Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The electronic properties of the active-sites of the structurally unrelated serine peptidases, alpha-chymotrypsin and subtilisin, have been expressed in the form of three-dimensional electrostatic potential maps derived from integrals calculated at the quantum chemistry level. As a consequence of the asymmetrical distribution of the secondary structures that occur within a 7 A sphere around the serine of the catalytic triad, the active sites are highly polarized entities and exhibit large dipole moments. One part of the active sites generates a nucleophilic suction-pump. Its isocontour at -10 kcal mol-1 defines an impressive, negatively-charged volume which bears a narrow channel in the immediate vicinity of the active-site serine 195 in alpha-chymotrypsin or 221 in subtilisin. In native alpha-chymotrypsin, there is a perfect complementation between this nucleophilic suction-pump and the positively-charged electrophilic hole that is generated by the backbone NH of Ser 195 and Gly 193. In subtilisin, generation of the complementing electrophilic hole requires binding of a carbonyl donor ligand and may be achieved by rotation of the side-chain amide of Asn 155 towards the backbone NH of Ser 221. Small variations in the atomic co-ordinates of alpha-chymotrypsin used for the calculations, the presence of water molecules in its active site and the occurrence of point mutations in the amino acid sequence of subtilisin have little effects on the shape and characteristics of the electrostatic potential.
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PMID:Electrostatic potential maps at the quantum chemistry level of the active sites of the serine peptidases, alpha-chymotrypsin and subtilisin. 220 58

Thirsty rats were trained to press a lever for either a sucrose solution or saline before performance was tested in extinction while the animals were either hungry alone or experiencing both hunger and a sodium appetite. Reinforcer-specific motivational control was observed in that the animals trained with the sucrose solution pressed more than those trained with the saline when they were tested hungry, but not when they were tested under combined hunger and sodium appetite. In order to assess the role of a Pavlovian incentive process in this effect, thirsty animals received non-contingent pairings of one stimulus with the sucrose solution and another with saline in the second experiment. In an extinction test the sucrose stimulus augmented lever pressing relative to the saline stimulus when the animals were hungry, but not when they were thirsty. In the subsequent experiments the contribution of the Pavlovian process was equated by giving concurrent training with both incentives. Lever pressing and chain pulling were reinforced concurrently, one with the sucrose solution and the other with saline, while the animals were thirsty. Once again, the animals pressed more in extinction if this action had been trained with the sucrose solution rather than the saline, but only if they were hungry rather than thirsty. Thus, instrumental performance across a thirst-to-hunger shift can also be controlled by an instrumental incentive process. The direct engagement of the instrumental process by this motivational shift contrasts to the absence of such control following a hunger-to-thirst transition (Dickinson & Dawson, 1987a), a fact attributed to the asymmetrical motivational interactions produced by water and food deprivation.
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PMID:Motivational control of instrumental performance following a shift from thirst to hunger. 228 40

1. The performance of brown egg laying hens was compared under conventional and asymmetrical interrupted-lighting conditions. 2. Egg numbers and mean weight were similar under the two conditions, provided the apparent day perceived by the hen was the same under both lighting treatments. 3. Daily food intakes of intermittently-illuminated hens were not significantly lower than those of conventionally-lit birds. However, the reductions were of the magnitude reported in the literature and observed under commercial conditions. 4. Shell quality was unaffected by interrupted lighting in the period up to 60 weeks of age in two of the 4 genotypes studied. All breeds had lower shell weights under interrupted lighting in the last three months of lay. 5. Intermittently-lit hens had lower body weights, which approached significance, and significantly less carcase fat. There were no differences in ash, protein (N x 6.25) or water contents of the carcases, or in fat content at a given body weight. 6. There were no significant differences in the production responses of the 4-brown-egg hybrids to interrupted lighting. 7. Diets with differing concentrations of energy and protein were included in both trials, but there was no evidence of interaction between these nutritional treatments and the lighting treatments.
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PMID:Response of laying hens to asymmetrical interrupted lighting regimens: reproductive performance, body weight and carcase composition. 235 79

