References of "Thiry, Marc"
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See detailStudy of intact virus-like particles of human papillomavirus by capillary electrophoresis
Bettonville, Virginie ULg; Nicol, Jérôme ULg; Thelen, Nicolas ULg et al

in Electrophoresis (in press)

Virus-like particles of human papillomavirus (HPV-VLP), resulting from the self-assembly of the capsid proteins (L1 or L1 and L2), have been widely used to study HPV as they are similar to the native ... [more ▼]

Virus-like particles of human papillomavirus (HPV-VLP), resulting from the self-assembly of the capsid proteins (L1 or L1 and L2), have been widely used to study HPV as they are similar to the native virion. Moreover, two prophylactic vaccines, Gardasil® and Cervarix®, are based on HPV-VLP L1. Analytical techniques currently used to characterize HPV-VLP, such as SDS-PAGE, Western blot, ELISA, are time-consuming and semi-quantitative. In this study, capillary electrophoresis (CE) was evaluated for the analysis of intact HPV16-VLP. The usefulness of capillary inner wall coating as well as various BGEs, pH and detergent additives were investigated. Reproducible HPV-VLP analysis in CE was achieved using poly(ethylene oxide) coated capillary and a BGE containing high salt concentration and low SDS concentration. The developed method enables HPV-VLP detection in less than 10 min (migration times RSD : 1.6 %). The identity of HPV-VLP peak was confirmed by comparison with a sample obtained from a wild-type baculovirus and with VLP-based vaccine, Gardasil®, after adjuvant dissolution. Finally, we applied the developed methodology to VLP-based vaccines, demonstrating that CE could be successfully used for vaccine quality control. [less ▲]

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See detailMyoferlin plays a key role in VEGFA secretion and impacts tumor-associated angiogenesis in human pancreas cancer
Fahmy, Karim ULg; Gonzalez, Arnaud; Arafa, Mohammad et al

in International Journal of Cancer = Journal International du Cancer (2016), 138

Pancreatic ductal adenocarcinoma is one of the most deadly forms of cancers with no satisfactory treatment to date. Recent studies have identified myoferlin, a ferlin family member, in human pancreas ... [more ▼]

Pancreatic ductal adenocarcinoma is one of the most deadly forms of cancers with no satisfactory treatment to date. Recent studies have identified myoferlin, a ferlin family member, in human pancreas adenocarcinoma where its expression was associated to a bad prognosis. However, the function of myoferlin in pancreas adenocarcinoma has not been reported. In other cell types, myoferlin is involved in several key plasma membrane processes such as fusion, repair, endocytosis and tyrosine kinase receptor activity. In this study, we showed that myoferlin silencing in BxPC-3 human pancreatic cancer cells resulted in the inhibition of cell proliferation in vitro and in a significant reduction of the tumor volume in chick chorioallantoic membrane assay. In addition to be smaller, the tumors formed by the myoferlin-silenced cells showed a marked absence of functional blood vessels. We further demonstrated that this effect was due, at least in part, to an inhibition of VEGFA secretion by BxPC-3 myoferlin-silenced cells. Using immunofluorescence and electron microscopy, we linked the decreased VEGFA secretion to an impairment of VEGFA exocytosis. The clinical relevance of our results was further strengthened by a significant correlation between myoferlin expression in a series of human pancreatic malignant lesions and their angiogenic status evaluated by the determination of the blood vessel density. [less ▲]

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See detailHypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes.
Delmaghani, Sedigheh; Defourny, Jean; Aghaie, Asadollah et al

in Cell (2015), 163(4), 894-906

A deficiency in pejvakin, a protein of unknown function, causes a strikingly heterogeneous form of human deafness. Pejvakin-deficient (Pjvk(-/-)) mice also exhibit variable auditory phenotypes ... [more ▼]

A deficiency in pejvakin, a protein of unknown function, causes a strikingly heterogeneous form of human deafness. Pejvakin-deficient (Pjvk(-/-)) mice also exhibit variable auditory phenotypes. Correlation between their hearing thresholds and the number of pups per cage suggest a possible harmful effect of pup vocalizations. Direct sound or electrical stimulation show that the cochlear sensory hair cells and auditory pathway neurons of Pjvk(-/-) mice and patients are exceptionally vulnerable to sound. Subcellular analysis revealed that pejvakin is associated with peroxisomes and required for their oxidative-stress-induced proliferation. Pjvk(-/-) cochleas display features of marked oxidative stress and impaired antioxidant defenses, and peroxisomes in Pjvk(-/-) hair cells show structural abnormalities after the onset of hearing. Noise exposure rapidly upregulates Pjvk cochlear transcription in wild-type mice and triggers peroxisome proliferation in hair cells and primary auditory neurons. Our results reveal that the antioxidant activity of peroxisomes protects the auditory system against noise-induced damage. [less ▲]

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See detailSpatio‑temporal dynamics of β‑tubulin isotypes during the development of the sensory auditory organ in rat
Renauld, Justine ULg; Johnen, Nicolas; Thelen, Nicolas ULg et al

in Histochemistry & Cell Biology (2015)

There are different β-tubulin isoforms in microtubules of vertebrate tissues. However, their functional significance is still largely unknown. In the present study, we investigated the localization of ... [more ▼]

There are different β-tubulin isoforms in microtubules of vertebrate tissues. However, their functional significance is still largely unknown. In the present study, we investigated the localization of five β-tubulin isotypes (β1– 5) within the hearing organ during development in rat. By using confocal microscopy, we showed that with the exception of the β3-tubulin isoform that was specific to nerve fibres, all the different β-tubulin isoforms were mainly present in the supporting cells. Contrary to β1–4-tubulins, we also found that the β5-tubulin isoform appeared only at a key stage of the post-natal development in specific cell types (pillar cells and Deiters’ cells). By using transmission electron microscopy, we revealed further that this developmental stage coincided with the formation of two separate bundles of microtubules from a unique one in these supporting cells. Together, these results suggest that the β5-tubulin isoform might be involved in the generation of new microtubule bundles from a pre-existing one. [less ▲]

