A IMPORTÂNCIA DO CONHECIMENTO LOCAL DOS AGRICULTORES FAMILIARES E DEMAIS POPULAÇÕES RURAIS PARA O DESENVOLVIMENTO RURAL SUSTENTÁVEL

Na sociedade do conhecimento, as pessoas são de grande importância para as organizações, pois são elas que possuem conhecimentos, muitas vezes tácitos, essenciais para o desenvolvimento de estratégias que visam ao aumento da competitividade e da produtividade. A busca pela valorização dos diversos saberes está se tornando cada vez mais uma dinâmica em todas as áreas do conhecimento. O processo de modernização da agricultura interferiu no modo de produção dos agricultores que, a partir de uma visão reducionista, buscou homogeneizar a forma de produção, fundamentada nos conhecimentos técnico-científicos, desconsiderando-se os saberes tradicionais das comunidades rurais. Nos últimos anos, estudos têm demonstrado a necessidade de se adotar uma abordagem Inter e Transdisciplinar com a preocupação quanto ao desenvolvimento sustentável, envolvendo diversos tipos de saberes. Assim, o objetivo deste artigo foi analisar o processo da gestão do conhecimento local ou tradicional no contexto da agricultura familiar e demais populações rurais na perspectiva do desenvolvimento rural sustentável, a partir de uma revisão sistemática na literatura. As bases de dados utilizadas para busca foram: web of Science, Scopus, Capes e BDTD. Os resultados das buscas foram oriundos dos seguintes Continentes: Ásia Meridional, Sudeste Asiático, Europa Ocidental, América do Sul e Oceania. Os estudos demonstraram que, na literatura e no meio acadêmico, nos últimos anos, houve uma valorização dos conhecimentos local ou tradicional. No entanto, na prática, ainda são poucas as iniciativas que estimulam o diálogo entre os conhecimentos técnico-científicos e os conhecimentos tradicionais

CORRENTE INTERFERENCIAL NA DOR MUSCULAR TARDIA

Indivíduos que iniciam uma nova atividade física ou que aumentam a intensidade do exercício podem desenvolver a Dor Muscular de Início Tardio (DMIT), levando a perda de força, coordenação e movimentos compensatórios. Alguns recursos podem ser utilizados para o tratamento da DMIT, dentre eles a eletrofototermoterapia. A Corrente Interferencial (CI) é uma técnica de estimulação elétrica, que penetra profundamente e mantém bons efeitos analgésicos, pela “teoria das comportas”, bloqueio nervoso, aumento da circulação local e placebo. Este trabalho teve como objetivo avaliar o uso do interferencial sobre a DMIT. Foram recrutados 14 indivíduos saudáveis, sedentários, com média de idade de 21,8 anos, que nunca tivessem realizado qualquer tipo de eletroestimulação. A amostra foi distribuída aleatoriamente em Grupo Placebo e Grupo Experimental. Para avaliação da dor foi utilizada a EVA e Algômetro de pressão. Visando promover a DMIT, os participantes realizaram movimentos concêntricos e excêntricos para o tríceps sural, realizando planti e dorsiflexões, em ortostatismo, sobre um degrau de 20 cm de altura (3 séries de 20 repetições). A carga foi dada apenas pelo peso do corpo e ação da gravidade. Para a eletroestimulação, os eletrodos foram posicionados no ventre no músculo gastrocnêmio lateral e medial, durante 20 minutos, com intensidade forte e confortável, com frequência base de 4 kHz, na forma bipolar e com frequência modulada pela amplitude (AMF) de 100Hz.  Para a comparação dos dados da EVA e do Algômetro de Pressão, foram realizadas comparações intragrupos com uso de Anova medidas repetidas e para a comparação entre os dois grupos, o Teste T não pareado. Em ambos os casos o nível de significância aceito foi 5%. Os dados foram apresentados em média e desvio padrão. Houve diferenças intragrupos. AV1 do grupo placebo foi diferente de todas as seguintes, o que não ocorreu no grupo experimental. Na comparação entre os grupos houve diferenças significativas: em AV3, AV4, AV6 e AV8. Na avaliação da dor à pressão houve diferença estatística intragrupo, apenas para o placebo, sendo que AV3 mostrou-se menor do que AV7. Conclui-se que a corrente interferencial foi eficaz para a redução da sensação de dor muscular de início tardio.

