweel, Cindy TJ van Velthoven, Tri Q Nguyen, Krista den Ouden, Dominique PV de Kleijn, Marie Goumans, Roel Goldschmeding, Marianne C Verhaar
Cardiovascular Diabetology , 2010, DOI: 10.1186/1475-2840-9-55
Abstract: We isolated SPC from C57Bl/6 mice with streptozotocin-induced diabetes and controls. SPC differentiation was evaluated by immunofluorescent staining for αSMA and collagen Type I. SPC mRNA expression of TGF-β and BMP-6 was quantified using real-time PCR. Intima formation was assessed in cuffed femoral arteries. Homing of bone marrow derived cells to cuffed arterial segments was evaluated in animals transplanted with bone marrow from GFP-transgenic mice.We observed that SPC differentiation was accelerated and numeric outgrowth increased in diabetic animals (24.6 ± 8.8 vs 8.3 ± 1.9 per HPF after 10 days, p < 0.05). Quantitative real-time PCR showed increased expression of TGF-β and decreased expression of the BMP-6 in diabetic SPC. SPC were MAC-3 positive, indicative of monocytic lineage. Intima formation in cuffed arterial segments was increased in diabetic mice (intima/media ratio 0.68 ± 0.15 vs 0.29 ± 0.06, p < 0.05). In GFP-chimeric mice, bone marrow derived cells were observed in the neointima (4.4 ± 3.3 cells per section) and particularly in the adventitia (43.6 ± 9.3 cells per section). GFP-positive cells were in part MAC-3 positive, but rarely expressed α-SMA.In conclusion, in a diabetic mouse model, SPC levels are increased and SPC TGF-β/BMP-6 expression is modulated. Altered TGF-β/BMP-6 expression is known to regulate smooth muscle cell differentiation and may facilitate SPC differentiation. This may contribute to exaggerated intimal hyperplasia in diabetes as bone marrow derived cells home to sites of neointima formation.Diabetes mellitus greatly increases the risk of cardiovascular disease (CVD) and adversely affects the outcome after endovascular procedures. Diabetic patients experience higher rates of restenosis due to intimal hyperplasia[1,2]. Previously it was thought that accumulation of smooth muscle cells in the neointima of restenotic lesions was exclusively due to migration and local proliferation of medial smooth muscle cells or adventitial fibrob
Akzent auf die Standardsprachen: Regionale Spuren in
Marie-José Kolly
Linguistik Online , 2013,
Abstract: Durch ihren fremdsprachlichen Akzent gibt eine Sprecherin ihre Herkunft, ihre Muttersprache preis. So werden die meisten Deutschschweizer beim Sprechen einer Fremdsprache als solche erkannt. Kann aber aufgrund dieses "Deutschschweizer" Akzents auch erkannt werden, aus welchem Dialektgebiet ein Sprecher stammt? Der vorliegende Beitrag stellt eine empirische Studie zur Perzeption dialektaler Akzente vor. Er besch ftigt sich mit dialektalen Akzenten im Standarddeutschen und im Franz sischen und zeigt mit quantitativen Methoden auf, dass dialektal bedingte Akzentunterschiede von native speakers durchaus wahrgenommen und lokalisiert werden k nnen. Darüber hinaus und als Basis für die Auswertung des empirischen Teils leistet die vorliegende Arbeit eine Beschreibung und Kategorisierung der dialektalen Lautlandschaft der Schweiz sowie einen Ansatz zur Beschreibung der Aussprache des Franz sischen durch Schweizer Dialektsprecher.
El grupo doméstico: concepto y realidades
Marie-José Devillard
Política y Sociedad , 1990, DOI: -
Abstract: Sin resumen
Antropología histórica de la familia, de Martine Segalen
Marie-José Devillard
Política y Sociedad , 1993, DOI: -
Abstract: Sin resumen
De los discursos antropológicos sobre naturaleza, cuerpo y cultura.
Marie José Devillard
Política y Sociedad , 2002, DOI: -
Abstract: Sin resumen
La ciudadanía de la Unión Europea: novedades desde Lisboa y Luxemburgo The citizenship of the European Union: news from Lisbon and Luxembourg
Marie-José Garot
Revista Direito GV , 2012,
Abstract: El Tratado de Lisboa, Siguiendo la fallida Constitución Europea, ha introducido un nuevo título II en el Tratado de la Unión Europea, llamado "disposiciones sobre los principios democráticos" que parece completar las ya existentes disposiciones sobre la ciudadanía europea. Una nueva concepción del ciudadano europeo se empieza a dibujar, distinta de la hasta ahora conocida. Además, la recién Jurisprudencia del Tribunal de Justicia de la Unión Europea ha reforzado a su vez la ciudadanía europea que aparece cada día más como el "estatuto de los nacionales de los Estados miembros", incluso en situaciones puramente internas. The Lisbon Treaty, In line with the failed European Constitution, introduced a new Title II in the Treaty on the European Union, called "Provisions on Democratic Principles", that seems to complement the already existing provisions on European citizenship. A new conception of the European citizen, distinct from the one already known, is being designed. Moreover, the recent case-law of the European Court of Justice has on its part reinforced the European citizenship that increasingly appears as the "Status of the Nationals of the Member States", even in purely internal situations.
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