Calcium ions and the nervous system plasticity

The nervous system is different from all other systems of the organism by extreme flexibility of the structural and functional properties of its elements. This unique feature of the nervous system can be best described as plasticity in a broad sense of the word. All forms of plastic changes in the nervous system functioning have common basic mechanisms, the changes at the free Ca2+ cytosol ions being the most important one. These "calcium signals" trigger an extremely complicated intracellular machinery capable of controlling the structural and functional properties of the nervous system during the whole life span. This review summarises data on the intracellular Ca2+ ions mechanisms controlling the developmental plasticity of neuronal elements, synaptic plasticity of the mature nervous system, and the decline of plastic capabilities with ageing.     

Salt contribution to the flexibility of single‐stranded nucleic acid of finite length

Nucleic acids are negatively charged macromolecules and their structure properties are strongly coupled to metal ions in solutions. In this article, the salt effects on the flexibility of single‐stranded (ss) nucleic acid chain ranging from 12 to 120 nucleotides are investigated systematically by the coarse‐grained Monte Carlo simulations where the salt ions are considered explicitly and the ss chain is modeled with the virtual‐bond structural model. Our calculations show that, the increase of ion concentration causes the structural collapse of ss chain and multivalent ions are much more efficient in causing such collapse, and both trivalent/small divalent ions can induce more compact state than a random relaxation state. We found that monovalent, divalent, and trivalent ions can all overcharge ss chain, and the dominating source for such overcharging changes from ion‐exclusion‐volume effect to ion Coulomb correlations. In addition, the predicted Na⁺ and Mg²⁺‐dependent persistence length l_p’s of ss nucleic acid are in accordance with the available experimental data, and through systematic calculations, we obtained the empirical formulas for l_p as a function of [Na⁺], [Mg²⁺] and chain length. © 2012 Wiley Periodicals, Inc. Biopolymers 99: 370–381, 2013.     

Flexible,Scalable, and Highly Conductive Garnet‐Polymer Solid Electrolyte Templated by Bacterial Cellulose

Solid‐state electrolytes are a promising candidate for the next‐generation lithium‐ion battery, as they have the advantages of eliminating the leakage hazard of liquid solvent and elevating stability. However, inherent limitations such as the low ionic conductivity of solid polymer electrolytes and the high brittleness of inorganic ceramic electrolytes severally impede their practical application. Here, an inexpensive, facile, and scalable strategy to fabricate a hybrid Li₇La₃Zr₂O₁₂ (LLZO) and poly(ethylene oxide)‐based electrolyte by exploiting bacterial cellulose as a template is reported. The well‐organized LLZO network significantly enhances the ionic conductivity by extending long transport pathways for Li ions, exhibiting an elevated conductivity of 1.12 × 10^?4 S cm^?1. In addition, the hybrid electrolyte presents a structural flexibility, with minor impedance increase after bending. The facile and applicable approach establishes new principles for the strategy of designing scalable and flexible hybrid polymer electrolytes that can be utilized for high‐energy‐density batteries.     

Beyond the random coil: stochastic conformational switching in intrinsically disordered proteins

Intrinsically disordered proteins (IDPs) participate in critical cellular functions that exploit the flexibility and rapid conformational fluctuations of their native state. Limited information about the native state of IDPs can be gained by the averaging over many heterogeneous molecules that is unavoidable in ensemble approaches. We used single molecule fluorescence to characterize native state conformational dynamics in five synaptic proteins confirmed to be disordered by other techniques. For three of the proteins, SNAP-25, synaptobrevin and complexin, their conformational dynamics could be described with a simple semiflexible polymer model. Surprisingly, two proteins, neuroligin and the NMDAR-2B glutamate receptor, were observed to stochastically switch among distinct conformational states despite the fact that they appeared intrinsically disordered by other measures. The hop-like intramolecular diffusion found in these proteins is suggested to define a class of functionality previously unrecognized for IDPs.     

