Interactions de la chloroquine avec la ferriprotoporphyrine IX: Étude par résonance magnétique nucléaire

Chloroquine is still the antimalarial drug which is the most utilized. Nevertheless the molecular mode of action of this drug is not very well understood. When mouse erythrocytes injected with Plasmodium berghei are exposed to chloroquine, the first biochemical event is rapid accumulation of the drug. This process is energy dependent, saturable and competively inhibited by drugs of the same therapeutic class (Quinine, Amodiaquine, Mefloquine). Receptors for chloroquine have been proposed for the process of accumulation. The nature of the chloroquine receptor is presently the subject of debates. The latest hypothesis proposed by Chou and coll. [12], is that ferriprotoporphyrin IX, formed by the degradation of hemoglobin by the parasite, binds to chloroquine with a dissociation constant of 3.5.10⁻⁹ M. We studied here the molecular interactions between these two species by Proton Nuclear Magnetic Resonance in order to elucidate the nature and the geometry of were undertaken.The perturbations of the NMR spectra of chloroquine (10⁻² M) induced by addition of hematin or hemin were measured. Two types of measures were indertaken.The first study carried out in organic solvent (DMSO) has shown that the interaction occured between the acidic functions of hemin and the sidechain nitrogen of chloroquine. The iron atom was not implicated in this process.The second study carried out in aqueous medium (phosphate buffer; 0.1 M; pH = 7) allowed us to demonstrate that chloroquine is able to intercalate into a polymer of hematin. The quinoleic nucleus of chloroquine was intercalated between two dimers of hematin as shown by the broadening of the signal of the quinoleic protons due to very large increase in the correlation time.Finally it was shown that chloroquine is associated as a dimer in aqueous medium by hydrophobic interactions. The association constant is 5.5 M⁻¹.     

Étude de la fixation de faible affinité du Ca par les membranes externe et interne des mitochondriest et par le réticulum endoplasmique lisse et rugueux de foie de rat

Two classes of low-affinity Ca²⁺-binding sites have been shown to exist. One type dissociates as pH rises, thereby increasing the amount of bound Ca²⁺. The other type, which does not change in number, has an affinity for Ca²⁺ which is dependent on ionic strength. The former is possibly a phospholipid, the latter possibly a protein.Under our experimental conditions, the inner mitochondrial membrane contained binding sites of the second class ony while other membranes contain both types. Rough endoplasmic reticulum contains yet another class of sites at the ribosomal level.

Résumé

L'existence de deux catégories de sites de fixation de faible affinité du Ca²⁺ a été mise en évidence. Les uns se dissocient de plus en plus quant le pH s'éléve permettant une augmentation des quantités de Ca²⁺ fixé, les autres sont invariables en nombre, mais leur affinité pour le Ca²⁺ est dépendante de la force ionique du milieu. Les premiers pourraient étre de nature phospholipidique, les seconds de nature protéique.Dans nos conditions expérimentales, la membrane interne des mitochondries possède uniquement des sites de la seconde catégorie. Les autres membranes renferment simultanément les deux sortes de sites. Le réticulum endoplasmique rugueux possède des sites supplémentaires au niveau des ribosomes.     

Groupement et ordination appliqués à l''étude de la répartition de l''épifaune benthique de l''estuaire maritime et du Golfe du Saint-Laurent

Forty-seven navigation buoys were used to collect quantitative samples of epibenthic fauna in the Lower Estuary and Gulf of St. Lawrence. Stations, as described by their sessile species and biomass composition, were grouped using multivariate analysis. A Gower similarity index, modified to take into account the importance of each species in the ecosystem, was used to compare stations. Results obtained by cluster and principal coordinate analyses showed comparable relations between stations. North Shore and Gaspé Coast stations were separated from those of the Lower North Shore, the Mingan Island sector and the Lower Estuary. Stations from the Lower North Shore were also separated from those of the Mingan Island region and of the Lower Estuary, but at a higher level of similarity. All animal assemblages consisted of the following sessile species: Obelia longissima (Pallas), Hiatella arctica (L.), Mytilus edulis L., Balanus balanoides (L.) and B. crenatus (Bruguière). These species formed over 95% of biomass of all sessile species. Differences between the various station assemblages were mainly due to changes in the relative abundance of these species. The geographical gradient of summer surface water temperature best explains the observed clusters. In the Lower Estuary, the spatio-temporal variations of physico-chemical factors and the surface circulation may influence the number of species and their abundance. The circulation systems of the Lower Estuary and near the Mingan Islands might account for the similarity between their assemblages. The same dominant species, Obelia longissima, characterizes the fauna of these two regions.     

