Effect of Tentoxin on the Activation and on the Catalytic Reaction of Reconstituted H+-ATPase from Chloroplasts

The proton-translocating ATPase from chloroplasts, CF0F1, was isolated, purified and reconstituted into asolectin liposomes. The effect of the energy transfer inhibitor, tentoxin, on different functions of the enzyme was investigated. Tentoxin does not inhibit the nucleotide release during energization by a pH /ΔΨ jump, i.e. the activation of the enzyme is not influenced. ATP synthesis driven by a pH /ΔΨ jump and multi-site ATP hydrolysis are completely inhibited by tentoxin, whereas uni-site ATP hydrolysis is not influenced

Synthese, Pharmakodynamik und Biotransformation des Fomocain-Derivats Oe 9000

2,2’-[4-(4-phenoxymethylphenyl)butylimino]diethanol (Oe 9000) is a highly potent local anesthetic related to fomocaine. It displays a long duration of the pharmacological action, low toxicity and is superior to fomocaine with regard to aqueous solubility and efficacy. In view of the development of new application forms, the elucidation of the biotransformation of the drug was required. Therefore, experiments with several biotransformation models including pig liver homogenates and precision cut liver slices from rats and a patient were conducted. Using specifically synthesized reference compounds eight phase I metabolites could be identified by LC(-MS). While in pig liver homogenates the oxidative N-deamination of the drug lead to the butyric acid derivative as main metabolite, in human and rat liver slices the N-oxidation of Oe 9000 was the predominant metabolizing reaction. Oe 9000, Oe 9000 metabolites and related compounds were examined in respect to their cytotoxicity as well as to their antioxidative and antimicrobial properties. In order to elucidate the mechanism of action of Oe 9000 we further characterized in patch clamp experiments on dorsal root ganglion cells of adult mice the strong inhibitory effect of the drug on tetrodotoxin resistant sodium currents

No Incidence of BRAF Mutations in Salivary Gland Carcinomas—Implications for Anti-EGFR Therapies

BRAF is the main effector of KRAS in the RAS-RAF-MAPK axis, a signaling pathway downstream of EGFR. The activation of this cascade is an important pathway in cancer development and is considered a key pathway for therapeutic molecules. Recent studies in metastatic colorectal cancer found that an oncogenic activation of BRAF by a point mutation in exon 15 (V600E) could bypass the EGFR-initiated signaling cascade with the effect that patients bearing the mutant BRAF allele are not likely to benefit from EGFR-targeted therapies. We designed an allele-specific PCR and screened 65 salivary gland carcinoma (SGC) of the main histopathological types for the BRAF V600E mutation. All 65 SGC in this cohort (100%) presented the BRAF wildtype. In a previous study, we found a KRAS wildtype in 98.5% of SGC. These findings imply that SGC rarely acquires mutations that result in a constitutive activation of the signaling cascade downstream of EGFR and this pleads in favor of further therapeutic trials with EGFR-targeting monoclonal antibodies

Antonieta de Barros: um história

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Filosofia e Ciências Humanas. Programa de Pós-Graduação em História.Antonieta de Barros é uma personagem feminina que inaugura o cenário político catarinense por ter sido eleita a primeira deputada na Assembléia Legislativa do Estado de Santa Catarina em um tempo (1934) e um espaço (um Estado onde não foram observados substanciais movimentos pró-sufrágio feminino) onde tal fato ainda estava muito distante da maioria das mulheres negras de nossa terra. Por ter representado, ainda que não intencionalmente, a quebra de estereótipos relacionados à etnia, classe social e gênero, acredito que sua trajetória tenha sido um marco na luta dos que se interessam em promover em nosso país uma democracia de fato, onde à todos, seja possível exercer os direitos da cidadania plena. Através da leitura de suas crônicas, propus-me observar os movimentos sociais, políticos, econômicos e culturais acontecidos no Brasil, sobretudo na década de trinta e sua repercussão em Florianópolis tentando manter o olhar da historiadora. Assim, este trabalho apresenta apenas uma parte da história de vida de Antonieta de Barros. Apresenta apenas uma, entre as tantas histórias possíveis de serem contadas

