Channel activation and AP dynamics in models with cooperative sodium channels.

<p>(<b>A,B</b>) Activation curves of sodium channels and (<b>C.D</b>) AP phase plots for the models with a small () and a large () fraction of cooperative channels, and a weak coupling (, blue traces) or strong coupling (, red traces).</p

Dependence of the sodium channel dynamics on the coupling strength ().

<p>(<b>A,B</b>) Simulated open probability of sodium channels in response to steps of holding potential of increasing amplitude. The voltage-clamp protocol is shown above the traces in (<b>A</b>). Simulations for independent channels (<b>A</b>, ) and for cooperative channels with the critical value of coupling strength (<b>B</b>, ). (<b>C</b>) Collective activation curves of sodium channels with an increasing coupling strength . Discontinuous portions of activation curves for are shown as interrupted lines.</p

Cooperative gating of and channels.

<p>(<b>A</b>) Simultaneous openings of pairs and triples of channels in inside-out patch from cardiac myocytes treated with the ischaemic metabolite lysophosphatidylchloline <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037629#pone.0037629-Undrovinas1" target="_blank">[2]</a>. In the left panel, zero corresponds to closed state; dotted lines and numbers 1,2,3 indicate openings to single, double and triple unitary conductance levels. Right panel shows histogram of current amplitude distribution. Note frequent occurrence of openings to double and triple unitary levels, but no openings to the unitary level. (<b>B</b>) Coopled gating of ryanodine R2 channels in cardiac cells <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037629#pone.0037629-Marx2" target="_blank">[6]</a>. Left panel shows example traces with openings to single, double and triple unitary conductance levels. Closed state is indicated by c; single, double and triple unitary conductance levels are indicated by 1,2,3. Right panel shows current amplitude histograms, corresponding to the traces on the left. Reproduced with permision from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037629#pone.0037629-Undrovinas1" target="_blank">[2]</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037629#pone.0037629-Marx2" target="_blank">[6]</a>.</p

AP onset rapidness and threshold variability in models with cooperative channels.

<p>(<b>A</b>) Dependence of the AP onset rapidness measured as the phase slope at on the coupling strength and the fraction of cooperative channels. White contours delimit the bounder lines between the monophasic and the biphasic APs (see insets). (<b>B</b>) Dependence of the threshold variability (blue symbols, scale on the left) and onset rapidness (red symbols, scale on the right) on the coupling strength for a model with a small fraction () of cooperative channels. Fluctuating current for injection that mimicked background synaptic noise was synthesized as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037629#s2" target="_blank">Methods</a> (see Eq. 3) (<b>C</b>) Relation between threshold variability and AP onset rapidness for the same model, data from (<b>B</b>).</p

Data_Sheet_1_Mesenchymal stem cell therapy for ischemic stroke: Novel insight into the crosstalk with immune cells.docx

Stroke, a cerebrovascular accident, is prevalent and the second highest cause of death globally across patient populations; it is as a significant cause of morbidity and mortality. Mesenchymal stem cell (MSC) transplantation is emerging as a promising treatment for alleviating neurological deficits, as indicated by a great number of animal and clinical studies. The potential of regulating the immune system is currently being explored as a therapeutic target after ischemic stroke. This study will discuss recent evidence that MSCs can harness the immune system by interacting with immune cells to boost neurologic recovery effectively. Moreover, a notion will be given to MSCs participating in multiple pathological processes, such as increasing cell survival angiogenesis and suppressing cell apoptosis and autophagy in several phases of ischemic stroke, consequently promoting neurological function recovery. We will conclude the review by highlighting the clinical opportunities for MSCs by reviewing the safety, feasibility, and efficacy of MSCs therapy.</p

MicroRNA-211 Regulates Proliferation, Expansion, and Immune Inhibitory Function of Myeloid-Derived Suppressor Cells via Mediation of CHOP Expression

Myeloid-derived suppressor cells (MDSCs) are capable of effectively repressing immune responses against tumors and orchestrating the tumor microenvironment, which can promote tumor angiogenesis and metastasis. The pathway networks used to modulate tumor-expanded MDSC accumulation and function remain unclear. This study identified microRNA-211 (miR-211), whose expression was significantly decreased by factors derived from tumors. miR-211 was assumed to be critical in modulating the accumulation and activity of MDSCs isolated from ovarian cancer (OC)-bearing mice by targeting C/EBP homologous protein (CHOP). The upregulation of miR-211 repressed MDSC proliferation, inhibited MDSC immunosuppressive functions, and increased the number of co-incubated CD4+ and CD8+ cells. Furthermore, overexpression of miR-211 led to decreased activities of the NF-κB, PI3K/Akt, and STAT3 pathways and the subsequent downregulation of matrix metalloproteinases to promote tumor cell invasion and metastasis. CHOP overexpression counteracted the effects of miR-211 elevation on these phenotypic changes. Upregulation of miR-211 also dramatically impaired the activity of MDSCs and suppressed OC tumor growth in vivo. These results indicated that the miR-211-CHOP axis in MDSCs plays an essential role in the metastasis and proliferation of tumor-expanded MDSCs and might represent a promising cancer treatment target.</p

