References of "Thiry, Marc"
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See detailDUSP3 Phosphatase Deficiency or Inhibition Limit Platelet Activation and Arterial Thrombosis
Musumeci, Lucia ULg; Kuijpers, Marijke; Gilio, Karen et al

in Circulation (2015), 131(7), 656-68

Background A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. Better understanding of the molecular mechanisms leading to platelet ... [more ▼]

Background A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. Better understanding of the molecular mechanisms leading to platelet activation is of importance for the development of improved therapies. Recently, protein tyrosine phosphatases (PTPs) have emerged as critical regulators of platelet function. Methods and Results This is the first report implicating the dual-specificity phosphatase 3 (DUSP3) in platelet signaling and thrombosis. This phosphatase is highly expressed in human and mouse platelets. Platelets from DUSP3-deficient mice displayed a selective impairment of aggregation and granule secretion mediated through the collagen receptor glycoprotein VI (GPVI) and the C-type lectin-like receptor 2 (CLEC-2). DUSP3-deficient mice were more resistant to collagen- and epinephrine-induced thromboembolism, compared to wild-type mice, and showed severely impaired thrombus formation upon ferric chloride-induced carotid artery injury. Intriguingly, bleeding times were not altered in DUSP3-deficient mice. At the molecular level, DUSP3 deficiency impaired Syk tyrosine phosphorylation, subsequently reducing phosphorylation of PLCγ2 and calcium fluxes. To investigate DUSP3 function in human platelets, a novel small-molecule inhibitor of DUSP3 was developed. This compound specifically inhibited collagen and CLEC-2-induced human platelet aggregation, thereby phenocopying the effect of DUSP3 deficiency in murine cells. Conclusions DUSP3 plays a selective and essential role in collagen- and CLEC-2-mediated platelet activation and thrombus formation in vivo. Inhibition of DUSP3 may prove therapeutic for arterial thrombosis. This is the first time a PTP, implicated in platelet signaling, has been targeted with a small-molecule drug. [less ▲]

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See detailMyoferlin: an indispensable component in VEGFA secretion by pancreas cancer cells
Fahmy, Karim ULg; Peulen, Olivier ULg; Castronovo, Vincenzo ULg et al

Poster (2015, January 31)

In this poster, our laboratory showed the importance of myoferlin, a biomarker of pancreas cancer, in the controle of VEGF-A mediated angiogenesis. Our laboratory showed that silencing myoferlin in ... [more ▼]

In this poster, our laboratory showed the importance of myoferlin, a biomarker of pancreas cancer, in the controle of VEGF-A mediated angiogenesis. Our laboratory showed that silencing myoferlin in pancreas cancer cells, BxPC-3, provoques a decrease in cell prolifération in vitro and a decrease in tumor volumes in animal model. Myoferlin silencing also provokes a decrease in VEGF-A secretion in the conditioned medium and that decrease was abserved in the animal model as a decrease in microvessels dencity. It appeared that this decrease in secretion is due to a a blockage in the exocytosis. Our data also showed a significate correlation between myoferlin expression and microvessels density in patients section. [less ▲]

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See detailMyoferlin Regulates Endosomal Trafficking and Tunes Cancer Cell Metabolism
Blomme, Arnaud; Costanza, Brunella; Thiry, Marc ULg et al

Poster (2015, January 31)

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See detailBacterial DNA mimetics activate platelets and promote thrombosis via CLEC-2
Delierneux, Céline; Hego, Alexandre; Lecut, Christelle et al

Poster (2015, January 27)

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See detailAccumulation of methylglyoxal, a glycolysis by-product modulates YAP1 transcription co-factor localization and activity in human breast cancer cells through HSP90 modification
Nokin, Marie-Julie; Durieux, Florence; Peixoto, Paul et al

Poster (2015, January 27)

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See detailMyoferlin: an indispensable component in VEGR-A secretion by pancreatic cancer cell
Fahmy, Karim; Gonzalez, Arnaud; Arafad, Mohamed et al

Poster (2015, January 27)

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See detailMyoferlin regulates endosomal trafficking and tunes cancer cell metabolism
Blomme, Arnaud; Costanza, Brunella; Thiry, Marc ULg et al

Poster (2015, January 27)

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See detailLocalization of rDNA transcription sites within reptilian nucleoli
Bartholomé, Odile ULg; Franck, Claire; Thiry, Marc ULg

Poster (2015, January 27)

