Protein kinase a distribution differentiates human glioblastoma from brain tissue

Brain tumor glioblastoma has no clear molecular signature and there is no effective therapy. In rodents, the intracellular distribution of the cyclic AMP (cAMP)-dependent protein kinase (Protein kinase A, PKA) R2Alpha subunit was previously shown to differentiate tumor cells from healthy brain cells. Now, we aim to validate this observation in human tumors. The distribution of regulatory (R1 and R2) and catalytic subunits of PKA was examined via immunohistochemistry and Western blot in primary cell cultures and biopsies from 11 glioblastoma patients. Data were compared with information obtained from 17 other different tumor samples. The R1 subunit was clearly detectable only in some samples. The catalytic subunit was variably distributed in the different tumors. Similar to rodent tumors, all human glioblastoma specimens showed perinuclear R2 distribution in the Golgi area, while it was undetectable outside the tumor. To test the effect of targeting PKA as a therapeutic strategy, the intracellular cyclic AMP concentration was modulated with different agents in four human glioblastoma cell lines. A significant increase in cell death was detected after increasing cAMP levels or modulating PKA activity. These data raise the possibility of targeting the PKA intracellular pathway for the development of diagnostic and/or therapeutic tools for human glioblastoma

Drug-induced Parkinson's disease modulates protein kinase A and Olfactory Marker Protein in the mouse olfactory bulb

Background Olfaction is often affected in parkinsonian patients, but dopaminergic cells in the olfactory bulb are not affected by some Parkinson-inducing drugs. We investigated whether the drug MPTP produces the olfactory deficits typical of Parkinson and affects the olfactory bulb in mice. Findings Lesioned and control mice were tested for olfactory search, for motor and exploratory behavior. Brains and olfactory mucosa were investigated via immunohistochemistry for thyrosine hydroxylase, Olfactory Marker Protein and cyclic AMP-dependent protein kinase as an intracellular pathway involved in dopaminergic neurotransmission. MPTP induced motor impairment, but no deficit in olfactory search. Thyrosine hydroxylase did not differ in olfactory bulb, while a strong decrease was detected in substantia nigra and tegmentum of MPTP mice. Olfactory Marker Protein decreased in the olfactory bulb of MPTP mice, while a cyclic AMP-dependent protein kinase increased in the inner granular layer of MPTP mice. Conclusions MPTP mice do not present behavioural deficits in olfactory search, yet immunoreactivity reveals modifications in the olfactory bulb, and suggests changes in intracellular signal processing, possibly linked to neuron survival after MPTP

Estimates of Marine Mammal, Sea Turtle, and Seabird Mortality in the California Drift Gillnet Fishery for Swordfish and Thresher Shark, 1996–2002

Estimates of incidental marine mammal, sea turtle, and seabird mortality in the California drift gillnet fishery for broadbill swordfish, Xiphias gladius, and common thresher shark, Alopias vulpinus, are summarized for the 7-year period, 1996 to 2002. Fishery observer coverage was 19% over the period (3,369 days observed/17,649 days fished). An experiment to test the effectiveness of acoustic pingers on reducing marine mammal entanglements in this fishery began in 1996 and resulted in statistically significant reductions in marine mammal bycatch. The most commonly entangled marine mammal species were the short-beaked common dolphin, Delphinus delphis; California sea lion, Zalophus californianus; and northern right whale dolphin, Lissodelphis borealis. Estimated mortality by species (CV and observed mortality in parentheses) from 1996 to 2002 is 861 (0.11, 133) short-beaked common dolphins; 553 (0.16, 103) California sea lions; 151 (0.25, 31) northern right whale dolphins; 150 (0.21, 27) northern elephant seals, Mirounga angustirostris; 54 (0.41, 10) long-beaked common dolphins, Delphinus capensis; 44 (0.53, 6) Dall’s porpoise, Phocoenoides dalli; 19 (0.60, 5) Risso’s dolphins, Grampus griseus; 11 (0.71, 2) gray whales, Eschrichtius robustus; 7 (0.83, 2) sperm whales, Physeter macrocephalus; 7 (0.96, 1) short-finned pilot whales, Globicephala macrorhychus; 12 (1.06, 1) minke whales, Balaenoptera acutorostrata; 5 (1.05, 1) fin whales, Balaenoptera physalus; 11 (0.68, 2) unidentified pinnipeds; 33 (0.52, 4) leatherback turtles, Dermochelys coriacea; 18 (0.57, 3) loggerhead turtles, Caretta caretta; 13 (0.73, 3) northern fulmars, Fulmarus glacialis; and 6 (0.86, 2) unidentified birds

