PubMed Health⌕ Search

Biomedical subjects

M Genest

Publications and source records attributed to M Genest.

At least 37 records · Page 2Linked to original sources
PubMed1994

Solution three-dimensional structure of surfactin: a cyclic lipopeptide studied by 1H-NMR, distance geometry, and molecular dynamics.

The solution three-dimensional structure of the protonated [Leu7]-surfactin, an heptapeptide extracted from Bacillus subtilis, has been determined from two-dimensional 1H-nmr performed in 2H6-dimethylsulfoxide and combined with molecular modeling. Experimental data included 9 coupling constants, 61 nuclear Overhauser effect derived distances, NH temperature coefficients, and 13C relaxation times. Two distance geometry (DISMAN) protocols converged toward models of the structure and the best of them were refined by restrained and unrestrained molecular dynamics (GROMOS). Two structures in accord with the set of experimental constraints are presented. Both are characterized by a "horse saddle" topology for ring atoms on which are attached the two polar Glu and Asp side chains showing an orientation clearly opposite to that of the C11-13 aliphatic chain. Amphipathic and surface properties of surfactin are certainly related to the existence of such minor polar and a major hydrophobic domains. The particular "claw" configuration of acidic residues observed in surfactin gives important clues for the understanding of its cation binding and transporting ability.

Amino Acid Sequence↗
PubMed1994

Influence of a mutation in the transmembrane domain of the p185c-erbB2 oncogene-encoded protein studied by molecular dynamics simulations.

The c-erbB2 proto-oncogene encodes for a protein of 185kDa (p185) which becomes transforming upon the Val-->Glu transmembrane amino acid substitution. The transforming ability seems to be due to a substitution-resulting constitutive activation of the tyrosine kinase cytosolic domain of the protein. These observations prompted us to evaluate the structural and dynamical behavior of the transmembrane region of the wild and transforming p185 protein in order to understand the role of this region in the transduction mechanism. 160 ps molecular dynamics simulations in vacuo have been performed on two peptides corresponding to the sequence [651-679] of p185c-erbB2 protein and its transforming mutant Val659-->Glu659. These two sequences include the transmembrane domain and are initially postulated to be in an alpha-helix conformation. Noticeable differences in the flexibility of the two peptides are shown. The nontransforming sequence seems rather flexible and several conformational changes are detected at the junction of the mutation point [658-659] and at position Val665-Val666 during the 160 ps simulations. On the contrary, no transitions were observed for the mutated sequence which adopts a stable alpha-helix conformation. This difference in flexibility could be hypothesized as a factor involved in the regulation of the tyrosine kinase activity of p185c-erbB2.

Amino Acid Sequence↗
PubMed1992

The Children of Alcoholics Screening Test: reliability and relationship to family environment, adjustment, and alcohol-related stressors of adolescent offspring of alcoholics.

The Children of Alcoholics Screening Test (CAST) had acceptably high internal consistency (.88 and .90) and test-retest reliabilities (.88) when administered to adolescents from intact alcoholic families. CAST scores were unrelated to measures of adolescent adjustment or indices that reflect general family environment. However, CAST scores did correlate positively with a measure of the more specific family environment related to alcohol abuse. The study suggested that CAST scores are best suited for screening respondents and not as a dependent variable because the relationships that one is likely to identify between CAST scores and any other variable would be primarily reflective of group differences between offspring of alcoholics and nonalcoholics.

Adaptation, Psychological↗
PubMed1990

The ideal self: schematic processing of perfectionistic content in dysphoric university students.

This study assessed ideal-self-schematic processing, recall of perfectionistic content rated as not descriptive of the actual self or ideal self, and content-specific processing as a function of dysphoria. College students (n = 219) made structural (ST), ideal-self (IS), and actual-self (AS) ratings on perfectionistic, negative, and neutral words, and completed an incidental recall task. Words rated with the IS task were recalled better tha words rated with the ST task, but recall did not differ between the IS and AS tasks. Subjects recalled no-rated perfectionistic words better with the IS and AS tasks than with the ST task. Finally, dysphoric and nondysphoric subjects did not differ in processing specific content. The results support the belief that the IS functions as a schema and suggest that non-self- and non-ideal-self-descriptive perfectionistic content is involved in ideal- and actual-self-schemas.

