References of "Luxen, André"
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See detailCyclosporine, a P-glycoprotein modulator, increases [18F]MPPF uptake in rat brain and peripheral tissues: microPET and ex vivo studies.
Lacan, Goran; Plenevaux, Alain ULiege; Rubins, Daniel J. et al

in European Journal of Nuclear Medicine and Molecular Imaging (2008), 35(12), 2256-66

PURPOSE: Pretreatment with cyclosporine, a P-glycoprotein (P-gp) modulator increases brain uptake of 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[(18)F]fluorobenzamido]ethylpiperaz ine ([(18)F]MPPF) for ... [more ▼]

PURPOSE: Pretreatment with cyclosporine, a P-glycoprotein (P-gp) modulator increases brain uptake of 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[(18)F]fluorobenzamido]ethylpiperaz ine ([(18)F]MPPF) for binding to hydroxytryptamine(1A) (5-HT(1A)) receptors. Those increases were quantified in rat brain with in vivo microPET and ex vivo tissue studies. MATERIALS AND METHODS: Each Sprague-Dawley rat (n = 4) received a baseline [(18)F]MPPF microPET scan followed by second scan 2-3 weeks later that included cyclosporine pretreatment (50 mg/kg, i.p.). Maximum a posteriori reconstructed images and volumetric ROIs were used to generate dynamic radioactivity concentration measurements for hippocampus, striatum, and cerebellum, with simplified reference tissue method (SRTM) analysis. Western blots were used to semiquantify P-gp regional distribution in brain. RESULTS: MicroPET studies showed that hippocampus uptake of [(18)F]MPPF was increased after cyclosporine; ex vivo studies showed similar increases in hippocampus and frontal cortex at 30 min, and for heart and kidney at 2.5 and 5 min, without concomitant increases in [(18)F]MPPF plasma concentration. P-gp content in cerebellum was twofold higher than in hippocampus or frontal cortex. CONCLUSIONS: These studies confirm and extend prior ex vivo results (J. Passchier, et al., Eur J Pharmacol, 2000) that showed [(18)F]MPPF as a substrate for P-gp. Our microPET results showed that P-gp modulation of [(18)F]MPPF binding to 5-HT(1A) receptors can be imaged in rat hippocampus. The heterogeneous brain distribution of P-gp appeared to invalidate the use of cerebellum as a nonspecific reference region for SRTM modeling. Regional quantitation of P-gp may be necessary for accurate PET assessment of 5-HT(1A) receptor density when based on tracer uptake sensitive to P-gp modulation. [less ▲]

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See detailQue mesure la neuro-imagerie fonctionnelle: IRMf, TEP & MEG?
Gosseries, Olivia ULiege; Demertzi, Athina ULiege; Noirhomme, Quentin ULiege et al

in Revue Médicale de Liège (2008), 63(5-6), 231-7

Functional cerebral imaging techniques allow the in vivo study of human cognitive and sensorimotor functions in physiological or pathological conditions. In this paper, we review the advantages and ... [more ▼]

Functional cerebral imaging techniques allow the in vivo study of human cognitive and sensorimotor functions in physiological or pathological conditions. In this paper, we review the advantages and limitations of functional magnetic resonance imaging (fMRI), positron emission tomography (PET) and magnetoencephalography (MEG). fMRI and PET measure haemodynamic changes induced by regional changes in neuronal activity. These techniques have a high spatial resolution (a few millimeters), but a poor temporal resolution (a few seconds to several minutes). Electroencephalogram (EEG) and MEG measure the neuronal electrical or magnetic activity with a high temporal resolution (i.e., milliseconds) albeit with a poorer spatial resolution (i.e., a few millimeters to one centimeter). The combination of these different neuroimaging techniques allows studying different components of the brain's activity (e.g., neurovascular coupling, electromagnetic activity) with both a high temporal and spatial resolution. [less ▲]

