Sample records for cgmp-activated cation conductance

  1. A calcium-permeable cGMP-activated cation conductance in hippocampal neurons

    NASA Technical Reports Server (NTRS)

    Leinders-Zufall, T.; Rosenboom, H.; Barnstable, C. J.; Shepherd, G. M.; Zufall, F.

    1995-01-01

    Whole-cell patch clamp recordings detected a previously unidentified cGMP-activated membrane conductance in cultured rat hippocampal neurons. This conductance is nonselectively permeable for cations and is completely but reversibly blocked by external Cd2+. The Ca2+ permeability of the hippocampal cGMP-activated conductance was examined in detail, indicating that the underlying ion channels display a high relative permeability for Ca2+. The results indicate that hippocampal neurons contain a cGMP-activated membrane conductance that has some properties similar to the cyclic nucleotide-gated channels previously shown in sensory receptor cells and retinal neurons. In hippocampal neurons this conductance similarly could mediate membrane depolarization and Ca2+ fluxes in response to intracellular cGMP elevation.

  2. An atypical CNG channel activated by a single cGMP molecule controls sperm chemotaxis.

    PubMed

    Bönigk, Wolfgang; Loogen, Astrid; Seifert, Reinhard; Kashikar, Nachiket; Klemm, Clementine; Krause, Eberhard; Hagen, Volker; Kremmer, Elisabeth; Strünker, Timo; Kaupp, U Benjamin

    2009-10-27

    Sperm of the sea urchin Arbacia punctulata can respond to a single molecule of chemoattractant released by an egg. The mechanism underlying this extreme sensitivity is unknown. Crucial signaling events in the response of A. punctulata sperm to chemoattractant include the rapid synthesis of the intracellular messenger guanosine 3',5'-monophosphate (cGMP) and the ensuing membrane hyperpolarization that results from the opening of potassium-selective cyclic nucleotide-gated (CNGK) channels. Here, we use calibrated photolysis of caged cGMP to show that approximately 45 cGMP molecules are generated during the response to a single molecule of chemoattractant. The CNGK channel can respond to such small cGMP changes because it is exquisitely sensitive to cGMP and activated in a noncooperative fashion. Like voltage-activated Ca(v) and Na(v) channels, the CNGK polypeptide consists of four homologous repeat sequences. Disabling each of the four cyclic nucleotide-binding sites through mutagenesis revealed that binding of a single cGMP molecule to repeat 3 is necessary and sufficient to activate the CNGK channel. Thus, CNGK has developed a mechanism of activation that is different from the activation of other CNG channels, which requires the cooperative binding of several ligands and operates in the micromolar rather than the nanomolar range.

  3. Partial reconstitution of photoreceptor cGMP phosphodiesterase characteristics in cGMP phosphodiesterase-5.

    PubMed

    Granovsky, A E; Artemyev, N O

    2001-06-15

    Photoreceptor cGMP phosphodiesterases (PDE6) are uniquely qualified to serve as effector enzymes in the vertebrate visual transduction cascade. In the dark-adapted photoreceptors, the activity of PDE6 is blocked via tight association with the inhibitory gamma-subunits (Pgamma). The Pgamma block is removed in the light-activated PDE6 by the visual G protein, transducin. Transducin-activated PDE6 exhibits an exceptionally high catalytic rate of cGMP hydrolysis ensuring high signal amplification. To identify the structural determinants for the inhibitory interaction with Pgamma and the remarkable cGMP hydrolytic ability, we sought to reproduce the PDE6 characteristics by mutagenesis of PDE5, a related cyclic GMP-specific, cGMP-binding PDE. PDE5 is insensitive to Pgamma and has a more than 100-fold lower k(cat) for cGMP hydrolysis. Our mutational analysis of chimeric PDE5/PDE6alpha' enzymes revealed that the inhibitory interaction of cone PDE6 catalytic subunits (PDE6alpha') with Pgamma is mediated primarily by three hydrophobic residues at the entry to the catalytic pocket, Met(758), Phe(777), and Phe(781). The maximal catalytic rate of PDE5 was enhanced by at least 10-fold with substitutions of PDE6alpha'-specific glycine residues for the corresponding PDE5 alanine residues, Ala(608) and Ala(612). The Gly residues are adjacent to the highly conserved metal binding motif His-Asn-X-X-His, which is essential for cGMP hydrolysis. Our results suggest that the unique Gly residues allow the PDE6 metal binding site to adopt a more favorable conformation for cGMP hydrolysis.

  4. cGMP accumulation causes photoreceptor degeneration in CNG channel deficiency: evidence of cGMP cytotoxicity independently of enhanced CNG channel function.

    PubMed

    Xu, Jianhua; Morris, Lynsie; Thapa, Arjun; Ma, Hongwei; Michalakis, Stylianos; Biel, Martin; Baehr, Wolfgang; Peshenko, Igor V; Dizhoor, Alexander M; Ding, Xi-Qin

    2013-09-11

    Photoreceptor cyclic nucleotide-gated (CNG) channels regulate Ca(2+) influx in rod and cone photoreceptors. cGMP, the native ligand of the photoreceptor CNG channels, has been associated with cytotoxicity when its levels rise above normal due to defects in photoreceptor phosphodiesterase (PDE6) or regulation of retinal guanylyl cyclase (retGC). We found a massive accumulation of cGMP in CNGA3-deficient retina and investigated whether cGMP accumulation plays a role in cone degeneration in CNG channel deficiency. The time course study showed that the retinal cGMP level in Cnga3(-/-);Nrl(-/-) mice with CNGA3 deficiency on a cone-dominant background was sharply increased at postnatal day 8 (P8), peaked around P10-P15, remained high through P30-P60, and returned to near control level at P90. This elevation pattern correlated with photoreceptor apoptotic death, which peaked around P15-P20. In Cnga3(-/-);Gucy2e(-/-) mice lacking retGC1, cone density and expression levels of cone-specific proteins were significantly increased compared with Cnga3(-/-), consistent with a role of cGMP accumulation as the major contributor to cone death caused by CNG channel deficiency. The activity and expression levels of cGMP-dependent protein kinase G (PKG) were significantly increased in Cnga3(-/-);Nrl(-/-) retina compared with Nrl(-/-), suggesting an involvement of PKG regulation in cell death. Our results indicate that cGMP accumulation in photoreceptors can itself exert cytotoxic effect in cones, independently of CNG channel activity and Ca(2+) influx.

  5. Design of CGMP Production of 18F- and 68Ga-Radiopharmaceuticals

    PubMed Central

    Chu, Pei-Chun; Chao, Hao-Yu; Shieh, Wei-Chen; Chen, Chuck C.

    2014-01-01

    Objective. Radiopharmaceutical production process must adhere to current good manufacturing process (CGMP) compliance to ensure the quality of precursor, prodrug (active pharmaceutical ingredient, API), and the final drug product that meet acceptance criteria. We aimed to develop an automated system for production of CGMP grade of PET radiopharmaceuticals. Methods. The hardware and software of the automated synthesizer that fit in the hot cell under cGMP requirement were developed. Examples of production yield and purity for 68Ga-DOTATATE and 18F-FDG at CGMP facility were optimized. Analytical assays and acceptance criteria for cGMP grade of 68Ga-DOTATATE and 18F-FDG were established. Results. CGMP facility for the production of PET radiopharmaceuticals has been established. Radio-TLC and HPLC analyses of 68Ga-DOTATATE and 18F-FDG showed that the radiochemical purity was 92% and 96%, respectively. The products were sterile and pyrogenic-free. Conclusion. CGMP compliance of radiopharmaceuticals has been reviewed. 68Ga-DOTATATE and 18F-FDG were synthesized with high radiochemical yield under CGMP process. PMID:25276810

  6. Attenuated vasodilatation in lambs with endogenous and exogenous activation of cGMP signaling: Role of protein kinase G nitration

    PubMed Central

    Aggarwal, Saurabh; Gross, Christine M.; Kumar, Sanjiv; Datar, Sanjeev; Oishi, Peter; Kalka, Gokhan; Schreiber, Christian; Fratz, Sohrab; Fineman, Jeffrey R.; Black, Stephen M.

    2012-01-01

    Pulmonary vasodilation is mediated through the activation of protein kinase G (PKG) via a signaling pathway involving nitric oxide (NO), natriuretic peptides (NP), and cyclic guanosine monophosphate (cGMP). In pulmonary hypertension secondary to congenital heart disease, this pathway is endogenously activated by an early vascular upregulation of NO and increased myocardial B-type NP expression and release. In the treatment of pulmonary hypertension, this pathway is exogenously activated using inhaled NO or other pharmacological agents. Despite this activation of cGMP, vascular dysfunction is present, suggesting that NO-cGMP independent mechanisms are involved and were the focus of this study. Exposure of pulmonary artery endothelial or smooth muscle cells to the NO donor, Spermine NONOate (SpNONOate), increased peroxynitrite (ONOO−) generation and PKG-1α nitration, while PKG-1α activity was decreased. These changes were prevented by superoxide dismutase (SOD) or manganese(III)tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP) and mimicked by the ONOO− donor, 3-morpholinosydnonimine N-ethylcarbamide (SIN-1). Peripheral lung extracts from 4-week old lambs with increased pulmonary blood flow and pulmonary hypertension (Shunt lambs with endogenous activation of cGMP) or juvenile lambs treated with inhaled NO for 24h (with exogenous activation of cGMP) revealed increased ONOO− levels, elevated PKG-1α nitration, and decreased kinase activity without changes in PKG-1α protein levels. However, in Shunt lambs treated with L-arginine or lambs administered polyethylene glycol conjugated-SOD (PEG-SOD) during inhaled NO exposure, ONOO− and PKG-1α nitration were diminished and kinase activity was preserved. Together our data reveal that vascular dysfunction can occur, despite elevated levels of cGMP, due to PKG-1α nitration and subsequent attenuation of activity. PMID:21351102

  7. Self-Incompatibility in Papaver rhoeas Activates Nonspecific Cation Conductance Permeable to Ca2+ and K+[W

    PubMed Central

    Wu, Juyou; Wang, Su; Gu, Yuchun; Zhang, Shaoling; Publicover, Stephen J.; Franklin-Tong, Vernonica E.

    2011-01-01

    Cellular responses rely on signaling. In plant cells, cytosolic free calcium is a major second messenger, and ion channels play a key role in mediating physiological responses. Self-incompatibility (SI) is an important genetically controlled mechanism to prevent self-fertilization. It uses interaction of matching S-determinants from the pistil and pollen to allow “self” recognition, which triggers rejection of incompatible pollen. In Papaver rhoeas, the S-determinants are PrsS and PrpS. PrsS is a small novel cysteine-rich protein; PrpS is a small novel transmembrane protein. Interaction of PrsS with incompatible pollen stimulates S-specific increases in cytosolic free calcium and alterations in the actin cytoskeleton, resulting in programmed cell death in incompatible but not compatible pollen. Here, we have used whole-cell patch clamping of pollen protoplasts to show that PrsS stimulates SI-specific activation of pollen grain plasma membrane conductance in incompatible but not compatible pollen grain protoplasts. The SI-activated conductance does not require voltage activation, but it is voltage sensitive. It is permeable to divalent cations (Ba2+ ≥ Ca2+ > Mg2+) and the monovalent ions K+ and NH4+ and is enhanced at voltages negative to −100 mV. The Ca2+ conductance is blocked by La3+ but not by verapamil; the K+ currents are tetraethylammonium chloride insensitive and do not require Ca2+. We propose that the SI-stimulated conductance may represent a nonspecific cation channel or possibly two conductances, permeable to monovalent and divalent cations. Our data provide insights into signal-response coupling involving a biologically important response. PrsS provides a rare example of a protein triggering alterations in ion channel activity. PMID:21177472

  8. cGMP inhibition of type 3 phosphodiesterase is the major mechanism by which C-type natriuretic peptide activates CFTR in the shark rectal gland

    PubMed Central

    De Jonge, Hugo R.; Tilly, Ben C.; Hogema, Boris M.; Pfau, Daniel J.; Kelley, Catherine A.; Kelley, Megan H.; Melita, August M.; Morris, Montana T.; Viola, Ryan M.

    2013-01-01

    The in vitro perfused rectal gland of the dogfish shark (Squalus acanthias) and filter-grown monolayers of primary cultures of shark rectal gland (SRG) epithelial cells were used to analyze the signal transduction pathway by which C-type natriuretic peptide (CNP) stimulates chloride secretion. CNP binds to natriuretic receptors in the basolateral membrane, elevates cellular cGMP, and opens cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels in the apical membrane. CNP-provoked chloride secretion was completely inhibitable by the nonspecific protein kinase inhibitor staurosporine and the PKA inhibitor H89 but insensitive to H8, an inhibitor of type I and II isoforms of cGMP-dependent protein kinase (cGKI and cGKII). CNP-induced secretion could not be mimicked by nonhydrolyzable cGMP analogs added alone or in combination with the protein kinase C activator phorbolester, arguing against a role for cGK or for cGMP-induced PKC signaling. We failed to detect a dogfish ortholog of cGKII by molecular cloning and affinity chromatography. However, inhibitors of the cGMP-inhibitable isoform of phosphodiesterase (PDE3) including milrinone, amrinone, and cilostamide but not inhibitors of other PDE isoenzymes mimicked the effect of CNP on chloride secretion in perfused glands and monolayers. CNP raised cGMP and cAMP levels in the SRG epithelial cells. This rise in cAMP as well as the CNP and amrinone-provoked chloride secretion, but not the rise in cGMP, was almost completely blocked by the Gαi-coupled adenylyl cyclase inhibitor somatostatin, arguing against a role for cGMP cross-activation of PKA in CNP action. These data provide molecular, functional, and pharmacological evidence for a CNP/cGMP/PDE3/cAMP/PKA signaling cascade coupled to CFTR in the SRG. PMID:24259420

  9. Optogenetic manipulation of cGMP in cells and animals by the tightly light-regulated guanylyl-cyclase opsin CyclOp

    PubMed Central

    Gao, Shiqiang; Nagpal, Jatin; Schneider, Martin W.; Kozjak-Pavlovic, Vera; Nagel, Georg; Gottschalk, Alexander

    2015-01-01

    Cyclic GMP (cGMP) signalling regulates multiple biological functions through activation of protein kinase G and cyclic nucleotide-gated (CNG) channels. In sensory neurons, cGMP permits signal modulation, amplification and encoding, before depolarization. Here we implement a guanylyl cyclase rhodopsin from Blastocladiella emersonii as a new optogenetic tool (BeCyclOp), enabling rapid light-triggered cGMP increase in heterologous cells (Xenopus oocytes, HEK293T cells) and in Caenorhabditis elegans. Among five different fungal CyclOps, exhibiting unusual eight transmembrane topologies and cytosolic N-termini, BeCyclOp is the superior optogenetic tool (light/dark activity ratio: 5,000; no cAMP production; turnover (20 °C) ∼17 cGMP s−1). Via co-expressed CNG channels (OLF in oocytes, TAX-2/4 in C. elegans muscle), BeCyclOp photoactivation induces a rapid conductance increase and depolarization at very low light intensities. In O2/CO2 sensory neurons of C. elegans, BeCyclOp activation evokes behavioural responses consistent with their normal sensory function. BeCyclOp therefore enables precise and rapid optogenetic manipulation of cGMP levels in cells and animals. PMID:26345128

  10. Optogenetic manipulation of cGMP in cells and animals by the tightly light-regulated guanylyl-cyclase opsin CyclOp.

    PubMed

    Gao, Shiqiang; Nagpal, Jatin; Schneider, Martin W; Kozjak-Pavlovic, Vera; Nagel, Georg; Gottschalk, Alexander

    2015-09-08

    Cyclic GMP (cGMP) signalling regulates multiple biological functions through activation of protein kinase G and cyclic nucleotide-gated (CNG) channels. In sensory neurons, cGMP permits signal modulation, amplification and encoding, before depolarization. Here we implement a guanylyl cyclase rhodopsin from Blastocladiella emersonii as a new optogenetic tool (BeCyclOp), enabling rapid light-triggered cGMP increase in heterologous cells (Xenopus oocytes, HEK293T cells) and in Caenorhabditis elegans. Among five different fungal CyclOps, exhibiting unusual eight transmembrane topologies and cytosolic N-termini, BeCyclOp is the superior optogenetic tool (light/dark activity ratio: 5,000; no cAMP production; turnover (20 °C) ∼17 cGMP s(-1)). Via co-expressed CNG channels (OLF in oocytes, TAX-2/4 in C. elegans muscle), BeCyclOp photoactivation induces a rapid conductance increase and depolarization at very low light intensities. In O2/CO2 sensory neurons of C. elegans, BeCyclOp activation evokes behavioural responses consistent with their normal sensory function. BeCyclOp therefore enables precise and rapid optogenetic manipulation of cGMP levels in cells and animals.

  11. Modulation of cGMP by human HO-1 retrovirus gene transfer in pulmonary microvessel endothelial cells.

    PubMed

    Abraham, Nader G; Quan, Shuo; Mieyal, Paul A; Yang, Liming; Burke-Wolin, Theresa; Mingone, Christopher J; Goodman, Alvin I; Nasjletti, Alberto; Wolin, Michael S

    2002-11-01

    Carbon monoxide (CO) stimulates guanylate cyclase (GC) and increases guanosine 3',5'-cyclic monophosphate (cGMP) levels. We transfected rat-lung pulmonary endothelial cells with a retrovirus-mediated human heme oxygenase (hHO)-1 gene. Pulmonary cells that expressed hHO-1 exhibited a fourfold increase in HO activity associated with decreases in the steady-state levels of heme and cGMP without changes in soluble GC (sGC) and endothelial nitric oxide synthase (NOS) proteins or basal nitrite production. Heme elicited significant increases in CO production and intracellular cGMP levels in both pulmonary endothelial and pulmonary hHO-1-expressing cells. N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS, significantly decreased cGMP levels in heme-treated pulmonary endothelial cells but not heme-treated hHO-1-expressing cells. In the presence of exogenous heme, CO and cGMP levels in hHO-1-expressing cells exceeded the corresponding levels in pulmonary endothelial cells. Acute exposure of endothelial cells to SnCl2, which is an inducer of HO-1, increased cGMP levels, whereas chronic exposure decreased heme and cGMP levels. These results indicate that prolonged overexpression of HO-1 ultimately decreases sGC activity by limiting the availability of cellular heme. Heme activates sGC and enhances cGMP levels via a mechanism that is largely insensitive to NOS inhibition.

  12. Nitric Oxide Mediates Glutamate-Linked Enhancement of cGMP Levels in the Cerebellum

    NASA Astrophysics Data System (ADS)

    Bredt, David S.; Snyder, Solomon H.

    1989-11-01

    Nitric oxide, which mediates influences of numerous neurotransmitters and modulators on vascular smooth muscle and leukocytes, can be formed in the brain from arginine by an enzymatic activity that stoichiometrically generates citrulline. We show that glutamate and related amino acids, such as N-methyl-D-aspartate, markedly stimulate arginine-citrulline transformation in cerebellar slices stoichiometrically with enhancement of cGMP levels. Nω-monomethyl-L-arginine blocks the augmentation both of citrulline and cGMP with identical potencies. Arginine competitively reverses both effects of Nω-monomethyl-L-arginine with the same potencies. Hemoglobin, which complexes nitric oxide, prevents the stimulation by N-methyl-D-aspartate of cGMP levels, and superoxide dismutase, which elevates nitric oxide levels, increases cGMP formation. These data establish that nitric oxide mediates the stimulation by glutamate of cGMP formation.

  13. Deciphering cGMP signatures and cGMP-dependent pathways in plant defence

    PubMed Central

    Meier, Stuart; Madeo, Laura; Ederli, Luisa; Donaldson, Lara; Gehring, Chris

    2009-01-01

    The second messenger, 3′,5′-cyclic monophosphate (cGMP), is a critical component of many different processes in plants while guanylyl cyclases that catalyse the formation of cGMP from GTP have remained somewhat elusive in higher plants. Consequently, two major aims are the discovery of novel GCs and the identification of cGMP mediated processes. Recently, we have reported temporal signatures of ozone (O3)-induced hydrogen peroxide (H2O2) and nitric oxide (NO) generation, their effect on cGMP generation, and consequent transcriptional changes of genes diagnostic for stress responses in tobacco. We demonstrated that O3 and NO induced early transcriptional activation of the scavenger encoding proteins, alternative oxidase (AOX1a), glutathione peroxidase (GPX) and the induction of ethylene production through aminocyclopropancarboxylic acid synthase (ACS2) are cGMP-independent. By contrast, the early response of the phenylalanine ammonia lyase gene (PALa) and the late response of the gene encoding the pathogenesis-related protein (PR1a) show critical dependence on cGMP. Here we show differential cGMP responses to virulent and avirulent Pseudomonas syringae strains and propose that host-pathogen recognition and/or down-stream processes are transduced by complex cGMP signatures. This is in accordance with the identification of a growing number of multi-domain molecules in Arabidopsis that are reported to contain putative functional GC catalytic centers. PMID:19794847

  14. cGMP in ozone and NO dependent responses

    PubMed Central

    Ederli, Luisa; Meier, Stuart; Borgogni, Andrea; Reale, Lara; Ferranti, Francesco; Gehring, Chris

    2008-01-01

    We have recently reported that ozone (O3) can inhibit mitochondrial respiration and induce activation of the alternative oxidase (AOX) pathway and in particular AOX1a in tobacco. While O3 causes mitochondrial H2O2, early leaf nitric oxide (NO) as well as transient ethylene (ET) accumulation, the levels of jasmonic acid and 12-oxo-phytodienoic acid remained unchanged. It was shown that both, NO and ET dependent pathways can induce AOX1a transcription by O3. AOX plays a role in reducing reactive oxygen species (ROS) which in turn are linked to biotic and abiotic plant stresses, much like the second messengers guanosine 3′, 5′-cyclic monophosphate (cGMP). The goal is to unravel specific cGMP signatures and induction pathways downstream from O3 and NO, including transcription of AOX1a. Here we propose that some late (>3 h) responses to NO, e.g., the accumulation of phenylalanine lyase (PAL) transcripts, are critically cGMP dependent, while the early (<2 h) responses, including AOX1a induction are not. PMID:19704720

  15. Highly conducting divalent Mg{sup 2+} cation solid electrolytes with well-ordered three-dimensional network structure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tamura, Shinji; Yamane, Megumi; Hoshino, Yasunori

    2016-03-15

    A three-dimensionally well-ordered NASICON-type Mg{sup 2+} cation conductor, (Mg{sub x}Hf{sub 1−x}){sub 4/(4−2x)}Nb(PO{sub 4}){sub 3}, was firstly developed by partial substitution of lower valent Mg{sup 2+} cation onto the Hf{sup 4+} sites in a HfNb(PO{sub 4}){sub 3} solid to realize high Mg{sup 2+} cation conductivity even at moderate temperatures. Due to the formation of well-ordered NASICON-type structure, both the high Mg{sup 2+} cation conductivity below 450 °C and the low activation energy for Mg{sup 2+} cation migration was successfully realized for the (Mg{sub 0.1}Hf{sub 0.9}){sub 4/3.8}Nb(PO{sub 4}){sub 3} solid. Pure Mg{sup 2+} cation conduction in the NASICON-type (Mg{sub 0.1}Hf{sub 0.9}){sub 4/3.8}Nb(PO{submore » 4}){sub 3} solid was directly and quantitatively demonstrated by means of two kinds of dc electrolysis. - Graphical abstract: Image of the Mg{sup 2+} cation conduction in NASICON-type (Mg{sub 0.1}Hf{sub 0.9}){sub 4/3.8}Nb(PO{sub 4}){sub 3} and its Mg{sup 2+} conductivity. - Highlights: • We develop a three-dimensionally well-ordered NASICON-type Mg{sup 2+} cation conductor. • A high magnesium cation conductivity is realized even at moderate temperatures. • Divalent magnesium cation conduction is demonstrated directly and quantitatively.« less

  16. Hydrocortisone normalizes oxygenation and cGMP regulation in lambs with persistent pulmonary hypertension of the newborn

    PubMed Central

    Lakshminrusimha, Satyan; Wedgwood, Stephen; Czech, Lyubov; Gugino, Sylvia F.; Russell, James A.; Farrow, Kathryn N.; Steinhorn, Robin H.

    2012-01-01

    In the pulmonary vasculature, cGMP levels are regulated by soluble guanylate cyclase (sGC) and phosphodiesterase 5 (PDE5). We previously reported that lambs with persistent pulmonary hypertension of the newborn (PPHN) demonstrate increased reactive oxygen species (ROS) and altered sGC and PDE5 activity, with resultant decreased cGMP. The objective of this study was to evaluate the effects of hydrocortisone on pulmonary vascular function, ROS, and cGMP in the ovine ductal ligation model of PPHN. PPHN lambs were ventilated with 100% O2 for 24 h. Six lambs received 5 mg/kg hydrocortisone every 8 h times three doses (PPHN-hiHC), five lambs received 3 mg/kg hydrocortisone followed by 1 mg·kg−1·dose−1 times two doses (PPHN-loHC), and six lambs were ventilated with O2 alone (PPHN). All groups were compared with healthy 1-day spontaneously breathing lambs (1DSB). O2 ventilation of PPHN lambs decreased sGC activity, increased PDE5 activity, and increased ROS vs. 1DSB lambs. Both hydrocortisone doses significantly improved arterial-to-alveolar ratios relative to PPHN lambs, decreased PDE5 activity, and increased cGMP relative to PPHN lambs. High-dose hydrocortisone also increased sGC activity, decreased PDE5 expression, decreased ROS, and increased total vascular SOD activity vs. PPHN lambs. These data suggest that hydrocortisone treatment in clinically relevant doses improves oxygenation and decreases hyperoxia-induced changes in sGC and PDE5 activity, increasing cGMP levels. Hydrocortisone reduces ROS levels in part by increasing SOD activity in PPHN lambs ventilated with 100% O2. We speculate that hydrocortisone increases cGMP by direct effects on sGC and PDE5 expression and by attenuating abnormalities induced by oxidant stress. PMID:22198909

  17. Antisense oligodeoxynucleotide inhibition of a swelling-activated cation channel in osteoblast-like osteosarcoma cells

    NASA Technical Reports Server (NTRS)

    Duncan, R. L.; Kizer, N.; Barry, E. L.; Friedman, P. A.; Hruska, K. A.

    1996-01-01

    By patch-clamp analysis, we have shown that chronic, intermittent mechanical strain (CMS) increases the activity of stretch-activated cation channels of osteoblast-like UMR-106.01 cells. CMS also produces a swelling-activated whole-cell conductance (Gm) regulated by varying strain levels. We questioned whether the swelling-activated conductance was produced by stretch-activated cation channel activity. We have identified a gene involved in the increase in conductance by using antisense oligodeoxynucleotides (ODN) derived from the alpha 1-subunit genes of calcium channels found in UMR-106.01 cells (alpha1S, alpha1C, and alpha1D). We demonstrate that alpha 1C antisense ODNs abolish the increase in Gm in response to hypotonic swelling following CMS. Antisense ODNs to alpha1S and alpha1D, sense ODNs to alpha1C, and sham permeabilization had no effect on the conductance increase. In addition, during cell-attached patch-clamp studies, antisense ODNs to alpha1c completely blocked the swelling-activated and stretch-activated nonselective cation channel response to strain. Antisense ODNs to alpha1S treatment produced no effect on either swelling-activated or stretch-activated cation channel activity. There were differences in the stretch-activated and swelling-activated cation channel activity, but whether they represent different channels could not be determined from our data. Our data indicate that the alpha1C gene product is involved in the Gm and the activation of the swelling-activated cation channels induced by CMS. The possibility that swelling-activated cation channel genes are members of the calcium channel superfamily exists, but if alpha1c is not the swelling-activated cation channel itself, then its expression is required for induction of swelling-activated cation channel activity by CMS.

  18. From bedside to bench--meeting report of the 7th International Conference on cGMP "cGMP: generators, effectors and therapeutic implications" in Trier, Germany, from June 19th to 21st 2015.

    PubMed

    Friebe, Andreas; Sandner, Peter; Seifert, Roland

    2015-12-01

    During the past decade, our knowledge on the physiology, pathophysiology, basic pharmacology, and clinical pharmacology of the second messenger (cGMP) has increased tremendously. It is now well-established that cGMP, generated by soluble and particulate guanylate cyclases, is highly compartmentalized in cells and regulates numerous body functions. New cGMP-regulated physiological functions include meiosis and temperature perception. cGMP is involved in the genesis of numerous pathologies including cardiovascular, pulmonary, endocrine, metabolic, neuropsychiatric, eye, and tumor diseases. Several new clinical uses of stimulators and activators of soluble guanylate cyclase and of phosphodiesterase inhibitors such as heart failure, kidney failure, cognitive disorders, obesity bronchial asthma, and osteoporosis are emerging. The combination of neprilysin inhibitors-enhancing stimulation of the particulate guanylate cyclase pathway by preventing natriuretic peptide degradation-with angiotensin AT1 receptor antagonists constitutes a novel promising strategy for heart failure treatment. The role of oxidative stress in cGMP signaling, application of cGMP sensors, and gene therapy for degenerative eye diseases are emerging topics. It is anticipated that cGMP research will further prosper over the next years and reach out into more and more basic and clinical disciplines.

  19. The permeability of the cGMP-activated channel to organic cations in retinal rods of the tiger salamander.

    PubMed Central

    Picco, C; Menini, A

    1993-01-01

    1. The permeability of the channel activated by guanosine 3',5'-cyclic monophosphate (cGMP) to many organic monovalent cations was determined by recording macroscopic currents in excised inside-out patches of plasma membrane from isolated retinal rod outer segments of the tiger salamander. 2. Current-voltage relations were measured when the NaCl of the bathing medium was replaced by salts of organic cations. Permeability ratios relative to Na+ ions were calculated with the Goldman-Hodgkin-Katz potential equation from the measured changes of reversal potentials. 3. Hydroxylammonium+, hydrazinium+ and methylammonium+, which are molecules of very similar shape and size, permeate the channel with very different permeability ratios: 5.92, 1.99 and 0.60 respectively. 4. Methylated and ethylated ammonium+ compounds were investigated. It was found that, not only methylammonium+, but also dimethylammonium+ and ethylammonium+ were permeant with permeability ratios of 0.6, 0.14 and 0.16 respectively. Trimethylammonium+, tetramethylammonium+, diethylammonium+, triethylammonium+, and tetraethylammonium+ were not permeant. 5. Guanidinium+ and its derivatives formamidinium+, aminoguanidinium+, acetamidinium+ and methylguanidinium+ were all permeant with permeability ratios 1.12, 1.00, 0.63, 0.36 and 0.33 respectively. 6. The cGMP-activated channel was found to be permeable to at least thirteen organic cations. Molecular models of the permeant cations indicate that the cross-section of the narrowest part of the pore must be at least as large as a rectangle of 0.38 x 0.5 nm dimensions. PMID:7683718

  20. Prolonged treatment of porcine pulmonary artery with nitric oxide decreases cGMP sensitivity and cGMP-dependent protein kinase specific activity

    PubMed Central

    Perkins, William J.; Warner, David O.; Jones, Keith A.

    2009-01-01

    A cultured porcine pulmonary artery (PA) model was used to examine the effects of prolonged nitric oxide (NO) treatment on the response to acutely applied NO, cGMP analog, or atrial natriuretic peptide (ANP). Twenty-four-hour treatment with the NO donor (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO) resulted in >10-fold decrease in the response to acutely applied DETA-NO. In parallel with this, the relaxant response to acutely applied cGMP analog, β-phenyl-1,N2-etheno-8-bromoguanosine-3′,5′-cyclic monophosphorothioate, Sp isomer (Sp-8-Br-PET-cGMPS), and ANP decreased. The reduction in ANP responsiveness in PA was not associated with a reduction in cGMP levels evoked by 10−6 M ANP. Twenty-four hours in culture and treatment with DETA-NO decreased total cGMP-dependent protein kinase (cGKI) mRNA level compared with that in freshly prepared PA (1.05 ± 0.12, 0.42 ± 0.08, and 0.11 ± 0.01 amol/μg, respectively). Total cGKI protein levels were decreased to a lesser extent by 24 h in culture and further decreased by 24-h DETA-NO treatment compared with that in freshly prepared PA (361 ± 33, 272 ± 20, and 238 ± 25 ng/mg total protein, respectively). Maximal cGMP-stimulated phosphotransferase activity was reduced in 24-h cultured and DETA-NO-treated PA (986 ± 84, 815 ± 81, and 549 ± 78 pmol Pi·min−1·mg soluble protein−1), but the cGMP concentration resulting in 50% of maximal phosphotransferase activity was not. cGKI specific activity (maximal cGMP-activated phosphotransferase activity/ng cGKI) was significantly reduced in PA treated with DETA-NO for 24 h compared with freshly prepared and 24-h cultured PA (1.95 ± 0.22, 2.64 ± 0.25, and 2.85 ± 0.28 pmol Pi·min−1·ng cGKI−1, respectively). We conclude that prolonged NO treatment induces decreased acute NO responsiveness in PA in part by decreasing cGMP sensitivity. It does so by decreasing both cGKI expression and cGKI specific activity. PMID:18952758

  1. The human red cell voltage-regulated cation channel. The interplay with the chloride conductance, the Ca(2+)-activated K(+) channel and the Ca(2+) pump.

    PubMed

    Bennekou, P; Kristensen, B I; Christophersen, P

    2003-09-01

    The activation/deactivation kinetics of the human erythrocyte voltage-dependent cation channel was characterized at the single-channel level using inside-out patches. It was found that the time dependence for voltage activation after steps to positive membrane potentials was slow ( t(1/2) about 30 s), whereas the deactivation was fast ( t(1/2) about 15 ms). Both activation and deactivation of this channel were also demonstrated in intact red cells in suspension. At very positive membrane potentials generated by suspension in extracellular low Cl(-) concentrations, the cation conductance switched on with a time constant of about 2 min. Deactivation of the cation channel was clearly demonstrated during transient activation of the Gárdos channel elicited by Ca(2+) influx via the cation channel and ensuing efflux via the Ca(2+) pump. Thus, the voltage-dependent cation channel, the Gárdos channel and the Ca(2+) pump constitute a coupled feedback-regulated system that may become operative under physiological conditions.

  2. A cGMP kinase mutant with increased sensitivity to the protein kinase inhibitor peptide PKI(5-24).

    PubMed

    Ruth, P; Kamm, S; Nau, U; Pfeifer, A; Hofmann, F

    1996-01-01

    Synthetic peptides corresponding to the active domain of the heat-stable inhibitor protein PKI are very potent inhibitors of cAMP-dependent protein kinase, but are extremely weak inhibitors of cGMP-dependent protein kinase. In this study, we tried to confer PKI sensitivity to cGMP kinase by site-directed mutagenesis. The molecular requirements for high affinity inhibition by PKI were deduced from the crystal structure of the cAMP kinase/PKI complex. A prominent site of interaction are residues Tyr235 and Phe239 in the catalytic subunit, which from a sandwich-like structure with Phe10 of the PKI(5-24) peptide. To increase the sensitivity for PKI, the cGMP kinase codons at the corresponding sites, Ser555 and Ser559, were changed to Tyr and Phe. The mutant cGMP kinase was stimulated half maximally by cGMP at 3-fold higher concentrations (240 nM) than the wild type (77 nM). Wild type and mutant cGMP kinase did not differ significantly in their Km and Vmax for three different substrate peptides. The PKI(5-24) peptide inhibited phosphotransferase activity of the mutant cGMP kinase with higher potency than that of wild type, with Ki values of 42 +/- .3 microM and 160 +/- .7 microM, respectively. The increased affinity of the mutant cGMP kinase was specific for the PKI(5-24) peptide. Mutation of the essential Phe10 in the PKI(5-24) sequence to an Ala yielded a peptide that inhibited mutant and wild type cGMP kinase with similar potency, with Ki values of 160 +/- 11 and 169 +/- 27 microM, respectively. These results suggest that the mutations Ser555Tyr and Ser559Phe are required, but not sufficient, for high affinity inhibition of cGMP kinase by PKI.