Modification de la fertilité du carpocapse Cydia pomonella à la suite du contact des adultes avec un régulateur ou un inhibiteur de croissance d'insectes

Résumé Des papillons de carpocapse Cydia pomonella L., mâles et femelles séparés, sont soumis au contact des résidus secs du CGA 184'699, un inhibiteur de croissance d'insectes (ICI) et du fenoxycarb, un régulateur de croissance d'insectes (RCI). Ils sont ensuite regroupés dans boîtes non traitées pour l'accouplement et la ponte. La fécondité du carpocapse n'est pratiquement pas affectée par ce conditionnement mais sa fertilité diminue avec l'augmentation de la concentration des produits et avec la durée d'exposition. Avec le CGA 184'699, l'efficacité ovicide induite atteint environ 50% suite à un contact de trois jours avec les résidus d'un traitement à 100 mg/l, alors qu'avec le fenoxycarb elle s'élève à 87% dans les mêmes conditions. Avec le CGA 184'699, seul le contact des femelles avec les résidus provoque cette réduction de fertilité, alors que le fenoxycarb agit sur les deux sexes.

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Summary Codling moth, Cydia pomonella L., males and females were exposed separately to contact with dry residues of CGA 184'699 an insect growth inhibitor (IGI) and fenoxycarb, an insect growth regulator (IGR), The sexes were then grouped together in non treated boxes for mating and egglaying. Fecundity of codling moth was little affected by this treatment but its fertility decreased with increases in the concentration of products and the duration of contact. Induced ovicidal efficacy was about 50% after three days contact with the residues of a 100 mg (a.i.)/l application of CGA 184'699, whereas the same conditions led to about 87% efficacy with fenoxycarb. With CGA 184'699, only contact by females affected egg eclosion whereas fenoxycarb acted on both sexes.

     

Étude,par diffusion centrale des Rayons X,des polyelectrolytes rigides en solution. Cas des sels de Li,Na et Cs du DNA

The study of polyelectrolytes in solution by small-angle x-ray scattering techniques involves special problems, raised by the presence of several species: solvent, macroions, counterions, and possibly the ions of an additional electrolyte. A theoretical treatment of this problem is developed, based upon geometric concepts; the treatment applies to globular and to rodlike particles for the case of x-ray experiments carried out on an absolute scale. The equation obtained involves several parameters: mass and radius of gyration for globular particles; mass per unit length and axial radius of gyration for rodlike particles; partial specific volumes of the neutral macromolecular component of the counterions and of the added electrolyte; solvation of the macromolecular species; fraction of the counterions osmotically free. The equation is used to interpret a series of experiments performed with the Li, Na, and Cs salts of DNA in solution in water containing variable amounts of the chlorides of each cation. The effects of concentration are first eliminated by extrapolating to infinite dilution the experiments carried out at different concentrations; then the effects of the solvation are eliminated by extrapolating to pure water the results obtained at different electrolyte concentration. The parameters still involved at this stage are the mass per unit length, the partial specific volumes of the DNA and of the counterions, and the fraction of the counterions osmotically free. If the partial specific volumes are chosen in agreement with other data of the literature, and if the fraction of the counterions osmotically free is assumed to be 0.30 for the three salts, as suggested by other workers, the structure of the DNA molecules turns out to be the same for three cations, and to agree with the Watson-Crick model. These results are confirmed by the study of the liquid–crystalline gels, obtained at higher concentration, that lead to a direct determination of the mass per unit length of the rods. Moreover the solvation of the DNA molecules is determined as is shown to be different for each of the three cations. These results are in excellent agreement with those obtained by other techniques.     

Biosynthèse de la cellulose bacterienne deutériée: étude par R. M. N. du taux d'incorporation et de la localisation du deutérium

The use of the NMR spectra (250 MHz) of cellulose triacetate allows the determination of the percentage of deuterium bonded to each of the six carbon atoms of the monomer residue (except for H_?1 and one of the protons bonded to C₆ where the signals overlap). Deuterated derivatives of D -glucose and/or deuterated water were used for the biosynthesis of bacterial cellulose by Acetobacter xylinum. Analysis of NMR spectra of acetylated samples gives the following results. About 90% of the protons linked to C₁ and C₆ come from the D -glucose used in the nutrition medium, whereas 10% are exchanged with other sources of protons. Over 40% of the protons linked to C₂, C₃, C₄, and C₅ arise from the water of the nutrition medium. Discrepancies between results of biosynthesis from deuterated water and from deuterated D -glucose can only be explained if more than one enzymatic process is involved in the biosynthesis of bacterial cellulose.     