Antonieta de Barros – A Novidade do Voto Feminino em Santa Catarina na Década de Trinta

Getúlio Vargas conceded the right to vote for women by decree in 1932. This news created intensive debates at that time: divergences and convergences. Despite the female movement around the legitimacy of this conquest in Coinstitution to be sanctioned in 1934, the most of women from the state of Santa Catarina didn't get involve in such debates. Horever, righ here in this state, a black woman was elected as deputy (elective position) – the teacher Antonieta de Barros. The unique personality in the historiography from the State of Santa Catarina who represented the break of stereotypes to the ethnic, social class and gender

CELL SEPARATION AND GENE EXPRESSION ANALYSIS IN A TUMOR-STROMA INTERACTION MODEL

A novel technique for co-culturing and separating fibroblasts and carcinoma cells in a 2-D model of tumorstroma interaction is presented. The methodology is based on cell co-cultivation on an 1.35 μm thin membrane followed by rapid immunostaining and microdissection of the different cell compartments using a laser microdissection system (P.A.L.M. Microlaser Technologies AG, Germany). For identifying the tumor cell compartment, immunolabeling for a marker that is expressed only in epithelial tumor cells is performed. The RNA quality from the microdissected co-cultured cells was successfully proved by RT-PCR for a housekeeping gene transcript and for the laminin gamma 2 chain gene transcript used before in the tumor cell immunostaining. Laminin cDNA was amplificable only in tumor cells and not in the co-cultivated fibroblasts indicating no cell-cross-contamination during microdissection. Microdissected tumor and stroma cells from the presented membrane based co-culture model can be used for gene expression profiling and DNA based analysis in the investigation of tumor-stroma interactions

Anti factor H autoantibodies block C-terminal recognition function of factor H in hemolytic uremic syndrome

The atypical form of the kidney disease hemolytic uremic syndrome (aHUS) is associated with defective complement regulation. In addition to mutations in complement regulators, factor H (FH)-specific autoantibodies have been reported for aHUS patients. The aim of the present study was to understand the role of these autoantibodies in aHUS. First, the binding sites of FH autoantibodies from 5 unrelated aHUS patients were mapped using recombinant FH fragments and competitor antibodies. For all 5 autoantibodies, the binding site was localized to the FH C-terminus. In a functional assay, isolated patient IgG inhibited FH binding to C3b. In addition, autoantibody-positive patients' plasma caused enhanced hemolysis of sheep erythrocytes, which was reversed by adding FH in excess. These results suggest that aHUS-associated FH autoantibodies mimic the effect of C-terminal FH mutations, as they inhibit the regulatory function of FH at cell surfaces by blocking its C-terminal recognition region

Santa Catarina no caminho da Revolução de Trinta: memórias de combates (1929-1931)

