NMR and conformational studies of linear and cyclic oligo-(1→6)-β-D-glucosamines

The conformational behavior of a series of linear and cyclic oligo-(1→6)-β-D-glucosamines and their N-acetylated derivatives, which are related to fragments of natural poly-N-acetylglucosamine, was studied by theoretical molecular modeling and experimental determination of transglycosidic vicinal coupling constants (3)J(C,H) and (3)J(H,H). Molecular dynamics simulations were performed under several types of conditions varying in the consideration of ionization of amino groups, solvent effect, and temperature. Neural network clustering and asphericity calculations were performed on the basis of molecular dynamics data. It was shown that disaccharide fragments in the studied linear oligosaccharides were not rigid, and tended to have several conformers, thus determining the overall twisted shape with helical elements. In addition, it was found that the behavior of C5-C6 bond depended significantly upon the simulation conditions. The cyclic di-, tri-, and tetrasaccharides mostly had symmetrical ring-shaped conformations. The larger cycles tended to adopt more complicated shapes, and the conformational behavior of their disaccharide fragments was close to that in the linear oligosaccharides.     

NMR and conformational studies of linear and cyclic oligo-(1→6)-β-d-glucosamines

The conformational behavior of a series of linear and cyclic oligo-(1→6)-β-d-glucosamines and their N-acetylated derivatives, which are related to fragments of natural poly-N-acetylglucosamine, was studied by theoretical molecular modeling and experimental determination of transglycosidic vicinal coupling constants ³J_C,H and ³J_H,H. Molecular dynamics simulations were performed under several types of conditions varying in the consideration of ionization of amino groups, solvent effect, and temperature. Neural network clustering and asphericity calculations were performed on the basis of molecular dynamics data. It was shown that disaccharide fragments in the studied linear oligosaccharides were not rigid, and tended to have several conformers, thus determining the overall twisted shape with helical elements. In addition, it was found that the behavior of C5–C6 bond depended significantly upon the simulation conditions. The cyclic di-, tri-, and tetrasaccharides mostly had symmetrical ring-shaped conformations. The larger cycles tended to adopt more complicated shapes, and the conformational behavior of their disaccharide fragments was close to that in the linear oligosaccharides.     

Effects of Bacillus Bacteria on Activity of Pathogen-Induced Proteins and Wheat Resistance to Bunt Caused by Tilletia caries (DC.) Tul.

Russian Journal of Plant Physiology - Effects of presowing seed treatment of Triticum aestivum L. and Tr. timopheevii Zhuk. wheat with bacteria Bacillussubtilis and B. thuringiensis were studied....     

A Nanoscale Modification of Materials at Thermoplasmonic Laser-Induced Backside Wet Etching of Sapphire

Plasmonics - Laser-induced backside wet etching using water solution of plasmon precursor (AgNO3) as an absorbing medium provides effective structuring of such a complex material as sapphire. At...     

Effects of age,territoriality and breeding on survival of Bonelli’s Eagle Aquila fasciata

Survival typically contributes most to population trends in long‐lived birds and its accurate estimation is therefore vital for population management and conservation. We evaluated the effects of age, territoriality and reproduction on survival in Bonelli’s Eagle Aquila fasciata through multistate capture‐mark‐recapture analyses on a long‐term dataset. Monitoring was carried out in southeast France (1990–2008) and involved the surveying of territorial Eagles, the marking of fledged chicks, and the recording of resightings and recoveries of marked non‐territorial and territorial birds. Survival improved with age, but territoriality was not retained in the best model; yearly survival was estimated at 0.479 for fledglings (to 1 year of age), 0.570 for 1‐ and 2‐year‐olds, and 0.870 for 3‐year‐old and older individuals. The second best model supported a further increase in survival from 3‐year‐olds (0.821) to older individuals (0.880). In the third best supported model, territoriality enhanced survival, but only in 2‐year‐olds (0.632 vs. 0.562 for non‐territorial). We found no correlation between the previous breeding stage and future survival, consistent with the long lifespan of the study species. Nevertheless, 4‐year‐old and older successful breeders were more likely to breed the following year than failed adult breeders (0.869 vs. 0.582), suggesting that the cost of reproduction is small in comparison with the variation in quality among individuals or their territories.     

