2,093 research outputs found

    The conduction pathway of potassium channels is water free under physiological conditions.

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    Ion conduction through potassium channels is a fundamental process of life. On the basis of crystallographic data, it was originally proposed that potassium ions and water molecules are transported through the selectivity filter in an alternating arrangement, suggesting a "water-mediated" knock-on mechanism. Later on, this view was challenged by results from molecular dynamics simulations that revealed a "direct" knock-on mechanism where ions are in direct contact. Using solid-state nuclear magnetic resonance techniques tailored to characterize the interaction between water molecules and the ion channel, we show here that the selectivity filter of a potassium channel is free of water under physiological conditions. Our results are fully consistent with the direct knock-on mechanism of ion conduction but contradict the previously proposed water-mediated knock-on mechanism

    Is it more feeling or thinking? The influence of affective and cognitive attitude on adolescents' intention to engage in binge drinking

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    Previous work has revealed that interventions aiming to reduce adolescent binge drinking commonly focus on cognitive attitudes, but are insufficiently effective in changing binge-drinking intentions. The focus on these cognitive attitudes might be the reason for this insufficient success. That is, other work has revealed that affective attitudes have a stronger influence on binge-drinking intention than cognitive attitudes. However, this relation has so far only been found among traditional college students and pre-vocational school students, therewith neglecting another important population at risk, namely vocational community college students. This study examines whether affective attitudes are also significantly stronger influencers of binge-drinking intentions among vocational community college students. Using a sample of 298 vocational community college students (Mage = 17.63), the current study shows that affective attitudes were more strongly related to vocational community college students' intention to engage in binge drinking than cognitive attitudes. This finding indicates that the effectiveness of interventions targeting adolescent binge drinking can be improved by incorporating content elements concerning affective attitudes

    Homotopy types of stabilizers and orbits of Morse functions on surfaces

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    Let MM be a smooth compact surface, orientable or not, with boundary or without it, PP either the real line R1R^1 or the circle S1S^1, and Diff(M)Diff(M) the group of diffeomorphisms of MM acting on C(M,P)C^{\infty}(M,P) by the rule hffh1h\cdot f\mapsto f \circ h^{-1}, where hDiff(M)h\in Diff(M) and fC(M,P)f \in C^{\infty}(M,P). Let f:MPf:M \to P be a Morse function and O(f)O(f) be the orbit of ff under this action. We prove that πkO(f)=πkM\pi_k O(f)=\pi_k M for k3k\geq 3, and π2O(f)=0\pi_2 O(f)=0 except for few cases. In particular, O(f)O(f) is aspherical, provided so is MM. Moreover, π1O(f)\pi_1 O(f) is an extension of a finitely generated free abelian group with a (finite) subgroup of the group of automorphisms of the Reeb graph of ff. We also give a complete proof of the fact that the orbit O(f)O(f) is tame Frechet submanifold of C(M,P)C^{\infty}(M,P) of finite codimension, and that the projection Diff(M)O(f)Diff(M) \to O(f) is a principal locally trivial S(f)S(f)-fibration.Comment: 49 pages, 8 figures. This version includes the proof of the fact that the orbits of a finite codimension of tame action of tame Lie group on tame Frechet manifold is a tame Frechet manifold itsel

    Properties of 3-manifolds for relativists

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    In canonical quantum gravity certain topological properties of 3-manifolds are of interest. This article gives an account of those properties which have so far received sufficient attention, especially those concerning the diffeomorphism groups of 3-manifolds. We give a summary of these properties and list some old and new results concerning them. The appendix contains a discussion of the group of large diffeomorphisms of the ll-handle 3-manifold.Comment: 20 pages. Plain-TeX, no figures, 1 Table (A4 format

    Direct detection of bound ammonium ions in the selectivity filter of ion channels by solid-state NMR.

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    The flow of ions across cell membranes facilitated by ion channels is an important function for all living cells. Despite the huge amount of structural data provided by crystallography, elucidating the exact interactions between the selectivity filter atoms and bound ions is challenging. Here, we detect bound 15 N-labeled ammonium ions as a mimic for potassium ions in ion channels using solid-state NMR under near-native conditions. The non-selective ion channel NaK showed two ammonium peaks corresponding to its two ion binding sites, while its potassium-selective mutant NaK2K that has a signature potassium- selective selectivity filter with four ion binding sites gave rise to four ammonium peaks. Ions bound in specific ion binding sites were identified based on magnetization transfer between the ions and carbon atoms in the selectivity filters. Magnetization transfer between bound ions and water molecules revealed that only one out of four ions in the selectivity filter of NaK2K is in close contact with water, which is in agreement with the direct knock-on ion conduction mechanism where ions are conducted through the channel by means of direct interactions without water molecules in between. Interestingly, the potassium-selective ion channels investigated here (NaK2K and, additionally, KcsA-Kv1.3) showed remarkably different chemical shifts for their bound ions, despite having identical amino acid sequences and crystal structures of their selectivity filters. Molecular dynamics simulations show similar ion binding and conduction behavior between ammonium and potassium ions and identify the origin of the differences between the investigated potassium channel

    Combined ecological risks of nitrogen and phosphorus in European freshwaters

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    Eutrophication is a key water quality issue triggered by increasing nitrogen (N) and phosphorus (P) levels and potentially posing risks to freshwater biota. We predicted the probability that an invertebrate species within a community assemblage becomes absent due to nutrient stress as the ecological risk (ER) for European lakes and streams subjected to N and P pollution from 1985 to 2011. The ER was calculated as a function of species-specific tolerances to NO3 - and total P concentrations and water quality monitoring data. Lake and stream ER averaged 50% in the last monitored year (i.e. 2011) and we observed a decrease by 22% and 38% in lake and stream ER (respectively) of river basins since 1985. Additionally, the ER from N stress surpassed that of P in both freshwater systems. The ER can be applied to identify river basins most subjected to eutrophication risks and the main drivers of impacts

    Structural plasticity of the selectivity filter in a nonselective ion channel

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    The sodium potassium ion channel (NaK) is a nonselective ion channel that conducts both sodium and potassium across the cellular membrane. A new crystallographic structure of NaK reveals conformational differences in the residues that make up the selectivity filter between the four subunits that form the ion channel and the inner helix of the ion channel. The crystallographic structure also identifies a side-entry, ion-conduction pathway for Na+ permeation that is unique to NaK. NMR studies and molecular dynamics simulations confirmed the dynamical nature of the top part of the selectivity filter and the inner helix in NaK as also observed in the crystal structure. Taken together, these results indicate that the structural plasticity of the selectivity filter combined with the dynamics of the inner helix of NaK are vital for the efficient conduction of different ions through the non-selective ion channel of NaK
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