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Peer Reviewed
See detailHuman placental growth hormone: proof of identity with the GH-V gene product by N-terminal microsequence analysis.
Scippo, Marie-Louise ULg; Frankenne, F.; Van Beumen, J. et al

in Archives Internationales de Physiologie et de Biochimie (1989), 97

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See detailHuman platelet glycoprotein VI function is antagonized by monoclonal antibody-derived Fab fragments.
Lecut, Christelle ULg; Feeney, L. A.; Kingsbury, G. et al

in Journal of Thrombosis and Haemostasis [=JTH] (2003), 1(12), 2653-62

Platelet interactions with adhesive ligands exposed at sites of vascular injury initiate the normal hemostatic response but may also lead to arterial thrombosis. Platelet membrane glycoprotein (GP)VI is a ... [more ▼]

Platelet interactions with adhesive ligands exposed at sites of vascular injury initiate the normal hemostatic response but may also lead to arterial thrombosis. Platelet membrane glycoprotein (GP)VI is a key receptor for collagen. Impairment of GPVI function in mice results in a long-term antithrombotic protection and prevents neointimal hyperplasia following arterial injury. On the other hand, GPVI deficiency in humans or mice does not result in serious bleeding tendencies. Blocking GPVI function may thus represent a new and safe antithrombotic approach, but no specific, potent anti-GPVI directed at the human receptor is yet available. Our aim was to produce accessible antagonists of human GPVI to evaluate the consequences of GPVI blockade. Amongst several monoclonal antibodies to the extracellular domain of human GPVI, one, 9O12.2, was selected for its capacity to disrupt the interaction of GPVI with collagen in a purified system and to prevent the adhesion of cells expressing recombinant GPVI to collagen and collagen-related peptides (CRP). While 9O12.2 IgGs induced platelet activation by a mechanism involving GPVI and Fc gamma RIIA, 9O12.2 Fab fragments completely blocked collagen-induced platelet aggregation and secretion from 5 microg mL-1 and fully prevented CRP-induced activation from 1.5 microg mL-1. 9O12.2 Fabs also inhibited the procoagulant activity of collagen-stimulated platelets and platelet adhesion to collagen in static conditions. Furthermore, 9O12.2 Fabs impaired platelet adhesion, and prevented thrombi formation under arterial flow conditions. We thus describe here for the first time a functional monoclonal antibody to human GPVI and demonstrate its effect on collagen-induced platelet aggregation and procoagulant activity, and on thrombus growth. [less ▲]

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See detailHuman pressure and the environment in Vietnam: focus on the Binh Thuan Province
Ozer, Pierre ULg

Conference (2011, March 08)

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See detailHuman prolactin. cDNA structural analysis and evolutionary comparisons
Cooke, Nancy E; Coit, Doris; Shine, John et al

in Journal of Biological Chemistry (1981), 256(8), 4007-16

Prolactin (Prl), growth hormone, and chorionic sommatomammotropin form a set (the "Prl set") of hormones which is thought to have evolved from a common ancestral gene. This assumption is based on several ... [more ▼]

Prolactin (Prl), growth hormone, and chorionic sommatomammotropin form a set (the "Prl set") of hormones which is thought to have evolved from a common ancestral gene. This assumption is based on several lines of evidence: overlap in their biological and immunological properties, similarities in their amino acid sequences, and homologies in the nucleic acid sequences of their structural genes. In the current study we report the cloning, amplification in bacteria, and sequence analysis of DNA complementary to Prl mRNA isolated from human pituitary Prl-secreting adenomas. The cloned DNA contains 914 bases, which includes the entire coding sequence of human prePrl as well as portions of the 5- and 3'-untranslated regions of the mRNA. The amino acid sequence predicted by our data differs from a previously reported amino acid sequence in 8 positions. With the results of this study we can now compare in one species the nucleotide sequences of the structural gene coding for each of the hormones of the Prl set. The sequence divergence at replacement sites is used to establish an evolutionary clock for the Prl set of genes. Using this clock, we postulate that the chromosomal segregation of human Prl and human growth hormone occurred about 392 million years ago and that growth hormone and chorionic sommatomammotropin underwent an intrachromosomal recombination within the last 10 million years. [less ▲]

