Galantamine antiacetylcholinesterase activity in rat brain influenced by L-carnitine

Galantamine (GAL) is a selective, competitive and reversible acetylcholinesterase (AChE) inhibitor, which increases the activity of the cholinergic system and hence gives rise to an improvement of cognitive functions in patients suffering from dementia of Alzheimer type. L-Carnitine (CAR) is a natural component of the mammalian tissue and is known to increase penetration of some chemical compounds/groups across biological membranes. The aim of this study was to evaluate the influence of pretreatment with CAR on AChE inhibition caused by GAL in selected brain parts in rat (basal ganglia, septum, frontal cortex, hippocampus) and in hypophysis, which does not lay beyond the blood-brain-barrier. During the first stage of the study, GAL was administered i.m. in different doses ranging from 2.5 to 10 mg/kg. The highest degree of AChE dose dependent inhibition was observed in hypophysis, while that in CNS was lower and became apparent in frontal cortex and hippocampus only after the administration of the dose of 10 mg/kg i.m. In the second stage, CAR was administered daily during 3 consecutive days at a dose of 250 mg/kg p.o. prior to the administration of GAL (10 mg/kg i.m.). Pretreatment with CAR enhanced trend of AChE inhibition in all selected brain parts comparing with single GAL administration, however, significant difference was not observed. Comparing these results with control group, statistical significance was found in frontal cortex, hippocampus and hypophysis.     

Degeneration of a production strain ofstreptomyces erythreus

Коммуникации занимается дегенерации производства штамма Streptomyces erythreus. Новые Jare представлены выводы:

1. (1)
   Штамма включает в себя как sporogenous и asporogenous морфологических компонент, каждая из которых может быть делится на подтипы далее. По оценке производственной деятельности индивидуального морфологические подтипов было показано что sporogenous компонент культуры включает в себя лиц, в то время производственного asporogenous компонент включает в себя только непроизводственной или с низким уровнем производственного лиц. Микроскопического изучения показали, что sporogenous подтипов формируется прямо вегетативной hyphae, в то время как asporogenous подтипов формируется толще и сморщенное вегетативной hyphae.     

PKCeta is required for beta1gamma2/beta3gamma2- and PKD-mediated transport to the cell surface and the organization of the Golgi apparatus

Protein kinase D (PKD) binds to a pool of diacylglycerol (DAG) in the TGN and undergoes a process of activation that involves heterotrimeric GTP-binding protein subunits betagamma to regulate membrane fission. This fission reaction is used to generate transport carriers at the TGN that are en route to the cell surface. We now report that PKD is activated specifically by G protein subunit beta1gamma2 and beta3gamma2 via the Golgi apparatus-associated PKCeta. Compromising the kinase activity of PKCeta-inhibited protein transport from TGN to the cell surface. Expression of constitutively activated PKCeta caused Golgi fragmentation, which was inhibited by a kinase inactive form of PKD. Our findings reveal that betagamma, PKCeta, and PKD act in series to generate transport carriers from the TGN and their overactivation results in complete vesiculation of the Golgi apparatus.     

Molecular dynamics simulations of glycosyltransferase LgtC

Molecular dynamics simulations have been performed on fully solvated alpha-(1-->4)-galactosyltransferase LgtC from Neisseria meningitidis with and without the donor substrate UDP-Gal and in the presence of the manganese ion. The analysis of the trajectories revealed a limited movement in the loop X (residues 75-80) and a larger conformational change in the loop Y (residues 246-251) in the simulation, when UDP-Gal was not present. In this case, the loops X and Y open by almost 10A, exposing the active site to the solvent. The 'hinge region' responsible for the opening is composed of residues 246-247. We have also analyzed the behavior of the manganese ion in the simulations. The coordination number is 6 when UDP-Gal is present and it increases to 7 when it is absent. In the latter case, three water molecules become coordinated to the ion. In both cases, the coordination is very stable implying that the manganese ion is tightly bound in the active site of the enzyme even if UDP-Gal is not present. Further analysis of the structural water molecules location confirmed that the mobility of water molecules in the active site and the accessibility of this site for solvent are higher in the absence of the substrate.     

Conformational analysis of complex oligosaccharides: the CICADA approach to the uromodulin O-glycans

Uromodulin is the pregnancy-associated Tamm-Horsfall glycoprotein, with the enhanced ability to inhibit T-cell proliferation. Pregnancy-associated structural changes mainly occur in the O-glycosylation of this glycoprotein. These include up to 12 glycan structures, made up of an unusual core type 2 sequence terminated with one, two, or three sialyl Lewis(x) sequences; this type of O-glycans could serve as E- and P-selectin ligands. The present work focuses on the most complex one; a tetradecamer made up of a type 2 core carrying three sialyl Lewis(x) branches. Five different monosaccharides are assembled by 14 glycosidic linkages. The conformational behavior of the constituting disaccharide segments was evaluated using the flexible residue procedure of the MM3 molecular mechanics procedure. For each disaccharide, the adiabatic energy surface, along with the local energy minima were established. All these results were used for the generation, prior to complete optimization of the tetradecamer. This was followed by a complete exploration of conformational hyperspace throughout the use of the single coordinate method as implemented in the CICADA program. Despite the potential flexibility of the tetradecasaccharide, only four conformational families occur, accounting for more than 95% of the total low energy conformations. For each family, the molecular properties (electrostatic, lipophilicity, and hydrogen potential) were studied. The shape of the tetradecasaccharide is best described as a flat ribbon, flanked by three branches having terminal sialyl residues. Two of the branches interact through nonbonded interactions, bringing further energy stabilization, and limiting the conformational flexibility of the sialyl residues. Only one branch maintains the original conformational features of sialyl Lewis(x). This O-glycan can be seen as a fascinating example of 'dendrimeric' structure, where the spatial arrangement of three S-Le(x) epitopes may favor its complementary 'presentations' for the interactions with E- and P-selectins.     

Finite element modeling and simulations in orthopedics: a bibliography 1998-2005

The paper gives a bibliographical review of the finite element modeling and simulations in orthopedics from the theoretical as well as practical points of view. The bibliography lists references to papers, conference proceedings and theses/dissertations that were published between 1998 and 2005. At the end of this paper 1264 references are given dealing with subjects as: bones and their parts, special tissues; spine mechanics; movable joints and computational modeling.     

Optimisation of n-octyl oleate enzymatic synthesis over Rhizomucor miehei lipase

Octyl oleate is a useful organic compound with several applications in cosmetic, lubricant and pharmaceutical industry. At first, the enzymatic synthesis of n-octyl oleate by direct lipase-catalysed esterification of oleic acid and 1-octanol was investigated in a stirred batch reactor in solvent-free system. A systematic screening and optimisation of the reaction parameters were performed to gain insight into the kinetics mechanism. Particularly, enzyme concentration, reaction temperature, stirrer speed, water content, substrates concentration and molar ratio were optimised with respect to the final product concentration and reaction rate. The kinetics mechanism of the reaction was investigated. Finally, a comparison of the experimental results obtained in a solvent free-system with those using two different solvents, supercritical carbon dioxide (SC-CO₂) and n-hexane, was proposed. It resulted that in SC-CO₂ higher concentration of the desired product was attained, requiring lower enzyme concentrations to achieve comparable conversion of free fatty acid into fatty acid ester.