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See detailLoss of T cell microRNA provides systemic protection against autoimmune pathology in mice
Tian, L.; De Hertogh, G.; Fedeli, M. et al

in Journal of Autoimmunity (2012)

With an increasing number of studies demonstrating alterations in T cell microRNA expression during autoimmune disease, modulation of the T cell microRNA network is considered a potential therapeutic ... [more ▼]

With an increasing number of studies demonstrating alterations in T cell microRNA expression during autoimmune disease, modulation of the T cell microRNA network is considered a potential therapeutic strategy. Due to the complex and often opposing interactions of individual microRNA, prioritization of therapeutic targets first requires dissecting the dominant effects of the T cell microRNA network. Initial results utilizing a unidirectional screen suggested that the tolerogenic functions were dominanat, with spontaneous colitis resulting from T cell-specific excision of Dicer. Here we performed a bidirectional screen for microRNA function by removing Dicer from the T cells of both wildtype mice and Transforming Growth Factor β (TGFβ) receptor-deficient mice. This allowed the impact of microRNA loss on T cell activation, effector T cell differentiation and autoimmune pathology to be systematically assessed. This bidirectional screen revealed a dominant immunogenic functionfor T cell microRNA, with potent suppression of T cell activation, IFNγ production and autoimmune pathology in all targeted organs except the colon, where Dicer-dependent microRNA demonstrated a dominant tolerogenic function. These results reverse the original conclusions of microRNA function in T cells by revealing a systemic pro-autoimmune function. [less ▲]

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See detailThe loss of the chloride channel, ClC-5, delays apical iodide efflux and induces a euthyroid goiter in the mouse thyroid gland.
van den Hove, Marie-France; Croizet-Berger, Karine; JOURET, François ULg et al

in Endocrinology (2006), 147(3), 1287-96

Genetic inactivation of ClC-5, a voltage-gated chloride channel prominently expressed in the kidney, leads to proteinuria because of defective apical endocytosis in proximal tubular cells. Because thyroid ... [more ▼]

Genetic inactivation of ClC-5, a voltage-gated chloride channel prominently expressed in the kidney, leads to proteinuria because of defective apical endocytosis in proximal tubular cells. Because thyroid hormone secretion depends on apical endocytosis of thyroglobulin (Tg), we investigated whether ClC-5 is expressed in the thyroid and affects its function, using Clcn5-deficient knockout (KO) mice. We found that ClC-5 is highly expressed in wild-type mouse thyroid ( approximately 40% of mRNA kidney level). The protein was immunolocalized at the apical pole of thyrocytes. In Percoll gradients, ClC-5 overlapped with plasma membrane and early endosome markers, but best codistributed with the late endosomal marker, Rab7. ClC-5 KO mice were euthyroid (normal T4 and TSH serum levels) but developed a goiter with parallel iodine and Tg accumulation (i.e. normal Tg iodination level). When comparing ClC-5 KO with wild-type mice, thyroid 125I uptake after 1 h was doubled, incorporation into Tg was decreased by approximately 2-fold, so that trichloroacetic acid-soluble 125I increased approximately 4-fold. Enhanced 125I- efflux upon perchlorate and presence of 125I-Tg as autoradiographic rings at follicle periphery demonstrated delayed iodide organification. Endocytic trafficking of 125I-Tg toward lysosomes was not inhibited. Expression of pendrin, an I-/Cl- exchanger involved in apical iodide efflux, was selectively decreased by 60% in KO mice at mRNA and protein levels. Thus, ClC-5 is well expressed in the thyroid but is not critical for apical endocytosis, contrary to the kidney. Instead, the goiter associated with ClC-5 KO results from impaired rate of apical iodide efflux by down-regulation of pendrin expression. [less ▲]

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See detailLoss of the VHR dual-specific phosphatase causes cell-cycle arrest and senescence
Rahmouni, Souad ULg; Cerignoli, Fabio; Alonso, Andres et al

in Nature Cell Biology (2006), 8(5), 524-178

Protein tyrosine phosphatases regulate important processes in eukaryotic cells and have critical functions in many human diseases including diabetes to cancer(1-3). Here, we report that the human Vaccinia ... [more ▼]

