Difference of binding modes among three ligands to a receptor mSin3B corresponding to their inhibitory activities

A preceding experiment suggested that a compound, which inhibits binding of the REST/NRSF segment to the cleft of a receptor protein mSin3B, can be a potential drug candidate to ameliorate many neuropathies. We have recently developed an enhanced conformational sampling method, genetic-algorithm-guided multi-dimensional virtual-system-coupled canonical molecular dynamics, and in the present study, applied it to three systems consisting of mSin3B and one of three compounds, sertraline, YN3, and acitretin. Other preceding experiments showed that only sertraline inhibits the binding of REST/NRSF to mSin3B. The current simulation study produced the spatial distribution of the compounds around mSin3B, and showed that sertraline and YN3 bound to the cleft of mSin3B with a high propensity, although acitretin did not. Further analyses of the simulation data indicated that only the sertraline–mSin3B complex produced a hydrophobic core similar to that observed in the molecular interface of the REST/NRSF-mSin3B complex: An aromatic ring of sertraline sunk deeply in the mSin3B’s cleft forming a hydrophobic core contacting to hydrophobic amino-acid residues located at the bottom of the cleft. The present study proposes a step to design a compound that inhibits competitively the binding of a ligand to its receptor.

Difference of Binding Modes Among Three Ligands to a Receptor mSin3B Corresponding to Their Inhibitory Activities

A preceding experiment suggested that a compound, which inhibits binding of the REST/NRSF segment to the cleft of a receptor protein mSin3B, can be a potential drug candidate to ameliorate many neuropathies. We have recently developed an enhanced conformational sampling method, genetic-algorithm-guided multi-dimensional virtual-system-coupled canonical molecular dynamics, and in the present study, applied it to three systems consisting of mSin3B and one of three compounds, sertraline, YN3, and acitretin. Other preceding experiments showed that only sertraline inhibits the binding of REST/NRSF to mSin3B. The current simulation study produced the spatial distribution of the compounds around mSin3B, and showed that sertraline and YN3 bound to the cleft of mSin3B with a high propensity, although acitretin did not. Further analyses of the simulation data indicated that only the sertraline–mSin3B complex produced a hydrophobic core similar to that observed in the molecular interface of the REST/NRSF–mSin3B complex: An aromatic ring of sertraline sunk deeply in the mSin3B’s cleft forming a hydrophobic core contacting to hydrophobic amino-acid residues located at the bottom of the cleft. The present study proposes a step to design a compound that inhibits competitively the binding of a ligand to its receptor.

Elimination of the type B uncertainty

An uncertainty of an estimated parameter can be, in general, decomposed into two parts, i.e. an uncertainty caused by errors in the actual experiment (the type A uncertainty) and an uncertainty caused by errors in preceding experiment, where some wanted constants were estimated (the type B uncertainty). These constants are necessary for an estimation of the useful parameters.The aim of the paper is to find a condition for elimination of the type B uncertainty.

243 Vegetative Growth of Malus domestica sp. Enhanced with the Use of the Mycorrhizal Fungus Glomus intraradices

Two experiments with Malus domestica sp. were planted in 1997 at the Laval Univ. experimental farm located south of the St. Lawrence river near Quebec City. These experiments examined the association of the mycorrhizal fungus Glomus intraradices with Malus domestica sp. The first experiment compared the vegetative growth of `McIntosh' apple trees on M.106 rootstock in presence or absence of a commercial inoculum of G. intraradices (Premier Tech, Riviere-du-Loup, Quebec) under three levels of phosphorus fertilization (P) to the soil (0%, 50%, and 100% of the usual recommandation for this crop). After two seasons, all the treatments had better growth than the control (0% P without G. intraradices). The best treatment was achieved with 100% of the P associated with mycorrhizal inoculation. The second experiment compared the vegetative growth of three apple rootstocks Bud.9, M.26, and M.106, inoculated with G. intraradices under the same three P levels as the preceding experiment. Uninoculated rootstocks receiving the usual phosphorus fertilization served as control. Two roostocks, M.26 and M.106, increased growth with G. intraradices, while the third one, Bud.9, did not respond to the presence of mycorrhizal fungus.

