Oxidative Stress Disruption of Receptor-Mediated Calcium Signaling Mechanisms

Background: Oxidative stress increases the cytosolic content of calcium in the cytoplasm through a combination of effects on calcium pumps, exchangers, channels and binding proteins. In this study, oxidative stress was produced by exposure to tert-butyl hydroperoxide (tBHP); cell viability was assessed using a dye reduction assay; receptor binding was characterized using [3H]N-methylscopolamine ([3H]MS); and cytosolic and luminal endoplasmic reticulum (ER) calcium concentrations ([Ca2+]i and [Ca2+]L, respectively) were measured by fluorescent imaging. Results: Activation of M3 muscarinic receptors induced a biphasic increase in [Ca2+]i: an initial, inositol trisphosphate (IP3)-mediated release of Ca2+ from endoplasmic reticulum (ER) stores followed by a sustained phase of Ca2+ entry (i.e., store-operated calcium entry; SOCE). Under non-cytotoxic conditions, tBHP increased resting [Ca2+]i; a 90 minute exposure to tBHP (0.5-10 mM) increased [Ca2+]i from 26 to up to 127 nM and decreased [Ca2+]L by 55%. The initial response to 10 μM carbamylcholine was depressed by tBHP in the absence, but not the presence, of extracellular calcium. SOCE, however, was depressed in both the presence and absence of extracellular calcium. Acute exposure to tBHP did not block calcium influx through open SOCE channels. Activation of SOCE following thapsigargin-induced depletion of ER calcium was depressed by tBHP exposure. In calcium-free media, tBHP depressed both SOCE and the extent of thapsigargin-induced release of Ca2+ from the ER. M3 receptor binding parameters (ligand affinity, guanine nucleotide sensitivity, allosteric modulation) were not affected by exposure to tBHP. Conclusions: Oxidative stress induced by tBHP affected several aspects of M3 receptor signaling pathway in CHO cells, including resting [Ca2+]i, [Ca2+]L, IP3 receptor mediated release of calcium from the ER, and calcium entry through the SOCE. tBHP had little effect on M3 receptor binding or G protein coupling. Thus, oxidative stress affects multiple aspects of calcium homeostasis and calcium dependent signaling

Majorana neutrinos and lepton-number-violating signals in top-quark and W-boson rare decays

We discuss rare lepton-number-violating top-quark and W-boson four-body decays to final states containing a same-charge lepton pair, of the same or of different flavors: t -> b W- li^+ lj^+ and W+ -> J J' li^+ lj^+, where i \ne j or i=j and J J' stands for two light jets originating from a (u-bar d) or a (c-bar s) pair. These \Delta L=2 decays are forbidden in the Standard Model and may be mediated by exchanges of Majorana neutrinos. We adopt a model independent approach for the Majorana neutrinos mixing pattern and calculate the branching ratios (BR) for these decays. We find, for example, that for O(1) mixings between heavy and light Majorana neutrinos (not likely but not ruled out) and if at least one of the heavy Majorana neutrinos has a mass of ~100 GeV, then the BR's for these decays are: BR(t -> b li^+ lj^+ W-) ~ 10^{-4} and BR(W+ -> li^+ lj^+ J J') ~ 10^{-7} if m_N ~ 100 GeV and BR(t -> b li^+ lj^+ J J') ~ BR(W+ -> li^+ lj^+ J J') ~ 0.01 if m_N < 50 GeV. Taking into account the present limits on the neutrino mixing parameters, we obtain more realistic values for these BR's: BR(t -> b li^+ lj^+ W-) ~ 10^{-6} and BR(W+ -> li^+ lj^+ J J') ~ 10^{-10} for m_N ~ 100 GeV and BR(t -> b li^+ lj^+ J J') ~ BR(W+ -> li^+ lj^+ J J') ~ 10^{-6} for m_N < 50 GeV.Comment: latex, 7 pages, 2 figures. V2 as published in PL

Heavy Majorana Neutrinos in the Effective Lagrangian Description: Application to Hadron Colliders

