1,684 research outputs found

    Identification of key genes for carcinogenic pathways associated with colorectal adenoma-to-carcinoma progression

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    Colorectal adenomas form a biologically and clinically distinct intermediate stage in development of colorectal cancer (CRC) from normal colon epithelium. Only 5% of adenomas progress into adenocarcinomas, indicating that malignant transformation requires other biological alterations than those involved in adenoma formation. The present study aimed to explore which cancer-related biological processes are affected during colorectal adenoma-to-carcinoma progression and to identify key genes within these pathways that can serve as tumor markers for malignant transformation. The activity of 12 cancer-related biological processes was compared between 37 colorectal adenomas and 31 adenocarcinomas, using the pathway analysis tool Gene Set Enrichment Analysis. Expression of six gene sets was significantly increased in CRCs compared to adenomas, representing chromosomal instability, proliferation, differentiation, invasion, stroma activation, and angiogenesis. In addition, 18 key genes were identified for these processes based on their significantly increased expression levels. For AURKA and PDGFRB, increased mRNA expression levels were verified at the protein level by immunohistochemical analysis of a series of adenomas and CRCs. This study revealed cancer-related biological processes whose activities are increased during malignant transformation and identified key genes which may be used as tumor markers to improve molecular characterization of colorectal tumors

    IL-6 and IL-10 Anti-Inflammatory Activity Links Exercise to Hypothalamic Insulin and Leptin Sensitivity through IKK beta and ER Stress Inhibition

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    Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Overnutrition caused by overeating is associated with insulin and leptin resistance through IKK beta activation and endoplasmic reticulum (ER) stress in the hypothalamus. Here we show that physical exercise suppresses hyperphagia and associated hypothalamic IKK beta/NF-k beta activation by a mechanism dependent upon the pro-inflammatory cytokine interleukin (IL)-6. The disruption of hypothalamic-specific IL-6 action blocked the beneficial effects of exercise on the re-balance of food intake and insulin and leptin resistance. This molecular mechanism, mediated by physical activity, involves the anti-inflammatory protein IL-10, a core inhibitor of IKK beta/NF-k beta signaling and ER stress. We report that exercise and recombinant IL-6 requires IL-10 expression to suppress hyperphagia-related obesity. Moreover, in contrast to control mice, exercise failed to reverse the pharmacological activation of IKK beta and ER stress in C3H/HeJ mice deficient in hypothalamic IL-6 and IL-10 signaling. Hence, inflammatory signaling in the hypothalamus links beneficial physiological effects of exercise to the central action of insulin and leptin.88Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

    Inducible Nitric Oxide Synthase in Heart Tissue and Nitric Oxide in Serum of Trypanosoma cruzi-Infected Rhesus Monkeys: Association with Heart Injury

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    Chagas disease, a neglected tropical disease caused by the protozoan Trypanosoma cruzi, afflicts from 8 to 15 million people in the Latin America. Chronic chagasic cardiomyopathy (CCC) is the most frequent manifestation of Chagas disease. Currently, patient management only mitigates CCC symptoms. The pathogenic factors leading to CCC remain unknown; therefore their comprehension may contribute to develop more efficient therapies. In patients, high nitric oxide (NO) levels have been associated with CCC severity. In T. cruzi-infected mice, NO, mainly produced via inducible nitric oxide synthase (iNOS/NOS2), is proposed to work in parasite control. However, the participation of iNOS/NOS2 and NO in T. cruzi control and heart injury has been questioned. Here, infected rhesus monkeys and iNOS/NOS2-deficient mice were used to explore the participation of iNOS/NOS2-derived NO in heart injury in T. cruzi infection. Chronically infected monkeys presented electrical abnormalities, myocarditis and fibrosis, resembling the spectrum of human CCC. Moreover, cardiomyocyte lesion correlated with iNOS/NOS2+ cells infiltrating the cardiac tissue. Our findings support that parasite-driven iNOS/NOS2+ cells accumulation in the cardiac tissue and NO overproduction contribute to cardiomyopathy severity, mainly disturbing the pathway involved in electrical synchrony in T. cruzi infection

    Epidemiological aspects of american cutaneous leishmaniasis and phlebotomine sandfly population, in the municipality of monte negro, state of RondĂ´nia, Brazil

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    Introduction: This work was carried out on the purpose of identifying the species of phlebotomine sandflies in the municipality of Monte Negro, state of Rondonia, Brazil, that may have been transmitting the American cutaneous leishmaniasis (ACL), and concisely describe epidemiological aspects of disease. Methods: The epidemiologic and socioeconomical indicators were obtained from government institutions and the local Municipal Secretary of Health. Phlebotomine sandflies were captured using CDC light traps between July 2006 to July 2008. The total of 1,240 of female sandflies were examined by PCR method directed to k-DNA. Results: There has been a significant decrease in the incidence of ACL of about 50% over the last ten years in the municipality. A total of 1,935 specimens of 53 sandfly species were captured, three of the genus Brumptomyia genus and 50 of the genus Lutzomyia. The predominant species was Lutzomyia acanthopharynx, Lutzomyia whitmani, Lutzomyia geniculata and Lutzomyia davisi. None were positive for Leishmania sp. Conclusions: Four sandflies species were found in the State of Rondonia for the first time: Brumptomyia brumpti, Lutzomyia tarapacaensis, Lutzomyia melloi and Lutzomyia lenti. The presence of Lutzomyia longipalpis, was also captured. Socioeconomical improvement of Brazilian economy and the increase of environmental surveillance in the last 15 years collaborated in the decrease of people exposed to vectors, reducing the incidence of ACL

    f(R) theories

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    Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom

    Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

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    The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO
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