145 research outputs found

    A coated-wire ion-selective electrode for ionic calcium measurements

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    A coated-wire ion-selective electrode for measuring ionic calcium was developed, in collaboration with Teknektron Sensor Development Corporation (TSDC). This coated wire electrode sensor makes use of advanced, ion-responsive polyvinyl chloride (PVC) membrane technology, whereby the electroactive agent is incorporated into a polymeric film. The technology greatly simplifies conventional ion-selective electrode measurement technology, and is envisioned to be used for real-time measurement of physiological and environment ionic constituents, initially calcium. A primary target biomedical application is the real-time measurement of urinary and blood calcium changes during extended exposure to microgravity, during prolonged hospital or fracture immobilization, and for osteoporosis research. Potential advanced life support applications include monitoring of calcium and other ions, heavy metals, and related parameters in closed-loop water processing and management systems. This technology provides a much simplified ionic calcium measurement capability, suitable for both automated in-vitro, in-vivo, and in-situ measurement applications, which should be of great interest to the medical, scientific, chemical, and space life sciences communities

    Alcohol promotes breast cancer cell invasion by regulating the Nm23-ITGA5 pathway

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    <p>Abstract</p> <p>Background</p> <p>Alcohol consumption is an established risk factor for breast cancer metastasis. Yet, the mechanism by which alcohol promotes breast cancer metastases is unknown. The ability of cancer cells to invade through tissue barriers (such as basement membrane and interstitial stroma) is an essential step towards establishing cancer metastasis. In the present study, we identify and examine the roles of two genes, <it>Nm23 </it>and <it>ITGA5</it>, in alcohol-induced breast cancer cell invasion.</p> <p>Methods</p> <p>Human breast cancer T47D cells were treated with ethanol at various concentrations. Boyden chamber invasion assays were used to measure cellular invasive ability. The mRNA expression level of metastasis suppressor genes including <it>Nm23 </it>was determined by qRT-PCR. <it>ITGA5 </it>was identified using a qRT-PCR array of 84 genes important for cell-cell and cell-extracellular matrix interactions. <it>Nm23 </it>overexpression in addition to <it>Nm23</it>- and <it>ITGA5 </it>knock-down were used to determine the role of the Nm23-ITGA5 pathway on cellular invasive ability of T47D cells. Protein expression levels were verified by Western blot.</p> <p>Results</p> <p>Alcohol increased the invasive ability of human breast cancer T47D cells in a dose-dependent manner through the suppression of the <it>Nm23 </it>metastatic suppressor gene. In turn, <it>Nm23 </it>down-regulation increased expression of fibronectin receptor subunit <it>ITGA5</it>, which subsequently led to increased cellular invasion. Moreover, <it>Nm23 </it>overexpression was effective in suppressing the effects of alcohol on cell invasion. In addition, we show that the effects of alcohol on invasion were also inhibited by knock-down of <it>ITGA5</it>.</p> <p>Conclusions</p> <p>Our results suggest that the Nm23-ITGA5 pathway plays a critical role in alcohol-induced breast cancer cell invasion. Thus, regulation of this pathway may potentially be used to prevent the establishment of alcohol-promoted metastases in human breast cancers.</p

    Loss-of-function analysis suggests that omi/htra2 is not an essential component of the pink1/parkin pathway in vivo

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    Recently, a mutation in the mitochondrial protease Omi/HtrA2, G399S, was found in sporadic Parkinson's disease (PD) patients, leading to the designation of Omi/HtrA2 as PD locus 13 (PARK13). G399S reportedly results in reduced Omi protease activity. In vitro studies have suggested that Omi/HtrA2 acts downstream of PINK1, mutations in which mediate recessive forms of PD. We, as well as other, have previously shown that the Drosophila homologs of the familial PD genes, PINK1 (PARK6) and PARKIN (PARK2), function in a common genetic pathway to regulate mitochondrial integrity and dynamics. Whether Omi/HtrA2 regulates mitochondrial integrity and whether it acts downstream of PINK1 in vivo remain to be explored. Here, we show that Omi/HtrA2 null mutants in Drosophila, in contrast to pink1 or parkin null mutants, do not show mitochondrial morphological defects. Extensive genetic interaction studies do not provide support for models in which Omi/HtrA2 functions in the same genetic pathway as pink1, or carries out partially redundant functions with pink1, at least with respect to regulation of mitochondrial integrity and dynamics. Furthermore, Omi/HtrA2 G399S retains significant, if not full, function of Omi/HtrA2, compared with expression of protease-compromised versions of the protein. In light of recent findings showing that G399S can be found at comparable frequencies in PD patients and healthy controls, we do not favor a hypothesis in which Omi/HtrA2 plays an essential role in PD pathogenesis, at least with respect to regulation of mitochondrial integrity in the pink1/parkin pathway

    A cross-sectional association of obesity with coronary calcium among Japanese, Koreans, Japanese-Americans, and US-Whites