  3. Effects of Cationic Pendant Groups on Ionic Conductivity for Anion Exchange Membranes: Structure Conductivity Relationships

    NASA Astrophysics Data System (ADS)

    Kim, Sojeong; Choi, Soo-Hyung; Lee, Won Bo

    Anion exchange membranes(AEMs) have been widely studied due to their various applications, especially for Fuel cells. Previous proton exchange membranes(PEMs), such as Nafions® have better conductivity than AEMs so far. However, technical limitations such as slow electrode kinetics, carbon monoxide (CO) poisoning of metal catalysts, high methanol crossover and high cost of Pt-based catalyst detered further usages. AEMs have advantages to supplement its drawbacks. AEMs are environmentally friendly and cost-efficient. Based on the well-defined block copolymer, self-assembled morphology is expected to have some relationship with its ionic conductivity. Recently AEMs based on various cations, including ammonium, phosphonium, guanidinium, imidazolium, metal cation, and benzimidazolium cations have been developed and extensively studied with the aim to prepare high- performance AEMs. But more fundamental approach, such as relationships between nanostructure and conductivity is needed. We use well-defined block copolymer Poly(styrene-block-isoprene) as a backbone which is synthesized by anionic polymerization. Then we graft various cationic functional groups and analysis the relation between morphology and conductivity. Theoretical and computational soft matter lab.

  4. Solution Structure of the cGMP Binding GAF Domain from Phosphodiesterase 5: Insights into Nucleotide Specificity, Dimerization, and cGMP-Dependent Conformational Change

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Heikaus, Clemens C.; Stout, Joseph R.; Sekharan, Monica R.

    2008-08-15

    Phosphodiesterase 5 (PDE5) controls intracellular levels of cGMP through its regulation of cGMP hydrolysis. Hydrolytic activity of the C-terminal catalytic domain is increased by cGMP binding to the N-terminal GAF A domain. We present the NMR solution structure of the cGMP-bound PDE5A GAF A domain. The cGMP orientation in the buried binding pocket was defined through 37 intermolecular NOEs.

  5. Angiotensin II increases phosphodiesterase 5A expression in vascular smooth muscle cells: A mechanism by which angiotensin II antagonizes cGMP signaling

    PubMed Central

    Kim, Dongsoo; Aizawa, Toru; Wei, Heng; Pi, Xinchun; Rybalkin, Sergei D.; Berk, Bradford C.; Yan, Chen

    2014-01-01

    Angiotensin II (Ang II) and nitric oxide (NO)/natriuretic peptide (NP) signaling pathways mutually regulate each other. Imbalance of Ang II and NO/NP has been implicated in the pathophysiology of many vascular diseases. cGMP functions as a key mediator in the interaction between Ang II and NO/NP. Cyclic nucleotide phosphodiesterase 5A (PDE5A) is important in modulating cGMP signaling by hydrolyzing cGMP in vascular smooth muscle cells (VSMC). Therefore, we examined whether Ang II negatively modulates intracellular cGMP signaling in VSMC by regulating PDE5A. Ang II rapidly and transiently increased PDE5A mRNA levels in rat aortic VSMC. Upregulation of PDE5A mRNA was associated with a time-dependent increase of both PDE5 protein expression and activity. Increased PDE5A mRNA level was transcription-dependent and mediated by the Ang II type 1 receptor. Ang II-mediated activation of extracellular signal-regulated kinases 1/2 (ERK1/2) was essential for Ang II-induced PDE5A upregulation. Pretreatment of VSMC with Ang II inhibited C-type NP (CNP) stimulated cGMP signaling, such as cGMP dependent protein kinase (PKG)-mediated phosphorylation of vasodilator-stimulated-phosphoprotein (VASP). Ang II-mediated inhibition of PKG was blocked when PDE5 activity was decreased by selective PDE5 inhibitors, suggesting that upregulation of PDE5A expression is an important mechanism for Ang II to attenuate cGMP signaling. PDE5A may also play a critical role in the growth promoting effects of Ang II because inhibition of PDE5A activity significantly decreased Ang II-stimulated VSMC growth. These observations establish a new mechanism by which Ang II antagonizes cGMP signaling and stimulates VSMC growth. PMID:15623434

  6. Biochemical activity and multiple locations of particulate guanylate cyclase in Rhyacophila dorsalis acutidens (Insecta: Trichoptera) provide insights into the cGMP signalling pathway in Malpighian tubules.

    PubMed

    Secca, T; Sciaccaluga, M; Marra, A; Barberini, L; Bicchierai, M C

    2011-04-01

    In insect renal physiology, cGMP and cAMP have important regulatory roles. In Drosophila melanogaster, considered a good model for molecular physiology studies, and in other insects, cGMP and cAMP act as signalling molecules in the Malpighian tubules (MTs). However, many questions related to cyclic nucleotide functions are unsolved in principal cells (PC) and stellate cells (SC), the two cell types that compose the MT. In PC, despite the large body of information available on soluble guanylate cyclase (sGC) in the cGMP pathway, the functional circuit of particulate guanylate cyclase (pGC) remains obscure. In SC, on the other side, the synthesis and physiological role of the cGMP are still unknown. Our biochemical data regarding the presence of cyclic nucleotides in the MTs of Rhyacophila dorsalis acutidens revealed a cGMP level above the 50%, in comparison with the cAMP. The specific activity values for the membrane-bound guanylate cyclase were also recorded, implying that, besides the sGC, pGC is a physiologically relevant source of cGMP in MTs. Cytochemical studies showed ultrastructurally that there was a great deal of pGC on the basolateral membranes of both the principal and stellate cells. In addition, pGC was also detected in the contact zone between the two cell types and in the apical microvillar region of the stellate cells bordering the tubule lumen. The pGC signal is so well represented in PC and, unexpectedly in SC of MTs, that it is possible to hypothesize the existence of still uncharacterized physiological processes regulated by the pGC-cGMP system. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Conformation changes, N-terminal involvement and cGMP signal relay in phosphodiesterase-5 GAF domain

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, H.; Robinson, H.; Ke, H.

    2010-12-03

    The activity of phosphodiesterase-5 (PDE5) is specific for cGMP and is regulated by cGMP binding to GAF-A in its regulatory domain. To better understand the regulatory mechanism, x-ray crystallographic and biochemical studies were performed on constructs of human PDE5A1 containing the N-terminal phosphorylation segment, GAF-A, and GAF-B. Superposition of this unliganded GAF-A with the previously reported NMR structure of cGMP-bound PDE5 revealed dramatic conformational differences and suggested that helix H4 and strand B3 probably serve as two lids to gate the cGMP-binding pocket in GAF-A. The structure also identified an interfacial region among GAF-A, GAF-B, and the N-terminal loop, whichmore » may serve as a relay of the cGMP signal from GAF-A to GAF-B. N-terminal loop 98-147 was physically associated with GAF-B domains of the dimer. Biochemical analyses showed an inhibitory effect of this loop on cGMP binding and its involvement in the cGMP-induced conformation changes.« less

  8. Effect of cations (Na +, Ca 2+, Fe 3+) on the conductivity of a Nafion membrane

    NASA Astrophysics Data System (ADS)

    Hongsirikarn, Kitiya; Goodwin, James G.; Greenway, Scott; Creager, Stephen

    It is known that trace amounts of cations have a detrimental effect on the liquid-phase conductivity of perfluorosulfonated membranes at room temperature. However, the conditions used were very different from typical fuel cell conditions. Recent research has shown the impact of conductivity measurement conditions on NH 4 + contaminated membranes. In this study, the impact of nonproton-containing cations (M n+ = Na +, Ca 2+, and Fe 3+) on Nafion membrane (N-211) conductivity was investigated both in deionized (DI) water at room temperature (∼25 °C) and in the gas phase at 80 °C under conditions similar to in a PEMFC. These conductivities were compared with those of Nafion membranes contaminated with NH 4 + ions. Under the same conditions, the conductivity of a metal cationic-contaminated membrane having the same proton composition (yH+m) was similar, but slightly lower than that of an NH 4 +-contaminated membrane. The conductivity in the purely H +-form of N-211 was more than 12 times greater than the M n+-form form at 25 °C in DI water. At 80 °C, the gas-phase conductivity was 6 times and 125 times greater at 100%RH and 30%RH, respectively. The quantitative results for conductivity and activation energy of contaminated membranes under typical fuel cell conditions are reported here for the first time.

  9. Improved genetically-encoded, FlincG-type fluorescent biosensors for neural cGMP imaging

    PubMed Central

    Bhargava, Yogesh; Hampden-Smith, Kathryn; Chachlaki, Konstantina; Wood, Katherine C.; Vernon, Jeffrey; Allerston, Charles K.; Batchelor, Andrew M.; Garthwaite, John

    2013-01-01

    Genetically-encoded biosensors are powerful tools for understanding cellular signal transduction mechanisms. In aiming to investigate cGMP signaling in neurones using the EGFP-based fluorescent biosensor, FlincG (fluorescent indicator for cGMP), we encountered weak or non-existent fluorescence after attempted transfection with plasmid DNA, even in HEK293T cells. Adenoviral infection of HEK293T cells with FlincG, however, had previously proved successful. Both constructs were found to harbor a mutation in the EGFP domain and had a tail of 17 amino acids at the C-terminus that differed from the published sequence. These discrepancies were systematically examined, together with mutations found beneficial for the related GCaMP family of Ca2+ biosensors, in a HEK293T cell line stably expressing both nitric oxide (NO)-activated guanylyl cyclase and phosphodiesterase-5. Restoring the mutated amino acid improved basal fluorescence whereas additional restoration of the correct C-terminal tail resulted in poor cGMP sensing as assessed by superfusion of either 8-bromo-cGMP or NO. Ultimately, two improved FlincGs were identified: one (FlincG2) had the divergent tail and gave moderate basal fluorescence and cGMP response amplitude and the other (FlincG3) had the correct tail, a GCaMP-like mutation in the EGFP region and an N-terminal tag, and was superior in both respects. All variants tested were strongly influenced by pH over the physiological range, in common with other EGFP-based biosensors. Purified FlincG3 protein exhibited a lower cGMP affinity (0.89 μM) than reported for the original FlincG (0.17 μM) but retained rapid kinetics and a 230-fold selectivity over cAMP. Successful expression of FlincG2 or FlincG3 in differentiated N1E-115 neuroblastoma cells and in primary cultures of hippocampal and dorsal root ganglion cells commends them for real-time imaging of cGMP dynamics in neural (and other) cells, and in their subcellular specializations. PMID:24068983

  10. Integrating high electrical conductivity and photocatalytic activity in cotton fabric by cationizing for enriched coating of negatively charged graphene oxide.

    PubMed

    Sahito, Iftikhar Ali; Sun, Kyung Chul; Arbab, Alvira Ayoub; Qadir, Muhammad Bilal; Jeong, Sung Hoon

    2015-10-05

    Electroconductive textiles have attended tremendous focus recently and researchers are making efforts to increase conductivity of e-textiles, in order to increase the use of such flexible and low cost textile materials. In this study, surface conductivity and photo catalytic activity of standard cotton fabric (SCF) was enhanced by modifying its surface charge, from negative to positive, using Bovine Serum Albumin (BSA) as a cationic agent, to convert it into cationised cotton fabric (CCF). Then, both types of fabrics were dip coated with a simple dip and dry technique for the adsorption of negatively charged graphene oxide (GO) sheets onto its surface. This resulted in 67.74% higher loading amount of GO on the CCF making self-assembly. Finally, this coating was chemically converted by vapor reduction using hydrazine hydrate to reduced graphene oxide (rGO) for restoration of a high electrical conductivity at the fabric surface. Our results revealed that with such high loading of GO, the surface resistance of CCF was only 40Ω/sq as compared to 510Ω/sq of the SCF and a 66% higher photo catalytic activity was also achieved through cationization for improved GO coating. Graphene coated SCF and CCF were characterized using FE-SEM, FTIR, Raman, UV-vis, WAXD, EDX and XPS spectroscopy to ascertain successful reduction of GO to rGO. The effect of BSA treatment on adsorption of cotton fabric was studied using drop shape analyzer to measure contact angle and for thermal and mechanical resistance, the fabric was tested for TGA and tensile strength, respectively. rGO coated fabric also showed slightly improved thermal stability yet a minor loss of strength was observed. The high flexibility, photocatalytic activity and excellent conductivity of this fabric suggests that it can be used as an electrode material for various applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Conformation Changes, N-terminal Involvement, and cGMP Signal Relay in the Phosphodiesterase-5 GAF Domain*

    PubMed Central

    Wang, Huanchen; Robinson, Howard; Ke, Hengming

    2010-01-01

    The activity of phosphodiesterase-5 (PDE5) is specific for cGMP and is regulated by cGMP binding to GAF-A in its regulatory domain. To better understand the regulatory mechanism, x-ray crystallographic and biochemical studies were performed on constructs of human PDE5A1 containing the N-terminal phosphorylation segment, GAF-A, and GAF-B. Superposition of this unliganded GAF-A with the previously reported NMR structure of cGMP-bound PDE5 revealed dramatic conformational differences and suggested that helix H4 and strand B3 probably serve as two lids to gate the cGMP-binding pocket in GAF-A. The structure also identified an interfacial region among GAF-A, GAF-B, and the N-terminal loop, which may serve as a relay of the cGMP signal from GAF-A to GAF-B. N-terminal loop 98–147 was physically associated with GAF-B domains of the dimer. Biochemical analyses showed an inhibitory effect of this loop on cGMP binding and its involvement in the cGMP-induced conformation changes. PMID:20861010

  12. Conformation Changes N-terminal Involvement and cGMP Signal Relay in the Phosphodiesterase-5 GAF Domain

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    H Wang; H Robinson; H Ke

    2011-12-31

    The activity of phosphodiesterase-5 (PDE5) is specific for cGMP and is regulated by cGMP binding to GAF-A in its regulatory domain. To better understand the regulatory mechanism, x-ray crystallographic and biochemical studies were performed on constructs of human PDE5A1 containing the N-terminal phosphorylation segment, GAF-A, and GAF-B. Superposition of this unliganded GAF-A with the previously reported NMR structure of cGMP-bound PDE5 revealed dramatic conformational differences and suggested that helix H4 and strand B3 probably serve as two lids to gate the cGMP-binding pocket in GAF-A. The structure also identified an interfacial region among GAF-A, GAF-B, and the N-terminal loop, whichmore » may serve as a relay of the cGMP signal from GAF-A to GAF-B. N-terminal loop 98-147 was physically associated with GAF-B domains of the dimer. Biochemical analyses showed an inhibitory effect of this loop on cGMP binding and its involvement in the cGMP-induced conformation changes.« less

  13. cGMP stimulates bile acid-independent bile formation and biliary bicarbonate excretion.

    PubMed

    Myers, N C; Grune, S; Jameson, H L; Sawkat-Anwer, M

    1996-03-01

    The effect of guanosine 3',5'-cyclic monophosphate (cGMP) on hepatic bile formation was studied in isolated perfused rat livers and rat hepatocytes. Studies in isolated perfused rat livers showed that infusion of 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP, 3 micromol/min or 100 microM) 1) increased bile flow without affecting biliary excretion of simultaneously infused taurocholate, 2) increased biliary concentration and excretion of HCO3(-) but did not affect biliary excretion of glutathione, and 3) increased net perfusate H+ efflux without affecting hepatic O2 uptake. Studies in isolated rat hepatocytes showed that 1) 8-BrcGMP increased intracellular pH in the presence (but not in the absence) of extracellular HCO-3, and effect inhibited by 4,4' -diisothiocyanostilbene-2,2'-disulfonic acid and Na+ replacement, 2) 8-BrcGMP did not affect taurocholate uptake and intracellular [Ca2+], and 3) bile acids, like ursodeoxycholate and cholate, did not increase cellular cGMP. Taken together, these results indicate that cGMP stimulates bile acid-independent bile formation, in part by stimulating biliary HCO3- excretion. cGMP may increase HCO3- excretion by stimulating sinusoidal Na+ - HCO3- cotransport, but not Na+/H+ exchange. cGMP, unlike adenosine 3',5'-cyclic monophosphate, may not regulate hepatic taurocholate transport, and bile acid-induced HCO3- rich choleresis may not be mediated via cGMP.

  14. The contribution of cationic conductances to the potential of rod photoreceptors.

    PubMed

    Moriondo, Andrea; Rispoli, Giorgio

    2010-05-01

    The contribution of cationic conductances in shaping the rod photovoltage was studied in light adapted cells recorded under whole-cell voltage- or current-clamp conditions. Depolarising current steps (of size comparable to the light-regulated current) produced monotonic responses when the prepulse holding potential (V (h)) was -40 mV (i.e. corresponding to the membrane potential in the dark). At V (h) = -60 mV (simulating the steady-state response to an intense background of light) current injections <35 pA (mimicking a light decrement) produced instead an initial depolarisation that declined to a plateau, and voltage transiently overshot V (h) at the stimulus offset. Current steps >40 pA produced a steady depolarisation to approximately -16 mV at both V (h). The difference between the responses at the two V (h) was primarily generated by the slow delayed-rectifier-like K(+) current (I (Kx)), which therefore strongly affects both the photoresponse rising and falling phase. The steady voltage observed at both V (h) in response to large current injections was instead generated by Ca-activated K(+) channels (I (KCa)), as previously found. Both I (Kx) and I (KCa) oppose the cation influx, occurring at the light stimulus offset through the cGMP-gated channels and the voltage-activated Ca(2+) channels (I (Ca)). This avoids that the cation influx could erratically depolarise the rod past its normal resting value, thus allowing a reliable dim stimuli detection, without slowing down the photovoltage recovery kinetics. The latter kinetics was instead accelerated by the hyperpolarisation-activated, non-selective current (I (h)) and I (Ca). Blockade of all K(+) currents with external TEA unmasked a I (Ca)-dependent regenerative behaviour.

  15. Endogenous cGMP regulates adult longevity via the insulin signaling pathway in Caenorhabditis elegans.

    PubMed

    Hahm, Jeong-Hoon; Kim, Sunhee; Paik, Young-Ki

    2009-08-01

    G-proteins, including GPA-3, play an important role in regulating physiological responses in Caenorhabditis elegans. When confronted with an environmental stimulus such as dauer pheromone, or poor nutrients, C. elegans receives and integrates external signals through its nervous system (i.e. amphid neurons), which interprets and translates them into biological action. Here it is shown that a suppressed neuronal cGMP level caused by GPA-3 activation leads to a significant increase (47.3%) in the mean lifespan of adult C. elegans through forkhead transcription factor family O (FOXO)-mediated signal. A reduced neuronal cGMP level was found to be caused by an increased cGMP-specific phosphodiesterase activity at the transcriptional level. Our results using C. elegans mutants with specific deficits in TGF-beta and FOXO RNAi system suggest a mechanism in that cGMP, TGF-beta, and FOXO signaling interact to differentially produce the insulin-like molecules, ins-7 and daf-28, causing suppression of the insulin/IGF-1 pathway and promoting lifespan extension. Our findings provide not only a new mechanism of cGMP-mediated induction of longevity in adult C. elegans but also a possible therapeutic strategy for neuronal disease, which has been likened to brain diabetes.

  16. Hypergravity differentially modulates cGMP efflux in human melanocytic cells stimulated by nitric oxide and natriuretic peptides

    NASA Astrophysics Data System (ADS)

    Ivanova, K.; Stieber, C.; Lambers, B.; Block, I.; Krieg, R.; Wellmann, A.; Gerzer, R.

    Nitric oxide NO plays a key role in many patho physiologic processes including inflammation and skin cancer The diverse cellular effects of NO are mainly mediated by activation of the soluble guanylyl cyclase sGC isoform that leads to increases in intracellular cGMP levels whereas the membrane-bound isoforms serve as receptors for natriuretic peptides e g ANP In human skin epidermal melanocytes represent the principal cells for skin pigmentation by synthesizing the pigment melanin Melanin acts as a scavenger for free radicals that may arise during metabolic stress as a result of potentially harmful effects of the environment In previous studies we found that long-term exposure to hypergravity stimulated cGMP efflux in normal human melanocytes NHMs and non-metastatic melanoma cells at least partly by an enhanced expression of the multidrug resistance proteins MRP and cGMP transporters MRP4 5 The present study investigated whether hypergravity generated by centrifugal acceleration may modulate the cGMP efflux in NO-stimulated NHMs and melanoma cells MCs with different metastatic potential The NONOates PAPA-NO and DETA-NO were used as direct NO donors for cell stimulation In the presence of 0 1 mM DETA-NO t 1 2 sim 20 h long-term application of hypergravity up to 5 g for 24 h reduced intracellular cGMP levels by stimulating cGMP efflux in NHMs and non-metastatic MCs in comparison to 1 g whereas exposure to 5 g for 6 h in the presence of 0 1 mM PAPA-NO t 1 2 sim 30 min was not effective The hypergravity-stimulated

  17. Auxin-induced nitric oxide, cGMP and gibberellins were involved in the gravitropism

    NASA Astrophysics Data System (ADS)

    Cai, Weiming; Hu, Liwei; Hu, Xiangyang; Cui, Dayong; Cai, Weiming

    Gravitropism is the asymmetric growth or curvature of plant organs in response to gravistimulation. There is a complex signal transduction cascade which involved in the differential growth of plants in response to changes in the gravity vector. The role of auxin in gravitropism has been demonstrated by many experiments, but little is known regarding the molecular details of such effects. In our studies before, mediation of the gravitropic bending of soybean roots and rice leaf sheath bases by nitric oxide, cGMP and gibberellins, are induced by auxin. The asymmetrical distribution of nitric oxide, cGMP and gibberellins resulted from the asymmetrical synthesis of them in bending sites. In soybean roots, inhibitions of NO and cGMP synthesis reduced differential NO and cGMP accumulation respectively, which both of these effects can lead to the reduction of gravitropic bending. Gibberellin-induced OsXET, OsEXPA4 and OsRWC3 were also found involved in the gravitropic bending. These data indicated that auxin-induced nitric oxide, cGMP and gibberellins were involved in the gravitropism. More experiments need to prove the more detailed mechanism of them.

  18. Cationic Covalent Organic Frameworks: A Simple Platform of Anionic Exchange for Porosity Tuning and Proton Conduction.

    PubMed

    Ma, Heping; Liu, Bailing; Li, Bin; Zhang, Liming; Li, Yang-Guang; Tan, Hua-Qiao; Zang, Hong-Ying; Zhu, Guangshan

    2016-05-11

    Mimicking proton conduction mechanism of Nafion to construct novel proton-conducting materials with low cost and high proton conductivity is of wide interest. Herein, we have designed and synthesized a cationic covalent organic framework with high thermal and chemical stability by combining a cationic monomer, ethidium bromide (EB) (3,8-diamino-5-ethyl-6-phenylphenanthridinium bromide), with 1,3,5-triformylphloroglucinol (TFP) in Schiff base reactions. This is the first time that the stable cationic crystalline frameworks allowed for the fabrication of a series of charged COFs (EB-COF:X, X = F, Cl, Br, I) through ion exchange processes. Exchange of the extra framework ions can finely modulate the COFs' porosity and pore sizes at nanoscale. More importantly, by introducing PW12O40(3-) into this porous cationic framework, we can greatly enhance the proton conductivity of ionic COF-based material. To the best of our knowledge, EB-COF:PW12 shows the best proton conductivity at room temperature among ever reported porous organic materials.

  19. Modulation of cGMP in Heart Failure

    PubMed Central

    Boerrigter, Guido; Lapp, Harald; Burnett, John C.

    2009-01-01

    Heart failure (HF) is a common disease that continues to be associated with high morbidity and mortality warranting novel therapeutic strategies. Cyclic guanosine monophosphate (cGMP) is the second messenger of several important signaling pathways based on distinct guanylate cyclases (GCs) in the cardiovascular system. Both the nitric oxide/soluble GC (NO/sGC) as well as the natriuretic peptide/GC-A (NP/GC-A) systems are disordered in HF, providing a rationale for their therapeutic augmentation. Soluble GC activation with conventional nitrovasodilators has been used for more than a century but is associated with cGMP-independent actions and the development of tolerance, actions which novel NO-independent sGC activators now in clinical development lack. Activation of GC-A by administration of naturally occurring or designer natriuretic peptides is an emerging field, as is the inhibition of enzymes that degrade endogenous NPs. Finally, inhibition of cGMP-degrading phosphodiesterases, particularly phosphodiesterase 5 provides an additional strategy to augment cGMP-signaling. PMID:19089342

  20. Involvement of the cGMP pathway in the osthole-facilitated glutamate release in rat hippocampal nerve endings.

    PubMed

    Lin, Tzu Yu; Lu, Cheng Wei; Huang, Wei-Jan; Wang, Su-Jane

    2012-03-01

    Osthole, an active constituent isolated from Cnidium monnieri (L.) Cusson, has previously been shown to have the capacity to increase depolarization-evoked glutamate release in rat hippocampal nerve terminals. As cGMP-dependent signaling cascade has been found to modulate glutamate release at the presynaptic level, the aim of this study was to further examine the role of cGMP signaling pathway in the regulation of osthole on glutamate release in hippocampal synaptosomes. Results showed that osthole dose-dependently increased intrasynaptosomal cGMP levels. The elevation of cGMP levels by osthole was prevented by the phosphodiesterase 5 inhibitor sildenafil but was insensitive to the guanylyl cyclase inhibitor ODQ. In addition, osthole-induced facilitation of 4-aminopyridine (4-AP)-evoked glutamate release was completely prevented by the cGMP-dependent protein kinase (PKG) inhibitors, KT5823, and Rp-8-Br-PET-cGMPS. Direct activation of PKG with 8-Br-cGMP or 8-pCPT-cGMP also occluded the osthole-mediated facilitation of 4-AP-evoked glutamate release. Furthermore, sildenafil exhibited a dose-dependent facilitation of 4-AP-evoked release of glutamate and occluded the effect of osthole on the 4-AP-evoked glutamate release. Collectively, our findings suggest that osthole-mediated facilitation of glutamate release involves the activation of cGMP/PKG-dependent pathway. Copyright © 2011 Wiley Periodicals, Inc.

  1. Chloride channel blockers activate an endogenous cationic current in oocytes of Bufo arenarum.

    PubMed

    Cavarra, M S; del Mónaco, S M; Kotsias, B A

    2004-07-01

    A two-electrode, voltage-clamp technique was used to measure the effect of the Cl(-) channel blockers, 9-anthracene carboxylic acid and niflumic acid, upon the ionic currents of oocytes of the South American toad Bufo arenarum. The main results were: (1) both blockers produced a reversible increase of the outward currents on a dose-dependent manner; (2) the activated outward current was voltage dependent; (3) the 9-anthracene carboxylic acid-sensitive current was blocked with barium; and (4) the effect of 9-anthracene carboxylic acid was more pronounced in a zero-K(+) solution than in standard (2 mmol l(-1)) or high (20 mmol l(-1)) K(+) solutions, indicating that a K(+) conductance is activated. The effect of the Cl(-) channel blockers could be due to a direct interaction with endogenous cationic channels. Another possible explanation is that Cl(-) that enter the cell during depolarizing steps in control solution inhibit this cationic conductance; thus, the blockade of Cl(-) channels by 9-anthracene carboxylic acid and niflumic acid would remove this inhibition, allowing the cationic current to flow freely.

  2. A concise discussion of the regulatory role of cGMP kinase I in cardiac physiology and pathology.

    PubMed

    Hofmann, Franz

    2018-06-22

    The underlying cause of cardiac hypertrophy, fibrosis, and heart failure has been investigated in great detail using different mouse models. These studies indicated that cGMP and cGMP-dependent protein kinase type I (cGKI) may ameliorate these negative phenotypes in the adult heart. Recently, evidence has been published that cardiac mitochondrial BKCa channels are a target for cGKI and that activation of mitoBKCa channels may cause some of the positive effects of conditioning in ischemia/reperfusion injury. It will be pointed out that most studies could not present convincing evidence that it is the cGMP level and the activity cGKI in specific cardiac cells that reduces hypertrophy or heart failure. However, anti-fibrotic compounds stimulating nitric oxide-sensitive guanylyl cyclase may be an upcoming therapy for abnormal cardiac remodeling.

  3. cGMP Signaling in the Cardiovascular System—The Role of Compartmentation and Its Live Cell Imaging

    PubMed Central

    Bork, Nadja I.; Nikolaev, Viacheslav O.

    2018-01-01

    The ubiquitous second messenger 3′,5′-cyclic guanosine monophosphate (cGMP) regulates multiple physiologic processes in the cardiovascular system. Its intracellular effects are mediated by stringently controlled subcellular microdomains. In this review, we will illustrate the current techniques available for real-time cGMP measurements with a specific focus on live cell imaging methods. We will also discuss currently accepted and emerging mechanisms of cGMP compartmentation in the cardiovascular system. PMID:29534460

  4. Monovalent Cation Activation of the Radical SAM Enzyme Pyruvate Formate-Lyase Activating Enzyme.

    PubMed

    Shisler, Krista A; Hutcheson, Rachel U; Horitani, Masaki; Duschene, Kaitlin S; Crain, Adam V; Byer, Amanda S; Shepard, Eric M; Rasmussen, Ashley; Yang, Jian; Broderick, William E; Vey, Jessica L; Drennan, Catherine L; Hoffman, Brian M; Broderick, Joan B

    2017-08-30

    Pyruvate formate-lyase activating enzyme (PFL-AE) is a radical S-adenosyl-l-methionine (SAM) enzyme that installs a catalytically essential glycyl radical on pyruvate formate-lyase. We show that PFL-AE binds a catalytically essential monovalent cation at its active site, yet another parallel with B 12 enzymes, and we characterize this cation site by a combination of structural, biochemical, and spectroscopic approaches. Refinement of the PFL-AE crystal structure reveals Na + as the most likely ion present in the solved structures, and pulsed electron nuclear double resonance (ENDOR) demonstrates that the same cation site is occupied by 23 Na in the solution state of the as-isolated enzyme. A SAM carboxylate-oxygen is an M + ligand, and EPR and circular dichroism spectroscopies reveal that both the site occupancy and the identity of the cation perturb the electronic properties of the SAM-chelated iron-sulfur cluster. ENDOR studies of the PFL-AE/[ 13 C-methyl]-SAM complex show that the target sulfonium positioning varies with the cation, while the observation of an isotropic hyperfine coupling to the cation by ENDOR measurements establishes its intimate, SAM-mediated interaction with the cluster. This monovalent cation site controls enzyme activity: (i) PFL-AE in the absence of any simple monovalent cations has little-no activity; and (ii) among monocations, going down Group 1 of the periodic table from Li + to Cs + , PFL-AE activity sharply maximizes at K + , with NH 4 + closely matching the efficacy of K + . PFL-AE is thus a type I M + -activated enzyme whose M + controls reactivity by interactions with the cosubstrate, SAM, which is bound to the catalytic iron-sulfur cluster.

  5. Low Temperature Extends the Lifespan of Bursaphelenchus xylophilus through the cGMP Pathway

    PubMed Central

    Wang, Bowen; Ma, Ling; Wang, Feng; Wang, Buyong; Hao, Xin; Xu, Jiayao; Ma, Yan

    2017-01-01

    The causal agent of pine wilt disease, pine wood nematode (PWN) (Bursaphelenchus xylophilus), revealed extended lifespan at low temperature. To discover the molecular mechanism of this phenomenon, we attempted to study the molecular characterization, transcript abundance, and functions of three genes of the cyclic guanosine monophosphate (cGMP) pathway from B. xylophilus. Three cGMP pathway genes were identified from B. xylophilus. Bioinformatic software was utilized to analyze the characteristics of the three putative proteins. Function of the three genes in cold tolerance was studied with RNA interference (RNAi). The results showed that the deduced protein of Bx-DAF-11 has an adenylate and guanylate cyclase catalytic domain, indicating an ability to bind to extracellular ligands and synthesizing cGMP. Both Bx-TAX-2 and Bx-TAX-4 have cyclic nucleotide-binding domains and ion transport protein domains, illustrating that they are cGMP-gated ion channels. The transcript level of Bx-daf-11, Bx-tax-2, and Bx-tax-4 increased at low temperature. The survival rates of three gene silenced B. xylophilus revealed a significant decrease at low temperature. This study illustrated that the cGMP pathway plays a key role in low-temperature-induced lifespan extension in B. xylophilus. PMID:29099744

  6. [Antioxidant activity of cationic whey protein isolate].

    PubMed

    titova, M E; Komolov, S A; Tikhomirova, N A

    2012-01-01

    The process of lipid peroxidation (LPO) in biological membranes of cells is carried out by free radical mechanism, a feature of which is the interaction of radicals with other molecules. In this work we investigated the antioxidant activity of cationic whey protein isolate, obtained by the cation-exchange chromatography on KM-cellulose from raw cow's milk, in vitro and in vivo. In biological liquids, which are milk, blood serum, fetal fluids, contains a complex of biologically active substances with a unique multifunctional properties, and which are carrying out a protective, antimicrobial, regenerating, antioxidant, immunomodulatory, regulatory and others functions. Contents of the isolate were determined electrophoretically and by its biological activity. Cationic whey protein isolate included lactoperoxidase, lactoferrin, pancreatic RNase, lysozyme and angeogenin. The given isolate significantly has an antioxidant effect in model experimental systems in vitro and therefore may be considered as a factor that can adjust the intensity of lipid oxidation. In model solutions products of lipid oxidation were obtained by oxidation of phosphatidylcholine by hydrogen peroxide in the presence of a source of iron. The composition of the reaction mixture: 0,4 mM H2O2; 50 mcM of hemin; 2 mg/ml L-alpha-phosphatidylcholine from soybean (Sigma, German). Lipid peroxidation products were formed during the incubation of the reaction mixture for two hours at 37 degrees C. In our studies rats in the adaptation period immediately after isolation from the nest obtained from food given orally native cationic whey protein isolate at the concentration three times higher than in fresh cow's milk. On the manifestation of the antioxidant activity of cationic whey protein isolate in vivo evidence decrease of lipid peroxidation products concentration in the blood of rats from the experimental group receipt whey protein isolate in dos 0,6 mg/g for more than 20% (p<0,05) with oral feeding. Thus

  7. Cationic Biomimetic Particles of Polystyrene/Cationic Bilayer/Gramicidin for Optimal Bactericidal Activity.

    PubMed

    Xavier, Gabriel R S; Carmona-Ribeiro, Ana M

    2017-12-02

    Nanostructured particles of polystyrene sulfate (PSS) covered by a cationic lipid bilayer of dioctadecyldimethylammonium bromide (DODAB) incorporated gramicidin D (Gr) yielding optimal and broadened bactericidal activity against both Escherichia coli and Staphylococcus aureus . The adsorption of DODAB/Gr bilayer onto PSS nanoparticles (NPs) increased the zeta-average diameter by 8-10 nm, changed the zeta-potential of the NPs from negative to positive, and yielded a narrow size distributions for the PSS/DODAB/Gr NPs, which displayed broad and maximal microbicidal activity at very small concentrations of the antimicrobials, namely, 0.057 and 0.0057 mM DODAB and Gr, respectively. The results emphasized the advantages of highly-organized, nanostructured, and cationic particles to achieve hybrid combinations of antimicrobials with broad spectrum activity at considerably reduced DODAB and Gr concentrations.

