Saccharin exposure increases the potency and aversive property of naloxone in drug-naive rats

In naive rats previously given saccharin (0.1%) as the only drinking fluid for 14 days, naloxone produced a conditioned taste aversion at a dose (0.09 mg/kg, SC) that had little or no effect in normal controls. The magnitude of this effect of the saccharin increased between 2 and 7 days after cessation of the treatment. Under these experimental conditions, evidence of an interaction between the saccharin exposure and a naloxone response was also seen with rectal temperature measurements. Therefore, in rats having no history of morphine, previous consumption of saccharin may potentiate various actions of naloxone including its aversive property.     

Catecholamines decrease leukotriene B4 and increase thromboxane B2 synthesis in A23187-stimulated human whole blood.

Catecholamines (adrenaline, dopamine, isoprenaline, noradrenaline) and caffeic acid (catecholic compound without adrenergic receptor activity) decreased leukotriene (LT)B4 synthesis in A23187-stimulated human whole blood. Salbutamol, a non-catecholic beta 2-adrenergic agonist, did not influence LTB4 synthesis. Catecholamines stimulated thromboxane (TX)B2 synthesis with a concomitant inhibition of LTB4 synthesis; caffeic acid and salbutamol did not stimulate TXB2 synthesis. These results, obtained in A23187-stimulated whole blood, which also takes into account the complex interaction between different cell types, are similar to our previous results with polymorphonuclear leukocytes. Catecholamines show an opposite effect on lipoxygenase and cyclooxygenase pathways, which may give rise to a marked change in LT/TX ratio in physiological or pathological conditions where sufficient concentrations of catecholamines are present.     

Preference conditioning produced by opioid active and inactive isomers of levorphanol and morphine in rat

Using taste and place preference conditioning, the present study examined the motivational properties produced in adult rats by systemic administration of (-) and (+) morphine, levorphanol, and dextrorphan. Conditioned place preference was stereospecific; it was only produced by the opioid receptor active isomers, levorphanol and (-) morphine. Similarly, a conditioned taste preference produced by a low dose of morphine was only seen with the active isomer. Conditioned taste aversion, however, was produced in a comparable dose range by both the active and the inactive isomers. In addition injections of inactive isomers also produced tolerance to the taste aversion produced by (-) morphine. Therefore, administration of both opioid active and inactive isomers of opioid agonists are unconditioned stimuli for the production of preference behaviors. In addition, it was concluded that the appetitive reinforcing properties of these drugs, seen as taste and place preferences, appear to require activation of specific opioid receptors, whereas the aversive effects, seen as taste aversion may also involve other mechanisms.     

Tracking interactions that stabilize the dimer structure of starch phosphorylase from Corynebacterium callunae. Roles of Arg234 and Arg242 revealed by sequence analysis and site-directed mutagenesis.

Glycogen phosphorylases (GPs) constitute a family of widely spread catabolic alpha1,4-glucosyltransferases that are active as dimers of two identical, pyridoxal 5'-phosphate-containing subunits. In GP from Corynebacterium callunae, physiological concentrations of phosphate are required to inhibit dissociation of protomers and cause a 100-fold increase in kinetic stability of the functional quarternary structure. To examine interactions involved in this large stabilization, we have cloned and sequenced the coding gene and have expressed fully active C. callunae GP in Escherichia coli. By comparing multiple sequence alignment to structure-function assignments for regulated and nonregulated GPs that are stable in the absence of phosphate, we have scrutinized the primary structure of C. callunae enzyme for sequence changes possibly related to phosphate-dependent dimer stability. Location of Arg234, Arg236, and Arg242 within the predicted subunit-to-subunit contact region made these residues primary candidates for site-directed mutagenesis. Individual Arg-->Ala mutants were purified and characterized using time-dependent denaturation assays in urea and at 45 degrees C. R234A and R242A are enzymatically active dimers and in the absence of added phosphate, they display a sixfold and fourfold greater kinetic stability of quarternary interactions than the wild-type, respectively. The stabilization by 10 mm of phosphate was, however, up to 20-fold greater in the wild-type than in the two mutants. The replacement of Arg236 by Ala was functionally silent under all conditions tested. Arg234 and Arg242 thus partially destabilize the C. callunae GP dimer structure, and phosphate binding causes a change of their tertiary or quartenary contacts, likely by an allosteric mechanism, which contributes to a reduced protomer dissociation rate.     

Tolerance to morphine analgesia and immobility measured in rats by changes in log-dose-response curves

Using the bar and tailflick tests, morphine log-dose-response (LDR) curves were determined for immobility and analgesia, respectively, in male Wistar rats following 15 daily i.p. injections of 0, 20, or 200 mg/kg of morphine sulfate. The LDR curves for the two measures were qualitatively similar. Chronic morphine treatment resulted in a shift to the right and flattening of both curves. These results indicate that the flattening of the LDR curve in morphine tolerant rats is general to a number of opiate effects, and raise the possibility that both morphine-produced immobility and analgesia are subserved, in part, by a similar mechanism. In addition, after a test dose of 900 mg/kg, more rats in the 20 mg/kg than in the 200 mg/kg treatment group died of convulsions. Thus, tolerance developed to lethality produced by the convulsive effects of opiates.     

Task-Based Core-Periphery Organization of Human Brain Dynamics

As a person learns a new skill, distinct synapses, brain regions, and circuits are engaged and change over time. In this paper, we develop methods to examine patterns of correlated activity across a large set of brain regions. Our goal is to identify properties that enable robust learning of a motor skill. We measure brain activity during motor sequencing and characterize network properties based on coherent activity between brain regions. Using recently developed algorithms to detect time-evolving communities, we find that the complex reconfiguration patterns of the brain''s putative functional modules that control learning can be described parsimoniously by the combined presence of a relatively stiff temporal core that is composed primarily of sensorimotor and visual regions whose connectivity changes little in time and a flexible temporal periphery that is composed primarily of multimodal association regions whose connectivity changes frequently. The separation between temporal core and periphery changes over the course of training and, importantly, is a good predictor of individual differences in learning success. The core of dynamically stiff regions exhibits dense connectivity, which is consistent with notions of core-periphery organization established previously in social networks. Our results demonstrate that core-periphery organization provides an insightful way to understand how putative functional modules are linked. This, in turn, enables the prediction of fundamental human capacities, including the production of complex goal-directed behavior.     

Fine root classification matters: nutrient levels in different functional categories,orders and diameters of roots in boreal Pinus sylvestris across a latitudinal gradient

Plant and Soil - Any grouping of tree species concerned with SOC sequestration should include trees that are as homogeneous as possible in their carbon sequestration. We propose a classification of...     

An integrated approach to the ligand binding specificity of Neisseria meningitidis M1 alanine aminopeptidase by fluorogenic substrate profiling,inhibitory studies and molecular modeling

Neisseria meningitides is a gram-negative diplococcus bacterium and is the main causative agent of meningitis and other meningococcal diseases. Alanine aminopeptidase from N. meningitides (NmAPN) belongs to the family of metallo-exopeptidase enzymes, which catalyze the removal of amino acids from the N-terminus of peptides and proteins, and are found among all the kingdoms of life. NmAPN is suggested to be mostly responsible for proteolysis and nutrition delivery, similar to the orthologs from other bacteria.