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See detailHuman recombinant erythropoietin and quality of life: a wonder drug or something to wonder about?
Bottomley, A.; Thomas, R.; Van Steen, Kristel ULg et al

in Lancet Oncology (2002), 3(3), 145-53

Over the past decade an increasing number of studies have supported the use of recombinant human erythropoietin (epoetin) in cancer patients, suggesting that it improves haemoglobin concentrations for ... [more ▼]

Over the past decade an increasing number of studies have supported the use of recombinant human erythropoietin (epoetin) in cancer patients, suggesting that it improves haemoglobin concentrations for some. There is also evidence that this treatment may lead to improvement in quality of life for cancer patients. This systematic review examines the issue. We identified and critically reviewed 13 trials. Although some of the results indicate that epoetin has positive effects on quality of life, methodological limitations inherent in most of the studies hamper interpretation of data. Evidence from this review suggests that more robust designs are required to show any significant quality-of-life benefits for cancer patients undergoing epoetin treatment. [less ▲]

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See detailHuman recombinant thiamine triphosphatase: purification, secondary structure and catalytic properties
Lakaye, Bernard ULg; Makarchikov, Alexander F; Wins, Pierre et al

in International Journal of Biochemistry & Cell Biology (2004), 36(7), 1348-1364

Thiamine triphosphate (ThTP) is found in most living organisms and it may act as a phosphate donor for protein phosphorylation. We have recently cloned the cDNA coding for a highly specific mammalian 25 ... [more ▼]

Thiamine triphosphate (ThTP) is found in most living organisms and it may act as a phosphate donor for protein phosphorylation. We have recently cloned the cDNA coding for a highly specific mammalian 25 kDa thiamine triphosphatase (ThTPase; EC 3.6.1.28). As the enzyme has a high catalytic efficiency and no sequence homology with known phosphohydrolases, it was worth investigating its structure and catalytic properties. For this purpose, we expressed the untagged recombinant human ThTPase (hThTPase) in E. coli, produced the protein on a large scale and purified it to homogeneity. Its kinetic properties were similar to those of the genuine human enzyme, indicating that the recombinant hThTPase is completely functional. Mg2+ ions were required for activity and Ca2+ inhibited the enzyme by competition with Mg2+. With ATP as substrate, the catalytic efficiency was 10(-4)-fold lower than with ThTP, confirming the nearly absolute specificity of the 25 kDa ThTPase for ThTP. The activity was maximum at pH 8.5 and very low at pH 6.0. Zn2+ ions were inhibitory at micromolar concentrations at pH 8.0 but activated at pH 6.0. Kinetic analysis suggests an activator site for Mg2+ and a separate regulatory site for Zn2+. The effects of group-specific reagents such as Woodward's reagent K and diethylpyrocarbonate suggest that at least one carboxyl group in the active site is essential for catalysis, while a positively charged amino group may be involved in substrate binding. The secondary structure of the enzyme, as determined by Fourier-transform infrared spectroscopy, was predominantly beta-sheet and alpha-helix. [less ▲]

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See detailHuman RelB (I-Rel) functions as a kappa B site-dependent transactivating member of the family of Rel-related proteins.
Bours, Vincent ULg; Azarenko, V.; Dejardin, Emmanuel ULg et al

in Oncogene (1994), 9(6), 1699-702

RelB belongs to the family of Rel-related proteins, dimers of which determine NF-kappa B activity. The murine RelB protein has been reported to be a dimerizing partner in kappa B-binding complexes which ... [more ▼]

RelB belongs to the family of Rel-related proteins, dimers of which determine NF-kappa B activity. The murine RelB protein has been reported to be a dimerizing partner in kappa B-binding complexes which are capable of transactivation. On the other hand, the I-Rel protein, the presumed human homolog of RelB, was proposed to be an inhibitor whose presence in dimeric complexes interfered with their kappa B binding and therefore interfered also with transactivation. We demonstrate that human RelB (I-Rel) forms with p50 and p52 (p50B) kappa B-binding heterodimeric complexes which potently transactivate kappa B-dependent constructs in transfection studies. It is concluded that human RelB (I-Rel) and murine RelB can both function as transactivators and that no significant species-specific differences exist. [less ▲]

