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See detailHuman cortical excitability depends on time spent awake and circadian phase
Ly, Julien ULg; Chellappa, Sarah Laxhmi ULg; Gaggioni, Giulia ULg et al

Conference (2014, September 17)

At any point in time, human performance results from the interaction of two main factors: a circadian signal varying with the time of the day and the sleep need accrued throughout the preceding waking ... [more ▼]

At any point in time, human performance results from the interaction of two main factors: a circadian signal varying with the time of the day and the sleep need accrued throughout the preceding waking period. But what’s happen at the cortical cerebral level? We used a novel technique coupling transcranial magnetic stimulation with electroencephalography (TMS/EEG) to assess the influence of time spent awake and circadian phasis on human cortical excitability. Twenty-two healthy young men underwent 8 TMS/EEG sessions during a 28 hour sleep deprivation protocole. We found that cortical excitability depends on both time spent awake and circadian phasis. [less ▲]

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See detailHuman Ehlers-Danlos syndrome type VII C and bovine dermatosparaxis are caused by mutations in the procollagen I N-proteinase gene.
Colige, Alain ULg; Sieron, A. L.; Li, S. W. et al

in American Journal of Human Genetics (1999), 65(2), 308-17

Ehlers-Danlos syndrome (EDS) type VIIC is a recessively inherited connective-tissue disorder, characterized by extreme skin fragility, characteristic facies, joint laxity, droopy skin, umbilical hernia ... [more ▼]

Ehlers-Danlos syndrome (EDS) type VIIC is a recessively inherited connective-tissue disorder, characterized by extreme skin fragility, characteristic facies, joint laxity, droopy skin, umbilical hernia, and blue sclera. Like the animal model dermatosparaxis, EDS type VIIC results from the absence of activity of procollagen I N-proteinase (pNPI), the enzyme that excises the N-propeptide of type I and type II procollagens. The pNPI enzyme is a metalloproteinase containing properdin repeats and a cysteine-rich domain with similarities to the disintegrin domain of reprolysins. We used bovine cDNA to isolate human pNPI. The human enzyme exists in two forms: a long version similar to the bovine enzyme and a short version that contains the Zn++-binding catalytic site but lacks the entire C-terminal domain in which the properdin repeats are located. We have identified the mutations that cause EDS type VIIC in the six known affected human individuals and also in one strain of dermatosparactic calf. Five of the individuals with EDS type VIIC were homozygous for a C-->T transition that results in a premature termination codon, Q225X. Four of these five patients were homozygous at three downstream polymorphic sites. The sixth patient was homozygous for a different transition that results in a premature termination codon, W795X. In the dermatosparactic calf, the mutation is a 17-bp deletion that changes the reading frame of the message. These data provide direct evidence that EDS type VIIC and dermatosparaxis result from mutations in the pNPI gene. [less ▲]

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See detailThe human epidermal growth factor receptor (EGFR) gene in European patients with advanced colorectal cancer harbors infrequent mutations in its tyrosine kinase domain.
Metzger, B.; Chambeau, L.; Begon, Dominique ULg et al

in BMC medical genetics (2011), 12(1), 144

ABSTRACT: BACKGROUND: The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptors, is a transmembrane tyrosine kinase (TK) activated by the binding of extracellular ligands of ... [more ▼]

ABSTRACT: BACKGROUND: The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptors, is a transmembrane tyrosine kinase (TK) activated by the binding of extracellular ligands of the EGF-family and involved in triggering the MAPK signaling pathway, which leads to cell proliferation. Mutations in the EGFR tyrosine kinase domain are frequent in non-small-cell lung cancer (NSCLC). However, to date, only very few, mainly non-European, studies have reported rare EGFR mutations in colorectal cancer (CRC). METHODS: We screened 236 clinical tumor samples from European patients with advanced CRC by direct DNA sequencing to detect potential, as yet unknown mutations, in the EGFR gene exons 18 to 21, mainly covering the EGFR TK catalytic domain. RESULTS: EGFR sequences showed somatic missense mutations in exons 18 and 20 at a frequency of 2.1% and 0.4% respectively. Somatic SNPs were also found in exons 20 and 21 at a frequency of about 3.1% and 0.4% respectively. Of these mutations, four have not yet been described elsewhere. CONCLUSIONS: These mutation frequencies are higher than in a similarly sized population characterized by Barber and colleagues, but still too low to account for a major role played by the EGFR gene in CRC. [less ▲]