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See detailActivation mechanism of recombinant Der p 3 allergen zymogen - Contribution of cysteine protease Der p 1 and effect of propeptide glycosylation
Dumez, Marie-Eve ULiege; Teller, Nathalie; Mercier, Frédéric ULiege et al

in Journal of Biological Chemistry (2008), 283(45), 30606-30617

The trypsin-like protease Der p 3, a major allergen of the house dust mite Dermatophagoides pteronyssinus, is synthesized as a zymogen, termed proDer p 3. No recombinant source of Der p 3 has been ... [more ▼]

The trypsin-like protease Der p 3, a major allergen of the house dust mite Dermatophagoides pteronyssinus, is synthesized as a zymogen, termed proDer p 3. No recombinant source of Der p 3 has been described yet, and the zymogen maturation mechanism remains to be elucidated. The Der p 3 zymogen was produced in Pichia pastoris. We demonstrated that the recombinant zymogen is glycosylated at the level of its propeptide. We showed that the activation mechanism of proDer p 3 is intermolecular and is mediated by the house dust mite cysteine protease Der p 1. The primary structure of the proDer p 3 propeptide is associated with a unique zymogen activation mechanism, which is different from those described for the trypsin-like family and relies on the house dust mite papain-like protease Der p 1. This is the first report of a recombinant source of Der p 3, with the same enzymatic activity as the natural enzyme and trypsin. Glycosylation of the propeptide was found to decrease the rate of maturation. Finally, we showed that recombinant Der p 3 is inhibited by the free modified prosequence TP1R. [less ▲]

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See detailProteomic changes in rat hippocampus and adrenals following short-term sleep deprivation.
Poirrier, Jean-Etienne; Guillonneau, Francois; Renaut, Jenny et al

in Proteome Science (2008), 6

ABSTRACT: BACKGROUND: To identify the biochemical changes induced by sleep deprivation at a proteomic level, we compared the hippocampal proteome of rats either after 4 hours of sleep or sleep deprivation ... [more ▼]

ABSTRACT: BACKGROUND: To identify the biochemical changes induced by sleep deprivation at a proteomic level, we compared the hippocampal proteome of rats either after 4 hours of sleep or sleep deprivation obtained by gentle handling. Because sleep deprivation might induce some stress, we also analyzed proteomic changes in rat adrenals in the same conditions. After sleep deprivation, proteins from both tissues were extracted and subjected to 2D-DIGE analysis followed by protein identification through mass spectrometry and database search. RESULTS: In the hippocampus, 87 spots showed significant variation between sleep and sleep deprivation, with more proteins showing higher abundance in the latter case. Of these, 16 proteins were present in sufficient amount for a sequencing attempt and among the 12 identified proteins, inferred affected cellular functions include cell metabolism, energy pathways, transport and vesicle trafficking, cytoskeleton and protein processing. Although we did not observe classical, macroscopic effect of stress in sleep-deprived rats, 47 protein spots showed significant variation in adrenal tissue between sleep and sleep deprivation, with more proteins showing higher abundance following sleep. Of these, 16 proteins were also present in sufficient amount for a sequencing attempt and among the 13 identified proteins, the most relevant cellular function that was affected was cell metabolism. CONCLUSION: At a proteomic level, short term sleep deprivation is characterized by a higher expression of some proteins in the hippocampus and a lower abundance of other proteins in the adrenals (compared to normal sleep control). Altogether, this could indicate a general activation of a number of cellular mechanisms involved in the maintenance of wakefulness and in increased energy expenditure during sleep deprivation. These findings are relevant to suggested functions of sleep like energy repletion and the restoration of molecular stocks or a more global homeostasis of synaptic processes. [less ▲]

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See detailThe role of sleep in motor memory consolidation assessed by fMRI and MEG
Albouy, G.; Sterpenich, V.; Darsaud, A. et al

Poster (2007, November)

