Visualization of the distribution of autophosphorylated calcium/calmodulin-dependent protein kinase II after tetanic stimulation in the CA1 area of the hippocampus

Autophosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) at threonine-286 produces Ca2+-independent kinase activity and has been proposed to be involved in induction of long-term potentiation by tetanic stimulation in the hippocampus. We have used an immunocytochemical method to visualize and quantify the pattern of autophosphorylation of CaMKII in hippocampal slices after tetanization of the Schaffer collateral pathway. Thirty minutes after tetanic stimulation, autophosphorylated CaM kinase II (P-CaMKII) is significantly increased in area CA1 both in apical dendrites and in pyramidal cell somas. In apical dendrites, this increase is accompanied by an equally significant increase in staining for nonphosphorylated CaM kinase II. Thus, the increase in P-CaMKII appears to be secondary to an increase in the total amount of CaMKII. In neuronal somas, however, the increase in P-CaMKII is not accompanied by an increase in the total amount of CaMKII. We suggest that tetanic stimulation of the Schaffer collateral pathway may induce new synthesis of CaMKII molecules in the apical dendrites, which contain mRNA encoding its alpha-subunit. In neuronal somas, however, tetanic stimulation appears to result in long-lasting increases in P-CaMKII independent of an increase in the total amount of CaMKII. Our findings are consistent with a role for autophosphorylation of CaMKII in the induction and/or maintenance of long-term potentiation, but they indicate that the effects of tetanus on the kinase and its activity are not confined to synapses and may involve induction of new synthesis of kinase in dendrites as well as increases in the level of autophosphorylated kinase

Effects of Self-Avoidance on the Tubular Phase of Anisotropic Membranes

We study the tubular phase of self-avoiding anisotropic membranes. We discuss the renormalizability of the model Hamiltonian describing this phase and derive from a renormalization group equation some general scaling relations for the exponents of the model. We show how particular choices of renormalization factors reproduce the Gaussian result, the Flory theory and the Gaussian Variational treatment of the problem. We then study the perturbative renormalization to one loop in the self-avoiding parameter using dimensional regularization and an epsilon-expansion about the upper critical dimension, and determine the critical exponents to first order in epsilon.Comment: 19 pages, TeX, uses Harvmac. Revised Title and updated references: to appear in Phys. Rev.

First-order phase transition in the tethered surface model on a sphere

We show that the tethered surface model of Helfrich and Polyakov-Kleinert undergoes a first-order phase transition separating the smooth phase from the crumpled one. The model is investigated by the canonical Monte Carlo simulations on spherical and fixed connectivity surfaces of size up to N=15212. The first-order transition is observed when N>7000, which is larger than those in previous numerical studies, and a continuous transition can also be observed on small-sized surfaces. Our results are, therefore, consistent with those obtained in previous studies on the phase structure of the model.Comment: 6 pages with 7 figure

Comprehensive Phenotyping in Multiple Sclerosis: Discovery Based Proteomics and the Current Understanding of Putative Biomarkers

Currently, there is no single test for multiple sclerosis (MS). Diagnosis is confirmed through clinical evaluation, abnormalities revealed by magnetic resonance imaging (MRI), and analysis of cerebrospinal fluid (CSF) chemistry. The early and accurate diagnosis of the disease, monitoring of progression, and gauging of therapeutic intervention are important but elusive elements of patient care. Moreover, a deeper understanding of the disease pathology is needed, including discovery of accurate biomarkers for MS. Herein we review putative biomarkers of MS relating to neurodegeneration and contributions to neuropathology, with particular focus on autoimmunity. In addition, novel assessments of biomarkers not driven by hypotheses are discussed, featuring our application of advanced proteomics and metabolomics for comprehensive phenotyping of CSF and blood. This strategy allows comparison of component expression levels in CSF and serum between MS and control groups. Examination of these preliminary data suggests that several CSF proteins in MS are differentially expressed, and thus, represent putative biomarkers deserving of further evaluation

Phase transitions of an intrinsic curvature model on dynamically triangulated spherical surfaces with point boundaries

