Statistical analysis of modal gating in ion channels

Ion channels regulate the concentrations of ions within cells. By stochastically opening and closing its pore, they enable or prevent ions from crossing the cell membrane. However, rather than opening with a constant probability, many ion channels switch between several different levels of activity even if the experimental conditions are unchanged. This phenomenon is known as modal gating: instead of directly adapting its activity, the channel seems to mix sojourns in active and inactive modes in order to exhibit intermediate open probabilities. Evidence is accumulating that modal gating rather than modulation of opening and closing at a faster time scale is the primary regulatory mechanism of ion channels. However, currently, no method is available for reliably calculating sojourns in different modes. In order to address this challenge, we develop a statistical framework for segmenting single-channel datasets into segments that are characteristic for particular modes. The algorithm finds the number of mode changes, detects their locations and infers the open probabilities of the modes. We apply our approach to data from the inositol-trisphosphate receptor. Based upon these results, we propose that mode changes originate from alternative conformational states of the channel protein that determine a certain level of channel activity

Data-Driven Modelling of the Inositol Trisphosphate Receptor (IPR) and its Role in Calcium-Induced Calcium Release (CICR)

We review the current state of the art of data-driven modelling of the inositol trisphosphate receptor (IPR). After explaining that the IPR plays a crucial role as a central regulator in calcium dynamics, several sources of relevant experimental data are introduced. Single ion channels are best studied by recording single-channel currents under different ligand concentrations via the patch-clamp technique. The particular relevance of modal gating, the spontaneous switching between different levels of channel activity that occur even at constant ligand concentrations, is highlighted. In order to investigate the interactions of IPRs, calcium release from small clusters of channels, so-called calcium puffs, can be used. We then present the mathematical framework common to all models based on single-channel data, aggregated continuous-time Markov models, and give a short review of statistical approaches for parameterising these models with experimental data. The process of building a Markov model that integrates various sources of experimental data is illustrated using two recent examples, the model by Ullah et al. and the “Park–Drive” model by Siekmann et al. (Biophys. J. 2012), the only models that account for all sources of data currently available. Finally, it is demonstrated that the essential features of the Park–Drive model in different models of calcium dynamics are preserved after reducing it to a two-state model that only accounts for the switching between the inactive “park” and the active “drive” modes. This highlights the fact that modal gating is the most important mechanism of ligand regulation in the IPR. It also emphasises that data-driven models of ion channels do not necessarily have to lead to detailed models but can be constructed so that relevant data is selected to represent ion channels at the appropriate level of complexity for a given application

Why do some institutional arrangements succeed? Voluntary protection of forest biodiversity in Southwestern Finland and of the Golden Eagle in Finnish Lapland

Despite global, regional, and national policy efforts, biodiversity is on the decline worldwide. The purpose of this paper is to explore the critically important institutional and social features of those economic instruments that in practice motivate beneficiaries and stakeholders to protect biodiversity. The paper presents two case studies: the natural values trading (NVT) scheme in southwestern Finland and the protection of the golden eagle (Aquila chrysaetos) in Finnish Lapland. NVT builds upon the voluntary actions of landowners, payments for ecosystem services, and a fixed-term period of protection (ten years). The protection of the golden eagle is based on tolerance payments. This paper combines legal studies and institutional economics to abduct the reasons underlying the success of both cases. In both cases, institutional entrepreneurship promoted the confidence of stakeholders and beneficiaries in the schemes and the consequent trust amongst the agents encouraged the actors to modify their behaviour

Hypolimnetic Transitions and Sand-bar Development in Aso-kai Lagoon (Central Japan) during the Past 1,200 Years, Inferred from Benthic Foraminifera

Resilience is increasingly being considered as a new paradigm of forest management among scientists, practitioners, and policymakers. However, metrics of resilience to environmental change are lacking. Faced with novel disturbances, forests may be able to sustain existing ecosystem services and biodiversity by exhibiting resilience, or alternatively these attributes may undergo either a linear or nonlinear decline. Here we provide a novel quantitative approach for assessing forest resilience that focuses on three components of resilience, namely resistance, recovery, and net change, using a spatially explicit model of forest dynamics. Under the pulse set scenarios, we explored the resilience of nine ecosystem services and four biodiversity measures following a one-off disturbance applied to an increasing percentage of forest area. Under the pulse + press set scenarios, the six disturbance intensities explored during the pulse set were followed by a continuous disturbance. We detected thresholds in net change under pulse + press scenarios for the majority of the ecosystem services and biodiversity measures, which started to decline sharply when disturbance affected \u3e40% of the landscape. Thresholds in net change were not observed under the pulse scenarios, with the exception of timber volume and ground flora species richness. Thresholds were most pronounced for aboveground biomass, timber volume with respect to the ecosystem services, and ectomycorrhizal fungi and ground flora species richness with respect to the biodiversity measures. Synthesis and applications. The approach presented here illustrates how the multidimensionality of stability research in ecology can be addressed and how forest resilience can be estimated in practice. Managers should adopt specific management actions to support each of the three components of resilience separately, as these may respond differently to disturbance. In addition, management interventions aiming to deliver resilience should incorporate an assessment of both pulse and press disturbances to ensure detection of threshold responses to disturbance, so that appropriate management interventions can be identified

Forest Ecostructure and Its Change in Finland, Germany and Peru

201