IL-12 Can Target Human Lung Adenocarcinoma Cells and Normal Bronchial Epithelial Cells Surrounding Tumor Lesions

BACKGROUND: Non small cell lung cancer (NSCLC) is a leading cause of cancer death. We have shown previously that IL-12rb2 KO mice develop spontaneously lung adenocarcinomas or bronchioalveolar carcinomas. Aim of the study was to investigate i) IL-12Rbeta2 expression in human primary lung adenocarcinomas and in their counterparts, i.e. normal bronchial epithelial cells (NBEC), ii) the direct anti-tumor activity of IL-12 on lung adenocarcinoma cells in vitro and vivo, and the mechanisms involved, and iii) IL-12 activity on NBEC. METHODOLOGY/PRINCIPAL FINDINGS: Stage I lung adenocarcinomas showed significantly (P = 0.012) higher frequency of IL-12Rbeta2 expressing samples than stage II/III tumors. IL-12 treatment of IL-12R(+) neoplastic cells isolated from primary adenocarcinoma (n = 6) inhibited angiogenesis in vitro through down-regulation of different pro-angiogenic genes (e.g. IL-6, VEGF-C, VEGF-D, and laminin-5), as assessed by chorioallantoic membrane (CAM) assay and PCR array. In order to perform in vivo studies, the Calu6 NSCLC cell line was transfected with the IL-12RB2 containing plasmid (Calu6/beta2). Similar to that observed in primary tumors, IL-12 treatment of Calu6/beta2(+) cells inhibited angiogenesis in vitro. Tumors formed by Calu6/beta2 cells in SCID/NOD mice, inoculated subcutaneously or orthotopically, were significantly smaller following IL-12 vs PBS treatment due to inhibition of angiogenesis, and of IL-6 and VEGF-C production. Explanted tumors were studied by histology, immuno-histochemistry and PCR array. NBEC cells were isolated and cultured from lung specimens of non neoplastic origin. NBEC expressed IL-12R and released constitutively tumor promoting cytokines (e.g. IL-6 and CCL2). Treatment of NBEC with IL-12 down-regulated production of these cytokines. CONCLUSIONS: This study demonstrates that IL-12 inhibits directly the growth of human lung adenocarcinoma and targets the adjacent NBEC. These novel anti-tumor activities of IL-12 add to the well known immune-modulatory properties of the cytokine and may provide a rational basis for the development of a clinical trial

Effect of CpG Depletion of Vector Genome on CD8+ T Cell Responses in AAV Gene Therapy

Adeno associated viral (AAV) vectors have emerged as a preferred platform for in vivo gene replacement therapy and represent one of the most promising strategies to treat monogenetic disorders such as hemophilia. However, immune responses to gene transfer have hampered human gene therapy in clinical trials. Over the past decade, it has become clear that innate immune recognition provides signals for the induction of antigen-specific responses against vector or transgene product. In particular, TLR9 recognition of the vector's DNA genome in plasmacytoid dendritic cells (pDCs) has been identified as a key factor. Data from clinical trials and pre-clinical studies implement CpG motifs in the vector genome as drivers of immune responses, especially of CD8+ T cell activation. Here, we demonstrate that cross-priming of AAV capsid-specific CD8+ T cells depends on XCR1+ dendritic cells (which are likely the main cross-presenting cell that cooperates with pDCs to activate CD8+ T cells) and can be minimized by the elimination of CpG motifs in the vector genome. Further, a CpG-depleted vector expressing human coagulation factor IX showed markedly reduced (albeit not entirely eliminated) CD8+ T cell infiltration upon intramuscular gene transfer in hemophilia B mice when compared to conventional CpG+ vector (comprised of native sequences), resulting in better preservation of transduced muscle fibers. Therefore, this deimmunization strategy is helpful in reducing the potential for CD8+ T cell responses to capsid or transgene product. However, CpG depletion had minimal effects on antibody responses against capsid or transgene product, which appear to be largely independent of CpG motifs

