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See detailNEMA NU4-2008 Performance Evaluation for the MicroPET FOCUS 120 and Iodine-124
Taleb, Dounia ULg; Bahri, Mohamed Ali ULg; Warnock, Geoffrey ULg et al

in IEEE proceedings of ANIMMA 2011 (2012, March 12)

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See detailNeural Correlates of Performance Variabilty during Motor Sequence Acquisition
Albouy, Geneviève ULg; Sterpenich, V.; Vandewalle, Gilles ULg et al

in NeuroImage (2012), 60(1), 324-331

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See detailInfluence of acute sleep loss on the neural correlates of alerting, orientating and executive attention components
Muto, Vincenzo ULg; Shaffii, Anahita ULg; Matarazzo, Luca et al

in Journal of Sleep Research (2012), 21(6), 648-58

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See detailCircadian preference modulates the neural substrate of conflict processing across the day
Schmidt, Christina ULg; Peigneux, Philippe ULg; Leclercq, Yves ULg et al

in PLoS ONE (2012), 7(1), 29658

Human morning and evening chronotypes differ in their preferred timing for sleep and wakefulness, as well as in optimal daytime periods to cope with cognitive challenges. Recent evidence suggests that ... [more ▼]

Human morning and evening chronotypes differ in their preferred timing for sleep and wakefulness, as well as in optimal daytime periods to cope with cognitive challenges. Recent evidence suggests that these preferences are not a simple by-product of socio-professional timing constraints, but can be driven by inter-individual differences in the expression of circadian and homeostatic sleep-wake promoting signals. Chronotypes thus constitute a unique tool to access the interplay between those processes under normally entrained day-night conditions, and to investigate how they impinge onto higher cognitive control processes. Using functional magnetic resonance imaging (fMRI), we assessed the influence of chronotype and time-of-day on conflict processing-related cerebral activity throughout a normal waking day. Sixteen morning and 15 evening types were recorded at two individually adapted time points (1.5 versus 10.5 hours spent awake) while performing the Stroop paradigm. Results show that interference-related hemodynamic responses are maintained or even increased in evening types from the subjective morning to the subjective evening in a set of brain areas playing a pivotal role in successful inhibitory functioning, whereas they decreased in morning types under the same conditions. Furthermore, during the evening hours, activity in a posterior hypothalamic region putatively involved in sleep-wake regulation correlated in a chronotype-specific manner with slow wave activity at the beginning of the night, an index of accumulated homeostatic sleep pressure. These results shed light into the cerebral mechanisms underlying inter-individual differences of higher-order cognitive state maintenance under normally entrained day-night conditions. [less ▲]

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See detailThe fate of incoming stimuli during NREM sleep is determined by spindles and the phase of the slow oscillation
Schabus, M.; Dang Vu, Thien Thanh ULg; Heib, D. P. J. et al

in Frontiers in Neurology (2012), 3(40), 1-11

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See detailThe neural correlates of recollection and familiarity during aging
Angel, Lucie; Bastin, Christine ULg; Genon, Sarah ULg et al

in Frontiers in Human Neuroscience (2012)

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See detailThe Neural Substrates of Memory Suppression: A fMRI Exploration of Directed Forgetting
Bastin, Christine ULg; Feyers, Dorothée ULg; Majerus, Steve ULg et al

in PLoS ONE (2012), 7(1), 29905

The directed forgetting paradigm is frequently used to determine the ability to voluntarily suppress information. However, little is known about brain areas associated with information to forget. The ... [more ▼]

The directed forgetting paradigm is frequently used to determine the ability to voluntarily suppress information. However, little is known about brain areas associated with information to forget. The present study used functional magnetic resonance imaging to determine brain activity during the encoding and retrieval phases of an item-method directed forgetting recognition task with neutral verbal material in order to apprehend all processing stages that information to forget and to remember undergoes. We hypothesized that regions supporting few selective processes, namely recollection and familiarity memory processes, working memory, inhibitory and selection processes should be differentially activated during the processing of to-be-remembered and to-be-forgotten items. Successful encoding and retrieval of items to remember engaged the entorhinal cortex, the hippocampus, the anterior medial prefrontal cortex, the left inferior parietal cortex, the posterior cingulate cortex and the precuneus; this set of regions is well known to support deep and associative encoding and retrieval processes in episodic memory. For items to forget, encoding was associated with higher activation in the right middle frontal and posterior parietal cortex, regions known to intervene in attentional control. Items to forget but nevertheless correctly recognized at retrieval yielded activation in the dorsomedial thalamus, associated with familiarity-based memory processes and in the posterior intraparietal sulcus and the anterior cingulate cortex, involved in attentional processes. [less ▲]