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See detailChange in the protofilamentnumber and β5-tubulin appearance in supporting cells during development of the hearing organ.
Renauld, Justine ULg; Thelen, Nicolas ULg; Johnen, Nicolas ULg et al

Poster (2015, January)

The supporting cells of the hearing organ are characterized by the presence of an abundant cytoskeleton which is mainly composed of microtubules. These supporting cells have also been shown to contain a ... [more ▼]

The supporting cells of the hearing organ are characterized by the presence of an abundant cytoskeleton which is mainly composed of microtubules. These supporting cells have also been shown to contain a minor mammalian tubulin, the β5-tubulin, recently reported as a biomarker of cell proliferation. It was shown that a β-tubulin isoform can specify the microtubule architecture, as seen with the expression of the Moth β2 tubulin in the Drosophila testes which imposes the 16-protofilament (16pf) structure on the corresponding subset of Drosophila microtubules. Moreover, supporting cell microtubules are formed by 15pf instead of the canonical 13, a unique fact among vertebrates. Such a protofilament configuration has been observed in C. elegans’ neurons which are responsible for the mechanosensory sense of touch. It was also shown that these 15pf microtubules were essential to the proper functioning of these neurons. To determine the role of this particular tubulin in the auditory organ and its possible involvement in the formation of the unusual 15pf microtubules of supporting cells, we studied the spatiotemporal localization of β5-tubulin during development in rats from embryonic day 18 until P25 (25th postnatal day). Then we examined the fine structure of microtubules at the transmission electron microscope level (TEM). Our results showed that β5-tubulin, contrary to other β-tubulins, had a unique distribution in the cochlea. This β-tubulin appeared at a postnatal stage, before the opening of the Corti’s tunnel and is restricted to supporting cells, especially in pillar and Deiters’ cells. Our TEM study further indicated that these cells were composed by 13pf microtubules at P2, but by 15pf microtubules at P25. In conclusion, the architecture and composition of microtubules present in the supporting cells change during development of the Corti organ. Further experiments are now required to determine if these changes are related to the appearance of β5-tubulin. [less ▲]

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See detailA dynamic unfolded protein response contributes to the control of cortical neurogenesis
LAGUESSE, Sophie ULg; Creppe, Catherine ULg; Nedialkova, Dany et al

in Developmental Cell (2015)

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See detailMicroRNA-124 Regulates Cell Specification in the Cochlea through Modulation of Sfrp4/5.
Huyghe, Aurelia; Van Den Ackerveken, Priscilla ULg; SACHELI, Rosalie ULg et al

in Cell Reports (2015), 13

The organ of Corti, the auditory organ of the mammalian inner ear, contains sensory hair cells and supporting cells that arise from a common sensory progenitor. The molecular bases allowing the ... [more ▼]

The organ of Corti, the auditory organ of the mammalian inner ear, contains sensory hair cells and supporting cells that arise from a common sensory progenitor. The molecular bases allowing the specification of these progenitors remain elusive. In the present study, by combining microarray analyses with conditional deletion of Dicer in the developing inner ear, we identified that miR-124 controls cell fate in the developing organ of Corti. By targeting secreted frizzled-related protein 4 (Sfrp4) and Sfrp5, two inhibitors of the Wnt pathway, we showed that miR-124 controls the β-catenin-dependent and also the PCP-related non-canonical Wnt pathways that contribute to HC differentiation and polarization in the organ of Corti. Thus, our work emphasizes the importance of miR-124 as an epigenetic safeguard that fine-tunes the expression of genes critical for cell patterning during cochlear differentiation. [less ▲]

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See detailExpanding the clinical and mutational spectrum of the Ehlers-Danlos syndrome Dermatosparaxis.
Van Damme, Tim; Colige, Alain ULg; Syx, Delfien et al

in Genetics in Medicine : Official Journal of the American College of Medical Genetics (2015)

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See detailEndothelial exosomes contribute to the antitumor response during breast cancer neoadjuvant chemotherapy via microRNA transfer.
Bovy, Nicolas ULg; Blomme, Benoît ULg; Freres, Pierre ULg et al

in Oncotarget (2015)

The interaction between tumor cells and their microenvironment is an essential aspect of tumor development. Therefore, understanding how this microenvironment communicates with tumor cells is crucial for ... [more ▼]