  8. Basally activated nonselective cation currents regulate the resting membrane potential in human and monkey colonic smooth muscle

    PubMed Central

    Dwyer, Laura; Rhee, Poong-Lyul; Lowe, Vanessa; Zheng, Haifeng; Peri, Lauren; Ro, Seungil; Sanders, Kenton M.

    2011-01-01

    Resting membrane potential (RMP) plays an important role in determining the basal excitability of gastrointestinal smooth muscle. The RMP in colonic muscles is significantly less negative than the equilibrium potential of K+, suggesting that it is regulated not only by K+ conductances but by inward conductances such as Na+ and/or Ca2+. We investigated the contribution of nonselective cation channels (NSCC) to the RMP in human and monkey colonic smooth muscle cells (SMC) using voltage- and current-clamp techniques. Qualitative reverse transcriptase-polymerase chain reaction was performed to examine potential molecular candidates for these channels among the transient receptor potential (TRP) channel superfamily. Spontaneous transient inward currents and holding currents were recorded in human and monkey SMC. Replacement of extracellular Na+ with equimolar tetraethylammonium or Ca2+ with Mn2+ inhibited basally activated nonselective cation currents. Trivalent cations inhibited these channels. Under current clamp, replacement of extracellular Na+ with N-methyl-d-glucamine or addition of trivalent cations caused hyperpolarization. Three unitary conductances of NSCC were observed in human and monkey colonic SMC. Molecular candidates for basally active NSCC were TRPC1, C3, C4, C7, M2, M4, M6, M7, V1, and V2 in human and monkey SMC. Comparison of the biophysical properties of these TRP channels with basally active NSCC (bINSCC) suggests that TRPM4 and specific TRPC heteromultimer combinations may underlie the three single-channel conductances of bINSCC. In conclusion, these findings suggest that basally activated NSCC contribute to the RMP in human and monkey colonic SMC and therefore may play an important role in determining basal excitability of colonic smooth muscle. PMID:21566016

  9. Activation of a Ca2+-dependent cation conductance with properties of TRPM2 by reactive oxygen species in lens epithelial cells.

    PubMed

    Keckeis, Susanne; Wernecke, Laura; Salchow, Daniel J; Reichhart, Nadine; Strauß, Olaf

    2017-08-01

    Ion channels are crucial for maintenance of ion homeostasis and transparency of the lens. The lens epithelium is the metabolically and electrophysiologically active cell type providing nutrients, ions and water to the lens fiber cells. Ca 2+ -dependent non-selective ion channels seem to play an important role for ion homeostasis. The aim of the study was to identify and characterize Ca 2+ - and reactive oxygen species (ROS)-dependent non-selective cation channels in human lens epithelial cells. RT-PCR revealed gene expression of the Ca 2+ -activated non-selective cation channels TRPC3, TRPM2, TRPM4 and Ano6 in both primary lens epithelial cells and the cell line HLE-B3, whereas TRPM5 mRNA was only found in HLE-B3 cells. Using whole-cell patch-clamp technique, ionomycin evoked non-selective cation currents with linear current-voltage relationship in both cell types. The current was decreased by flufenamic acid (FFA), 2-APB, 9-phenanthrol and miconazole, but insensitive to DIDS, ruthenium red, and intracellularly applied spermine. H 2 O 2 evoked a comparable current, abolished by FFA. TRPM2 protein expression in HLE-B3 cells was confirmed by means of immunocytochemistry and western blot. In summary, we conclude that lens epithelial cells functionally express Ca 2+ - and H 2 O 2 -activated non-selective cation channels with properties of TRPM2. Copyright © 2017. Published by Elsevier Ltd.

  10. Dephosphorylation and inactivation of NPR2 guanylyl cyclase in granulosa cells contributes to the LH-induced decrease in cGMP that causes resumption of meiosis in rat oocytes

    PubMed Central

    Egbert, Jeremy R.; Shuhaibar, Leia C.; Edmund, Aaron B.; Van Helden, Dusty A.; Robinson, Jerid W.; Uliasz, Tracy F.; Baena, Valentina; Geerts, Andreas; Wunder, Frank; Potter, Lincoln R.; Jaffe, Laurinda A.

    2014-01-01

    In mammals, the meiotic cell cycle of oocytes starts during embryogenesis and then pauses. Much later, in preparation for fertilization, oocytes within preovulatory follicles resume meiosis in response to luteinizing hormone (LH). Before LH stimulation, the arrest is maintained by diffusion of cyclic (c)GMP into the oocyte from the surrounding granulosa cells, where it is produced by the guanylyl cyclase natriuretic peptide receptor 2 (NPR2). LH rapidly reduces the production of cGMP, but how this occurs is unknown. Here, using rat follicles, we show that within 10 min, LH signaling causes dephosphorylation and inactivation of NPR2 through a process that requires the activity of phosphoprotein phosphatase (PPP)-family members. The rapid dephosphorylation of NPR2 is accompanied by a rapid phosphorylation of the cGMP phosphodiesterase PDE5, an enzyme whose activity is increased upon phosphorylation. Later, levels of the NPR2 agonist C-type natriuretic peptide decrease in the follicle, and these sequential events contribute to the decrease in cGMP that causes meiosis to resume in the oocyte. PMID:25183874

  11. The role of cGMP as a mediator of lipolysis in bovine oocytes and its effects on embryo development and cryopreservation.

    PubMed

    Schwarz, Kátia R L; de Castro, Fernanda C; Schefer, Letícia; Botigelli, Ramon C; Paschoal, Daniela M; Fernandes, Hugo; Leal, Cláudia L V

    2018-01-01

    This study aimed to determine the influence of cyclic guanosine 3'5'-monophosphate (cGMP) and cGMP-dependent kinase (PKG) during in vitro maturation (IVM) on lipolysis-related parameters in bovine cumulus-oocyte complexes (COCs), and on embryo development and cryosurvival. COCs were matured with cGMP/PKG modulators and assessed for metaphase II rates (MII), cGMP levels, lipid content in oocytes (OO), transcript abundance for genes involved in lipolysis (ATGL) and lipid droplets (PLIN2) in cumulus cells (CC) and OO, and presence of phosphorylated (active) hormone sensitive lipase (HSLser563) in OO. Embryo development, lipid contents and survival to vitrification were also assessed. Phosphodiesterase 5 inhibition (PDE5; cGMP-hydrolyzing enzyme) with 10-5M sildenafil (SDF) during 24 h IVM increased cGMP in COCs (56.9 vs 9.5 fMol/COC in untreated controls, p<0.05) and did not affect on maturation rate (84.3±6.4% MII). Fetal calf serum (FCS) in IVM medium decreased cGMP in COCs compared to bovine serum albumin (BSA) + SDF (19.6 vs 66.5 fMol/COC, respectively, p<0.05). FCS increased lipid content in OO (40.1 FI, p<0.05) compared to BSA (34.6 FI), while SDF decreased (29.8 and 29.6 FI, with BSA or FCS, respectively p<0.05). PKG inhibitor (KT5823) reversed this effect (38.9 FI, p<0.05). ATGL and PLIN2 transcripts were detected in CC and OO, but were affected by cGMP and PKG only in CC. HSLser563 was detected in OO matured with or without modulators. Reduced lipid content in embryos were observed only when SDF was added during IVM and IVC (27.6 FI) compared to its use in either or none of the culture periods (34.2 FI, p<0.05). Survival to vitrification was unaffected by SDF. In conclusion, cGMP and PKG are involved in lipolysis in OO and possibly in CC and embryos; serum negatively affects this pathway, contributing to lipid accumulation, and cGMP modulation may reduce lipid contents in oocytes and embryos, but without improving embryo cryotolerance.

  12. Monovalent cation conductance in Xenopus laevis oocytes expressing hCAT-3.

    PubMed

    Gilles, Wolfgang; Vulcu, Sebastian D; Liewald, Jana F; Habermeier, Alice; Vékony, Nicole; Closs, Ellen I; Rupp, Johanna; Nawrath, Hermann

    2005-03-01

    hCAT-3 (human cationic amino acid transporter type three) was investigated with both the two-electrode voltage clamp method and tracer experiments. Oocytes expressing hCAT-3 displayed less negative membrane potentials and larger voltage-dependent currents than native or water-injected oocytes did. Ion substitution experiments in hCAT-3-expressing oocytes revealed a large conductance for Na+ and K+. In the presence of L-Arg, voltage-dependent inward and outward currents were observed. At symmetrical (inside/outside) concentrations of L-Arg, the conductance of the transporter increased monoexponentially with the L-Arg concentrations; the calculated Vmax and KM values amounted to 8.3 microS and 0.36 mM, respectively. The time constants of influx and efflux of [3H]L-Arg, at symmetrically inside/outside L-Arg concentrations (1 mM), amounted to 79 and 77 min, respectively. The flux data and electrophysiological experiments suggest that the transport of L-Arg through hCAT-3 is symmetric, when the steady state of L-Arg flux has been reached. It is concluded that hCAT-3 is a passive transport system that conducts monovalent cations including L-Arg. The particular role of hCAT-3 in the diverse tissues remains to be elucidated.

  13. Synthesis, activity, and structure--activity relationship studies of novel cationic lipids for DNA transfer.

    PubMed

    Byk, G; Dubertret, C; Escriou, V; Frederic, M; Jaslin, G; Rangara, R; Pitard, B; Crouzet, J; Wils, P; Schwartz, B; Scherman, D

    1998-01-15

    We have designed and synthesized original cationic lipids for gene delivery. A synthetic method on solid support allowed easy access to unsymmetrically monofunctionalized polyamine building blocks of variable geometries. These polyamine building blocks were introduced into cationic lipids. To optimize the transfection efficiency in the novel series, we have carried out structure-activity relationship studies by introduction of variable-length lipids, of variable-length linkers between lipid and cationic moiety, and of substituted linkers. We introduce the concept of using the linkers within cationic lipids molecules as carriers of side groups harboring various functionalities (side chain entity), as assessed by the introduction of a library composed of cationic entities, additional lipid chains, targeting groups, and finally the molecular probes rhodamine and biotin for cellular traffic studies. The transfection activity of the products was assayed in vitro on Hela carcinoma, on NIH3T3, and on CV1 fibroblasts and in vivo on the Lewis Lung carcinoma model. Products from the series displayed high transfection activities. Results indicated that the introduction of a targeting side chain moiety into the cationic lipid is permitted. A primary physicochemical characterization of the DNA/lipid complexes was demonstrated with this leading compound. Selected products from the series are currently being developed for preclinical studies, and the labeled lipopolyamines can be used to study the intracellular traffic of DNA/cationic lipid complexes.

  14. Ca2+ and Mn2+ Influx Through Receptor-Mediated Activation of Nonspecific Cation Channels in Mast Cells

    NASA Astrophysics Data System (ADS)

    Fasolato, Cristina; Hoth, Markus; Matthews, Gary; Penner, Reinhold

    1993-04-01

    Whole-cell patch-clamp recordings of membrane currents and Fura-2 measurements of free intracellular calcium concentration ([Ca2+]_i) were used to study calcium influx through receptor-activated cation channels in rat peritoneal mast cells. Cation channels were activated by the secretagogue compound 48/80, whereas a possible concomitant Ca2+ entry through pathways activated by depletion of calcium stores was blocked by dialyzing cells with heparin. Heparin effectively suppressed the transient Ca2+ release induced by 48/80 and abrogated inositol 1,4,5-trisphosphate-induced calcium influx without affecting activation of 50-pS cation channels. There was a clear correlation between changes in [Ca2+]_i and the activity of 50-pS channels. The changes in [Ca2+]_i increased with elevation of extracellular Ca2+. At the same time, inward currents through 50-pS channels were diminished as more Ca2+ permeated. This effect was due to a decrease in slope conductance and a reduction in the open probability of the cation channels. In physiological solutions, 3.6% of the total current was carried by Ca2+. The cation channels were not only permeable to Ca2+ but also to Mn2+, as evidenced by the quench of Fura-2 fluorescence. Mn2+ current through 50-pS channels could not be resolved at the single-channel level. Our results suggest that 50-pS cation channels partially contribute to sustained increases of [Ca2+]_i in mast cells following receptor activation.

  15. Direct interaction of the inhibitory gamma-subunit of Rod cGMP phosphodiesterase (PDE6) with the PDE6 GAFa domains.

    PubMed

    Muradov, Khakim G; Granovsky, Alexey E; Schey, Kevin L; Artemyev, Nikolai O

    2002-03-26

    Retinal rod and cone cGMP phosphodiesterases (PDE6 family) function as the effector enzyme in the vertebrate visual transduction cascade. The activity of PDE6 catalytic subunits is controlled by the Pgamma-subunits. In addition to the inhibition of cGMP hydrolysis at the catalytic sites, Pgamma is known to stimulate a noncatalytic binding of cGMP to the regulatory GAFa-GAFb domains of PDE6. The latter role of Pgamma has been attributed to its polycationic region. To elucidate the structural basis for the regulation of cGMP binding to the GAF domains of PDE6, a photoexcitable peptide probe corresponding to the polycationic region of Pgamma, Pgamma-21-45, was specifically cross-linked to rod PDE6alphabeta. The site of Pgamma-21-45 cross-linking was localized to Met138Gly139 within the PDE6alpha GAFa domain using mass spectrometric analysis. Chimeras between PDE5 and cone PDE6alpha', containing GAFa and/or GAFb domains of PDE6alpha' have been generated to probe a potential role of the GAFb domains in binding to Pgamma. Analysis of the inhibition of the PDE5/PDE6alpha' chimeras by Pgamma supported the role of PDE6 GAFa but not GAFb domains in the interaction with Pgamma. Our results suggest that a direct binding of the polycationic region of Pgamma to the GAFa domains of PDE6 may lead to a stabilization of the noncatalytic cGMP-binding sites.

  16. Cation-Dependent Intrinsic Electrical Conductivity in Isostructural Tetrathiafulvalene-Based Microporous Metal–Organic Frameworks

    DOE PAGES

    Park, Sarah S.; Hontz, Eric R.; Sun, Lei; ...

    2015-01-26

    Isostructural metal-organic frameworks (MOFs) M 2(TTFTB) (M = Mn, Co, Zn, and Cd; H4TTFTB = tetrathiafulvalene tetrabenzoate) exhibit a striking correlation between their single-crystal conductivities and the shortest S···S interaction defined by neighboring TTF cores, which inversely correlates with the ionic radius of the metal ions. The larger cations cause a pinching of the S···S contact, which is responsible for better orbital overlap between p z orbitals on neighboring S and C atoms. Density functional theory calculations show that these orbitals are critically involved in the valence band of these materials, such that modulation of the S···S distance has anmore » important effect on band dispersion and, implicitly, on the conductivity. The Cd analogue, with the largest cation and shortest S···S contact, shows the largest electrical conductivity, σ = 2.86 (±0.53) × 10 -4 S/cm, which is also among the highest in microporous MOFs. These results describe the first demonstration of tunable intrinsic electrical conductivity in this class of materials and serve as a blueprint for controlling charge transport in MOFs with π-stacked motifs.« less

  17. Ion-exclusion/cation-exchange chromatography with dual detection of the conductivity and spectrophotometry for the simultaneous determination of common inorganic anionic species and cations in river and wastewater.

    PubMed

    Nakatani, Nobutake; Kozaki, Daisuke; Mori, Masanobu; Hasebe, Kiyoshi; Nakagoshi, Nobukazu; Tanaka, Kazuhiko

    2011-01-01

    Simultaneous determinations of common inorganic anionic species (SO(4)(2-), Cl(-), NO(3)(-), phosphate and silicate) and cations (Na(+), NH(4)(+), K(+), Mg(2+) and Ca(2+)) were conducted using an ion-chromatography system with dual detection of conductivity and spectrophotometry in tandem. The separation of ionic species on a weakly acidic cation-exchange resin was accomplished using a mixture of 100 mM ascorbic acid and 4 mM 18-crown-6 as an acidic eluent (pH 2.6), after which the ions were detected using a conductivity detector. Subsequently, phosphate and silicate were analyzed based on derivatization with molybdate and spectrophotometry at 700 nm. The detection limits at S/N = 3 ranged from 0.11 to 2.9 µM for analyte ionic species. This method was applied to practical river water and wastewater with acceptable criteria for the anion-cation balance and comparisons of the measured and calculated electrical conductivity, demonstrating the usefulness of the present method for water quality monitoring.

  18. Immunocytology on microwave-fixed cells reveals rapid and agonist-specific changes in subcellular accumulation patterns for cAMP or cGMP.

    PubMed Central

    Barsony, J; Marx, S J

    1990-01-01

    We developed a method for cAMP and cGMP immunocytology based upon fixation by microwave irradiation. Fixation by microwave irradiation prevented three problems found with other fixation methods: nucleotide loss from cells, nucleotide diffusion within cells, and chemical modification of immunologic epitopes. Six agonists (four that stimulate adenylate cyclase and two that stimulate guanylate cyclase) produced cAMP or cGMP accumulation patterns that were agonist-specific, dose-dependent, detectable at physiologic concentrations of hormone, and time-dependent within 15 sec to 30 min. cAMP accumulation after 1 mM forskolin was greatest in the nucleus. Isoproterenol, prostaglandin E2, or calcitonin caused initial accumulation of cAMP along the plasma membrane, but later accumulation was greater in the cytoplasm. With calcitonin the later accumulation of cAMP was selectively perinuclear and along the nuclear membrane. Sodium nitroprusside stimulated cGMP accumulation diffusely throughout the cytoplasm. Atrial natriuretic peptide initiated cGMP accumulation near the plasma membrane, and cGMP accumulation moved from there into the cytoplasm. In conclusion, microwave irradiation preserved cell structure and allowed visualization of expected as well as unsuspected changes in intracellular accumulation patterns of cAMP and cGMP. Images PMID:2153973

  19. Reduced cGMP levels in CSF of AD patients correlate with severity of dementia and current depression.

    PubMed

    Hesse, Raphael; Lausser, Ludwig; Gummert, Pauline; Schmid, Florian; Wahler, Anke; Schnack, Cathrin; Kroker, Katja S; Otto, Markus; Tumani, Hayrettin; Kestler, Hans A; Rosenbrock, Holger; von Arnim, Christine A F

    2017-03-09

    Alzheimer's disease (AD) is a neurodegenerative disorder, primarily affecting memory. That disorder is thought to be a consequence of neuronal network disturbances and synapse loss. Decline in cognitive function is associated with a high burden of neuropsychiatric symptoms (NPSs) such as depression. The cyclic nucleotides cyclic adenosine-3',5'-monophosphate (cAMP) and cyclic guanosine-3',5'-monophosphate (cGMP) are essential second messengers that play a crucial role in memory processing as well as synaptic plasticity and are potential therapeutic targets. Biomarkers that are able to monitor potential treatment effects and that reflect the underlying pathology are of crucial interest. In this study, we measured cGMP and cAMP in cerebrospinal fluid (CSF) in a cohort of 133 subjects including 68 AD patients and 65 control subjects. To address the association with disease progression we correlated cognitive status with cyclic nucleotide levels. Because a high burden of NPSs is associated with decrease in cognitive function, we performed an exhaustive evaluation of AD-relevant marker combinations in a depressive subgroup. We show that cGMP, but not cAMP, levels in the CSF of AD patients are significantly reduced compared with the control group. Reduced cGMP levels in AD patients correlate with memory impairment based on Mini-Mental State Examination score (r = 0.17, p = 0.048) and tau as a marker of neurodegeneration (r = -0.28, p = 0.001). Moreover, we were able to show that AD patients suffering from current depression show reduced cGMP levels (p = 0.07) and exhibit a higher degree of cognitive impairment than non-depressed AD patients. These results provide further evidence for an involvement of cGMP in AD pathogenesis and accompanying co-morbidities, and may contribute to elucidating synaptic plasticity alterations during disease progression.

  20. Hemin/G-quadruplex structure and activity alteration induced by magnesium cations.

    PubMed

    Kosman, J; Juskowiak, B

    2016-04-01

    The influence of metal cations on G-quadruplex structure and peroxidase-mimicking DNAzyme activity was investigated. Experiments revealed a significant role of magnesium ion, which in the presence of potassium cation influenced DNAzyme activity. This ability has been associated with alteration of G-quadruplex topology and consequently affinity to bind hemin molecule. It has been demonstrated that G-quadruplex based on PS2.M sequence under these conditions formed parallel topology, which exhibited lower activity than that observed in standard potassium-containing solution. On the other hand DNAzyme/magnesium ion system based on telomeric sequence, which did not undergo significant structural changes, exhibited higher peroxidase activity upon magnesium ion addition. In both cases, the stabilization effect of magnesium cations on G-quadruplex structure was observed. The mechanism of DNAzyme activity alteration by magnesium ion can be explained by its influence on the pKa value of DNAzyme. Magnesium ion decreased pKa for PS2.M based system but increased it for telomeric DNAzyme. Magnesium cation effect on G-quadruplex structure as well as DNAzyme activity is particularly important since this ion is one of the most common metal cations in biological samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Different cation stresses affect specifically osmotic root hydraulic conductance, involving aquaporins, ATPase and xylem loading of ions in Capsicum annuum, L. plants.

    PubMed

    Cabañero, Francisco J; Carvajal, Micaela

    2007-10-01

    In order to study the effect of nutrient stress on water uptake in pepper plants (Capsicum annuum L.), the excess or deficiency of the main cations involved in plant nutrition (K(+), Mg(2+), Ca(2+)) and two different degrees of salinity were related to the activity of plasma membrane H(+)-ATPase, the pH of the xylem sap, nutrient flux into the xylem (J(s)) and to a number of parameters related to water relations, such as root hydraulic conductance (L(0)), stomatal conductance (g(s)) and aquaporin activity. Excess of K(+), Ca(+) and NaCl produced a toxic effect on L(0) while Mg(2+) starvation produced a positive effect, which was in agreement with aquaporin functionality, but not with ATPase activity. The xylem pH was altered only by Ca treatments. The results obtained with each treatment could suggest that detection of the quality of the nutrient supply being received by roots can be related to aquaporins functionality, but also that each cation stress triggers specific responses that have to be assessed individually.

  2. Ternary mixtures of ionic liquids for better salt solubility, conductivity and cation transference number improvement

    PubMed Central

    Karpierz, E.; Niedzicki, L.; Trzeciak, T.; Zawadzki, M.; Dranka, M.; Zachara, J.; Żukowska, G. Z.; Bitner-Michalska, A.; Wieczorek, W.

    2016-01-01

    We hereby present the new class of ionic liquid systems in which lithium salt is introduced into the solution as a lithium cation−glyme solvate. This modification leads to the reorganisation of solution structure, which entails release of free mobile lithium cation solvate and hence leads to the significant enhancement of ionic conductivity and lithium cation transference numbers. This new approach in composing electrolytes also enables even three-fold increase of salt concentration in ionic liquids. PMID:27767069

  3. [Effect of twirling-reinforcing-reducing needling manipulations on contents of serum acetylcholine and arterial NOS and cGMP in stress-induced hypertension rats].

    PubMed

    Liu, Wei; Zhu, Ling-Qun; Chen, Si-Si; Lu, Shu-Chao; Tang, Jie; Liu, Qing-Guo

    2015-04-01

    To observe the effect of twirling-reinforcing or reducing needling manipulations on plasma acetylcholine (Ach) content and expression of nitric oxide synthetase (NOS) and cyclic guanosine monophosphate (cGMP) in thoracic artery tissue in stress-induced hypertension rats. A total of 60 male rats were randomly divided into blank control, model, acupuncture (no-needle-manipulation) , twirling-reinforcing needling and twirling-reducing needling groups (n = 12 in each group). The stress hypertension model was established by giving the animals with noise and electric shock stimulation (paw), twice a day for 15 days. Acupuncture stimulation was applied to bilateral "Taichong" (LR 3) for 1 min, followed by retaining the needles for 20 min. The treatment was conducted once daily for 7 days. Systolic blood pressure of the rat's tail was detected with non-invasive method and plasma Ach, and NOS and cGMP contents in the thoracic artery tissue were measured using ELISA method. Compared with the control group, the systolic blood pressure was significantly higher in the model group after 15 days' stress stimulation (P < 0.01), while the contents of plasma Ach, arterial NOS and cGMP were markedly down-regulated (P < 0.01). Following 7 days' acupuncture interventions, the increased blood pressure was down-regulated in the no-needle-manipulation, twirling-reinforcing needling and twirling-reducing needling groups (P < 0.05, P < 0.01); and the decreased Ach and NOS in the 3 treatment groups, and cGMP levels in the twirling-reinforcing and twirling-reducing needling groups were remarkably up-regulated (P < 0.01, P < 0.05). No significant change of arterial cGMP content was found in the no-needle-manipulation group (P > 0.05). The effect of the twirling-reducing needling was superior to that of no-needle-manipulation and twirling-reinforcing needling in lowering blood pressure and raising plasma Ach content (P < 0.05, P < 0.01). The twirling-reducing needling of acupuncture has a

  4. Cytotoxic activity of aminoderivatized cationic chitosan derivatives.

    PubMed

    Lee, Jung-Kul; Lim, Hyun-Soo; Kim, Jung-Hoe

    2002-10-21

    Chitosan derivatives were prepared by dialkylaminoalkylation and reductive amination followed by quaternization. In this study, the cytotoxic activity of the chitosan derivatives was investigated and a relationship between structure and activity is suggested. The cationic chitosan derivatives elicited dose-dependent inhibitory effects on the proliferation of tumor cell lines.

  5. Anxiolytic effects of phosphodiesterase-2 inhibitors associated with increased cGMP signaling.

    PubMed

    Masood, Anbrin; Huang, Ying; Hajjhussein, Hassan; Xiao, Lan; Li, Hao; Wang, Wei; Hamza, Adel; Zhan, Chang-Guo; O'Donnell, James M

    2009-11-01

    Phosphodiesterase (PDE)-2 is a component of the nitric-oxide synthase (NOS)/guanylyl cyclase signaling pathway in the brain. Given recent evidence that pharmacologically induced changes in NO-cGMP signaling can affect anxiety-related behaviors, the effects of the PDE2 inhibitors (2-(3,4-dimethoxybenzyl)-7-det-5-methylimidazo-[5,1-f][1,2,4]triazin-4(3H)-one) (Bay 60-7550) and 3-(8-methoxy-1-methyl-2-oxo-7-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)benzamide (ND7001), as well as modulators of NO, were assessed on cGMP signaling in neurons and on the behavior of mice in the elevated plus-maze, hole-board, and open-field tests, well established procedures for the evaluation of anxiolytics. Bay 60-7550 (1 microM) and ND7001 (10 microM) increased basal and N-methyl-d-aspartate- or detanonoate-stimulated cGMP in primary cultures of rat cerebral cortical neurons; Bay 60-7550, but not ND7001, also increased cAMP. Increased cGMP signaling, either by administration of the PDE2 inhibitors Bay 60-7550 (0.5, 1, and 3 mg/kg) or ND7001 (1 mg/kg), or the NO donor detanonoate (0.5 mg/kg), antagonized the anxiogenic effects of restraint stress on behavior in the three tests. These drugs also produced anxiolytic effects on behavior in nonstressed mice in the elevated plus-maze and hole-board tests; these effects were antagonized by the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (20 mg/kg). By contrast, the NOS inhibitor N(omega)-nitro-l-arginine methyl ester (50 mg/kg), which reduces cGMP signaling, produced anxiogenic effects similar to restraint stress. Overall, the present behavioral and neurochemical data suggest that PDE2 may be a novel pharmacological target for the development of drugs for the treatment of anxiety disorders.

  6. Now that you want to take your HIV/AIDS vaccine/biological product research concept into the clinic: what are the "cGMP"?

    PubMed

    Sheets, Rebecca L; Rangavajhula, Vijaya; Pullen, Jeffrey K; Butler, Chris; Mehra, Vijay; Shapiro, Stuart; Pensiero, Michael

    2015-04-08

    The Division of AIDS Vaccine Research Program funds the discovery and development of HIV/AIDS vaccine candidates. Basic researchers, having discovered a potential vaccine in the laboratory, next want to take that candidate into the clinic to test the concept in humans, to see if it translates. Many of them have heard of "cGMP" and know that they are supposed to make a "GMP product" to take into the clinic, but often they are not very familiar with what "cGMP" means and why these good practices are so important. As members of the Vaccine Translational Research Branch, we frequently get asked "can't we use the material we made in the lab in the clinic?" or "aren't Phase 1 studies exempt from cGMP?" Over the years, we have had many experiences where researchers or their selected contract manufacturing organizations have not applied an appropriate degree of compliance with cGMP suitable for the clinical phase of development. We share some of these experiences and the lessons learned, along with explaining the importance of cGMP, just what cGMP means, and what they can assure, in an effort to de-mystify this subject and facilitate the rapid and safe translational development of HIV vaccines. Published by Elsevier Ltd.

  7. White - cGMP Interaction Promotes Fast Locomotor Recovery from Anoxia in Adult Drosophila

    PubMed Central

    2017-01-01

    Increasing evidence indicates that the white (w) gene in Drosophila possesses extra-retinal functions in addition to its classical role in eye pigmentation. We have previously shown that w+ promotes fast and consistent locomotor recovery from anoxia, but how w+ modulates locomotor recovery is largely unknown. Here we show that in the absence of w+, several PDE mutants, especially cyclic guanosine monophosphate (cGMP)-specific PDE mutants, display wildtype-like fast locomotor recovery from anoxia, and that during the night time, locomotor recovery was light-sensitive in white-eyed mutant w1118, and light-insensitive in PDE mutants under w1118 background. Data indicate the involvement of cGMP in the modulation of recovery timing and presumably, light-evoked cGMP fluctuation is associated with light sensitivity of locomotor recovery. This was further supported by the observations that w-RNAi-induced delay of locomotor recovery was completely eliminated by upregulation of cGMP through multiple approaches, including PDE mutation, simultaneous overexpression of an atypical soluble guanylyl cyclase Gyc88E, or sildenafil feeding. Lastly, prolonged sildenafil feeding promoted fast locomotor recovery from anoxia in w1118. Taken together, these data suggest that a White-cGMP interaction modulates the timing of locomotor recovery from anoxia. PMID:28060942

  8. Antibacterial Activity of Geminized Amphiphilic Cationic Homopolymers.

    PubMed

    Wang, Hui; Shi, Xuefeng; Yu, Danfeng; Zhang, Jian; Yang, Guang; Cui, Yingxian; Sun, Keji; Wang, Jinben; Yan, Haike

    2015-12-22

    The current study is aimed at investigating the effect of cationic charge density and hydrophobicity on the antibacterial and hemolytic activities. Two kinds of cationic surfmers, containing single or double hydrophobic tails (octyl chains or benzyl groups), and the corresponding homopolymers were synthesized. The antimicrobial activity of these candidate antibacterials was studied by microbial growth inhibition assays against Escherichia coli, and hemolysis activity was carried out using human red blood cells. It was interestingly found that the homopolymers were much more effective in antibacterial property than their corresponding monomers. Furthermore, the geminized homopolymers had significantly higher antibacterial activity than that of their counterparts but with single amphiphilic side chains in each repeated unit. Geminized homopolymers, with high positive charge density and moderate hydrophobicity (such as benzyl groups), combine both advantages of efficient antibacterial property and prominently high selectivity. To further explain the antibacterial performance of the novel polymer series, the molecular interaction mechanism is proposed according to experimental data which shows that these specimens are likely to kill microbes by disrupting bacterial membranes, leading them unlikely to induce resistance.

  9. Cationic lipids: molecular structure/ transfection activity relationships and interactions with biomembranes.

    PubMed

    Koynova, Rumiana; Tenchov, Boris

    2010-01-01

    Abstract Synthetic cationic lipids, which form complexes (lipoplexes) with polyanionic DNA, are presently the most widely used constituents of nonviral gene carriers. A large number of cationic amphiphiles have been synthesized and tested in transfection studies. However, due to the complexity of the transfection pathway, no general schemes have emerged for correlating the cationic lipid chemistry with their transfection efficacy and the approaches for optimizing their molecular structures are still largely empirical. Here we summarize data on the relationships between transfection activity and cationic lipid molecular structure and demonstrate that the transfection activity depends in a systematic way on the lipid hydrocarbon chain structure. A number of examples, including a large series of cationic phosphatidylcholine derivatives, show that optimum transfection is displayed by lipids with chain length of approximately 14 carbon atoms and that the transfection efficiency strongly increases with increase of chain unsaturation, specifically upon replacement of saturated with monounsaturated chains.

  10. Aging has the opposite effect on cAMP and cGMP circadian variations in rat Leydig cells.

    PubMed

    Baburski, Aleksandar Z; Sokanovic, Srdjan J; Andric, Silvana A; Kostic, Tatjana S

    2017-05-01

    The Leydig cell physiology displays a circadian rhythm driven by a complex interaction of the reproductive axis hormones and circadian system. The final output of this regulatory process is circadian pattern of steroidogenic genes expression and testosterone production. Aging gradually decreases robustness of rhythmic testosterone secretion without change in pattern of LH secretion. Here, we analyzed effect of aging on circadian variation of cAMP and cGMP signaling in Leydig cells. Results showed opposite effect of aging on cAMP and cGMP daily variation. Reduced amplitude of cAMP circadian oscillation was probably associated with changed expression of genes involved in cAMP production (increased circadian pattern of Adcy7, Adcy9, Adcy10 and decreased Adcy3); cAMP degradation (increased Pde4a, decreased Pde8b, canceled rhythm of Pde4d, completely reversed circadian pattern of Pde7b and Pde8a); and circadian expression of protein kinase A subunits (Prkac/PRKAC and Prkar2a). Aging stimulates expression of genes responsible for cGMP production (Nos2, Gucy1a3 and Gucy1b3/GUCYB3) and degradation (Pde5a, Pde6a and Pde6h) but the overall net effect is elevation of cGMP circadian oscillations in Leydig cells. In addition, the expression of cGMP-dependent kinase, Prkg1/PRKG1 is up-regulated. It seems that aging potentiate cGMP- and reduce cAMP-signaling in Leydig cells. Since both signaling pathways affect testosterone production and clockwork in the cells, further insights into these signaling pathways will help to unravel disorders linked to the circadian timing system, aging and reproduction.

  11. Determination of Inorganic Cations and Anions in Chitooligosaccharides by Ion Chromatography with Conductivity Detection.

