O abaixamento das médias pretônicas no português falado em Aurora do Pará – PA: uma análise variacionista

A presente pesquisa teve como objeto de estudo a investigação do abaixamento das médias pretônicas na variedade do português falado em Aurora do Pará (PA). Pautou-se nos pressupostos da sociolinguística quantitativa de Labov (1972), suporte necessário para investigar e sistematizar a variação de uma comunidade linguística. Além destes, foram utilizados alguns procedimentos metodológicos adotados por Bortoni-Ricardo (1985) para as análises de redes sociais, importantes para o estudo de dialetos em comunidades de migração, como é o caso de Aurora do Pará, localizada na Mesorregião do Nordeste Paraense e que apresenta como particularidade o fato de ter recebido intenso fluxo migratório nas décadas de 60,70 e 80 do século passado. O corpus foi formado a partir de gravações de entrevistas de 28 informantes, divididos em dois grupos: a) um grupo de ancoragem, com 19 informantes migrantes do Ceará (9 (nove) do sexo masculino e 10 (dez) do sexo feminino), distribuídos nas faixas etárias de 30 a 46 anos e de 50 anos acima; b) outro de controle, com 9 (nove) informantes (3 (três) do sexo masculino e 6 (seis) do sexo feminino), paraenses descendentes do grupo de ancoragem. Os dados do corpus submetidos às análises somaram 4.033 ocorrências das vogais-objeto, anterior (2.394) e posterior (1.639). Foram estabelecidas como variáveis extralinguísticas: sexo, grupo de amostra, tempo de residência, e localidade. Para variáveis linguísticas, foram consideradas: natureza da vogal tônica, vogal pre-pretônica quando for oral, vogal pré-pretônica quando for nasal, vogal contígua, distância relativa à sílaba tônica, atonicidade, natureza do sufixo, consoante do onset da sílaba da vogal-alvo, consoante do onset da sílaba da vogal seguinte e peso silábico. Após as análises estatísticas computadas pelo software Goldvarb, os resultados mostraram que no dialeto de Aurora do Pará/PA predominam as variantes de não abaixamento – [.i,e] .71 e [o,u] .74 em detrimento das do abaixamento [E] .28 e [O] .26. Para o abaixamento, as variáveis favorecedoras foram: (i) natureza da vogal tônica, (ii) Vogal pré-pretônica, quando for oral, (iii) Vogal contígua, (iv) Distância relativamente à Sílaba Tônica, (v) Atonicidade, (vi) Natureza do sufixo, (vii) Consoante do onset da sílaba da vogal-alvo, (viii) Consoante do onset da sílaba seguinte, (ix) Peso silábico em relação à sílaba vogal alvo, (x) Sexo, (xi) Faixa etária, (xii) Tempo de residência. Os resultados revelaram perda da marca dialetal dos migrantes cearenses por conta do contato dialetal com outros dialetos e evidenciaram que o abaixamento vocálico no dialeto em questão é motivado, sobretudo pelo processo de harmonia vocálica. Tais resultados são reflexos da rede social dos informantes a qual tem baixa densidade e é uniplex, caracterizando-os como mais propensos a mudanças culturais e inovações linguísticas.

Processamento mínimo de pêssegos ‘Aurora-1’: estádio de maturação, embalagens, temperaturas de conservação e aditivos naturais

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Fertilidade e fauna edáfica em solo sob reflorestamento com paricá (Schizolobium amazonicum Huber ex Ducke) no município de Aurora do Pará

