Insights into the physiological function of cellular prion protein

Prions have been extensively studied since they represent a new class of infectious agents in which a protein, PrPsc (prion scrapie), appears to be the sole component of the infectious particle. They are responsible for transmissible spongiform encephalopathies, which affect both humans and animals. The mechanism of disease propagation is well understood and involves the interaction of PrPsc with its cellular isoform (PrPc) and subsequently abnormal structural conversion of the latter. PrPc is a glycoprotein anchored on the cell surface by a glycosylphosphatidylinositol moiety and expressed in most cell types but mainly in neurons. Prion diseases have been associated with the accumulation of the abnormally folded protein and its neurotoxic effects; however, it is not known if PrPc loss of function is an important component. New efforts are addressing this question and trying to characterize the physiological function of PrPc. At least four different mouse strains in which the PrP gene was ablated were generated and the results regarding their phenotype are controversial. Localization of PrPc on the cell membrane makes it a potential candidate for a ligand uptake, cell adhesion and recognition molecule or a membrane signaling molecule. Recent data have shown a potential role for PrPc in the metabolism of copper and moreover that this metal stimulates PrPc endocytosis. Our group has recently demonstrated that PrPc is a high affinity laminin ligand and that this interaction mediates neuronal cell adhesion and neurite extension and maintenance. Moreover, PrPc-caveolin-1 dependent coupling seems to trigger the tyrosine kinase Fyn activation. These data provide the first evidence for PrPc involvement in signal transduction

Insights into the physiological function of cellular prion protein

Prions have been extensively studied since they represent a new class of infectious agents in which a protein, PrPsc (prion scrapie), appears to be the sole component of the infectious particle. They are responsible for transmissible spongiform encephalopathies, which affect both humans and animals. The mechanism of disease propagation is well understood and involves the interaction of PrPsc with its cellular isoform (PrPc) and subsequently abnormal structural conversion of the latter. PrPc is a glycoprotein anchored on the cell surface by a glycosylphosphatidylinositol moiety and expressed in most cell types but mainly in neurons. Prion diseases have been associated with the accumulation of the abnormally folded protein and its neurotoxic effects; however, it is not known if PrPc loss of function is an important component. New efforts are addressing this question and trying to characterize the physiological function of PrPc. At least four different mouse strains in which the PrP gene was ablated were generated and the results regarding their phenotype are controversial. Localization of PrPc on the cell membrane makes it a potential candidate for a ligand uptake, cell adhesion and recognition molecule or a membrane signaling molecule. Recent data have shown a potential role for PrPc in the metabolism of copper and moreover that this metal stimulates PrPc endocytosis. Our group has recently demonstrated that PrPc is a high affinity laminin ligand and that this interaction mediates neuronal cell adhesion and neurite extension and maintenance. Moreover, PrPc-caveolin-1 dependent coupling seems to trigger the tyrosine kinase Fyn activation. These data provide the first evidence for PrPc involvement in signal transduction

Synthesis, spectroscopic characterization, DFT studies and biological assays of a novel gold(I) complex with 2-mercaptothiazoline

A new gold(I) complex with 2-mercaptothiazoline (MTZ) with the coordination formula [AuCN(C3H5NS2)] was synthesized and characterized by chemical and spectroscopic measurements, DFT studies and biological assays. Infrared (IR) and 1H, 13C and 15N nuclear magnetic resonance (NMR) spectroscopic measurements indicate coordination of the ligand to gold(I) through the nitrogen atom. Studies based on DFT confirmed nitrogen coordination to gold(I) as a minimum of the potential energy surface with calculations of the hessians showing no imaginary frequencies. Thermal decomposition starts at temperatures near 160°C, leading to the formation of Au0 as the final residue at 1000°C. The gold(I) complex with 2-mercaptothiazoline (Au-MTZ) is soluble in dimethyl sulfoxide (DMSO), and is insoluble in water, methanol, ethanol, acetonitrile and hexane. The antibacterial activities of the Au-MTZ complex were evaluated by an antibiogram assay using the disc diffusion method. The compound showed an effective antibacterial activity against Staphylococcus aureus (Gram-positive) and Escherichia coli and Pseudomonas aeruginosa (Gram-negative) bacterial cells. Biological analysis for evaluation of the cytotoxic effect of the Au-MTZ complex was performed using HeLa cells derived from human cervical adenocarcinoma. The complex presented a potent cytotoxic activity, inducing 85% of cell death at a concentration of 2.0 μmol L-1.301323542359CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP141617/2010-12006/55367-

Reproduction of a South American population of pumpkinseed sunfish Lepomis gibbosus (Linnaeus) (Osteichthyes, Centrarchidae): a comparison with the European and North American populations

The reproductive biology of the introduced pumpkinseed sunfish Lepomis gibbosus (Linnaeus, 1758) in the Custódio's Dam, rio Doce high basin, state of Minas Gerais, Brazil was studied from February/2001 to March/2002 and compared with introduced and native populations. Reproduction occurred almost along the entire period of study with a high frequency of fishes in the advanced ripening/mature and spawned/spent stages. The microscopic analyses indicated that the pumpkinseed sunfish presents multiple spawning. The egg diameter of the Brazilian population is similar to the Spanish, Greek and American ones. The standard length at maturity and the gonadosomatic index of the introduced populations are smaller when compared with native ones. The spawning season of the Brazilian population was the longest among all comparisons made in the present work.<br>Estudou-se de fevereiro/2001 a março/2002 a biologia reprodutiva da exótica perca-sol Lepomis gibbosus (Linnaeus, 1758) na represa do Custódio, bacia do alto rio Doce, Brasil, comparando-a à de populações exóticas e nativas. A reprodução ocorreu praticamente ao longo de todo o período de estudo e a análise microscópica de ovários indicou desova do tipo parcelada para a espécie. O diâmetro ovocitário da população brasileira é semelhante à espanhola, grega e americana. O comprimento padrão na maturidade e o índice gonadossomático de populações introduzidas são menores do que as nativas. O período de desova da população brasileira foi o maior dentre todas as populações analisadas no presente trabalho