Protein tyrosine phosphatases regulate important processes in eukaryotic cells and have critical functions in many human diseases including diabetes to cancer(1-3). Here, we report that the human Vaccinia H1-related (VHR) dual-specific protein tyrosine phosphatase regulates cell-cycle progression and is itself modulated during the cell cycle. Using RNA interference (RNAi), we demonstrate that cells lacking VHR arrest at the G1-S and G2-M transitions of the cell cycle and show the initial signs of senescence, such as flattening, spreading, appearance of autophagosomes, beta-galactosidase staining and decreased telomerase activity. In agreement with this notion, cells lacking VHR were found to upregulate p21(Cip-Waf1), whereas they downregulated the expression of genes for cell-cycle regulators, DNA replication, transcription and mRNA processing. Loss of VHR also caused a several-fold increase in serum-induced activation of its substrates, the mitogen-activated protein ( MAP) kinases Jnk and Erk. VHR-induced cell-cycle arrest was dependent on this hyperactivation of Jnk and Erk, and was reversed by Jnk and Erk inhibition or knock-down. We conclude that VHR is required for cell-cycle progression as it modulates MAP kinase activation in a cell-cycle phase-dependent manner. [less ▲]

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See detailLoss of the Y Chromosome in Bone Marrow Cells: Results on 1907 Consecutive Cases of Leukaemia and Preleukaemia
Herens, Christian ULg; Brasseur, Edmond ULg; Jamar, Michelle ULg et al

in Clinical & Laboratory Haematology (1999), 21(1), 17-20

Loss of the Y chromosome with a resulting 45, X0 karyotype is observed in normal bone marrow cells of elderly males but also in haematological malignancies. Whether Y loss in neoplastic cells is related ... [more ▼]

Loss of the Y chromosome with a resulting 45, X0 karyotype is observed in normal bone marrow cells of elderly males but also in haematological malignancies. Whether Y loss in neoplastic cells is related to the process seen in normal ageing or is part of the carcinogenic process is unknown. The present study concerns the cytogenetic data from 1907 consecutive leukaemic or preleukaemic male patients with special regard to the presence or absence of the Y chromosome. Sixty-five patients (3.4%) had a 45, X-Y clone in their bone marrow (BM) cells. Loss of Y was rare below the age of 50 but increased in older patients, reaching 25% of the men over 80. Sixteen patients (0.08%) had more than 90% X0 cells in their BM. A correlation between Y loss and leukaemia could be established in seven cases, three of which were acute myeloid leukaemia M2 subtype where -Y is known to be a secondary event. In three other cases, -Y was part of a complex karyotype. Only one patient exhibited a 45, X0 karyotype, with no other rearrangement, that could be positively correlated with the neoplastic process. [less ▲]

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See detailLoss of type IV collagen alpha 5 and alpha 6 chains in human invasive prostate carcinomas
Dehan, Pierre ULg; Waltregny, David ULg; Beschin, Alain et al

in American Journal of Pathology (1997), 151(4), 1097-104

Type IV collagen, a major component of basement membranes, is organized in a network responsible for the mechanical resistance of the basement membranes. It also plays a key role in epithelial cell ... [more ▼]

Type IV collagen, a major component of basement membranes, is organized in a network responsible for the mechanical resistance of the basement membranes. It also plays a key role in epithelial cell adhesion to basement membranes. This study was designed to investigate the distribution of type IV collagen alpha-chains in normal, preneoplastic, and malignant prostate basement membranes. For this purpose, immunohistochemistry using specific antibodies raised against the different alpha-chains of type IV collagen was performed in eight normal samples, six prostatic intraepithelial neoplasia, and 20 malignant lesions of the prostate. Our results demonstrate the presence of the "novel" alpha 5 (IV) and alpha 6 (IV) chains along with the "classical" alpha 1 (IV)/alpha 2 (IV) chains in the basement membrane of the normal prostate gland. The alpha 3 (IV) chain was never detected in any prostate specimen. Prostatic intraepithelial neoplasia showed a similar immunostaining pattern to that found in normal glands. In cancer gland basement membranes, we demonstrate for the first time a specific loss of the alpha 5 (IV) and alpha 6 (IV) chains, whereas the classical alpha 1 (IV) and alpha 2 (IV) chains were consistently exhibited. Additionally, type VII collagen colocalized with alpha 5 (IV) collagen chain, and these two proteins, which were always observed in normal and prostatic intraepithelial neoplasia gland basement membranes, were lost in invasive carcinoma basement membranes. This observation raises questions about the possible association or cooperation between alpha 5 (IV)/alpha 6 (IV) chains and anchoring fibrils in prostate glands basement membrane. [less ▲]

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See detailLoss-of-function mutations in ATP6V0A2 impair vesicular trafficking, tropoelastin secretion and cell survival.
Hucthagowder, Vishwanathan; Morava, Eva; Kornak, Uwe et al

in Human Molecular Genetics (2009), 18(12), 2149-65

Autosomal recessive cutis laxa type 2 (ARCL2), a syndrome of growth and developmental delay and redundant, inelastic skin, is caused by mutations in the a2 subunit of the vesicular ATPase H+-pump ... [more ▼]

