456 research outputs found

    APC Activation Restores Functional CD4+CD25+ Regulatory T Cells in NOD Mice that Can Prevent Diabetes Development

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    BACKGROUND: Defects in APC and regulatory cells are associated with diabetes development in NOD mice. We have shown previously that NOD APC are not effective at stimulating CD4(+)CD25(+) regulatory cell function in vitro. We hypothesize that failure of NOD APC to properly activate CD4(+)CD25(+) regulatory cells in vivo could compromise their ability to control pathogenic cells, and activation of NOD APC could restore this defect, thereby preventing disease. METHODOLOGY/PRINCIPAL FINDINGS: To test these hypotheses, we used the well-documented ability of complete Freund's adjuvant (CFA), an APC activator, to prevent disease in NOD mice. Phenotype and function of CD4(+)CD25(+) regulatory cells from untreated and CFA-treated NOD mice were determined by FACS, and in vitro and in vivo assays. APC from these mice were also evaluated for their ability to activate regulatory cells in vitro. We have found that sick NOD CD4(+)CD25(+) cells expressed Foxp3 at the same percentages, but decreased levels per cell, compared to young NOD or non-NOD controls. Treatment with CFA increased Foxp3 expression in NOD cells, and also increased the percentages of CD4(+)CD25(+)Foxp3(+) cells infiltrating the pancreas compared to untreated NOD mice. Moreover, CD4(+)CD25(+) cells from pancreatic LN of CFA-treated, but not untreated, NOD mice transferred protection from diabetes. Finally, APC isolated from CFA-treated mice increased Foxp3 and granzyme B expression as well as regulatory function by NOD CD4(+)CD25(+) cells in vitro compared to APC from untreated NOD mice. CONCLUSIONS/SIGNIFICANCE: These data suggest that regulatory T cell function and ability to control pathogenic cells can be enhanced in NOD mice by activating NOD APC

    Ultrasound imaging versus morphopathology in cardiovascular diseases. Coronary collateral circulation and atherosclerotic plaque

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    This review article is aimed at comparing the results of histopathological and clinical imaging studies to assess coronary collateral circulation in humans. The role of collaterals, as emerging from morphological studies in both normal and atherosclerotic coronary vessels, is described; in addition, present role and future perpectives of echocardiographic techniques in assessing collateral circulation are briefly summarized

    All-linear time reversal by a dynamic artificial crystal

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    The time reversal of pulsed signals or propagating wave packets has long been recognized to have profound scientific and technological significance. Until now, all experimentally verified time-reversal mechanisms have been reliant upon nonlinear phenomena such as four-wave mixing. In this paper, we report the experimental realization of all-linear time reversal. The time-reversal mechanism we propose is based on the dynamic control of an artificial crystal structure, and is demonstrated in a spin-wave system using a dynamic magnonic crystal. The crystal is switched from an homogeneous state to one in which its properties vary with spatial period a, while a propagating wave packet is inside. As a result, a linear coupling between wave components with wave vectors k≈π/a and k′=k−2ππ/a≈−π/a is produced, which leads to spectral inversion, and thus to the formation of a time-reversed wave packet. The reversal mechanism is entirely general and so applicable to artificial crystal systems of any physical nature

    Internal Wave Turbulence Near a Texel Beach

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    A summer bather entering a calm sea from the beach may sense alternating warm and cold water. This can be felt when moving forward into the sea (‘vertically homogeneous’ and ‘horizontally different’), but also when standing still between one’s feet and body (‘vertically different’). On a calm summer-day, an array of high-precision sensors has measured fast temperature-changes up to 1°C near a Texel-island (NL) beach. The measurements show that sensed variations are in fact internal waves, fronts and turbulence, supported in part by vertical stable stratification in density (temperature). Such motions are common in the deep ocean, but generally not in shallow seas where turbulent mixing is expected strong enough to homogenize. The internal beach-waves have amplitudes ten-times larger than those of the small surface wind waves. Quantifying their turbulent mixing gives diffusivity estimates of 10−4–10−3 m2 s−1, which are larger than found in open-ocean but smaller than wave breaking above deep sloping topography

    A physiological time analysis of the duration of the gonotrophic cycle of Anopheles pseudopunctipennis and its implications for malaria transmission in Bolivia

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    <p>Abstract</p> <p>Background</p> <p>The length of the gonotrophic cycle varies the vectorial capacity of a mosquito vector and therefore its exact estimation is important in epidemiological modelling. Because the gonotrophic cycle length depends on temperature, its estimation can be satisfactorily computed by means of physiological time analysis.</p> <p>Methods</p> <p>A model of physiological time was developed and calibrated for <it>Anopheles pseudopunctipennis</it>, one of the main malaria vectors in South America, using data from laboratory temperature controlled experiments. The model was validated under varying temperatures and could predict the time elapsed from blood engorgement to oviposition according to the temperature.</p> <p>Results</p> <p>In laboratory experiments, a batch of <it>An. pseudopunctipennis </it>fed at the same time may lay eggs during several consecutive nights (2–3 at high temperature and > 10 at low temperature). The model took into account such pattern and was used to predict the range of the gonotrophic cycle duration of <it>An. pseudopunctipennis </it>in four characteristic sites of Bolivia. It showed that the predicted cycle duration for <it>An. pseudopunctipennis </it>exhibited a seasonal pattern, with higher variances where climatic conditions were less stable. Predicted mean values of the (minimum) duration ranged from 3.3 days up to > 10 days, depending on the season and the geographical location. The analysis of ovaries development stages of field collected biting mosquitoes indicated that the phase 1 of Beklemishev might be of significant duration for <it>An. pseudopunctipennis</it>. The gonotrophic cycle length of <it>An. pseudopunctipennis </it>correlates with malaria transmission patterns observed in Bolivia which depend on locations and seasons.</p> <p>Conclusion</p> <p>A new presentation of cycle length results taking into account the number of ovipositing nights and the proportion of mosquitoes laying eggs is suggested. The present approach using physiological time analysis might serve as an outline to other similar studies and allows the inclusion of temperature effects on the gonotrophic cycle in transmission models. However, to better explore the effects of temperature on malaria transmission, the others parameters of the vectorial capacity should be included in the analysis and modelled accordingly.</p

