1,721,140 research outputs found
Computationally efficient simulation of electrical activity at cell membranes interacting with self-generated and externally imposed electric fields
No full textObjective. We present a computational method that implements a reduced set of Maxwell's equations to allow simulation of cells under realistic conditions: sub-micron cell morphology, a conductive non-homogeneous space and various ion channel properties and distributions. Approach. While a reduced set of Maxwell's equations can be used to couple membrane currents to extra-and intracellular potentials, this approach is rarely taken, most likely because adequate computational tools are missing. By using these equations, and introducing an implicit solver, numerical stability is attained even with large time steps. The time steps are limited only by the time development of the membrane potentials. Main results. This method allows simulation times of tens of minutes instead of weeks, even for complex problems. The extracellular fields are accurately represented, including secondary fields, which originate at inhomogeneities of the extracellular space and can reach several millivolts. We present a set of instructive examples that show how this method can be used to obtain reference solutions for problems, which might not be accurately captured by the traditional approaches. This includes the simulation of realistic magnitudes of extracellular action potential signals in restricted extracellular space. Significance. The electric activity of neurons creates extracellular potentials. Recent findings show that these endogenous fields act back onto the neurons, contributing to the synchronization of population activity. The influence of endogenous fields is also relevant for understanding therapeutic approaches such as transcranial direct current, transcranial magnetic and deep brain stimulation. The mutual interaction between fields and membrane currents is not captured by today's concepts of cellular electrophysiology, including the commonly used activation function, as those concepts are based on isolated membranes in an infinite, isopotential extracellular space. The presented tool makes simulations with detailed morphology and implicit interactions of currents and fields available to the electrophysiology community
Measurements of membrane patch capacitance using a software-based lock-in system
No full textOn-cell patch-clamp capacitance measurements can resolve the fusion of individual vesicles to a membrane patch and the accompanying dilation of the fusion pore. So far, these measurements have used a patch-clamp amplifier in combination with a hardware lock-in amplifier. Usually, solely the capacitance and conductance outputs of hardware lock-in amplifiers were recorded, which needed to be filtered rather heavily to suppress spectral components at the stimulus frequency. Therefore, the temporal resolution was limited, and information carried in the patch current was not utilized. In this paper, we describe an alternative and more versatile approach for measuring patch capacitance and conductance, using a digitally controlled patch-clamp amplifier. The software lock-in system showed better bandwidth and identical signal-to-noise performance needing less instrumentation. High temporal resolution measurements on patches of chromaffin cells showed that vesicle fission can be completed in only tens of microseconds. Capacitance calculation based on the patch current allows for straightforward offline phase correction. Moreover, the close inspection of direct current for the first time revealed small current changes accompanying the fusion and fission of large secretory vesicles, promising new insights into the vesicles' membrane properties. A practical guide to high-resolution on-cell patch-clamp capacitance measurements using the software lock-in is provided
Intersections of Community Responses and Humanitarian Interventions in the Aftermath of the 2014 Floods in Solomon Islands
No full textThis chapter presents an exploration of the ways in which humanitarian non-government organisations (NGOs) and communities affected by the 2014 floods in Solomon Islands interpreted and responded to the disaster, identifying factors that assisted and constrained stakeholders in disaster response and recovery. The research investigates the extent to which communities were consulted and participated in NGO responses, and the factors which informed community–NGO relationships. A qualitative case study approach was used, employing interviews, focus groups and document analysis, guided by a reflexive discourse analysis and narrative inquiry approach, which places the focus of the study on the experiences of participants. Communities played very limited roles in NGO responses, especially non-dominant or marginalised sectors of society, such as youth, women and people with disabilities. Failure to respond appropriately to the differentiated needs of affected populations can exacerbate their risk of experiencing secondary disaster. The authors argue that there is a need to improve the inclusiveness of responses to disaster, engaging women, youth and people with disabilities in decision making in order to respond more appropriately to their needs
State-Led and Voluntary Climate-Related Relocations in Fiji: Policy, Practice and Protection Gaps
