OS MUSEUS BRASILEIROS E A CONSTITUIÇÃO DO IMAGINÁRIO NACIONAL

Este artigo investiga a construção de mitos de origempresentes nos museus brasileiros, especialmente no MuseuNacional, e sua relação com imaginários coletivos que seconstituem sobre o Brasil durante o Império. São analisados osmuseus brasileiros do século dezenove, sua relação comos museus europeus da mesma época, bem como elementosinerentes à sociedade brasileira. Procura-se mostrar, primeiro,a formação de narrativas em que tradições clássicas seentrelaçam com uma visão romântica da natureza local; segundo,a ênfase na natureza como fonte de conhecimento científico e,finalmente, um descaso por tradições passadas e valorizaçãode narrativas orientadas para realizações futuras. A manutençãoda desvalorização do passado contribui para a dificuldade delegitimação dos museus que se voltam para a preservaçãode tradições culturais

Caracterização da perda auditiva de crianças atendidas em um programa de saúde auditiva

Objective: to characterize the hearing loss of children assessed and attended by the Hearing Health Program of the Hospital das Clínicas de Ribeirão Preto - Brazil. Methodology: The study was approved by the Ethics Committee of the University Hospital of Ribeirão Preto, University of São Paulo. This was a retrospective study of a sample of 279 medical records of children aged 2 to 12 years attended from October 2001 to August 2005; 133 cases with confirmed hearing loss were selected for analysis of the results. Results: bilateral profound sensorineural hearing loss predominated in 35 cases (70 ears - 26,30%). In cases of unilateral hearing loss the conductive type of mild degree persisted in 14 cases (14 ears - 10,52%). The risk factors most frequently detected were suspected familial language, speech and hearing delay (32 cases - 24.06%); recurrent otitis media or otitis media persisting for more than three months (30 cases - 22.56%), and use of ototoxic drugs (26 cases - 19.55%). Mean patient age at the time of suspicion, diagnosis ad intervention for all types of hearing loss was 40.8, 50.4 and 62.4 months, respectively. Conclusions: there was a predominance of bilateral profound sensorineural hearing loss; in the cases of unilateral hearing loss there was a prevalence of the conductive type of mild degree and the most frequent risk factor was familial suspicion of language, speech and hearing delay. It was concluded that an early diagnosis and intervention regarding these children in practice has not been achieved.  Objetivo: caracterizar a perda auditiva de crianças avaliadas e atendidas no Programa de Saúde Auditiva do Hospital das Clínicas de Ribeirão Preto. Metodologia:   Aprovado no Comitê de Ética do Hospital das Clínicas de Ribeirão Preto da Universidade de São Paulo. Estudo retrospectivo em uma amostra de 279 prontuários de crianças na faixa etária entre 2 a 12 anos de idade, atendidas no período de outubro de 2001 a agosto de 2005, sendo selecionados para a análise de resultados 133 casos que tiveram a confirmação da perda auditiva. Resultados: predominou a perda auditiva neurossensorial de grau profundo bilateral em 35 casos (70 orelhas - 26,30%). Nos casos de perdas auditivas unilaterais,prevaleceu o tipo condutivo de grau leve em 14 casos (14 orelhas - 10,52%). Os fatores de risco mais encontrados foram queixa familiar de atraso na aquisição e desenvolvimento da linguagem, fala e audição (32 casos - 24,06%); otite média recorrente ou persistente por mais de três meses (30 casos - 22,56%) e uso de drogas ototóxicas (26 casos - 19,55%).  As médias de idades encontradas no momento da suspeita, diagnóstico e intervenção para todos os tipos de perda auditiva foram 40,8; 50,4 e 62,4 meses, respectivamente. Conclusões: predominou a perda auditiva neurossensorial de grau profundo bilateral; nos casos de perdas auditivas unilaterais prevaleceu o tipo condutivo de grau leve e o fator de risco mais frequente foi a queixa da família de atraso na aquisição e desenvolvimento da linguagem, fala e audição. Concluiu-se que o diagnóstico e a intervenção precoces da criança portadora de deficiência auditiva na prática ainda não têm sido atingidos

pp32 (ANP32A) Expression Inhibits Pancreatic Cancer Cell Growth and Induces Gemcitabine Resistance by Disrupting HuR Binding to mRNAs