State transitions through inhibitory interneurons in a cortical network model

Inhibitory interneurons shape the spiking characteristics and computational properties of cortical networks. Interneuron subtypes can precisely regulate cortical function but the roles of interneuron subtypes for promoting different regimes of cortical activity remains unclear. Therefore, we investigated the impact of fast spiking and non-fast spiking interneuron subtypes on cortical activity using a network model with connectivity and synaptic properties constrained by experimental data. We found that network properties were more sensitive to modulation of the fast spiking population, with reductions of fast spiking excitability generating strong spike correlations and network oscillations. Paradoxically, reduced fast spiking excitability produced a reduction of global excitation-inhibition balance and features of an inhibition stabilised network, in which firing rates were driven by the activity of excitatory neurons within the network. Further analysis revealed that the synaptic interactions and biophysical features associated with fast spiking interneurons, in particular their rapid intrinsic response properties and short synaptic latency, enabled this state transition by enhancing gain within the excitatory population. Therefore, fast spiking interneurons may be uniquely positioned to control the strength of recurrent excitatory connectivity and the transition to an inhibition stabilised regime. Overall, our results suggest that interneuron subtypes can exert selective control over excitatory gain allowing for differential modulation of global network state.     

The fusogenic substance dimethyl sulfoxide enhances exocytosis in motor nerve endings

Fusion of synaptic vesicles with the surface membrane of the nerve terminal is a key step in synaptic transmission, which normally requires the entry of calcium ions into the cell. We report that this fusion and the subsequent liberation of transmitter can also be induced by the fusogenic substances DMSO (dimethyl sulfoxide) and PEG (poly(ethylene glycol)). Calcium ions and DMSO exhibit a synergistic effect in the fusion of synaptic vesicles with the axolemma, resembling their action on fusion phenomena in liposomes.     

Associative recognition and storage in a model network of physiological neurons

We consider a neural network model in which the single neurons are chosen to closely resemble known physiological properties. The neurons are assumed to be linked by synapses which change their strength according to Hebbian rules on a short time scale (100ms). The dynamics of the network — the time evolution of the cell potentials and the synapses — is investigated by computer simulation. As in more abstract network models (Cooper 1973; Hopfield 1982; Kohonen 1984) it is found that the local dynamics of the cell potentials and the synaptic strengths result in global cooperative properties of the network and enable the network to process an incoming flux of information and to learn and store patterns associatively. A trained net can associate missing details of a pattern, can correct wrong details and can suppress noise in a pattern. The network can further abstract the prototype from a series of patterns with variations. A suitable coupling constant connecting the dynamics of the cell potentials with the synaptic strengths is derived by a mean field approximation. This coupling constant controls the neural sensitivity and thereby avoids both extremes of the network state, the state of permanent inactivity and the state of epileptic hyperactivity.     

Stable Seamless Interfaces and Rapid Ionic Conductivity of Ca–CeO2/LiTFSI/PEO Composite Electrolyte for High‐Rate and High‐Voltage All‐Solid‐State Battery

Stable and seamless interfaces among solid components in all‐solid‐state batteries (ASSBs) are crucial for high ionic conductivity and high rate performance. This can be achieved by the combination of functional inorganic material and flexible polymer solid electrolyte. In this work, a flexible all‐solid‐state composite electrolyte is synthesized based on oxygen‐vacancy‐rich Ca‐doped CeO₂ (Ca–CeO₂) nanotube, lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), and poly(ethylene oxide) (PEO), namely Ca–CeO₂/LiTFSI/PEO. Ca–CeO₂ nanotubes play a key role in enhancing the ionic conductivity and mechanical strength while the PEO offers flexibility and assures the stable seamless contact between the solid electrolyte and the electrodes in ASSBs. The as‐prepared electrolyte exhibits high ionic conductivity of 1.3 × 10^?4 S cm^?1 at 60 °C, a high lithium ion transference number of 0.453, and high‐voltage stability. More importantly, various electrochemical characterizations and density functional theory (DFT) calculations reveal that Ca–CeO₂ helps dissociate LiTFSI, produce free Li ions, and therefore enhance ionic conductivity. The ASSBs based on the as‐prepared Ca–CeO₂/LiTFSI/PEO composite electrolyte deliver high‐rate capability and high‐voltage stability.     