A new Late Jurassic turtle from Spain: phylogenetic implications,taphonomy and palaeoecology

Abstract: The Jurassic was an important period in the evolution of Testudinata and encompasses the origin of many clades, and this is especially true of Jurassic turtles from Western Europe. A new genus and species of Late Jurassic turtle, Hispaniachelys prebetica gen. et sp. nov. from the upper Oxfordian of the Prebetic (Southern Spain), is described on the basis of postcranial material. The specimen is the only known tetrapod from the Mesozoic of the Prebetic and the oldest turtle from southern Europe. A mosaic of characters indicates this is a new genus: it displays basal features including dorsal epiplastral processes/reduced cleithra, no medial contact of the extragulars and a long first thoracic rib, alongside derived characters including an absence of mesoplastra and the vertebral 3/4 sulcus crossing neural 5. The phylogenetic position of the new taxon is hard to resolve, and it might be either a paracryptodire or a basal testudine, but it is distinct from Plesiochelys. A complex taphonomic history is shown by a range of overlying grazing traces and bioerosion on the carapace. The carapace was subsequently overturned and buried ventrally up, terminating grazing activity, and was then bored by sponges before final burial. Scanning electron microscopy reveals phosphatic microspheroids associated with bacterial decay in the vascular cavities of the cancellous bone, suggesting the carapace may have acted as a closed microenvironment in which decay‐derived authigenic minerals formed.     

Peculiarities of dopamine receptors on the membrane of multipolar spinal cord neurons of the brook lamprey <Emphasis Type="Italic">Lampetra planeri</Emphasis>

On isolated multipolar neurons of spinal cord of amniocoete (larva of the brook lamprey Lampetra planeri) by the patch-clamp method in configuration “the whole cell,” a modulating effect of dopamine on potential-activated Na⁺ currents was studied. Application of dopamine (10 μM) was shown to produce a complex action on the sodium current amplitude. In some cases a decrease of the amplitude, on average, by 13.5 ± 2.2% was found, while in others—an increase, on average, by 8.6 ± 6.1%. The modulation dopamine effect was not accompanied by any changes either of the threshold of the current appearance or of resistance of neuronal cell membranes. Pharmacological analysis with use of dopamine agonist has shown that the agonist of D1-receptors (−)-SKF-38393 (10 μM) decreases the Na+ current amplitude, whereas the agonist of D2-receptors (−)-quinpirole (10 μM) can produce in different cells both an increase, by 30.7 ± 17.0%, and a decrease, by 13.2 ± 3.1%, of the Na+ current amplitude. The obtained data indicate the existence of D1-and D2-receptors on the membrane of multipolar spinal neurons of the amniocoete (larva of the brook lamprey). Study of action of antagonists has shown that the antagonist of D1-receptors (+)-SCH-23390 (10 μM) does not affect action of the agonist of D1-receptors (−)-SKF-38393 (10 μM); the antagonist of D2-receptors (−)-sulpiride (10 μM) blocks completely effects both of the agonist of D1-receptors (−)-SKF-38393 (10 μM) and of the agonist of D2-receptors (−)-quinpirole (10 μM). The antagonist of D1-receptors (+)-SCH-23390 (10 μM) produced no effect on action of the agonist of D1-receptors (−)-SKF-38393 (10 μM). The obtained data indicate peculiarities of dopamine receptors of Cyclostomata as compared with those in mammals. Original Russian Text ? A. A. Bukinich, E. A. Tsvetkov, and N. P. Vesselkin, 2007, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2007, Vol. 43, No. 1, pp. 39–45.     

