Expressão da progranulina durante os primeiros estágios de desenvolvimento hepático em ratos Fischer 344

Transplants are the only effective therapy for the treatment of advanced liver diseases such as cirrhosis. Given the limited number of organ donors, regenerative medicine has sought for sources of cells and tissues for replacement therapy. Embryonic stem cells are a promising source of material for transplantation because of their exclusive property of being expanded indefinitely in culture, thus, they are a source of replacement tissue. Moreover, they are capable of differentiating into practically all cell types, and may be utilized in replacement therapy in various diseases. The liver bud has bipotent stem cells that have not yet differentiated into hepatocytes or biliary duct cells; however, they have great potential of proliferation and differentiation. Thus, the challenge is to identify methods that promote their differentiation in specific and functional strains. This study aimed to evaluate the role of the progranulin growth factor PGRN during the liver development of rats F344, since this growth factor could be utilized in protocols of differentiation of stem cells of the liver bud in functional hepatocytes. The results showed that PGRN is present during different periods of hepatogenesis in F344 rats, and that this growth factor should be involved in the process of differentiation of hepatoblasts into hepatocytes after activation by HNF4α , however, PGRN seems not to exert a cellular proliferation function during the hepatogenesis. Thus, PGRN can be used in future protocols of liver cell differentiation directed toward cellular therapy in Regenerative Medicine.Os transplantes são a única terapia eficaz para o tratamento de doenças hepáticas avançadas, como a cirrose. Dado o número limitado de doadores de órgãos, a medicina regenerativa tem procurado fontes de células para a terapia de substituição. As células embrionárias são uma fonte promissora de material para o transplante devido à sua propriedade exclusiva de ser expandida indefinidamente em cultura, assim, elas são uma fonte de tecido de substituição. Além disso, são capazes de se diferenciar em praticamente todos os tipos celulares, e podem ser utilizadas na terapia de substituição em várias doenças. O broto hepático tem células-tronco (CT) bipotenciais que ainda não se diferenciam em hepatócitos ou células do ducto biliar, contudo, elas têm um grande potencial de proliferação e de diferenciação. Desse modo, o desafio é identificar métodos que promovam sua diferenciação em linhagens específicas e funcionais. Este estudo teve como objetivo avaliar o papel do fator de crescimento progranulina (PGRN) durante o desenvolvimento hepático em ratos F344, uma vez que a PGRN poderia ser utilizada em protocolos de diferenciação de CT do broto hepático em hepatócitos funcionais. Os resultados mostraram que PGRN está presente durante diferentes períodos da hepatogênese em ratos F344, e que a mesma deve estar envolvida no processo de diferenciação de hepatoblastos em hepatócitos após ativação por HNF4α, no entanto, a PGRN parece não desempenhar uma função de proliferação celular durante a hepatogênese. Assim, a PGRN pode ser usada em futuros protocolos de diferenciação de células hepáticas voltadas para a terapia celular na medicina regenerativa

Pyrites in a salt marsh-ria system: quantification, morphology, and mobilization

Galician Rias are among the most productive ecosystems in the world. Consequently, the soils of their salt marshes and sediments of the intertidal flats show high organic matter contents, reactive Fe, and sulfate, which promote pyrite synthesis and accumulation, using sulfate for organic matter decomposition. This work studies the morphological variability and concentration of pyrites (individual crystals and framboids) in different geochemical environments found in the Ria de Ortigueira (salt marsh soils and bottom sediments in the inner, middle, and outer section), addressing their dynamics in the marsh-ria system in relation to the hydrodynamic characteristics defined by tides and river discharges. Framboidal pyrites were the dominant morphology in marsh soils and sediments in the middle and inner sections of the Ria, while isolated crystals dominated its outer section. The results showed that lower marsh soils (colonized by Spartina) are the most favorable environment for pyrite synthesis, showing high pyritic Fe concentrations and high degrees of pyritization, largely exceeding the values observed in sediments from Galician Rias and from most sedimentary environments worldwide. However, the amount of framboidal pyrites present in the lower marsh (SPE: 4–5 × 104 framboids) was clearly lower than in bottom sediments of the inner and middle part of the Ria de Ortigueira (∼2–7 × 106 framboids), mainly due to the fact that pyrites were found to form large framboids in lower salt marsh soils. Thus, the amount of framboidal pyrites does not seem to be a good indicator of redox conditions in modern marine sediments. Pyrite crystals found in the sediments of the Ria showed poorly defined vertices and facets, indicating their degradation and suggesting that a significant amount of the pyrites found in the middle and inner sections derive from marsh collapse. Finally, the output of framboidal pyrites towards the outer Ria de Ortigueira reflects the low intensity of residual flows in this Ria. Therefore, the pyrites observed in the outer section consisted only of isolated crystals, presumably formed in situ under low sulfate-reducing activity conditionsS