Interactions between postprandial thermogenesis, sensory stimulation of feeding, and hunger

An early thermogenic response has been described following the ingestion of palatable food. This study was designed to investigate the possible relationship between this so-called cephalic response, the sensory stimulation of feeding, and the declining feeling of hunger as the meal progresses. O2 consumption, carbohydrate and lipid oxidation, as well as ratings of hunger were measured in four experimental situations in which the subjects, after overnight fast, ate either two small caramel cakes at one time or the same amount of calories divided in eight portions that were eaten at 10-min intervals. The third experiment, the sham-feeding experiment, was similar to the last one except that the food was spit out instead of being swallowed after being chewed. A control experiment was added in which no food was given but during which the subject mimicked the act of chewing as was done in the preceding experiment. A small increase in O2 consumed was observed in the control experiment. After the one-meal experiment, the increase was larger for the first 90 min and declined thereafter. During the first 40 min of the sham-feeding experiment, O2 consumption increased more than when the eight meals were eaten, indicating that during this period the sensory stimulation per se is responsible for the cephalic thermic response to food. At 90 min, the ratings of hunger were diminished not only in the eight meals experiment but in the eight sham meals experiment as well, showing the role of sensory stimulation in the control of hunger. These results indicate a possible causal relationship between the cephalic thermogenesis, the control of hunger, and the prandial sensory stimulations.

Effect of thermal history of aqueous solutions of KCl on the metastable zone width

The metastable zone width of an aqueous solution of KCI was measured as a function of the time and temperature of overheating above the equilibrium solubility temperature. It has been found that when the experiments follow close upon one another, the parameters of the preceding experiment affect the results of the experiment to follow.The results are interpreted in terms of hypotheses advanced in the literature to account for the effect of thermal history of solution. The plausibility and applicability of these hypotheses are assessed for the given cause of aqueous solution of a well soluble electrolyte.

189. The effect of commercial sterilization on the nutritive value of milk. VI. Comparison of the total nutritive value of raw and commercially sterilized milks

1. The effect of commercial sterilization on the total nutritive value of milk was studied in five separate experiments.2. In the first experiment raw and sterilized milks supplemented with minerals were given in equal amounts to pairs of litter-mate male rats. No differences were found in the growth performance of the rats, but the rats on sterilized milk consumed it more readily than their mates on raw milk. This difference was statistically significant.3. Rats getting limited but equal amounts of milk in addition to a basal diet which supplied only protein, energy and minerals grew better on raw than on sterilized milk.4. When the basal diet contained in addition 5% brewer's yeast and the milk intakes were the same as in the previous experiment no difference was found between the two groups.5. Rats receiving raw milk to which 15 g. of cane sugar was added per 100 ml. grew better than rats receiving equal quantities of similarly treated sterilized milk.6. Rats given raw milk containing 30 g. per 100 ml. of sugar grew as well as the rats on sterilized milk in the preceding experiment, but rats receiving similarly treated sterilized milk took much less milk than the raw milk rats, grew very poorly and some of them developed symptoms of beri-beri.7. The difference between raw and sterilized milk is discussed and it is concluded that in these experiments on the total nutritive value of milk vitamin B1 was the first limiting factor of sterilized milk.

Some remarks on the mechanism of respiration

1. In performing some experiments on recently slaughtered animals, for the elucidation of a subject which I was then engaged in investigating, I was struck with the remarkable arched tension of the diaphragm, a condition which continued unabated until air was admitted into the pleural spaces, and then it became flaccid and descended. This altered condition was attended by collapse of the lungs, which receded from the thoracic walls, and occupied a much smaller space than previously. 2. In order to measure the quantity of air expelled from the lungs in the preceding experiment, and to ascertain how far the collapse of the., lungs and the altered condition of the diaphragm were dependent on each other, the following experiment was performed. The trachea of a sheep, immediately after death, was exposed in the neck, divided, and tied over a glass tube, which was put in communication with a graduated receiver placed under water, and guarded by a stopcock. The pleurae were then opened, and as air entered the diaphragm became flaccid; but the lungs remained unchanged in position and form. The stopcock was then opened, and a rush of air, displacing the water in the receiver, was accompanied by collapse of the lungs. The quantity of air thus forcibly expelled was from ten to twelve cubic inches.

A further list of the specific gravitys of bodys, being inproportion as the following numbers

The last Experiment was tryd with another quantity of quicksilver, which had been used in water in the preceding experiment : however I rather trust the last, for that I found a small mistake (tho' here in the calculation allowed for,) in the weight of the glass containig the Quicksilver in the tryal before.