201 research outputs found

    Vibrational and rotational sequences in 101 Mo and 103,4 Ru studied via multinucleon transfer reactions

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    The near yrast states of 101 Mo and 103,104 Ru have been studied following their population via heavy ion multinucleon transfer reactions between a 136 Xe beam and a thin, self supporting 100 Mo target. The ground state sequence in 104 Ru can be understood as demonstrating a simple evolution from a quasi vibrational structure at lower spins to statically deformed, quasi rotational excitation involving the population of a pair of low Omega h11 2 neutron orbitals. The effect of the decoupled h11 2 orbital on this vibration to rotational evolution is demonstrated by an extension of the E GOS prescription to include odd A nuclei. The experimental results are also compared with self consistent Total Routhian Surface calculations which also highlight the polarising role of the highly aligned neutron h11 2 orbital in these nucle

    Timp1 interacts with beta-1 integrin and CD63 along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway independently of Akt phosphorylation

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    Background: Anoikis resistance is one of the abilities acquired along tumor progression. This characteristic is associated with metastasis development, since tumorigenic cells must survive independently of cell-matrix interactions in this process. in our laboratory, it was developed a murine melanocyte malignant transformation model associated with a sustained stressful condition. After subjecting melan-a melanocytes to 1, 2, 3 and 4 cycles of anchorage impediment, anoikis resistant cells were established and named 1C, 2C, 3C and 4C, respectively. These cells showed altered morphology and PMA independent cell growth, but were not tumorigenic, corresponding to pre-malignant cells. After limiting dilution of 4C pre-malignant cells, melanoma cell lines with different characteristics were obtained. Previous data from our group showed that increased Timp1 expression correlated with anoikis-resistant phenotype. Timp1 was shown to confer anchorage-independent growth capability to melan-a melanocytes and render melanoma cells more aggressive when injected into mice. However, the mechanisms involved in anoikis regulation by Timp1 in tumorigenic cells are not clear yet.Methods: the beta 1-integrin and Timp1 expression were evaluated by Western blotting and CD63 protein expression by flow cytometry using specific antibodies. To analyze the interaction among Timp1, CD63 and beta 1-integrin, immunoprecipitation assays were performed, anoikis resistance capability was evaluated in the presence or not of the PI3-K inhibitors, Wortmannin and LY294002. Relative expression of TIMP1 and CD63 in human metastatic melanoma cells was analyzed by real time PCR.Results: Differential association among Timp1, CD63 and beta 1-integrins was observed in melan-a melanocytes, 4C pre-malignant melanocytes and 4C11- and 4C11+ melanoma cells. Timp1 present in conditioned medium of melanoma cells rendered melan-a melanocytes anoikis-resistant through PI3-K signaling pathway independently of Akt activation. in human melanoma cell lines, in which TIMP1 and beta-1 integrin were also found to be interacting, TIMP1 and CD63 levels together was shown to correlate significantly with colony formation capacity.Conclusions: Our results show that Timp1 is assembled in a supramolecular complex containing CD63 and beta 1-integrins along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway, independently of Akt phosphorylation. in addition, our data point TIMP1, mainly together with CD63, as a potential biomarker of melanoma.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Pharmacol, São Paulo, BrazilUniversidade Federal de São Paulo, Microbiol Immunol & Parasitol Dept, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, São Paulo, BrazilLudwig Inst Canc Res, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, São Paulo, BrazilUniversidade Federal de São Paulo, Microbiol Immunol & Parasitol Dept, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, São Paulo, BrazilFAPESP: 2011/12306-1FAPESP: 2010/18715-8CAPES: 2867/10Web of Scienc

    Prevalence and Associated Factors of Dyslipidemia in the Adult Chinese Population

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    To determine the prevalence, associated factors, awareness and control of dyslipidemia in Chinese living in Greater Beijing, we measured the serum cholesterol concentration in 3251 Chinese adults (age: 45 to 89 years) as participants of the population-based Beijing Eye Study 2006. Additional information on treatment of dyslipidemia was obtained using a standard questionnaire. The mean concentrations of total, HDL cholesterol, LDL cholesterol and triglycerides were 4.92±1.01 mmol/L, 1.61±0.36 mmol/L, 2.88±0.85 mmol/L, and 1.76±1.29 mmol/L, respectively. Prevalence of dyslipidemia was 56.1±0.9%%. Presence of dyslipidemia was significantly associated with increasing age (odds ratio (OR):1.02; 95% confidence interval (CI): 1.01, 1.03), female gender (OR:1.51; 95%CI: 1.25, 1.83), urban region (OR:1.82; 95%CI: 1.30, 2.55), body mass index (OR:1.13; 95%CI: 1.10, 1.15), income (OR:1.11; 95%CI:1.02, 1.21), blood glucose concentration (OR:1.10; 95%CI:1.05, 1.16), diastolic blood pressure (OR:1.02; 95%CI: 1.01, 1.03), and smoking (OR:1.23; 1.01, 1.51). Among those who had dyslipidemia, the proportion of subjects who were aware, treated and controlled was 50.9%, 23.8%, and 39.91%, respectively. The awareness rate was associated with urban region (P = 0.001; OR: 6.50), body mass index (P = 0.001; OR:1.06), and income (P = 0.02; OR:1.14). The data suggest that dyslipidemia may be present in about 56% of the population aged 45+ years in Greater Beijing. Factors likely associated with dyslipidemia were higher age, female gender, urban region, higher body mass index, higher income, higher blood concentration of glucose, higher diastolic blood pressure, and smoking. In the examined study population, treatment rate was 24% with about 60% of the treated subjects still having uncontrolled dyslipidemia