Interaction entre la cochenille du manioc Phenacoccus manihoti et ses différentes plantes-hôtes: étude de la teneur de la sève en acide aminé et en sucre

Résumé L'analyse (acides aminés et sucres) d'extrait de feuille, de 5 variétés de manioc (Manihot esculenta), du Faux caoutchouc (Hybride deM. esculenta x M.glaziovii), du Poinsettia (Euphorbia pulcherrina) et du Talinum (Talinum triangularae), caractérisés par différents degrés de résistance par antibiose à la cochenille du manioc (Phenacoccus manihoti (Mat. Ferr.)) (Homoptera: Pseudococcidae), a été réalisée sur des extraits obtenus par centrifugation du matériel foliaire. Les teneurs en acids aminés, très différentes d'une plante à l'autre, apparaissent aussi importantes entre les variétés de l'espèce manioc qu'entre les différentes espèces végétales avec respectivement un rapport de variation de 4,5 et 5,5. De même, les teneurs en sucres (exprimées en équivalent saccharose), sont très différentes d'une plante à l'autre avec un rapport de variation de 1 à 33 entre les deux extrêmes, si l'on ne considère que l'espèceM. esculenta, il n'est plus que de 3,5.Des différences dans les proportions relatives des acids aminés libres d'extrait de feuille sont observées aussi bien entre les variétés de manioc qu'entre les espèces végétales. Cependant pour toutes les plantes étudiées l'acide glutamique, la glutamine, l'ethanolamine, et l'alanine représentent près de 50% des acides aminés de l'extrait de feuille; l'acide aspertique, l'asparagine et la sérine près de 20% tandis que la tyrosine, la méthionine, l'isoleucine, la leucine et la lysine sont présents en très faibles pourcentages.Le degré de résistance à la cochenille du manioc des différentes plantes-hôtes n'a pu être relié, ni à la teneur de leur extrait de feuille en acides aminés et en sucres, ni à leur composition relative en acides aminés. Il n'a pu être non plus relié au rapport Sucres/Acides aminés Nos résultats suggèrent que des caractéristiques biochimiques autres que celles étudiées dans ce travail interviennent dans les mécanismes de résistance vis-à-vis de la cochenille du manioc.

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Summary The levels of sugars and amino acids were determined in leaf extracts from a number of plants showing different levels of resistance to the cassava mealybug,Phenacoccus manihoti (Homoptera: Pseudococcidae). There were five varieties of cassava (Manihot esculenta), as well as a hybrid obtained by crossingM. esculenta andM. glaziovii, poinsettia (Euphorbia pulcherrina) and talinum (Talinum triangularae). The variability in the total concentration of amino acid concentrations was as great between varieties of cassava as at the species level. In contrast, there was much less variability in the concentration of sugars at the intervarietal that at the interspecies level.While there were both intervarietal and interspecific differences in the amino acid composition, glutamic acid, glutamine, ethanolamine and alanine represented nearly 50% of the total in all plants examined. Aspartic acid, asparagine and serine accounted for approximately 20%, while tyrosine, methionine, isoleucine, leucine and lysine are present at low levels.The different levels of resistance noted in the different plants were not associated with the concentrations of either amino acids or sugars, the ratios of sugar/amino concentrations or the amino acid compositions obtained from leaf extracts. This suggests that other aspects of plant chemistry confer resistance to cassava mealybugs.

     

Conséquences du traitement préalable par le précocène 2 sur les réponses du criquet migrateur,Locusta migratoria, à un apport en hormone juvénile exogène

Un apport unique de 10 g d'hormone juvénile 1, réalisé chez des criquets du dernier stade larvaire à corpora allata intacts ou préalablement soumis à une application de precocène 2, provoque, à la mue suivante, l'apparition d'individus dont les caractéristiques sont intermédiaires entre celles du dernier stade larvaire et celles de l'imago. Cependant, les criquets traités par le précocène 2 présentent des variations phénotypiques plus prononcées, se traduisant par un maintien accru des caractéristiques larvaires. Les études ultrastructurales montrent que les corpora allata dégénèrent rapidement sous l'action des 400 g de précocène 2.