    In Vivo Human Apolipoprotein E Isoform Fractional Turnover Rates in the CNS

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    Apolipoprotein E (ApoE) is the strongest genetic risk factor for Alzheimer’s disease and has been implicated in the risk for other neurological disorders. The three common ApoE isoforms (ApoE2, E3, and E4) each differ by a single amino acid, with ApoE4 increasing and ApoE2 decreasing the risk of Alzheimer’s disease (AD). Both the isoform and amount of ApoE in the brain modulate AD pathology by altering the extent of amyloid beta (Aβ) peptide deposition. Therefore, quantifying ApoE isoform production and clearance rates may advance our understanding of the role of ApoE in health and disease. To measure the kinetics of ApoE in the central nervous system (CNS), we applied in vivo stable isotope labeling to quantify the fractional turnover rates of ApoE isoforms in 18 cognitively-normal adults and in ApoE3 and ApoE4 targeted-replacement mice. No isoform-specific differences in CNS ApoE3 and ApoE4 turnover rates were observed when measured in human CSF or mouse brain. However, CNS and peripheral ApoE isoform turnover rates differed substantially, which is consistent with previous reports and suggests that the pathways responsible for ApoE metabolism are different in the CNS and the periphery. We also demonstrate a slower turnover rate for CSF ApoE than that for amyloid beta, another molecule critically important in AD pathogenesis

    Practices participating in a dental PBRN have substantial and advantageous diversity even though as a group they have much in common with dentists at large

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    <p>Abstract</p> <p>Background</p> <p>Practice-based research networks offer important opportunities to move recent advances into routine clinical practice. If their findings are not only generalizable to dental practices at large, but can also elucidate how practice characteristics are related to treatment outcome, their importance is even further elevated. Our objective was to determine whether we met a key objective for The Dental Practice-Based Research Network (DPBRN): to recruit a diverse range of practitioner-investigators interested in doing DPBRN studies.</p> <p>Methods</p> <p>DPBRN participants completed an enrollment questionnaire about their practices and themselves. To date, more than 1100 practitioners from the five participating regions have completed the questionnaire. The regions consist of: Alabama/Mississippi, Florida/Georgia, Minnesota, Permanente Dental Associates, and Scandinavia (Denmark, Norway, and Sweden). We tested the hypothesis that there are statistically significant differences in key characteristics among DPBRN practices, based on responses from dentists who participated in DPBRN's first network-wide study (n = 546).</p> <p>Results</p> <p>There were statistically significant, substantive regional differences among DPBRN-participating dentists, their practices, and their patient populations.</p> <p>Conclusion</p> <p>Although as a group, participants have much in common with practices at large; their substantial diversity offers important advantages, such as being able to evaluate how practice differences may affect treatment outcomes, while simultaneously offering generalizability to dentists at large. This should help foster knowledge transfer in both the research-to-practice and practice-to-research directions.</p

    Anti-tumor effect of bisphosphonate (YM529) on non-small cell lung cancer cell lines

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    BACKGROUND: YM529 is a newly developed nitrogen-containing bisphosphonate (BP) classified as a third-generation BP that shows a 100-fold greater potency against bone resorption than pamidronate, a second-generation BP. This agent is, therefore expected to be extremely useful clinically for the treatment of osteoporosis and hypercalcemia. Recently, YM529 as well as other third-generation BPs have also been shown to exert anti-tumor effects against various types of cancer cells both in vitro or/and in vivo. In this study, we investigate the anti-tumor effect of YM529 on non-small cell lung cancer (NSCLC). METHODS: Direct anti-tumor effect of YM529 against 8 NSCLC cell lines (adenocarcinoma: H23, H1299, NCI-H1819, NCI-H2009, H44, A549, adenosquamous cell carcinoma: NCI-H125, squamous cell carcinoma: NCI-H157) were measured by MTS assay and calculated inhibition concentration 50 % (IC(50)) values. YM529 induced apoptosis of NCI-H1819 was examined by DNA fragmentation of 2 % agarose gel electrophoresis and flowcytometric analysis (sub-G(1 )method). We examined where YM529 given effect to apoptosis of NSCLC cells in signaling pathway of the mevalonate pathway by western blotting analysis. RESULTS: We found that there was direct anti-tumor effect of YM529 on 8 NSCLC cell lines in a dose-dependent manner and their IC(50 )values were 2.1 to 7.9 μM and YM529 induced apoptosis and G(1 )arrest cell cycle with dose-dependent manner and YM529 caused down regulation of phospholyration of ERK1/2 in signaling pathways of NSCLC cell line (NCI-H1819). CONCLUSION: Our study demonstrate that YM529 showed direct anti-tumor effect on NSCLC cell lines in vitro, which supports the possibility that third-generation BPs including YM529 can be one of therapeutic options for NSCLC
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