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Filosofia e Ciências Humanas. Programa de Pós-Graduação em História.Quando em outubro de 1930 os políticos e militares dos estados do Rio Grande do Sul, Paraíba e Minas Gerais deflagraram o movimento que culminou naquilo que o repertório histórico convencionou designar como a Revolução de 1930, as tropas constituídas pelas Forças Revolucionárias do Rio Grande do Sul marcharam objetivando unir-se aos aliados e combater àqueles que então eram tidos como reacionários. O objetivo era chegar à então capital do Brasil e depor o presidente Washington Luiz. A estratégia consistia em concentrar toda a força revolucionária em Ponta Grossa, no Paraná, para, a partir dali, seguirem mais fortes rumo à capital, prevendo-se um confronto armado com as Forças Federais Legalistas em São Paulo. Mas o estado de Santa Catarina estava geográfica, política e militarmente no caminho das tropas gaúchas, pois seu governador, Fúlvio Aducci, manteve-se contra a Revolução e disposto a empreender defesa pela manutenção da ordem política vigente. Contudo, os próceres oligarcas liberais catarinenses a apoiavam e engrossavam o contingente das Forças Revolucionárias com homens e armas. O estado e o país foram divididos entre os grupos que eram simpáticos e apoiavam a Revolução e os que eram contra e a combatiam. Revolucionários e Legalistas passaram a se reconhecer e a se rechaçar a partir de seus posicionamentos políticos. O desejo pelo poder lhes movia as ações e intenções e os conduzia a combates de ordens diversas: políticos, militares e pela instituição de uma memória. Em Santa Catarina verificaram-se combates quando da passagem das tropas revolucionárias, no entanto, dificilmente eles aparecem como temas na historiografia nacional, pois a memória histórica do Movimento de Trinta ainda tende a ser a dos grupos vencedores. Estes, talvez como parte do exercício de dominação e poder, construíram lugares de memórias sob seus prismas, invisibilizando, apagando, minimizando ou mesmo desqualificando os dos vencidos. O trabalho apresentado nesta tese evidencia e analisa aspectos das ações políticas de alguns próceres e títeres no estado de Santa Catarina na Revolução de 1930, visibilizando feições das tramas e redes de sociabilidade no período compreendido entre 1929 e 1931. Analisa especificidades das estratégias militares dos Revolucionários nas tentativas de avanço e de defesa legalista narradas em documentos como boletins militares. Aborda a reverberação dessas sobre as memórias e imagens produzidas a partir da movimentação e tenta perceber como se constroem simpatias, ódios e ressentimentos gerados e alimentados antes, durante e após o Movimento de Trinta.In October of 1930, politics and militaries of Rio Grande do Sul, Paraíba and Minas Gerais started the movement which became the so called 1930s Revolution in Brazil that is the conventional historical repertoire title. The Revolutionary Force troops of Rio Grande do Sul marched with the intent of joining the allied troops, and to fight the ones considered reactionary, at that time. The goal was to enter the capital of Brazil, Rio de Janeiro, and to dispose Washington Luiz of his presidential title. The strategy was to get the Revolutionary Forces together in Ponta Grossa, Paraná, so that they could go to the capital, stronger than before. That strategy was thought because it was already imagined that an armed struggle against the Federal Legalist Forces would happen along the way, in São Paulo. The state of Santa Catarina was geographically, politically and military in the middle of the way of the Revolutionary Troops, because the governor of Santa Catarina, Fúvio Aducci, positioned himself in opposition to the Revolution and was prompt to fight in order to defend the political status quo. However, the local liberal oligarchy, besides supporting the Revolutionary Forces, provided them with men and weapons. Santa Catarina and Brazil were divided into groups: some were sympathetic or supportive to the Revolution and others that were against the Revolution. Revolutionaries and Legalists started to know each other and to disagree, based on their political standards. The desire for power inspired their actions and intentions, and led them to fight in many different arenas: political, military and for the institution of a certain memory. There were many struggles in Santa Catarina when the Revolutionary Troops passed by; however, these were not contemplated in the national historiography, because this historical record, of the 1930s Revolution, was registered by the winners. The winners constructed places of memory based on their views, as an exercise of dominance and power. Through this, they attempted to erase, and even to disqualify, the ones who lost. This thesis addresses the political actions of some leaders and some pawns of Santa Catarina during the 1930#s Revolution, mainly trying to reconstruct the nets formed between 1929 and 1931. This thesis also analyses the military strategy of the revolutionaries while trying to move forward and to defend themselves from the legalists, based on military documents and bulletins. This thesis also addresses the consequences of theses memories and the images produced during the movement of the troops. Finally, this thesis tries to demonstrate how sympathy, hate and resentment are constructed and maintained, before, during and after the 1930s Revolution

Detection of drug-sensitizing EGFR exon 19 deletion mutations in salivary gland carcinoma

Activating mutations within the epidermal growth factor receptor (EGFR) identify lung adenocarcinoma patients with improved clinical responses to tyrosine kinase inhibitors gefitinib and erlotinib. By screening salivary gland carcinoma, two drug-sensitizing EGFR exon 19 delE746-A750 mutations were identified in an adenocystic and in a mucoepidermoid carcinoma of the parotid gland