BAG-1 associates with Hsc70.Tau complex and regulates the proteasomal degradation of Tau protein

Intraneuronal accumulation of phosphorylated Tau protein is a molecular pathology found in many forms of dementia, including Alzheimer disease. Research into possible mechanisms leading to the accumulation of modified Tau protein and the possibility of removing Tau protein from the system have revealed that the chaperone protein system can interact with Tau and mediate its degradation. Hsp70/Hsc70, a member of the chaperone protein family, interacts with Tau protein and mediates proper folding of Tau and can promote degradation of Tau protein under certain circumstances. However, because Hsp70/Hsc70 has many binding partners that can mediate its activity, there is still much to discover about how Hsp70 acts in vivo to regulate Tau protein. BAG-1, an Hsp70/Hsc70 binding partner, has been implicated as a mediator of neuronal function. In this work we show that BAG-1 associates with Tau protein in an Hsc70-dependent manner. Overexpression of BAG-1 induced an increase in Tau levels, which is shown to be due to an inhibition of protein degradation. We further show that BAG-1 can inhibit the degradation of Tau protein by the 20 S proteasome but does not affect the ubiquitination of Tau protein. RNA-mediated interference depletion of BAG-1 leads to a decrease in total Tau protein levels as well as promoting hyperphosphorylation of the remaining protein. Induction of Hsp70 by heat shock enhanced the increase of Tau levels in cells overexpressing BAG-1 but induced a decrease of Tau levels in cells that were depleted of BAG-1. Finally, BAG-1 is highly expressed in neurons bearing Tau tangles in a mouse model of Alzheimer disease. This data suggests a molecular mechanism through which Tau protein levels are regulated in the cell and possible consequences for the pathology and treatment of Alzheimer disease.     

The interaction between glycine and GABA postsynaptic effects in the spinal cord neurons of frog Rana temporaria

Patch-clamp study in the whole multipolar cell (presumably motoneuron) was performed, the cells having been mechanically isolated from the spinal cord of the frog Rana ridibunda. It was shown that GABA and glycine, when applied simultaneously, produced a transmembrane current. Its amplitude was lower than the summed amplitude of currents produced in the same neuron by separate applications of GABA and glycine. The investigation of this occlusion showed that the superfusion of the neurons with solution containing 0.2 mM of glycine totally blocked the responses to GABA (5 mM) application, and vice versa. The crossinhibition can lie in the basis of this phenomenon. It could be due to either the existence of a common receptor complex sensitive to both GABA and glycine or to interaction between GABA and glycine receptors.     

Vinflunine, a novel microtubule inhibitor, suppresses calmodulin interaction with the microtubule-associated protein STOP

Vinca alkaloids vinblastine and vincristine and some of their derivatives such as vinorelbine are widely used in therapy of leukemia and several solid tumors. Their action is associated with alterations of the mitotic spindle functions that prevent the cell cycle progression and lead to mitotic block. A number of studies show that some Vinca alkaloids inhibit CaM-target interaction. The newest microtubule inhibitor, vinflunine (Javlor), currently in clinical trials, is remarkably more active than vinblastine against a number of tumors. Moreover, vinflunine is significantly less toxic than other Vinca alkaloids. The high antitumor activity of this molecule is not well understood since it binds to tubulin with an overall affinity several-fold lower than that of vinblastine or vincristine. In this study, we examined the interaction of Ca2+-CaM with vinflunine, vinblastine, and stable tubule only polypeptide (STOP) by using a combination of thermodynamic and mass spectrometric approaches. We characterized the influence of Vinca alkaloids on Ca2+-CaM-STOP complex formation. Our results revealed different binding modes to Ca2+-CaM for vinflunine and vinblastine, highlighting that adding fluorine atoms on the cleavamine moiety of the Vinca alkaloid molecule is critical for the localization of the drug on calmodulin. We demonstrate that vinflunine is a better inhibitor for STOP binding to calmodulin than vinblastine. We suggest that vinflunine action on calmodulin can have an effect on microtubule dynamics. These data may contribute to a better understanding of the superior antitumor efficiency and lower toxicity of vinflunine.