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See detailHuman error : Towards a systemic approach: a case study in anesthesia
Nyssen, Anne-Sophie ULg

Doctoral thesis (1997)

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See detailHuman erythroleukemia: is the two-hit model of mouse leukemogenesis valid in human disease?
Coulon, Séverine; Vandekerckhove, Julie; Dussiot, Michael et al

in Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K (2007)

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See detailHuman Exposure of Bisphenol A: Review of the Urinary Biomarker Levels in the General Population
PIRARD, Catherine ULg; Charlier, Corinne ULg

in Gibert, Yann (Ed.) Bisphenol A: Sources, Risks of Environmental Exposure and Human Health Effects (2014)

Bipshenol A (2,2’-bis-[4-hydroxyphenyl]propane) involved as monomer in the manufacture of polycarbonate plastics and epoxy resins, is found in a wide variety of products including food packaging, baby ... [more ▼]

Bipshenol A (2,2’-bis-[4-hydroxyphenyl]propane) involved as monomer in the manufacture of polycarbonate plastics and epoxy resins, is found in a wide variety of products including food packaging, baby bottles, food and drink cans or containers. Because of the migration of bisphenol A from the food container to the food itself, the dietary ingestion has been estimated to be the main source for the general population. The Human exposure is increasingly studied either through the determination of dietary intake or more frequently via the measurement of urinary biomarker. This chapter is reporting results from roughly 200 publications dedicated to the bisphenol A levels found in the urine of the worldwide general population and measured within the different Human biomonitoring (HBM) studies conducted in this last decade. The exposure of children and pregnant women, both known as particularly vulnerable populations, is separately examined. The impact of the different legislations implemented in different countries to reduce children’s exposure on one hand and the different campaigns dedicated to the general public on the other hand, is not observed yet through temporal trend, likely because of the quite recent character of these actions. The advantages and the limitations of biomonitoring studies are also addressed, like the high within-person variability, the difficulties to access to reliable analytical techniques, the poor inter-study comparability, and the current need of longitudinal studies to establish links between BPA exposure and chronic diseases. [less ▲]

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See detailHuman exposure to endocrine disrupters: consequences of gastroplasty on plasma concentration of toxic pollutants
Charlier, Corinne ULg; Desaive, Claude ULg; Plomteux, Guy ULg

in International Journal of Obesity (2002), 26(11), 1465-1468

BACKGROUND: Body weight loss occurring after a hypoenergetic diet or a gastroplasty could be followed by an increase in blood concentration of potentially toxic pollutants that can interfere with the ... [more ▼]

BACKGROUND: Body weight loss occurring after a hypoenergetic diet or a gastroplasty could be followed by an increase in blood concentration of potentially toxic pollutants that can interfere with the hormonal system (endocrine disrupters). DESIGN: Thirty obese individuals recruited for gastroplasty were compared before and after treatment with 45 normal-weight people. MEASUREMENTS: Blood samples were analyzed for DDT, DDE, HCB and PCBs no. 28, 52, 101, 118, 138, 153 and 180, by gas chromatography-mass spectrometry. RESULTS: The results indicate clearly that body weight loss occurring after gastroplasty increases plasma concentration of lipophilic pollutants. CONCLUSION: Gastroplasty increases plasma concentration of organochlorine pesticides and PCBs, which could be a risk factor of endocrine disruption. Future longitudinal research will have to determine if the advantages of body weight loss are reduced by this potentially harmful effect. [less ▲]

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See detailHuman Factors main cause of accidents and main factor for preventing accidents
Nyssen, Anne-Sophie ULg

Scientific conference (2004, April)

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See detailHuman Fdc Express Prpc in Vivo and in Vitro
Thielen, Caroline ULg; Antoine, Nadine ULg; Mélot, France ULg et al

in Developmental Immunology (2001), 8(3-4), 259-66

Prion diseases are fatal neurodegenerative disorders caused by accumulation of abnormal prion protein (protease-resistant prion, PrPres). PrPres accumulation is also detected in lymphoid organs after ... [more ▼]

Prion diseases are fatal neurodegenerative disorders caused by accumulation of abnormal prion protein (protease-resistant prion, PrPres). PrPres accumulation is also detected in lymphoid organs after peripheral infection. Several studies suggest that follicular dendritic cells (FDC) could be the site of PrPres retention and amplification. Here we show that human follicular dendritic cells can express normal cellular prion protein (PrPc) both in situ and in vitro. When tonsillar cryosections were treated with anti-PrP antibody, the label was found on some very delicate cell extensions inside the lymphoid follicles, especially in the germinal centres. These extensions react with DRC1 antibody, used frequently to label FDC. Other structures labelled with anti-PrP antibody were the keratinocytes. To confirm the ability of FDC to synthesise PrPc, we isolated FDC by a non-enzymatic procedure and cultured them. By cytochemistry and flow cytometry it was clearly shown that FDC do produce PrPc. [less ▲]