Com este estudo objetivou-se avaliar a variação na fertilidade do solo e na fauna edáfica sob reflorestamento com paricá (Schizolobium amazonicum Heber ex. Ducke) em monocultivo ou em sistema agroflorestal quando comparados com floresta secundária em área experimental considerando a sazonalidade da precipitação no período de 2009 e 2010. A área experimental pertence a Fazenda Tramontina Belém S/A, localizada no nordeste paraense, no município de Aurora do Pará. Foram analisados quatro tratamentos submetidos a reflorestamento com: Curauá (Ananas comosus var. erectifolius L.B.Smith), Paricá (Shizolobium var. amazonicum Huber ex Ducke) sob a forma de monocultivos, Paricá + curauá (Ananas comosus var. erectifolius L.B.Smith; Shizolobium var. amazonicum Huber ex Ducke); Paricá + Mogno + Freijó + Curauá (Shizolobium var. amazonicum Huber ex Ducke; Switenia macrophylla, King; Cordia goeldiana Huber; Ananas comosus var. erectifolius L.B.Smith). As amostragens foram realizadas em dezembro de 2009, abril e julho de 2010, o que caracterizou o período sazonal de transição (estiagem para chuva intensa), chuva intensa e estiagem respectivamente, para avaliar a granulometria, densidade aparente, densidade da partícula, porosidade total e umidade atual, bases trocáveis, soma de bases, CTC, acidez, fósforo, teor de carbono orgânico, pH, em três profundidades diferentes (0 – 10 cm. 10 - 20 cm; 20 – 40 cm) e a ocorrência de macrofauna edáfica. Os resultados mostraram a ação dos períodos sazonais sobre a densidade aparente, densidade da partícula, porosidade total do solo. Fatores químicos como, por exemplo, carbono orgânico, cujos teores variaram entre 5,85 g/kg e 13,00 g/kg, com teores elevados no sistema de cultivo S2, sofreu alterações nos períodos sazonais chuva intensa e estiagem. Quanto a fauna edáfica, foram capturados 9.964 invertebrados pertencentes a 26 táxons diferentes. Os mais abundantes foram Hymenoptera- Formicidae (5.805), Coleoptera (1.454), Acari (862), Collembola (649), Diplopoda (307) e Isopoda (110). Dos 26 táxons identificados, aproximadamente 40% deles apresentaram apenas um representante nas três amostragens efetuadas ou em apenas uma delas. Os maiores valores para frequência relativa ocorreu no sistema de cultivo S2, S4 e S3, respectivamente. O maior valor para frequência absoluta ocorreu durante o período sazonal chuva intensa em S1. As áreas sob reflorestamento com monocultivo e sistema agroflorestal paricà + curauá mostraram melhores desempenhos na recuperação da fertilidade do solo e da fauna edáfica comprovando a eficácia do paricá em monocultivo ou em sistema agroflorestal na recuperação da fertilidade do solo e da fauna edáfica.

Efeito de atmosfera controlada no desenvolvimento de Monilinia fructicola e na qualidade pós-colheita de pêssegos 'Aurora-1'

Pós-graduação em Agronomia (Produção Vegetal) - FCAV

Clonagem do pessegueiro 'Aurora-1' e de portaenxertos de umezeiro

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The Aurora A and B kinases are up-regulated in bone marrow-derived chronic lymphocytic leukemia cells and represent potential therapeutic targets

Background The malignant B cells in chronic lymphocytic leukemia receive signals from the bone marrow and lymph node microenvironments which regulate their survival and proliferation. Characterization of these signals and the pathways that propagate them to the interior of the cell is important for the identification of novel potential targets for therapeutic intervention. Design and Methods We compared the gene expression profiles of chronic lymphocytic leukemia B cells purified from bone marrow and peripheral blood to identify genes that are induced by the bone marrow microenvironment. Two of the differentially expressed genes were further studied in cell culture experiments and in an animal model to determine whether they could represent appropriate therapeutic targets in chronic lymphocytic leukemia. Results Functional classification analysis revealed that the majority of differentially expressed genes belong to gene ontology categories related to cell cycle and mitosis. Significantly up-regulated genes in bone marrow-derived tumor cells included important cell cycle regulators, such as Aurora A and B, survivin and CDK6. Down-regulation of Aurora A and B by RNA interference inhibited proliferation of chronic lymphocytic leukemia-derived cell lines and induced low levels of apoptosis. A similar effect was observed with the Aurora kinase inhibitor VX-680 in primary chronic lymphocytic leukemia cells that were induced to proliferate by CpG-oligonucleotides and interleukin-2. Moreover, VX-680 significantly blocked leukemia growth in a mouse model of chronic lymphocytic leukemia. Conclusions Aurora A and B are up-regulated in proliferating chronic lymphocytic leukemia cells and represent potential therapeutic targets in this disease.