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See detailCharacterization of 4-(2-hydroxyphenyl)-1-[2 '-[N-(2 ''-pyridinyl)-p-fluorobenzamido]ethyl]piperazine (p-DMPPF) as a new potent 5-HT1A antagonist
Defraiteur, Caroline ULiege; Plenevaux, Alain ULiege; Scuvée-Moreau, Jacqueline ULiege et al

in British Journal of Pharmacology (2007), 152(6), 952-958

Background and purpose: The identification of potent and selective radioligands for the mapping of 5-HT receptors is interesting both for clinical and experimental research. The aim of this study was to ... [more ▼]

Background and purpose: The identification of potent and selective radioligands for the mapping of 5-HT receptors is interesting both for clinical and experimental research. The aim of this study was to compare the potency of a new putative 5-HT1A receptor antagonist, p-DMPPF, (4-(2-hydroxyphenyl)-1-[2'-[N-(2''-pyridinyl)-p-fluorobenzamido]-ethyl] piperazine) with that of the well-known 5-HT1A antagonists, WAY-100635(N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide) and its fluorobenzoyl analogue, p-MPPF (4-(2-methoxyphenyl)-1-[2'-[N-(2''-pyridinyl)p-fluorobenzamido] ethyl] piperazine). Experimental approach: Single cell extracellular recordings of dorsal raphe (DR) neurones were performed in rat brain slices. The potency of each compound at antagonizing the effect of the 5-HT1A agonist, 8-OH-DPAT [8-hydroxy-2-(di-npropylamino)tetraline], was quantified using the Schild equation. The pharmacological profile of p-DMPPF was defined using competition binding assays. Key results: Consistently with a 5-HT1A receptor antagonist profile, incubation of slices with an equimolar (10 nM) concentration of each compound markedly reduced the inhibitory effect of 8-OH-DPAT on the firing rate of DR neurones, causing a significant rightward shift in its concentration-response curve. The rank order of potency of the antagonists was WAY-100635 > p-DMPPF >= p-MPPF. The sensitivity of DR neurones to the inhibitory effect of 8-OH-DPAT was found to be heterogeneous. The binding experiments demonstrated that p-DMPPF is highly selective for 5-HT1A receptors, with a K-i value of 7 nM on these receptors. Conclusions and implications: The potency of the new compound, p-DMPPF, as a 5-HT1A antagonist is similar to that of p-MPPF in our electrophysiological assay. Its selectivity towards 5-HT1A receptors makes it a good candidate for clinical development. [less ▲]

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See detailStructural and mechanistic basis of penicillin-binding protein inhibition by lactivicins
Macheboeuf, Pauline; Fischer, Delphine S; Brown, Tom Jr et al

in Nature Chemical Biology (2007), 3(9), 565-569

beta-lactam antibiotics, including penicillins and cephalosporins, inhibit penicillin-binding proteins (PBPs), which are essential for bacterial cell wall biogenesis. Pathogenic bacteria have evolved ... [more ▼]

beta-lactam antibiotics, including penicillins and cephalosporins, inhibit penicillin-binding proteins (PBPs), which are essential for bacterial cell wall biogenesis. Pathogenic bacteria have evolved efficient antibiotic resistance mechanisms that, in Gram-positive bacteria, include mutations to PBPs that enable them to avoid beta-lactam inhibition(1). Lactivicin (LTV; 1) contains separate cycloserine and c-lactone rings and is the only known natural PBP inhibitor that does not contain a beta-lactam(2-4). Here we show that LTV and a more potent analog, phenoxyacetyl-LTV (PLTV; 2), are active against clinically isolated, penicillin-resistant Streptococcus pneumoniae strains. Crystallographic analyses of S. pneumoniae PBP1b reveal that LTV and PLTV inhibition involves opening of both monocyclic cycloserine and gamma-lactone rings. In PBP1b complexes, the ring-derived atoms from LTV and PLTV show a notable structural convergence with those derived from a complexed cephalosporin (cefotaxime; 3). The structures imply that derivatives of LTV will be useful in the search for new antibiotics with activity against beta-lactam-resistant bacteria. [less ▲]