No full textAs more attention globally is directed towards how climate-related mobilities should be managed, it is increasingly important to look at early adopters of policy and practice and learn from these experiences. Fiji is a unique case study in this space. Not only has the Fijian Government relocated several communities, but it has also developed world-leading policies on planned relocations and climate-related displacement. However, the principles these policies strive to uphold have not always carried through to the lived experience of the people materially affected by climate-related hazards. In particular, we identify a key conceptual and practical protection gap for those who choose to move before state-led relocation processes commence. When mobility occurs due to slow-onset or recurrent climate processes, the line between forced and voluntary displacement blurs further, and it is unclear which protections apply, to what degree states are obliged to assist, and exactly when this assistance should be provided. Fijian authorities have attempted to manage this uncertainty through the development of policies like their Planned Relocation Guidelines and Displacement Guidelines. However, the experiences of communities in Fiji show that these policies are not always translated into practice. As other states look to policies like Fiji’s for guidance on issues of climate mobilities, it is increasingly important that such discrepancies are identified and adequately addressed
Planned Relocation as a Contentious Strategy of Climate Change Adaptation in Fiji
No full textPlanned relocation’ has emerged in the international climate policy arena as an ‘adaptation’ solution with the potential to enhance resilience, address underdevelopment and debunk age-old narratives around migration as a risk to peace and security. In 2018, Fiji became one of the first countries to develop Planned Relocation Guidelines, with upwards of 80 villages thought to require relocation over the coming years due to the impact of climate change. Through interviews carried out with representatives from organisations involved in planning for community relocations in Fiji, this chapter explores the creation of planned relocation as a form of climate change adaptation and development. Looking specifically at the value-based challenges of implementation in Fiji, this research provides insight into what happens when dominant international policy narratives play out in practice. Through the presentation of culturally nuanced ways of understanding the problem of climate-induced migration, this chapter invites policymakers to seek out these voices when devising displacement solutions
Embodying Resilience: Narrating Gendered Experiences of Disasters in Fiji
No full textThis chapter explores the local narration of gendered experience of disasters in two iTaukei (Indigenous Fijian) communities, Votua and Navala, both located in the Ba River catchment, Fiji. The methodology consisted of semi-formal interviews, talanoa, mapping sessions and journal entries from community members in Votua and Navala. Local narratives of post-disaster response and recovery in the aftermath of 2016 Tropical Cyclone Winston showed that women were not perceived as embodying a heightened vulnerability to disasters in comparison to men in either Votua or Navala. Rather perceptions of vulnerability were based on the experiences of those who physically struggled, such as people with disabilities, the elderly and those who had lost their homes. While gender roles and responsibilities underlay perceptions and gender relations, the roles and responsibilities were predominantly perceived as changing over time, either to a more shared sense of responsibilities or a shift from male responsibilities to female. This shift may lay the foundations for future changes in vulnerability and experiences towards disasters
Cortical population coding critically depends on fine-tuning of cell physiology
No full textCortical function reflects the coordinated activities of populations of neurons, which, in turn, depend on the speed with which each neuron can respond to input, as revealed by dynamic gain analysis. In Layer 4 of the rodent barrel cortex, a finite population of interconnected, small, excitatory neurons rapidly and briefly relays input from the specific thalamus to the rest of the cortical column. Theory predicts that the determinants of a population’s dynamic gain - cell number, cell size and the correlation time of the background noise - control the speed with which the population can respond to input. Here, we demonstrate how these parameters are optimized such that a single thalamocortical input spike is reliably reflected in the output population response of layer 4. We show that the synaptic receptor dynamics that dominate the background noise in layer 4 are slower than in other layers. We further show that the speed with which the spike-generation machinery can respond depends on the activity of KV7 channels, suggesting that the relay function of layer 4 is under muscarinic control
Revealing a hidden conducting state by manipulating the intracellular domains in KV10.1 exposes the coupling between two gating mechanisms
No full textThe KCNH family of potassium channels serves relevant physiological functions in both excitable and non-excitable cells, reflected in the massive consequences of mutations or pharmacological manipulation of their function. This group of channels shares structural homology with other voltage-gated K + channels, but the mechanisms of gating in this family show significant differences with respect to the canonical electromechanical coupling in these molecules. In particular, the large intracellular domains of KCNH channels play a crucial role in gating that is still only partly understood. Using KCNH1 (K V 10.1) as a model, we have characterized the behavior of a series of modified channels that could not be explained by the current models. With electrophysiological and biochemical methods combined with mathematical modeling, we show that the uncovering of an open state can explain the behavior of the mutants. This open state, which is not detectable in wild-type channels, appears to lack the rapid flicker block of the conventional open state. Because it is accessed from deep closed states, it elucidates intermediate gating events well ahead of channel opening in the wild type. This allowed us to study gating steps prior to opening, which, for example, explain the mechanism of gating inhibition by Ca 2+ -Calmodulin and generate a model that describes the characteristic features of KCNH channels gating.Max-Planck-GesellschaftInternational Max Planck Research School for NeurosciencesDeutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/50110000165
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