Design and implementation of a seismic Newtonian-noise cancellation system for the Virgo gravitational-wave detector

Terrestrial gravity perturbations caused by seismic fields produce the so-called Newtonian noise in gravitational-wave detectors, which is predicted to limit their sensitivity in the upcoming observing runs. In the past, this noise was seen as an infrastructural limitation, i.e., something that cannot be overcome without major investments to improve a detector's infrastructure. However, it is possible to have at least an indirect estimate of this noise by using the data from a large number of seismometers deployed around a detector's suspended test masses. The noise estimate can be subtracted from the gravitational-wave data; a process called Newtonian-noise cancellation (NNC). In this article, we present the design and implementation of the first NNC system at the Virgo detector as part of its AdV+ upgrade. It uses data from 110 vertical geophones deployed inside the Virgo buildings in optimized array configurations. We use a separate tiltmeter channel to test the pipeline in a proof-of-principle. The system has been running with good performance over months

Antitumor and antiangiogenic effect of the dual EGFR and HER-2 tyrosine kinase inhibitor lapatinib in a lung cancer model

<p>Abstract</p> <p>Background</p> <p>There is strong evidence demonstrating that activation of epidermal growth factor receptors (EGFRs) leads to tumor growth, progression, invasion and metastasis. Erlotinib and gefitinib, two EGFR-targeted agents, have been shown to be relevant drugs for lung cancer treatment. Recent studies demonstrate that lapatinib, a dual tyrosine kinase inhibitor of EGFR and HER-2 receptors, is clinically effective against HER-2-overexpressing metastatic breast cancer. In this report, we investigated the activity of lapatinib against non-small cell lung cancer (NSCLC).</p> <p>Methods</p> <p>We selected the lung cancer cell line A549, which harbors genomic amplification of EGFR and HER-2. Proliferation, cell cycle analysis, clonogenic assays, and signaling cascade analyses (by western blot) were performed <it>in vitro</it>. <it>In vivo </it>experiments with A549 cells xenotransplanted into nude mice treated with lapatinib (with or without radiotherapy) were also carried out.</p> <p>Results</p> <p>Lapatinib dramatically reduced cell proliferation (<it>P </it>< 0.0001), DNA synthesis (<it>P </it>< 0.006), and colony formation capacity (<it>P </it>< 0.0001) in A549 cells <it>in vitro</it>. Furthermore, lapatinib induced G1 cell cycle arrest (<it>P </it>< 0.0001) and apoptotic cell death (<it>P </it>< 0.0006) and reduced cyclin A and B1 levels, which are regulators of S and G2/M cell cycle stages, respectively. Stimulation of apoptosis in lapatinib-treated A549 cells was correlated with increased cleaved PARP, active caspase-3, and proapoptotic Bak-1 levels, and reduction in the antiapoptic IAP-2 and Bcl-xL protein levels. We also demonstrate that lapatinib altered EGFR/HER-2 signaling pathways reducing p-EGFR, p-HER-2, p-ERK1/2, p-AKT, c-Myc and PCNA levels. <it>In vivo </it>experiments revealed that A549 tumor-bearing mice treated with lapatinib had significantly less active tumors (as assessed by PET analysis) (<it>P </it>< 0.04) and smaller in size than controls. In addition, tumors from lapatinib-treated mice showed a dramatic reduction in angiogenesis (<it>P </it>< 0.0001).</p> <p>Conclusion</p> <p>Overall, these data suggest that lapatinib may be a clinically useful agent for the treatment of lung cancer.</p

