Voltage-Gated Channel Mechanosensitivity: Fact or Friction?

The heart is a continually active pulsatile fluid pump. It generates appropriate forces by precisely timed and spaced engagement of its contractile machinery. Largely, it makes its own control signals, the most crucial of which are precisely timed and spaced fluxes of ions across the sarcolemma, achieved by the timely opening and closing of diverse voltage-gated channels (VGC). VGCs have four voltage sensors around a central ion-selective pore that opens and closes under the influence of membrane voltage. Operation of any VGC is secondarily tuned by the mechanical state (i.e., structure) of the bilayer in which it is embedded. Rates of opening and closing, in other words, vary with bilayer structure. Thus, in the intensely mechanical environment of the myocardium and its vasculature, VGCs kinetics might be routinely modulated by reversible and irreversible nano-scale changes in bilayer structure. If subtle bilayer deformations are routine in the pumping heart, VGCs could be subtly transducing bilayer mechanical signals, thereby tuning cardiac rhythmicity, collectively contributing to mechano-electric feedback. Reversible bilayer deformations would be expected with changing shear flows and tissue distension, while irreversible bilayer restructuring occurs with ischemia, inflammation, membrane remodeling, etc. I suggest that tools now available could be deployed to help probe whether/how the inherent mechanosensitivity of VGCs – an attribute substantially reflecting the dependence of voltage sensor stability on bilayer structure – contributes to cardiac rhythmicity. Chief among these tools are voltage sensor toxins (whose inhibitory efficacy varies with the mechanical state of bilayer) and arrhythmia-inducing VGC mutants with distinctive mechano-phenotypes

Liberalism Versus Fundamentalism: The Ideological Conflict Between Tocqueville and Qtub

This paper seeks to conclude whether Qtub has successfully discredited the values supported by Tocqueville to draw more Muslims to support an increased role of religion in society and influence the majority of Muslims to conduct violent jihad. It is hypothesized that Muslims agree with Qtub that Islam must be increasingly influential in society, but the majority do not seek to increase its role through, or for the purposes of, violent jihad. Differing in their views on freedom and liberty, freedom of religion and separation of church and state, and man-made laws but agreeing on the negative effects of materialism, Tocqueville impacted American society by promoting values considered “American” today that allowed for freedom, while Qtub inspired the radicalization of Islam by joining the Muslim Brotherhood and calling for jihad by all Muslims to discredit the values supported by Tocqueville. By analyzing Tocqueville’s and Qtub’s thinking on Western principles, as well as by taking into account the studies conducted, it has been concluded that Muslims agree with Qtub that Islam must the central most tenet in society, as well as support many of his other ideas, but they ultimately do not support his call for violent jihad. Overall, Qtub has inspired many Muslims to commit violent jihad but has not succeeded radicalizing all moderate Muslims. As a result, the U.S. must determine how to better engage with the Muslim world to combat violent extremism and support peace and stability in the region. If current strategies do not prove to be successful in countering Islamism, radicalization, and terrorism, the U.S. must continue to assess and evaluate its policies, as it has committed itself to the G.M.E for many decades and will face immense challenges in attempting to fully withdraw from or ignore the region

The influence of early questions on learning from text

In this research we explored the use of short-answer questions to improve learning from chapter-like texts (3395 words). Experiment 1 investigated the influence of pre-questions on recall from a text passage when tested a week later; two question sets were counterbalanced within the experimental group. Participants with pre-questions scored higher both overall (d = 3.6, 95%CI [2.4, 4.8]) and on novel questions (d = 2.0 [1.6, 2.4]). In Experiment 2, questions were made available immediately after studying the text either alongside the text, open-book, or closed-book with the opportunity to check answers, or not at all with additional study time. Learning was tested after a week. Although the immediate test scores were substantially higher for open- than closed-book tests, week-delayed performance on the same items was much worse for open-book tests and was moderately improved for closed-book tests. For seen questions, closed-book tests led to better delayed recall than did open-book tests, d = 0.7 [0.02, 1.5]. For novel questions, observed differences were small; ds = .2 [-0.6, 0.9] for both comparisons

Membrane Tension Accelerates Rate-limiting Voltage-dependent Activation and Slow Inactivation Steps in a Shaker Channel