Additional file 1: Figure S1. of Modification of the fatty acid composition in Arabidopsis and maize seeds using a stearoyl-acyl carrier protein desaturase-1 (ZmSAD1) gene

Schematic diagrams of the different ZmSAD1 constructs. (a, d) ZmSAD1 constructs; (b) anti-ZmSAD1; and (c, e) ZmSAD1 RNAi (not to scale). a, b, and c were in the pBI121 vector and used for Arabidopsis transformation. d and e were in the pCAMBIA3301 vector and used for maize transformation. (f) Part of the ZmSAD1 cDNA sequence used for RNAi. (g) Sequence used as a loop in the RNAi construct. LB and RB, T-DNA left and right borders, respectively; Pnos, nopaline synthase gene promoter; Tnos, nopaline synthase gene terminator; NPTII, neomycin phosphotransferase II; FAE1, promoter of fatty acid elongation 1 condensing enzyme; SAD1, stearoyl-acyl carrier protein desaturase1; bar, phosphinothricin acetyltransferase; T35s, CaMV 35S terminator; and P35s: CaMV35S promoter. The full-length cDNA of ZmSAD1 was used in the ZmSAD1 and anti-ZmSAD1 constructs. (DOCX 964 kb

Cation Clock Permits Distinction Between the Mechanisms of α- and β‑O- and β‑C-Glycosylation in the Mannopyranose Series: Evidence for the Existence of a Mannopyranosyl Oxocarbenium Ion

The use of a cationic cyclization reaction as a probe of the glycosylation mechanism has been developed and applied to the 4,6-<i>O</i>-benzylidene-protected mannopyranoside system. Cyclization results in the formation of both cis- and trans-fused tricyclic systems, invoking an intermediate glycosyl oxocarbenium ion reacting through a boat conformation. Competition reactions with isopropanol and trimethyl­(methallyl)­silane are interpreted as indicating that β-O-mannosylation proceeds via an associative S_N2-like mechanism, whereas α-O-mannosylation and β-C-mannosylation are dissociative and S_N1-like. Relative rate constants for reactions going via a common intermediate can be estimated

Cation Clock Permits Distinction Between the Mechanisms of α- and β‑O- and β‑C-Glycosylation in the Mannopyranose Series: Evidence for the Existence of a Mannopyranosyl Oxocarbenium Ion

The use of a cationic cyclization reaction as a probe of the glycosylation mechanism has been developed and applied to the 4,6-<i>O</i>-benzylidene-protected mannopyranoside system. Cyclization results in the formation of both cis- and trans-fused tricyclic systems, invoking an intermediate glycosyl oxocarbenium ion reacting through a boat conformation. Competition reactions with isopropanol and trimethyl­(methallyl)­silane are interpreted as indicating that β-O-mannosylation proceeds via an associative S_N2-like mechanism, whereas α-O-mannosylation and β-C-mannosylation are dissociative and S_N1-like. Relative rate constants for reactions going via a common intermediate can be estimated

Novel perovskite structured Nd_0.5Ba_0.5Co_1/3Ni_1/3Mn_1/3O_3−δ as highly efficient catalyst for oxygen electrode in solid oxide electrochemical cells

Developing catalytic materials with highly efficient oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is essential for lower-temperature solid oxide fuel cell (SOFC) and electrolysis cell (SOEC) technologies. In this work, a novel triple perovskite material, Nd0.5Ba0.5Co1/3Ni1/3Mn1/3O3−δ, has been developed and employed as a catalyst for both ORR and OER in SOFC and SOEC operations at relatively lower temperatures, showing a low polarization resistance of 0.327 Ω cm2, high-power output of SOFC up to 773 mW cm–2 at 650 °C, and a high current density of 1.57 A cm–2 from SOEC operation at 1.5 V at 600 °C. The relaxation time distribution reveals that Nd0.5Ba0.5Co1/3Ni1/3Mn1/3O3−δ could maintain a slow polarization process at the relatively low operating temperature, offering a significant antipolarization advantage over other perovskite electrode materials. The Nd0.5Ba0.5Co1/3Ni1/3Mn1/3O3−δ electrode provides a low energy barrier of about 0.36 eV in oxygen ion mobility, which is beneficent for oxygen reduction/evolution reaction processes.</p