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See detailBaseline brain activity fluctuations predict somatosensory perception in humans
Boly, Mélanie ULiege; Balteau, Evelyne ULiege; Schnakers, Caroline ULiege et al

in Proceedings of the National Academy of Sciences of the United States of America (2007), 104(29), 12187-12192

In perceptual experiments, within-individual fluctuations in perception are observed across multiple presentations of the same stimuli, a phenomenon that remains only partially understood. Here, by means ... [more ▼]

In perceptual experiments, within-individual fluctuations in perception are observed across multiple presentations of the same stimuli, a phenomenon that remains only partially understood. Here, by means of thulium-yttrium/aluminum- garnet laser and event-related functional MRI, we tested whether variability in perception of identical stimuli relates to differences in prestimulus, baseline brain activity. Results indicate a positive relationship between conscious perception of low-intensity somatosensory stimuli and immediately preceding levels of baseline activity in medial thalamus and the lateral frontoparietal network, respectively, which are thought to relate to vigilance and "external monitoring." Conversely, there was a negative correlation between subsequent reporting of conscious perception and baseline activity in a set of regions encompassing posterior cingulate/ precuneus and temporoparietal cortices, possibly relating to introspection and self-oriented processes. At nociceptive levels of stimulation, pain-intensity ratings positively correlated with baseline fluctuations in anterior cingulate cortex in an area known to be involved in the affective dimension of pain. These results suggest that baseline brain-activity fluctuations may profoundly modify our conscious perception of the external world. [less ▲]

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See detailExploration of the neuronal substrates of Directed Forgetting with fMRI.
Feyers, Dorothée ULiege; Hogge, Michaël; Salmon, Eric ULiege et al

Conference (2007, June 26)

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See detailExploration of the neuronal substrates of Directed Forgetting with fMRI
Feyers, Dorothée ULiege; Hogge, Michaël; Salmon, Eric ULiege et al

Conference (2007, June 01)

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See detailDistinct regions of the medial prefrontal cortex are associated with self-referential processing and perspective taking
D'Argembeau, Arnaud ULiege; Ruby, Perinne; Collette, Fabienne ULiege et al

in Journal of Cognitive Neuroscience (2007), 19(6), 935-944

The medial prefrontal cortex (MPFC) appears to play a prominent role in two fundamental aspects of social cognition, that is, self-referential processing and perspective taking. However, it is currently ... [more ▼]

The medial prefrontal cortex (MPFC) appears to play a prominent role in two fundamental aspects of social cognition, that is, self-referential processing and perspective taking. However, it is currently unclear whether the same or different regions of the MPFC mediate these two interdependent processes. This functional magnetic resonance imaging study sought to clarify the issue by manipulating both dimensions in a factorial design. Participants judged the extent to which trait adjectives described their own personality (e.g., 'Are you sociable?') or the personality of a close friend (e.g., 'Is Caroline sociable?') and were also asked to put themselves in the place of their friend (i.e., to take a third-person perspective) and estimate how this person would judge the adjectives, with the target of the judgments again being either the self (e.g., 'According to Caroline, are you sociable?') or the other person (e.g., 'According to Caroline, is she sociable?'). We found that self-referential processing (i.e., judgments targeting the self vs. the other person) yielded activation in the ventral and dorsal anterior MPFC, whereas perspective taking (i.e., adopting the other person's perspective, rather than one's own, when making judgments) resulted in activation in the posterior dorsal MPFC; the interaction between the two dimensions yielded activation in the left dorsal MPFC. These findings show that self-referential processing and perspective taking recruit distinct regions of the MPFC and suggest that the left dorsal MPFC may be involved in decoupling one's own from other people's perspectives on the self. [less ▲]