    PubMed

    Cao, Lidong; Li, Xiuhuan; Fan, Li; Zheng, Li; Wu, Miaomiao; Zhang, Shanxue; Huang, Qiliang

    2017-02-22

    Chitooligosaccharides (COSs) are a promising drug candidate and food ingredient because they are innately biocompatible, non-toxic, and non-allergenic to living tissues. Therefore, the impurities in COSs must be clearly elucidated and precisely determined. As for COSs, most analytical methods focus on the determination of the average degrees of polymerization (DPs) and deacetylation (DD), as well as separation and analysis of the single COSs with different DPs. However, little is known about the concentrations of inorganic cations and anions in COSs. In the present study, an efficient and sensitive ion chromatography coupled with conductivity detection (IC-CD) for the determination of inorganic cations Na⁺, NH₄⁺, K⁺, Mg 2+ , Ca 2+ , and chloride, acetate and lactate anions was developed. Detection limits were 0.01-0.05 μM for cations and 0.5-0.6 μM for anions. The linear range was 0.001-0.8 mM. The optimized analysis was carried out on IonPac CS12A and IonPac AS12A analytical column for cations and anions, respectively, using isocratic elution with 20 mM methanesulfonic acid and 4 mM sodium hydroxide aqueous solution as the mobile phase at a 1.0 mL/min flow rate. Quality parameters, including precision and accuracy, were fully validated and found to be satisfactory. The fully validated IC-CD method was readily applied for the quantification of various cations and anions in commercial COS technical concentrate.

  12. Determination of Inorganic Cations and Anions in Chitooligosaccharides by Ion Chromatography with Conductivity Detection

    PubMed Central

    Cao, Lidong; Li, Xiuhuan; Fan, Li; Zheng, Li; Wu, Miaomiao; Zhang, Shanxue; Huang, Qiliang

    2017-01-01

    Chitooligosaccharides (COSs) are a promising drug candidate and food ingredient because they are innately biocompatible, non-toxic, and non-allergenic to living tissues. Therefore, the impurities in COSs must be clearly elucidated and precisely determined. As for COSs, most analytical methods focus on the determination of the average degrees of polymerization (DPs) and deacetylation (DD), as well as separation and analysis of the single COSs with different DPs. However, little is known about the concentrations of inorganic cations and anions in COSs. In the present study, an efficient and sensitive ion chromatography coupled with conductivity detection (IC-CD) for the determination of inorganic cations Na+, NH4+, K+, Mg2+, Ca2+, and chloride, acetate and lactate anions was developed. Detection limits were 0.01–0.05 μM for cations and 0.5–0.6 μM for anions. The linear range was 0.001–0.8 mM. The optimized analysis was carried out on IonPac CS12A and IonPac AS12A analytical column for cations and anions, respectively, using isocratic elution with 20 mM methanesulfonic acid and 4 mM sodium hydroxide aqueous solution as the mobile phase at a 1.0 mL/min flow rate. Quality parameters, including precision and accuracy, were fully validated and found to be satisfactory. The fully validated IC-CD method was readily applied for the quantification of various cations and anions in commercial COS technical concentrate. PMID:28241416

  13. Kilogram-scale prexasertib monolactate monohydrate synthesis under continuous-flow CGMP conditions.

    PubMed

    Cole, Kevin P; Groh, Jennifer McClary; Johnson, Martin D; Burcham, Christopher L; Campbell, Bradley M; Diseroad, William D; Heller, Michael R; Howell, John R; Kallman, Neil J; Koenig, Thomas M; May, Scott A; Miller, Richard D; Mitchell, David; Myers, David P; Myers, Steven S; Phillips, Joseph L; Polster, Christopher S; White, Timothy D; Cashman, Jim; Hurley, Declan; Moylan, Robert; Sheehan, Paul; Spencer, Richard D; Desmond, Kenneth; Desmond, Paul; Gowran, Olivia

    2017-06-16

    Advances in drug potency and tailored therapeutics are promoting pharmaceutical manufacturing to transition from a traditional batch paradigm to more flexible continuous processing. Here we report the development of a multistep continuous-flow CGMP (current good manufacturing practices) process that produced 24 kilograms of prexasertib monolactate monohydrate suitable for use in human clinical trials. Eight continuous unit operations were conducted to produce the target at roughly 3 kilograms per day using small continuous reactors, extractors, evaporators, crystallizers, and filters in laboratory fume hoods. Success was enabled by advances in chemistry, engineering, analytical science, process modeling, and equipment design. Substantial technical and business drivers were identified, which merited the continuous process. The continuous process afforded improved performance and safety relative to batch processes and also improved containment of a highly potent compound. Copyright © 2017, American Association for the Advancement of Science.

  14. Phosphodiesterase 9A regulates central cGMP and modulates responses to cholinergic and monoaminergic perturbation in vivo.

    PubMed

    Kleiman, Robin J; Chapin, Douglas S; Christoffersen, Curt; Freeman, Jody; Fonseca, Kari R; Geoghegan, Kieran F; Grimwood, Sarah; Guanowsky, Victor; Hajós, Mihály; Harms, John F; Helal, Christopher J; Hoffmann, William E; Kocan, Geralyn P; Majchrzak, Mark J; McGinnis, Dina; McLean, Stafford; Menniti, Frank S; Nelson, Fredrick; Roof, Robin; Schmidt, Anne W; Seymour, Patricia A; Stephenson, Diane T; Tingley, Francis David; Vanase-Frawley, Michelle; Verhoest, Patrick R; Schmidt, Christopher J

    2012-05-01

    Cyclic nucleotides are critical regulators of synaptic plasticity and participate in requisite signaling cascades implicated across multiple neurotransmitter systems. Phosphodiesterase 9A (PDE9A) is a high-affinity, cGMP-specific enzyme widely expressed in the rodent central nervous system. In the current study, we observed neuronal staining with antibodies raised against PDE9A protein in human cortex, cerebellum, and subiculum. We have also developed several potent, selective, and brain-penetrant PDE9A inhibitors and used them to probe the function of PDE9A in vivo. Administration of these compounds to animals led to dose-dependent accumulation of cGMP in brain tissue and cerebrospinal fluid, producing a range of biological effects that implied functional significance for PDE9A-regulated cGMP in dopaminergic, cholinergic, and serotonergic neurotransmission and were consistent with the widespread distribution of PDE9A. In vivo effects of PDE9A inhibition included reversal of the respective disruptions of working memory by ketamine, episodic and spatial memory by scopolamine, and auditory gating by amphetamine, as well as potentiation of risperidone-induced improvements in sensorimotor gating and reversal of the stereotypic scratching response to the hallucinogenic 5-hydroxytryptamine 2A agonist mescaline. The results suggested a role for PDE9A in the regulation of monoaminergic circuitry associated with sensory processing and memory. Thus, PDE9A activity regulates neuronal cGMP signaling downstream of multiple neurotransmitter systems, and inhibition of PDE9A may provide therapeutic benefits in psychiatric and neurodegenerative diseases promoted by the dysfunction of these diverse neurotransmitter systems.

  15. Effects of cation contaminants in conductive TiO2 ceramics

    NASA Astrophysics Data System (ADS)

    Yan, M. F.; Rhodes, W. W.

    1982-12-01

    Ten cation contaminants, namely Al, Ga, Co, Fe, Mg, Zn, Zr, Ca, Sr, and Ba were investigated for their effects on the electrical properties, microstructures, and discoloration of conductive TiO2 ceramics. It was found that Al, Ga, Co, Fe, and Mg cause discoloration and increase the electrical resistivity by a factor of 104 to 106 in Nb-doped TiO2 ceramics. The other dopants do not introduce such changes in TiO2. The electrical properties, microstructures, and discoloration were measured in specimens of AlxNb0.007Ti0.993-xO2 with 0≤x≤0.01. When the Al content exceeds a critical value, ranging from 0.48% at 1400 °C to 0.25% at 1200 °C, the electrical resistivities and grain size increase rapidly, and the specimen is discolored from the original black to an ivory white color. Color boundary migration induced by Al diffusion in Nb-doped TiO2 was quantitatively measured. From the kinetics of the boundary migration, the Al diffusivity (D) was calculated to be D=2.67 exp(-53.3 kcal/mole/RT) cm2/s in the temperature range of 1200 to 1400 °C. The rapid diffusion of the small cations, namely Al, Ga, Co, Fe, and Mg, results from an interstitial diffusion mechanism. However, other cations, having a radius larger than the interstitial channel (˜0.77 Å radius), cannot diffuse by this mechanism. Defect reactions are proposed to explain the increase in the electrical resistivity and microstructural changes due to Al diffusion. These defect reactions also show that the problem of acceptor contamination cannot be avoided by adding an excess quantity of donor dopant if the solubility of the donor is much less than that of the acceptor contaminant.

  16. Establishing a cGMP pancreatic islet processing facility: the first experience in Iran.

    PubMed

    Larijani, Bagher; Arjmand, Babak; Amoli, Mahsa M; Ao, Ziliang; Jafarian, Ali; Mahdavi-Mazdah, Mitra; Ghanaati, Hossein; Baradar-Jalili, Reza; Sharghi, Sasan; Norouzi-Javidan, Abbas; Aghayan, Hamid Reza

    2012-12-01

    It has been predicted that one of the greatest increase in prevalence of diabetes will happen in the Middle East bear in the next decades. The aim of standard therapeutic strategies for diabetes is better control of complications. In contrast, some new strategies like cell and gene therapy have aimed to cure the disease. In recent years, significant progress has occurred in beta-cell replacement therapies with a progressive improvement of short-term and long term outcomes. In year 2005, considering the impact of the disease in Iran and the promising results of the Edmonton protocol, the funding for establishing a current Good Manufacturing Practice (cGMP) islet processing facility by Endocrinology and Metabolism Research Center was approved by Tehran University of Medical Sciences. Several islet isolations were performed following establishment of cGMP facility and recruitment of all required equipments for process validation and experimental purpose. Finally the first successful clinical islet isolation and transplantation was performed in September 2010. In spite of a high cost of the procedure it is considered beneficial and may prevent long term complications and the costs associated with secondary cares. In this article we will briefly describe our experience in setting up a cGMP islet processing facility which can provide valuable information for regional countries interested to establish similar facilities.

  17. Synthesis and structure-activity relationships of novel cationic lipids with anti-inflammatory and antimicrobial activities.

    PubMed

    Myint, Melissa; Bucki, Robert; Janmey, Paul A; Diamond, Scott L

    2015-07-15

    Certain membrane-active cationic steroids are known to also possess both anti-inflammatory and antimicrobial properties. This combined functionality is particularly relevant for potential therapies of infections associated with elevated tissue damage, for example, cystic fibrosis airway disease, a condition characterized by chronic bacterial infections and ongoing inflammation. In this study, six novel cationic glucocorticoids were synthesized using beclomethasone, budesonide, and flumethasone. Products were either monosubstituted or disubstituted, containing one or two steroidal groups, respectively. In vitro evaluation of biological activities demonstrated dual anti-inflammatory and antimicrobial properties with limited cytotoxicity for all synthesized compounds. Budesonide-derived compounds showed the highest degree of both glucocorticoid and antimicrobial properties within their respective mono- and disubstituted categories. Structure-activity analyses revealed that activity was generally related to the potency of the parent glucocorticoid. Taken together, these data indicate that these types of dual acting cationic lipids can be synthesized with the appropriate starting steroid to tailor activities as desired. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. In vivo administration of extracellular cGMP normalizes TNF-α and membrane expression of AMPA receptors in hippocampus and spatial reference memory but not IL-1β, NMDA receptors in membrane and working memory in hyperammonemic rats.

    PubMed

    Cabrera-Pastor, Andrea; Hernandez-Rabaza, Vicente; Taoro-Gonzalez, Lucas; Balzano, Tiziano; Llansola, Marta; Felipo, Vicente

    2016-10-01

    Patients with hepatic encephalopathy (HE) show working memory and visuo-spatial orientation deficits. Hyperammonemia is a main contributor to cognitive impairment in HE. Hyperammonemic rats show impaired spatial learning and learning ability in the Y maze. Intracerebral administration of extracellular cGMP restores learning in the Y-maze. The underlying mechanisms remain unknown. It also remains unknown whether extracellular cGMP improves neuroinflammation or restores spatial learning in hyperammonemic rats and if it affects differently reference and working memory. The aims of this work were: Spatial working and reference memory were assessed using the radial and Morris water mazes and neuroinflammation by immunohistochemistry and Western blot. Membrane expression of NMDA and AMPA receptor subunits was analyzed using the BS3 crosslinker. Extracellular cGMP was administered intracerebrally using osmotic minipumps. Chronic hyperammonemia induces neuroinflammation in hippocampus, with astrocytes activation and increased IL-1β, which are associated with increased NMDA receptors membrane expression and impaired working memory. This process is not affected by extracellular cGMP. Hyperammonemia also activates microglia and increases TNF-α, alters membrane expression of AMPA receptor subunits (increased GluA1 and reduced GluA2) and impairs reference memory. All these changes are reversed by extracellular cGMP. These results show that extracellular cGMP modulates spatial reference memory but not working memory. This would be mediated by modulation of TNF-α levels and of membrane expression of GluA1 and GluA2 subunits of AMPA receptors. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Exploring backbone-cation alkyl spacers for multi-cation side chain anion exchange membranes

    NASA Astrophysics Data System (ADS)

    Zhu, Liang; Yu, Xuedi; Hickner, Michael A.

    2018-01-01

    In order to systematically study how the arrangement of cations on the side chain and length of alkyl spacers between cations impact the performance of multi-cation AEMs for alkaline fuel cells, a series of polyphenylene oxide (PPO)-based AEMs with different cationic side chains were synthesized. This work resulted in samples with two or three cations in a side chain pendant to the PPO backbone. More importantly, the length of the spacer between cations varied from 3 methylene (-CH2-) (C3) groups to 8 methylene (C8) groups. The highest conductivity, up to 99 mS/cm in liquid water at room temperature, was observed for the triple-cation side chain AEM with pentyl (C5) or hexyl (C6) spacers. The multi-cation AEMs were found to have decreased water uptake and ionic conductivity when the spacer chains between cations were lengthened from pentyl (C5) or hexyl (C6) to octyl (C8) linking groups. The triple-cation membranes with pentyl (C5) or hexyl (C6) groups between cations showed greatest stability after immersion in 1 M NaOH at 80 °C for 500 h.

  20. Involvement of the cGMP pathway in mediating the insulin-inhibitory effect of melatonin in pancreatic beta-cells.

    PubMed

    Stumpf, Ina; Mühlbauer, Eckhard; Peschke, Elmar

    2008-10-01

    Recent investigations have demonstrated an influence of melatonin on insulin secretion in pancreatic beta-cells. The effects are receptor-mediated via two parallel signaling pathways. The aim of this study was to examine the relevance of a second melatonin receptor (MT2) as well as the involvement of a third signaling cascade in mediating melatonin effects, i.e. the cyclic guanosine monophosphate (cGMP) pathway. Our results demonstrate that the insulin-inhibiting effect of melatonin could be partly reversed by preincubation with the unspecific melatonin receptor antagonist luzindole as well as by the MT2-receptor-specific antagonist 4P-PDOT (4-phenyl-2-propionamidotetraline). As melatonin is known to modulate cGMP concentration via the MT2 receptor, these data indicate transmission of the melatonin effects via the cGMP transduction cascade. Molecular investigations established the presence of different types of guanylate cyclases, cGMP-specific phosphodiesterases and cyclic nucleotide-gated channels in rat insulinoma beta-cells (INS1). Moreover, variations in mRNA expression were found when comparing day and night values as well as different states of glucose metabolism. Incubation experiments provided evidence that 3-isobutyl-1-methylxanthine (IBMX)-stimulated cGMP concentrations were significantly decreased in INS1 cells exposed to melatonin for 1 hr in a dose- and time-dependent manner. This effect could also be reversed by application of luzindole and 4P-PDOT. Stimulation with 8-Br-cGMP resulted in significantly increased insulin production. In conclusion, it could be demonstrated that the melatonin receptor subtype MT2 as well as the cGMP signaling pathway are involved in mediating the insulin-inhibiting effect of melatonin.

  1. Activation by divalent cations of a Ca2+-activated K+ channel from skeletal muscle membrane.

    PubMed

    Oberhauser, A; Alvarez, O; Latorre, R

    1988-07-01

    Several divalent cations were studied as agonists of a Ca2+-activated K+ channel obtained from rat muscle membranes and incorporated into planar lipid bilayers. The effect of these agonists on single-channel currents was tested in the absence and in the presence of Ca2+. Among the divalent cations that activate the channel, Ca2+ is the most effective, followed by Cd2+, Sr2+, Mn2+, Fe2+, and Co2+. Mg2+, Ni2+, Ba2+, Cu2+, Zn2+, Hg2+, and Sn2+ are ineffective. The voltage dependence of channel activation is the same for all the divalent cations. The time-averaged probability of the open state is a sigmoidal function of the divalent cation concentration. The sigmoidal curves are described by a dissociation constant K and a Hill coefficient N. The values of these parameters, measured at 80 mV are: N = 2.1, K = 4 X 10(-7) mMN for Ca2+; N = 3.0, K = 0.02 mMN for Cd2+; N = 1.45, K = 0.63 mMN for Sr2+; N = 1.7, K = 0.94 mMN for Mn2+; N = 1.1, K = 3.0 mMN for Fe2+; and N = 1.1 K = 4.35 mMN for Co2+. In the presence of Ca2+, the divalent cations Cd2+, Co2+, Mn2+, Ni2+, and Mg2+ are able to increase the apparent affinity of the channel for Ca2+ and they increase the Hill coefficient in a concentration-dependent fashion. These divalent cations are only effective when added to the cytoplasmic side of the channel. We suggest that these divalent cations can bind to the channel, unmasking new Ca2+ sites.

  2. The implementation of tissue banking experiences for setting up a cGMP cell manufacturing facility.

    PubMed

    Arjmand, Babak; Emami-Razavi, Seyed Hassan; Larijani, Bagher; Norouzi-Javidan, Abbas; Aghayan, Hamid Reza

    2012-12-01

    Cell manufacturing for clinical applications is a unique form of biologics manufacturing that relies on maintenance of stringent work practices designed to ensure product consistency and prevent contamination by microorganisms or by another patient's cells. More extensive, prolonged laboratory processes involve greater risk of complications and possibly adverse events for the recipient, and so the need for control is correspondingly greater. To minimize the associate risks of cell manufacturing adhering to international quality standards is critical. Current good tissue practice (cGTP) and current good manufacturing practice (cGMP) are examples of general standards that draw a baseline for cell manufacturing facilities. In recent years, stem cell researches have found great public interest in Iran and different cell therapy projects have been started in country. In this review we described the role of our tissue banking experiences in establishing a new cGMP cell manufacturing facility. The authors concluded that, tissue banks and tissue banking experts can broaden their roles from preparing tissue grafts to manufacturing cell and tissue engineered products for translational researches and phase I clinical trials. Also they can collaborate with cell processing laboratories to develop SOPs, implement quality management system, and design cGMP facilities.

  3. Side Chain Degradable Cationic-Amphiphilic Polymers with Tunable Hydrophobicity Show in Vivo Activity.

    PubMed

    Uppu, Divakara S S M; Samaddar, Sandip; Hoque, Jiaul; Konai, Mohini M; Krishnamoorthy, Paramanandham; Shome, Bibek R; Haldar, Jayanta

    2016-09-12

    Cationic-amphiphilic antibacterial polymers with optimal amphiphilicity generally target the bacterial membranes instead of mammalian membranes. To date, this balance has been achieved by varying the cationic charge or side chain hydrophobicity in a variety of cationic-amphiphilic polymers. Optimal hydrophobicity of cationic-amphiphilic polymers has been considered as the governing factor for potent antibacterial activity yet minimal mammalian cell toxicity. However, the concomitant role of hydrogen bonding and hydrophobicity with constant cationic charge in the interactions of antibacterial polymers with bacterial membranes is not understood. Also, degradable polymers that result in nontoxic degradation byproducts offer promise as safe antibacterial agents. Here we show that amide- and ester (degradable)-bearing cationic-amphiphilic polymers with tunable side chain hydrophobicity can modulate antibacterial activity and cytotoxicity. Our results suggest that an amide polymer can be a potent antibacterial agent with lower hydrophobicity whereas the corresponding ester polymer needs a relatively higher hydrophobicity to be as effective as its amide counterpart. Our studies reveal that at higher hydrophobicities both amide and ester polymers have similar profiles of membrane-active antibacterial activity and mammalian cell toxicity. On the contrary, at lower hydrophobicities, amide and ester polymers are less cytotoxic, but the former have potent antibacterial and membrane activity compared to the latter. Incorporation of amide and ester moieties made these polymers side chain degradable, with amide polymers being more stable than the ester polymers. Further, the polymers are less toxic, and their degradation byproducts are nontoxic to mice. More importantly, the optimized amide polymer reduces the bacterial burden of burn wound infections in mice models. Our design introduces a new strategy of interplay between the hydrophobic and hydrogen bonding interactions

  4. Atomistic Detailed Mechanism and Weak Cation-Conducting Activity of HIV-1 Vpu Revealed by Free Energy Calculations

    PubMed Central

    Padhi, Siladitya; Burri, Raghunadha Reddy; Jameel, Shahid; Priyakumar, U. Deva

    2014-01-01

    The viral protein U (Vpu) encoded by HIV-1 has been shown to assist in the detachment of virion particles from infected cells. Vpu forms cation-specific ion channels in host cells, and has been proposed as a potential drug target. An understanding of the mechanism of ion transport through Vpu is desirable, but remains limited because of the unavailability of an experimental structure of the channel. Using a structure of the pentameric form of Vpu – modeled and validated based on available experimental data – umbrella sampling molecular dynamics simulations (cumulative simulation time of more than 0.4 µs) were employed to elucidate the energetics and the molecular mechanism of ion transport in Vpu. Free energy profiles corresponding to the permeation of Na+ and K+ were found to be similar to each other indicating lack of ion selection, consistent with previous experimental studies. The Ser23 residue is shown to enhance ion transport via two mechanisms: creating a weak binding site, and increasing the effective hydrophilic length of the channel, both of which have previously been hypothesized in experiments. A two-dimensional free energy landscape has been computed to model multiple ion permeation, based on which a mechanism for ion conduction is proposed. It is shown that only one ion can pass through the channel at a time. This, along with a stretch of hydrophobic residues in the transmembrane domain of Vpu, explains the slow kinetics of ion conduction. The results are consistent with previous conductance studies that showed Vpu to be a weakly conducting ion channel. PMID:25392993

  5. cGMP may have trophic effects on beta cell function comparable to those of cAMP, implying a role for high-dose biotin in prevention/treatment of diabetes.

    PubMed

    McCarty, Mark F

    2006-01-01

    Incretin hormones have trophic effects on beta cell function that can aid prevention and treatment of diabetes. cAMP is the primary mediator of these effects, and has been shown to potentiate glucose-stimulated insulin secretion, promote proper beta cells differentiation by increasing expression of the crucial transcription factor PDX-1, and prevent beta cell apoptosis. cGMP's role in beta cell function has received far less scrutiny, but there is emerging evidence that it may have a trophic impact on beta cell function analogous to that of cAMP. An increase in plasma glucose boosts beta cell production of cGMP, which acts as a feed-forward mediator to enhance glucose-stimulated insulin secretion. cGMP also has an anti-apoptotic effect in beta cells, and there is now indirect evidence that it promotes expression of PDX-1. Supraphysiological concentrations of biotin can directly activate guanylate cyclase, and there is limited evidence that high intakes of this vitamin can be therapeutically beneficial in diabetics and in rodent models of diabetes. Beneficial effects of cGMP on muscle insulin sensitivity and on control of hepatic glucose output may contribute to biotin's utility in diabetes. The fact that nitric oxide/cGMP exert a range of favorable effects on vascular health should further encourage exploration of biotin's preventive and therapeutic potential. If an appropriate high-dose biotin regimen could achieve a modest systemic increase in guanylate cyclase activity, without entailing unacceptable side effects or risks, such a regimen might have considerable potential for promoting vascular health and preventing or managing diabetes.

  6. Effects of Biotin Supplementation in the Diet on Adipose Tissue cGMP Concentrations, AMPK Activation, Lipolysis, and Serum-Free Fatty Acid Levels.

    PubMed

    Boone-Villa, Daniel; Aguilera-Méndez, Asdrubal; Miranda-Cervantes, Adriana; Fernandez-Mejia, Cristina

    2015-10-01

    Several studies have shown that pharmacological concentrations of biotin decrease hyperlipidemia. The molecular mechanisms by which pharmacological concentrations of biotin modify lipid metabolism are largely unknown. Adipose tissue plays a central role in lipid homeostasis. In the present study, we analyzed the effects of biotin supplementation in adipose tissue on signaling pathways and critical proteins that regulate lipid metabolism, as well as on lipolysis. In addition, we assessed serum fatty acid concentrations. Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet (control: 1.76 mg biotin/kg; supplemented: 97.7 mg biotin/kg diet) over 8 weeks postweaning. Compared with the control group, biotin-supplemented mice showed an increase in the levels of adipose guanosine 3',5'-cyclic monophosphate (cGMP) (control: 30.3±3.27 pmol/g wet tissue; supplemented: 49.5±3.44 pmol/g wet tissue) and of phosphorylated forms of adenosine 5'-monophosphate-activated protein kinase (AMPK; 65.2%±1.06%), acetyl-coenzyme A (CoA), carboxylase-1 (196%±68%), and acetyl-CoA carboxylase-2 (78.1%±18%). Serum fatty acid concentrations were decreased (control: 1.12±0.04 mM; supplemented: 0.91±0.03 mM), and no change in lipolysis was found (control: 0.29±0.05 μmol/mL; supplemented: 0.33±0.08 μmol/mL). In conclusion, 8 weeks of dietary biotin supplementation increased adipose tissue cGMP content and protein expression of the active form of AMPK and of the inactive forms of acetyl-CoA carboxylase-1 and acetyl-CoA carboxylase-2. Serum fatty acid levels fell, and no change in lipolysis was observed. These findings provide insight into the effects of biotin supplementation on adipose tissue and support its use in the treatment of dyslipidemia.

  7. Early markers of retinal degeneration in rd/rd mice.

    PubMed

    Acosta, Monica L; Fletcher, Erica L; Azizoglu, Serap; Foster, Lisa E; Farber, Debora B; Kalloniatis, Michael

    2005-09-06

    In the rd/rd mouse, the cell death of rod photoreceptors has been correlated to abnormal levels of the cyclic nucleotide cGMP within photoreceptors. Given that cGMP is required for opening of the cationic channels, there is the possibility that a high cGMP concentration would maintain these channels open, at a high energy cost for the retina. We investigated whether cation channels were maintained in an open state in the rd/rd mouse retina by determining the labeling pattern of an organic cationic probe (agmatine, AGB) which selectively enters cells through open cationic channels. The metabolic activity of the rd/rd mice was measured by assaying lactate dehydrogenase (LDH) activity in several tissues and Na+/K+ ATPase activity was measured as a function of development and degeneration of the retina. AGB neuronal labeling showed a systematic increase consistent with the known neuronal functional maturation in the normal retina. There was a significant higher AGB labeling of photoreceptors in the rd/rd mouse retina from P6 supporting the possibility of open cationic channels from an early age. There were no changes in the LDH activity of tissues that contain PDE6 or that have a similar LDH distribution as the retina. However, LDH activity was significantly higher in the rd/rd mouse retina than in those of control mice from birth to P6, and it dramatically decreased from P9 as the photoreceptors degenerated. The predominant LDH isoenzyme changes and loss after degeneration appeared to be LDH5. ATPase activity increased with age, reaching adult levels by P16. Unlike LDH activity, there was no significant difference in Na+/K+ ATPase activity between control and rd/rd mice at any age examined. We conclude that AGB is a useful marker of photoreceptors destined to degenerate. We discard the possibility of a generalized metabolic effect in the rd/rd mice. However, the elevated LDH activity present before photoreceptor differentiation indicated altered retinal metabolic

  8. PPARα autocrine regulation of Ca²⁺-regulated exocytosis in guinea pig antral mucous cells: NO and cGMP accumulation.

    PubMed

    Tanaka, Saori; Sugiyama, Nanae; Takahashi, Yuko; Mantoku, Daiki; Sawabe, Yukinori; Kuwabara, Hiroko; Nakano, Takashi; Shimamoto, Chikao; Matsumura, Hitoshi; Marunaka, Yoshinori; Nakahari, Takashi

    2014-12-15

    In antral mucous cells, acetylcholine (ACh, 1 μM) activates Ca(2+)-regulated exocytosis, consisting of a peak in exocytotic events that declines rapidly (initial phase) followed by a second slower decline (late phase) lasting during ACh stimulation. GW7647 [a peroxisome proliferation activation receptor α (PPARα) agonist] enhanced the ACh-stimulated initial phase, and GW6471 (a PPARα antagonist) abolished the GW7647-induced enhancement. However, GW6471 produced the delayed, but transient, increase in the ACh-stimulated late phase, and it also decreased the initial phase and produced the delayed increase in the late phase during stimulation with ACh alone. A similar delayed increase in the ACh-stimulated late phase is induced by an inhibitor of the PKG, Rp8BrPETcGMPS, suggesting that GW6471 inhibits cGMP accumulation. An inhibitor of nitric oxide synthase 1 (NOS1), N(5)-[imino(propylamino)methyl]-L-ornithine hydrochloride (N-PLA), also abolished the GW7647-induced-enhancement of ACh-stimulated initial phase but produced the delayed increase in the late phase. However, in the presence of N-PLA, an NO donor or 8BrcGMP enhanced the ACh-stimulated initial phase and abolished the delayed increase in the late phase. Moreover, GW7647 and ACh stimulated NO production and cGMP accumulation in antral mucosae, which was inhibited by GW6471 or N-PLA. Western blotting and immunohistochemistry revealed that NOS1 and PPARα colocalize in antral mucous cells. In conclusion, during ACh stimulation, a PPARα autocrine mechanism, which accumulates NO via NOS1 leading to cGMP accumulation, modulates the Ca(2+)-regulated exocytosis in antral mucous cells. Copyright © 2014 the American Physiological Society.

  9. Decreased levels of guanosine 3', 5'-monophosphate (cGMP) in cerebrospinal fluid (CSF) are associated with cognitive decline and amyloid pathology in Alzheimer's disease.

    PubMed

    Ugarte, Ana; Gil-Bea, Francisco; García-Barroso, Carolina; Cedazo-Minguez, Ángel; Ramírez, M Javier; Franco, Rafael; García-Osta, Ana; Oyarzabal, Julen; Cuadrado-Tejedor, Mar

    2015-06-01

    Levels of the cyclic nucleotides guanosine 3', 5'-monophosphate (cGMP) or adenosine 3', 5'-monophosphate (cAMP) that play important roles in memory processes are not characterized in Alzheimer's disease (AD). The aim of this study was to analyse the levels of these nucleotides in cerebrospinal fluid (CSF) samples from patients diagnosed with clinical and prodromal stages of AD and study the expression level of the enzymes that hydrolyzed them [phosphodiesterases (PDEs)] in the brain of AD patients vs. For cGMP and cAMP CSF analysis, the cohort (n = 79) included cognitively normal participants (subjective cognitive impairment), individuals with stable mild cognitive impairment or AD converters (sMCI and cMCI), and mild AD patients. A high throughput liquid chromatography-tandem mass spectrometry method was used. Interactions between CSF cGMP or cAMP with mini-mental state examination (MMSE) score, CSF Aβ(1-42) and CSF p-tau were analysed. For PDE4, 5, 9 and 10 expression analysis, brains of AD patients vs. controls (n = 7 and n = 8) were used. cGMP, and not cAMP levels, were significantly lower in the CSF of patients diagnosed with mild AD when compared with nondemented controls. CSF levels of cGMP showed a significant association with MMSE-diagnosed clinical dementia and with CSF biomarker Aβ42 in AD patients. Significant increase in PDE5 expression was detected in temporal cortex of AD patients compared with that of age-matched healthy control subjects. No changes in the expression of others PDEs were detected. These results support the potential involvement of cGMP in the pathological and clinical development of AD. The cGMP reduction in early stages of AD might participate in the aggravation of amyloid pathology and cognitive decline. © 2014 British Neuropathological Society.

  10. Structure-transfection activity relationships in a series of novel cationic lipids with heterocyclic head-groups.

    PubMed

    Ivanova, Ekaterina A; Maslov, Mikhail A; Kabilova, Tatyana O; Puchkov, Pavel A; Alekseeva, Anna S; Boldyrev, Ivan A; Vlassov, Valentin V; Serebrennikova, Galina A; Morozova, Nina G; Zenkova, Marina A

    2013-11-07

    Cationic liposomes are promising candidates for the delivery of various therapeutic nucleic acids. Here, we report a convenient synthesis of carbamate-type cationic lipids with various hydrophobic domains (tetradecanol, dialkylglycerol, cholesterol) and positively charged head-groups (pyridinium, N-methylimidazolium, N-methylmorpholinium) and data on the structure-transfection activity relationships. It was found that single-chain lipids possess high surface activity, which correlates with high cytotoxicity due to their ability to disrupt the cellular membrane by combined hydrophobic and electrostatic interactions. Liposomes containing these lipids also display high cytotoxicity with respect to all cell lines. Irrespective of chemical structures, all cationic lipids form liposomes with similar sizes and surface potentials. The characteristics of complexes composed of cationic liposomes and nucleic acids depend mostly on the type of nucleic acid and P/N ratios. In the case of oligodeoxyribonucleotide delivery, the transfection activity depends on the type of cationic head-group regardless of the type of hydrophobic domain: all types of cationic liposomes mediate efficient oligonucleotide transfer into 80-90% of the eukaryotic cells, and liposomes based on lipids with N-methylmorpholinium cationic head-group display the highest transfection activity. In the case of plasmid DNA and siRNA, the type of hydrophobic domain determines the transfection activity: liposomes composed of cholesterol-based lipids were the most efficient in DNA transfer, while liposomes containing glycerol-based lipids exhibited reasonable activity in siRNA delivery under serum-free conditions.