Autosomal recessive cutis laxa type 2 (ARCL2), a syndrome of growth and developmental delay and redundant, inelastic skin, is caused by mutations in the a2 subunit of the vesicular ATPase H+-pump (ATP6V0A2). The goal of this study was to define the disease mechanisms that lead to connective tissue lesions in ARCL2. In a new cohort of 17 patients, DNA sequencing of ATP6V0A2 detected either homozygous or compound heterozygous mutations. Considerable allelic and phenotypic heterogeneity was observed, with a missense mutation of a moderately conserved residue p.P87L leading to unusually mild disease. Abnormal N- and/or mucin type O-glycosylation was observed in all patients tested. Premature stop codon mutations led to decreased ATP6V0A2 mRNA levels by destabilizing the mutant mRNA via the nonsense-mediated decay pathway. Loss of ATP6V0A2 either by siRNA knockdown or in ARCL2 cells resulted in distended Golgi cisternae, accumulation of abnormal lysosomes and multivesicular bodies. Immunostaining of ARCL2 cells showed the accumulation of tropoelastin (TE) in the Golgi and in large, abnormal intracellular and extracellular aggregates. Pulse-chase studies confirmed impaired secretion and increased intracellular retention of TE, and insoluble elastin assays showed significantly reduced extracellular deposition of mature elastin. Fibrillin-1 microfibril assembly and secreted lysyl oxidase activity were normal in ARCL2 cells. TUNEL staining demonstrated increased rates of apoptosis in ARCL2 cell cultures. We conclude that loss-of-function mutations in ATP6V0A2 lead to TE aggregation in the Golgi, impaired clearance of TE aggregates and increased apoptosis of elastogenic cells. [less ▲]

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See detailLosses – Marks&Spencer
Richelle, Isabelle ULg

Conference (2014, January 23)

This conference will explore the history, impact, and potential for further development of the CJEU’s and the EFTA Court’s landmark decisions relating to direct taxation.

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See detailLost and found: Rediscovery of de Ryckholt's collection of Cretaceous Mollusca (Belgium and N. France)
Fischer, Valentin ULg; Denayer, Julien ULg; Mottequin, Bernard ULg

in 4th International Palaeontological Congress, Mendoza, Abstracts volume (2014)

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See detailLost Memories
Havelange, Carl ULg; DELRUE Rony

Book published by Hapax (2007)

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See detailLotissement périurbain et développement durable : les surcoûts collectifs
Halleux, Jean-Marie ULg

Conference given outside the academic context (2001)

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See detailA LOTOS Data Facility Compiler (DAFY)
Lallemand, Eric; Leduc, Guy ULg

in Parther, Ken; Rose, Gordon (Eds.) Formal Description Techniques IV (1991, November)

If we take a look at existing LOTOS specifications, we notice that the description of the needed data types is very often huge. This causes the lack of concision of most descriptions of complex systems ... [more ▼]

If we take a look at existing LOTOS specifications, we notice that the description of the needed data types is very often huge. This causes the lack of concision of most descriptions of complex systems. We propose to tackle this problem in two steps. First, we define extensions to the LOTOS language allowing short definitions of most of the data types used in practical LOTOS specifications. Second, we propose a tool called `'DAFY'' (Data Facility Compiler) which is able to translate these extensions into standard LOTOS. [less ▲]

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See detailLOTOS, un outil utile ou un autre langage académique ?
Leduc, Guy ULg

in Danthine, André (Ed.) Les réseaux de communication - nouveaux outils et tendances actuelles (1987, January)

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See detailLotze en Amérique. Le renouveau réaliste en philosophie chez Santayana
Boccaccini, Federico ULg

in Boccaccini, Federico (Ed.) Lotze et son héritage. Son influence et son impact sur la philosophie du XXème siècle (2014)

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See detailLotze en Amérique. Le renouveau réaliste en philosophie chez Santayana
Boccaccini, Federico ULg

Conference (2011, December)

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See detailLotze et la psychologie physiologique
Seron, Denis ULg

in Boccaccini, Federico (Ed.) Lotze et son héritage: Son influence et son impact sur la philosophie du XXe siècle (in press)

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See detailLotze et son héritage. Son influence et son impact sur la philosophie du XXème siècle
Boccaccini, Federico ULg

Book published by Peter Lang (2014)

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See detailLoud & Bright Purple Birds & Blue Eyed Bitches Dancing. A Task for Poetry # 2
Spinoy, Erik ULg

Book published by Onomatopee (2009)

The present volume is an introduction to the work of the young Belgian artist Tamara Van San. It contains two articles, an interview and a portfolio.

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See detailLouis Couperus: Eline Vere (study pack)
Steyaert, Kris ULg; Eagar, Erna

Learning material (2002)

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See detailLouis Paul Boon in de Engelse neerlandistiek
Steyaert, Kris ULg

in Boelvaar Poef. Tijdschrift van het Louis Paul Boongenootschap (2002), 2(2), 69-77

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