1,037 research outputs found

    Entropic Tension in Crowded Membranes

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    Unlike their model membrane counterparts, biological membranes are richly decorated with a heterogeneous assembly of membrane proteins. These proteins are so tightly packed that their excluded area interactions can alter the free energy landscape controlling the conformational transitions suffered by such proteins. For membrane channels, this effect can alter the critical membrane tension at which they undergo a transition from a closed to an open state, and therefore influence protein function \emph{in vivo}. Despite their obvious importance, crowding phenomena in membranes are much less well studied than in the cytoplasm. Using statistical mechanics results for hard disk liquids, we show that crowding induces an entropic tension in the membrane, which influences transitions that alter the projected area and circumference of a membrane protein. As a specific case study in this effect, we consider the impact of crowding on the gating properties of bacterial mechanosensitive membrane channels, which are thought to confer osmoprotection when these cells are subjected to osmotic shock. We find that crowding can alter the gating energies by more than 2  kBT2\;k_BT in physiological conditions, a substantial fraction of the total gating energies in some cases. Given the ubiquity of membrane crowding, the nonspecific nature of excluded volume interactions, and the fact that the function of many membrane proteins involve significant conformational changes, this specific case study highlights a general aspect in the function of membrane proteins.Comment: 20 pages (inclduing supporting information), 4 figures, to appear in PLoS Comp. Bio

    An Integrated Modeling Approach for Predicting Process Maps of Residual Stress and Distortion in a Laser Weld: A Combined CFD–FE Methodology

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    Laser welding has become an important joining methodology within a number of industries for the structural joining of metallic parts. It offers a high power density welding capability which is desirable for deep weld sections, but is equally suited to performing thinner welded joints with sensible amendments to key process variables. However, as with any welding process, the introduction of severe thermal gradients at the weld line will inevitably lead to process-induced residual stress formation and distortions. Finite element (FE) predictions for weld simulation have been made within academia and industrial research for a number of years, although given the fluid nature of the molten weld pool, FE methodologies have limited capabilities. An improvement upon this established method would be to incorporate a computational fluid dynamics (CFD) model formulation prior to the FE model, to predict the weld pool shape and fluid flow, such that details can be fed into FE from CFD as a starting condition. The key outputs of residual stress and distortions predicted by the FE model can then be monitored against the process variables input to the model. Further, a link between the thermal results and the microstructural properties is of interest. Therefore, an empirical relationship between lamellar spacing and the cooling rate was developed and used to make predictions about the lamellar spacing for welds of different process parameters. Processing parameter combinations that lead to regions of high residual stress formation and high distortion have been determined, and the impact of processing parameters upon the predicted lamellar spacing has been presented

    Advancement of photospheric radius expansion and clocked type-I x-ray burst models with the new 22Mg(α,p)25 Al reaction rate determined at Gamow energy

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    We report the first (in)elastic scattering measurement of 25Al+p^{25}\mathrm{Al}+p with the capability to select and measure in a broad energy range the proton resonances in 26^{26}Si contributing to the 22^{22}Mg(α,p)(\alpha,p) reaction at type I x-ray burst energies. We measured spin-parities of four resonances above the α\alpha threshold of 26^{26}Si that are found to strongly impact the 22^{22}Mg(α,p)(\alpha,p) rate. The new rate advances a state-of-the-art model to remarkably reproduce light curves of the GS 1826-24 clocked burster with mean deviation <9<9 % and permits us to discover a strong correlation between the He abundance in the accreting envelope of photospheric radius expansion burster and the dominance of 22^{22}Mg(α,p)(\alpha,p) branch.Comment: accepted by Physical Review Letters on 5 August 2021, published 19 October 202

    The potential determinants of young people's sense of justice: an international study