Conformational study of valinomycin: a molecular dynamics approach

Valinomycin is a highly flexible cyclic dodecadepsipeptide that transports ions across membranes. Such a flexibility in the conformation is required for its biological function since it has to encounter a variety of environments and liganding state. Exploration of conformational space of this molecule is therefore important and is one of the objectives of the present study that has been carried out by means of high temperature Molecular Dynamics. Further, the stability of the known bracelet-like structure of the uncomplexed valinomycin and the inherent flexibility around this structure has been investigated. The uncomplexed form of valinomycin has been simulated at 75-100 K for 1 ns in order to elucidate the average conformational properties. An alanine-analog of valinomycin has been simulated under identical conditions in order to evaluate the effect of sidechain on the conformational properties, The studies confirm the effect of sidechain on conformational equilibrium.     

Self-organized dynamics in plastic neural networks: bistability and coherence

 In this paper, we study the combined dynamics of the neural activity and the synaptic efficiency changes in a fully connected network of biologically realistic neurons with simple synaptic plasticity dynamics including both potentiation and depression. Using a mean-field of technique, we analyzed the equilibrium states of neural networks with dynamic synaptic connections and found a class of bistable networks. For this class of networks, one of the stable equilibrium states shows strong connectivity and coherent responses to external input. In the other stable equilibrium, the network is loosely connected and responds non coherently to external input. Transitions between the two states can be achieved by positively or negatively correlated external inputs. Such networks can therefore switch between their phases according to the statistical properties of the external input. Non-coherent input can only “rcad” the state of the network, while a correlated one can change its state. We speculate that this property, specific for plastic neural networks, can give a clue to understand fully unsupervised learning models. Received: 8 August 1999 / Accepted in revised form: 16 March 2000     

Oxidative phosphorylation and proton translocation in membrane vesicles prepared from Escherichia coli

This paper reports physical-chemical properties of proteins L7 and L12 from E. coli 50 S subunits. Evidence is presented that these two proteins behave in their native state as a dimer of molecular weight 24000. From sedimentation velocity and intrinsic viscosity data the actual frictional ratio of the dimer has been obtained revealing an asymmetric particle which can be described as a rod with cell dimensions of L = 130 Å and a diameter of D = 17.0 Å. From small X-ray scattering the radius of gyration (Rg = 37.0 Å), the thickness factor, and the degree of hydration were determined. This indicates that the extended shape of the dimer is due to the asymmetry of the molecule and not to the hydration.     

Sulfide Solid Electrolytes for Lithium Battery Applications

The use of solid electrolytes is a promising direction to improve the energy density of lithium‐ion batteries. However, the low ionic conductivity of many solid electrolytes currently hinders the performance of solid‐state batteries. Sulfide solid electrolytes can be processed in a number of forms (glass, glass‐ceramic, and crystalline) and have a wide range of available chemistries. Crystalline sulfide materials demonstrate ionic conductivity on par with those of liquid electrolytes through the utilization of near ideal conduction pathways. Low‐temperature processing is also possible for these materials due to their favorable mechanical properties. The main drawback of sulfide solid electrolytes remains their electrochemical stability, but this can be addressed through compositional tuning or the use of artificial solid electrolyte interphase (SEI). Implementation of sulfide solid electrolytes, with proper treatment for stability, can lead to substantial improvements in solid‐state battery performance leading to significant advancement in electric vehicle technology.     