    B Cell Activating Factor (BAFF) and T Cells Cooperate to Breach B Cell Tolerance in Lupus-Prone New Zealand Black (NZB) Mice

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    The presence of autoantibodies in New Zealand Black (NZB) mice suggests a B cell tolerance defect however the nature of this defect is unknown. To determine whether defects in B cell anergy contribute to the autoimmune phenotype in NZB mice, soluble hen egg lysozyme (sHEL) and anti-HEL Ig transgenes were bred onto the NZB background to generate double transgenic (dTg) mice. NZB dTg mice had elevated levels of anti-HEL antibodies, despite apparently normal B cell functional anergy in-vitro. NZB dTg B cells also demonstrated increased survival and abnormal entry into the follicular compartment following transfer into sHEL mice. Since this process is dependent on BAFF, BAFF serum and mRNA levels were assessed and were found to be significantly elevated in NZB dTg mice. Treatment of NZB sHEL recipient mice with TACI-Ig reduced NZB dTg B cell survival following adoptive transfer, confirming the role of BAFF in this process. Although NZB mice had modestly elevated BAFF, the enhanced NZB B cell survival response appeared to result from an altered response to BAFF. In contrast, T cell blockade had a minimal effect on B cell survival, but inhibited anti-HEL antibody production. The findings suggest that the modest BAFF elevations in NZB mice are sufficient to perturb B cell tolerance, particularly when acting in concert with B cell functional abnormalities and T cell help

    Effects of dietary l-arginine or N-carbamylglutamate supplementation during late gestation of sows on the miR-15b/16, miR-221/222, VEGFA and eNOS expression in umbilical vein

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    Placental vascular formation and blood flow are crucial for fetal survival, growth and development, and arginine regulates vascular development and function. This study determined the effects of dietary arginine or N-carbamylglutamate (NCG) supplementation during late gestation of sows on the microRNAs, vascular endothelial growth factor A (VEGFA) and endothelial nitric oxide synthase (eNOS) expression in umbilical vein. Twenty-seven landrace × large white sows at day (d) 90 of gestation were assigned randomly to three groups and fed the following diets: a control diet and the control diet supplemented with 1.0% l-arginine or 0.10% NCG. Umbilical vein of fetuses with body weight around 2.0 kg (oversized), 1.5 kg (normal) and 0.6 kg (intrauterine growth restriction, IUGR) were obtained immediately after farrowing for miR-15b, miR-16, miR-221, miR-222, VEGFA and eNOS real-time PCR analysis. Compared with the control diets, dietary Arg or NCG supplementation enhanced the reproductive performance of sows, significantly increased (P < 0.05) plasma arginine and decreased plasma VEGF and eNOS (P < 0.05). The miR-15b expression in the umbilical vein was higher (P < 0.05) in the NCG-supplemented group than in the control group. There was a trend in that the miR-222 expression in the umbilical vein of the oversized fetuses was higher (0.05 < P < 0.1) than in the normal and IUGR fetuses. The expression of eNOS in both Arg-supplemented and NCG-supplemented group were lower (P < 0.05) than in the control group. The expression of VEGFA was higher (P < 0.05) in the NCG-supplemented group than in the Arg-supplemented and the control group. Meanwhile, the expression of VEGFA of the oversized fetuses was higher (P < 0.05) than the normal and IUGR fetuses. In conclusion, this study demonstrated that dietary Arg or NCG supplementation may affect microRNAs (miR-15b, miR-222) targeting VEGFA and eNOS gene expressions in umbilical vein, so as to regulate the function and volume of the umbilical vein, provide more nutrients and oxygen from the maternal to the fetus tissue for fetal development and survival, and enhance the reproductive performance of sows

    Neonatal cerebrovascular autoregulation.

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    Cerebrovascular pressure autoregulation is the physiologic mechanism that holds cerebral blood flow (CBF) relatively constant across changes in cerebral perfusion pressure (CPP). Cerebral vasoreactivity refers to the vasoconstriction and vasodilation that occur during fluctuations in arterial blood pressure (ABP) to maintain autoregulation. These are vital protective mechanisms of the brain. Impairments in pressure autoregulation increase the risk of brain injury and persistent neurologic disability. Autoregulation may be impaired during various neonatal disease states including prematurity, hypoxic-ischemic encephalopathy (HIE), intraventricular hemorrhage, congenital cardiac disease, and infants requiring extracorporeal membrane oxygenation (ECMO). Because infants are exquisitely sensitive to changes in cerebral blood flow (CBF), both hypoperfusion and hyperperfusion can cause significant neurologic injury. We will review neonatal pressure autoregulation and autoregulation monitoring techniques with a focus on brain protection. Current clinical therapies have failed to fully prevent permanent brain injuries in neonates. Adjuvant treatments that support and optimize autoregulation may improve neurologic outcomes
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