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See detailHuman Serum biomonitoring: Methodology and Intercalibration
Focant, Jean-François ULg; Eppe, Gauthier ULg

Scientific conference (2009, March)

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See detailHuman T-cell leukemia virus type-1 Tax oncoprotein regulates G-protein signaling.
Twizere, Jean-Claude ULg; Springael, Jean-Yves; Boxus, Mathieu ULg et al

in Blood (2007), 109(3), 1051-60

Human T-cell leukemia virus type-1 (HTLV-1) is associated with adult T-cell leukemia (ATL) and neurological syndromes. HTLV-1 encodes the oncoprotein Tax-1, which modulates viral and cellular gene ... [more ▼]

Human T-cell leukemia virus type-1 (HTLV-1) is associated with adult T-cell leukemia (ATL) and neurological syndromes. HTLV-1 encodes the oncoprotein Tax-1, which modulates viral and cellular gene expression leading to T-cell transformation. Guanine nucleotide-binding proteins (G proteins) and G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins known and are involved in the regulation of most biological functions. Here, we report an interaction between HTLV-1 Tax oncoprotein and the G-protein beta subunit. Interestingly, though the G-protein beta subunit inhibits Tax-mediated viral transcription, Tax-1 perturbs G-protein beta subcellular localization. Functional evidence for these observations was obtained using conditional Tax-1-expressing transformed T-lymphocytes, where Tax expression correlated with activation of the SDF-1/CXCR4 axis. Our data indicated that HTLV-1 developed a strategy based on the activation of the SDF-1/CXCR4 axis in the infected cell; this could have tremendous implications for new therapeutic strategies. [less ▲]

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See detailHuman TEF-5 is preferentially expressed in placenta and binds to multiple functional elements of the human chorionic somatomammotropin-B gene enhancer
Jacquemin, Patrick; Martial, Joseph ULg; Davidson, Irwin

in Journal of Biological Chemistry (1997), 272(20), 12928-37

We report the cloning of a cDNA encoding the human transcription factor hTEF-5, containing the TEA/ATTS DNA binding domain and related to the TEF family of transcription factors. hTEF-5 is expressed in ... [more ▼]

We report the cloning of a cDNA encoding the human transcription factor hTEF-5, containing the TEA/ATTS DNA binding domain and related to the TEF family of transcription factors. hTEF-5 is expressed in skeletal and cardiac muscle, but the strongest expression is observed in the placenta and in placenta-derived JEG-3 choriocarcinoma cells. In correlation with its placental expression, we show that hTEF-5 binds to several functional enhansons of the human chorionic somatomammotropin (hCS)-B gene enhancer. We define a novel functional element in this enhancer comprising tandemly repeated sites to which hTEF-5 binds cooperatively. In the corresponding region of the hCS-A enhancer, which is known to be inactive, this element is inactivated by a naturally occurring single base mutation that disrupts hTEF-5 binding. We further show that the binding of the previously described placental protein f/chorionic somatomammotropin enhancer factor-1 to TEF-binding sites is disrupted by monoclonal antibodies directed against the TEA domain and that this factor is a proteolytic degradation product of the TEF factors. These results strongly suggest that hTEF-5 regulates the activity of the hCS-B gene enhancer. [less ▲]

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See detailHuman thymic epithelial cells are potential targets for the diabetogenic coxsackievirus B4
Brilot, Fabienne; Hober, Didier; Geenen, Vincent ULg

Poster (2000, July)

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See detailHuman TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance.
Tischfield, Max A; Baris, Hagit N; Wu, Chen et al

in Cell (2010), 140(1), 74-87

We report that eight heterozygous missense mutations in TUBB3, encoding the neuron-specific beta-tubulin isotype III, result in a spectrum of human nervous system disorders that we now call the TUBB3 ... [more ▼]