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See detailHuman follicular dendritic cells in vitro
Tsunoda, R.; Heinen, Ernst ULg; Imai, Y. et al

in Dendritic Cells (1994), 4

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See detailHuman follicular dendritic cells in vitro and follicular dendritic-cell-like cells.
Tsunoda, R.; Bosseloir, A.; Onozaki, K. et al

in Cell & Tissue Research (1997), 288(2), 381-9

Human follicular dendritic cell (FDC)-like cells (FLC) have been utilized for the in vitro analysis of germinal center reactions. However, there is no consensus whether FLC represent FDC in vitro. The ... [more ▼]

Human follicular dendritic cell (FDC)-like cells (FLC) have been utilized for the in vitro analysis of germinal center reactions. However, there is no consensus whether FLC represent FDC in vitro. The purpose of the present study has therefore been to determine distinguishing features of FDC and FLC in vitro. The expression of CD40, CD54, CD49d, cytokine (gamma-IFN and IL-4)-dependent MHC-class II, and CD106 was observed to be specific for the determination of FDC in long-term culture. The cytokine-dependent emperipolesis of germinal center B cells was establised as another discriminating property for FDC in vitro. In 2 out of 72 long-term cultures of FDC, we encountered dividing cells among the non-dividing population of FDC. The dividing cells expressed accessory molecules similar to those of FDC but showed emperipolesis only for the initial few days of their growth. FDC did not enhance the CD40-dependent proliferation of germinal center B cells; in contrast, FLC augumented it. Both types of cells produced a significant amount of cytokine-dependent IL-6. Further studies are needed to determine whether FLC originate from FDC in vitro. [less ▲]

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See detailHuman gene organization driven by the coordination of replication and transcription
Huvet, Maxime; Nicolay, Samuel ULg; Touchon, Marie et al

in Genome Research (2007), 17(9), 1278-1285

In this work, we investigated a large-scale organization of the human genes with respect to putative replication origins. We developed an appropriate multiscale method to analyze the nucleotide ... [more ▼]

In this work, we investigated a large-scale organization of the human genes with respect to putative replication origins. We developed an appropriate multiscale method to analyze the nucleotide compositional skew along the genome and found that in more than one-quarter of the genome, the skew profile presents characteristic patterns consisting of successions of N-shaped structures, designated here N-domains, bordered by putative replication origins. Our analysis of recent experimental timing data confirmed that, in a number of cases, domain borders coincide with replication initiation zones active in the early S phase, whereas the central regions replicate in the late S phase. Around the putative origins, genes are abundant and broadly expressed, and their transcription is co-oriented with replication fork progression. These features weaken progressively with the distance from putative replication origins. At the center of domains, genes are rare and expressed in few tissues. We propose that this specific organization could result from the constraints of accommodating the replication and transcription initiation processes at chromatin level, and reducing head-on collisions between the two machineries. Our findings provide a new model of gene organization in the human genome, which integrates transcription, replication, and chromatin structure as coordinated determinants of genome architecture. [less ▲]

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See detailThe human genome contains hundreds of genes coding for finger proteins of the Kruppel type
Bellefroid, Eric J.; Lecocq, P.; Benhida, A. et al

in DNA (1989), 8(6), 377-87

Our aim was to identify new human proteins with potential DNA binding activity, related to the Kruppel protein which regulates Drosophila segmentation. We screened a human placenta cDNA library and a ... [more ▼]

Our aim was to identify new human proteins with potential DNA binding activity, related to the Kruppel protein which regulates Drosophila segmentation. We screened a human placenta cDNA library and a human genomic DNA library with a synthetic oligonucleotide probe corresponding to the H/C link region that connects finger loops in the multifingered Kruppel protein. We found more than 100 different mRNAs encoding Kruppel multifingered proteins in the human placenta. In the whole human genome, the number of genes encoding such proteins reaches about 300. Sequence analysis of 14 cloned cDNAs indicated that they code for at least nine undescribed human finger proteins. The sequences of the 106 finger repeats present in these nine proteins are highly homologous. Most of the variability lies in a limited number of positions located in their postulated alpha-helical structure, and therefore could be implicated in their DNA-binding specificity. [less ▲]

