Obtenção e caracterização óptica e elétrica de 'La''Ta'O IND.4' e LiTaO Ind.3 puros e dopados com Eu POT.3+

Eletronicalceramics are used in many applications such as: multilayer capacitor, transducer, pyroelectric sensors and electrooptic devices. In recent years there has been a growing demand for eletronicalceramics with better performance and functionality. This demand has accelerated the development of synthesis techniques to produce powders with well-defined particle size, shape and crystallinity. The eletronicalceramics in the form of bulk are determined by their performance characteristics of the powders used and the preparation process. So, physical and chemical properties of powders, such as chemical control of stoichiometry, purity, homogeneity, particle size and shape should be observed when choosing the methods of synthesis. Among the techniques used so far, the polymeric precursor method, also known as Pechini, has been considered ideal for the preparation of nanosized powders. Thus, this research project aims to use the polymeric precursor method to prepare powders of lithium tantalate and lanthanum tantalate, with good chemical stability. In this aspect is proposed to investigate the effects of variation of the concentration of europium about the properties of tantalate because doping with Eu3 + indicates that they may occupy different sites in the crystal structure, as in the case of LiTaO3. Effects of things like occupation sites, stability of phases and formation temperature have been previously investigated by the group, which motivated the formulation of this project. Our proposal aims to introduce the Eu3 + LaTaO4 and LiTaO3 and study the structural and optical properties of the powders obtained by Pechini method, as well as correlate these studies with the electrical properties of the material, mainly the Ironelectricty Hysteresis.

Design, synthesis and the effect of 1,2,3-triazole sialylmimetic neoglycoconjugates on Trypanosoma cruzi and its cell surface trans-sialidase

This work describes the synthesis of a series of sialylmimetic neoglycoconjugates represented by 1,4-disubstituted 1,2,3-triazole-sialic acid derivatives containing galactose modified at either C-1 or C-6 positions, glucose or gulose at C-3 position, and by the amino acid derivative 1,2,3-triazole fused threonine-3-O-galactose as potential TcTS inhibitors and anti-trypanosomal agents. This series was obtained by Cu(I)-catalysed azide-alkyne cycloaddition reaction ('click chemistry') between the azido-functionalized sugars 1-N(3)-Gal (commercial), 6-N(3)-Gal, 3-N(3)-Glc and 3-N(3)-Gul with the corresponding alkyne-based 2-propynyl-sialic acid, as well as by click chemistry reaction between the amino acid N(3)-ThrOBn with 3-O-propynyl-GalOMe. The 1,2,3-triazole linked sialic acid-6-O-galactose and the sialic acid-galactopyranoside showed high Trypanosoma cruzi trans-sialidase (TcTS) inhibitory activity at 1.0 mM (approx. 90%), whilst only the former displayed relevant trypanocidal activity (IC(50) 260 mu M). These results highlight the 1,2,3-triazole linked sialic acid-6-O-galactose as a prototype for further design of new neoglycoconjugates against Chagas' disease. (C) 2011 Elsevier Ltd. All rights reserved.

Protein quality control disruption by PKC beta II in heart failure: rescue by the selective PKC beta II inhibitor, beta IIV5-3

Myocardial remodeling and heart failure (HF) are common sequelae of many forms of cardiovascular disease and a leading cause of mortality worldwide. Accumulation of damaged cardiac proteins in heart failure has been described. However, how protein quality control (PQC) is regulated and its contribution to HF development are not known. Here, we describe a novel role for activated protein kinase C isoform beta II (PKC beta II) in disrupting PQC. We show that active PKC beta II directly phosphorylated the proteasome and inhibited proteasomal activity in vitro and in cultured neonatal cardiomyocytes. Importantly, inhibition of PKC beta II, using a selective PKC beta II peptide inhibitor (beta IIV5-3), improved proteasomal activity and conferred protection in cultured neonatal cardiomyocytes. We also show that sustained inhibition of PKC beta II increased proteasomal activity, decreased accumulation of damaged and misfolded proteins and increased animal survival in two rat models of HF. Interestingly, beta IIV5-3-mediated protection was blunted by sustained proteasomal inhibition in HF. Finally, increased cardiac PKC beta II activity and accumulation of misfolded proteins associated with decreased proteasomal function were found also in remodeled and failing human hearts, indicating a potential clinical relevance of our findings. Together, our data highlights PKC beta II as a novel inhibitor of proteasomal function. PQC disruption by increased PKC beta II activity in vivo appears to contribute to the pathophysiology of heart failure, suggesting that PKC beta II inhibition may benefit patients with heart failure. (218 words)

One-Pot, Three-Step Reaction of 5-[(Trimethylsilyl)ethynyl]pyrrolidin-2-one with Azides Catalyzed by Cu-I: Synthesis of a Novel Class of 1,4-Disubstituted 1,2,3-Triazoles

A very fast, easy and efficient synthesis is described for a novel and biologically important class of 1,4-disubstituted-4-(5-pyrrolidin-2-one)-1,2,3-triazoles by an ultrasound-assisted one-pot, three-step click reaction sequence of 5-[(trimethylsilyl)ethynyl]pyrrolidin-2-one with organic azides mediated by catalytic Cu-I salts.