The cuticle of the gill lamina of the crayfish Astacus leptodactylus (E), mechanically isolated, was mounted in an Ussing chamber and examined for its electrical properties. The cuticle of the gill lamina obtained from exuviae had similar properties. When perfused with artificial fresh water (AFW) outside and Van Harreveld solution (VH) inside, the transcuticular potential Voi was negative with respect to the inside, and close to the equilibrium potential for Cl- (ECl-). CH3COO-, HCO3-, SO4(2-) and cations (Na+, K+, Ca2+, Mg2+ and NH4+) behaved as impermeant ions with respect to Cl-. A decrease of pH (brought about with CO2) from 8.5 to 6.0 in AFW, VH or both had no effect on the potential. The cuticle area specific conductance was 20-30 mS/cm2 when superfused with AFW outside and VH inside. The conductance decreased linearly with log [Cl-] when Cl- was replaced by CH3COO-. Rectification was obvious when internal Cl- was reduced to 5 mmol/l. The Cl- selectivity of the cuticle could also be demonstrated in perfusing the cuticle with a single salt (NaCl, KCl, CaCl2, MgCl2 or LaCl3) and in diluting that salt on one side of the preparation or in replacing Cl- by CH3COO-, SO4(2-) and HCO3-. The potential changed almost linearly with log [Cl-] and was close to ECl-. The inner face of the cuticle was found to be slightly less selective than the outer face. The relative permeabilities were calculated to be: PCl- = 1, PNa+ = 0.001, PHCO3- = 0.0006, PCH3COO- = 0.0002. The dilution of a Cl- -free salt resulted in a cationic potential. The relative permeabilities of cations (NH4+, K+, Na+, Ca2+ and Mg2+) were found to range within a factor 2. The permeability of the cuticle to HCO3-, CH3COO- and SO4(2-) was 2-5 times lower. The cuticle conductance was linearly related to the activity of the salt perfusing the two sides of the preparation at equal concentrations. The molar area specific conductance to chloride salts was 14 (mS/cm2)/(mmol/l). That of Cl- -free salts ranged from 1 to 20 (microS/cm2)/(mmol/l) depending on the salt used. It was deduced that PCl- is 2 X 10(-3) cm/s and that all the other ions tested have permeabilities of 10(-7)-10(-6) cm/s. With large intensity current pulses the cuticle exhibited rectifying properties and an asymmetrical behaviour. Increasing the pH of the perfusing solution reduced the transcuticular potential established with a Cl- gradient.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ionic permeabilities of the gill lamina cuticle of the crayfish, Astacus leptodactylus (E). 241 Jun 7

These experiments were designed to test the thesis that prostaglandins produced by the cortical collecting tubule cells could modulate the vasopressin-induced osmotic water permeability (Pf). The dose-response curve for vasopressin-sensitive Pf showed the Km to be 1 microU ml-1. Exogenous PGE2 and PGF2 alpha (0.1 microM) inhibited the Pf induced by 1 microU ml-1 vasopressin when they were present in the bath solution. PGE2 (0.1 microM) in the lumen failed to inhibit the normal vasopressin-induced Pf, thus indicating an asymmetrical effect. Exposure of the tubule to 10 microM meclofenamate following stimulation of Pf by 0.2, 1.0, 10, or 100 microU ml-1 vasopressin failed to further increase the Pf. Pretreatment with meclofenamate or arachidonic acid (AA) failed to produce a different Pf response from controls. Neither naproxen (10 microM) nor AA altered significantly the Pf induced by 1 microU ml-1 vasopressin while methylisobutylxanthine, as expected, significantly enhanced Pf. The stable endoperoxide analogs U-44069 and U-46619, which mimic the actions of thromboxane A2 in many systems and which can stimulate osmotic water flow in the toad bladder, had no effect on Pf. Acidifying the lumen to pH 5.2 enhanced the Pf induced by 1 microU ml-1 vasopressin but subsequent exposure to meclofenamate did not cause an additional increment. These experiments demonstrate that exogenous prostaglandins are effective only from the basolateral surface of the cortical collecting tubule; that endogenous prostaglandins, if produced by these epithelial cells, do not produce demonstrable effects on vasopressin-sensitive Pf; and that endogenously produced thromboxane is not the likely reason for these results. Finally, the cortical collecting tubule response to many factors modulating Pf is considerably different from salientian urinary bladders.
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PMID:Modulation of vasopressin-induced water permeability of the cortical collecting tubule by endogenous and exogenous prostaglandins. 241 98

Concentrations of dopamine, serotonin, and some of their metabolites were analyzed by means of high-performance liquid chromatography in brain samples obtained from rats operantly conditioned to use one paw for water-reinforced lever pressing. In the first experiment, the side of paw usage was determined by physical constraint (forced-handedness condition), whereas in the second experiment the side of paw usage was not restricted (paw-preference condition). Differences in dopamine metabolism were detected between brain samples from the hemispheres located ipsi- and contralaterally to the side of paw usage. A higher dopamine metabolism (indicated by higher metabolite/transmitter ratios) was found in the amygdala ipsilateral to the paw used both under the forced-handedness and paw-preference condition. A higher level of dopamine in the contralateral septum was found in rats sacrificed immediately after 15 min of forced-handedness and an ipsilateral increase was found in rats analyzed 2 h after performance of this task. In addition, a higher dopamine metabolism in the ventral striatum, dorsal striatum, and amygdala was found in the forced-handedness and yoked controls groups than in rats analyzed 2 h after lever pressing. In the second experiment, rats in the paw preference group had a lower dopamine metabolism in the ventral and dorsal striatum, septum, and substantia nigra than did their yoked controls. These results show that changes in dopamine metabolism during conditioned lever pressing can be asymmetrical with respect to the side of paw usage, indicating that the dopamine neurons in the two brain hemispheres are asymmetrically involved in such behavioral tasks.
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PMID:Asymmetries of brain dopamine metabolism related to conditioned paw usage in the rat. 244 21