An intrinsic curvature model is investigated using the canonical Monte Carlo simulations on dynamically triangulated spherical surfaces of size upto N=4842 with two fixed-vertices separated by the distance 2L. We found a first-order transition at finite curvature coefficient \alpha, and moreover that the order of the transition remains unchanged even when L is enlarged such that the surfaces become sufficiently oblong. This is in sharp contrast to the known results of the same model on tethered surfaces, where the transition weakens to a second-order one as L is increased. The phase transition of the model in this paper separates the smooth phase from the crumpled phase. The surfaces become string-like between two point-boundaries in the crumpled phase. On the contrary, we can see a spherical lump on the oblong surfaces in the smooth phase. The string tension was calculated and was found to have a jump at the transition point. The value of \sigma is independent of L in the smooth phase, while it increases with increasing L in the crumpled phase. This behavior of \sigma is consistent with the observed scaling relation \sigma \sim (2L/N)^\nu, where \nu\simeq 0 in the smooth phase, and \nu=0.93\pm 0.14 in the crumpled phase. We should note that a possibility of a continuous transition is not completely eliminated.Comment: 15 pages with 10 figure

The Theory of Dynamical Random Surfaces with Extrinsic Curvature

We analyze numerically the critical properties of a two-dimensional discretized random surface with extrinsic curvature embedded in a three-dimensional space. The use of the toroidal topology enables us to enforce the non-zero external extension without the necessity of defining a boundary and allows us to measure directly the string tension. We show that a phase transition from the crumpled phase to the smooth phase observed earlier for a spherical topology appears also for a toroidal surface for the same finite value of the coupling constant of the extrinsic curvature term. The phase transition is characterized by the vanishing of the string tension. We discuss the possible non-trivial continuum limit of the theory, when approaching the critical point. Numerically we find a value of the critical exponent \n to be between .38 and .42. The specific heat, related to the extrinsic curvature term seems not to diverge (or diverge slower than logarithmically) at the critical point.Comment: figures available as postscript files on request. 28 pages plus figure

Universal Negative Poisson Ratio of Self Avoiding Fixed Connectivity Membranes

We determine the Poisson ratio of self-avoiding fixed-connectivity membranes, modeled as impenetrable plaquettes, to be sigma=-0.37(6), in statistical agreement with the Poisson ratio of phantom fixed-connectivity membranes sigma=-0.32(4). Together with the equality of critical exponents, this result implies a unique universality class for fixed-connectivity membranes. Our findings thus establish that physical fixed-connectivity membranes provide a wide class of auxetic (negative Poisson ratio) materials with significant potential applications in materials science.Comment: 4 pages, 3 figures, LaTeX (revtex) Published version - title changed, one figure improved and one reference change

Phase transition of triangulated spherical surfaces with elastic skeletons

A first-order transition is numerically found in a spherical surface model with skeletons, which are linked to each other at junctions. The shape of the triangulated surfaces is maintained by skeletons, which have a one-dimensional bending elasticity characterized by the bending rigidity $b$, and the surfaces have no two-dimensional bending elasticity except at the junctions. The surfaces swell and become spherical at large $b$ and collapse and crumple at small $b$. These two phases are separated from each other by the first-order transition. Although both of the surfaces and the skeleton are allowed to self-intersect and, hence, phantom, our results indicate a possible phase transition in biological or artificial membranes whose shape is maintained by cytoskeletons.Comment: 15 pages with 10 figure

Fluctuations of elastic interfaces in fluids: Theory and simulation

We study the dynamics of elastic interfaces-membranes-immersed in thermally excited fluids. The work contains three components: the development of a numerical method, a purely theoretical approach, and numerical simulation. In developing a numerical method, we first discuss the dynamical coupling between the interface and the surrounding fluids. An argument is then presented that generalizes the single-relaxation time lattice-Boltzmann method for the simulation of hydrodynamic interfaces to include the elastic properties of the boundary. The implementation of the new method is outlined and it is tested by simulating the static behavior of spherical bubbles and the dynamics of bending waves. By means of the fluctuation-dissipation theorem we recover analytically the equilibrium frequency power spectrum of thermally fluctuating membranes and the correlation function of the excitations. Also, the non-equilibrium scaling properties of the membrane roughening are deduced, leading us to formulate a scaling law describing the interface growth, W^2(L,T)=L^3 g[t/L^(5/2)], where W, L and T are the width of the interface, the linear size of the system and the temperature respectively, and g is a scaling function. Finally, the phenomenology of thermally fluctuating membranes is simulated and the frequency power spectrum is recovered, confirming the decay of the correlation function of the fluctuations. As a further numerical study of fluctuating elastic interfaces, the non-equilibrium regime is reproduced by initializing the system as an interface immersed in thermally pre-excited fluids.Comment: 15 pages, 11 figure