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See detailDevelopment of new drugs for an old target — the penicillin binding proteins.
Zervosen, Astrid ULg; Sauvage, Eric ULg; Frère, Jean-Marie ULg et al

in Molecules (2012), 17(11), 12478-505

The widespread use of β-lactam antibiotics has led to the worldwide appearance of drug-resistant strains. Bacteria have developed resistance to β-lactams by two main mechanisms: the production of β ... [more ▼]

The widespread use of β-lactam antibiotics has led to the worldwide appearance of drug-resistant strains. Bacteria have developed resistance to β-lactams by two main mechanisms: the production of β-lactamases, sometimes accompanied by a decrease of outer membrane permeability, and the production of low-affinity, drug resistant Penicillin Binding Proteins (PBPs). PBPs remain attractive targets for developing new antibiotic agents because they catalyse the last steps of the biosynthesis of peptidoglycan, which is unique to bacteria, and lies outside the cytoplasmic membrane. Here we summarize the “current state of the art” of non-β-lactam inhibitors of PBPs, which have being developed in an attempt to counter the emergence of β-lactam resistance. These molecules are not susceptible to hydrolysis by β-lactamases and thus present a real alternative to β-lactams. We present transition state analogs such as boronic acids, which can covalently bind to the active serine residue in the catalytic site. Molecules containing ring structures different from the β-lactam-ring like lactivicin are able to acylate the active serine residue. High throughput screening methods, in combination with virtual screening methods and structure based design, have allowed the development of new molecules. Some of these novel inhibitors are active against major pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and thus open avenues new for the discovery of novel antibiotics. [less ▲]

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See detailModulation of brain activity during a Stroop inhibitory task by the kind of cognitive control required
Grandjean, Julien ULg; D'Ostilio, Kevin ULg; Phillips, Christophe ULg et al

in PLoS ONE (2012), 7(7), 41513

This study used a proportion congruency manipulation in the Stroop task in order to investigate, at the behavioral and brain substrate levels, the predictions derived from the Dual Mechanisms of Control ... [more ▼]

This study used a proportion congruency manipulation in the Stroop task in order to investigate, at the behavioral and brain substrate levels, the predictions derived from the Dual Mechanisms of Control (DMC) account of two distinct modes of cognitive control depending on the task context. Three experimental conditions were created that varied the proportion congruency: mostly incongruent (MI), mostly congruent (MC), and mostly neutral (MN) contexts. A reactive control strategy, which corresponds to transient interference resolution processes after conflict detection, was expected for the rare conflicting stimuli in the MC context, and a proactive strategy, characterized by a sustained task-relevant focus prior to the occurrence of conflict, was expected in the MI context. Results at the behavioral level supported the proactive/reactive distinction, with the replication of the classic proportion congruent effect (i.e., less interference and facilitation effects in the MI context). fMRI data only partially supported our predictions. Whereas reactive control for incongruent trials in the MC context engaged the expected fronto-parietal network including dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex, proactive control in the MI context was not associated with any sustained lateral prefrontal cortex activations, contrary to our hypothesis. Surprisingly, incongruent trials in the MI context elicited transient activation in common with incongruent trials in the MC context, especially in DLPFC, superior parietal lobe, and insula. This lack of sustained activity in MI is discussed in reference to the possible involvement of item-specific rather than list-wide mechanisms of control in the implementation of a high task-relevant focus. [less ▲]

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See detailExploration of the chemical space of novel naphthalene-sulfonamide and anthranilic acid-based inhibitors of penicillin-binding Proteins
Sosic, Izidor; Turk, Samo; Sinreih, Masa et al

in Acta Chimica Slovenica (2012), 59(2), 380-388

Penicillin-binding proteins are a well established, validated and still a very promising target for the design and development of new antibacterial agents. Based on our previous discovery of several ... [more ▼]