We report that eight heterozygous missense mutations in TUBB3, encoding the neuron-specific beta-tubulin isotype III, result in a spectrum of human nervous system disorders that we now call the TUBB3 syndromes. Each mutation causes the ocular motility disorder CFEOM3, whereas some also result in intellectual and behavioral impairments, facial paralysis, and/or later-onset axonal sensorimotor polyneuropathy. Neuroimaging reveals a spectrum of abnormalities including hypoplasia of oculomotor nerves and dysgenesis of the corpus callosum, anterior commissure, and corticospinal tracts. A knock-in disease mouse model reveals axon guidance defects without evidence of cortical cell migration abnormalities. We show that the disease-associated mutations can impair tubulin heterodimer formation in vitro, although folded mutant heterodimers can still polymerize into microtubules. Modeling each mutation in yeast tubulin demonstrates that all alter dynamic instability whereas a subset disrupts the interaction of microtubules with kinesin motors. These findings demonstrate that normal TUBB3 is required for axon guidance and maintenance in mammals. [less ▲]

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See detailThe human tumor-associated antigen RCAS1 in pregnancies complicated by pre-eclampsia.
Tskitishvili, Ekaterine ULg; Komoto, Yoshiko; Kinugasa, Yukiko et al

in Journal of Reproductive Immunology (2008), 77(1), 100-8

The human tumor-associated antigen RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is considered to play a role in the escape of tumor cells from immune surveillance and, at the same time ... [more ▼]

The human tumor-associated antigen RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is considered to play a role in the escape of tumor cells from immune surveillance and, at the same time, participates in the inhibition of the maternal immune response during pregnancy. The aim of our study was to investigate the expression of tumor-associated RCAS1 protein in the placenta and amniotic membranes and to assess and compare its concentration in amniotic fluid, maternal and cord blood sera in pregnancies complicated by pre-eclampsia. Samples were obtained from women with pre-eclampsia (N=9), pre-eclampsia with IUGR (N=4), normotensive IUGR (N=7) and healthy term controls (N=25) after delivery. Placentas were studied by immunohistochemistry, Western blot analysis and real-time (RT)-PCR. For assessment of RCAS1 protein concentrations in biological fluids, ELISA was performed. RCAS1 mRNA expression in the placentas of pre-eclamptic patients was significantly lower than in controls (p<0.01). The maternal blood serum RCAS1 protein concentration in the pre-eclampsia cases was also significantly lower than in controls (p=0.0207). The other study groups did not differ significantly. This study reveals the possible role of the RCAS1 protein in the development of pre-eclampsia through an immunological pathway. [less ▲]

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See detailHuman viral infections derived from food
Scipioni, Alexandra ULg; Daube, Georges ULg; Thiry, Etienne ULg

in Point Vétérinaire (2001), 32(218, AUG-SEP),

Several viruses may be transmitted to humans via food including hepatitis A and E virus (VHA and VHE), Norwalk type calicivirus, rotavirus and astrovirus. Enterovirus and enteric adenovirus may also be ... [more ▼]

Several viruses may be transmitted to humans via food including hepatitis A and E virus (VHA and VHE), Norwalk type calicivirus, rotavirus and astrovirus. Enterovirus and enteric adenovirus may also be transmitted. Sick people or healthy carriers excrete these viruses in their stools. Shellfish and water are the most frequently contaminated foodstuffs. Another route of infection is during handling of food. Detection of these viruses in food is complex for several reasons: the interaction of virus and food makes viral concentration and purification difficult, in vitro culture of these viruses is difficult if not impossible, and the quantity of virus present in the sample is low. Molecular technology (PCR) is the most suitable method of detection. Another method is to choose an indicator of viral faecal contamination. [less ▲]

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See detailThe Human Vpac(1) Receptor - Three-Dimensional Model And Mutagenesis Of The N-Terminal Domain
Lins, Laurence ULg; Couvineau, A.; Rouyer-Fessard, C. et al

in Journal of Biological Chemistry (2001), 276(13),

The human VPAC(1) receptor for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide belongs to the class II family of G-protein-coupled receptors with seven transmembrane ... [more ▼]