We consider the effects of heavy Majorana neutrinos N with sub-TeV masses. We argue that the mere presence of these particles would be a signal of physics beyond the minimal seesaw mechanism and their interactions are, therefore, best described using an effective Lagrangian. We then consider the complete set of leading effective operators (up to dimension 6) involving the N and Standard Model fields and show that these interactions can be relatively easy to track at high-energy colliders. For example, we find that an exchange of a TeV-scale heavy vector field can yield thousands of characteristic same-sign lepton number violating l^+ l^+ j j events (j=light jet) at the LHC if m_N < 600 GeV, which can also have a distinctive forward-backward asymmetry signal; even the Tevatron has good prospects for this signature if m_N < 300 GeV.Comment: 4 pages, 1 figur

Using Forums in Moodle to Provide Peer Feedback

In 2014, the Bloomsbury Learning Environment (BLE) Consortium initiated a wide-ranging, two-year-long research and dissemination project focusing on the use of technology in assessment and feedback. Our aim was to understand and improve processes, practices, opportunities and tools available to the institutional members of the BLE Consortium. From the project, we produced three research papers investigating current practice and 21 case studies describing both technology-enabled pedagogy and technical development. Now presented as a free ebook, co-edited by <strong>Leo Havemann</strong> and <strong>Sarah Sherman</strong>, we offer the flavour of the variety and breadth of the BLE’s activities relating to the project theme as a contribution to the education sector’s widening conversation about the interplay of assessment, feedback, pedagogy and technology

Electromagnetic Wave Theory and Applications

Contains table of contents for Section 3, reports on four research projects and a list of publications.National Aeronautics and Space Administration Grant NAGW-1617National Aeronautics and Space Administration Agreement 958461National Aeronautics and Space Administration Grant NAGW-1272U.S. Army Corp of Engineers Contract DACA39-87-K-0022U.S. Navy - Office of Naval Research Grant N00014-89-J-1107U.S. Navy - Office of Naval Research Grant N00014-92-J-1616Digital Equipment CorporationJoint Services Electronics Program Contract DAAL03-92-C-0001U.S. Navy - Office of Naval Research Grant N00014-90-J-1002U.S. Navy - Office of Naval Research Grant N00014-89-J-1019U.S. Department of Transportation Agreement DTRS-57-88-C-00078TTD13U.S. Department of Transportation Agreement DTRS-57-88-C-00078TTD30U.S. Department of Transportation Agreement DTRS-57-92-C-00054TTD1DARPA/Consortium for Superconducting Electronics Contract MDA972-90-C-0021National Science Foundation Fellowship MIP 88-5876

Comparison of the Associations between Self-Reported Sleep Quality and Sleep Duration Concerning the Risk of Depression: A Nationwide Population-Based Study in Indonesia

There is substantial evidence that a lack of sleep quality and duration can increase the risk of depression in adults. Still, few studies have compared sleep quality and duration to the risk of depression in Indonesia. Therefore, this study aimed to compare the prevalence and risk of depression associated with both sleep quality and duration and identified those factors associated with sleep quality with sleep duration. This study was a cross-sectional study, and the data were obtained from the 2014 Indonesian Family Life Survey, with a total sample comprised of 19,675 respondents aged older than 15 years old. A self-reported questionnaire was used to assess sleep quality and duration. Depression was assessed using the Center for Epidemiologic Studies Depression (CESD-10) questionnaire. Logistic regression was used to examine the risk of depression, and multinomial logistic regression was used to examine the risk of poor sleep quality with consideration to sleep duration. The prevalence of depression was the highest in the poor sleep quality and long sleep duration groups (48.5%). After all variables associated with depression were adjusted, poor sleep quality was identified as a factor leading to a higher risk of depression (OR = 4.2; 95% CI: 3.7&ndash;4.6; p &lt; 0.001) than long sleep duration (OR = 1.4; 95% CI: 1.2&ndash;1.6; p &lt; 0.001). Furthermore, the interaction between poor sleep quality and long sleep duration gave the highest risk of depression (OR = 4.4; 95% CI: 3.6&ndash;5.3); p &lt; 0.001). Multinomial logistic regression revealed that the factors leading to a significant increase in the risk of poor sleep quality, with consideration to sleep duration, in the population were age, gender, marital status, education, wealth index, physical activity, chronic illness, season, and urban area (p &lt; 0.05). Sleep quality was found to be associated with a higher risk of depression than sleep duration. The findings of this study may be beneficial to healthcare professionals who develop health promotion strategies for reducing the incidence of depression in communities