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See detailHuman germinal center CD4+CD57+ T cells act differently on B cells than do classical T-helper cells.
Bouzahzah, F.; Bosseloir, A.; Heinen, Ernst ULg et al

in Developmental Immunology (1995), 4(3), 189-97

We have isolated two subtypes of helper T cells from human tonsils: CD4+CD57+ cells, mostly located in the germinal center (GC), and CD4+CD57- cells, distributed through the interfollicular areas but also ... [more ▼]

We have isolated two subtypes of helper T cells from human tonsils: CD4+CD57+ cells, mostly located in the germinal center (GC), and CD4+CD57- cells, distributed through the interfollicular areas but also present in the GC. In a functional study, we have compared the capacities of these T-cell subtypes to stimulate B cells in cocultures. In order to block T-cell proliferation while maintaining their activation level, we pretreated isolated T cells with mitomycin C prior to culture in the presence of B cells and added polyclonal activators such as PHA and Con A, combined or not with IL-2. Contrary to CD4+ CD57- cells, CD4+CD57+ cells did not markedly enhance B-cell proliferation. Even when sIgD.B cells typical of germinal center cells were tested, the CD4+CD57+ cells had no significant effect. This is in accordance with the location of these cells: They mainly occupy the light zones of the GC where few B cells divide. Even when added to preactivated, actively proliferating cells, CD4+CD57 cells failed to modulate B-cell multiplication. On the supernatants of B-cell-T-cell cocultures, we examined by the ELISA technique the effect of T cells on Ig synthesis. Contrary to CD57+ T cells, whose effect was strong, CD57- T cells weakly stimulated Ig synthesis. More IgM than IgG was generally found. Because CD57 antigen is a typical marker of natural killer cells, we tested the cytolytic activity of tonsillar CD4+CD57+ cells on K562 target cells. Unlike NK cells, neither CD4+CD57+ nor CD4+CD57- cells exhibit any cytotoxicity. Thus, germinal center CD4+CD57+ cells are not cytolytic and do not strongly stimulate either B-cell proliferation or Ig secretion. CD4+CD57- cells, however, enhance B-cell proliferation and differentiation, thus acting like the classical helper cells of the T-dependent areas. [less ▲]

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See detailHuman glioblastoma-initiating cells invade specifically the subventricular zones and olfactory bulbs of mice after striatal injection.
Kroonen, Jérôme ULg; Nassen, Jessica ULg; Boulanger, Yves-Gauthier et al

in International Journal of Cancer = Journal International du Cancer (2011), 129(3), 574-585

This study reports the subsequent isolation of human glioblatoma cells able to initiate experimental brain tumors, specifically and repeatedly found in the subventricular zones and olfactory bulbs ... [more ▼]

This study reports the subsequent isolation of human glioblatoma cells able to initiate experimental brain tumors, specifically and repeatedly found in the subventricular zones and olfactory bulbs following xenograft in the caudate putamen of immunodeficient mice.In patients with glioblastoma multiforme, recurrence is the rule despite continuous advances in surgery, radiotherapy and chemotherapy. Within these malignant gliomas, glioblastoma stem cells or initiating cells have been recently described and they were shown to be specifically involved in experimental tumorigenesis. In this study, we show that some human glioblastoma cells injected into the striatum of immunodeficient nude mice exhibit a tropism for the subventricular zones. There and similarily to neurogenic stem cells, these subventricular glioblastoma cells were then able to migrate towards the olfactory bulbs. Finally, the glioblastoma cells isolated from the adult mouse subventricular zones and olfactory bulbs display high tumorigenicity when secondary injected in a new mouse brain. Together, these data suggest that neurogenic zones could be a reservoir for particular cancer-initiating cells. [less ▲]

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See detailHuman growth hormone: complementary DNA cloning and expression in bacteria
Martial, Joseph ULg; Hallewell, R. A.; Baxter, J. D. et al

in Science (1979), 205(4406), 602-7

The nucleotide sequence of a DNA complementary to human growth hormone messenger RNA was cloned; it contains 29 nucleotides in its 5' untranslated region, the 651 nucleotides coding for the prehormone ... [more ▼]

