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See detailModular mutagenesis of a TIM-barrel enzyme: the crystal structure of a chimeric E. coli TIM having the eighth beta alpha-unit replaced by the equivalent unit of chicken TIM
Kishan, Radha; Zeelen, Ph. Johan; Noble, Martin E.M. et al

in Protein Engineering (1994), 7(8), 945-51

The crystal structure of a hybrid Escherichia coli triosephosphate isomerase (TIM) has been determined at 2.8 A resolution. The hybrid TIM (ETIM8CHI) was constructed by replacing the eighth beta alpha ... [more ▼]

The crystal structure of a hybrid Escherichia coli triosephosphate isomerase (TIM) has been determined at 2.8 A resolution. The hybrid TIM (ETIM8CHI) was constructed by replacing the eighth beta alpha-unit of E. coli TIM with the equivalent unit of chicken TIM. This replacement involves 10 sequence changes. One of the changes concerns the mutation of a buried alanine (Ala232 in strand 8) into a phenylalanine. The ETIM8CHI structure shows that the A232F sequence change can be incorporated by a side-chain rotation of Phe224 (in helix 7). No cavities or strained dihedrals are observed in ETIM8CHI in the region near position 232, which is in agreement with the observation that ETIM8CHI and E.coli TIM have similar stabilities. The largest CA (C-alpha atom) movements, approximately 3 A, are seen for the C-terminal end of helix 8 (associated with the outward rotation of Phe224) and for the residues in the loop after helix 1 (associated with sequence changes in helix 8). From the structure it is not clear why the kcat of ETIM8CHI is 10 times lower than in wild type E.coli TIM. [less ▲]

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See detailModular Structure, Local Flexibility and Cold-Activity of a Novel Chitobiase from a Psychrophilic Antarctic Bacterium
Lonhienne, T.; Zoidakis, J.; Vorgias, C. E. et al

in Journal of Molecular Biology (2001), 310(2), 291-7

The gene archb encoding for the cell-bound chitobiase from the Antarctic Gram-positive bacterium Arthrobacter sp. TAD20 was cloned and expressed in Escherichia coli in a soluble form. The mature ... [more ▼]

The gene archb encoding for the cell-bound chitobiase from the Antarctic Gram-positive bacterium Arthrobacter sp. TAD20 was cloned and expressed in Escherichia coli in a soluble form. The mature chitobiase ArChb possesses four functionally independent domains: a catalytic domain stabilized by Ca(2+), a galactose-binding domain and an immunoglobulin-like domain followed by a cell-wall anchorage signal, typical of cell-surface proteins from Gram-positive bacteria. Binding of saccharides was analyzed by differential scanning calorimetry, allowing to distinguish unequivocally the catalytic domain from the galactose-binding domain and to study binding specificities. The results suggest that ArChb could play a role in bacterium attachment to natural hosts. Kinetic parameters of ArChb demonstrate perfect adaptation to catalysis at low temperatures, as shown by a low activation energy associated with unusually low K(m) and high k(cat) values. Thermodependence of these parameters indicates that discrete amino acid substitutions in the catalytic center have optimized the thermodynamic properties of weak interactions involved in substrate binding at low temperatures. Microcalorimetry also reveals that heat-lability, a general trait of psychrophilic enzymes, only affects the active site domain of ArChb. [less ▲]

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See detailModularity of mind and the role of incentive motivation in representing novelty
Anselme, Patrick ULg

in Animal Cognition (2012), 15(4), 443-459

Animal and human brains contain a myriad of mental representations that have to be successfully tracked within fractions of a second in a large number of situations. This retrieval process is hard to ... [more ▼]

Animal and human brains contain a myriad of mental representations that have to be successfully tracked within fractions of a second in a large number of situations. This retrieval process is hard to explain without postulating the massive modularity of cognition. Assuming that the mind is massively modular, it is then necessary to understand how cognitive modules can efficiently represent dynamic environments – in which some modules may have to deal with change-induced novelty and uncertainty. Novelty of a stimulus is a problem for a module when unknown, significant stimuli do not satisfy the module’s processing criteria – or domain specificity – and cannot therefore be included in its database. It is suggested that the brain mechanisms of incentive motivation, recruited when faced with novelty and uncertainty, induce transient variations in the domain specificity of cognitive modules in order to allow them to process information they were not prepared to learn. It is hypothesised that the behavioural transitions leading from exploratory activity to habit formation are correlated with (and possibly caused by) the organism’s ability to counter novelty-induced uncertainty. [less ▲]