The expression of protein phosphatase 32 (PP32, ANP32A) is low in poorly differentiated pancreatic cancers and is linked to the levels of HuR (ELAV1), a predictive marker for gemcitabine response. In pancreatic cancer cells, exogenous overexpression of pp32 inhibited cell growth, supporting its long-recognized role as a tumor suppressor in pancreatic cancer. In chemotherapeutic sensitivity screening assays, cells overexpressing pp32 were selectively resistant to the nucleoside analogs gemcitabine and cytarabine (ARA-C), but were sensitized to 5-fluorouracil; conversely, silencing pp32 in pancreatic cancer cells enhanced gemcitabine sensitivity. The cytoplasmic levels of pp32 increased after cancer cells are treated with certain stressors, including gemcitabine. pp32 overexpression reduced the association of HuR with the mRNA encoding the gemcitabine-metabolizing enzyme deoxycytidine kinase (dCK), causing a significant reduction in dCK protein levels. Similarly, ectopic pp32 expression caused a reduction in HuR binding of mRNAs encoding tumor-promoting proteins (e.g., VEGF and HuR), while silencing pp32 dramatically enhanced the binding of these mRNA targets. Low pp32 nuclear expression correlated with high-grade tumors and the presence of lymph node metastasis, as compared to patients' tumors with high nuclear pp32 expression. Although pp32 expression levels did not enhance the predictive power of cytoplasmic HuR status, nuclear pp32 levels and cytoplasmic HuR levels associated significantly in patient samples. Thus, we provide novel evidence that the tumor suppressor function of pp32 can be attributed to its ability to disrupt HuR binding to target mRNAs encoding key proteins for cancer cell survival and drug efficacy

Global Mapping of DNA Methylation in Mouse Promoters Reveals Epigenetic Reprogramming of Pluripotency Genes

DNA methylation patterns are reprogrammed in primordial germ cells and in preimplantation embryos by demethylation and subsequent de novo methylation. It has been suggested that epigenetic reprogramming may be necessary for the embryonic genome to return to a pluripotent state. We have carried out a genome-wide promoter analysis of DNA methylation in mouse embryonic stem (ES) cells, embryonic germ (EG) cells, sperm, trophoblast stem (TS) cells, and primary embryonic fibroblasts (pMEFs). Global clustering analysis shows that methylation patterns of ES cells, EG cells, and sperm are surprisingly similar, suggesting that while the sperm is a highly specialized cell type, its promoter epigenome is already largely reprogrammed and resembles a pluripotent state. Comparisons between pluripotent tissues and pMEFs reveal that a number of pluripotency related genes, including Nanog, Lefty1 and Tdgf1, as well as the nucleosome remodeller Smarcd1, are hypomethylated in stem cells and hypermethylated in differentiated cells. Differences in promoter methylation are associated with significant differences in transcription levels in more than 60% of genes analysed. Our comparative approach to promoter methylation thus identifies gene candidates for the regulation of pluripotency and epigenetic reprogramming. While the sperm genome is, overall, similarly methylated to that of ES and EG cells, there are some key exceptions, including Nanog and Lefty1, that are highly methylated in sperm. Nanog promoter methylation is erased by active and passive demethylation after fertilisation before expression commences in the morula. In ES cells the normally active Nanog promoter is silenced when targeted by de novo methylation. Our study suggests that reprogramming of promoter methylation is one of the key determinants of the epigenetic regulation of pluripotency genes. Epigenetic reprogramming in the germline prior to fertilisation and the reprogramming of key pluripotency genes in the early embryo is thus crucial for transmission of pluripotency

Autophagy and ATP-induced anti-apoptosis in antigen presenting cells (APC) follows the cytokine storm in patients after major trauma

Severe trauma and the systemic inflammatory response syndrome (SIRS) occur as a result of a cytokine storm which is in part due to ATP released from damaged tissue. This pathology also leads to increased numbers of immature antigen presenting cells (APC) sharing properties of dendritic cells (DC) or macrophages (MΦ). The occurrence of immature APC appears to coincide with the reactivation of herpes virus infections such as Epstein Barr virus (EBV). The aim of this study was the comparative analysis of the ultrastructural and functional characteristics of such immature APC. In addition, we investigated EBV infection/ reactivation and whether immature APC might be targets for natural killers (NK). Significant macroautophagy, mitochondrial degradation and multivesicular body formation together with the identification of herpes virus particles were morphological findings associated with immature APC. Exogenous stressors such as ATP further increased morphological signs of autophagy, including LC3 expression. Functional tests using fluorescent bacteria proved impaired phagolysosome fusion. However, immature APC were susceptible to NK-92-mediated cytolysis. We found evidence for EBV latency state II infection by detecting EBV-specific LMP1 and EBNA2 in immature APC and in whole blood of these patients. In summary, trauma-induced cytokine storms may induce maturation arrest of APC, promote ATP-induced autophagy, support EBV persistence and impair the degradation of phagocytozed bacteria through inefficient phagolysosome fusion. The susceptibility to NK-mediated cytolysis supports the hypothesis that NK function is likely to contribute to immune reconstitution after major trauma by regulating immature APC, and ATP-induced autophagy and survival