Penicillin-binding proteins are a well established, validated and still a very promising target for the design and development of new antibacterial agents. Based on our previous discovery of several noncovalent small-molecule inhibitor hits for resistant PBPs we decided to additionally explore the chemical space around these compounds. In order to clarify their structure-activity relationships for PBP inhibition two new series of compounds were synthesized, characterized and evaluated biochemically: the derivatives of anthranilic acid and naphthalene-sulfonamide derivatives. The target compounds were tested for their inhibitory activities on three different transpeptidases: PBP2a from methicillin-resistant Staphylococcus aureus (MRSA) strains, PBP5fm from Enterococcus faecium strains, and PBP1b from Streptococcus pneumoniae strains. The most promising results for both of these series of compounds were obtained against the PBP2a enzyme with the IC50 values in the micromolar range. Although these results do not represent a significant breakthrough in the field of noncovalent PBP inhibitors, they do provide useful structure-activity relationship data, and thus a more solid basis for the design of potent and noncovalent inhibitors of resistant PBPs. [less ▲]

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See detailSynthesis and evaluation of boronic acids as inhibitors of Penicillin Binding Proteins of classes A, B and C.
Zervosen, Astrid ULg; Bouillez, André ULg; Herman, Alexandre et al

in Bioorganic & Medicinal Chemistry (2012), 20(12), 3915-24

In response to the widespread use of beta-lactam antibiotics bacteria have evolved drug resistance mechanisms that include the production of resistant Penicillin Binding Proteins (PBPs). Boronic acids are ... [more ▼]

In response to the widespread use of beta-lactam antibiotics bacteria have evolved drug resistance mechanisms that include the production of resistant Penicillin Binding Proteins (PBPs). Boronic acids are potent beta-lactamase inhibitors and have been shown to display some specificity for soluble transpeptidases and PBPs, but their potential as inhibitors of the latter enzymes is yet to be widely explored. Recently, a (2,6-dimethoxybenzamido)methylboronic acid was identified as being a potent inhibitor of Actinomadura sp. R39 transpeptidase (IC(50): 1.3muM). In this work, we synthesized and studied the potential of a number of acylaminomethylboronic acids as inhibitors of PBPs from different classes. Several derivatives inhibited PBPs of classes A, B and C from penicillin sensitive strains. The (2-nitrobenzamido)methylboronic acid was identified as a good inhibitor of a class A PBP (PBP1b from Streptococcus pneumoniae, IC(50)=26muM), a class B PBP (PBP2xR6 from Streptococcus pneumoniae, IC(50)=138muM) and a class C PBP (R39 from Actinomadura sp., IC(50)=0.6muM). This work opens new avenues towards the development of molecules that inhibit PBPs, and eventually display bactericidal effects, on distinct bacterial species. [less ▲]

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See detailA peptidoglycan fragment triggers beta-lactam resistance in Bacillus licheniformis.
Amoroso, Ana Maria ULg; Boudet, Julien; Berzigotti, Stephanie et al

in PLoS Pathogens (2012), 8(3), 1002571

To resist to beta-lactam antibiotics Eubacteria either constitutively synthesize a beta-lactamase or a low affinity penicillin-binding protein target, or induce its synthesis in response to the presence ... [more ▼]

To resist to beta-lactam antibiotics Eubacteria either constitutively synthesize a beta-lactamase or a low affinity penicillin-binding protein target, or induce its synthesis in response to the presence of antibiotic outside the cell. In Bacillus licheniformis and Staphylococcus aureus, a membrane-bound penicillin receptor (BlaR/MecR) detects the presence of beta-lactam and launches a cytoplasmic signal leading to the inactivation of BlaI/MecI repressor, and the synthesis of a beta-lactamase or a low affinity target. We identified a dipeptide, resulting from the peptidoglycan turnover and present in bacterial cytoplasm, which is able to directly bind to the BlaI/MecI repressor and to destabilize the BlaI/MecI-DNA complex. We propose a general model, in which the acylation of BlaR/MecR receptor and the cellular stress induced by the antibiotic, are both necessary to generate a cell wall-derived coactivator responsible for the expression of an inducible beta-lactam-resistance factor. The new model proposed confirms and emphasizes the role of peptidoglycan degradation fragments in bacterial cell regulation. [less ▲]

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See detailStealth macromolecular platforms for the design of MRI blood pool contrast agents
Grogna, Mathurin ULg; Cloots, Rudi ULg; Luxen, André ULg et al

in Polymer Chemistry (2011), 2(10), 2316-2327

Stealth macromolecular platforms bearing alkyne groups and poly(ethylene oxide) brushes were synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization. The anchoring of Gd3 ... [more ▼]