Inhibition of Aurora kinases enhances chemosensitivity to temozolomide and causes radiosensitization in glioblastoma cells

Glioblastoma remains one of the most devastating human malignancies, and despite therapeutic advances, there are no drugs that significantly improve the patient survival. Altered expression of the Aurora kinases was found in different malignancies, and their inhibition has been studied in cancer therapy. In this study, we analyzed the expression of Aurora A and Aurora B in glioblastoma samples and also analyzed whether the effects of Aurora kinase inhibition were associated with temozolomide or not on cell lines and primary cultures of glioblastoma. RT-PCR assays were used to determine the mRNA expression in glioblastoma tumor samples and in the cell lines. Cell proliferation was measured by XTT assay, and apoptosis was determined by flow cytometry. Drug combination analyses were made based in Chou-Talalay method. Gamma radiation for clonogenic survival used the doses of 2, 4 and 6 Gy. Changes in Aurora B level were assessed by Western blot analysis. Aurora A and B were expressed in glioblastoma samples as well as in the glioblastoma cell lines (n = 6). Moreover, ZM447439, a selective Aurora kinase inhibitor, decreased the proliferation separately and synergistically with temozolomide in primary cultures and cell lines of glioblastoma. ZM also enhanced the effects of radiation on the two cell lines studied (U343 and U251), mainly when associated with TMZ in U343 cells. Treatment with ZM induced apoptotic cell death and diminished Aurora B protein level. These data suggest that Aurora kinase inhibition may be a target for glioblastoma treatment and could be used as adjuvant to chemo- and radiotherapy.

Aurora kinases as anticancer drug targets

The human aurora family of serine-threonine kinases comprises three members, which act in concert with many other proteins to control chromosome assembly and segregation during mitosis. Aurora dysfunction can cause aneuploidy, mitotic arrest, and cell death. Aurora kinases are strongly expressed in a broad range of cancer types. Aurora A expression in tumors is often associated with gene amplification, genetic instability, poor histologic differentiation, and poor prognosis. Aurora B is frequently expressed at high levels in a variety of tumors, often coincidently with aurora A, and expression level has also been associated with increased genetic instability and clinical outcome. Further, aurora kinase gene polymorphisms are associated with increased risk or early onset of cancer. The expression of aurora C in cancer is less well studied. In recent years, several small-molecule aurora kinase inhibitors have been developed that exhibit preclinical activity against a wide range of solid tumors. Preliminary clinical data from phase I trials have largely been consistent with cytostatic effects, with disease stabilization as the best response achieved in solid tumors. Objective responses have been noted in leukemia patients, although this might conceivably be due to inhibition of the Abl kinase. Current challenges include the optimization of drug administration, the identification of potential biomarkers of tumor sensitivity, and combination studies with cytotoxic drugs. Here, we summarize the most recent preclinical and clinical data and discuss new directions in the development of aurora kinase inhibitors as antineoplastic agents.

A NOVEL FUNCTION FOR AURORA B KINASE IN THE REGULATION OF P53 BY PHOSPHORYLATION

The mitotic kinase Aurora B plays a pivotal role in mitosis and cytokinesis and governs the spindle assembly checkpoint which ensures correct chromosome segregation and normal progression through mitosis. Aurora B is overexpressed in breast and other cancers and may be an important molecular target for chemotherapy. Tumor suppressor p53 is the guardian of the genome and an important negative regulator of the cell cycle. Previously, it was unknown whether Aurora B and p53 had mutual regulation during the cell cycle. A small molecule specific inhibitor of Aurora B, AZD1152, gave us an indication that Aurora B negatively impacted p53 during interphase and mitosis. Here, we show the antineoplastic activity of AZD1152 in six human breast cancer cell lines, three of which overexpress HER2. AZD1152 specifically inhibited Aurora B kinase activity, thereby causing mitotic catastrophe, polyploidy and apoptosis, which in turn led to apoptotic death. Further, AZD1152 administration efficiently suppressed tumor growth in orthotopic and metastatic breast cancer cell xenograft models. Notably, it was found that the protein level of Aurora B kinase declined after inhibition of Aurora B kinase activity. Investigation of the underlying mechanism suggested that AZD1152 accelerated the protein turnover of Aurora B by enhancing its ubiquitination. As a consequence of inhibition of Aurora B, p53 levels were increased in tissue culture and murine models. This hinted at a possible direct interaction between p53 and Aurora B. Indeed, it was found that p53 and Aurora B exist in complex and interact directly during interphase and at the centromere in mitosis. Further, Aurora B was shown to phosphorylate p53 at several serine/threonine residues in the DNA binding domain and these events caused downregulation of p53 levels via ubiquitination mediated by Mdm2. Importantly, phosphorylation of threonine 211 was shown to reduce p53’s transcriptional activity while other phosphorylation sites did not. On a functional level, Aurora B was shown to reduce p53’s capacity to mediate apoptosis in response to the DNA damaging agent, cisplatin. These results define a novel mechanism for p53 inactivation by Aurora B and imply that oncogenic hyperactivation or overexpression of Aurora B may compromise p53’s tumor suppressor function.