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See detailModulated misfit structure of the thermoelectric [Bi0.84CaO 2]2[CoO2]1.69 cobalt oxide
Muguerra, H.; Grebille, D.; Guilmeau, E. et al

in Inorganic Chemistry (2008), 47(7), 2464-2471

The structure of the thermoelectric lamellar misfit cobalt oxide [Bi 0.84CaO2]2[CoO2]1.69 has been refined using single crystal X-ray diffraction data. Using the four dimensional superspace formalism for ... [more ▼]

The structure of the thermoelectric lamellar misfit cobalt oxide [Bi 0.84CaO2]2[CoO2]1.69 has been refined using single crystal X-ray diffraction data. Using the four dimensional superspace formalism for aperiodic structures, the superspace group is confirmed P2/m(0δ1/2) (a1 = 4.9069(4), b1 = 4.7135(7), b2 = 2.8256(4), c1 = 14.668(5) Å, β1 = 93.32(1)°). The modulated displacements and site occupancies have been refined and are both compatible with the misfit character of the structure, and with a longitudinal modulation of the Bi-O layers of the structure. This modulation is similar to the corresponding one in the related Sr phase [Bi0.87SrO2]2[CoO2]1.82, but now oriented in the orthogonal direction. Because its incommensurate wavelength is locked with the aperiodicity of the misfit structure, it is possible to distinguish between the modulation parameters induced by the accommodation of both subsystems and those related to the longitudinal modulation of the Bi-O layers. In this original structure, two independent aperiodic phenomena coexist in an single crystallographic direction. A particular attention has been paid to the structural configuration of the CoO2 layer, in relation with other similar phases. The thermoelectric properties are probably directly related to the specific distortion of the compressed layer, but the different measured values for the Seebeck coefficient cannot be related to a significant modification of the CoO6 octahedra. © 2008 American Chemical Society. [less ▲]

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See detailModulating absorption and postprandial handling of dietary fatty acids by structuring fat in the meal : a randomized cross-over clinical trial
Vors, C; Pineau, G; Gabert, L et al

in American Journal of Clinical Nutrition (2013), 97(1), 23-36

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See detailModulating effect of COMT genotype on the brain regions underlying inhibition
Jaspar, Mathieu ULg; Grandjean, Julien ULg; Salmon, Eric ULg et al

Poster (2011, June 26)

Introduction Catechol-O-methytransferase (COMT) is an important enzyme which degrades catecholamines, such dopamine, notably in the prefrontal cortex (Männistö & Kaakkola, 1999). Actually, a transition of ... [more ▼]

Introduction Catechol-O-methytransferase (COMT) is an important enzyme which degrades catecholamines, such dopamine, notably in the prefrontal cortex (Männistö & Kaakkola, 1999). Actually, a transition of guanine to adenine at codon 158 of the COMT gene results in a valine to methionine substitution (Lotta & al., 1995). This phenomenon leads to different COMT genotypes, each associated with a different COMT enzymatic activity (Weinshilboum, & al., 1999). A large number of studies reported an effect of COMT on executive functioning. However, most of them used multi-determined executive tasks (e.g., Barnett & al., 2007). We are interested here to determine the effect of COMT Val158Met genotype on the activity of frontal and parietal areas (Nee & al., 2007; Laird & al., 2005) underlying the specific executive process of inhibition. Methods Procedure In an event-related fMRI experiment, a modified form of the Stroop task was administered to 44 young adults (age range: 18-30) separated into three groups according to their COMT Val158Met genotype: 15 homozygous val/val (VV), 14 homozygous met/met (MM) and 15 heterozygotes val/met (VM) carriers. The Stroop task consisted in the presentation of color words printed in various ink colors (e.g the word blue written in red). Subjects were instructed to name of ink color as fast and accurately as possible by avoiding to read the word. In this version of the Stroop task, three different contexts were created (data not showed here): (1) a congruent context (MC) with a majority of facilitator items (IC), (2) a non-congruent context (MI) with mainly interfering items (II), (3) a neutral context (MN) with mainly neutral items (IN, series of %%% written in different colors). MRI acquisition, data analysis Functional MRI time series were acquired on a 3T head-only scanner operated with the standard transmit-receive quadrature head coil. Multislice T2*-weighted functional images were acquired with a gradient-echo echo-planar imaging sequence using axial slice orientation and covering the whole brain (32 slices, FoV = 220x220 mm², voxel size 3.4x3.4x3 mm³, 30% interslice gap, matrix size 64x64x32, TR = 2130 ms, TE = 40 ms, FA = 90°). Structural images were obtained using a high resolution T1-weighted sequence (3D MDEFT [Deichmann & al., (2004)] ; TR = 7.92 ms, TE = 2.4 ms, TI = 910 ms, FA = 15°, FoV = 256 x 224 x 176 mm³, 1 mm isotropic spatial resolution). Preprocessing and statistical analyses were performed with SPM8 (p<.001 uncorrected). Results Behavioral results indicated the presence of a general interference effect (II – IN items) for reaction time (F(1,41) = 292,44 ; p < 0,001) but no significant difference in interference between the three groups (F(2,41) = 0,27; p = 0,76). FMRI results revealed that interference effect [(MI_II-MI_IN) + (MC_II-MC_IN) + (MN_II-MN_IN)] observed in our three groups is mainly associated with cerebral activity in frontal and parietal areas. Moreover, group comparisons indicates that this effect is associated with increased medial frontal and precentral gyrus activity in VV and VM groups by comparison with MM group, but also in the superior temporal gyrus and in the thalamus in the VM by comparison to MM . Conversely, no supplementary brain area was observed for the comparison of the MM to the two other groups. Conclusions The fronto-parietal brain network associated with interference resolution observed here is consistent with prior reports (Nee & al., 2007; Laird & al., 2005). Moreover, results showed activity in different brain areas according to the COMT genotype. Indeed, a similar behavioral performance is associated to the recruitment of supplementary areas in the carriers of the val allele. This observation, paralleling with the lower COMT enzymatic activity and, thus, the higher cortical dopamine level in met/met individuals, confirms our expectation of a COMT Val158Met genotype modulation of the brain regions underlying inhibition efficiency. [less ▲]