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See detailfMRI study of hypnosis-induced analgesia
Boly, Mélanie ULiege; Balteau, Evelyne ULiege; Schnakers, Caroline ULiege et al

in Journal of Neurology (2007, May), 254(Suppl. 3), 38-39

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See detailCerebral resting state fluctuations predict somatosensory perception
Boly, Mélanie ULiege; Balteau, Evelyne ULiege; Schnakers, Caroline ULiege et al

in Journal of Neurology (2007, May), 254(Suppl. 3), 42

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See detailSynthesis of anhydro-muramic acid derivatives as substrates for MurNAc amidase
Mercier, Frédéric; Zervosen, Astrid ULiege; Lemaire, Christian ULiege et al

Poster (2007, March 22)

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See detailMapping the updating process: common and specific brain activations across different versions of the running span task
Collette, Fabienne ULiege; Van der Linden, Martial ULiege; Laureys, Steven ULiege et al

in Cortex : A Journal Devoted to the Study of the Nervous System & Behavior (2007), 43(1), 146-158

Neuroimaging studies exploring the neural substrates of executive functioning have only rarely investigated whether the non-executive characteristics of the experimental executive tasks could contribute ... [more ▼]

Neuroimaging studies exploring the neural substrates of executive functioning have only rarely investigated whether the non-executive characteristics of the experimental executive tasks could contribute to the observed brain activations. The aim of this study was to determine cerebral activity in three different tasks involving the updating executive function. The experimental updating tasks required subjects to process strings of items (respectively letters, words, and sounds) of unknown lengths, and then to recall or identify a specific number of presented items. Conjunction and functional connectivity analyses demonstrated that the cerebral areas activated by all three experimental tasks are the left frontopolar cortex, bilateral dorsolateral prefrontal and premotor cortex, bilateral intraparietal sulcus, right inferior parietal lobule and cerebellum. Some regions of this network appear to be more specific to each updating task. These results clearly indicate that the neural substrates underlying a specific executive process (in this case, updating) are modulated by the exact requirements of the task (such as the material to process or the kind of response) and the specific cognitive processes associated with updating. [less ▲]

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See detailEffects of attention on emotional face processing in depression : a functional MRI study
Desseilles, Martin ULiege; Maquet, Pierre ULiege; Dang Vu, Thien Thanh et al

Poster (2007)

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See detailBrain responses to violet, blue, and green monochromatic light exposures in humans: prominent role of blue light and the brainstem
Vandewalle, Gilles ULiege; Schmidt, Christina ULiege; Albouy, Geneviève ULiege et al

in PLoS ONE (2007), 2(11), 1247

BACKGROUND: Relatively long duration retinal light exposure elicits nonvisual responses in humans, including modulation of alertness and cognition. These responses are thought to be mediated in part by ... [more ▼]

BACKGROUND: Relatively long duration retinal light exposure elicits nonvisual responses in humans, including modulation of alertness and cognition. These responses are thought to be mediated in part by melanopsin-expressing retinal ganglion cells which are more sensitive to blue light than violet or green light. The contribution of the melanopsin system and the brain mechanisms involved in the establishment of such responses to light remain to be established. METHODOLOGY/PRINCIPAL FINDINGS: We exposed 15 participants to short duration (50 s) monochromatic violet (430 nm), blue (473 nm), and green (527 nm) light exposures of equal photon flux (10(13)ph/cm(2)/s) while they were performing a working memory task in fMRI. At light onset, blue light, as compared to green light, increased activity in the left hippocampus, left thalamus, and right amygdala. During the task, blue light, as compared to violet light, increased activity in the left middle frontal gyrus, left thalamus and a bilateral area of the brainstem consistent with activation of the locus coeruleus. CONCLUSION/SIGNIFICANCE: These results support a prominent contribution of melanopsin-expressing retinal ganglion cells to brain responses to light within the very first seconds of an exposure. The results also demonstrate the implication of the brainstem in mediating these responses in humans and speak for a broad involvement of light in the regulation of brain function. [less ▲]

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