Stealth macromolecular platforms bearing alkyne groups and poly(ethylene oxide) brushes were synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization. The anchoring of Gd3+-chelates bearing an azide group was then carried out by the Huisgen 1,3-dipolar cycloaddition (“click”) reaction in mild conditions, leading to macrocontrast agents for MRI applications. The gadolinium complex is hidden in the PEO shell that renders the macrocontrast agents free of any cytotoxicity and stealth to proteins of the immune system. Relaxometry measurements have evidenced an improved relaxivity of the macrocontrast agent compared to ungrafted gadolinium chelate. Moreover, this relaxivity is further enhanced when the spacer length between the Gd3+-chelate and the polymer backbone is shorter, as the result of its decreased tumbling rate. These novel products are therefore promising candidates for MRI applications. [less ▲]

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See detailConvenient grafting through approach for the preparation of stealth polymeric blood pool magnetic resonance imaging contrast agents
Grogna, Mathurin ULg; Cloots, Rudi ULg; Luxen, André ULg et al

in Journal of Polymer Science. Part A, Polymer Chemistry (2011), 49(17), 3700-3708

New hydrosoluble magnetic resonance imaging (MRI) macrocontrast agents are synthesized by reversible addition fragmentation chain transfer (RAFT) copolymerization of poly(ethylene oxide) methyl ether ... [more ▼]

New hydrosoluble magnetic resonance imaging (MRI) macrocontrast agents are synthesized by reversible addition fragmentation chain transfer (RAFT) copolymerization of poly(ethylene oxide) methyl ether acrylate (PEOMA) with an acrylamide bearing a ligand for gadolinium, followed by the complexation of Gd3+. This convenient and simple grafting through approach leads to macrocontrast agents with a high relaxivity at high frequency that is imparted by the restricted tumbling of the Gd3+ complex caused by its attachment to the polymer backbone. Importantly a very low protein adsorption is also evidenced by the hemolytic CH50 test. It is the result of the poly(ethylene oxide) (PEO) brush that efficiently hides the gadolinium complex and renders it stealth to the proteins of the immune system. Improved contrast and long blood circulating properties are thus expected for these macrocontrast agents. [less ▲]

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See detailAutomated synthesis of [18F] FBEM for labeling of thiol containing compounds
Paris, Jérôme ULg; Thonon, David ULg; Kaisin, Geoffroy ULg et al

Poster (2011, September 01)

[18F]FBEM, i.e. N-[2-(4-[18F]fluorobenzamido)ethyl]maleimide, is a useful synthon employed for the specific radiolabeling of thiol containing compounds, including peptides and proteins. The aim of the ... [more ▼]

[18F]FBEM, i.e. N-[2-(4-[18F]fluorobenzamido)ethyl]maleimide, is a useful synthon employed for the specific radiolabeling of thiol containing compounds, including peptides and proteins. The aim of the present work was to develop a fast, reproducible and fully automated synthesis of this compound in order to improve its availabilty as well as for obvious radioprotection matters. [less ▲]

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See detailHypnotic modulation of resting state fMRI default mode and extrinsic network connectivity
Demertzi, Athina ULg; Soddu, Andrea ULg; FAYMONVILLE, Marie-Elisabeth ULg et al

in Progress in Brain Research (2011), 193

Resting state fMRI (functional magnetic resonance imaging) acquisitions are characterized by low-frequency spontaneous activity in a default mode network (encompassing medial brain areas and linked to ... [more ▼]

Resting state fMRI (functional magnetic resonance imaging) acquisitions are characterized by low-frequency spontaneous activity in a default mode network (encompassing medial brain areas and linked to self-related processes) and an anticorrelated “extrinsic” system (encompassing lateral frontoparietal areas and modulated via external sensory stimulation). In order to better determine the functional contribution of these networks to conscious awareness, we here sought to transiently modulate their relationship by means of hypnosis. We used independent component analysis (ICA) on resting state fMRI acquisitions during normal wakefulness, under hypnotic state, and during a control condition of autobiographical mental imagery. As compared to mental imagery, hypnosis-induced modulation of resting state fMRI networks resulted in a reduced “extrinsic” lateral frontoparietal cortical connectivity, possibly reflecting a decreased sensory awareness. The default mode network showed an increased connectivity in bilateral angular and middle frontal gyri, whereas its posterior midline and parahippocampal structures decreased their connectivity during hypnosis, supposedly related to an altered “self” awareness and posthypnotic amnesia. In our view, fMRI resting state studies of physiological (e.g., sleep or hypnosis), pharmacological (e.g., sedation or anesthesia), and pathological modulation (e.g., coma or related states) of “intrinsic” default mode and anticorrelated “extrinsic” sensory networks, and their interaction with other cerebral networks, will further improve our understanding of the neural correlates of subjective awareness. [less ▲]