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See detailModulating effect of COMT genotype on the brain regions underlying proactive control process during inhibition
Jaspar, Mathieu ULg; Genon, Sarah ULg; Muto, Vincenzo ULg et al

in Cortex : A Journal Devoted to the Study of the Nervous System & Behavior (2014), 50

Introduction. Genetic variability related to the catechol-O-methyltransferase (COMT) gene (Val158Met polymorphism) has received increasing attention as a possible modulator of cognitive control functions ... [more ▼]

Introduction. Genetic variability related to the catechol-O-methyltransferase (COMT) gene (Val158Met polymorphism) has received increasing attention as a possible modulator of cognitive control functions. Methods. In an event-related fMRI study, a modified version of the Stroop task was administered to three groups of 15 young adults according to their COMT Val158Met genotype [Val/Val (VV), Val/Met (VM) and Met/Met (MM)]. Based on the theory of dual mechanisms of control (Braver, et al., 2007), the Stroop task has been built to induce proactive or reactive control processes according to the task context. Results. Behavioral results did not show any significant group differences for reaction times but Val allele carriers individuals are less accurate in the processing of incongruent items. fMRI results revealed that proactive control is specifically associated with increased activity in the anterior cingulate cortex (ACC) in carriers of the Met allele, while increased activity is observed in the middle frontal gyrus (MFG) in carriers of the Val allele. Conclusion. These observations, in keeping with a higher cortical dopamine level in MM individuals, support the hypothesis of a COMT Val158Met genotype modulation of the brain regions underlying proactive control, especially in frontal areas as suggested by Braver et al. [less ▲]

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See detailModulating effect of COMT genotype on the brains regions underlying inhibition
Jaspar, Mathieu ULg; Grandjean, Julien ULg; SALMON, Eric ULg et al

Conference (2012, May)

Catechol-O-methyltransferase (COMT) is an important enzyme which degrades catecholamines, such dopamine, notably in the prefrontal cortex (Männistö & Kaakkola, 1999). A large number of studies reported an ... [more ▼]

Catechol-O-methyltransferase (COMT) is an important enzyme which degrades catecholamines, such dopamine, notably in the prefrontal cortex (Männistö & Kaakkola, 1999). A large number of studies reported an effect on executive functioning of COMT genotype (Barnett & al., 2007), each genotype being associated with a different COMT enzymatic activity (Weinshilboum & al., 1999). In an event-related fMRI study, a modified form of the Stroop task was administered to 45 young adults separated in three groups according to their COMT val158met genotype : 15 homozygous val/val (VV), 15 homozygous met/met (MM) and 15 heterozygotes val/met (VM). Both behavioral and fMRI results indicated the presence of a general interference effect consistent with prior reports (Nee & al., 2007). More interestingly, group comparisons indicate that this effect is associated, for a similar behavioral performance, with increased medial frontal and precentral gyrus activity in VV and VM groups by comparison with MM group. Conversely, no supplementary brain areas were observed for the comparison of the MM to the two other groups. These observations, paralleling with the lower COMT enzymatic activity and, thus, the higher cortical dopamine level in met/met individuals, confirms our expectation of a COMT Val158Met genotype modulation of the brain regions underlying inhibition efficiency. [less ▲]

