Optimized g-ratio for different neural systems.

<p>A: Efficiency index curves for a 1 µm diameter axon where δ = β = 1 (CNS-black curve) and where volume is less of a constraint <i>δ</i> = 0.6β (PNS-grey curve). Note that the peak is shifted to the right indicating that when volume is less of a constraint then the optimal sheath thickness is larger. B: Plots of <i>d_i</i> versus <i>d_o</i> representing different neural systems. In grey (circles) is when volume is less of a constraint (<i>δ</i> = 0.6<i>β</i>). In black (triangles) is when volume is as equally important as the other parameters (<i>δ</i> = <i>β</i> = 1) in defining an optimal structure (re-plotted from previous figure for comparison). The slopes of the lines, which represent the g-ratio, correspond to approximately 0.58–0.59 for the grey (PNS; correlation coefficient r = 1.0, R² = 0.99; p<0.0001) and 0.76–0.77 for the black (CNS). Curves were generated using the parameters defined in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007754#pone-0007754-g001" target="_blank">Figure 1</a> and were the same for both the “CNS” and “PNS” plots with the exception of <i>δ</i>.</p

Some summarized experimental g-ratio data.

<p>Some previously published g-ratio values for myelinated axons. The data are reported as the mean value (or range of means - except for the anterior commissure that only reported a range). Note that mean values are in good agreement with our predictions (g-ratio<i>_observed</i>≈0.76–0.81) for CNS and some PNS axons. Sources: a, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007754#pone.0007754-Arnett1" target="_blank">[10]</a>; b, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007754#pone.0007754-Benninger1" target="_blank">[12]</a>; c, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007754#pone.0007754-Mason1" target="_blank">[16]</a>; d, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007754#pone.0007754-Waxman3" target="_blank">[32]</a>; e, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007754#pone.0007754-Guy1" target="_blank">[15]</a>; f, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007754#pone.0007754-Chau1" target="_blank">[36]</a>; g, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007754#pone.0007754-Blakemore2" target="_blank">[13]</a>; h, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007754#pone.0007754-Ehrlich1" target="_blank">[63]</a>; i, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007754#pone.0007754-Grandis1" target="_blank">[64]</a>; j, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007754#pone.0007754-Michailov1" target="_blank">[65]</a>; k, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007754#pone.0007754-Wallace1" target="_blank">[66]</a>; l, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007754#pone.0007754-Jeronimo1" target="_blank">[67]</a>; m, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007754#pone.0007754-Malik1" target="_blank">[68]</a>; n, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007754#pone.0007754-Fahrenkamp1" target="_blank">[69]</a>; o, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007754#pone.0007754-Thomas1" target="_blank">[70]</a>; p, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007754#pone.0007754-Kerns1" target="_blank">[58]</a>; q, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007754#pone.0007754-Fraher1" target="_blank">[71]</a>. ^†signifies data from the present study (rat internal capsule raw data; 0.78±0.01 SEM, n = 85; and rat brainstem raw data; 0.81±0.01 SEM, n = 70).</p

Geometrical and electrical properties of a myelinated axon internodal segment of unit length and a schematic of the equivalent circuit.

<p><i>d_i</i> and <i>d_o</i> represent the inner and outer (i.e., <i>d_i</i> + total myelin sheath thickness) axon diameters respectively. <i>R_m</i> and <i>C_m</i> used in the model can be related to the axolemma (ax) and myelin (my) electrical components as follows: <i>R_m</i> = R_ax+nR_my and 1/<i>C_m</i> = 1/C_ax+n/C_my, where n is the number of myelin lamellae with a periodicity of 16 nm (naïve). R_a depends on both the geometric properties of the inner core and the core resistivity (<i>p</i>). Axon electrical parameters; <i>p</i> = 70 Ω·cm, R_ax = 4.7×10³ Ω·cm², R_my = 800 Ω·cm² (per lamellae), C_ax = 1 µF/cm², C_my = 0.6 µF/cm² (per lamellae). All values are based on published work (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007754#pone.0007754-Tasaki1" target="_blank">[30]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007754#pone.0007754-Awiszus1" target="_blank">[59]</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007754#pone.0007754-CurtisHaC1" target="_blank">[62]</a> and text).</p

The model can predict an optimized level of myelination for a given axon.