The interaction between tumor cells and their microenvironment is an essential aspect of tumor development. Therefore, understanding how this microenvironment communicates with tumor cells is crucial for the development of new anti-cancer therapies. MicroRNAs (miRNAs) are small non-coding RNAs that inhibit gene expression. They are secreted into the extracellular medium in vesicles called exosomes, which allow communication between cells via the transfer of their cargo. Consequently, we hypothesized that circulating endothelial miRNAs could be transferred to tumor cells and modify their phenotype. Using exogenous miRNA, we demonstrated that endothelial cells can transfer miRNA to tumor cells via exosomes. Using miRNA profiling, we identified miR-503, which exhibited downregulated levels in exosomes released from endothelial cells cultured under tumoral conditions. The modulation of miR-503 in breast cancer cells altered their proliferative and invasive capacities. We then identified two targets of miR-503, CCND2 and CCND3. Moreover, we measured increased plasmatic miR-503 in breast cancer patients after neoadjuvant chemotherapy, which could be partly due to increased miRNA secretion by endothelial cells. Taken together, our data are the first to reveal the involvement of the endothelium in the modulation of tumor development via the secretion of circulating miR-503 in response to chemotherapy treatment. [less ▲]

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See detailDetection of rRNA synthesis sites within reptilian nucleoli
Bartholomé, Odile ULg; Thiry, Marc ULg; Franck, Claire

Poster (2014, December 13)

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See detailCytoskeletal changes in supporting cells of the auditory organ during development in rodents: the appearance of 15-protofilament microtubules and β5-tubulin isoform.
Renauld, Justine ULg; Thelen, Nicolas ULg; Johnen, Nicolas et al

Poster (2014, December)

A feature of the supporting cells of the organ of Corti is the presence of an abundant cytoskeleton which is mainly composed of microtubules. These supporting cells have also been shown to contain a minor ... [more ▼]

A feature of the supporting cells of the organ of Corti is the presence of an abundant cytoskeleton which is mainly composed of microtubules. These supporting cells have also been shown to contain a minor mammalian tubulin, the β5-tubulin [1], recently reported to be a biomarker for cancer outcome [2] and cell proliferation [3]. It was shown that a β-tubulin isoform can specify the microtubule architecture, as seen with the expression of the Moth β2 tubulin in the Drosophila testes which imposes the 16-protofilament (16pf) structure on the corresponding subset of Drosophila microtubules, which normally contain 13pf [4]. Moreover, supporting cell microtubules are formed by 15pf instead of the canonical 13, a unique fact among vertebrates [5]. Such a protofilament configuration has been observed in C. elegans’ neurons which are responsible for the mechanosensory sense of touch [6]. It was also shown that these 15pf microtubules were essential to the proper functioning of these mechanosensory neurons [6]. To determine the role of this particular tubulin in the auditory organ and its possible involvement in the formation of the unusual 15pf microtubules of supporting cells, we studied the spatiotemporal localization of β5-tubulin during development in rats from embryonic day 18 until P25 (25th postnatal day). Then we examined the fine structure of microtubules at the transmission electron microscope level. Our results showed that β5-tubulin, contrary to other β-tubulins, had a unique distribution in the cochlea. This β-tubulin appeared at a postnatal stage, before the opening of the Corti’s tunnel and are restricted to supporting cells, especially in pillar and Deiters’ cells. Electron microscopy further indicated that pillar and Deiters cells were composed by 13pf microtubules at P2, but by 15pf microtubules at P25. In conclusion, the architecture of microtubules seems to evolve during the development of the organ of Corti. Furthermore, β5-tubulin has the same localization than this structure and could be an interesting target. [less ▲]

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See detailLa symétrie du vivant : des organismes aux molécules
Thiry, Marc ULg

in Bulletin de la Société Royale des Sciences de Liège (2014, October 28), 83

Les êtres vivants possèdent des caractéristiques communes de symétrie et de dissymétrie. Celles-ci ne concernent pas uniquement l’organisation externe des organismes vivants mais impliquent aussi tous ... [more ▼]

Les êtres vivants possèdent des caractéristiques communes de symétrie et de dissymétrie. Celles-ci ne concernent pas uniquement l’organisation externe des organismes vivants mais impliquent aussi tous leurs niveaux d’organisation jusqu’aux molécules qui les constituent. Le monde vivant se singularise du monde inanimé par l’homochiralité des molécules biologiques. [less ▲]

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See detailUnveiling the effects of berenil, a DNA-binding drug, on Trypanosoma cruzi: implications for kDNA ultrastructure and replication.
Zuma, Aline Araujo; Cavalcanti, Danielle Pereira; Zogovich, Marcelo et al

in Parasitology research (2014)