Biochemische Charakterisierung des Exopolysaccharids von Pediococcus parvulus B399, sowie dessen Hydrolyse durch eine neue beta-1,3-Glucanase aus Delftia sp. MV01

In der vorliegenden Arbeit wurde die erste β-1,3-Glucanase aus Delftia beschrieben. Es konnte gezeigt werden, dass das Enzym unter anderem gegen das nur schwer zu hydrolysierende Exopolysaccharid aus Pediococcus parvulus wirkte. rnrnIm Einzelnen wurde zunächst das Exopolysaccharid aus Pediococcus parvulus B399 aus einem eigens zusammengestellten β-Glucan-Synthesemedium (Medium M) isoliert und gereinigt. Anschließend erfolgte eine umfassende Charakterisierung des Biopolymers. Hierzu gehörten neben der sauren Hydrolyse zur Bestimmung der Monomerzusammensetzung des Polymers, auch spektroskopische Methoden, darunter 1H und 13C-NMR. Mithilfe der NMR-Spektroskopie konnte die Struktur des Exopolysaccharids aus Pediococcus parvulus B399 bestimmt werden. Es handelte sich hierbei ebenfalls um ein β-1,3(1,2)-Glucan, wie es bereits für Pediococcus parvulus 2.6 beschrieben wurde. Darüber hinaus wurde erstmals ein ATR-FTIR-Spektrum für ein Exopolysaccharid aus Pediokokken gezeigt. Über GPC-Messungen konnte auch die molekulare Größe des β-1,3(1,2)-Glucans aus Pediococcus parvulus B399 bestimmt werden. Es wurde nachgewiesen, dass sich das Exopolysaccharid bei Anzucht in Medium M aus einer hochmolekularen Fraktion (5*106 g/mol) und vier niedermolekularen Fraktionen (347; 818; 10048 und 20836 g/mol) zusammensetzte. Neben der strukturellen Charakterisierung, wurde das Exopolysaccharid auch rheologisch untersucht. Dabei konnte festgestellt werden, dass es sich durch seine schwach gelbildenen Eigenschaften auch zum Einsatz in der Lebensmittelindustrie als Stabilisator, Fettersatzmittel oder ähnliches eignen würde. Die erwähnte gelbildende Netzwerkstruktur konnte für das Exopolysaccharid aus Pediococcus parvulus B399 auch erstmals im AFM bestätigt werden. rnEin weiterer Teil der Arbeit umfasste ein breites Screeningverfahren nach einem geeigneten Organismus, der das Exopolysaccharid aus Pediococcus parvulus B399 effektiv hydrolysieren sollte. Aus einer Anreicherungskultur des Termitendarms (Wenzel et al., 2002), konnte Delftia sp. MV01 isoliert werden. Dieser Organismus produzierte bei Wachstum in β glucanhaltigem Medium (Exopolysaccharid aus Pediococcus parvulus B399, sowie weitere kommerziell erhältliche β-1,3-Glucane) eine Glucanase, die in folgenden Schritten konventionell gereinigt und charakterisiert wurde.

The ω3-polyunsaturated fatty acid derivatives AVX001 and AVX002 directly inhibit cytosolic phospholipase A(2) and suppress PGE(2) formation in mesangial cells

ω3-polyunsaturated fatty acids (ω3-PUFAs) are known to exert anti-inflammatory effects in various disease models although their direct targets are only poorly characterized.

Highly potent 4-amino-indolo[2,3-c]azepin-3-one-containing somatostatin mimetics with a range of sst receptor selectivities

The synthesis, biological evaluation, and conformational analysis of 4-amino-indolo[2,3-c]azepin-3-one (Aia)-containing SRIF mimetics are reported. Different subtype selectivities are observed depending on the N- and C-terminal substituents of the D-Aia-Lys dipeptide mimetic. An sst(5)-selective analogue with subnanomolar binding affinity was obtained that is the most potent agonist reported to date. A nonselective mimetic with high potency was also identified. This study allows a better definition of the bioactive conformation of the essential D-Trp side chain in the somatostatin pharmacophore.