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See detailIdentification of VZV ORF9p potential cellular partners that could be important for the viral egress.
Lebrun, Marielle ULg; riva, laura; Rambout, Xavier ULg et al

Poster (2015, July 26)

ORF9p (homologous to HSV-1 VP22) is a VZV tegument protein essential for the viral replication. During the lytic cycle it is the mostly expressed gene. We have recently demonstrated that it is a substrate ... [more ▼]

ORF9p (homologous to HSV-1 VP22) is a VZV tegument protein essential for the viral replication. During the lytic cycle it is the mostly expressed gene. We have recently demonstrated that it is a substrate of the viral kinase ORF47p and that its ORF47p-dependent phosphorylation is important for the secondary envelopment process. We also have identified an acidic cluster (AC) within the protein that is important for its correct localization in the infected cells and for the interaction with ORF47p. The recombinant VZV expressing ORF9p-ΔAC presents an accumulation of capsids in the perinuclear space. ORF9p seems then to play an important role in several steps of the egress process. In this context, we sought to identify cellular partners of ORF9p that might be important for these functions. We performed a yeast two hybrid screen against the human ORFeome 5.1. and picked out 44 candidates among which 5 proteins playing roles in membrane organization and targeting. We currently are trying to confirm these interactions in infected cells and to assess the role of these interactions for the viral lytic cycle. [less ▲]

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See detailDUSP3 Phosphatase Deficiency or Inhibition Limits Platelet Activation and Arterial Thrombosis
Rahmouni, Souad ULg; MUSUMECI, Lucia ULg; Kuijpers, Marijke J et al

Conference (2015, June 24)

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See detailSpatio-temporal dynamics of β-tubulin isotypes and acetyl-alpha tubulin during the development of the sensory auditory organ in rodents.
Renauld, Justine ULg; Thelen, Nicolas ULg; Johnen, Nicolas ULg et al

Poster (2015, June 05)

The auditory organ is a highly specialized structure composed by specific cellular types. The sensory cells are characterized by stereocilia at their apex and are necessary for the sound perception. These ... [more ▼]

The auditory organ is a highly specialized structure composed by specific cellular types. The sensory cells are characterized by stereocilia at their apex and are necessary for the sound perception. These cells are supported by supporting cells. Supporting cells possess a characteristic cytoskeleton in direct relation with their morphological features and their development. There are different β-tubulin isoforms in microtubules of vertebrate tissues. However, their functional significance is still largely unknown. In the present study, we investigated the localization of five β-tubulin isotypes (β 1 to 5) as well as acetyl-α-tubulin within the hearing organ during development in rodents. By using confocal microscopy, we showed that with the exception of the β3-tubulin isoform that was specific to nerve fibres, all the different β-tubulin isoforms and acetyl-α-tubulin were mainly present in the supporting cells. Contrary to β1-4-tubulins, we also found that the β5-tubulin isoform appeared only at a key stage of the postnatal development in specific cell types (pillar cells and Deiters’ cells). By using transmission electron microscopy, we revealed further that this developmental stage coincided with the formation of two separate bundles of microtubules from a unique one in these supporting cells. In conclusion, these results suggest that the β5-tubulin isoform might be involved in the generation of new microtubule bundles from a pre-existing one. [less ▲]

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See detailVaricella-Zoster Virus (VZV) assemblons interplay with PML bodies
Lebrun, Marielle ULg; Thiry, Marc ULg; Sadzot, Catherine ULg

Poster (2015, May 15)

Using a virus expressing the small capsid protein fused to an eGFP tag (eGFP-ORF23 VZV), we recently identified, in the nuclei of infected cells, the presence of dynamic capsid aggegrates. Because we ... [more ▼]

Using a virus expressing the small capsid protein fused to an eGFP tag (eGFP-ORF23 VZV), we recently identified, in the nuclei of infected cells, the presence of dynamic capsid aggegrates. Because we believe that these structures might represent sites of preferential caspid assembly and by analogy with HSV-1, we referred to them as “VZV assemblons”. Structures resembling these assemblons and identified as capsids entrapped in some “PML-cages” were recently described in the nuclei of wild-type VZV infected cells (Reichelt et al., 2011). We then wonder if there was a link between these independent observations. When we infected MeWo cells in which the expression of each PML subunit is downregulated by shRNA, VZV assemblons still formed. Immunostaining of MeWo cells infected by eGFP-ORF23 VZV with an antibody against the PML protein showed that VZV assemblons only partially colocalize with PML bodies. However, overexpression of PML-I-eGFP in HEK293 cells followed by infection with a tagRFP-T-ORF23 VZV, where the ORF23 protein is fused to a red tag, showed a complete colocalization is complete. The same result was obtained with all tested PML isoforms. This suggests that the partial colocalization in normal cells could be due to the expression level of PML proteins. Altogether, these results suggest that rather than a progressive accumulation of newly formed capsids within PML cages, it is likely that PML protein is recruited to the sites where VZV assemblons develop. It correlates with the fact that the number of PML bodies decreases with the infection. Obviously, even if this phenomenon might impede the egress of a substantial amount of capsids and, in this regard, limit the infection progression, all the tested cell lines are permissive to VZV. It would then be interesting to investigate the relationship between VZV assemblons and PML bodies in latent or non permissive VZV infection models. [less ▲]

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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 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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