Trypanosoma cruzi, the etiological agent of Chagas disease, exhibits a single mitochondrion with an enlarged portion termed kinetoplast. This unique structure harbors the mitochondrial DNA (kDNA ... [more ▼]

Trypanosoma cruzi, the etiological agent of Chagas disease, exhibits a single mitochondrion with an enlarged portion termed kinetoplast. This unique structure harbors the mitochondrial DNA (kDNA), composed of interlocked molecules: minicircles and maxicircles. kDNA is a hallmark of kinetoplastids and for this reason constitutes a valuable target in chemotherapeutic and cell biology studies. In the present work, we analyzed the effects of berenil, a minor-groove-binding agent that acts preferentially at the kDNA, thereby affecting cell proliferation, ultrastructure, and mitochondrial activity of T. cruzi epimastigote form. Our results showed that berenil promoted a reduction on parasite growth when high concentrations were used; however, cell viability was not affected. This compound caused significant changes in kDNA arrangement, including the appearance of membrane profiles in the network and electron-lucent areas in the kinetoplast matrix, but nuclear ultrastructure was not modified. The use of the TdT technique, which specifically labels DNA, conjugated to atomic force microscopy analysis indicates that berenil prevents the minicircle decatenation of the network, thus impairing DNA replication and culminating in the appearance of dyskinetoplastic cells. Alterations in the kinetoplast network may be associated with kDNA lesions, as suggested by the quantitative PCR (qPCR) technique. Furthermore, parasites treated with berenil presented higher levels of reactive oxygen species and a slight decrease in the mitochondrial membrane potential and oxygen consumption. Taken together, our results reveal that this DNA-binding drug mainly affects kDNA topology and replication, reinforcing the idea that the kinetoplast represents a potential target for chemotherapy against trypanosomatids. [less ▲]

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See detailUnveil the Mechanism of Action of Berenil, a DNA Binding Drug, on Trypanosoma cruzi
Zuma, Aline Araujo; Cavalcanti, Danielle Pereira; Thiry, Marc ULg et al

Poster (2014, September)

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See detailβ 5 tubulin and 15-protofilament microtubules appeared in supporting cells of the Corti’s organ during development in rodents
Renauld, Justine ULg; Thelen, Nicolas ULg; Johnen, Nicolas et al

Conference (2014, August 31)

A feature of the organ of Corti’s supporting cells is the presence of an abundant cytoskeleton which is mainly composed of microtubules. These supporting cells have also been shown to contain a minor ... [more ▼]

A feature of the organ of Corti’s supporting cells is the presence of an abundant cytoskeleton which is mainly composed of microtubules. These supporting cells have also been shown to contain a minor mammalian tubulin, the β5-tubulin [1], recently related as a biomarker for cancer outcome [2] and cell proliferation [3]. It was shown that a β-tubulin isoform can specified the microtubule architecture, such as the expression of the Moth β2 in the Drosophila testes imposed the 16 protofilaments (16pf) structure on the corresponding subset of Drosophila microtubules, which normally contain 13pf [4]. Moreover, supporting cell microtubules are formed by 15pf instead of the canonical 13, a unique fact among vertebrates [5]. Such a protofilament configuration has been observed in C. elegans’ neurons which are responsible for the mechanosensory sense of touch [6]. It was also shown that these 15pf microtubules were essential to the proper functioning of these mechanosensory neurons [6]. To determine the role of this particular tubulin in the auditory organ and its possible involvement in the formation of the unusual 15pf microtubules of supporting cells, we studied the spatiotemporal localization of β5-tubulin during development in rats from embryonic day 18 until P25 (25th postnatal day). We also analyzed the localization of β5-tubulin mRNA expression in the Corti’s organ. Then we examined the fine structure of microtubules at the electron microscope level. For these experiments, we used an early postnatal stage and a late postnatal stage. Our results showed that β5-tubulin, contrary to other β-tubulins, had a unique distribution in the cochlea. This β-tubulin appeared at a postnatal stage, before the opening of the Corti’s tunnel and being restricted to supporting cells, especially in pillar and Deiters cells,. The same localization of β5-tubulin mRNA was observed by in Situ Hybridization. Electron microscopy indicated further that Pillar and Deiters cells were composed by 15-protofilament microtubules at the late postnatal stage (P25). In conclusion, all these data strongly suggest that there is a relationship between the presence of β5-tubulin and 15-protofilament microtubules in the supporting cells of the auditory organ. Further studies are now needed to elucidate their role. [less ▲]

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