Self-organized models of selectivity in calcium channels

The role of flexibility in the selectivity of calcium channels is studied using a simple model with two parameters that accounts for the selectivity of calcium (and sodium) channels in many ionic solutions of different compositions and concentrations using two parameters with unchanging values. We compare the distribution of side chains (oxygens) and cations (Na(+) and Ca(2+)) and integrated quantities. We compare the occupancies of cations Ca(2+)/Na(+) and linearized conductance of Na(+). The distributions show a strong dependence on the locations of fixed side chains and the flexibility of the side chains. Holding the side chains fixed at certain predetermined locations in the selectivity filter distorts the distribution of Ca(2+) and Na(+) in the selectivity filter. However, integrated quantities-occupancy and normalized conductance-are much less sensitive. Our results show that some flexibility of side chains is necessary to avoid obstruction of the ionic pathway by oxygen ions in 'unfortunate' fixed positions. When oxygen ions are mobile, they adjust 'automatically' and move 'out of the way', so they can accommodate the permeable cations in the selectivity filter. Structure is the computed consequence of the forces in this model. The structures are self-organized, at their free energy minimum. The relationship of ions and side chains varies with an ionic solution. Monte Carlo simulations are particularly well suited to compute induced-fit, self-organized structures because the simulations yield an ensemble of structures near their free energy minimum. The exact location and mobility of oxygen ions has little effect on the selectivity behavior of calcium channels. Seemingly, nature has chosen a robust mechanism to control selectivity in calcium channels: the first-order determinant of selectivity is the density of charge in the selectivity filter. The density is determined by filter volume along with the charge and excluded volume of structural ions confined within it. Flexibility seems a second-order determinant. These results justify our original assumption that the important factor in Ca(2+) versus Na(+) selectivity is the density of oxygen ions in the selectivity filter along with (charge) polarization (i.e. dielectric properties). The assumption of maximum mobility of oxygens seems to be an excellent approximate working hypothesis in the absence of exact structural information. These conclusions, of course, apply to what we study here. Flexibility and fine structural details may have an important role in other properties of calcium channels that are not studied in this paper. They surely have important roles in other channels, enzymes, and proteins.     

Molecular dynamics simulations of apocupredoxins: insights into the formation and stabilization of copper sites under entatic control

Cupredoxins perform copper-mediated long-range electron transfer (ET) in biological systems. Their copper-binding sites have evolved to force copper ions into ET-competent systems with decreased reorganization energy, increased reduction potential, and a distinct electronic structure compared with those of non-ET-competent copper complexes. The entatic or rack-induced state hypothesis explains these special properties in terms of the strain that the protein matrix exerts on the metal ions. This idea is supported by X-ray structures of apocupredoxins displaying “closed” arrangements of the copper ligands like those observed in the holoproteins; however, it implies completely buried copper-binding atoms, conflicting with the notion that they must be exposed for copper loading. On the other hand, a recent work based on NMR showed that the copper-binding regions of apocupredoxins are flexible in solution. We have explored five cupredoxins in their “closed” apo forms through molecular dynamics simulations. We observed that prearranged ligand conformations are not stable as the X-ray data suggest, although they do form part of the dynamic landscape of the apoproteins. This translates into variable flexibility of the copper-binding regions within a rigid fold, accompanied by fluctuations of the hydrogen bonds around the copper ligands. Major conformations with solvent-exposed copper-binding atoms could allow initial binding of the copper ions. An eventual subsequent incursion to the closed state would result in binding of the remaining ligands, trapping the closed conformation thanks to the additional binding energy and the fastening of noncovalent interactions that make up the rack.     

Ferrous ions and reactive oxygen species increase antigen-binding and anti-inflammatory activities of immunoglobulin G

Polyspecific antibodies represent a first line of defense against infection and regulate inflammation, properties hypothesized to rely on their ability to interact with multiple antigens. We demonstrated that IgG exposure to pro-oxidative ferrous ions or to reactive oxygen species enhances paratope flexibility and hydrophobicity, leading to expansion of the spectrum of recognized antigens, regulation of cell proliferation, and protection in experimental sepsis. We propose that ferrous ions, released from transferrin and ferritin at sites of inflammation, synergize with reactive oxygen species to modify the immunoglobulins present in the surrounding microenvironment, thus quenching pro-inflammatory signals, while facilitating neutralization of pathogens.     

Normal protein composition of synapses in Ts65Dn mice: a mouse model of Down syndrome

Down syndrome (DS) is the most prevalent form of intellectual disability caused by the triplication of ∼230 genes on chromosome 21. Recent data in Ts65Dn mice, the foremost mouse model of DS, strongly suggest that cognitive impairment in individuals with DS is a consequence of reduced synaptic plasticity because of chronic over-inhibition. It remains unclear however whether changes in plasticity are tied to global molecular changes at synapses, or are due to regional changes in the functional properties of synaptic circuits. One interesting framework for evaluating the activity state of the DS brain comes from in vitro studies showing that chronic pharmacological silencing of neuronal excitability orchestrates stereotyped changes in the protein composition of synaptic junctions. In the present study, we use proteomic strategies to evaluate whether synapses from the Ts65Dn cerebrum carry signatures characteristic of inactive cortical neurons. Our data reveal that synaptic junctions do not exhibit overt alterations in protein composition. Only modest changes in the levels of synaptic proteins and in their phosphorylation are observed. This suggests that subtle changes in the functional properties of specific synaptic circuits rather than large-scale homeostatic shifts in the expression of synaptic molecules contribute to cognitive impairment in people with DS.     