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    This paper uses reports from 13,000 Grade Nine pupils in five countries to examine issues such as whether they were treated fairly at school, trust their teachers and adults in wider society, are willing to sacrifice teacher attention to help others, and support the cultural integration of recent immigrants. Using such reports as ‘outcomes’ in a multi‐stage regression model, it is clear that they are largely unrelated to school‐level pupil mix variables. To some extent, these outcomes are stratified by pupil and family background in the same way for all countries. However, the largest association is with pupil‐reported experience of interactions with their teachers. Teachers appear to be a major influence on young people's sense of justice and the principles they apply in deciding whether something is fair. The paper concludes by suggesting ways in which schools and teachers could take advantage of this finding

    Single Molecule Conformational Memory Extraction: P5ab RNA Hairpin

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    Extracting kinetic models from single molecule data is an important route to mechanistic insight in biophysics, chemistry, and biology. Data collected from force spectroscopy can probe discrete hops of a single molecule between different conformational states. Model extraction from such data is a challenging inverse problem because single molecule data are noisy and rich in structure. Standard modeling methods normally assume (i) a prespecified number of discrete states and (ii) that transitions between states are Markovian. The data set is then fit to this predetermined model to find a handful of rates describing the transitions between states. We show that it is unnecessary to assume either (i) or (ii) and focus our analysis on the zipping/unzipping transitions of an RNA hairpin. The key is in starting with a very broad class of non-Markov models in order to let the data guide us toward the best model from this very broad class. Our method suggests that there exists a folding intermediate for the P5ab RNA hairpin whose zipping/unzipping is monitored by force spectroscopy experiments. This intermediate would not have been resolved if a Markov model had been assumed from the onset. We compare the merits of our method with those of others

    Errors in the measurement of voltage-activated ion channels in cell-attached patch-clamp recordings

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    Patch-clamp recording techniques have revolutionized understanding of the function and sub-cellular location of ion channels in excitable cells. The cell-attached patch-clamp configuration represents the method of choice to describe the endogenous properties of voltage-activated ion channels in the axonal, somatic and dendritic membrane of neurons, without disturbance of the intracellular milieu. Here, we directly examine the errors associated with cell-attached patch-clamp measurement of ensemble ion channel activity. We find for a number of classes of voltage-activated channels, recorded from the soma and dendrites of neurons in acute brain-slices and isolated cells, that the amplitude and kinetics of ensemble ion channel activity recorded in cell-attached patches is significantly distorted by transmembrane voltage changes generated by the flow of current through the activated ion channels. We outline simple error–correction procedures that allow a more accurate description of the density and properties of voltage-activated channels to be incorporated into computational models of neurons

    Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation.

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    Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion. Here we demonstrate that the pattern of activation of D1 and D2 neurons in the nucleus accumbens (NAc) predicts motivational drive, and that optogenetic activation of either neuronal population enhances motivation in mice. Using a different approach in rats, we further show that activating NAc D2 neurons increases cue-induced motivational drive in control animals and in a model that presents anhedonia and motivational deficits; conversely, optogenetic inhibition of D2 neurons decreases motivation. Our results suggest that the classic view of D1-D2 functional antagonism does not hold true for all dimensions of reward-related behaviours, and that D2 neurons may play a more prominent pro-motivation role than originally anticipated.A special acknowledgement to Karl Deisseroth from Stanford University, for providing viral constructs and for comments on the manuscript, and to Alan Dorval from the University of Utah, for providing mouse strains. Thanks to Luis Jacinto, Joao Oliveira and Joana Silva that helped in some technical aspects of the experiments. C.S.-C., B.C., A.D.-P. and S.B. are recipients of Fundacao para a Ciencia e Tecnologia (FCT) fellowships (SFRH/BD/51992/2012; SFRH/BD/98675/2013; SFRH/BD/90374/2012; SFRH/BD/89936/2012). A.J.R. is a FCT Investigator (IF/00883/2013). This work was co-financed by the Portuguese North Regional Operational Program (ON.2 - O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER). Part of the work was supported by the Janssen Neuroscience Prize (1st edition).info:eu-repo/semantics/publishedVersio
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