A classical voltage-sensitive channel is tension sensitive—the kinetics of Shaker and S3–S4 linker deletion mutants change with membrane stretch (Tabarean, I.V., and C.E. Morris. 2002. Biophys. J. 82:2982–2994.). Does stretch distort the channel protein, producing novel channel states, or, more interestingly, are existing transitions inherently tension sensitive? We examined stretch and voltage dependence of mutant 5aa, whose ultra-simple activation (Gonzalez, C., E. Rosenman, F. Bezanilla, O. Alvarez, and R. Latorre. 2000. J. Gen. Physiol. 115:193–208.) and temporally matched activation and slow inactivation were ideal for these studies. We focused on macroscopic patch current parameters related to elementary channel transitions: maximum slope and delay of current rise, and time constant of current decline. Stretch altered the magnitude of these parameters, but not, or minimally, their voltage dependence. Maximum slope and delay versus voltage with and without stretch as well as current rising phases were well described by expressions derived for an irreversible four-step activation model, indicating there is no separate stretch-activated opening pathway. This model, with slow inactivation added, explains most of our data. From this we infer that the voltage-dependent activation path is inherently stretch sensitive. Simulated currents for schemes with additional activation steps were compared against datasets; this showed that generally, additional complexity was not called for. Because the voltage sensitivities of activation and inactivation differ, it was not possible to substitute depolarization for stretch so as to produce the same overall PO time course. What we found, however, was that at a given voltage, stretch-accelerated current rise and decline almost identically—normalized current traces with and without stretch could be matched by a rescaling of time. Rate-limitation of the current falling phase by activation was ruled out. We hypothesize, therefore, that stretch-induced bilayer decompression facilitates an in-plane expansion of the protein in both activation and inactivation. Dynamic structural models of this class of channels will need to take into account the inherent mechanosensitivity of voltage-dependent gating

Modeled CO2 Emissions from Coastal Wetland Transitions to Other Land Uses: Tidal Marshes, Mangrove Forests, and Seagrass Beds

The sediments of coastal wetlands contain large stores of carbon which are vulnerable to oxidation once disturbed, resulting in high levels of CO2 emissions that may be avoided if coastal ecosystems are conserved or restored. We used a simple model to estimate CO2 emissions from mangrove forests, seagrass beds, and tidal marshes based on known decomposition rates for organic matter in these ecosystems under either oxic or anoxic conditions combined with assumptions of the proportion of sediment carbon being deposited in either oxic or anoxic environments following a disturbance of the habitat. Our model found that over 40 years after disturbance the cumulative CO2 emitted from tidal marshes, mangrove forests, and seagrass beds were ∼70–80% of the initial carbon stocks in the top meter of the sediment. Comparison of our estimates of CO2 emissions with empirical studies suggests that (1) assuming 50% of organic material moves to an oxic environment after disturbance gives rise to estimates that are similar to CO2 emissions reported for tidal marshes; (2) field measurements of CO2 emissions in disturbed mangrove forests were generally higher than our modeled emissions that assumed 50% of organic matter was deposited in oxic conditions, suggesting higher proportions of organic matter may be exposed to oxic conditions after disturbance in mangrove ecosystems; and (3) the generally low observed rates of CO2 emissions from disturbed seagrasses compared to our estimates, assuming removal of 50% of the organic matter to oxic environments, suggests that lower proportions may be exposed to oxic conditions in seagrass ecosystems. There are significant gaps in our knowledge of the fate of wetland sediment carbon in the marine environment after disturbance. Greater knowledge of the distribution, form, decomposition, and emission rates of wetland sediment carbon after disturbance would help to improve models

The role of leadership in establishing a positive staff culture in a secondary school

This Australian case study explored the implementation of strategies to support the development of a positive school culture among whole school staff. A participatory action research approach was used to involve leadership staff in the development of a mixed method assessment of the school organisation. Baseline data from the School Organisational Health Questionnaire (n = 28) and qualitative data from focus groups (n = 15) were collected and presented to the leadership team who identified four foci for the study: appraisal and recognition, participative decision-making, professional growth and supportive leadership. After a range of interventions, findings from both post-test surveys (n = 22) and qualitative data (n = 30) suggested a change in leadership style was a key factor of school cultural change across all factors. The case study highlights a number of visible strategies that were employed to increase morale and improve staff wellbeing

Effect of the National Resident Assessment Instrument on Selected Health Conditions and Problems

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111253/1/j.1532-5415.1997.tb02972.x.pd