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Summary In fifth instar locusts, with intact corpora allata or previously subjected to precocene 2 action, a single injection of 10 g juvenile hormone 1 leads, at the next molt, to the appearance of individuals displaying characters ranging from the typical larval to the typical imaginal ones. But, unexpectedly, the phenotypic variations are more marked in the precocene 2 treated locusts, and are typified by an increased retention of larval characters. Electron microscopic studies indicate that the use of 400 g of precocene 2 rapidly leads to the degeneration of the corpora allata.

     

Modéliser les interactions moléculaires par la théorie des réseaux de jeux

We present a method to model biological systems, the theory of games networks. It extends game theory by multiplying the number of games, and by allowing agents to play several games simultaneously. Some important notions of biological systems, such as locality of interactions and modularity, can then be modelled. To cite this article: M. Manceny et al., C. R. Biologies 329 (2006).     

Biosynthèse de cellulose bacterienne à partir de glucose sélectivement deuterié en position 6: Étude par RMN

D-glucose specifically deuterated at C-6 was prepared and used for the biosynthesis of bacterial cellulose with Acetobacter xylinum. The material obtained was converted into glucitol hexaacetate and analyzed by 250 MHz n.m.r. and mass spectrometry. These spectra indicated that about 70% of the starting D-glucose was incorporated without modification of deuteriation at the C-6 position. However an explanation is required of the finding that deuterium was also incorporated at the C-2 and C-1 positions of the cellulose, arising respectively from the 6 pro-R and 6 pro-S positions of the initial D-glucose.     

Les groupements mitochondriaux des cellules germinales des poissons téléostéens cyprinidés : II. Étude autoradiographique à haute résolution de l'incorporation de phénylalanine H et d' uridine H

A high resolution autoradiographic study of the incorporation of tritiated uridine and amino acids by the mitochondrial groups, which are typical of most of germ cells at the beginning of gametogenesis, has been made on tench spermatocytes. By this technique, we confirm the partially proteinacious composition of the intermitochondrial “cement”; and for the first time, the presence of RNA in the “cement” is demonstrated by autoradiography. Moreover, a study of the kinetics of the incorporation of both precursors makes likely the hypothesis that at least a part of the “cement” derived from nucleocytoplasmic transfer. Since the biogenesis of mitochondria results from the complementary functioning of the two protein synthesic systems, the cytoplasmic one, which is preponderant, and the mitochondrial one, the mitochondrial groups seem to be the direct visualization of the contribution of the nuclear genome to the edification of new mitochondria.L'étude par autoradiographie à haute résolution de l'incorporation d'uridine et d'acides aminés tritiés par les groupements mitochondriaux, formations caractéristiques de la plupart des cellules germinales en début de gamétogenèse, a été effectuée dans les spermatocytes de tanche. Elle permet de confirmer la nature partiellement protéique du ciment intermitochondrial, et de mettre enévidence, pour la première fois par autoradiographie, la présence d'ARN dans ce ciment . En outre, l'étude cinétique de l'incorporation des deux catégories de précurseurs rend fort vraisemblable l'hypothèse de l'origine d'une partie au moins du ciment par transfert nucléocytoplasmique. La biogenèse des mitochondries résultant du fonctionnement complémentaire de deux systèmes de synthèse protéique, l'un prépondérant, cytoplasmique, l'autre minoritaire, mitochondrial, les groupements mitochondriaux semblent bien être une visualisation directe de la contribution du génome nucléaire à l'édification de mitochondries nouvelles.     

Quelques aspects du métabolisme des acides gras à longue chaîne par les cellules bathmotropes de cœur de rat en culture

As a preliminary to the study of the metabolism of erucic acid by beating heart cells of post natal rats in culture, the activity of lipoprotein lipase and the oxidation of palmitic acid have been studied. The results have led us to use 14 day cultures as the material of choice for experiments on the incorporation of erucic acid into cardiac cells, and on its subsequent distribution into different classes of lipid. Work on fatty acid oxidation has been carried out on 5–8 day cultures.We have shown that erucic acid enters cardiac muscle cells, but that the cells are not capable of oxidizing it directly.We have suggested two independent mechanisms by which this is done, namely shortening of the chain followed by the complete utilization of this smaller molecules by β-oxidation. The delay which this implies would explain the accumulation of erucic acid in the heart cells.We have also proposed that the accumulation of large quantities of erucic acid in phospholipids and esters of cholesterol may modify the structure of cellular and mitochondrial membranes, thus explaining the pathological effects of erucic acid.