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See detailPerformance evaluation of the General Electric eXplore CT 120 micro-CT using the vmCT phantom.
Bahri, Mohamed Ali ULg; Warnock, Geoffrey ULg; Plenevaux, Alain ULg et al

in Nuclear Instruments & Methods in Physics Research Section A (2011), 648

The eXplore CT 120 is the latest generation micro-CT from General Electric. It is equipped with a high power tube and a flat panel detector. It allows high resolution and high contrast fast CT scanning of ... [more ▼]

The eXplore CT 120 is the latest generation micro-CT from General Electric. It is equipped with a high power tube and a flat panel detector. It allows high resolution and high contrast fast CT scanning of small animals. The aim of this study was to compare the performance of the eXplore CT 120 with the one of the eXplore Ultra, its predecessor for which the methodology using the vmCT phantom was already described [1]. The phantom was imaged using typical rat (fast scan or F) or mouse (in vivo bone scan or H) scanning protocols. With the slanted edge method, a 10% modulation transfer function (MTF) was observed at 4.4 (F) and 3.9-4.4 (H) mm-1 corresponding to 114 μm resolution. A fairly larger MTF was obtained with the coil method with the MTF for the thinnest coil (3.3 mm-1 ) equal to 0.32 (F) and 0.34 (H). The geometric accuracy was better than 0.3%. There was a highly linear (R2 > 0.999) relationship between measured and expected CT numbers for both the CT number accuracy and linearity sections of the phantom. A cupping effect was clearly seen on the uniform slices and the uniformity-to-noise ratio ranged from 0.52 (F) to 0.89 (H). The air CT number depended on the amount of polycarbonate surrounding the area where it was measured: a difference as high as approximately 200 HU was observed. This hindered the calibration of this scanner in HU. This is likely due to the absence of corrections for beam hardening and scatter in the reconstruction software. However in view of the high linearity of the system, the implementation of these corrections would allow a good quality calibration of the scanner in HU. In conclusion, the eXplore CT 120 achieved a better spatial resolution than the eXplore Ultra (based on previously reported specifications) and future software developments to include beam hardening and scatter corrections will make the new generation CT scanner even more promising. [less ▲]

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See detailUse of a beta microprobe system to measure arterial input function in PET via an arteriovenous shunt in rats
Warnock, Geoffrey ULg; Bahri, Mohamed Ali ULg; Goblet, David ULg et al

in European Journal of Nuclear Medicine and Molecular Imaging Research (2011), 1

Kinetic modeling of physiological function using imaging techniques requires the accurate measurement of the time-activity curve of the tracer in plasma, known as the arterial input function (IF). The ... [more ▼]

Kinetic modeling of physiological function using imaging techniques requires the accurate measurement of the time-activity curve of the tracer in plasma, known as the arterial input function (IF). The measurement of IF can be achieved through manual blood sampling, the use of small counting systems such as beta microprobes, or by derivation from PET images. Previous studies using beta microprobe systems to continuously measure IF have suffered from high background counts. In the present study, a light-insensitive beta microprobe with a temporal resolution of up to 1 s was used in combination with a pump-driven femoral arteriovenous shunt to measure IF in rats. The shunt apparatus was designed such that the placement of the beta microprobe was highly reproducible. The probe-derived IF was compared to that obtained from manual sampling at 5-s intervals and IF derived from a left ventricle VOI in a dynamic PET image of the heart. Probe-derived IFs were very well matched to that obtained by "gold standard" manual blood sampling, but with an increased temporal resolution of up to 1 s. The area under the curve (AUC) ratio between probe- and manually derived IFs was 1.07 ± 0.05 with a coefficient of variation of 0.04. However, image-derived IFs were significantly underestimated compared to the manually sampled IFs, with an AUC ratio of 0.76 ± 0.24 with a coefficient of variation of 0.32. IF derived from the beta microprobe accurately represented the IF as measured by blood sampling, was reproducible, and was more accurate than an image-derived technique. The use of the shunt removed problems of tissue-background activity, and the use of a light-tight probe with minimal gamma sensitivity refined the system. The probe/shunt apparatus can be used in both microprobe and PET studies. [less ▲]

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