Polyethylene glycols (PEG) with molecular weight less than or equal to 3000 were shown to effectively protect human erythrocytes from osmotic lysis induced by alpha-staphylotoxin (ST). PEG with MW less than 3000 do not change the conductivity of ion channels induced by ST in bilayer lipid membranes (BLM). Changing the bilayer from a pure phosphatidylcholine (PC) to a negatively charged phosphatidylserine (PS) film results in an asymmetry of the current-voltage characteristics. This is evidenced by the asymmetrical position of the ST-channel pore in bilayer membranes. The results obtained allow to conclude that the ST-channel is an interprotein pore filled with water (with an inner diameter of 2.5-3 nm and a length of approximately 10 nm). It is composed of six molecules of alpha-toxin from Staphylococcus aureus. The ST-channel incorporates into a membrane with only one mouth in contact with the polar lipid heads and the other one protruding 4.5-5 nm from the bilayer plane in water solution.
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PMID:The structure of Staphylococcus aureus alpha-toxin-induced ionic channel. 246 32

Focused acoustic shock waves were studied for their effects on human tumor cell viability, clonogenicity, and sensitivity to chemotherapeutic agents. The elastic shock waves used in this investigation were generated with the Dornier HM3-Lithotripter by underwater spark discharge with fixed electrical parameters employing a voltage of 18 kV and a capacitance of 80 nanoFarads. These waves are characterized by a fast varying compression phase, strong asymmetrical pressure and tension phases, and a maximum amplitude of roughly 10(8) Pascal (kg.m-1 s-2). Doses as high as 2000 focused shocks showed little effect on the viability of two different cell lines. There was, however, a dose dependent inhibition of tumor cell proliferation as determined by the growth of clones in soft agarose. Each of the two cell lines showed a unique degree of colony inhibition by shock waves. It was demonstrated that shock wave effects resulted from elastic shock wave interaction with the cells and were not caused by the emission of ultraviolet light coincident with shock wave generation. Shocks were applied at a rate of 100 minute-1 in a 200 l. water bath, thereby removing the possibility for temperature changes during treatments. After treatment with shock waves it was found that tumor cells became more sensitive to growth inhibition by chemotherapeutic agents. Cisplatin, doxorubicin, and 4-hydroperoxycyclophosphamide were each more effective in blocking cell growth after the target cells had been treated with acoustic shocks. Enhanced efficacies ranged from three to 10-fold potentiation of colony inhibition. These results indicate that weak shock waves, which can be focused to a defined target region, may have utility as a cancer treatment modality either alone or in combination with cytotoxic agents.
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PMID:Effect of acoustic shock waves on clonogenic growth and drug sensitivity of human tumor cells in vitro. 279 37

Temperature changes at different locations in the labyrinth were measured in human temporal bone preparations after syringing with water. In order to simulate physiological conditions, the preparations were placed in a water bath at 37 degrees C. The maximum temperature changes in the horizontal semicircular canal after syringing with temperatures symmetrical to body temperature (44 degrees or 30 degrees C) were found to be clearly asymmetrical (with mean values of 0.6 and -0.3K). From measurements in the external auditory meatus, findings showed that the reference temperature was 34 degrees C in front of the tympanic membrane, which explains the asymmetry recorded. Measurements at different locations showed that the temperature first changes in the regions of the ampullae of the horizontal and the superior semicircular canals. In the vestibule the onset and decay of the temperature change is delayed. The time courses of the temperature difference between locations demonstrate that the temperature difference across the horizontal semicircular canal, which would be responsible for any convective effect in the endolymph, is of shorter duration than the absolute temperature change, which would be responsible for any temperature-mediated volume changes.
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PMID:Conduction of thermal stimuli in the human temporal bone. 324 69

The urinary bladder epithelium in mammals, including humans, has a low permeability to ions and small molecules such as sodium, urea and water. Two structures, asymmetrical luminal plasma membrane and tight junction between superficial cells, have been said responsible for the urine-blood barrier. The permeability of junctional complex between superficial cells to lanthanum was observed in rat urinary bladder epithelium by transmission electron microscopy (TEM). In the normal bladder epithelium, confirmed by bacteriological examination, most junctions between superficial cells are the tight junctions and 1 to 9% of the junctions are leaky. The lanthanum, known to penetrate the leaky junctions, is demonstrated in the intercellular space between intermediate and basal cells. This suggests that desmosomes between these cells have no barrier function. In the experimentally inflammatory bladder epithelium all junctions are tight and no leaky junction is found between superficial cells. In contrast, if the superficial cells were stripped off in the inflammatory change, the lanthanum penetrates the junction between denuded intermediate cells. In the normal bladder epithelium the structural junctions between superficial cells have no changes during contraction and distension. Thus this suggests that the permeability to lanthanum does not change during contraction and distension.
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PMID:[Architectural ultrastructure of the urinary bladder epithelium. II. Changes in the urine-blood barrier in the contracted and distended state in the normal and inflammatory bladder]. 337 2


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