Protein kinase a distribution in meningioma

Deregulation of intracellular signal transduction pathways is a hallmark of cancer cells, clearly differentiating them from healthy cells. Differential intracellular distribution of the cAMP-dependent protein kinases (PKA) was previously detected in cell cultures and in vivo in glioblastoma and medulloblastoma. Our goal is to extend this observation to meningioma, to explore possible differences among tumors of different origins and prospective outcomes. The distribution of regulatory and catalytic subunits of PKA has been examined in tissue specimens obtained during surgery from meningioma patients. PKA RI subunit appeared more evenly distributed throughout the cytoplasm, but it was clearly detectable only in some tumors. RII was present in discrete spots, presumably at high local concentration; these aggregates could also be visualized under equilibrium binding conditions with fluorescent 8-substituted cAMP analogues, at variance with normal brain tissue and other brain tumors. The PKA catalytic subunit showed exactly overlapping pattern to RII and in fixed sections could be visualized by fluorescent cAMP analogues. Gene expression analysis showed that the PKA catalytic subunit revealed a significant correlation pattern with genes involved in meningioma. Hence, meningioma patients show a distinctive distribution pattern of PKA regulatory and catalytic subunits, different from glioblastoma, medulloblastoma, and healthy brain tissue. These observations raise the possibility of exploiting the PKA intracellular pathway as a diagnostic tool and possible therapeutic interventions

THE CONSTRUCTION OF A EUROPEAN IDENTITY Refugees and Europe’s Identity Crisis

The fundamental purpose of my thesis is to consider the ongoing formation of European identity within the context of the contemporary refugee/migrant crisis in Europe. In doing so, I will briefly survey how a European identity has been conceived and constructed through legal documents, treaties, and political speeches. Moreover, I will use different theories such as Anderson’s imagined communities to consider whether European identity is post-modern and post-national as it is sometimes celebrated to be. The EU is frequently regarded as a unique experiment in history and the first real post-modern political entity. However, looking deeper into the identity construction process, it does not seem to reflect a post-national construction but rather an identity often constructed on national and primordial resources, making the EU more supranational than a post-national entity. This is particularly true in relation to the refugee crisis which has been framed as a threat to European identity and culture. The role of borders, the Mediterranean Sea, and fortress Europe are critical terms I will analyze to consider the refugee crisis case study. Refugees have become the “other” or the “enemy” in contrast to the “Europeans.” Migrants are seen as a threat to one’s culture and identity, but if the European identity is still evolving and not clearly defined, how can migrants pose a threat to it? The migrant crisis provides the context that clearly demonstrates the contradictions and paradox inside the idea of a European identity

Challenging hierarchical research relations and improving research trustworthiness: the use of member checking

This contribution discusses the use of member checking in Tot, Kenya and Engaruka, Tanzania as enriching practices for both the researched and the researcher. By utilising a series of pamphlets produced in local languages, participants are able to see the result of their contribution to the research and give them a chance to have a second say by adding or rectifying what they would have reported earlier. In this way, member checking enables a researcher to realise any erroneous understanding of community practices under examination. Member checking is indeed far from perfect, but its employment improved the trustworthiness, transferability and confirmability of the study, writes Martina Angela Caretta

Letramento e formação social

Material em formato .pdf - Parte do material do curso de Aperfeiçoamento em Políticas Públicas para Educação Escolar Indígena – COMFOR – SEB – SECADI – MINISTÉRIO DA EDUCAÇÃOCoordenação pedagógica do curso: Coordenador: Sandro Luis da Silva / Vice-Coordenadora: Indaiá de Santana BassaniEquipe de Produção (SEAD/UNIFESP): Felipe Vieira Pacheco (Coordenador de Produção) / Sandro Takeshi Munakata da Silva (Designer Instrucional) / Fabrício Sawczen (Designer Gráfico)Disciplina pertencente ao Módulo 4: Métodos de Ensino e Aprendizagem de LínguasNesta disciplina será abordado o conceito de letramento, enfatizando a sua importância no processo de formação social de um cidadão. Será apresentado um tópico sobre Letramento em gêneros multimodais e multimídias. Gêneros discursivos são tomados como elemento orientador a fim de levar à compreensão que não se pode pensar no mito de uma língua uniforme, mas que é preciso observá-la em todas as variedades que compõem o multilinguismo. Propõem uma reflexão sobre o preconceito linguístico como um grande empecilho no processo de construção de uma sociedade mais igualitária, diversificada e democrática, com a proposta de trabalhar com os conteúdos referentes às relações entre oralidade e escrita no ensino de língua, com o objetivo principal de compreender a língua como uma prática social e não apenas como código linguístico.Outr