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See detailModulating effects of acepromazine on the reactive oxygen species production by stimulated equine neutrophils
Sandersen, Charlotte ULg; Mouithys-Mickalad, Ange ULg; de la Rebière de Pouyade, Geoffroy ULg et al

in Veterinary Anaesthesia & Analgesia (2011), 38

To investigate the effect of acepromazine (ACP) on reactive oxygen species (ROS) production by stimulated equine neutrophils.

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See detailModulating mouse innate immunity to RNA viruses by expressing the Bos taurus Mx system.
Garigliany, Mutien-Marie ULg; Cloquette, Karine ULg; Leroy, Michael et al

in Transgenic Research (2009), 18(5), 719-32

Mx proteins are interferon-induced members of the dynamin superfamily of large guanosine triphosphatases. These proteins have attracted much attention because some display antiviral activity against ... [more ▼]

Mx proteins are interferon-induced members of the dynamin superfamily of large guanosine triphosphatases. These proteins have attracted much attention because some display antiviral activity against pathogenic RNA viruses, such as members of the orthomyxoviridae, bunyaviridae, and rhabdoviridae families. Among the diverse mammalian Mx proteins examined so far, we have recently demonstrated in vitro that the Bos taurus isoform 1 (boMx1) is endowed with exceptional anti-rabies-virus activity. This finding has prompted us to seek an appropriate in vivo model for confirming and evaluating gene therapy strategies. Using a BAC transgene, we have generated transgenic mouse lines expressing the antiviral boMx1 protein and boMx2 proteins under the control of their natural promoter and short- and long-range regulatory elements. Expressed boMx1 and boMx2 are correctly assembled, as deduced from mRNA sequencing and western blotting. Poly-I/C-subordinated expression of boMx1 was detected in various organs by immunohistochemistry, and transgenic lines were readily classified as high- or low-expression lines on the basis of tissue boMx1 concentrations measured by ELISA. Poly-I/C-induced Madin-Darby bovine kidney cells, bovine turbinate cells, and cultured cells from high-expression line of transgenic mice were found to contain about the same concentration of boMx1, suggesting that this protein is produced at near-physiological levels. Furthermore, insertion of the bovine Mx system rendered transgenic mice resistant to vesicular-stomatitis-virus-associated morbidity and mortality, and embryonic fibroblasts derived from high-expression transgenic mice were far less permissive to the virus. These results demonstrate that the Bos taurus Mx system is a powerful anti-VSV agent in vivo and suggest that the transgenic mouse lines generated here constitute a good model for studying in vivo the various antiviral functions-known and yet to be discovered-exerted by bovine Mx proteins, with priority emphasis on the antirabic function of boMx1. [less ▲]

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See detailModulating skeletal muscle mass by postnatal, muscle-specific inactivation of the myostatin gene.
Grobet, Luc ULg; Pirottin, Dimitri ULg; Farnir, Frédéric ULg et al

in Genesis (2003), 35(4), 227-38

By using a conditional gene targeting approach exploiting the cre-lox system, we show that postnatal inactivation of the myostatin gene in striated muscle is sufficient to cause a generalized muscular ... [more ▼]

By using a conditional gene targeting approach exploiting the cre-lox system, we show that postnatal inactivation of the myostatin gene in striated muscle is sufficient to cause a generalized muscular hypertrophy of the same magnitude as that observed for constitutive myostatin knockout mice. This formally demonstrates that striated muscle is the production site of functional myostatin and that this member of the TGFbeta family of growth and differentiation factors regulates muscle mass not only during early embryogenesis but throughout development. It indicates that myostatin antagonist could be used to treat muscle wasting and to promote muscle growth in man and animals. [less ▲]

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See detailModulation and mechanism of action of BPDZ 44 on ATP-sensitive potassium channels in isolated rat insulin-secreting cells
Kane, C.; Harding, E. A.; Pirotte, Bernard ULg et al

in Journal of Physiology (1995), 482 P

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See detailModulation by intracellular calcium of a GABA receptor-mediated chloride current via a calcium/calmodulin-dependent protein kinase in insect neurosecretory cells
Alix, Philippe ULg; Grolleau, Françoise; Hue, Bernard

in European Journal of Neuroscience (2000), 12

Detailed reference viewed: 7 (1 ULg)