  11. CHBPR: Decreased cGMP level contributes to increased contraction in arteries from hypertensive rats: role of PDE1

    PubMed Central

    Giachini, Fernanda R.; Lima, Victor V.; Carneiro, Fernando S.; Tostes, Rita C.; Webb, R. Clinton

    2011-01-01

    Recent evidence suggests that angiotensin II (Ang II) upregulates phosphodiesterase (PDE)-1A expression. We hypothesized that Ang II augmented PDE1 activation, decreasing the bioavailability of cyclic cyclic guanosine 3', 5'-monophosphate (cGMP), contributing to increased vascular contractility. Male Sprague-Dawley rats received mini-osmotic pumps with Ang II (60 ng.min−1) or saline for 14 days. PE-induced contractions were increased in aorta (Emax168±8 vs. 136±4%) and small-mesenteric arteries [(SMA), Emax170±6 vs. 143±3%] from Ang II infused rats compared to control. PDE1 inhibition with vinpocetine (10µM) reduced PE-induced contraction in aortas from Ang II rats (Emax94±12%) but not in control (154±7%). Vinpocetine decreased the sensitivity to PE in SMA from Ang II rats compared to vehicle (pD2 5.1±0.1 vs. 5.9±0.06), but not in control (6.0±0.03 vs. 6.1±0.04). Sildenafil (10µM), a PDE5 inhibitor reduced PE-induced maximal contraction similarly in Ang II and control rats. Arteries were contracted with PE (1µM) and concentration-dependent relaxation to vinpocetine and sildenafil was evaluated. Aortas from Ang II rats displayed increased relaxation to vinpocetine compared to control (Emax82±12 vs. 44±5%). SMA from Ang II rats showed greater sensitivity during vinpocetine-induced relaxation, compared to control (pD2 6.1±0.3 vs. 5.3±0.1). No differences in sildenafil-induced relaxation were observed. PDE1A and PDE1C expressions in aorta and PDE1A expression in SMA were increased in Ang II rats. cGMP production, which is decreased in arteries from Ang II rats, was restored after PDE1 blockade. We conclude that PDE1 activation reduces cGMP bioavailability in arteries from ANG II, contributing to increased contractile responsiveness. PMID:21282562

  12. Cationic polypeptides contribute to the anti-HIV-1 activity of human seminal plasma

    PubMed Central

    Martellini, Julie A.; Cole, Amy L.; Venkataraman, Nitya; Quinn, Gerry A.; Svoboda, Pavel; Gangrade, Bhushan K.; Pohl, Jan; Sørensen, Ole E.; Cole, Alexander M.

    2009-01-01

    Mucosal surfaces of the reproductive tract as well as their secretions have important roles in preventing sexual transmission of HIV-1. In the current study, the majority of the intrinsic anti-HIV-1 activity of human seminal plasma (SP) was determined to reside in the cationic polypeptide fraction. Antiviral assays utilizing luciferase reporter cells and lymphocytic cells revealed the ability of whole SP to prevent HIV-1 infection, even when SP was diluted 3200-fold. Subsequent fractionation by continuous flow acid-urea (AU)-PAGE and antiviral testing revealed that cationic polypeptides within SP were responsible for the majority of anti-HIV-1 activity. A proteomic approach was utilized to resolve and identify 52 individual cationic polypeptides that contribute to the aggregate anti-HIV-1 activity of SP. One peptide fragment of semenogelin I, termed SG-1, was purified from SP by a multistep chromatographic approach, protein sequenced, and determined to exhibit anti-HIV-1 activity against HIV-1. Anti-HIV-1 activity was transient, as whole SP incubated for prolonged time intervals exhibited a proportional decrease in anti-HIV-1 activity that was directly attributed to the degradation of semenogelin I peptides. Collectively, these results indicate that the cationic polypeptide fraction of SP is active against HIV-1, and that semenogelin-derived peptides contribute to the intrinsic anti-HIV-1 activity of SP.—Martellini, J. A., Cole, A. C., Venkataraman, N., Quinn, G. A., Svoboda, P., Gangrade, B. K., Pohl, J., Sørensen, O. E., Cole, A. M. Cationic polypeptides contribute to the anti-HIV-1 activity of human seminal plasma. PMID:19487309

  13. Thermodynamics of Activation Gating in Olfactory-Type Cyclic Nucleotide-Gated (CNGA2) Channels

    PubMed Central

    Nache, Vasilica; Kusch, Jana; Biskup, Christoph; Schulz, Eckhard; Zimmer, Thomas; Hagen, Volker; Benndorf, Klaus

    2008-01-01

    Olfactory-type cyclic nucleotide-gated (CNG) ion channels open by the binding of cyclic nucleotides to a binding domain in the C-terminus. Employing the Eyring rate theory, we performed a thermodynamic analysis of the activation gating in homotetrameric CNGA2 channels. Lowering the temperature shifted the concentration-response relationship to lower concentrations, resulting in a decrease of both the enthalpy ΔH and entropy ΔS upon channel opening, suggesting that the order of an open CNGA2 channel plus its environment is higher than that of the closed channel. Activation time courses induced by cGMP concentration jumps were used to study thermodynamics of the transition state. The activation enthalpies ΔH‡ were positive at all cGMP concentrations. In contrast, the activation entropy ΔS‡ was positive at low cGMP concentrations and became then negative at increasing cGMP concentrations. The enthalpic and entropic parts of the activation energies approximately balance each other at all cGMP concentrations, leaving the free enthalpy of activation in the range between 19 and 21 kcal/mol. We conclude that channel activation proceeds through different pathways at different cGMP concentrations. Compared to the unliganded channel, low cGMP concentrations generate a transitional state of lower order whereas high cGMP concentrations generate a transitional state of higher order. PMID:18567637

  14. EFFECT OF INORGANIC CATIONS ON BACTERICIDAL ACTIVITY OF ANIONIC SURFACTANTS

    PubMed Central

    Voss, J. G.

    1963-01-01

    Voss, J. G. (Procter & Gamble Co., Cincinnati, Ohio). Effect of inorganic cations on bactericidal activity of anionic surfactants. J. Bacteriol. 86:207–211. 1963.—The bactericidal effectiveness of two alkyl benzene sulfonates and of three other types of anionic surfactants against Staphylococcus aureus is increased in the presence of low concentrations of divalent cations, especially alkaline earths and metals of group IIB of the periodic table. The cations may act by decreasing the negative charge at the cell surface and increasing adsorption of the surfactant anions, leading to damage to the cytoplasmic membrane and death of the cell. Increased adsorption of surfactant is also found with Escherichia coli, but does not lead to death of the cell. PMID:14058942

  15. Short-term dehydroepiandrosterone treatment increases platelet cGMP production in elderly male subjects.

    PubMed

    Martina, Valentino; Benso, Andrea; Gigliardi, Valentina Ramella; Masha, Andi; Origlia, Carla; Granata, Riccarda; Ghigo, Ezio

    2006-03-01

    Several clinical and population-based studies suggest that dehydroepiandrosterone (DHEA) and its sulphate (DHEA-S) play a protective role against atherosclerosis and coronary artery disease in human. However, the mechanisms underlying this action are still unknown. It has recently been suggested that DHEA-S could delay atheroma formation through an increase in nitric oxide (NO) production. Twenty-four aged male subjects [age (mean +/- SEM): 65.4 +/- 0.7 year; range: 58.2-67.6 years] underwent a blinded placebo controlled study receiving DHEA (50 mg p.o. daily at bedtime) or placebo for 2 months. Platelet cyclic guanosine-monophosphate (cGMP) concentration (as marker of NO production) and serum levels of DHEA-S, DHEA, IGF-I, insulin, glucose, oestradiol (E(2)), testosterone, plasminogen activator inhibitor (PAI)-1 antigen (PAI-1 Ag), homocysteine and lipid profile were evaluated before and after the 2-month treatment with DHEA or placebo. At the baseline, all variables in the two groups were overlapping. All parameters were unchanged after treatment with placebo. Conversely, treatment with DHEA (a) increased (P < 0.001 vs. baseline) platelet cGMP (111.9 +/- 7.1 vs. 50.1 +/- 4.1 fmol/10(6) plts), DHEA-S (13.6 +/- 0.8 vs. 3.0 +/- 0.3 micromol/l), DHEA (23.6 +/- 1.7 vs. 15.3 +/- 1.4 nmol/l), testosterone (23.6 +/- 1.0 vs. 17.7 +/- 1.0 nmol/l) and E(2) (72.0 +/- 5.0 vs. 60.0 +/- 4.0 pmol/l); and (b) decreased (P < 0.05 vs. baseline) PAI-1 Ag (27.4 +/- 3.8 vs. 21.5 +/- 2.5 ng/ml) and low-density lipoprotein (LDL) cholesterol (3.4 +/- 0.2 vs. 3.0 +/- 0.2 mmol/l). IGF-I, insulin, glucose, triglycerides, total cholesterol, HDL cholesterol, HDL2 cholesterol, HDL3 cholesterol, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and homocysteine levels were not modified by DHEA treatment. This study shows that short-term treatment with DHEA increased platelet cGMP production, a marker of NO production, in healthy elderly subjects. This effect is coupled with a decrease in PAI-1

  16. cGMP signaling as a target for the prevention and treatment of breast cancer.

    PubMed

    Windham, Perrin F; Tinsley, Heather N

    2015-04-01

    One in eight women in the United States will be diagnosed with invasive breast cancer in her lifetime. Advances in therapeutic strategies, diagnosis, and improved awareness have resulted in a significant reduction in breast cancer related mortality. However, there is a continued need for more effective and less toxic drugs for both the prevention and the treatment of breast cancer in order to see a continued decline in the morbidity and mortality associated with this disease. Recent studies suggest that the cGMP signaling pathway may be aberrantly regulated in breast cancer. As such, this pathway may serve as a source of novel targets for future breast cancer drug discovery efforts. This review provides an overview of cGMP signaling in normal physiology and in breast cancer as well as current strategies being investigated for targeting this pathway in breast cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Identification of the gamma subunit-interacting residues on photoreceptor cGMP phosphodiesterase, PDE6alpha '.

    PubMed

    Granovsky, A E; Artemyev, N O

    2000-12-29

    Photoreceptor cGMP phosphodiesterase (PDE6) is the effector enzyme in the G protein-mediated visual transduction cascade. In the dark, the activity of PDE6 is shut off by the inhibitory gamma subunit (Pgamma). Chimeric proteins between cone PDE6alpha' and cGMP-binding and cGMP-specific PDE (PDE5) have been constructed and expressed in Sf9 cells to study the mechanism of inhibition of PDE6 catalytic activity by Pgamma. Substitution of the segment PDE5-(773-820) by the corresponding PDE6alpha'-(737-784) sequence in the wild-type PDE5 or in a PDE5/PDE6alpha' chimera containing the catalytic domain of PDE5 results in chimeric enzymes capable of inhibitory interaction with Pgamma. The catalytic properties of the chimeric PDEs remained similar to those of PDE5. Ala-scanning mutational analysis of the Pgamma-binding region, PDE6alpha'-(750-760), revealed PDE6alpha' residues essential for the interaction. The M758A mutation markedly impaired and the Q752A mutation moderately impaired the inhibition of chimeric PDE by Pgamma. The analysis of the catalytic properties of mutant PDEs and a model of the PDE6 catalytic domain suggest that residues Met(758) and Gln(752) directly bind Pgamma. A model of the PDE6 catalytic site shows that PDE6alpha'-(750-760) forms a loop at the entrance to the cGMP-binding pocket. Binding of Pgamma to Met(758) would effectively block access of cGMP to the catalytic cavity, providing a structural basis for the mechanism of PDE6 inhibition.

  18. cGMP signalling in pre- and post-conditioning: the role of mitochondria.

    PubMed

    Costa, Alexandre D T; Pierre, Sandrine V; Cohen, Michael V; Downey, James M; Garlid, Keith D

    2008-01-15

    Much of cell death from ischaemia/reperfusion in heart and other tissues is generally thought to arise from mitochondrial permeability transition (MPT) in the first minutes of reperfusion. In ischaemic pre-conditioning, agonist binding to G(i) protein-coupled receptors prior to ischaemia triggers a signalling cascade that protects the heart from MPT. We believe that the cytosolic component of this trigger pathway terminates in activation of guanylyl cyclase resulting in increased production of cGMP and subsequent activation of protein kinase G (PKG). PKG phosphorylates a protein on the mitochondrial outer membrane (MOM), which then causes the mitochondrial K(ATP) channel (mitoK(ATP)) on the mitochondrial inner membrane to open, leading to increased production of reactive oxygen species (ROS) by the mitochondria. This implies that the protective signal is somehow transmitted from the MOM to its inner membrane. This is accomplished by a series of intermembrane signalling steps that includes protein kinase C (PKCepsilon) activation. The resulting ROS then activate a second PKC pool which, through another signal transduction pathway termed the mediator pathway, causes inhibition of MPT and reduction in cell death.

  19. Cardioprotective cGMP favors exogenous fatty acid incorporation into tyiglycerides over direct beta-oxidation

    USDA-ARS?s Scientific Manuscript database

    While cardiac hypertrophy has been associated with a shift in substrate selection for energy production from fatty acids (FA) to carbohydrates (CHO), it remains controversial whether this shift is adaptive or maladaptive. Since enhanced cGMP signalling can prevent hypertrophy, we hypothesized that t...

  20. Engineering Fast Ion Conduction and Selective Cation Channels for a High-Rate and High-Voltage Hybrid Aqueous Battery.

    PubMed

    Liu, Chunyi; Wang, Xusheng; Deng, Wenjun; Li, Chang; Chen, Jitao; Xue, Mianqi; Li, Rui; Pan, Feng

    2018-03-14

    The rechargeable aqueous metal-ion battery (RAMB) has attracted considerable attention due to its safety, low costs, and environmental friendliness. Yet the poor-performance electrode materials lead to a low feasibility of practical application. A hybrid aqueous battery (HAB) built from electrode materials with selective cation channels could increase the electrode applicability and thus enlarge the application of RAMB. Herein, we construct a high-voltage K-Na HAB based on K 2 FeFe(CN) 6 cathode and carbon-coated NaTi 2 (PO 4 ) 3 (NTP/C) anode. Due to the unique cation selectivity of both materials and ultrafast ion conduction of NTP/C, the hybrid battery delivers a high capacity of 160 mAh g -1 at a 0.5 C rate. Considerable capacity retention of 94.3 % is also obtained after 1000 cycles at even 60 C rate. Meanwhile, high energy density of 69.6 Wh kg -1 based on the total mass of active electrode materials is obtained, which is comparable and even superior to that of the lead acid, Ni/Cd, and Ni/MH batteries. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Divalent cations potentiate TRPV1 channel by lowering the heat activation threshold

    PubMed Central

    Cao, Xu; Ma, Linlin; Yang, Fan

    2014-01-01

    Transient receptor potential vanilloid type 1 (TRPV1) channel responds to a wide spectrum of physical and chemical stimuli. In doing so, it serves as a polymodal cellular sensor for temperature change and pain. Many chemicals are known to strongly potentiate TRPV1 activation, though how this is achieved remains unclear. In this study we investigated the molecular mechanism underlying the gating effects of divalent cations Mg2+ and Ba2+. Using a combination of fluorescence imaging and patch-clamp analysis, we found that these cations potentiate TRPV1 gating by most likely promoting the heat activation process. Mg2+ substantially lowers the activation threshold temperature; as a result, a significant fraction of channels are heat-activated at room temperature. Although Mg2+ also potentiates capsaicin- and voltage-dependent activation, these processes were found either to be not required (in the case of capsaicin) or insufficient (in the case of voltage) to mediate the activating effect. In support of a selective effect on heat activation, Mg2+ and Ba2+ cause a Ca2+-independent desensitization that specifically prevents heat-induced channel activation but does not prevent capsaicin-induced activation. These results can be satisfactorily explained within an allosteric gating framework in which divalent cations strongly promote the heat-dependent conformational change or its coupling to channel activation, which is further coupled to the voltage- and capsaicin-dependent processes. PMID:24344247

  2. Cyclic guanosine monophosphate does not inhibit gonadotropin-induced activation of mitogen-activated protein kinase 3/1 in pig cumulus-oocyte complexes.

    PubMed

    Blaha, Milan; Nemcova, Lucie; Prochazka, Radek

    2015-01-07

    Recent results indicate a key role for cyclic guanosine monophosphate (cGMP) in the regulation of oocyte meiotic arrest in preovulatory mammalian follicles. The aim of our study was to determine whether the resumption of oocyte meiosis and expansion of cumulus cells in isolated pig cumulus-oocyte complexes (COCs) can be blocked by a high intracellular concentration of cGMP, and whether this effect is mediated by a cGMP-dependent inhibition of mitogen-activated protein kinase 3/1 (MAPK3/1). The COCs were isolated from ovaries of slaughtered gilts and cultured in vitro in M199 supplemented with 5% fetal calf serum. The expression levels of the C-type natriuretic peptide (CNP) precursor (NPPC) and its receptor (NPR2) mRNAs during the culture of COCs were determined by real-time RT-PCR. To control the intracellular concentration of cGMP in the COCs, the culture medium was further supplemented with CNP or various concentrations of synthetic cGMP analogues; the concentration of cGMP in COCs was then assessed by ELISA. The effect of the drugs on oocyte maturation was assessed after 24 and 44 h of culture by determining nuclear maturation. The expansion of cumulus cells was assessed by light microscopy and the expression of cumulus expansion-related genes by real-time RT-PCR. A possible effect of cGMP on FSH-induced activation of MAPK3/1 was assessed by immunoblotting the COC proteins with phospho-specific and total anti-Erk1/2 antibodies. The COCs expressed NPPC and NPR2, the key components of cGMP synthesis, and produced a large amount of cGMP upon stimulation with exogenous CNP, which lead to a significant (P < 0.05) delay in oocyte meiotic resumption. The COCs also responded to cGMP analogues by inhibiting the resumption of oocyte meiosis. The inhibitory effect of cGMP on meiotic resumption was reversed by stimulating the COCs with FSH. However, high concentration of intracellular cGMP was not able to suppress FSH-induced activation of MAPK3/1 in cumulus cells, cumulus

  3. Probing the structure of the conduction pathway of the sheep cardiac sarcoplasmic reticulum calcium-release channel with permeant and impermeant organic cations

    PubMed Central

    1993-01-01

    The sarcoplasmic reticulum Ca(2+)-release channel plays a central role in cardiac muscle function by providing a ligand-regulated pathway for the release of sequestered Ca2+ to initiate contraction following cell excitation. The efficiency of the channel as a Ca(2+)-release pathway will be influenced by both gating and conductance properties of the system. In the past we have investigated conduction and discrimination of inorganic mono- and divalent cations with the aim of describing the mechanisms governing ion handling in the channel (Tinker, A., A.R. G. Lindsay, and A.J. Williams. 1992. Journal of General Physiology. 100:495-517.). In the present study, we have used permeant and impermeant organic cations to provide additional information on structural features of the conduction pathway. The use of permeant organic cations in biological channels to explore structural motifs underlying selectivity has been an important tool for the electrophysiologist. We have examined the conduction properties of a series of monovalent organic cations of varying size in the purified sheep cardiac sarcoplasmic reticulum Ca(2+)-release channel. Relative permeability, determined from the reversal potential measured under bi- ionic conditions with 210-mM test cation at the cytoplasmic face of the channel and 210 mM K+ at the luminal, was related inversely to the minimum circular cation radius. The reversal potential was concentration-independent. The excluded area hypothesis, with and without a term for solute-wall friction, described the data well and gave a lower estimate for minimum pore radius of 3.3-3.5 A. Blocking studies with the impermeant charged derivative of triethylamine reveal that this narrowing occurs over the first 10-20% of the voltage drop when crossing from the lumen of the SR to the cytoplasm. Single-channel conductances were measured in symmetrical 210 mM salt. Factors other than relative permeability determine conductance as ions with similar relative

  4. Active-site monovalent cations revealed in a 1.55-Å-resolution hammerhead ribozyme structure.

    PubMed

    Anderson, Michael; Schultz, Eric P; Martick, Monika; Scott, William G

    2013-10-23

    We have obtained a 1.55-Å crystal structure of a hammerhead ribozyme derived from Schistosoma mansoni under conditions that permit detailed observations of Na(+) ion binding in the ribozyme's active site. At least two such Na(+) ions are observed. The first Na(+) ion binds to the N7 of G10.1 and the adjacent A9 phosphate in a manner identical with that previously observed for divalent cations. A second Na(+) ion binds to the Hoogsteen face of G12, the general base in the hammerhead cleavage reaction, thereby potentially dissipating the negative charge of the catalytically active enolate form of the nucleotide base. A potential but more ambiguous third site bridges the A9 and scissile phosphates in a manner consistent with that of previous predictions. Hammerhead ribozymes have been observed to be active in the presence of high concentrations of monovalent cations, including Na(+), but the mechanism by which monovalent cations substitute for divalent cations in hammerhead catalysis remains unclear. Our results enable us to suggest that Na(+) directly and specifically substitutes for divalent cations in the hammerhead active site. The detailed geometry of the pre-catalytic active-site complex is also revealed with a new level of precision, thanks to the quality of the electron density maps obtained from what is currently the highest-resolution ribozyme structure in the Protein Data Bank. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Effects of gene knockdown of CNP on ventricular remodeling after myocardial ischemia-reperfusion injury through NPRB/Cgmp signaling pathway in rats.

    PubMed

    Wu, Lian-He; Zhang, Qi; Zhang, Shen; Meng, Lu-Yu; Wang, Yan-Chi; Sheng, Cun-Jian

    2018-02-01

    This study aimed to explore effects of CNP on ventricular remodeling following myocardial ischemia-reperfusion (I/R) injury through the NPRB/cGMP signaling pathway. Rat cardiomyocytes were assigned into: control, I/R, I/R + CNP, and I/R + 8-Br-cGMP groups. ELISA, qRT-PCR, and Western blotting were used to detect cGMP content and expression, respectively. After model establishment of I/R rats, normal control, CNP -/- control, I/R, and CNP -/- groups were set. Indexes of heart were detected using echocardiography and hemodynamics. ELISA was used to measure serum CNP, cGMP, LDH, cTn I, CK-MB, TNF-α, and IL-6 levels. Myocardial infarct was identified by TTC staining, and apoptosis conditions by TUNEL staining. QRT-PCR and Western blotting were adopted to detect expressions of CNP, NPRB, cGMP, and apoptosis-related genes. Compared with control group, cGMP contents and expression in the I/R, I/R + CNP and I/R + 8-Br-cGMP groups were decreased. Levels of LVEDV, LVESV, LVDS, LVDD, IVSD, LVM, LVEDP, and LVSP were higher in the I/R, CNP -/- control, and CNP -/- groups than normal control group while LVEF, SV, CO, and ±dp/dtmax were lower. Compared with the normal control group, LDH, cTn I, CK-MB, TNF-α, and IL-6 were higher in the I/R, CNP -/- control and CNP -/- groups; pathological changes and myocardial infarction were observed in the I/R, CNP -/- control, and CNP -/- groups; expressions of apoptosis-related genes in those groups were higher; while CNP, NPRB, cGMP, and Bcl-2 expressions were decreased. We came to the conclusion that gene knockdown of CNP blocks the NPRB/cGMP signaling pathway, thereby aggravating myocardial I/R injury and causing ventricular remodeling in rats. © 2017 Wiley Periodicals, Inc.

  6. Influence of naturally occurring dissolved organic matter, colloids, and cations on nanofiltration of pharmaceutically active and endocrine disrupting compounds.

    PubMed

    Sadmani, A H M Anwar; Andrews, Robert C; Bagley, David M

    2014-12-01

    This study examined the rejection of selected pharmaceutically active (PhAC) and endocrine disrupting compounds (EDCs) when using nanofiltration as a function of naturally occurring dissolved organic matter (DOM), colloidal particles, cations and their interactions. Lake Ontario water served as a source of natural DOM and colloidal particles. PhAC/EDC rejection experiments were conducted using raw Lake Ontario water and Lake Ontario water that was pre-treated with either ultrafiltration to remove colloidal particles, or fluidized ion exchange resins to remove DOM. Additionally, the concentration of cations (Ca(2+), Mg(2+), and Na(+)) in the raw and pre-treated water matrices was varied. While ionic PhACs and EDCs exhibited high rejections from all the water matrices examined, neutral compounds were most effectively rejected in water containing DOM and no colloids, and least effectively rejected from colloid-containing water with increased cations but no DOM. The presence of DOM significantly improved compound rejection and the increase in cation concentration significantly decreased rejection. The presence of colloids had comparatively little effect except to mitigate the impact of increased cation concentration, apparently providing some cation-buffering capacity. The sequence in which constituents are removed from waters during treatment may significantly impact PhAC and EDC removal, especially of neutral compounds. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Thermodynamics and Cation Diffusion in the Oxygen Ion Conductor Lsgm

    NASA Astrophysics Data System (ADS)

    Martin, M.; Schulz, O.

    Perovskite type oxides based on LaGaO3 are of large technical interest because of their high oxygen-ion conductivity. Lanthanum gallate doped with Sr on A- and Mg on B-sites, La1-xSrxGa1-yMgyO3-(x+y)/2 (LSGM), reaches higher oxygen-ion conductivities than yttria-doped zirconia (YSZ). Thus LSGM represents a promising alternative for YSZ as electrolyte in solid oxide fuel cells (SOFC). Cells using thin LSGM-layers as electrolyte are expected to operate at intermediate temperatures around 700°C for more than 30000 hours without severe degradation. A potential long term degradation effect of LSGM is kinetic demixing of the electrolyte, caused by different cation diffusion coefficients. In this paper we report on experimental studies concerning the phase diagram of LSGM and the diffusion of cations. Cation self-diffusion of 139La, 84Sr and 25Mg and cation impurity diffusion of 144Nd, 89Y and 56Fe in polycrystalline LSGM samples was investigated by secondary ion mass spectrometry (SIMS) for temperatures between 900°C and 1400°C. It was found that diffusion occurs by means of bulk and grain boundaries. The bulk diffusion coefficients are similar for all cations with activation energies which are strongly dependent on temperature. At high temperatures, the activation energies are about 5 eV, while at low temperatures values of about 2 eV are found. These results are explained by a frozen in defect structure at low temperatures. This means that the observed activation energy at low temperatures represents only the migration energy of the different cations while the observed activation energy at high temperatures is the sum of the defect formation energy and the migration energy. The migration energies for all cations are nearly identical, although 139La, 84Sr and 144Nd are occupying A-sites while 25Mg and 56Fe are occupying B-sites in the perovskite-structure. To explain these experimental findings we propose a defect cluster containing cation vacancies in both the A

  8. Nitric oxide attenuates matrix metalloproteinase-9 production by endothelial cells independent of cGMP- or NFκB-mediated mechanisms.

    PubMed

    Meschiari, Cesar A; Izidoro-Toledo, Tatiane; Gerlach, Raquel F; Tanus-Santos, Jose E

    2013-06-01

    Cardiovascular diseases involve critical mechanisms including impaired nitric oxide (NO) levels and abnormal matrix metalloproteinase (MMP) activity. While NO downregulates MMP expression in some cell types, no previous study has examined whether NO downregulates MMP levels in endothelial cells. We hypothesized that NO donors could attenuate MMP-9 production by human umbilical vein endothelial cells (HUVECs) as a result of less NFκB activation or cyclic GMP (cGMP)-mediated mechanisms. We studied the effects of DetaNONOate (10-400 μM) or SNAP (50-400 μM) on phorbol 12-myristate 13-acetate (PMA; 10 nM)-induced increases in MMP-9 activity (by gel zymography) or concentrations (by ELISA) as well as on a tissue inhibitor of MMPs' (TIMP)-1 concentrations (by ELISA) in the conditioned medium of HUVECs incubated for 24 h with these drugs. We also examined whether the irreversible inhibitor of soluble guanylyl cyclase ODQ modified the effects of SNAP or whether 8-bromo-cGMP (a cell-permeable analog of cGMP) influenced PMA-induced effects on MMP-9 expression. Total and phospho-NFκB p65 concentrations were measured in HUVEC lysates to assess NFκB activation. Both NO donors attenuated PMA-induced increases in MMP-9 activity and concentrations without significantly affecting TIMP-1 concentrations. This effect was not modified by ODQ, and 8-bromo-cGMP did not affect MMP-9 concentrations. While PMA increased phospho-NFκB p65 concentrations, SNAP had no influence on this effect. In conclusion, this study shows that NO donors may attenuate imbalanced MMP expression and activity in endothelial cells independent of cGMP- or NFκB-mediated mechanisms. Our results may offer an important pharmacological strategy to approach cardiovascular diseases.

  9. Pharmacology of the human red cell voltage-dependent cation channel; Part I. Activation by clotrimazole and analogues.

    PubMed

    Barksmann, Trine L; Kristensen, Berit I; Christophersen, Palle; Bennekou, Poul

    2004-01-01

    The activation and pharmacological modulation of the nonselective voltage-dependent cation (NSVDC) channel from human erythrocytes were studied. Basic channel activation was achieved by suspending red cells in a low Cl(-) Ringer (2 mM), where a positive membrane potential (V(m) = E(Cl)) immediately developed. Voltage- and time-dependent activation of the NSVDC channel occurred, reaching a cation conductance (g+) of 1.5-2.0 microS cm(-2). In the presence of the classical Gárdos channel blocker clotrimazole (0-50 microM), activation occurred faster, and g+ saturated dose-dependently (EC50 = 14 microM) at a value of about 4 microS cm(-2). The clotrimazole analogues TRAM-34, econazole, and miconazole also stimulated the channel, whereas the chemically more distant Gárdos channel inhibitors nitrendipine and cetiedil had no effects. Although the potency for modulation of the NSVDC channel is much lower than the IC50 value for Gárdos channel inhibition, clotrimazole (and its analogues) constitutes the first chemical class of positive modulators of the NSVDC channel. This may be an important pharmacological "fingerprint" in the identification of the cloned equivalent of the erythrocyte channel.

  10. Identification of loop D domain amino acids in the human Aquaporin-1 channel involved in activation of the ionic conductance and inhibition by AqB011

    NASA Astrophysics Data System (ADS)

    Kourghi, Mohamad; De Ieso, Michael L.; Nourmohammadi, Saeed; Pei, Jinxin V.; Yool, Andrea J.

    2018-04-01

    Aquaporins are integral proteins that facilitate the transmembrane transport of water and small solutes. In addition to enabling water flux, mammalian Aquaporin-1 (AQP1) channels activated by cyclic GMP can carry non-selective monovalent cation currents, selectively blocked by arylsulfonamide compounds AqB007 (IC50 170 µM) and AqB011 (IC50 14 µM). In silico models suggested that ligand docking might involve the cytoplasmic loop D (between AQP1 transmembrane domains 4 and 5), but the predicted site of interaction remained to be tested. Work here shows that mutagenesis of two conserved arginine residues in loop D slowed the activation of the AQP1 ion conductance and impaired the sensitivity of the channel to block by AqB011. Substitution of residues in loop D with proline showed effects on ion conductance amplitude that varied with position, suggesting that the structural conformation of loop D is important for AQP1 channel gating. Human AQP1 wild type, AQP1 mutant channels with alanines substituted for two arginines (R159A+R160A), and mutants with proline substituted for single residues threonine (T157P), aspartate (D158P), arginine (R159P, R160P) or glycine (G165P) were expressed in Xenopus laevis oocytes. Conductance responses were analyzed by two-electrode voltage clamp. Optical osmotic swelling assays and confocal microscopy were used to confirm mutant and wild type AQP1-expressing oocytes were expressed in the plasma membrane. After application of membrane-permeable cGMP, R159A+R160A channels had a significantly slower rate of activation as compared with wild type, consistent with impaired gating. AQP1 R159A+R160A channels showed no significant block by AqB011 at 50 µM, in contrast to the wild type channel which was blocked effectively. T157P, D158P and R160P mutations had impaired activation compared to wild type; R159P showed no significant effect; and G165P appeared to augment the conductance amplitude. These findings provide evidence for the role of the

  11. Development and validation of an LC-MS/MS method for quantification of cyclic guanosine 3',5'-monophosphate (cGMP) in clinical applications: a comparison with a EIA method.

    PubMed

    Zhang, Yanhua; Dufield, Dawn; Klover, Jon; Li, Wenlin; Szekely-Klepser, Gabriella; Lepsy, Christopher; Sadagopan, Nalini

    2009-02-15

    An LC-MS/MS method was developed and validated to quantify endogenous cyclic guanosine 3',5'-monophosphate (cGMP) in human plasma. The LC-MS/MS and competitive enzyme immunoassay (EIA) assays were compared. cGMP concentrations of 20 human plasma samples were measured by both methods. For the MS-based assay, plasma samples were subjected to a simple protein precipitation procedure by acetonitrile prior to analysis by electrospray ionization LC-MS/MS. De-protonated analytes generated in negative ionization mode were monitored through multiple reaction monitoring (MRM). A stable isotope-labeled internal standard, (13)C(10),(15)N(5)-cGMP, which was biosynthesized in-house, was used in the LC-MS/MS method. The competitive EIA was validated using a commercially available cGMP fluorescence assay kit. The intra-assay accuracy and precision for MS-based assay for cGMP were 6-10.1% CV and -3.6% to 7.3% relative error (RE), respectively, while inter-assay precision and accuracy were 5.6-8.1% CV and -2.1% to 6.3% RE, respectively. The intra-assay accuracy and precision for EIA were 17.9-27.1% CV and -4.9% to 24.5% RE, respectively, while inter-assay precision and accuracy were 15.1-39.5% CV and -30.8% to 4.37% RE, respectively. Near the lower limits of detection, there was little correlation between the cGMP concentration values in human plasma generated by these two methods (R(2)=0.197, P=0.05). Overall, the MS-based assay offered better selectivity, recovery, precision and accuracy over a linear range of 0.5-20ng/mL. The LC-MS/MS method provides an effective tool for the quantitation of cGMP to support clinical mechanistic studies of curative pharmaceuticals.

  12. Selective Antimicrobial Activities and Action Mechanism of Micelles Self-Assembled by Cationic Oligomeric Surfactants.

    PubMed

    Zhou, Chengcheng; Wang, Fengyan; Chen, Hui; Li, Meng; Qiao, Fulin; Liu, Zhang; Hou, Yanbo; Wu, Chunxian; Fan, Yaxun; Liu, Libing; Wang, Shu; Wang, Yilin

    2016-02-17

    This work reports that cationic micelles formed by cationic trimeric, tetrameric, and hexameric surfactants bearing amide moieties in spacers can efficiently kill Gram-negative E. coli with a very low minimum inhibitory concentration (1.70-0.93 μM), and do not cause obvious toxicity to mammalian cells at the concentrations used. With the increase of the oligomerization degree, the antibacterial activity of the oligomeric surfactants increases, i.e., hexameric surfactant > tetrameric surfactant > trimeric surfactant. Isothermal titration microcalorimetry, scanning electron microscopy, and zeta potential results reveal that the cationic micelles interact with the cell membrane of E. coli through two processes. First, the integrity of outer membrane of E. coli is disrupted by the electrostatic interaction of the cationic ammonium groups of the surfactants with anionic groups of E. coli, resulting in loss of the barrier function of the outer membrane. The inner membrane then is disintegrated by the hydrophobic interaction of the surfactant hydrocarbon chains with the hydrophobic domains of the inner membrane, leading to the cytoplast leakage. The formation of micelles of these cationic oligomeric surfactants at very low concentration enables more efficient interaction with bacterial cell membrane, which endows the oligomeric surfactants with high antibacterial activity.

  13. Cationic peptides from peptic hydrolysates of rice endosperm protein exhibit antimicrobial, LPS-neutralizing, and angiogenic activities.