Exploiting Mitochondrial Dysfunction for Effective Elimination of Imatinib-Resistant Leukemic Cells

Challenges today concern chronic myeloid leukemia (CML) patients resistant to imatinib. There is growing evidence that imatinib-resistant leukemic cells present abnormal glucose metabolism but the impact on mitochondria has been neglected. Our work aimed to better understand and exploit the metabolic alterations of imatinib-resistant leukemic cells. Imatinib-resistant cells presented high glycolysis as compared to sensitive cells. Consistently, expression of key glycolytic enzymes, at least partly mediated by HIF-1α, was modified in imatinib-resistant cells suggesting that imatinib-resistant cells uncouple glycolytic flux from pyruvate oxidation. Interestingly, mitochondria of imatinib-resistant cells exhibited accumulation of TCA cycle intermediates, increased NADH and low oxygen consumption. These mitochondrial alterations due to the partial failure of ETC were further confirmed in leukemic cells isolated from some imatinib-resistant CML patients. As a consequence, mitochondria generated more ROS than those of imatinib-sensitive cells. This, in turn, resulted in increased death of imatinib-resistant leukemic cells following in vitro or in vivo treatment with the pro-oxidants, PEITC and Trisenox, in a syngeneic mouse tumor model. Conversely, inhibition of glycolysis caused derepression of respiration leading to lower cellular ROS. In conclusion, these findings indicate that imatinib-resistant leukemic cells have an unexpected mitochondrial dysfunction that could be exploited for selective therapeutic intervention

Gestational weight gain charts for different body mass index groups for women in Europe, North America, and Oceania

BackgroundGestational weight gain differs according to pre-pregnancy body mass index and is related to the risks of adverse maternal and child health outcomes. Gestational weight gain charts for women in different pre-pregnancy body mass index groups enable identification of women and offspring at risk for adverse health outcomes. We aimed to construct gestational weight gain reference charts for underweight, normal weight, overweight, and grades 1, 2 and 3 obese women and to compare these charts with those obtained in women with uncomplicated term pregnancies.MethodsWe used individual participant data from 218,216 pregnant women participating in 33 cohorts from Europe, North America, and Oceania. Of these women, 9065 (4.2%), 148,697 (68.1%), 42,678 (19.6%), 13,084 (6.0%), 3597 (1.6%), and 1095 (0.5%) were underweight, normal weight, overweight, and grades 1, 2, and 3 obese women, respectively. A total of 138, 517 women from 26 cohorts had pregnancies with no hypertensive or diabetic disorders and with term deliveries of appropriate for gestational age at birth infants. Gestational weight gain charts for underweight, normal weight, overweight, and grade 1, 2, and 3 obese women were derived by the Box-Cox t method using the generalized additive model for location, scale, and shape.ResultsWe observed that gestational weight gain strongly differed per maternal pre-pregnancy body mass index group. The median (interquartile range) gestational weight gain at 40weeks was 14.2kg (11.4-17.4) for underweight women, 14.5kg (11.5-17.7) for normal weight women, 13.9kg (10.1-17.9) for overweight women, and 11.2kg (7.0-15.7), 8.7kg (4.3-13.4) and 6.3kg (1.9-11.1) for grades 1, 2, and 3 obese women, respectively. The rate of weight gain was lower in the first half than in the second half of pregnancy. No differences in the patterns of weight gain were observed between cohorts or countries. Similar weight gain patterns were observed in mothers without pregnancy complications.ConclusionsGestational weight gain patterns are strongly related to pre-pregnancy body mass index. The derived charts can be used to assess gestational weight gain in etiological research and as a monitoring tool for weight gain during pregnancy in clinical practice.Peer reviewe