Adolescent↗
PubMed1988

Structure and energetics of ligand binding to proteins: Escherichia coli dihydrofolate reductase-trimethoprim, a drug-receptor system.

A study of the binding of the antibacterial agent trimethoprim to Escherichia coli dihydrofolate reductase was carried out using energy minimization techniques with both a full, all-atom valence force field and a united atom force field. Convergence criteria ensured that no significant structural or energetic changes would occur with further minimization. Root-mean-square (RMS) deviations of both minimized structures with the experimental structure were calculated for selected regions of the protein. In the active site, the all-atom minimized structure fit the experimental structure much better than did the united atom structure. To ascertain what constitutes a good fit, the RMS deviations between crystal structures of the same enzyme either from different species or in different crystal environments were compared. The differences between the active site of the all-atom minimized structure and the experimental structure are similar to differences observed between crystal structures of the same protein. Finally, the energetics of ligand binding were analyzed for the all-atom minimized coordinates. Strain energy induced in the ligand, the corresponding entropy loss due to shifts in harmonic frequencies, and the role of specific residues in ligand binding were examined. Water molecules, even those not in direct contact with the ligand, were found to have significant interaction energies with the ligand. Thus, the inclusion of at least one shell of waters may be vital for accurate simulations of enzyme complexes.

Computer Simulation↗
PubMed1988

Reconsideration of the psychological effects of contact lenses.

The potential psychological impact of switching from glasses to contact lenses was investigated within a controlled quasi-experimental design. Contrary to anecdotal reports and some previous investigations, the hypothesis that a switch from glasses to contact lenses leads to psychological benefits was not supported.

Adolescent↗
PubMed1987

Modelling and refinement of the conformation of mycosubtilin in solution from two-dimensional NMR data.

The conformation in solution of mycosubtilin, an antifungal lipopeptide [cyclo(L-Asn-D-Tyr-D-Asn-L-Gln-L-Pro-D-Asn-L-Ser-beta-amino acid)]has been probed by two-dimensional nuclear magnetic resonance and restrained energy minimization. Several structures have been proposed belonging to the same family with minor local variations related to different orientations of amide planes. The molecular topology was found to be completely different from that of iturin A, an analogue which exhibits quite different biological properties. The cyclic peptide of mycosubtilin is shown to be rather rigid in the region of L-proline and stabilized by C7 structures; in contrast, the neighbourhood of D-tyrosine-2 was found to be more flexible. The validity of our models is discussed first in terms of distance violation and second on the basis of reconstructed NOE spectroscopy maps. The different limitations towards higher-resolution structures are discussed.

Antifungal Agents↗
PubMed1987

Reconstruction of NOESY maps. A requirement for a reliable conformational analysis of biomolecules using 2D NMR.

The modelling of the conformation of a biomolecule in solution is based mainly on the internuclear distances deduced from measurements of nuclear Overhauser effects (nOe) in NOESY correlation maps. The distances are then used as restraints in the energy minimization procedure, which leads to one or several optimized conformations. A general and safe technique for validating these structures with respect to the experimental data is here proposed: from the internuclear distances, the relaxation matrix can be computed under the assumption of a unique rotational correlation time. By stepwise integration of these relaxation equations, the NOESY maps can be accurately reconstructed for any mixing time. Because multi-spin effects are correctly taken into account, any difference between the experimental and theoretical maps can be easily interpreted in terms of conformation, and possible inconsistencies due to conformational averaging can be pointed out. The technique is illustrated for a bacterial lipopeptide, mycosubtilin, the spectrum of which is completely assigned.

Biopolymers↗
PubMed1987

Variables associated with the adjustment of offspring of alcoholic fathers.

A multivariate model of adjustment was used to examine the role of moderator variables hypothesized to provide insight into the adjustment of children of alcoholics. The moderator variables (family environment, social support and coping behaviors) were assessed retrospectively. Present adjustment was also assessed using the Depression-Proneness Rating Scale and the Tennessee Self-Concept Scale. As hypothesized, children of alcoholics, compared with children of nonalcoholics, described their families as more dysfunctional and reported receiving less guidance from others. Children of alcoholics also reported engaging in avoidant coping behaviors (e.g., smoking, drinking, eating) more than did comparison subjects. Despite their disadvantages, many children of alcoholics were functioning at, or well above, the average level of children from nonalcoholic families. Through regression analysis it was found that the moderator variables were extremely useful in accounting for the variability in offsprings' adjustment, providing support for the use of a multivariate approach for understanding offsprings' adjustment.