Potassium and sodium binding to the outer mouth of the K+ channel.

Molecular dynamics simulations of the K+ channel from Streptomyces lividans (KcsA channel) were performed in a membrane-mimetic environment with Na+ and K+ in different initial locations. The structure of the channel remained stable and well preserved for simulations lasting up to 1.5 ns. Salt bridges between Asp80 and Arg89 of neighboring subunits, not detected in the X-ray structure, enhanced the stability of the tetrameric structure. Na+ or K+ ions located in the channel vestibule lost part of their hydration shell and diffused into the channel inner pore in less than a few hundred picoseconds. This powerful catalytic action was caused by strong electrostatic interactions with Asp80 and Glu71. The hydration state of the metal ions turned out to depend significantly on the conformational flexibility of the channel. Furthermore, Na+ entered the channel inner pore bound to more water molecules than K+. The different hydration state of the two ions may be a determinant factor in the ion selectivity of the channel.     

Improvements to the Overpotential of All‐Solid‐State Lithium‐Ion Batteries during the Past Ten Years

After the research that shows that Li₁₀GeP₂S₁₂ (LGPS)‐type sulfide solid electrolytes can reach the high ionic conductivity at the room temperature, sulfide solid electrolytes have been intensively developed with regard to ionic conductivity and mechanical properties. As a result, an increasing volume of research has been conducted to employ all‐solid‐state lithium batteries in electric automobiles within the next five years. To achieve this goal, it is important to review the research over the past decade, and understand the requirements for future research necessary to realize the practical applications of all‐solid‐state lithium batteries. To date, research on all‐solid‐state lithium batteries has focused on achieving overpotential properties similar to those of conventional liquid‐lithium‐ion batteries by increasing the ionic conductivity of the solid electrolytes. However, the increase in the ionic conductivity should be accompanied by improvements of the electronic conductivity within the electrode to enable practical applications. This essay provides a critical overview of the recent progress and future research directions of the all‐solid‐state lithium batteries for practical applications.     

不同密度柚木人工林林下植被及土壤理化性质的研究

研究不同密度柚木人工林对林下植被及土壤理化性质的影响,为柚木人工林营建与可持续经营提供理论依据。以广东揭阳14~16年生不同林分密度（650、900、1 050、1 200和1 450 株·hm^-2）柚木人工林为研究对象,通过样方调查植被的种名、株数、高度及盖度等,并采集0~20和20~40 cm土样进行理化性质分析,对林下植被物种多样性指数及其土壤理化性质进行主成分分析评价,来评价不同林分密度下柚木人工林的立地质量。结果表明：随着林分密度增加,柚木人工林林下植被盖度整体表现出降低趋势,草本优势物种由阳生性到中生性,逐渐向阴生性的过渡,林下植被Shannon-Wiener指数、Simpson优势度指数、丰富度指数和均匀度指数表现出先增加后减少的趋势;相同密度下,表层土土壤理化性质优于下层土,随着林分密度增大,土壤理化性质整体呈现出先改善后退化的变化过程,不同林分密度间柚木人工林土壤毛管孔隙度、非毛管孔隙度、速效K、速效P、全P、交换性酸和交换性Al等指标差异性显著（P<0.05）;基于林下植被物种多样性和土壤理化性质主成分分析,不同林分密度柚木人工林物种多样性和土壤理化性质综合得分由大到小依次是：1 050 株·hm^-2（4.82）、900 株·hm^-2（1.58）、650 株·hm^-2（-1.30）、1 200 株·hm^-2（-1.81）、1 450 株·hm^-2（-3.29）。因此,说明适宜的林分密度（1 050 株·hm^-2）有利于保持较好的林下植被物种多样性和土壤理化性质,在柚木人工林经营的过程中,可以根据实际情况合理调整林分的密度。