    PubMed

    Taniguchi, Masayuki; Kawabe, Junya; Toyoda, Ryu; Namae, Toshiki; Ochiai, Akihito; Saitoh, Eiichi; Tanaka, Takaaki

    2017-11-01

    In this study, we hydrolyzed rice endosperm protein (REP) with pepsin and generated 20 fractions containing multifunctional cationic peptides with varying isoelectric point (pI) values using ampholyte-free isoelectric focusing (autofocusing). Subsequently, we determined antimicrobial activities of each fraction against the pathogens Prophyromonas gingivalis, Propionibacterium acnes, Streptocossus mutans, and Candida albicans. Fractions 18, 19, and 20 had pI values greater than 12 and exhibited antimicrobial activity against P. gingivalis, P. acnes, and C. albicans, but not against S. mutans. In further experiments, we purified and identified cationic peptides from fractions 18, 19, and 20 using reversed-phase high-performance liquid chromatography and matrix-assisted laser/desorption ionization-time-of-flight mass spectroscopy. We also chemically synthesized five identified peptides (RSVSKSR, RRVIEPR, ERFQPMFRRPG, RVRQNIDNPNRADTYNPRAG, and VVRRVIEPRGLL) with pI values greater than 10.5 and evaluated antimicrobial, lipopolysaccharide (LPS)-neutralizing, and angiogenic activities. Among these synthetic peptides, only VVRRVIEPRGLL exhibited antimicrobial activity against P. gingivalis, with an IC 50 value of 87μM. However, all five cationic peptides exhibited LPS-neutralizing and angiogenic activities with little or no hemolytic activity against mammalian red blood cells at functional concentrations. These present data show dual or multiple functions of the five identified cationic peptides with little or no hemolytic activity. Therefore, fractions containing cationic peptides from REP hydrolysates have the potential to be used as dietary supplements and functional ingredients in food products. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Non-Cationic Proteins Are Associated with HIV Neutralizing Activity in Genital Secretions of Female Sex Workers.

    PubMed

    Birse, Kenzie D M; Cole, Amy L; Hirbod, Taha; McKinnon, Lyle; Ball, Terry B; Westmacott, Garrett R; Kimani, Joshua; Plummer, Frank; Cole, Alexander M; Burgener, Adam; Broliden, Kristina

    2015-01-01

    Cationic proteins found in cervicovaginal secretions (CVS) are known to contribute to the early antiviral immune response against HIV-infection in vitro. We here aimed to define additional antiviral factors that are over-expressed in CVS from female sex workers at high risk of infection. CVS were collected from Kenyan HIV-seronegative (n = 34) and HIV-seropositive (n = 12) female sex workers, and were compared with those from HIV-seronegative low-risk women (n = 12). The highly exposed seronegative (HESN) sex workers were further divided into those with less (n = 22) or more (n = 12) than three years of documented sex work. Cationic protein-depleted CVS were assessed for HIV-neutralizing activity by a PBMC-based HIV-neutralizing assay, and then characterized by proteomics. HIV neutralizing activity was detected in all unprocessed CVS, however only CVS from the female sex worker groups maintained its HIV neutralizing activity after cationic protein-depletion. Differentially abundant proteins were identified in the cationic protein-depleted secretions including 26, 42, and 11 in the HESN>3 yr, HESN<3 yr, and HIV-positive groups, respectively. Gene ontology placed these proteins into functional categories including proteolysis, oxidation-reduction, and epidermal development. The proteins identified in this study include proteins previously associated with the HESN phenotype in other cohorts as well as novel proteins not yet associated with anti-HIV activities. While cationic proteins appear to contribute to the majority of the intrinsic HIV neutralizing activity in the CVS of low-risk women, a broader range of non-cationic proteins were associated with HIV neutralizing activity in HESN and HIV-positive female sex workers. These results indicate that novel protein factors found in CVS of women with high-risk sexual practices may have inherent antiviral activity, or are involved in other aspects of anti-HIV host defense, and warrant further exploration into their mode

  15. Non-Surface Activity of Cationic Amphiphilic Diblock Copolymers

    NASA Astrophysics Data System (ADS)

    Ranjan Nayak, Rati; Yamada, Tasuku; Matsuoka, Hideki

    2011-09-01

    Cationic amphiphilic diblock copolymers containing quaternized poly (2-vinylpyridine) chain as a hydrophilic segment (PIp-b-PNMe2VP) were synthesized by living anionic polymerization. By IR measurement, we confirmed the quaternization of the polymer (PIp-b-PNMe2VP), and determined the degree of quaternization by conductometric titration. The surface tension experiment showed that the polymers are non-surface active in nature. The foam formation of the polymer solutions was also investigated with or without added salt. Almost no foam formation behavior was observed without added salt, while a little foam was observed in the presence of 1M NaCl. The critical micelle concentration (cmc) of the diblock copolymers with 3 different chain lengths was measured by the static light scattering method. The cmc values obtained in this study were much lower than the values obtained for anionic non-surface active diblock polymers studied previously. The hydrodynamic radii of the polymer micelle increased slightly in the presence of 1 M NaCl. The transmission electron microscopic images revealed spherical micelles in pure water. In the presence of salt, the cmc values increased as was the case for anionic polymers, which is unlike conventional surfactant systems but consistent with non-surface active anionic block copolymers. The microviscosity of the micelle core was evaluated using Coumarin-153 as a fluorescent anisotropy probe using steady-sate fluorescence depolarization. Non-surface activity has been proved to be universal for ionic amphiphilic block copolymers both for anionic and cationic. Hence, the origin of non-surface activity is not the charged state of water surface itself, but should be an image charge repulsion at the air/water interface.

  16. Effects of Kaempferia parviflora Wall. Ex. Baker and sildenafil citrate on cGMP level, cardiac function, and intracellular Ca2+ regulation in rat hearts.

    PubMed

    Weerateerangkul, Punate; Palee, Siripong; Chinda, Kroekkiat; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2012-09-01

    Although Kaempferia parviflora extract (KPE) and its flavonoids have positive effects on the nitric oxide (NO) signaling pathway, its mechanisms on the heart are still unclear. Because our previous studies demonstrated that KPE decreased defibrillation efficacy in swine similar to that of sildenafil citrate, the phosphodiesterase-5 inhibitor, it is possible that KPE may affect the cardiac NO signaling pathway. In the present study, the effects of KPE and sildenafil citrate on cyclic guanosine monophosphate (cGMP) level, modulation of cardiac function, and Ca transients in ventricular myocytes were investigated. In a rat model, cardiac cGMP level, cardiac function, and Ca transients were measured before and after treatment with KPE and sildenafil citrate. KPE significantly increased the cGMP level and decreased cardiac function and Ca transient. These effects were similar to those found in the sildenafil citrate-treated group. Furthermore, the nonspecific NOS inhibitor could abolish the effects of KPE and sildenafil citrate on Ca transient. KPE has positive effect on NO signaling in the heart, resulting in an increased cGMP level, similar to that of sildenafil citrate. This effect was found to influence the physiology of normal heart via the attenuation of cardiac function and the reduction of Ca transient in ventricular myocytes.

  17. Potentiation of cGMP signaling increases oxygen delivery and oxidative metabolism in contracting skeletal muscle of older but not young humans

    PubMed Central

    Nyberg, Michael; Piil, Peter; Egelund, Jon; Sprague, Randy S; Mortensen, Stefan P; Hellsten, Ylva

    2015-01-01

    Aging is associated with progressive loss of cardiovascular and skeletal muscle function. The impairment in physical capacity with advancing age could be related to an insufficient peripheral O2 delivery to the exercising muscles. Furthermore, the mechanisms underlying an impaired blood flow regulation remain unresolved. Cyclic guanosine monophosphate (cGMP) is one of the main second messengers that mediate smooth muscle vasodilation and alterations in cGMP signaling could, therefore, be one mechanism by which skeletal muscle perfusion is impaired with advancing age. The current study aimed to evaluate the effect of inhibiting the main enzyme involved in cGMP degradation, phosphodiesterase 5 (PDE5), on blood flow and O2 delivery in contracting skeletal muscle of young and older humans. A group of young (23 ± 1 years) and a group of older (72 ± 2 years) male human subjects performed submaximal knee-extensor exercise in a control setting and following intake of the highly selective PDE5 inhibitor sildenafil. Sildenafil increased leg O2 delivery (6–9%) and leg O2 uptake (10–12%) at all three exercise intensities in older but not young subjects. The increase in leg O2 delivery with sildenafil in the older subjects correlated with the increase in leg O2 uptake (r2 = 0.843). These findings suggest an insufficient O2 delivery to the contracting skeletal muscle of aged individuals and that reduced cGMP availability is a novel mechanism underlying impaired skeletal muscle perfusion with advancing age. PMID:26272735

  18. Charge Shielding of PIP2 by Cations Regulates Enzyme Activity of Phospholipase C

    PubMed Central

    Seo, Jong Bae; Jung, Seung-Ryoung; Huang, Weigang; Zhang, Qisheng; Koh, Duk-Su

    2015-01-01

    Hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) of the plasma membrane by phospholipase C (PLC) generates two critical second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. For the enzymatic reaction, PIP2 binds to positively charged amino acids in the pleckstrin homology domain of PLC. Here we tested the hypothesis that positively charged divalent and multivalent cations accumulate around the negatively charged PIP2, a process called electrostatic charge shielding, and therefore inhibit electrostatic PIP2-PLC interaction. This charge shielding of PIP2 was measured quantitatively with an in vitro enzyme assay using WH-15, a PIP2 analog, and various recombinant PLC proteins (β1, γ1, and δ1). Reduction of PLC activity by divalent cations, polyamines, and neomycin was well described by a theoretical model considering accumulation of cations around PIP2 via their electrostatic interaction and chemical binding. Finally, the charge shielding of PIP2 was also observed in live cells. Perfusion of the cations into cells via patch clamp pipette reduced PIP2 hydrolysis by PLC as triggered by M1 muscarinic receptors with a potency order of Mg2+ < spermine4+ < neomycin6+. Accumulation of divalent cations into cells through divalent-permeable TRPM7 channel had the same effect. Altogether our results suggest that Mg2+ and polyamines modulate the activity of PLCs by controlling the amount of free PIP2 available for the enzymes and that highly charged biomolecules can be inactivated by counterions electrostatically. PMID:26658739

  19. Charge Shielding of PIP2 by Cations Regulates Enzyme Activity of Phospholipase C.

    PubMed

    Seo, Jong Bae; Jung, Seung-Ryoung; Huang, Weigang; Zhang, Qisheng; Koh, Duk-Su

    2015-01-01

    Hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) of the plasma membrane by phospholipase C (PLC) generates two critical second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. For the enzymatic reaction, PIP2 binds to positively charged amino acids in the pleckstrin homology domain of PLC. Here we tested the hypothesis that positively charged divalent and multivalent cations accumulate around the negatively charged PIP2, a process called electrostatic charge shielding, and therefore inhibit electrostatic PIP2-PLC interaction. This charge shielding of PIP2 was measured quantitatively with an in vitro enzyme assay using WH-15, a PIP2 analog, and various recombinant PLC proteins (β1, γ1, and δ1). Reduction of PLC activity by divalent cations, polyamines, and neomycin was well described by a theoretical model considering accumulation of cations around PIP2 via their electrostatic interaction and chemical binding. Finally, the charge shielding of PIP2 was also observed in live cells. Perfusion of the cations into cells via patch clamp pipette reduced PIP2 hydrolysis by PLC as triggered by M1 muscarinic receptors with a potency order of Mg2+ < spermine4+ < neomycin6+. Accumulation of divalent cations into cells through divalent-permeable TRPM7 channel had the same effect. Altogether our results suggest that Mg2+ and polyamines modulate the activity of PLCs by controlling the amount of free PIP2 available for the enzymes and that highly charged biomolecules can be inactivated by counterions electrostatically.

  20. Improvement of ion chromatography with ultraviolet photometric detection and comparison with conductivity detection for the determination of serum cations.

    PubMed

    Shintani, H

    1985-05-31

    Studies were made of the analytical conditions required for indirect photometric ion chromatography using ultraviolet photometric detection (UV method) for the determination of serum cations following a previously developed serum pre-treatment. The sensitivities of the conductivity detection (CD) and UV methods and the amounts of serum cations determined by both methods were compared. Attempts to improve the sensitivity of the conventional UV method are reported. It was found that the mobile phase previously reported by Small and Miller showed no quantitative response when more than 4 mM copper(II) sulphate pentahydrate was used. As a result, there was no significant difference in the amounts of serum cations shown by the CD and UV methods. However, by adding 0.5-5 mM cobalt(II) sulphate heptahydrate, nickel(II) sulphate hexahydrate, zinc(II) sulphate heptahydrate or cobalt(II) diammonium sulphate hexahydrate to 0.5-1.5 mM copper(II) sulphate pentahydrate, higher sensitivity and a quantitative response were attained.

  1. Activation of particulate guanylate cyclase by adrenomedullin in cultured SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells.

    PubMed

    Ali, N; Yousufzai, S Y; Abdel-Latif, A A

    2000-07-01

    We investigated the effects of adrenomedullin (ADM) on cGMP production in cultured SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells. ADM increased cGMP accumulation in a time- and concentration- dependent manner. The peptide increased cGMP formation in the transformed cells by 405-fold as compared to 1. 6-fold in primary cultured CISM cells. The basal cGMP concentrations in both cell types were comparable. In addition, ADM increased cAMP accumulation in SV-CISM-2 cells and in primary cultured cells by 18. 9- and 5.8-fold, respectively. The ADM receptor antagonist, ADM(26-52), but not the atrial natriuretic peptide (ANP) receptor antagonist, anantin, inhibited ADM-induced cGMP formation. The phorbol ester, phorbol 12, 13-dibutyrate (PDBu), which inhibits particulate guanylate cyclases in smooth muscle, blocked ADM-stimulated cGMP accumulation. In contrast, inhibitors of the soluble guanylate cyclases, such as LY83583 and ODQ, and inhibitors of the nitric oxide cascade had little effect on ADM-stimulated cGMP production. The stimulatory effect of ADM on cGMP formation is due to activation of the guanylate cyclase system and not to a much reduced phosphodiesterase activity. ADM stimulated guanylate cyclase activity in membrane fractions isolated from SV-CISM-2 cells in a concentration-dependent manner with EC(50) value of 72 nM. Pertussis toxin, an activator of the G-protein, Gi, inhibited ADM-stimulated cGMP accumulation, whereas cholera toxin, a stimulator of the Gs G-protein and subsequently cAMP accumulation, had little effect. Pretreatment of the plasma membrane fraction with Gialpha antibody attenuated ADM-stimulated guanylate cyclase activity by 75%. We conclude that ADM increases intracellular cGMP levels in SV-CISM-2 cells through activation of the ADM receptor and subsequent stimulation of a Gi-mediated membrane-bound guanylate cyclase.

  2. Synthetic cation-selective nanotube: permeant cations chaperoned by anions.

    PubMed

    Hilder, Tamsyn A; Gordon, Dan; Chung, Shin-Ho

    2011-01-28

    The ability to design ion-selective, synthetic nanotubes which mimic biological ion channels may have significant implications for the future treatment of bacteria, diseases, and as ultrasensitive biosensors. We present the design of a synthetic nanotube made from carbon atoms that selectively allows monovalent cations to move across and rejects all anions. The cation-selective nanotube mimics some of the salient properties of biological ion channels. Before practical nanodevices are successfully fabricated it is vital that proof-of-concept computational studies are performed. With this in mind we use molecular and stochastic dynamics simulations to characterize the dynamics of ion permeation across a single-walled (10, 10), 36 Å long, carbon nanotube terminated with carboxylic acid with an effective radius of 5.08 Å. Although cations encounter a high energy barrier of 7 kT, its height is drastically reduced by a chloride ion in the nanotube. The presence of a chloride ion near the pore entrance thus enables a cation to enter the pore and, once in the pore, it is chaperoned by the resident counterion across the narrow pore. The moment the chaperoned cation transits the pore, the counterion moves back to the entrance to ferry another ion. The synthetic nanotube has a high sodium conductance of 124 pS and shows linear current-voltage and current-concentration profiles. The cation-anion selectivity ratio ranges from 8 to 25, depending on the ionic concentrations in the reservoirs.

  3. Effects of cations on Helicobacter pylori urease activity, release, and stability.

    PubMed Central

    Pérez-Pérez, G I; Gower, C B; Blaser, M J

    1994-01-01

    The urease of Helicobacter pylori is an important antigen and appears critical for colonization and virulence. Several studies have indicated a superficial localization for the H. pylori urease, and the purpose of this study was to determine the effects of cations on the release and stability of urease activity from H. pylori cells. Incubation of partially purified H. pylori urease in water containing 1, 5, or 10 mM Ca2+, Mg2+, K+, Na+, EDTA, or EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] had little effect on activity. In contrast, 1 mM Fe3+, Cu2+, Co2+, or Zn2+ substantially (> 80%) inhibited activity, and 10 mM Fe2+, Mn2+, and Ni2+ inhibited about 30% of the activity. Addition of Ca2+ or Mg2+ markedly decreased extraction of urease from intact H. pylori cells by water, but 1 mM Na+, K+, EGTA, or EDTA each had minimal effects on release, suggesting that divalent cations have a role in attachment of urease to H. pylori cells. The stability of enzymatic activity at 4 degrees C was enhanced by addition of glycerol or 2-mercaptoethanol; however, even after loss of activity, full antigenicity for human serum was retained. PMID:8262643

  4. Double C-H activation of ethane by metal-free SO2*+ radical cations.

    PubMed

    de Petris, Giulia; Cartoni, Antonella; Troiani, Anna; Barone, Vincenzo; Cimino, Paola; Angelini, Giancarlo; Ursini, Ornella

    2010-06-01

    The room-temperature C-H activation of ethane by metal-free SO(2)(*+) radical cations has been investigated under different pressure regimes by mass spectrometric techniques. The major reaction channel is the conversion of ethane to ethylene accompanied by the formation of H(2)SO(2)(*+), the radical cation of sulfoxylic acid. The mechanism of the double C-H activation, in the absence of the single activation product HSO(2)(+), is elucidated by kinetic studies and quantum chemical calculations. Under near single-collision conditions the reaction occurs with rate constant k=1.0 x 10(-9) (+/-30%) cm(3) s(-1) molecule(-1), efficiency=90%, kinetic isotope effect k(H)/k(D)=1.1, and partial H/D scrambling. The theoretical analysis shows that the interaction of SO(2)(*+) with ethane through an oxygen atom directly leads to the C-H activation intermediate. The interaction through sulfur leads to an encounter complex that rapidly converts to the same intermediate. The double C-H activation occurs by a reaction path that lies below the reactants and involves intermediates separated by very low energy barriers, which include a complex of the ethyl cation suitable to undergo H/D scrambling. Key issues in the observed reactivity are electron-transfer processes, in which a crucial role is played by geometrical constraints. The work shows how mechanistic details disclosed by the reactions of metal-free electrophiles may contribute to the current understanding of the C-H activation of ethane.

  5. Biological and surface-active properties of double-chain cationic amino acid-based surfactants.

    PubMed

    Greber, Katarzyna E; Dawgul, Małgorzata; Kamysz, Wojciech; Sawicki, Wiesław; Łukasiak, Jerzy

    2014-08-01

    Cationic amino acid-based surfactants were synthesized via solid phase peptide synthesis and terminal acylation of their α and ε positions with saturated fatty acids. Five new lipopeptides, N-α-acyl-N-ε-acyl lysine analogues, were obtained. Minimum inhibitory concentration and minimum bactericidal (fungicidal) concentration were determined on reference strains of bacteria and fungi to evaluate the antimicrobial activity of the lipopeptides. Toxicity to eukaryotic cells was examined via determination of the haemolytic activities. The surface-active properties of these compounds were evaluated by measuring the surface tension and formation of micelles as a function of concentration in aqueous solution. The cationic surfactants demonstrated diverse antibacterial activities dependent on the length of the fatty acid chain. Gram-negative bacteria and fungi showed a higher resistance than Gram-positive bacterial strains. It was found that the haemolytic activities were also chain length-dependent values. The surface-active properties showed a linear correlation between the alkyl chain length and the critical micelle concentration.

  6. Preparation of metallic cation conducting polymers based on sterically hindered phenols containing polymeric systems

    DOEpatents

    Skotheim, Terje A.; Okamoto, Yoshiyuki; Lee, Hung S.

    1989-01-01

    The present invention relates to ion-conducting solvent-free polymeric systems characterized as being cationic single ion conductors. The solvent-free polymer electrolytes comprise a flexible polymer backbone to which is attached a metal salt, such as a lithium, sodium or potassium salt, of a sterically hindered phenol. The solid polymer electrolyte may be prepared either by (1) attaching the hindered phenol directly to a flexible polymeric backbone, followed by neutralization of the phenolic OH's or (2) reacting the hindered phenol with a polymer precursor which is then polymerized to form a flexible polymer having phenolic OH's which are subsequently neutralized. Preferably the hindered phenol-modified polymeric backbone contains a polyether segment. The ionic conductivity of these solvent-free polymer electrolytes has been measured to be in the range of 10.sup.-4 to 10.sup.-7 S cm.sup.-1 at room temperature.

  7. Preparation of metallic cation conducting polymers based on sterically hindered phenols containing polymeric systems

    DOEpatents

    Skotheim, T.A.; Okamoto, Yoshiyuki; Lee, H.S.

    1989-11-21

    The present invention relates to ion-conducting solvent-free polymeric systems characterized as being cationic single ion conductors. The solvent-free polymer electrolytes comprise a flexible polymer backbone to which is attached a metal salt, such as a lithium, sodium or potassium salt, of a sterically hindered phenol. The solid polymer electrolyte may be prepared either by (1) attaching the hindered phenol directly to a flexible polymeric backbone, followed by neutralization of the phenolic OH's or (2) reacting the hindered phenol with a polymer precursor which is then polymerized to form a flexible polymer having phenolic OH's which are subsequently neutralized. Preferably the hindered phenol-modified polymeric backbone contains a polyether segment. The ionic conductivity of these solvent-free polymer electrolytes has been measured to be in the range of 10[sup [minus]4] to 10[sup [minus]7] S cm[sup [minus]1] at room temperature.

  8. Ion transport with charge-protected and non-charge-protected cations using the compensated Arrhenius formalism. Part 2. Relationship between ionic conductivity and diffusion.

    PubMed

    Petrowsky, Matt; Fleshman, Allison; Bopege, Dharshani N; Frech, Roger

    2012-08-09

    Temperature-dependent ionic conductivities and cation/anion self-diffusion coefficients are measured for four electrolyte families: TbaTf-linear primary alcohols, LiTf-linear primary alcohols, TbaTf-n-alkyl acetates, and LiTf-n-alkyl acetates. The Nernst-Einstein equation does not adequately describe the data. Instead, the compensated Arrhenius formalism is applied to both conductivity and diffusion data. General trends based on temperature and alkyl chain length are observed when conductivity is plotted against cation or anion diffusion coefficient, but there is no clear pattern to the data. However, plotting conductivity exponential prefactors against those for diffusion results in four distinct curves, one each for the alcohol and acetate families described above. Furthermore, the TbaTf-alcohol and TbaTf-acetate data are "in line" with each other. The conductivity prefactors for the LiTf-alcohol data are smaller than those for the TbaTf data. The LiTf-acetate data have the lowest conductivity prefactors. This trend in prefactors mirrors the observed trend in degree of ionic association for these electrolytes.

  9. Non-Arrhenius ionic conductivities in glasses due to a distribution of activation energies.

    PubMed

    Bischoff, C; Schuller, K; Beckman, S P; Martin, S W

    2012-08-17

    Previously observed non-Arrhenius behavior in fast ion conducting glasses [J. Kincs and S. W. Martin, Phys. Rev. Lett. 76, 70 (1996)] occurs at temperatures near the glass transition temperature, T(g), and is attributed to changes in the ion mobility due to ion trapping mechanisms that diminish the conductivity and result in a decreasing conductivity with increasing temperature. It is intuitive that disorder in glass will also result in a distribution of the activation energies (DAE) for ion conduction, which should increase the conductivity with increasing temperature, yet this has not been identified in the literature. In this Letter, a series of high precision ionic conductivity measurements are reported for 0.5Na(2)S + 0.5[xGeS(2) + (1-x)PS(5/2)] glasses with compositions ranging from 0 ≤ x ≤ 1. The impact of the cation site disorder on the activation energy is identified and explained using a DAE model. The absence of the non-Arrhenius behavior in other glasses is explained and it is predicted which glasses are expected to accentuate the DAE effect on the ionic conductivity.

  10. Synthesis and biological activity of lipophilic analogs of the cationic antimicrobial active peptide anoplin.

    PubMed

    Chionis, Kostas; Krikorian, Dimitrios; Koukkou, Anna-Irini; Sakarellos-Daitsiotis, Maria; Panou-Pomonis, Eugenia

    2016-11-01

    Anoplin is a short natural cationic antimicrobial peptide which is derived from the venom sac of the solitary wasp, Anoplius samariensis. Due to its short sequence G 1 LLKR 5 IKT 8 LL-NH 2 , it is ideal for research tests. In this study, novel analogs of anoplin were prepared and examined for their antimicrobial, hemolytic activity, and proteolytic stability. Specific substitutions were introduced in amino acids Gly 1 , Arg 5 , and Thr 8 and lipophilic groups with different lengths in the N-terminus in order to investigate how these modifications affect their antimicrobial activity. These cationic analogs exhibited higher antimicrobial activity than the native peptide; they are also nontoxic at their minimum inhibitory concentration (MIC) values and resistant to enzymatic degradation. The substituted peptide GLLKF 5 IKK 8 LL-NH 2 exhibited high activity against Gram-negative bacterium Zymomonas mobilis (MIC = 7 µg/ml), and the insertion of octanoic, decanoic, and dodecanoic acid residues in its N-terminus increased the antimicrobial activity against Gram-positive and Gram-negative bacteria (MIC = 5 µg/ml). The conformational characteristics of the peptide analogs were studied by circular dichroism. Structure activity studies revealed that the substitution of specific amino acids and the incorporation of lipophilic groups enhanced the amphipathic α-helical conformation inducing better antimicrobial effects. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

  11. cGMP production of patient-specific iPSCs and photoreceptor precursor cells to treat retinal degenerative blindness

    PubMed Central

    Wiley, Luke A.; Burnight, Erin R.; DeLuca, Adam P.; Anfinson, Kristin R.; Cranston, Cathryn M.; Kaalberg, Emily E.; Penticoff, Jessica A.; Affatigato, Louisa M.; Mullins, Robert F.; Stone, Edwin M.; Tucker, Budd A.

    2016-01-01

    Immunologically-matched, induced pluripotent stem cell (iPSC)-derived photoreceptor precursor cells have the potential to restore vision to patients with retinal degenerative diseases like retinitis pigmentosa. The purpose of this study was to develop clinically-compatible methods for manufacturing photoreceptor precursor cells from adult skin in a non-profit cGMP environment. Biopsies were obtained from 35 adult patients with inherited retinal degeneration and fibroblast lines were established under ISO class 5 cGMP conditions. Patient-specific iPSCs were then generated, clonally expanded and validated. Post-mitotic photoreceptor precursor cells were generated using a stepwise cGMP-compliant 3D differentiation protocol. The recapitulation of the enhanced S-cone phenotype in retinal organoids generated from a patient with NR2E3 mutations demonstrated the fidelity of these protocols. Transplantation into immune compromised animals revealed no evidence of abnormal proliferation or tumor formation. These studies will enable clinical trials to test the safety and efficiency of patient-specific photoreceptor cell replacement in humans. PMID:27471043

  12. Thermally Activated Motion of Sodium Cations in Insulating Parent Low-Silica X Zeolite

    NASA Astrophysics Data System (ADS)

    Igarashi, Mutsuo; Jeglič, Peter; Mežnaršič, Tadej; Nakano, Takehito; Nozue, Yasuo; Watanabe, Naohiro; Arčon, Denis

    2017-07-01

    We report a 23Na spin-lattice relaxation rate, T1 - 1, in low-silica X zeolite. T1 - 1 follows multiple BPP-type behavior as a result of thermal motion of sodium cations in insulating material. The estimated lowest activation energy of 15 meV is much lower than 100 meV observed previously for sodium motion in heavily Na-loaded samples and is most likely attributed to short-distance jumps of sodium cations between sites within the same supercage.

  13. Non-selective cation channels in plasma and vacuolar membranes and their contribution to K+ transport.

    PubMed

    Pottosin, Igor; Dobrovinskaya, Oxana

    2014-05-15

    Both in vacuolar and plasma membranes, in addition to truly K(+)-selective channels there is a variety of non-selective channels, which conduct K(+) and other ions with little preference. Many non-selective channels in the plasma membrane are active at depolarized potentials, thus, contributing to K(+) efflux rather than to K(+) uptake. They may play important roles in xylem loading or contribute to a K(+) leak, induced by salt or oxidative stress. Here, three currents, expressed in root cells, are considered: voltage-insensitive cation current, non-selective outwardly rectifying current, and low-selective conductance, activated by reactive oxygen species. The latter two do not only poorly discriminate between different cations (like K(+)vs Na(+)), but also conduct anions. Such solute channels may mediate massive electroneutral transport of salts and might be involved in osmotic adjustment or volume decrease, associated with cell death. In the tonoplast two major currents are mediated by SV (slow) and FV (fast) vacuolar channels, respectively, which are virtually impermeable for anions. SV channels conduct mono- and divalent cations indiscriminately and are activated by high cytosolic Ca(2+) and depolarized voltages. FV channels are inhibited by micromolar cytosolic Ca(2+), Mg(2+), and polyamines, and conduct a variety of monovalent cations, including K(+). Strikingly, both SV and FV channels sense the K(+) content of vacuoles, which modulates their voltage dependence, and in case of SV, also alleviates channel's inhibition by luminal Ca(2+). Therefore, SV and FV channels may operate as K(+)-sensing valves, controlling K(+) distribution between the vacuole and the cytosol. Copyright © 2014 Elsevier GmbH. All rights reserved.

  14. Extraordinary Effects of Specific Monovalent Cations on Activation of Reovirus Transcriptase by Chymotrypsin In Vitro

    PubMed Central

    Borsa, J.; Sargent, M. D.; Long, D. G.; Chapman, J. D.

    1973-01-01

    Activation of reovirus transcriptase activity, latent in intact virions, by digestion of purified virions with chymotrypsin (CHT) in vitro shows a stringent requirement for specific monovalent cations. Cs+, Rb+, or K+ ions are capable of facilitating activation by chymotryptic digestion. Na+, Li+, or NH4+ ions are not capable of facilitating the CHT activation of polymerase activity and are antagonistic towards the effects of the facilitating ions. The data indicate that the effect of the cations is exerted on activation of the polymerase activity by CHT as opposed to an effect on polymerization per se. This effect may be important biologically in that it provides a mechanism whereby the virion can sense whether it is in an intracellular or an extracellular environment and thereby can avoid premature uncoating. PMID:4347424

  15. Extraordinary effects of specific monovalent cations on activation of reovirus transcriptase by chymotrypsin in vitro.

    PubMed

    Borsa, J; Sargent, M D; Long, D G; Chapman, J D

    1973-02-01

    Activation of reovirus transcriptase activity, latent in intact virions, by digestion of purified virions with chymotrypsin (CHT) in vitro shows a stringent requirement for specific monovalent cations. Cs(+), Rb(+), or K(+) ions are capable of facilitating activation by chymotryptic digestion. Na(+), Li(+), or NH(4) (+) ions are not capable of facilitating the CHT activation of polymerase activity and are antagonistic towards the effects of the facilitating ions. The data indicate that the effect of the cations is exerted on activation of the polymerase activity by CHT as opposed to an effect on polymerization per se. This effect may be important biologically in that it provides a mechanism whereby the virion can sense whether it is in an intracellular or an extracellular environment and thereby can avoid premature uncoating.

  16. Effect of alcaline cations in zeolites on their dielectric properties.

    PubMed

    Legras, Benoît; Polaert, Isabelle; Estel, Lionel; Thomas, Michel

    2012-01-01

    The effect on dielectric properties of alkaline cations Li+, Na+ and K+ incorporated in a zeolite Faujasite structure X or Y, has been investigated. Two major phenomena have been proved to occur: ionic conductivity and rotational polarization of the water molecules adsorbed. The polarizability of the cation which is directly linked to its radius, affects ionic conductivity as well as rotational polarization. Li cations are more strongly Linked to the framework than K+ and Na+ and induce a lower ionic conductivity. K+ is weakly fixed and induces a ionic conductivity even at low solvation level. At low water content, the cation nature and number mainly control the free rotation of the water molecules and affect the relaxation frequency. Close to saturation, the water molecules are mainly linked together by H bonds: the cation nature and number do not really affect the global dielectric properties anymore.

  17. Correlation between cation conduction and ionic morphology in a PEO-based single ion conductor

    NASA Astrophysics Data System (ADS)

    Lin, Kan-Ju; Maranas, Janna

    2011-03-01

    We use molecular dynamics simulation to study ion transport and backbone mobility of a PEO-based single ion conductor. Ion mobility depends on the chemical structure and the local environment of the ions, which consequently impact ionic conductivity. We characterize the aggregation state of the ions, and assess the role of ion complexes in ionomer dynamics. In addition to solvated cations and pairs, higher order ion clusters are found. Most of the ion clusters are in string-like structure and cross-link two or more different ionomer chains through ionic binding. Ionic crosslinks decrease mobility at the ionic co-monomer; hence the mobility of the adjacent PEO segment is influenced. Na ions show slow mobility when they are inside large clusters. The hopping timescale for Na varies from 20 ns to 200. A correlation is found between Na mobility and the number of hops from one coordination site to another. Besides ether oxygens, Na ions in the ionomer also use the anion and the edge of the cluster as hopping sites. The string-like structure of clusters provide less stable sites at the two ends thus ions are more mobile in those regions. We observed Grotthus like mechanism in our ionomer, in which the positive charge migrates within the string-like cluster without the cations actually moving.

  18. Nitric oxide synthesis leads to vascular endothelial growth factor synthesis via the NO/cyclic guanosine 3',5'-monophosphate (cGMP) pathway in human corpus cavernosal smooth muscle cells.