Anatomical aspects and phytochemical potential of Caryocar villosum (Aubl.) Pers. (pequiá)/ Aspectos anatômicos e potencial fitoquímico de Caryocar villosum (Aubl.) Pers. (pequiá)

The knowledge of anatomical and phytochemical structures of many species has drawn the attention of researchers in several areas, because these species are characterized by the production of chemical compounds, mainly fixed and essential oils, which are of great industrial interest. The “pequiá” tree is a majestic tree from primary forest and represents huge economic potential. This work aimed to study the anatomical aspects, extraction and characterization of the fixed oil present in the fruit and the seed of Caryocar villosum. There were used fifty fruits of pequiá collected from the municipality of Tartarugalzinho (Amapá). The identification of species was made by comparison with exsiccates available in the Amapá Herbarium – HAMAB. For anatomical and phytochemical analyses, conventional methodology was used. The result in the macerate of the mesocarp corresponds to a yellow mass impregnated by lipids; in the endocarp there were registered trichomes which secret these lipids, forming an arc in all its extension. In the solvent-based phytochemical analyses of the mass of pericarp, mesocarp and fixed oil seed, favorable and satisfactory oil yields were obtained. The analyses of the acidity, saponification, ester and peroxide indexes are parameters that are related to the quality of the oil, therefore, the values obtained meet the Anvisa/2015 Resolution. It is thus concluded that the fixed oil obtained from the mesocarp/seed of C. villosum is indicated for alimentary purposes, with potential to reduce total cholesterol and LDL cholesterol, as well as in cosmetic industry. Therefore, anatomical analyses help phytochemical studies (CNPq/IEPA)

Os(AS) COZINHEIROS(AS) NEGROS(AS) NO PARÃ E SUAS POSSÃVEIS ABORDAGENS (1870-1888).

Neste artigo apresentamos um levantamento sobre cozinheiros negros do Pará, no período de 1870-1888. Muitos escravizados trabalhavam no “mundo da cozinhaâ€, no caso daqueles que trabalhavam em casas, padarias e mesmo nas ruas essa atividade requeria certa qualificação, não era apenas cozinhar, mas, acima de tudo cozinhar bem. Os cozinheiros geralmente ocupavam o mundo do trabalho fora do ambiente doméstico. Por outro lado, as cozinheiras também ocupavam papel importante em casas de família ou vendendo seus produtos como escravizadas de ganho. Enfim, na perspectiva dos anunciantes que desejavam comprar, vender ou alugar trabalhadores cativos, seria necessário além de saber o ofício ser sadio, sem vícios e de bons costumes.Palavras-Chaves: Cozinheiros, Escravizados, Belém, Alimentação, Ofício.Â

Kidney of Minke Whale (Baleanoptera acutorostrata): architecture and structure

Entre os mamíferos marinhos, a baleia é um dos animais que mais desperta atenção, especialmente no atinente ao seu sistema urinário. Este sistema segue o padrão entre os mamíferos quanto a sua constituição, entretanto, difere na morfologia renal, em número de lobos, que por sua vez, forma renículos completos, aglutinados às centenas. Esta estrutura é sustentada por tecido conjuntivo fibroso, mas altamente capaz de manter o equilíbrio hidroeletrolítico. Foram dissecados 6 pares de rins de baleia Minke (Balaenoptera acutorostrata), colhidos em 1982, Cabedelo, Estado da Paraíba, Brasil, na última pesca autorizada. Estes rins estavam conservados em formol 10% e apresentaram uma camada histológica de colágeno muito grande circundando a parede medular. O duto coletor urinário forma cálices papilares, desembocando num único centro coletor que desemboca no ureter. Verificou-se que o rim da baleia Minke apresenta característica lobulada possuindo em média 700 renículos, cada renículo possui características anatômicas e funcionais de um rim unipiramidal, com uma camada interna (medula), e uma camada externa (córtex), e irrigação independente, com formação das artérias arqueadas individualmente, como observadas em mamíferos terrestres unipiramidais. Entretanto, o conjunto destes renículos constitui ao final um rim multilobular e polipiramidal, contrariando a morfologia da maioria dos mamíferos terrestres. Não foi possível distinguir ao nível de microscopia de luz as estruturas do córtex renicular da baleia Minke. Na microscopia eletrônica de varredura foi possível visualizar uma camada cortical que fica localizada entre duas cápsulas fibrosas. Esta junção por sua vez é feita por tecido conjuntivo o qual juntamente com uma camada de colágeno e fibras elásticas, separa o córtex da medula , foram visualizados os glomérulos renais, completamente tomados pelos vasos glomerulares e dispostos em várias camadas. Percebe-se que a cavidade glomerular é praticamente um espaço virtual para onde o filtrado glomerular é drenado, não apresentando o formato globular. A vascularização intensifica-se ao chegar à região medular. A diferença entre rins de mamíferos terrestres e marinhos está na disposição dos componentes morfológicos, favorecendo a fisiologia do órgão

MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors

There is increasing evidence that oncogenic transformation modifies the metabolic program of cells. A common alteration is the upregulation of glycolysis, and efforts to target glycolytic enzymes for anticancer therapy are under way. Here, we performed a genome-wide haploid genetic screen to identify resistance mechanisms to 3-bromopyruvate (3-BrPA), a drug candidate that inhibits glycolysis in a poorly understood fashion. We identified the SLC16A1 gene product, MCT1, as the main determinant of 3-BrPA sensitivity. MCT1 is necessary and sufficient for 3-BrPA uptake by cancer cells. Additionally, SLC16A1 mRNA levels are the best predictor of 3-BrPA sensitivity and are most elevated in glycolytic cancer cells. Furthermore, forced MCT1 expression in 3-BrPA–resistant cancer cells sensitizes tumor xenografts to 3-BrPA treatment in vivo. Our results identify a potential biomarker for 3-BrPA sensitivity and provide proof of concept that the selectivity of cancer-expressed transporters can be exploited for delivering toxic molecules to tumors.National Institutes of Health (U.S.) (NIH CA103866)Jane Coffin Childs Memorial Fund for Medical Research (Fellowship)National Science Foundation (U.S.) (Fellowship)Howard Hughes Medical Institute (Investigator

Implicating Calpain in Tau-Mediated Toxicity In Vivo

Alzheimer's disease and other related neurodegenerative disorders known as tauopathies are characterized by the accumulation of abnormally phosphorylated and aggregated forms of the microtubule-associated protein tau. Several laboratories have identified a 17 kD proteolytic fragment of tau in degenerating neurons and in numerous cell culture models that is generated by calpain cleavage and speculated to contribute to tau toxicity. In the current study, we employed a Drosophila tauopathy model to investigate the importance of calpain-mediated tau proteolysis in contributing to tau neurotoxicity in an animal model of human neurodegenerative disease. We found that mutations that disrupted endogenous calpainA or calpainB activity in transgenic flies suppressed tau toxicity. Expression of a calpain-resistant form of tau in Drosophila revealed that mutating the putative calpain cleavage sites that produce the 17 kD fragment was sufficient to abrogate tau toxicity in vivo. Furthermore, we found significant toxicity in the fly retina associated with expression of only the 17 kD tau fragment. Collectively, our data implicate calpain-mediated proteolysis of tau as an important pathway mediating tau neurotoxicity in vivo

Protective Effector Memory CD4 T Cells Depend on ICOS for Survival

Memory CD4 T cells play a vital role in protection against re-infection by pathogens as diverse as helminthes or influenza viruses. Inducible costimulator (ICOS) is highly expressed on memory CD4 T cells and has been shown to augment proliferation and survival of activated CD4 T cells. However, the role of ICOS costimulation on the development and maintenance of memory CD4 T cells remains controversial. Herein, we describe a significant defect in the number of effector memory (EM) phenotype cells in ICOS−/− and ICOSL−/− mice that becomes progressively more dramatic as the mice age. This decrease was not due to a defect in the homeostatic proliferation of EM phenotype CD4 T cells in ICOS−/− or ICOSL−/− mice. To determine whether ICOS regulated the development or survival of EM CD4 T cells, we utilized an adoptive transfer model. We found no defect in development of EM CD4 T cells, but long-term survival of ICOS−/− EM CD4 T cells was significantly compromised compared to wild-type cells. The defect in survival was specific to EM cells as the central memory (CM) ICOS−/− CD4 T cells persisted as well as wild type cells. To determine the physiological consequences of a specific defect in EM CD4 T cells, wild-type and ICOS−/− mice were infected with influenza virus. ICOS−/− mice developed significantly fewer influenza-specific EM CD4 T cells and were more susceptible to re-infection than wild-type mice. Collectively, our findings demonstrate a role for ICOS costimulation in the maintenance of EM but not CM CD4 T cells