CD24 + Liver Tumor-Initiating Cells Drive Self-Renewal and Tumor Initiation through STAT3-Mediated NANOG Regulation

Tumor-initiating cells (T-ICs) are a subpopulation of chemoresistant tumor cells that have been shown to cause tumor recurrence upon chemotherapy. Identification of T-ICs and their related pathways are therefore priorities for the development of new therapeutic paradigms. We established chemoresistant hepatocellular carcinoma (HCC) xenograft tumors in immunocompromised mice in which an enriched T-IC population was capable of tumor initiation and self-renewal. With this model, we found CD24 to be upregulated in residual chemoresistant tumors when compared with bulk tumor upon cisplatin treatment. CD24 + HCC cells were found to be critical for the maintenance, self-renewal, differentiation, and metastasis of tumors and to significantly impact patients' clinical outcome. With a lentiviral-based knockdown approach, CD24 was found to be a functional liver T-IC marker that drives T-IC genesis through STAT3-mediated NANOG regulation. Our findings point to a CD24 cascade in liver T-ICs that may provide an attractive therapeutic target for HCC patients. © 2011 Elsevier Inc.postprin

Parkin Ubiquitination of Kindlin-2 Enables Mitochondria-Associated Metastasis Suppression

Mitochondria are signaling organelles implicated in cancer, but the mechanisms are elusive. Here, we show that Parkin, an E3 ubiquitination (Ub) ligase altered in Parkinson\u27s disease, forms a complex with the regulator of cell motility, Kindlin-2 (K2), at mitochondria of tumor cells. In turn, Parkin ubiquitinates Lys581 and Lys582 using Lys48 linkages, resulting in proteasomal degradation of K2 and shortened half-life from ∼5 h to ∼1.5 h. Loss of K2 inhibits focal adhesion turnover and β1 integrin activation, impairs membrane lamellipodia size and frequency, and inhibits mitochondrial dynamics, altogether suppressing tumor cell-extracellular matrix interactions, migration, and invasion. Conversely, Parkin does not affect tumor cell proliferation, cell cycle transitions, or apoptosis. Expression of a Parkin Ub-resistant K2 Lys581Ala/Lys582Ala double mutant is sufficient to restore membrane lamellipodia dynamics, correct mitochondrial fusion/fission, and preserve single-cell migration and invasion. In a 3D model of mammary gland developmental morphogenesis, impaired K2 Ub drives multiple oncogenic traits of EMT, increased cell proliferation, reduced apoptosis, and disrupted basal-apical polarity. Therefore, deregulated K2 is a potent oncogene, and its Ub by Parkin enables mitochondria-associated metastasis suppression

Search for gravitational waves from low mass compact binary coalescence in LIGO's sixth science run and Virgo's science runs 2 and 3

We report on a search for gravitational waves from coalescing compact binaries using LIGO and Virgo observations between July 7, 2009, and October 20, 2010. We searched for signals from binaries with total mass between 2 and 25M⊙; this includes binary neutron stars, binary black holes, and binaries consisting of a black hole and neutron star. The detectors were sensitive to systems up to 40 Mpc distant for binary neutron stars, and further for higher mass systems. No gravitational-wave signals were detected. We report upper limits on the rate of compact binary coalescence as a function of total mass, including the results from previous LIGO and Virgo observations. The cumulative 90% confidence rate upper limits of the binary coalescence of binary neutron star, neutron star-black hole, and binary black hole systems are 1.3×10−4, 3.1×10−5, and 6.4×10−6  Mpc−3 yr−1, respectively. These upper limits are up to a factor 1.4 lower than previously derived limits. We also report on results from a blind injection challenge. © 2012 The American Physical Societ