Polymorphic Aβ42 fibrils adopt similar secondary structure but differ in cross-strand side chain stacking interactions within the same β-sheet.

Formation of polymorphic amyloid fibrils is a common feature in neurodegenerative diseases involving protein aggregation. In Alzheimer's disease, different fibril structures may be associated with different clinical sub-types. Structural basis of fibril polymorphism is thus important for understanding the role of amyloid fibrils in the pathogenesis and progression of these diseases. Here we studied two types of Aβ42 fibrils prepared under quiescent and agitated conditions. Quiescent Aβ42 fibrils adopt a long and twisted morphology, while agitated fibrils are short and straight, forming large bundles via lateral association. EPR studies of these two types of Aβ42 fibrils show that the secondary structure is similar in both fibril polymorphs. At the same time, agitated Aβ42 fibrils show stronger interactions between spin labels across the full range of the Aβ42 sequence, suggesting a more tightly packed structure. Our data suggest that cross-strand side chain packing interactions within the same β-sheet may play a critical role in the formation of polymorphic fibrils

Baicalin Weakens Staphylococcus aureus Pathogenicity by Targeting Sortase B

Staphylococcus aureus (S. aureus) is a human and other animal pathogen that contributes to the primary etiology of nosocomial pneumonia, a disease with high mortality rates and costs. Treatment of multidrug-resistant S. aureus infection is extremely challenging, and new therapeutic strategies beyond antibiotic treatment are needed. Anti-virulence agents that specifically target the molecular determinants of virulence may be a novel method for treating drug-resistant nosocomial infections. Sortase B (SrtB) is a crucial virulence factor in S. aureus and plays an important role during infection. In this study, we find that baicalin suppresses the activity of SrtB. Minimum inhibitory concentration and growth curve assays confirmed that baicalin has no anti-S. aureus properties. We performed live/dead, lactate dehydrogenase (LDH), adherence, and enzyme-linked immunosorbent assays to confirm that baicalin reduced human alveolar epithelial A549 cell injury caused by S. aureus, reduced the adherence of S. aureus to A549 cells, and significantly attenuated the inflammatory response of mouse macrophage J774 cells to S. aureus. Additionally, we were able to elucidate the binding mechanics and identify the interacting sites of baicalin and SrtB via a molecular dynamics simulation, site-directed mutagenesis, and fluorescence spectroscopy quenching. Finally, we confirmed that baicalin directly binds to the active center of SrtB, and the residues Asn92 and Tyr128 perform an important function in the interaction of SrtB and baicalin. Taken together, these data indicate that baicalin is a promising candidate to combat S. aureus infections

Os sistemas de informação como ferramenta de controle na gestão de estacionamentos em shoppings

Orientador : Luiz Carlos SouzaMonografia (especialização) - Universidade Federal do Paraná, Setor de Ciências Sociais Aplicadas. Curso de Especialização em Contabilidade e FinançasInclui referênciasResumo : A pesquisa em tela trata da analise das ferramentas utilizadas pela controladoria na gestão de estacionamentos em shoppings centers, visando demonstrar os tipos de relatórios gerados pelos sistemas de gerenciamento desenvolvidos por empresas especializadas em software focado em tecnologias de gestão em estacionamentos. Observado que atualmente, grande parte dos gestores da área de gestão direcionada a estacionamento, tem dificuldade de desenvolver fatores de informação ao qual forneça dados comparativos e financeiros em que os gestores consigam elaborar projeções e estratégias visando maior retorno financeiro e amenizando as despesas operacionais. A pesquisa em questão trata também da importância da controladoria e os setores envolvidos e interligados, buscando cada vez mais ampliar o índice de informações que envolvem a operacionalidade, as metas a ser atingidas pela gestão do negócio