Farmacocinética pré-clínica e avaliação toxicológica preliminar da nova tiazolidinadiona desenvolvida para o tratamento do diabetes mellitus tipo 2: 5-(4-cloro-benzilideno)-3-(4-metil-benzil)-tiazolidina-2,4-diona (GQ-2)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

First genome sequence of St. Louis encephalitis virus (SLEV) isolated from a human in Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Atypical manifestations in Brazilian patients with neuro-Behcet's disease

Type and frequency of systemic and neurologic manifestations of Beh double dagger et's disease (BD) vary with ethnicity. In Brazil, BD occurs as sporadic cases. We describe clinical and radiological features of 36 Brazilian patients of mixed ethnicity with neuro-Beh double dagger et's disease (NBD). Medical records of 178 BD patients were reviewed and 36 (20%) NBD patients were identified. Twenty-one NBD patients (58.3%) were female and 27 (75%) presented with parenchymal manifestations. Brainstem involvement was the most common neurologic syndrome (41.7%). Seizures (27.8%), isolated aseptic meningitis (16.7%), optic neuropathy (ON) (16.7%), cerebral venous thrombosis (CVT) (8.3%), peripheral neuropathy (2.8%), and spinal cord involvement (5.6%) were other neurologic manifestations observed among Brazilian NBD patients. Eighteen (50%) had at least one relapse, and isolated aseptic meningitis was the most common relapsing manifestation. No significant differences concerning the number of relapses between parenchymal and non-parenchymal groups were found. A multivariate model including disease duration, cell count in spinal fluid, cyclosporine use, immunosuppressive use at disease onset, age at NBD onset, and ON did not reveal any significant associations with NBD relapse. There was a low frequency of CVT and an unexpected higher number of isolated aseptic meningitis. Brazilian NBD patients present more parenchymal and atypical manifestations, and relapse more often than NBD patients from other populations.

Grain-size distribution and frictional behaviour of sediment cores from the Nice Slope

The upper shelf of the landslide-prone Ligurian Margin (Western Mediterranean Sea) off Nice well-known for the 1979 Airport Landslide is a natural laboratory to study preconditioning factors and trigger mechanisms for submarine landslides. For this study low-stress ring shear experiments have been carried out on a variety of sediments from >50 gravity cores to characterise the velocity-dependent frictional behaviour. Mean values of the peak coefficient of friction vary from 0.46 for clay-dominated samples (53 % clay, 46 % silt, 1 %) sand up to 0.76 for coarse-grained sediments (26 % clay, 57 % silt, 17 % sand). The majority of the sediments tested show velocity strengthening regardless of the grain size distribution. For clayey sediments the peak and residual cohesive strength increases with increasing normal stress, with values from 1.3 to 10.6 kPa and up to 25 % of all strength supported by cohesive forces in the shallowmost samples. A pseudo-static slope stability analysis reveals that the different lithologies (even clay-rich material with clay content >=50 %) tested are stable up to slope angles <26° under quasi-drained conditions.

Genetic Interactions between KAR7/SEC71, KAR8/JEM1, KAR5, and KAR2 during Nuclear Fusion in Saccharomyces cerevisiae

During mating of Saccharomyces cerevisiae, two nuclei fuse to produce a single diploid nucleus. Two genes, KAR7 and KAR8, were previously identified by mutations that cause defects in nuclear membrane fusion. KAR7 is allelic to SEC71, a gene involved in protein translocation into the endoplasmic reticulum. Two other translocation mutants, sec63-1 and sec72Δ, also exhibited moderate karyogamy defects. Membranes from kar7/sec71Δ and sec72Δ, but not sec63-1, exhibited reduced membrane fusion in vitro, but only at elevated temperatures. Genetic interactions between kar7 and kar5 mutations were suggestive of protein–protein interactions. Moreover, in sec71 mutants, Kar5p was absent from the SPB and was not detected by Western blot or immunoprecipitation of pulse-labeled protein. KAR8 is allelic to JEMI, encoding an endoplasmic reticulum resident DnaJ protein required for nuclear fusion. Overexpression of KAR8/JEM1 (but not SEC63) strongly suppressed the mating defect of kar2-1, suggesting that Kar2p interacts with Kar8/Jem1p for nuclear fusion. Electron microscopy analysis of kar8 mutant zygotes revealed a nuclear fusion defect different from kar2, kar5, and kar7/sec71 mutants. Analysis of double mutants suggested that Kar5p acts before Kar8/Jem1p. We propose the existence of a nuclear envelope fusion chaperone complex in which Kar2p, Kar5p, and Kar8/Jem1p are key components and Sec71p and Sec72p play auxiliary roles.

Two redundant systems maintain levels of resident proteins within the yeast endoplasmic reticulum.

The Saccharomyces cerevisiae gene ERD2 is responsible for the retrieval of lumenal resident proteins of the endoplasmic reticulum (ER) lost to the next secretory compartment. Previous studies have suggested that the retrieval of proteins by ERD2 is not essential. Here, we find that ERD2-mediated retrieval is not an essential process only because, on its failure, a second inducible system acts to maintain levels of ER proteins. The second system is controlled by the ER membrane-bound kinase encoded by IRE1. We conclude that IRE1 and ERD2 together maintain normal concentrations of resident proteins within the ER.

Kitab alhidayaḧ ili faraʾiṫs alḳulub = Sefer Torat Ḥovot ha-levavot /

"Die dritte, vierte und fünfte Pforte des Naturbetrachtung, des Gottesdienstes und des Gottvertrauens".

Impacto de la resiliencia en pacientes con Artritis Reumatoide

Introducción: La artritis reumatoide (AR) es una enfermedad autoinmune-inflamatoria, que compromete las articulaciones diartrodiales. Tiene una importante repercusión sistémica que incluye la depresión; por lo tanto, tiene un severo impacto sobre la calidad de vida. Es posible que mecanismos de defensa, tales como la resiliencia, puedan amortiguar dicho impacto. Metodología: estudio de corte transversal, multicéntrico (análisis inicial dentro del grupo AR, con muestra no probabilística de 66 pacientes, posterior selección aleatoria simple de 16 pacientes de la muestra inicial y selección de 16 individuos sanos pareados). Posteriormente, se comparó la resiliencia entre sujetos con AR y sujetos sanos, mediante las escalas RS y CD-RISC25. Adicionalmente, se aplicaron las escalas EEAE, EADZ, SF-36 y PANAS. Los datos fueron evaluados mediante el coeficiente de correlación de Spearman, las pruebas U Mann-Whitney, Kruskall-Wallis, T de Student y análisis de varianza. Resultados: se encontraron diferencias significativas en las estrategias de afrontamiento no espirituales en grupos de resiliencia baja, media y alta; diferencias en las medianas de resiliencia en los grupos de depresión por EAZD en los pacientes. No se encontraron resultados significativos en las variables clínicas de la AR ni en la comparación con sujetos sanos. Conclusiones: el uso de estrategias de afrontamiento no espirituales y la ausencia de depresión, se asoció a mayores niveles de resiliencia en los pacientes con AR, por lo cual, los componentes emocionales y cognitivos se asocian a la resiliencia.