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    [Aims] Conflicting evidence exists regarding whether obesity is independently associated with coronary artery calcium (CAC), a measure of coronary atherosclerosis. We examined an independent association of obesity with prevalent CAC among samples of multi-ethnic groups whose background populations have varying levels of obesity and coronary heart disease (CHD). [Methods and results] We analysed a population-based sample of 1212 men, aged 40–49 years free of clinical cardiovascular disease recruited in 2002–06; 310 Japanese in Japan (JJ), 294 Koreans in South Korea (KN), 300 Japanese Americans (JA), and 308 Whites in the USA (UW). We defined prevalent CAC as an Agatston score of ≄10. Prevalent CAC was calculated by tertile of the body mass index (BMI) in each ethnic group and was plotted against the corresponding median of tertile BMI. Additionally, logistic regression was conducted to examine whether an association of the BMI was independent of conventional risk factors. The median BMI and crude prevalence of CAC for JJ, KN, JA, and UW were 23.4, 24.4, 27.4, and 27.1 (kg/m2); 12, 11, 32, and 26 (%), respectively. Despite the absolute difference in levels of BMI and CAC across groups, higher BMI was generally associated with higher prevalent CAC in each group. After adjusting for age, smoking, alcohol, hypertension, lipids, and diabetes mellitus, the BMI was positively and independently associated with prevalent CAC in JJ, KN, UW, but not in JA. [Conclusion] In this multi-ethnic study, obesity was independently associated with subclinical stage of coronary atherosclerosis among men aged 40–49 years regardless of the BMI level

    Study of e+e−→ppˉe^+e^- \rightarrow p\bar{p} in the vicinity of ψ(3770)\psi(3770)

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    Using 2917 pb−1\rm{pb}^{-1} of data accumulated at 3.773~GeV\rm{GeV}, 44.5~pb−1\rm{pb}^{-1} of data accumulated at 3.65~GeV\rm{GeV} and data accumulated during a ψ(3770)\psi(3770) line-shape scan with the BESIII detector, the reaction e+e−→ppˉe^+e^-\rightarrow p\bar{p} is studied considering a possible interference between resonant and continuum amplitudes. The cross section of e+e−→ψ(3770)→ppˉe^+e^-\rightarrow\psi(3770)\rightarrow p\bar{p}, σ(e+e−→ψ(3770)→ppˉ)\sigma(e^+e^-\rightarrow\psi(3770)\rightarrow p\bar{p}), is found to have two solutions, determined to be (0.059±0.032±0.0120.059\pm0.032\pm0.012) pb with the phase angle ϕ=(255.8±37.9±4.8)∘\phi = (255.8\pm37.9\pm4.8)^\circ (<<0.11 pb at the 90% confidence level), or σ(e+e−→ψ(3770)→ppˉ)=(2.57±0.12±0.12\sigma(e^+e^-\rightarrow\psi(3770)\rightarrow p\bar{p}) = (2.57\pm0.12\pm0.12) pb with ϕ=(266.9±6.1±0.9)∘\phi = (266.9\pm6.1\pm0.9)^\circ both of which agree with a destructive interference. Using the obtained cross section of ψ(3770)→ppˉ\psi(3770)\rightarrow p\bar{p}, the cross section of ppˉ→ψ(3770)p\bar{p}\rightarrow \psi(3770), which is useful information for the future PANDA experiment, is estimated to be either (9.8±5.79.8\pm5.7) nb (<17.2<17.2 nb at 90% C.L.) or (425.6±42.9)(425.6\pm42.9) nb

    Measurement of W+W− production in association with one jet in proton–proton collisions at sqrt(s) = 8TeV with the ATLAS detector

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    The production of W boson pairs in association with one jet in pp collisions at View the MathML sources=8 TeV is studied using data corresponding to an integrated luminosity of 20.3 fb−1 collected by the ATLAS detector during 2012 at the CERN Large Hadron Collider. The cross section is measured in a fiducial phase-space region defined by the presence of exactly one electron and one muon, missing transverse momentum and exactly one jet with a transverse momentum above 25 GeV and a pseudorapidity of |η|<4.5|η|<4.5. The leptons are required to have opposite electric charge and to pass transverse momentum and pseudorapidity requirements. The fiducial cross section is found to be View the MathML sourceσWWfid,1-jet=136±6(stat)±14(syst)±3(lumi) fb. In combination with a previous measurement restricted to leptonic final states with no associated jets, the fiducial cross section of WW production with zero or one jet is measured to be View the MathML sourceσWWfid,≀1-jet=511±9(stat)±26(syst)±10(lumi) fb. The ratio of fiducial cross sections in final states with one and zero jets is determined to be 0.36±0.050.36±0.05. Finally, a total cross section extrapolated from the fiducial measurement of WW production with zero or one associated jet is reported. The measurements are compared to theoretical predictions and found in good agreement

    Pharmaceutical pollution of the world's rivers

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    Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world's rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to middle-income countries and were associated with areas with poor wastewater and waste management infrastructure and pharmaceutical manufacturing. The most frequently detected APIs were carbamazepine, metformin, and caffeine (a compound also arising from lifestyle use), which were detected at over half of the sites monitored. Concentrations of at least one API at 25.7% of the sampling sites were greater than concentrations considered safe for aquatic organisms, or which are of concern in terms of selection for antimicrobial resistance. Therefore, pharmaceutical pollution poses a global threat to environmental and human health, as well as to delivery of the United Nations Sustainable Development Goals
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