    PubMed

    Komori, Kazuhiko; Tsujimura, Akira; Takao, Tetsuya; Matsuoka, Yasuhiro; Miyagawa, Yasushi; Takada, Shingo; Nonomura, Norio; Okuyama, Akihiko

    2008-07-01

    Vascular smooth muscle cells express endothelial nitric oxide synthase (eNOS) and produce nitric oxide (NO). Recently, increased NO production has been reported to induce the synthesis and secretion of vascular endothelial growth factor (VEGF) via the NO/cyclic guanosine 3',5'-monophosphate (cGMP) pathway. L-arginine (L-arg), the precursor of NO, and selective phosphodiesterase type 5 (PDE-5) inhibitors that increase levels of intracellular cGMP may complementarily enhance VEGF synthesis in corpus cavernosal smooth muscle cells (CCSMCs), and may consequently restore impaired endothelial function. Expression of eNOS in corpus cavernosal smooth muscle has also been reported. However, it is unclear whether CCSMCs can generate NO. To elucidate whether CCSMCs can synthesize NO and whether NO synthesis enhances VEGF synthesis via the NO/cGMP pathway. Corpus cavernosal cells were cultured and characterized by immunocytochemistry and immunoblotting. CCSMCs were treated with L-arg. CCSMCs were also incubated with L-arg and with vardenafil, an inhibitor of PDE-5. Release of NO from cells was confirmed by assay of NO metabolites (NOx). Intracellular cGMP concentration and VEGF concentration in the medium were measured. Isolated cells were determined to be CCSMCs. The expression of eNOS by CCSMCs was also identified. NOx and cGMP levels in the L-arg-treated group were significantly greater than those in the control group. VEGF and cGMP levels in the L-arg-treated group were also significantly greater than those in the control group. VEGF and cGMP levels in the L-arg + vardenafil-treated group were significantly greater than those in the L-arg-treated group and the control group. CCSMCs express eNOS and synthesize NO. NO synthesis leads to enhancement of VEGF synthesis via the NO/cGMP pathway. Combined L-arg and vardenafil treatment, which can enhance VEGF production, may provide a novel therapeutic strategy for the treatment of erectile dysfunction as well as endothelial

  19. Adsorption of anionic and cationic dyes on activated carbon from aqueous solutions: equilibrium and kinetics.

    PubMed

    Rodríguez, Araceli; García, Juan; Ovejero, Gabriel; Mestanza, María

    2009-12-30

    Activated carbon was utilized as adsorbent to remove anionic dye, Orange II (OII), and cationic dye, Methylene blue (MB), from aqueous solutions by adsorption. Batch experiments were conducted to study the effects of temperature (30-65 degrees C), initial concentration of adsorbate (300-500 mg L(-1)) and pH (3.0-9.0) on dyes adsorption. Equilibrium adsorption isotherms and kinetics were investigated. The equilibrium experimental data were analyzed by the Langmuir, Freundlich, Toth and Redlich-Peterson models. The kinetic data obtained with different carbon mass were analyzed using a pseudo-first order, pseudo-second order, intraparticle diffusion, Bangham and Chien-Clayton equations. The best results were achieved with the Langmuir isotherm equilibrium model and with the pseudo-second order kinetic model. The activated carbon was found to be very effective as adsorbent for MB and OII from aqueous solutions.

  20. Cationic cell-penetrating peptide binds to planar lipid bilayers containing negatively charged lipids but does not induce conductive pores.

    PubMed

    Gurnev, Philip A; Yang, Sung-Tae; Melikov, Kamran C; Chernomordik, Leonid V; Bezrukov, Sergey M

    2013-05-07

    Using a cation-selective gramicidin A channel as a sensor of the membrane surface charge, we studied interactions of oligoarginine peptide R9C, a prototype cationic cell-penetrating peptide (CPP), with planar lipid membranes. We have found that R9C sorption to the membrane depends strongly on its lipid composition from virtually nonexistent for membranes made of uncharged lipids to very pronounced for membranes containing negatively charged lipids, with charge overcompensation at R9C concentrations exceeding 1 μM. The sorption was reversible as it was removed by addition of polyanionic dextran sulfate to the membrane bathing solution. No membrane poration activity of R9C (as would be manifested by increased bilayer conductance) was detected in the charged or neutral membranes, including those with asymmetric negative/neutral and negative/positive lipid leaflets. We conclude that interaction of R9C with planar lipid bilayers does not involve pore formation in all studied lipid combinations up to 20 μM peptide concentration. However, R9C induces leakage of negatively charged but not neutral liposomes in a process that involves lipid mixing between liposomes. Our findings suggest that direct traversing of CPPs through the uncharged outer leaflet of the plasma membrane bilayer is unlikely and that permeabilization necessarily involves both anionic lipids and CPP-dependent fusion between opposing membranes. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  1. The role of cGMP signalling in regulating life cycle progression of Plasmodium.

    PubMed

    Hopp, Christine S; Bowyer, Paul W; Baker, David A

    2012-08-01

    The 3'-5'-cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is the main mediator of cGMP signalling in the malaria parasite. This article reviews the role of PKG in Plasmodium falciparum during gametogenesis and blood stage schizont rupture, as well as the role of the Plasmodium berghei orthologue in ookinete differentiation and motility, and liver stage schizont development. The current views on potential effector proteins downstream of PKG and the mechanisms that may regulate cyclic nucleotide levels are presented. Copyright © 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  2. Promoter Effects of Alkali Metal Cations on the Electrochemical Reduction of Carbon Dioxide

    DOE PAGES

    Resasco, Joaquin; Chen, Leanne D.; Clark, Ezra; ...

    2017-07-24

    The electrochemical reduction of CO 2 is known to be influenced by the identity of the alkali metal cation in the electrolyte; however, a satisfactory explanation for this phenomenon has not been developed. Here we present the results of experimental and theoretical studies aimed at elucidating the effects of electrolyte cation size on the intrinsic activity and selectivity of metal catalysts for the reduction of CO 2. Experiments were conducted under conditions where the influence of electrolyte polarization is minimal in order to show that cation size affects the intrinsic rates of formation of certain reaction products, most notably formore » HCOO –, C 2H 4, and C 2H 5OH over Cu(100)- and Cu(111)-oriented thin films, and for CO and HCOO– over polycrystalline Ag and Sn. Interpretation of the findings for CO 2 reduction was informed by studies of the reduction of glyoxal and CO, key intermediates along the reaction pathway to final products. Density functional theory calculations show that the alkali metal cations influence the distribution of products formed as a consequence of electrostatic interactions between solvated cations present at the outer Helmholtz plane and adsorbed species having large dipole moments. As a result, the observed trends in activity with cation size are attributed to an increase in the concentration of cations at the outer Helmholtz plane with increasing cation size.« less

  3. Promoter Effects of Alkali Metal Cations on the Electrochemical Reduction of Carbon Dioxide

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Resasco, Joaquin; Chen, Leanne D.; Clark, Ezra

    The electrochemical reduction of CO 2 is known to be influenced by the identity of the alkali metal cation in the electrolyte; however, a satisfactory explanation for this phenomenon has not been developed. Here we present the results of experimental and theoretical studies aimed at elucidating the effects of electrolyte cation size on the intrinsic activity and selectivity of metal catalysts for the reduction of CO 2. Experiments were conducted under conditions where the influence of electrolyte polarization is minimal in order to show that cation size affects the intrinsic rates of formation of certain reaction products, most notably formore » HCOO –, C 2H 4, and C 2H 5OH over Cu(100)- and Cu(111)-oriented thin films, and for CO and HCOO– over polycrystalline Ag and Sn. Interpretation of the findings for CO 2 reduction was informed by studies of the reduction of glyoxal and CO, key intermediates along the reaction pathway to final products. Density functional theory calculations show that the alkali metal cations influence the distribution of products formed as a consequence of electrostatic interactions between solvated cations present at the outer Helmholtz plane and adsorbed species having large dipole moments. As a result, the observed trends in activity with cation size are attributed to an increase in the concentration of cations at the outer Helmholtz plane with increasing cation size.« less

  4. Cation and anion sequences in dark-adapted Balanus photoreceptor

    PubMed Central

    1977-01-01

    Anion and cation permeabilities in dark-adapted Balanus photoreceptors were determined by comparing changes in the membrane potential in response to replacement of the dominant anion (Cl-) or cation (Na+) by test anions or cations in the superfusing solution. The anion permeability sequence obtained was PI greater than PSO4 greater than PBr greater than PCl greater than Pisethionate greater than Pmethanesulfonate. Gluconate, glucuronate, and glutamate generally appeared more permeable and propionate less permeable than Cl-. The alkali-metal cation permeability sequence obtained was PK greater than PRb greater than PCx greater than PNa approximately PLi. This corresponds to Eisenman's IV which is the same sequencethat has been obtained for other classes of nerve cells in the resting state. The values obtained for the permeability ratios of the alkali-metal cations are considered to be minimal. The membrane conductance measured by passing inward current pulses in the different test cations followed the sequence, GK greater than GRb greater than GCs greater than GNa greater than GLi. The conductance ratios obtained for a full substitution of the test cation agreed quite well with permeability ratios for all the alkali-metal cations except K+ which was generally higher. PMID:199688

  5. The effects of forskolin and rolipram on cAMP, cGMP and free fatty acid levels in diet induced obesity.

    PubMed

    Doseyici, S; Mehmetoglu, I; Toker, A; Yerlikaya, F H; Erbay, E

    2014-07-01

    Obesity is a major health problem. We investigated the effects of forskolin and rolipram in the diet of animals in which obesity had been induced. We used 50 female albino Wistar rats that were assigned randomly into five groups as follows: group 1, control; group 2, high fat diet; group 3, high fat diet + forskolin; group 4, high fat diet + rolipram; and group 5, high fat diet + rolipram + forskolin. The rats were fed for 10 weeks and rolipram and forskolin were administered during last two weeks. The animals were sacrificed and blood samples were obtained. Serum cAMP, cGMP and free fatty acids (FFA) levels were measured using ELISA assays. We also measured weight gain during the 10 week period. cAMP and FFA levels of groups 3, 4 and 5 were significantly higher than those of groups 1 and 2. We found no significant differences in serum cGMP levels among the groups. The weight gain in groups 3, 4 and 5 was significantly less than for group 2. We also found that the weight gain in group 5 was significantly less than in groups 3 and 4. We found that both forskolin and rolipram stimulated lipolysis and inhibited body weight increase by increasing cAMP levels. Also, combination therapy using the two agents may be more effective in preventing diet induced obesity than either agent alone. We found also that these agents did not effect cellular cGMP levels in diet induced obesity.

  6. Influence of acidic eluent for retention behaviors of common anions and cations by ion-exclusion/cation-exchange chromatography on a weakly acidic cation-exchange resin in the H+ -form.

    PubMed

    Mori, Masanobu; Tanaka, Kazuhiko; Satori, Tatsuya; Ikedo, Mikaru; Hu, Wenzhi; Itabashi, Hideyuki

    2006-06-16

    Influence of acidic eluent on retention behaviors of common anions and cations by ion-exclusion/cation-exchange chromatography (ion-exclusion/CEC) were investigated on a weakly acidic cation-exchange resin in the H(+)-form with conductivity. Sensitivities of analyte ions, especially weak acid anions (F(-) and HCOO(-)), were affected with degree of background conductivity level with pK(a1) (first dissociation constant) of acid in eluent. The retention behaviors of anions and cations were related to that of elution dip induced after eluting acid to separation column and injecting analyte sample. These results were largely dependent on the natures of acid as eluent. Through this study, succinic acid as the eluent was suitable for simultaneous separation of strong acid anions (SO(4)(2-), Cl(-), NO(3)(-) and I(-)), weak acid anions (F(-), HCOO(-) and CH(3)COO(-)), and cations (Na(+), K(+), NH(4)(+), Mg(2+) and Ca(2+)). The separation was achieved in 20 min under the optimum eluent condition, 20 mM succinic acid/2 mM 18-crown-6. Detection limits at S/N=3 ranged from 0.10 to 0.51 microM for strong acid anions, 0.20 to 5.04 microM for weak acid anions and 0.75 to 1.72 microM for cations. The relative standard deviations of peak areas in the repeated chromatographic runs (n=10) were in the range of 1.1-2.9% for anions and 1.8-4.5% for cations. This method was successfully applied to hot spring water containing strong acid anions, weak acid anions and cations, with satisfactory results.

  7. Glyphosate sensitivity of 5-enol-pyruvylshikimate-3-phosphate synthase from Bacillus subtilis depends upon state of activation induced by monovalent cations.

    PubMed

    Fischer, R S; Rubin, J L; Gaines, C G; Jensen, R A

    1987-07-01

    The 5-enol-pyruvylshikimate-3-phosphate (EPSP) synthase from Bacillus subtilis was activated by monovalent cations, catalytic activity being negligible in the absence of monovalent cations. The order of cation effectiveness (NH4+ greater than K+ greater than Rb+ greater than Na+ = Cs+ = Li+) indicated that the extent of activation was directly related to the unhydrated cation radius. Ammonium salts, at physiological concentrations, were dramatically more effective than other cations. Activation by ammonium was instantaneous, was not influenced by the counter ion, and gave a hyperbolic saturation curve. Hill plots did not show detectable cooperativity in the binding of ammonium. Double-reciprocal plots indicated that ammonium increases the maximal velocity and decreases the apparent Michaelis constants of EPSP synthase with respect to both phosphoenol pyruvate (PEP) and shikimate 3-phosphate (S3P). A direct relationship between sensitivity to inhibition by glyphosate and the activation state of EPSP synthase was demonstrated. Hill plots indicated a single value for glyphosate binding throughout the range of ammonium activation. Double-reciprocal plots of substrate saturation data obtained with ammonium-activated enzyme in the presence of glyphosate showed glyphosate to behave as a competitive inhibitor with respect to PEP and as a mixed-type inhibitor relative to S3P. The increased glyphosate sensitivity of ammonium-activated EPSP synthase is attributed to a lowering of the inhibitor constant of glyphosate with respect to PEP. Erroneous underestimates of sensitivities of some bacterial EPSP synthases to inhibition by glyphosate may result from failure to recognize cation requirements of EPSP synthases.

  8. Determination of cyclic guanosine- and cyclic adenosine monophosphate (cGMP and cAMP) in human plasma and animal tissues by solid phase extraction on silica and liquid chromatography-triple quadrupole mass spectrometry.

    PubMed

    Van Damme, Thomas; Zhang, Yanhua; Lynen, Frédéric; Sandra, Pat

    2012-11-15

    3',5'-Cyclic guanosine monophosphate (cGMP) and 3',5'-cyclic adenosine monophosphate (cAMP) are essential second messenger molecules. They are involved in signal transduction within cells, in physiological functions such as neurotransmission and in the modulation of cell growth and differentiation of organisms, respectively. A quantitative solid phase extraction method (SPE) based on hydrophilic interaction on silica was developed and applied to both plasma and tissue samples. The stable isotope-labeled internal standards ²D₁, ¹⁵N₃-3',5'-cGMP and ¹³C₁₀, ¹⁵N₅-3',5'-cAMP were added prior to the sample preparation to ensure high precision and accuracy. The samples were analyzed by reversed-phase liquid chromatography (RP-LC). Negative electrospray (ESI)-MS/MS was used to selectively monitor several transitions of each metabolite. The method for the analysis of 3',5'-cAMP and 3',5'-cGMP in plasma was validated in the range of 0.15-20 ng/mL (R²=0.9996 and 0.9994 for 3',5'-cAMP and 3',5'-cGMP, respectively). Basal plasma concentrations for fifteen healthy human patients determined with this method varied between 4.66-9.20 ng/mL for 3',5'-cAMP and between 0.30-1.20 ng/mL for 3',5'-cGMP, with precisions better than 9.1%. 3',5'-cGMP and 3',5'-cAMP together with their 2',3'-isomers were also determined in a semi quantitative way in animal tissues. The structures of the isomers were confirmed by analysis with LC-high resolution time-of-flight MS and subsequently by comparison of retention times with standards. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Highly Active Electrolytes for Rechargeable Mg Batteries Based on [Mg2(μ-Cl)2]2+ Cation Complex in Dimethoxyethane

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cheng, Yingwen; Stolley, Ryan M.; Han, Kee Sung

    2015-01-01

    Highly active electrolytes based on a novel [Mg2(μ-Cl)2]2+ cation complex for reversible Mg deposition were developed and analyzed in this work. These electrolytes were formulated in dimethoxyethane through dehalodimerization of non-nucleophilic MgCl2 by reacting with either Mg salts (such as Mg(TFSI)2, TFSI= bis(trifluoromethane)sulfonylimide) or Lewis acid salts (such as AlEtCl2 or AlCl3). The cation complex was identified for the first time as [Mg2(μ-Cl)2(DME)4]2+ (DME=dimethoxyethane) and its molecular structure was characterized by single crystal X-ray diffraction, Raman spectroscopy and NMR. The electrolyte synthesis process was studied and rational approaches for formulating highly active electrolytes were proposed. Through control of the anions,more » electrolytes with efficiency close to 100%, wide electrochemical window (up to 3.5V) and high ionic conductivity (> 6 mS/cm) were obtained. The electrolyte synthesis and understandings developed in this work could bring significant opportunities for rational formulation of electrolytes with the general formula [Mg2(μ-Cl)2(DME)4][anion]x for practical Mg batteries.« less

  10. On two alternative mechanisms of ethane activation over ZSM-5 zeolite modified by Zn2+ and Ga1+ cations.

    PubMed

    Kazansky, V B; Subbotina, I R; Rane, N; van Santen, R A; Hensen, E J M

    2005-08-21

    The activation of ethane over zinc- and gallium-modified HZSM-5 dehydrogenation catalysts was studied by diffuse reflectance infrared spectroscopy. Hydrocarbon activation on HZSM-5 modified by bivalent Zn and univalent Ga cations proceeds via two distinctly different mechanisms. The stronger molecular adsorption of ethane by the acid-base pairs formed by distantly separated cationic Zn2+ and basic oxygen sites results already at room temperature in strong polarizability of adsorbed ethane and subsequent heterolytic dissociative adsorption at moderate temperatures. In contrast, molecular adsorption of ethane on Ga+ cations is weak. At high temperatures dissociative hydrocarbon adsorption takes place, resulting in the formation of ethyl and hydride fragments coordinating to the cationic gallium species. Whereas in the zinc case a Brønsted acid proton is formed upon ethane dissociation, decomposition of the ethyl fragment on gallium results in gallium dihydride species and does not lead to Brønsted acid protons. This difference in alkane activation has direct consequences for hydrocarbon conversions involving dehydrogenation.

  11. Effects of multivalent cations on cell wall-associated acid phosphatase activity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tu, S.I.; Brouillette, J.N.; Nagahashi, G.

    1988-09-01

    Primary cell walls, free from cytoplasmic contamination were prepared from corn (Zea mays L.) roots and potato (Solanum tuberosum) tubers. After EDTA treatment, the bound acid phosphatase activities were measured in the presence of various multivalent cations. Under the conditions of minimized Donnan effect and at pH 4.2, the bound enzyme activity of potato tuber cell walls (PCW) was stimulated by Cu/sup 2 +/, Mg/sup 2 +/, Za/sup 2 +/, and Mn/sup 2 +/; unaffected by Ba/sup 2 +/, Cd/sup 2 +/, and Pb/sup 2 +/; and inhibited by Al/sup 3 +/. The bound acid phosphatase of PCW was stimulatedmore » by a low concentration but inhibited by a higher concentration of Hg/sup 2 +/. On the other hand, in the case of corn root cells walls (CCW), only inhibition of the bound acid phosphatase by Al/sup 3 +/ and Hg/sup 2 +/ was observed. Kinetic analyses revealed that PCW acid phosphatase exhibited a negative cooperativity under all employed experimental conditions except in the presence of Mg/sup 2 +/. In contrast, CCW acid phosphatase showed no cooperative behavior. The presence of Ca/sup 2 +/ significantly reduced the effects of Hg/sup 2 +/ or Al/sup 3 +/, but not Mg/sup 2 +/, to the bound cell wall acid phosphatases. The salt solubilized (free) acid phosphatases from both PCW and CCW were not affected by the presence of tested cations except for Hg/sup 2 +/ or Al/sup 3 +/ which caused a Ca/sup 2 +/-insensitive inhibition of the enzymes. The induced stimulation or inhibition of bound acid phosphatases was quantitatively related to cation binding in the cell wall structure.« less

  12. The Role of cGMP on Adenosine A1 Receptor-mediated Inhibition of Synaptic Transmission at the Hippocampus

    PubMed Central

    Pinto, Isa; Serpa, André; Sebastião, Ana M.; Cascalheira, José F.

    2016-01-01

    Both adenosine A1 receptor and cGMP inhibit synaptic transmission at the hippocampus and recently it was found that A1 receptor increased cGMP levels in hippocampus, but the role of cGMP on A1 receptor-mediated inhibition of synaptic transmission remains to be established. In the present work we investigated if blocking the NOS/sGC/cGMP/PKG pathway using nitric oxide synthase (NOS), protein kinase G (PKG), and soluble guanylyl cyclase (sGC) inhibitors modify the A1 receptor effect on synaptic transmission. Neurotransmission was evaluated by measuring the slope of field excitatory postsynaptic potentials (fEPSPs) evoked by electrical stimulation at hippocampal slices. N6-cyclopentyladenosine (CPA, 15 nM), a selective A1 receptor agonist, reversibly decreased the fEPSPs by 54 ± 5%. Incubation of the slices with an inhibitor of NOS (L-NAME, 200 μM) decreased the CPA effect on fEPSPs by 57 ± 9% in female rats. In males, ODQ (10 μM), an sGC inhibitor, decreased the CPA inhibitory effect on fEPSPs by 23 ± 6%, but only when adenosine deaminase (ADA,1 U/ml) was present; similar results were found in females, where ODQ decreased CPA-induced inhibition of fEPSP slope by 23 ± 7%. In male rats, the presence of the PKG inhibitor (KT5823, 1 nM) decreased the CPA effect by 45.0 ± 9%; similar results were obtained in females, where KT5823 caused a 32 ± 9% decrease on the CPA effect. In conclusion, the results suggest that the inhibitory action of adenosine A1 receptors on synaptic transmission at hippocampus is, in part, mediated by the NOS/sGC/cGMP/PKG pathway. PMID:27148059

  13. Luteinizing hormone signaling phosphorylates and activates the cyclic GMP phosphodiesterase PDE5 in mouse ovarian follicles, contributing an additional component to the hormonally induced decrease in cyclic GMP that reinitiates meiosis.

    PubMed

    Egbert, Jeremy R; Yee, Siu-Pok; Jaffe, Laurinda A

    2018-03-01

    Prior to birth, oocytes within mammalian ovarian follicles initiate meiosis, but then arrest in prophase until puberty, when with each reproductive cycle, one or more follicles are stimulated by luteinizing hormone (LH) to resume meiosis in preparation for fertilization. Within preovulatory follicles, granulosa cells produce high levels of cGMP, which diffuses into the oocyte to maintain meiotic arrest. LH signaling restarts meiosis by rapidly lowering the levels of cGMP in the follicle and oocyte. Part of this decrease is mediated by the dephosphorylation and inactivation the NPR2 guanylyl cyclase in response to LH, but the mechanism for the remainder of the cGMP decrease is unknown. At least one cGMP phosphodiesterase, PDE5, is activated by LH signaling, which would contribute to lowering cGMP. PDE5 exhibits increased cGMP-hydrolytic activity when phosphorylated on serine 92, and we recently demonstrated that LH signaling phosphorylates PDE5 on this serine and increases its activity in rat follicles. To test the extent to which this mechanism contributes to the cGMP decrease that restarts meiosis, we generated a mouse line in which serine 92 was mutated to alanine (Pde5-S92A), such that it cannot be phosphorylated. Here we show that PDE5 phosphorylation is required for the LH-induced increase in cGMP-hydrolytic activity, but that this increase has only a modest effect on the LH-induced cGMP decrease in mouse follicles, and does not affect the timing of meiotic resumption. Though we show that the activation of PDE5 is among the mechanisms contributing to the cGMP decrease, these results suggest that another cGMP phosphodiesterase is also activated by LH signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Cationic antimicrobial peptides inactivate Shiga toxin-encoding bacteriophages

    NASA Astrophysics Data System (ADS)

    Del Cogliano, Manuel E.; Hollmann, Axel; Martinez, Melina; Semorile, Liliana; Ghiringhelli, Pablo D.; Maffía, Paulo C.; Bentancor, Leticia V.

    2017-12-01

    Shiga toxin (Stx) is the principal virulence factor during Shiga toxin-producing Escherichia coli (STEC) infections. We have previously reported the inactivation of bacteriophage encoding Stx after treatment with chitosan, a linear polysaccharide polymer with cationic properties. Cationic antimicrobial peptides (cAMPs) are short linear aminoacidic sequences, with a positive net charge, which display bactericidal or bacteriostatic activity against a wide range of bacterial species. They are promising novel antibiotics since they have shown bactericidal effects against multiresistant bacteria. To evaluate whether cationic properties are responsible for bacteriophage inactivation, we tested seven cationic peptides with proven antimicrobial activity as anti-bacteriophage agents, and one random sequence cationic peptide with no antimicrobial activity as a control. We observed bacteriophage inactivation after incubation with five cAMPs, but no inactivating activity was observed with the random sequence cationic peptide or with the non alpha helical cAMP Omiganan. Finally, to confirm peptide-bacteriophage interaction, zeta potential was analyzed by following changes on bacteriophage surface charges after peptide incubation. According to our results we could propose that: 1) direct interaction of peptides with phage is a necessary step for bacteriophage inactivation, 2) cationic properties are necessary but not sufficient for bacteriophage inactivation, and 3) inactivation by cationic peptides could be sequence (or structure) specific. Overall our data suggest that these peptides could be considered a new family of molecules potentially useful to decrease bacteriophage replication and Stx expression.

  15. HIV-Neutralizing Activity of Cationic Polypeptides in Cervicovaginal Secretions of Women in HIV-Serodiscordant Relationships

    PubMed Central

    Levinson, Pauline; Choi, Robert Y.; Cole, Amy L.; Hirbod, Taha; Rhedin, Samuel; Payne, Barbara; Guthrie, Brandon L.; Bosire, Rose; Cole, Alexander M.; Farquhar, Carey; Broliden, Kristina

    2012-01-01

    Background HIV exposed seronegative (HESN) women represent the population most in need of a prophylactic antiviral strategy. Mucosal cationic polypeptides can potentially be regulated for this purpose and we here aimed to determine their endogenous expression and HIV neutralizing activity in genital secretions of women at risk of HIV infection. Methodology/Principal Findings Cervicovaginal secretions (CVS) of Kenyan women in HIV-serodiscordant relationships (HESN, n = 164; HIV seropositive, n = 60) and low-risk controls (n = 72) were assessed for the cationic polypeptides HNP1–3, LL-37 and SLPI by ELISA and for HIV neutralizing activity by a PBMC-based assay using an HIV primary isolate. Median levels of HNP1–3 and LL-37 in CVS were similar across study groups. Neither HSV-2 serostatus, nor presence of bacterial vaginosis, correlated with levels of HNP1–3 or LL-37 in the HESN women. However, an association with their partner's viral load was observed. High viral load (>10,000 HIV RNA copies/ml plasma) correlated with higher levels of HNP1–3 and LL-37 (p = 0.04 and 0.03, respectively). SLPI was most abundant in the low-risk group and did not correlate with male partner's viral load in the HESN women. HIV neutralizing activity was found in CVS of all study groups. In experimental studies, selective depletion of cationic polypeptides from CVS rendered the remaining CVS fraction non-neutralizing, whereas the cationic polypeptide fraction retained the activity. Furthermore, recombinant HNP1–3 and LL-37 could induce neutralizing activity when added to CVS lacking intrinsic activity. Conclusions/Significance These findings show that CVS from HESN, low-risk, and HIV seropositive women contain HIV neutralizing activity. Although several innate immune proteins, including HNP1–3 and LL-37, contribute to this activity these molecules can also have inflammatory properties. This balance is influenced by hormonal and environmental factors and in the

  16. Inversion of membrane surface charge by trivalent cations probed with a cation-selective channel

    PubMed Central

    Gurnev, Philip A.; Bezrukov, Sergey M.

    2014-01-01

    We demonstrate that the cation-selective channel formed by gramicidin A can be used as a reliable sensor for studying the multivalent ion accumulation at the surfaces of charged lipid membranes and the “charge inversion” phenomenon. In asymmetrically charged membranes with the individual leaflets formed from pure negative and positive lipids bathed by 0.1 M CsCl solutions the channel exhibits current rectification which is comparable to that of a typical n/p semiconductor diode. We show that even at these highly asymmetrical conditions the channel conductance can be satisfactorily described by the electrodiffusion equation in the constant field approximation but, due to predictable limitations, only when the applied voltages do not exceed 50 mV. Analysis of the changes in the voltage-dependent channel conductance upon addition of trivalent cations allows us to gauge their interactions with the membrane surface. The inversion of the sign of the effective surface charge takes place at the concentrations which correlate with the cation size. Specifically, these concentrations are close to 0.05 mM for lanthanum, 0.25 mM for hexaamminecobalt, and 4 mM for spermidine. PMID:23088396

  17. Inversion of membrane surface charge by trivalent cations probed with a cation-selective channel.

    PubMed

    Gurnev, Philip A; Bezrukov, Sergey M

    2012-11-13

    We demonstrate that the cation-selective channel formed by gramicidin A can be used as a reliable sensor for studying the multivalent ion accumulation at the surfaces of charged lipid membranes and the "charge inversion" phenomenon. In asymmetrically charged membranes with the individual leaflets formed from pure negative and positive lipids bathed by 0.1 M CsCl solutions the channel exhibits current rectification, which is comparable to that of a typical n/p semiconductor diode. We show that even at these highly asymmetrical conditions the channel conductance can be satisfactorily described by the electrodiffusion equation in the constant field approximation but, due to predictable limitations, only when the applied voltages do not exceed 50 mV. Analysis of the changes in the voltage-dependent channel conductance upon addition of trivalent cations allows us to gauge their interactions with the membrane surface. The inversion of the sign of the effective surface charge takes place at the concentrations, which correlate with the cation size. Specifically, these concentrations are close to 0.05 mM for lanthanum, 0.25 mM for hexaamminecobalt, and 4 mM for spermidine.

  18. Insulin receptor regulates photoreceptor CNG channel activity.

    PubMed

    Gupta, Vivek K; Rajala, Ammaji; Rajala, Raju V S

    2012-12-01

    Photoreceptor cyclic nucleotide gated (CNG) channels are critical elements in phototransduction and light adaptation. Here we report that insulin receptor (IR), an integral membrane protein, directly phosphorylates the CNGA1 subunit of CNG channels that in turn affects the function of these channels negatively. The IR phosphorylates Tyr(498) and Tyr(503) residues on CNGA1 that are situated at the membrane-cytoplasmic interface. The IR tyrosine kinase activity is essential for the inhibition of CNG channel. To maintain the channels in an off state, it is necessary not only to have a precise balance of the cGMP levels but also to have a control on the cGMP sensitivity of the CNG channels itself. In this study, we observed that the channel opens at a lower concentration of cGMP in IR(-/-) mice. These studies suggest that IR regulates the modulation of CNG channel activity in vivo.

  19. Dominant-negative suppression of big brain ion channel activity by mutation of a conserved glutamate in the first transmembrane domain.

    PubMed

    Yool, Andrea J

    2007-01-01

    The neurogenic protein Drosophila big brain (BIB), which is involved in the process of neuroblast determination, and the water channel aquaporin-1 (AQP1) are among a subset of the major intrinsic protein (MIP) channels that have been found to show gated monovalent cation channel activity. A glutamate residue in the first transmembrane (M1) domain is conserved throughout the MIP family. Mutation of this residue to asparagine in BIB (E71N) knocks out ion channel activity, and when coexpressed with BIB wild-type as shown here generates a dominant-negative effect on ion channel function, measured in the Xenopus oocyte expression system using two-electrode voltage clamp. cRNAs for wild-type and mutant BIB or AQP1 channels were injected individually or as mixtures. The magnitude of the BIB ionic conductance response was greatly reduced by coexpression of the mutant E71N subunit, suggesting a dominant-negative mechanism of action. The analogous mutation in AQP1 (E17N) did not impair ion channel activation by cGMP, but did knock out water channel function, although not via a dominant-negative effect. This contrast in sensitivity between BIB and AQP1 to mutation of the M1 glutamate suggests the possibility of interesting structural differences in the molecular basis of the ion permeation between these two classes of channels. The dominant-negative construct of BIB could be a tool for testing a role for BIB ion channels during nervous system development in Drosophila. The neurogenic protein Drosophila big brain (BIB), which is involved in the process of neuroblast determination, and the water channel aquaporin-1 (AQP1) are among a subset of the major intrinsic protein (MIP) channels that have been found to show gated monovalent cation channel activity. A glutamate residue in the first transmembrane (M1) domain is conserved throughout the MIP family. Mutation of this residue to asparagine in BIB (E71N) knocks out ion channel activity, and when coexpressed with BIB wild

  20. Cation disorder in Ga1212.

    PubMed

    Greenwood, K B; Ko, D; Vander Griend, D A; Sarjeant, G M; Milgram, J W; Garrity, E S; DeLoach, D I; Poeppelmeier, K R; Salvador, P A; Mason, T O

    2000-07-24

    Substitution of calcium for strontium in LnSr2-xCaxCu2GaO7 (Ln = La, Pr, Nd, Gd, Ho, Er, Tm, and Yb) materials at ambient pressure and 975 degrees C results in complete substitution of calcium for strontium in the lanthanum and praseodymium systems and partial substitution in the other lanthanide systems. The calcium saturation level depends on the size of the Ln cation, and in all cases, a decrease in the lattice parameters with calcium concentration was observed until a common, lower bound, average A-cation size is reached. Site occupancies from X-ray and neutron diffraction experiments for LnSr2-xCaxCu2GaO7 (x = 0 and x = 2) confirm that the A-cations distribute between the two blocking-layer sites and the active-layer site based on size. A quantitative link between cation distribution and relative site-specific cation enthalpy for calcium, strontium, and lanthanum within the gallate structure is derived. The cation distribution in other similar materials can potentially be modeled.

  1. Research for preparation of cation-conducting solids by high-pressure synthesis and other methods

    NASA Technical Reports Server (NTRS)

    Goodenough, J. B.; Hong, H. Y. P.; Kafalas, J. A.; Dwight, K., Jr.

    1975-01-01

    It was shown that two body-centered-cubic skeleton structures, the Im3 KSbO3 phase and the defect-pyrochlore phase A(+)B2X6, do exhibit fast Na(+)-ion transport. The placement of anions at the tunnel intersection sites does not impede Na(+)-ion transport in (NaSb)3)(1/6 NaF), and may not in (Na(1+2x)Ta2 5F)(Ox). The activation energies are higher than those found in beta-alumina. There are two possible explanations for the higher activation energy: breathing of the bottleneck (site face or edge) through which the A(+) ions must pass on jumping from one site to another may be easier in a layer structure and/or A(+)-O bonding may be stronger in the cubic structures because the O(2-) ion bonds with two (instead of three) cations of the skeleton. If the former explanation is dominant, a lower activation energy may be achieved by optimizing the lattice parameter. If the latter is dominant, a new structural principle may have to be explored.

  2. Tuning the optical bandgap in multi-cation compound transparent conducting-oxides: The examples of In2ZnO4 and In4Sn3O12

    NASA Astrophysics Data System (ADS)

    Sabino, Fernando P.; Oliveira, Luiz N.; Wei, Su-Huai; Da Silva, Juarez L. F.

    2018-02-01

    Transparent conducting oxides such as the bixbyite In2O3 and rutile SnO2 systems have large disparities between the optical and fundamental bandgaps, ΔEgO F , because selection rules forbid dipolar transitions from the top of the valence band to the conduction-band minimum; however, the optical gaps of multi-cation compounds with the same chemical species often coincide with their fundamental gaps. To explain this conundrum, we have employed density-functional theory to compute the optical properties of multi-cation compounds, In2ZnO4 and In4Sn3O12, in several crystal structures. We show that a recently proposed mechanism to explain the disparity between the optical and fundamental gaps of M2O3 (M = Al, Ga, and In) applies also to other binary systems and to multi-compounds. Namely, a gap disparity will arise if the following three conditions are satisfied: (i) the crystal structure has inversion symmetry; (ii) the conduction-band minimum is formed by the cation and O s-orbitals; and (iii) there is strong p-d coupling and weak p-p in the vicinity of the valence-band maximum. The third property depends critically on the cationic chemical species. In the structures with inversion symmetry, Zn (Sn) strengthens (weakens) the p-d coupling in In2ZnO4 (In4Sn3O12), enhancing (reducing) the gap disparity. Furthermore, we have also identified a In4Sn3O12 structure that is 31.80 meV per formula unit more stable than a recently proposed alternative model.