<p>A: Relative efficiency index with increasing lamellae (i.e. increasing sheath thickness) without volume as a constraint (i.e., <i>δ</i> = 0). A global optimum does not exist. B: Top, a schematic illustrating a 2 µm inner diameter (<i>d_i</i>) axon with an increasing (1→3) myelin sheath thickness; where the total myelin sheath thickness equals the difference between the outer (<i>d_o</i>) and inner diameters (i.e., <i>d_o</i>-<i>d_i</i>). Bottom, relative efficiency index for different myelin sheath thicknesses. “2” represents the level of “optimized” (i.e, maximal efficiency) myelination for this particular axon. “1” and “3” illustrate that lower or higher levels of myelination provide a less efficient myelo-architectural design. Here volume is a constraint (<i>δ</i> = <i>β</i> = 1).</p

Enhancing Gelation of Doubly Thermosensitive Hydrophilic ABC Linear Triblock Copolymers in Water by Thermoresponsive Hairy Nanoparticles

A method is reported for enhancing the gelation of doubly thermosensitive hydrophilic linear ABC triblock copolymers in water using thermoresponsive polymer brush-grafted nanoparticles (hairy NPs). A linear ABC triblock copolymer (ABC-Q) composed of a hydrophilic, charged middle block, and two thermosensitive outer blocks with different LCSTs, LCST_A of the lower LCST A block and LCST_C of the higher LCST C block, and two batches of hairy NPs with distinct thermoresponsive properties were prepared. When the temperature was raised from 0 °C to above the LCST_A but below the LCST_C, ABC-Q self-assembled into micelles in water with the lower LCST A block forming the core; further heating to above the LCST_C triggered the collapse of the C block, producing a two-compartment 3-D network micellar hydrogel when the polymer concentration was sufficiently high. Rheological studies showed that adding thermoresponsive hairy NPs with a LCST similar to the LCST_C of ABC-Q led to a significant increase in dynamic storage modulus (<i>G</i>′). For 6 wt % aqueous solutions of ABC-Q, the maximum value of <i>G</i>′ (<i>G</i>′_max) increased with increasing amount of hairy NPs; a 45% increase in <i>G</i>′_max was observed at the NP-to-polymer mass ratio of 60:100. It is believed that hairy NPs acted as “seeds” to adsorb the collapsed C block of ABC-Q, promoting the formation of bridging chains among micellar cores and NPs and thus enhancing the gelation. In contrast, no benefit was observed when adding hairy NPs with a LCST much higher than LCST_C; the <i>G</i>′_max exhibited little change with increasing NP-to-polymer mass ratio. Our explanations for the rheological observations were supported by fluorescence resonance energy transfer studies

Mobility of Proteins in Porous Substrates under Electrospray Ionization Conditions

Proteins are important substances in living organisms and characterization of proteins is an indispensible part for protein study. Analysis of proteins using electrospray ionization-mass spectrometry (ESI-MS) with porous substrates was investigated in this study. The results revealed that the ionization process had two stages. At the first stage, mobility and resulting spectra of proteins were similar to those obtained with conventional capillary-based ESI-MS. At the second stage, hydrophobic–hydrophobic interactions between proteins and the tip surfaces played an important role in mobility and detectability of protein ions, which were size and shape dependent, and a linear relationship could be found between the peak area of selected ion chromatogram and the cross section of protein ions. Preparative separation of proteins could be achieved by collecting the proteins remained on the porous substrates. These results led us to propose that electrospray ionization from porous substrates offer a potential approach for analysis of proteins and investigation of protein structures and conformations

Genetically Engineered Excitable Cardiac Myofibroblasts Coupled to Cardiomyocytes Rescue Normal Propagation and Reduce Arrhythmia Complexity in Heterocellular Monolayers