The human VPAC(1) receptor for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide belongs to the class II family of G-protein-coupled receptors with seven transmembrane segments. Like for all class II receptors, the extracellular N-terminal domain of the human VPAC(1) receptor plays a predominant role in peptide ligand recognition. To determine the three-dimensional structure of this N-terminal domain (residues 1-144), the Protein Data Bank (PDB) was screened for a homologous protein. A subdomain of yeast lipase B was found to have 27% sequence identity and 50% sequence homology with the N-terminal domain (8) of the VPAC(1) receptor together with a good alignment of the hydrophobic clusters. A model of the N-terminal domain of VPAC(1) receptor was thus constructed by homology. It indicated the presence of a putative signal sequence in the N-terminal extremity. Moreover, residues (Glu(36), Trp(67), Asp(68), Trp(73), and Gly(109)) which were shown to be crucial for VIP binding are gathered around a groove that is essentially negatively charged. New putatively important residues for VIP binding were suggested from the model analysis. Site-directed mutagenesis and stable transfection of mutants in CHO cells indicated that Pro(74), Pro(87), Phe(90), and Trp(110) are indeed important for VIP binding and activation of adenylyl cyclase activation. Combination of molecular modeling and directed mutagenesis provided the first partial three-dimensional structure of a VIP-binding domain, constituted of an electronegative groove with an outspanning tryptophan shell at one end, in the N-terminal extracellular region of the human VPAC(1) receptor. [less ▲]

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See detailHuman xeroderman group G gene encodes a DNA endonuclease
Habraken, Yvette ULg; Sung, Patrick; Prakash, Louise et al

in Nucleic Acids Research (1994), 22(16), 3312-6

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See detailThe human-macaque interface: the impact of anthropogenic factors on the behavioural ecology of Macaca fascicularis in Bangkok (Thailand) and Bali (Indonesia)
Brotcorne, Fany ULg; Huynen, Marie-Claude ULg; Wandia, I Nengah

Conference (2010, October 11)

The human-macaque interface is increasingly the focus of many researches in East and South-east Asia. The efforts target the understanding of human impacts on macaques and the risks of pathogen ... [more ▼]

The human-macaque interface is increasingly the focus of many researches in East and South-east Asia. The efforts target the understanding of human impacts on macaques and the risks of pathogen transmission, the mitigation of conflicts as well as the establishment of suitable management programs. Commensal relationships between humans and several species of macaques exist for centuries in some Asian locations, like in Bali (Indonesia), Japan or India. However, the frequency and the intensity of these interactions are strongly increasing over the recent decades, due to the extensive urbanization and recruitment of forestlands for cropping. We conducted a comparative study on two commensal long-tailed macaque (Macaca fascicularis) populations, one in Bangkok (Thailand) and the other in Bali (Indonesia), in order to assess the impact of anthropogenic factors (human presence and food provisioning frequency) on some eco-behavioural aspects of this macaque species living in urban landscapes. We found a consistent impact on the activity budget and the diet composition in both populations, suggesting an important role played by these anthropogenic factors for this species. Additionally, we did not find any impact of food provisioning on agonistic interactions in the two populations, contrary to previous studies in other macaque species. We suggest this surprising result could be explained by the high abundance and constant availability of human food in both sites, decreasing foraging pressures and the associated social competition. Further field studies are in progress in other populations of Macaca fascicularis in Bali in order to confirm this consistency of human impact on the behavioural ecology [less ▲]

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See detailHuman-Phosphate-Binding-Protein inhibits HIV-1 gene transcription and replication.
Cherrier, Thomas ULg; Elias, Mikael; Jeudy, Alicia et al

in Virology Journal (2011), 8

The Human Phosphate-Binding protein (HPBP) is a serendipitously discovered lipoprotein that binds phosphate with high affinity. HPBP belongs to the DING protein family, involved in various biological ... [more ▼]

The Human Phosphate-Binding protein (HPBP) is a serendipitously discovered lipoprotein that binds phosphate with high affinity. HPBP belongs to the DING protein family, involved in various biological processes like cell cycle regulation. We report that HPBP inhibits HIV-1 gene transcription and replication in T cell line, primary peripherical blood lymphocytes and primary macrophages. We show that HPBP is efficient in naive and HIV-1 AZT-resistant strains. Our results revealed HPBP as a new and potent anti HIV molecule that inhibits transcription of the virus, which has not yet been targeted by HAART and therefore opens new strategies in the treatment of HIV infection. [less ▲]

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