Adaptation, Psychological↗
PubMed1986

[Continuing eco-pathological survey: 6. Influence of zootechnical and space-time factors on some biochemical variables in the dairy cow].

Several hundred of blood samplings were performed on dairy cows in four French departments, from 1978 to 1982. They were used to analyse the effect of eight factors on the physiological variations of twelve biochemical variables. Only the blood withdrawal date related to calving date or milk production were able to explain more than 15% of the variance of free or total cholesterol or phospholipids.

3-Hydroxybutyric Acid↗
PubMed1986

[Continuing eco-pathological survey: 10. Variation of pathological frequency in dairy cow stock as a function of season, year and number of lactations].

The distribution of main herd diseases in course of time is studied with the season, the year and number of lactation. There is a seasonal effect for retained placenta, spring and summer being a favorable time for the increase of their frequency. Milk fever is also more frequent during summer. Out-calving pathologies are more frequent during housing time, but we do not observe any monthly variation for ovarian pathology. The age is a risk factor for milk fever and retained placenta. On the contrary, dystocia and stillbirth are more common on heifers. All the metabolic disorders and infectious diseases (mastitis-metritis) seem to be more frequent on old cows. The variations between years are interpretable with difficulty because they depend on the regularity in the quality of collected data. More, the necessity for the breeders to observe conscientiously their animals is a favouring factor for the improvement of the health status of the herd.

Age Factors↗
PubMed1986

[Continuing eco-pathological survey: 8. Epidemiological approach to postpartum mastitis in the dairy cow: discriminating biochemical parameters].

To discriminate two groups of dairy cows (with or without post-partum mastitis), with blood parameters, we used discriminant analysis on two samples of dairy cows: one sample where blood was collected around parturition (15 days before and 15 days after calving); one sample where blood was collected at any time of the lactation, but with the same mean interval calving-blood collection in the two groups of animals. Blood parameters which differenciate the two groups (ill and safe) are essentially parameters of energetic metabolism i.e. glucose and 3-hydroxybutyrate. Results are discussed according to the possibility of glucose to be an indicator of energetic status.

3-Hydroxybutyric Acid↗
PubMed1985

Calculations of the conformations of Iturin A in relation with NMR studies.

Iturin A is an antifungal antibiotic which was isolated from a strain of Bacillus subtilis, and contains a lipophilic beta amino acid closing an heptapeptide cycle with polar L and D residues. Iturin A belongs to a lipopeptide family of which the LDDLLDL sequence is kept constant. NMR spectroscopy and semi-empirical energy calculations are combined to design the conformations of Iturin A in pyridine solution. J coupling constants and nOes (nuclear Overhauser enhancements) are used as guiding line for energy calculations. This preliminary study shows that Iturin A in pyridine appears as rather rigid, especially in the L Pro 5-D Asn 6 region, probably involved in a beta turn. The polar side chains can form different networks of intramolecular hydrogen bonds. The Tyr side chain, relatively mobile, could be involved in interactions with an hydrophobic environment as the beta amino acid side chain found away from the peptide cycle.

Amino Acid Sequence↗
PubMed1982

Interactions between Asp, His, Ser residues within models of the active site of serine proteases. A theoretical empirical study.

Empirical theoretical calculations have been performed on a simplified model of the active site of two serine proteases: alpha-chymotrypsin and subtilisin Novo. The stability of the catalytic triad and the hydrogen bond formation between the Asp-His and His-Ser pairs have been examined for different protonation states. The results show that the Asp-His interactions prevail upon the His-Ser ones. Agreement between calculated configurations and the crystal structure of the site suggests that the presence of other residues near the functional residues is not determinant for the stability of the triad in alpha-chymotrypsin. In subtilisin Novo, on the contrary, the presence of the neighbouring residues seems to contribute more largely to the stability. Strong hydrogen bond interactions between the His and Ser residues do not exist in the resting enzymes. Any improvement of the His-Ser interactions requires large destabilization of the Asp-His diad. Our results suggest that the mechanism of the proton transfer can occur only from perturbations of the active site structure induced by the presence of the substrate.

Aspartic Acid↗