<div><h3>Rationale and Objective</h3><p>The use of genetic engineering of unexcitable cells to enable expression of gap junctions and inward rectifier potassium channels has suggested that cell therapies aimed at establishing electrical coupling of unexcitable donor cells to host cardiomyocytes may be arrhythmogenic. Whether similar considerations apply when the donor cells are electrically excitable has not been investigated. Here we tested the hypothesis that adenoviral transfer of genes coding Kir2.1 (I_K1), Na_V1.5 (I_Na) and connexin-43 (Cx43) proteins into neonatal rat ventricular myofibroblasts (NRVF) will convert them into fully excitable cells, rescue rapid conduction velocity (CV) and reduce the incidence of complex reentry arrhythmias in an <em>in vitro</em> model.</p> <h3>Methods and Results</h3><p>We used adenoviral (Ad-) constructs encoding Kir2.1, Na_V1.5 and Cx43 in NRVF. In single NRVF, Ad-Kir2.1 or Ad-Na_V1.5 infection enabled us to regulate the densities of I_K1 and I_Na, respectively. At varying MOI ratios of 10/10, 5/10 and 5/20, NRVF co-infected with Ad-Kir2.1+ Na_V1.5 were hyperpolarized and generated action potentials (APs) with upstroke velocities >100 V/s. However, when forming monolayers only the addition of Ad-Cx43 made the excitable NRVF capable of conducting electrical impulses (CV = 20.71±0.79 cm/s). When genetically engineered excitable NRVF overexpressing Kir2.1, Na_V1.5 and Cx43 were used to replace normal NRVF in heterocellular monolayers that included neonatal rat ventricular myocytes (NRVM), CV was significantly increased (27.59±0.76 cm/s vs. 21.18±0.65 cm/s, p<0.05), reaching values similar to those of pure myocytes monolayers (27.27±0.72 cm/s). Moreover, during reentry, propagation was faster and more organized, with a significantly lower number of wavebreaks in heterocellular monolayers formed by excitable compared with unexcitable NRVF.</p> <h3>Conclusion</h3><p>Viral transfer of genes coding Kir2.1, Na_V1.5 and Cx43 to cardiac myofibroblasts endows them with the ability to generate and propagate APs. The results provide proof of concept that cell therapies with excitable donor cells increase safety and reduce arrhythmogenic potential.</p> </div

K/Na/Cx43 NRVF rescued normal conduction velocity. A.

<p>Activation maps from monolayers of myocytes only (M, left), uninfected NRVF/NRVM co-culture (UI Fb/M, middle), and K/Na/Cx43 NRVF/NRVM co-culture (K/Na/Cx43 Fb/M, right). <b>B.</b> Quantification of conduction velocities at varies pacing cycle lengths in monolayers of myocytes (filled circles), UI Fb/M (open circle), and K/Na/Cx43 Fb/M (filled square).</p

Densities and Molar Volumes of Aqueous Solutions of Li₂SO₄ at Temperatures from 343 to 573 K

Densities of aqueous solutions of lithium sulfate (Li₂SO₄) at solute molalities ranging from 0.05 to 2.7 mol·kg^–1 have been measured by vibrating-tube densimetry over the temperature range 373.15 ≤ <i>T</i>/K ≤ 573.15 at pressures close to the saturated vapor pressure of pure water. The apparent molar volumes (<i>V</i>_ϕ) of Li₂SO₄(aq) calculated from these data together with previously published data at 323.15 and 343.15 K were fitted using a modified Redlich–Rosenfeld–Meyer equation, which in turn was used to extrapolate the experimental data to infinite dilution to obtain the standard partial molar volumes. A comparison of the present and literature data revealed the latter are inaccurate at low concentrations and are increasingly unreliable at higher temperatures. The combination of the present results with selected literature data produced a reliable equation of state for Li₂SO₄(aq) covering the temperature and pressure ranges 323.15 ≤ <i>T</i>/K ≤ 573.15 and 0.1 ≤ <i>p</i>/MPa ≤ 40. The volumetric behavior of Li₂SO₄(aq) was found to differ dramatically from that of Na₂SO₄(aq) and K₂SO₄(aq), especially at higher temperatures, higher concentrations, and lower pressures, reflecting the exceptional character of lithium ion hydration. Isobaric expansibilities indicated that Li₂SO₄(aq) remains a water structure maker over the investigated conditions

Cell size of NRVF and NRVM.

<p>Cell size of NRVF and NRVM.</p