The Set1 methyltransferase opposes Ipl1 aurora kinase functions in chromosome segregation

A phosphorylation balance governed by Ipl1 Aurora kinase and the Glc7 phosphatase is essential for normal chromosome segregation in S. cerevisiae . Deletion of SET1, a histone K4 methyltransferase, suppresses the temperature sensitive phenotype of ipl1-2, and loss the catalytic activity of Set1 is important for this suppression. SET1 deletion also suppresses chromosome loss in ipl1-2 cells. Deletion of other Set1 complex components suppresses the temperature sensitivity of ipl1-2 as well. In contrast, SET1 deletion is synthetic lethal combined with glc7-127. Strikingly, these effects are independent of previously defined functions for Set1 in transcription initiation and histone H3 methylation. I find that Set1 methylates conserved lysines in a kinetochore protein, Dam1, a key mitotic substrate of Ipl1/Glc7. Biochemical and genetic experiments indicate that Dam1 methylation inhibits Ipl1-mediated phosphorylation of flanking serines. My studies demonstrate that Set1 has important, unexpected functions in mitosis through modulating the phosphorylation balance regulated by Ipl1/Glc7. Moreover, my findings suggest that antagonism between lysine methylation and serine phosphorylation is a fundamental mechanism for controlling protein function. ^

Identification and analysis of novel mitotic inhibitors of the Caenorhabditis elegans Aurora B kinase

Proper execution of mitosis requires the accurate segregation of replicated DNA into each daughter cell. The highly conserved mitotic kinase AIR-2/Aurora B is a dynamic protein that interacts with subsets of cofactors and substrates to coordinate chromosome segregation and cytokinesis in Caenorhabdiris elegans. To identify components of the AIR-2 regulatory pathway, a genome-wide RNAi-based screen for suppressors of air-2 temperature-sensitive mutant lethality was conducted. Here, I present evidence that two classes of suppressors identified in this screen are bona fide regulators of the AIR-2 kinase. The strongest suppressor cdc-48.3, encodes an Afg2/Spaf-related Cdc48-like AAA+ ATPase that regulates AIR-2 kinase activity and stability during C. elegans embryogenesis. Loss of CDC-48.3 suppresses the lethality of air-2 mutant embryos, marked by the restoration of the dynamic behavior of AIR-2 and rescue of chromosome segregation and cytokinesis defects. Loss of CDC-48.3 leads to mitotic delays and abnormal accumulation of AIR-2 during late telophase/mitotic exit. In addition, AIR-2 kinase activity is significantly upregulated from metaphase through mitotic exit in CDC-48.3 depleted embryos. Inhibition of the AIR-2 kinase is dependent on (1) a direct physical interaction between CDC-48.3 and AIR-2, and (2) CDC-48.3 ATPase activity. Importantly, the increase in AIR-2 kinase activity does not correlate with the stabilization of AIR-2 in late mitosis. Hence, CDC-48.3 is a bi-functional inhibitor of AIR-2 that is likely to act via distinct mechanisms. The second class of suppressors consists of psy-2/smk-1 and pph-4.1, which encode two components of the conserved PP4 phosphatase complex that is essential for spindle assembly, chromosome segregation, and overall mitotic progression. AIR-2 and its substrates are likely to be targets of this complex since mitotic AIR-2 kinase activity is significantly increased during mitosis when either PSY-2/SMK-1 or PPH-4.l is depleted. Altogether, this study demonstrates that during the C. elegans embryonic cell cycle, regulators including the CDC-48.3 ATPase and PP4 phosphatase complex interact with and control the kinase activity, targeting behavior and protein stability of the Aurora B kinase to ensure accurate and timely progression of mitosis. ^