Insights into the bromination of 3-aryl-5-methyl-isoxazole-4-carboxylate: Synthesis of 3-aryl-5-bromomethyl-isoxazole-4-carboxylate as precursor to 3-aryl-5-formyl-isoxazole-4-carboxylate

Results of the detailed investigations on the bromination of the methyl group of 3-aryl-5-methyl-isoxazole-4-carboxylate a precursor to obtain 3-aryl-5-formyl-isoxazole-4-carboxylate are described. The products generated during the study have been utilized as substrates for the syntheses of isoxazole-fused heterocycles.

Studies toward the construction of substituted piperidine-2-ones and pyridine-2-ones from Baylis-Hillman adducts: Discovery of a facile synthesis of 5-methyl-4-oxo-6-aryl-3-aza-bicyclo[3.1.0]hexane-1-carboxylates

Studies toward the construction of functionalised piperidone derivatives from derivatives of Baylis-Hillman adducts are described. Interestingly the 6-oxo-4-aryl-piperidine-3-carboxylates generated during the study serve as precursor for the facile synthesis of 4-oxo-6-aryl-3-aza-bicyclo[3.1.0]hexane-1-carboxylates

Adenosine Kinase of T. b. Rhodesiense identified as the putative target of 4-[5-(4-phenoxyphenyl)-2H-pyrazol-3-yl]morpholine using chemical proteomics

BACKGROUND: Human African trypanosomiasis (HAT), a major parasitic disease spread in Africa, urgently needs novel targets and new efficacious chemotherapeutic agents. Recently, we discovered that 4-[5-(4-phenoxyphenyl)-2H-pyrazol-3-yl]morpholine (compound 1) exhibits specific antitrypanosomal activity with an IC(50) of 1.0 microM on Trypanosoma brucei rhodesiense (T. b. rhodesiense), the causative agent of the acute form of HAT. METHODOLOGY/PRINCIPAL FINDINGS: In this work we show adenosine kinase of T. b. rhodesiense (TbrAK), a key enzyme of the parasite purine salvage pathway which is vital for parasite survival, to be the putative intracellular target of compound 1 using a chemical proteomics approach. This finding was confirmed by RNA interference experiments showing that down-regulation of adenosine kinase counteracts compound 1 activity. Further chemical validation demonstrated that compound 1 interacts specifically and tightly with TbrAK with nanomolar affinity, and in vitro activity measurements showed that compound 1 is an enhancer of TbrAK activity. The subsequent kinetic analysis provided strong evidence that the observed hyperactivation of TbrAK is due to the abolishment of the intrinsic substrate-inhibition. CONCLUSIONS/SIGNIFICANCE: The results suggest that TbrAK is the putative target of this compound, and that hyperactivation of TbrAK may represent a novel therapeutic strategy for the development of trypanocides.

Reduced bone breakage and increased bone strength in free range laying hens fed omega-3 polyunsaturated fatty acid supplemented diets

INTRODUCTION The omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are the immediate precursors to a number of important mediators of immunity, inflammation and bone function, with products of omega-6 generally thought to promote inflammation and favour bone resorption. Western diets generally provide a 10 to 20-fold deficit in omega-3 PUFAs compared with omega-6, and this is thought to have contributed to the marked rise in incidence of disorders of modern human societies, such as heart disease, colitis and perhaps osteoporosis. Many of our food production animals, fed on grains rich in omega-6, are also exposed to a dietary deficit in omega-3, with perhaps similar health consequences. Bone fragility due to osteoporotic changes in laying hens is a major economic and welfare problem, with our recent estimates of breakage rates indicating up to 95% of free range hens suffer breaks during lay. METHODS Free range hens housed in full scale commercial systems were provided diets supplemented with omega-3 alpha linolenic acid, and the skeletal benefits were investigated by comparison to standard diets rich in omega-6. RESULTS There was a significant 40-60% reduction in keel bone breakage rate, and a corresponding reduction in breakage severity in the omega-3 supplemented hens. There was significantly greater bone density and bone mineral content, alongside increases in total bone and trabecular volumes. The mechanical properties of the omega-3 supplemented hens were improved, with strength, energy to break and stiffness demonstrating significant increases. Alkaline phosphatase (an osteoblast marker) and tartrate-resistant acid phosphatase (an osteoclast marker) both showed significant increases with the omega-3 diets, indicating enhanced bone turnover. This was corroborated by the significantly lower levels of the mature collagen crosslinks, hydroxylysyl pyridinoline, lysyl pyridinoline and histidinohydroxy-lysinonorleucine, with a corresponding significant shift in the mature:immature crosslink ratio. CONCLUSIONS The improved skeletal health in laying hens corresponds to as many as 68million fewer hens suffering keel fractures in the EU each year. The biomechanical and biochemical evidence suggests that increased bone turnover has enhanced the bone mechanical properties, and that this may suggest potential benefits for human osteoporosis.