The nucleotide sequence of a DNA complementary to human growth hormone messenger RNA was cloned; it contains 29 nucleotides in its 5' untranslated region, the 651 nucleotides coding for the prehormone, and the entire 3' untranslated region (108 nucleotides). The data reported predict the previously unknown sequence of the signal peptide of human growth hormone and, by comparison with the previously determined sequences of rat growth hormone and human chorionic somatomammotropin, strengthens the hypothesis that these genes evolved by gene duplication from a common ancestral sequence. The human growth hormone gene sequences have been linked in phase to a fragment of the trp D gene of Escherichia coli in a plasmid vehicle, and a fusion protein is synthesized at high level (approximately 3 percent of bacterial protein) under the control of the regulatory region of the trp operon. This fusion protein (70 percent of whose amino acids are coded for by the human growth hormone gene) reacts specifically with antibodies to human growth hormone and is stable in E. coli. [less ▲]

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See detailHuman growth hormone: complementary DNA cloning and expression in bacteria. 1979
Martial, Joseph ULg; Hallewell, R. A.; Baxter, J. D. et al

in Biotechnology (Reading, Mass.) (1992), 24

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See detailHuman immune cells express ppMCH mRNA and functional MCHR1 receptor
Verlaet, Myriam ULg; Adamantidis, Antoine ULg; Coumans, Bernard ULg et al

in FEBS Letters (2002), 527(1-3), 205-210

Melanin-concentrating hormone (MCH) is highly expressed in the brain and modulates feeding behavior. It is also expressed in some peripheral tissues where its role remains unknown. We have investigated ... [more ▼]

Melanin-concentrating hormone (MCH) is highly expressed in the brain and modulates feeding behavior. It is also expressed in some peripheral tissues where its role remains unknown. We have investigated MCH function in human and mouse immune cells. RT-PCR analysis revealed a low expression of prepro-MCH and MCH receptor 1 (MCHR1) but not of MCHR2 transcript in tissular and peripheral blood immune cells. FACS and in vitro assay studies demonstrated that MCHR1 receptor expression on most cell types can trigger, in the presence of MCH, cAMP synthesis and calcium mobilization in peripheral blood mononuclear cells (PBMCs). Moreover, MCH treatment decreases the CD3-stimulated PBMC proliferation in vitro. Accordingly, our data indicate for the first time that MCH and MCHR1 may exert immunomodulatory functions. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved. [less ▲]

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See detailHuman impacts on Antarctic ecosystems: do not forget the microorganisms!
Hughes, Kevin; Verleyen, Elie; Vyverman, Wim et al

Conference (2013, July)

The tiny and microscopic creatures that are the permanent inhabitants of the Antarctic continent are often overlooked in environmental impact assessments and when new management and protection strategies ... [more ▼]

The tiny and microscopic creatures that are the permanent inhabitants of the Antarctic continent are often overlooked in environmental impact assessments and when new management and protection strategies are designed. This lack of consideration is probably due to their small size and the need of sophisticated molecular methods to study their diversity, evolution and geographic distribution. However, considerable progress has been made in the field of molecular diversity in the last two decennia, and is still ongoing for Antarctic bacteria, cyanobacteria, protists, fungi, etc. Recent studies have shown the presence of highly diverse microbial communities and the existence of species endemic to Antarctic in some taxonomic groups. With the emergence of High Throughput Sequencing methodologies that are able to detect ‘rare’ taxa, it becomes crucial to find Antarctic locations that have not yet been impacted by human presence. These ‘pristine’ areas are essential to serve as reference sites and allow to distinguish the true Antarctic organisms from the imported ones. Indeed, recent studies have shown that humans unintentionally disperse their own microbial flora but may also spread organisms from other locations. In the extreme biotopes with a reduced diversity that are currently found in Antarctica, such contaminations might have a profound impact. It is important to raise the awareness of scientists, environmental managers and policy makers about the necessity to single out some areas that are kept untouched, or where stringent biosecurity measures are taken. The purpose is not to hinder scientific research, but to weigh carefully, when exploring a new area, the importance of the acquired piece of knowledge in relation to the possibility of hindering future microbiological research. Some parallels with other fields of research are interesting to consider. Archeologists are used to keeping some parts of the explored caves untouched because they foresee that technological progress will allow better analyses in future. The COSPAR Panel on Planetary Protection makes recommendations to avoid the contamination of other planets with microbes from Earth, which would obscure any discovery of extraterrestrial indigenous life forms. These examples illustrate the essential need to integrate the delineation of reference areas for future analyses in the design and execution of scientific research. In fact, the Madrid Protocol foresees the possibility to designate ‘inviolate areas’ (Annex V, Article 3), though this tool has rarely been used. It would be useful if scientists of all disciplines would reflect how to use this management option. [less ▲]

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