  3. Ion transport with charge-protected and non-charge-protected cations in alcohol-based electrolytes using the compensated Arrhenius formalism. Part I: ionic conductivity and the static dielectric constant.

    PubMed

    Petrowsky, Matt; Fleshman, Allison; Frech, Roger

    2012-05-17

    The temperature dependence of ionic conductivity and the static dielectric constant is examined for 0.30 m TbaTf- or LiTf-1-alcohol solutions. Above ambient temperature, the conductivity increases with temperature to a greater extent in electrolytes whose salt has a charge-protected cation. Below ambient temperature, the dielectric constant changes only slightly with temperature in electrolytes whose salt has a cation that is not charge-protected. The compensated Arrhenius formalism is used to describe the temperature-dependent conductivity in terms of the contributions from both the exponential prefactor σo and Boltzmann factor exp(-Ea/RT). This analysis explains why the conductivity decreases with increasing temperature above 65 °C for the LiTf-dodecanol electrolyte. At higher temperatures, the decrease in the exponential prefactor is greater than the increase in the Boltzmann factor.

  4. Restructuring of a Peat in Interaction with Multivalent Cations: Effect of Cation Type and Aging Time

    PubMed Central

    Kunhi Mouvenchery, Yamuna; Jaeger, Alexander; Aquino, Adelia J. A.; Tunega, Daniel; Diehl, Dörte; Bertmer, Marko; Schaumann, Gabriele Ellen

    2013-01-01

    It is assumed to be common knowledge that multivalent cations cross-link soil organic matter (SOM) molecules via cation bridges (CaB). The concept has not been explicitly demonstrated in solid SOM by targeted experiments, yet. Therefore, the requirements for and characteristics of CaB remain unidentified. In this study, a combined experimental and molecular modeling approach was adopted to investigate the interaction of cations on a peat OM from physicochemical perspective. Before treatment with salt solutions of Al3+, Ca2+ or Na+, respectively, the original exchangeable cations were removed using cation exchange resin. Cation treatment was conducted at two different values of pH prior to adjusting pH to 4.1. Cation sorption is slower (>>2 h) than deprotonation of functional groups (<2 h) and was described by a Langmuir model. The maximum uptake increased with pH of cation addition and decreased with increasing cation valency. Sorption coefficients were similar for all cations and at both pH. This contradicts the general expectations for electrostatic interactions, suggesting that not only the interaction chemistry but also spatial distribution of functional groups in OM determines binding of cations in this peat. The reaction of contact angle, matrix rigidity due to water molecule bridges (WaMB) and molecular mobility of water (NMR analysis) suggested that cross-linking via CaB has low relevance in this peat. This unexpected finding is probably due to the low cation exchange capacity, resulting in low abundance of charged functionalities. Molecular modeling demonstrates that large average distances between functionalities (∼3 nm in this peat) cannot be bridged by CaB-WaMB associations. However, aging strongly increased matrix rigidity, suggesting successive increase of WaMB size to connect functionalities and thus increasing degree of cross-linking by CaB-WaMB associations. Results thus demonstrated that the physicochemical structure of OM is decisive for Ca

  5. Restructuring of a peat in interaction with multivalent cations: effect of cation type and aging time.

    PubMed

    Kunhi Mouvenchery, Yamuna; Jaeger, Alexander; Aquino, Adelia J A; Tunega, Daniel; Diehl, Dörte; Bertmer, Marko; Schaumann, Gabriele Ellen

    2013-01-01

    It is assumed to be common knowledge that multivalent cations cross-link soil organic matter (SOM) molecules via cation bridges (CaB). The concept has not been explicitly demonstrated in solid SOM by targeted experiments, yet. Therefore, the requirements for and characteristics of CaB remain unidentified. In this study, a combined experimental and molecular modeling approach was adopted to investigate the interaction of cations on a peat OM from physicochemical perspective. Before treatment with salt solutions of Al(3+), Ca(2+) or Na(+), respectively, the original exchangeable cations were removed using cation exchange resin. Cation treatment was conducted at two different values of pH prior to adjusting pH to 4.1. Cation sorption is slower (>2 h) than deprotonation of functional groups (<2 h) and was described by a Langmuir model. The maximum uptake increased with pH of cation addition and decreased with increasing cation valency. Sorption coefficients were similar for all cations and at both pH. This contradicts the general expectations for electrostatic interactions, suggesting that not only the interaction chemistry but also spatial distribution of functional groups in OM determines binding of cations in this peat. The reaction of contact angle, matrix rigidity due to water molecule bridges (WaMB) and molecular mobility of water (NMR analysis) suggested that cross-linking via CaB has low relevance in this peat. This unexpected finding is probably due to the low cation exchange capacity, resulting in low abundance of charged functionalities. Molecular modeling demonstrates that large average distances between functionalities (∼3 nm in this peat) cannot be bridged by CaB-WaMB associations. However, aging strongly increased matrix rigidity, suggesting successive increase of WaMB size to connect functionalities and thus increasing degree of cross-linking by CaB-WaMB associations. Results thus demonstrated that the physicochemical structure of OM is decisive for

  6. Esterification of phenyl acetic acid with p-cresol using metal cation exchanged montmorillonite nanoclay catalysts

    PubMed Central

    Bhaskar, M.; Surekha, M.; Suma, N.

    2018-01-01

    The liquid phase esterification of phenyl acetic acid with p-cresol over different metal cation exchanged montmorillonite nanoclays yields p-cresyl phenyl acetate. Different metal cation exchanged montmorillonite nanoclays (Mn+ = Al3+, Zn2+, Mn2+, Fe3+, Cu2+) were prepared and the catalytic activity was studied. The esterification reaction was conducted by varying molar ratio of the reactants, reaction time and catalyst amount on the yield of the ester. Among the different metal cation exchanged catalysts used, Al3+-montmorillonite nanoclay was found to be more active. The characterization of the material used was studied under different techniques, namely X-ray diffraction, scanning electron microscopy and thermogravimetric analysis. The product obtained, p-cresyl phenyl acetate, was identified by thin-layer chromotography and confirmed by Fourier transform infrared, 1H NMR and 13C NMR. The regeneration activity of used catalyst was also investigated up to fourth generation. PMID:29515855

  7. Esterification of phenyl acetic acid with p-cresol using metal cation exchanged montmorillonite nanoclay catalysts.

    PubMed

    Bhaskar, M; Surekha, M; Suma, N

    2018-02-01

    The liquid phase esterification of phenyl acetic acid with p -cresol over different metal cation exchanged montmorillonite nanoclays yields p -cresyl phenyl acetate. Different metal cation exchanged montmorillonite nanoclays (M n +  = Al 3+ , Zn 2+ , Mn 2+ , Fe 3+ , Cu 2+ ) were prepared and the catalytic activity was studied. The esterification reaction was conducted by varying molar ratio of the reactants, reaction time and catalyst amount on the yield of the ester. Among the different metal cation exchanged catalysts used, Al 3+ -montmorillonite nanoclay was found to be more active. The characterization of the material used was studied under different techniques, namely X-ray diffraction, scanning electron microscopy and thermogravimetric analysis. The product obtained, p -cresyl phenyl acetate, was identified by thin-layer chromotography and confirmed by Fourier transform infrared, 1 H NMR and 13 C NMR. The regeneration activity of used catalyst was also investigated up to fourth generation.

  8. Zn2+, not Ca2+, is the most effective cation for activation of dolichol kinase of mammalian brain.

    PubMed

    Sakakihara, Y; Volpe, J J

    1985-12-15

    The cation specificity of dolichol kinase of mammalian brain and the potential involvement of a Ca2+-calmodulin system in regulation of this enzyme have been studied. Among 10 divalent cations examined, Zn2+ was found to be most effective for the activation of dolichol kinase of rat and calf brain and cultured C-6 glial cells. The activations with Ca2+, Co2+, and Mg2+ were 53%, 32%, and 18% of the full activation with Zn2+, respectively. No combinations of the cations could activate the enzyme as much as Zn2+ alone. A role for a Ca2+-calmodulin system in the regulation of brain dolichol kinase was not supported by our data. First, the concentration of free Ca2+ required for the maximum activation of dolichol kinase was two to three orders of magnitude greater than the concentration required by typical calmodulin-dependent enzymes. Second, neither the depletion of calmodulin from the microsomal fraction nor the addition of exogenous calmodulin caused an alteration in the activation of dolichol kinase by Ca2+ (or Zn2+). Third, antagonists of calmodulin failed to suppress the activation of the enzyme by Ca2+ (or Zn2+). The data raise the possibility that Zn2+ is involved in the regulation of dolichol kinase in brain.

  9. Antimicrobial Activity and Cell Selectivity of Synthetic and Biosynthetic Cationic Polymers

    PubMed Central

    Venkatesh, Mayandi; Barathi, Veluchamy Amutha; Goh, Eunice Tze Leng; Anggara, Raditya; Fazil, Mobashar Hussain Urf Turabe; Ng, Alice Jie Ying; Harini, Sriram; Aung, Thet Tun; Fox, Stephen John; Liu, Shouping; Barkham, Timothy Mark Sebastian; Loh, Xian Jun

    2017-01-01

    ABSTRACT The mammalian and microbial cell selectivity of synthetic and biosynthetic cationic polymers has been investigated. Among the polymers with peptide backbones, polymers containing amino side chains display greater antimicrobial activity than those with guanidine side chains, whereas ethylenimines display superior activity over allylamines. The biosynthetic polymer ε-polylysine (εPL) is noncytotoxic to primary human dermal fibroblasts at concentrations of up to 2,000 μg/ml, suggesting that the presence of an isopeptide backbone has greater cell selectivity than the presence of α-peptide backbones. Both εPL and linear polyethylenimine (LPEI) exhibit bactericidal properties by depolarizing the cytoplasmic membrane and disrupt preformed biofilms. εPL displays broad-spectrum antimicrobial properties against antibiotic-resistant Gram-negative and Gram-positive strains and fungi. εPL elicits rapid bactericidal activity against both Gram-negative and Gram-positive bacteria, and its biocompatibility index is superior to those of cationic antiseptic agents and LPEI. εPL does not interfere with the wound closure of injured rabbit corneas. In a rabbit model of bacterial keratitis, the topical application of εPL (0.3%, wt/vol) decreases the bacterial burden and severity of infections caused by Pseudomonas aeruginosa and Staphylococcus aureus strains. In vivo imaging studies confirm that εPL-treated corneas appeared transparent and nonedematous compared to untreated infected corneas. Taken together, our results highlight the potential of εPL in resolving topical microbial infections. PMID:28784676

  10. New cationic vesicles prepared with double chain surfactants from arginine: Role of the hydrophobic group on the antimicrobial activity and cytotoxicity.

    PubMed

    Pinazo, A; Petrizelli, V; Bustelo, M; Pons, R; Vinardell, M P; Mitjans, M; Manresa, A; Perez, L

    2016-05-01

    Cationic double chain surfactants have attracted much interest because they can give rise to cationic vesicles that can be used in biomedical applications. Using a simple and economical synthetic approach, we have synthesized four double-chain surfactants with different alkyl chain lengths (LANHCx). The critical aggregation concentration of the double chain surfactants is at least one order of magnitude lower than the CMC of their corresponding single-chain LAM and the solutions prepared with the LANHCx contain stable cationic vesicles. Encouragingly, these new arginine derivatives show very low haemolytic activity and weaker cytotoxic effects than conventional dialkyl dimethyl ammonium surfactants. In addition, the surfactant with the shortest alkyl chain exhibits good antimicrobial activity against Gram-positive bacteria. The results show that a rational design applied to cationic double chain surfactants might serve as a promising strategy for the development of safe cationic vesicular systems. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Human proximal tubule epithelial cells cultured on hollow fibers: living membranes that actively transport organic cations

    PubMed Central

    Jansen, J.; De Napoli, I. E; Fedecostante, M.; Schophuizen, C. M. S.; Chevtchik, N. V.; Wilmer, M. J.; van Asbeck, A. H.; Croes, H. J.; Pertijs, J. C.; Wetzels, J. F. M.; Hilbrands, L. B.; van den Heuvel, L. P.; Hoenderop, J. G.; Stamatialis, D.; Masereeuw, R.

    2015-01-01

    The bioartificial kidney (BAK) aims at improving dialysis by developing ‘living membranes’ for cells-aided removal of uremic metabolites. Here, unique human conditionally immortalized proximal tubule epithelial cell (ciPTEC) monolayers were cultured on biofunctionalized MicroPES (polyethersulfone) hollow fiber membranes (HFM) and functionally tested using microfluidics. Tight monolayer formation was demonstrated by abundant zonula occludens-1 (ZO-1) protein expression along the tight junctions of matured ciPTEC on HFM. A clear barrier function of the monolayer was confirmed by limited diffusion of FITC-inulin. The activity of the organic cation transporter 2 (OCT2) in ciPTEC was evaluated in real-time using a perfusion system by confocal microscopy using 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (ASP+) as a fluorescent substrate. Initial ASP+ uptake was inhibited by a cationic uremic metabolites mixture and by the histamine H2-receptor antagonist, cimetidine. In conclusion, a ‘living membrane’ of renal epithelial cells on MicroPES HFM with demonstrated active organic cation transport was successfully established as a first step in BAK engineering. PMID:26567716

  12. Multifunctional cationic polyurethanes designed for non-viral cancer gene therapy.

    PubMed

    Cheng, Jian; Tang, Xin; Zhao, Jie; Shi, Ting; Zhao, Peng; Lin, Chao

    2016-01-01

    Nano-polyplexes from bioreducible cationic polymers have a massive promise for cancer gene therapy. However, the feasibility of cationic polyurethanes for non-viral gene therapy is so far not well studied. In this work, a linear cationic polyurethane containing disulfide bonds, urethane linkages and protonable tertiary amino groups was successfully generated by stepwise polycondensation reaction between 2,2'-dithiodiethanol bis(p-nitrophenyl carbonate) and 1,4-bis(3-aminopropyl)piperazine (BAP). We confirmed that the cationic polyurethane (denoted as PUBAP) displayed superior gene delivery properties to its cationic polyamide analogue, thus causing higher in vitro transfection efficiency in MCF-7 and SKOV-3 cells. Besides, further folate-PEGylation and hydrophobic deoxycholic acid (DCA) conjugation to amino-containing PUBAP can be conducted to afford multifunctional polyurethane gene delivery system. After optimization, folate-decorated nano-polyplexes from the PUBAP conjugated with 8 folate-PEG chains and 12 DCA residues exhibited superb colloidal stability under physiological conditions, and performed rapid uptake via folate receptor-mediated endocytosis, efficient intracellular gene release and nucleus translocation into SKOV-3 cells in vitro and in vivo. Importantly, PUBAP based polyplexes possess low cytotoxicity as a result of PUBAP biodegradability. Therefore, marked growth inhibition of SKOV-3 tumor xenografted in Balb/c nude mice was achieved with negligible side effects on the mouse health after intravenous administration of PUBAP based polyplexes with a therapeutic plasmid encoding for TNF-related apoptosis-inducing ligand. This work provides a new insight into biomedical application of bio-responsive polyurethanes for cancer therapy. In this study, we have confirmed that disulfide-based cationic polyurethane presents a new non-viral vector for gene transfer and cancer gene therapy. The significance of this work includes: (1) design and synthesis of a

  13. Insulin receptor regulates photoreceptor CNG channel activity

    PubMed Central

    Gupta, Vivek K.; Rajala, Ammaji

    2012-01-01

    Photoreceptor cyclic nucleotide gated (CNG) channels are critical elements in phototransduction and light adaptation. Here we report that insulin receptor (IR), an integral membrane protein, directly phosphorylates the CNGA1 subunit of CNG channels that in turn affects the function of these channels negatively. The IR phosphorylates Tyr498 and Tyr503 residues on CNGA1 that are situated at the membrane-cytoplasmic interface. The IR tyrosine kinase activity is essential for the inhibition of CNG channel. To maintain the channels in an off state, it is necessary not only to have a precise balance of the cGMP levels but also to have a control on the cGMP sensitivity of the CNG channels itself. In this study, we observed that the channel opens at a lower concentration of cGMP in IR−/− mice. These studies suggest that IR regulates the modulation of CNG channel activity in vivo. PMID:23032687

  14. CATALASE ACTIVITY OF TWO STREPTOCOCCUS FAECALIS STRAINS AND ITS ENHANCEMENT BY AEROBIOSIS AND ADDED CATIONS1

    PubMed Central

    Jones, Dorothy; Deibel, R. H.; Niven, C. F.

    1964-01-01

    Jones, Dorothy (American Meat Institute Foundation, Chicago, Ill.), R. H. Deibel, and C. F. Niven, Jr. Catalase activity of two Streptococcus faecalis strains and its enhancement by aerobiosis and added cations. J. Bacteriol. 88:602–610. 1964.—The nature of catalase activity noted in two unusual Streptococcus faecalis strains was determined. Enzyme activity was lost slowly when cultures were maintained by daily transfer in test tubes of broth media. Loss of activity could be prevented by aerobic culture. Supplementation of the growth medium with ferric, manganese, and zinc ions, as well as aerobiosis, enhanced catalase activity. However, addition of these cations to cell suspensions or to cell-free extracts did not increase catalase activity. Although oxygen was observed to be one of the reaction end products, the catalase activity was not inhibited by cyanide or azide, and the iron-porphyrin coenzyme of classical catalase was not detected. The enzyme was purified 185-fold by precipitation with ammonium sulfate, followed by chromotography on a diethylaminoethyl cellulose column. PMID:14208495

  15. Cation Uptake and Allocation by Red Pine Seedlings under Cation-Nutrient Stress in a Column Growth Experiment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shi, Zhenqing; Balogh-Brunstad, Zsuzsanna; Grant, Michael R.

    Background and Aims Plant nutrient uptake is affected by environmental stress, but how plants respond to cation-nutrient stress is poorly understood. We assessed the impact of varying degrees of cation-nutrient limitation on cation uptake in an experimental plant-mineral system. Methods Column experiments, with red pine (Pinus resinosa Ait.) seedlings growing in sand/mineral mixtures, were conducted for up to nine months under a range of Ca- and K-limited conditions. The Ca and K were supplied from both minerals and nutrient solutions with varying Ca and K concentrations. Results Cation nutrient stress had little impact on carbon allocation after nine months ofmore » plant growth and K was the limiting nutrient for biomass production. The Ca/Sr and K/Rb ratio results allowed independent estimation of dissolution incongruency and discrimination against Sr and Rb during cation uptake processes. The fraction of K in biomass from biotite increased with decreasing K supply from nutrient solutions. The mineral anorthite was consistently the major source of Ca, regardless of nutrient treatment. Conclusions Red pine seedlings exploited more mineral K in response to more severe K deficiency. This did not occur for Ca. Plant discrimination factors must be carefully considered to accurately identify nutrient sources using cation tracers.« less

  16. Membrane perturbation activity of cationic phenylene ethynylene oligomers and polymers: selectivity against model bacterial and mammalian membranes.

    PubMed

    Wang, Ying; Tang, Yanli; Zhou, Zhijun; Ji, Eunkyung; Lopez, Gabriel P; Chi, Eva Y; Schanze, Kirk S; Whitten, David G

    2010-08-03

    Poly(phenylene ethyneylene) (PPE)-based cationic conjugated polyelectrolytes (CPEs) and cationic phenylene ethynylene oligomers (OPEs) exhibit broad-spectrum antimicrobial activity, and their main target is believed to be the cell membrane. To understand better how these antimicrobial molecules interact with membranes, a series of PPE-based CPEs and OPEs with different side chains were studied. Large unilamellar vesicles with lipid compositions mimicking those of mammalian or bacterial membranes were used as model membranes. Among the CPEs and OPEs tested, the anionic CPE, PPE-SO(3)(2-) and the smallest cationic OPE-1 are inactive against all vesicles. Other cationic CPEs and OPEs show significant membrane perturbation ability against bacterial membrane mimics but are inactive against a mammalian cell membrane mimic with the exception of PPE-DABCO and two end-only-functionalized OPEs, which also disrupted a mammalian cell membrane mimic. The results suggest that the phospholipid composition of vesicles dominates the interaction of CPE and OPE with lipid membranes.

  17. cGMP Signalling Mediates Water Sensation (Hydrosensation) and Hydrotaxis in Caenorhabditis elegans

    PubMed Central

    Wang, Wei; Qin, Li-Wei; Wu, Tai-Hong; Ge, Chang-Li; Wu, Ya-Qian; Zhang, Qiang; Song, Yan-Xue; Chen, Yuan-Hua; Ge, Ming-Hai; Wu, Jing-Jing; Liu, Hui; Xu, Yao; Su, Chun-Ming; Li, Lan-Lan; Tang, Jing; Li, Zhao-Yu; Wu, Zheng-Xing

    2016-01-01

    Animals have developed the ability to sense the water content in their habitats, including hygrosensation (sensing humidity in the air) and hydrosensation (sensing the water content in other microenvironments), and they display preferences for specific water contents that influence their mating, reproduction and geographic distribution. We developed and employed four quantitative behavioural test paradigms to investigate the molecular and cellular mechanisms underlying sensing the water content in an agar substrate (hydrosensation) and hydrotaxis in Caenorhabditis elegans. By combining a reverse genetic screen with genetic manipulation, optogenetic neuronal manipulation and in vivo Ca2+ imaging, we demonstrate that adult worms avoid the wetter areas of agar plates and hypo-osmotic water droplets. We found that the cGMP signalling pathway in ciliated sensory neurons is involved in hydrosensation and hydrotaxis in Caenorhabditis elegans. PMID:26891989

  18. Structural evolution of the methane cation in subfemtosecond photodynamics

    NASA Astrophysics Data System (ADS)

    Mondal, T.; Varandas, A. J. C.

    2015-07-01

    An ab initio quantum dynamics study has been performed to explore the structural rearrangement of ground state CH 4+ in subfemtosecond resolved photodynamics. The method utilizes time-dependent wave-packet propagation on the X ˜ 2 T 2 electronic manifold of the title cation in full dimensionality, including nonadiabatic coupling of the three electronic sheets. Good agreement is obtained with recent experiments [Baker et al., Science 312, 424 (2006)] which use high-order harmonic generation to probe the attosecond proton dynamics. The novel results provide direct theoretical support of the observations while unravelling the underlying details. With the geometrical changes obtained by calculating the expectation values of the nuclear coordinates as a function of time, the structural evolution is predicted to begin through activation of the totally symmetric a1 and doubly degenerate e modes. While the former retains the original Td symmetry of the cation, the Jahn-Teller active e mode conducts it to a D2d structure. At ˜1.85 fs, the intermediate D2d structure is further predicted to rearrange to local C2v minimum geometry via Jahn-Teller active bending vibrations of t2 symmetry.

  19. Hyperactivity and memory/learning deficits evoked by developmental exposure to nicotine and/or ethanol are mitigated by cAMP and cGMP signaling cascades activation.

    PubMed

    Abreu-Villaça, Yael; Carvalho-Graça, Anna C; Skinner, Gabriela; Lotufo, Bruna M; Duarte-Pinheiro, Vitor H S; Ribeiro-Carvalho, Anderson; Manhães, Alex C; Filgueiras, Claudio C

    2018-05-01

    Pregnant smoking women are frequently episodic drinkers. Here, we investigated whether ethanol exposure restricted to the brain growth spurt period when combined with chronic developmental exposure to nicotine aggravates memory/learning deficits and hyperactivity, and associated cAMP and cGMP signaling disruption. To further investigate the role of these signaling cascades, we verified whether vinpocetine (a phosphodiesterase inhibitor) ameliorates the neurochemical and behavioral outcomes. Swiss mice had free access to nicotine (NIC, 50 μg/ml) or water to drink during gestation and until the 8th postnatal day (PN8). Ethanol (ETOH, 5 g/kg, i.p.) or saline were injected in the pups every other day from PN2 to PN8. At PN30, animals either received vinpocetine (20 mg/kg, i.p.) or vehicle before being tested in the step-down passive avoidance or open field. Memory/learning was impaired in NIC, ETOH and NIC + ETOH mice, and vinpocetine mitigated ETOH- and NIC + ETOH-induced deficits. Locomotor hyperactivity identified in ETOH and NIC + ETOH mice was ameliorated by vinpocetine. While cyclic nucleotides levels in cerebral cortex and hippocampus were reduced by NIC, ETOH and NIC + ETOH, this outcome was more consistent in the latter group. As observed for behavior, vinpocetine normalized NIC + ETOH nucleotides levels. pCREB levels were also increased in response to vinpocetine, with stronger effects in the NIC + ETOH group. Exposure to both drugs of abuse worsens behavioral and neurochemical disruption. These findings and the amelioration of deleterious effects by vinpocetine support the idea that cAMP and cGMP signaling contribute to nicotine- and ethanol-induced hyperactivity and memory/learning deficits. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. The Rubella Virus Nonstructural Protease Requires Divalent Cations for Activity and Functions in trans

    PubMed Central

    Liu, Xin; Ropp, Susan L.; Jackson, Richard J.; Frey, Teryl K.

    1998-01-01

    The rubella virus (RUB) nonstructural (NS) protease is a papain-like cysteine protease (PCP) located in the NS-protein open reading frame (NSP-ORF) that cleaves the NSP-ORF translation product at a single site to produce two products, P150 (the N-terminal product) and P90 (the C-terminal product). The RUB NS protease was found not to function following translation in vitro in a standard rabbit reticulocyte lysate system, although all of the other viral PCPs do so. However, in the presence of divalent cations such as Zn2+, Cd2+, and Co2+, the RUB NS protease functioned efficiently, indicating that these cations are required either as direct cofactors in catalytic activity or for correct acquisition of three-dimensional conformation of the protease. Since other viral and cell PCPs do not require cations for activity and the RUB NS protease contains a putative zinc binding motif, the latter possibility is more likely. Previous in vivo expression studies of the RUB NS protease failed to demonstrate trans cleavage activity (J.-P. Chen et al., J. Virol. 70:4707–4713, 1996). To study whether trans cleavage could be detected in vitro, a protease catalytic site mutant and a mutant in which the C-terminal 31 amino acids of P90 were deleted were independently introduced into plasmid constructs that express the complete NSP-ORF. Cotranslation of these mutants in vitro yielded both the native and the mutated forms of P90, indicating that the protease present in the mutated construct cleaved the catalytic-site mutant precursor. Thus, RUB NS protease can function in trans. PMID:9557742

  1. Differential Regulation of cGMP Signaling in Human Melanoma Cells at Altered Gravity: Simulated Microgravity Down-Regulates Cancer-Related Gene Expression and Motility

    NASA Astrophysics Data System (ADS)

    Ivanova, Krassimira; Eiermann, Peter; Tsiockas, Wasiliki; Hemmersbach, Ruth; Gerzer, Rupert

    2018-03-01

    Altered gravity is known to affect cellular function by changes in gene expression and cellular signaling. The intracellular signaling molecule cyclic guanosine-3',5'-monophosphate (cGMP), a product of guanylyl cyclases (GC), e.g., the nitric oxide (NO)-sensitive soluble GC (sGC) or natriuretic peptide-activated GC (GC-A/GC-B), is involved in melanocyte response to environmental stress. NO-sGC-cGMP signaling is operational in human melanocytes and non-metastatic melanoma cells, whereas up-regulated expression of GC-A/GC-B and inducible NO synthase (iNOS) are found in metastatic melanoma cells, the deadliest skin cancer. Here, we investigated the effects of altered gravity on the mRNA expression of NOS isoforms, sGC, GC-A/GC-B and multidrug resistance-associated proteins 4/5 (MRP4/MRP5) as selective cGMP exporters in human melanoma cells with different metastatic potential and pigmentation. A specific centrifuge (DLR, Cologne Germany) was used to generate hypergravity (5 g for 24 h) and a fast-rotating 2-D clinostat (60 rpm) to simulate microgravity values ≤ 0.012 g for 24 h. The results demonstrate that hypergravity up-regulates the endothelial NOS-sGC-MRP4/MRP5 pathway in non-metastatic melanoma cells, but down-regulates it in simulated microgravity when compared to 1 g. Additionally, the suppression of sGC expression and activity has been suggested to correlate inversely to tumor aggressiveness. Finally, hypergravity is ineffective in highly metastatic melanoma cells, whereas simulated microgravity down-regulates predominantly the expression of the cancer-related genes iNOS and GC-A/GC-B (shown additionally on protein levels) as well as motility in comparison to 1 g. The results suggest that future studies in real microgravity can benefit from considering GC-cGMP signaling as possible factor for melanocyte transformation.

  2. Hyperforin activates nonselective cation channels (NSCCs).

    PubMed

    Treiber, Kristina; Singer, Andrea; Henke, Bettina; Müller, Walter E

    2005-05-01

    A large body of evidence supports the preclinical antidepressant profile of hyperforin including inhibition of the synaptosomal uptake of several neurotransmitters by hyperforin and studies in behavioural models. In contrast to other antidepressants, hyperforin does not directly inhibit neurotransmitter transporters, but instead uptake inhibition seems to be the consequence of an elevated intracellular sodium concentration ([Na+]i). The mechanism of hyperforin-induced elevation of [Na+]i was investigated using two different cell types: human platelets and rat pheochromocytoma cells (PC12 cells). In both cell systems, hyperforin increased both [Na+]i and free intracellular Ca2+ concentration ([Ca2+]i). One pathway for Na+ and Ca2+ entry is mediated by nonselective cation channels (NSCCs), which can be blocked by SK&F 96365 and LOE 908. LOE 908 is a blocker of both NSCC1 and NSCC2 subclasses, while SK&F 96365 blocks NSCC2 only. Both SK&F 96365 and LOE 908 completely inhibited the hyperforin-induced influx of Na+ and Ca2+ into platelets and PC12 cells. This indicates that hyperforin is mainly active upon NSCC2. The effect of hyperforin is inhibited by La3+ and Gd3+, indicating that there is a potential homology with canonical transient receptor potential protein channels (TRPC channels). Moreover, La3+ and Gd3+ attenuate the effect of hyperforin on serotonin uptake in human platelets. Additionally, hyperforin induces barium influx in PC12 cells and this influx can be inhibited by SK&F 96365, LOE 908, Gd3+ and La3+. In summary, these findings suggest that hyperforin represents a new principle for preclinical antidepressant activity, modulating brain neurotransmission by inhibition of neurotransmitter uptake via activation of NSCCs.British Journal of Pharmacology (2005) 145, 75-83. doi:10.1038/sj.bjp.0706155.

  3. Hyperforin activates nonselective cation channels (NSCCs)

    PubMed Central

    Treiber, Kristina; Singer, Andrea; Henke, Bettina; Müller, Walter E

    2005-01-01

    A large body of evidence supports the preclinical antidepressant profile of hyperforin including inhibition of the synaptosomal uptake of several neurotransmitters by hyperforin and studies in behavioural models. In contrast to other antidepressants, hyperforin does not directly inhibit neurotransmitter transporters, but instead uptake inhibition seems to be the consequence of an elevated intracellular sodium concentration ([Na+]i). The mechanism of hyperforin-induced elevation of [Na+]i was investigated using two different cell types: human platelets and rat pheochromocytoma cells (PC12 cells). In both cell systems, hyperforin increased both [Na+]i and free intracellular Ca2+ concentration ([Ca2+]i). One pathway for Na+ and Ca2+ entry is mediated by nonselective cation channels (NSCCs), which can be blocked by SK&F 96365 and LOE 908. LOE 908 is a blocker of both NSCC1 and NSCC2 subclasses, while SK&F 96365 blocks NSCC2 only. Both SK&F 96365 and LOE 908 completely inhibited the hyperforin-induced influx of Na+ and Ca2+ into platelets and PC12 cells. This indicates that hyperforin is mainly active upon NSCC2. The effect of hyperforin is inhibited by La3+ and Gd3+, indicating that there is a potential homology with canonical transient receptor potential protein channels (TRPC channels). Moreover, La3+ and Gd3+ attenuate the effect of hyperforin on serotonin uptake in human platelets. Additionally, hyperforin induces barium influx in PC12 cells and this influx can be inhibited by SK&F 96365, LOE 908, Gd3+ and La3+. In summary, these findings suggest that hyperforin represents a new principle for preclinical antidepressant activity, modulating brain neurotransmission by inhibition of neurotransmitter uptake via activation of NSCCs. PMID:15723093

  4. Studying the silver nanoparticles influence on thermodynamic behavior and antimicrobial activities of novel amide Gemini cationic surfactants.

    PubMed

    Shaban, Samy M; Abd-Elaal, Ali A

    2017-07-01

    Three novels amide Gemini cationic surfactants with various alkyl chains and their silver nanohybrid with silver nanoparticles were synthesized and a confirmation study for surfactant and their nanoparticles formation has been established using IR, 1 HNMR, TEM and UV-Vis spectroscopy. The surface-active properties of these surfactants and their nanoform were investigated through surface tension and electrical conductivity measurements and a comparative study has been established. The thermodynamic parameters of micellization and adsorption were assessed at temperatures range from 25 to 65°C. The effect of silver particles on the surface behavior of the synthesized surfactant has been discussed. The aggregation behavior of silver nanoparticles with these synthesized Gemini surfactants in water were investigated using dynamic light scattering and transmission electron microscopy. Furthermore, the antimicrobial activities of these synthesized amide Gemini surfactants and their nanostructure with silver against both Gram positive and Gram negative bacteria were also investigated. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Direct intrathecal drug delivery in mice for detecting in vivo effects of cGMP on pain processing.

    PubMed

    Lu, Ruirui; Schmidtko, Achim

    2013-01-01

    Intrathecal delivery of drugs is an important method in pain research in order to investigate pain-relevant effects in the spinal cord in vivo. Here, we describe a method of intrathecal drug delivery by direct lumbar puncture in mice. The procedure does not require surgery, is rapidly performed, and does not produce neurological deficits. If cGMP analogs are injected, a state of transient hindpaw hypersensitivity can be induced which is quantifiable by measurement of hindpaw withdrawal latency in response to mechanical stimulation.

  6. [The nature of pacemaker activity].

    PubMed

    Kabakov, A Iu

    1991-01-01

    A general equation of the membrane resting potential (RP) has been derived for closed cell membrane (CM) model. It is shown that Na,K-ATPase of cardiomyocytes is in the antielectrogenic phase. A hypothesis is proposed: a pacemaker cell is an excitable cell, which has RP corresponding to the given activity of Na,K-ATPase and non-activated cationic conductivities of CM higher than the activation threshold of Na-channels. The equation of the equipotential levels of the membrane RP on the surface of the cationic conductivities has been derived. It is shown that the substances (e. g. neuromediator) that change the membrane cation permeability are able to depolarize or to hyperpolarize CM. The direction of polarization is dependent on the state of the cell electrogenic system. The following factors promote the hyperpolarizing effect of the magnifying cation permeability substances: 1) high activity of Na,K-ATPase, 2) low background cation permeability of CM (among their number the integrity of CM) and 3) high ratio of the potassium permeability alteration in respect to that of sodium which is evoked by the substance (delta gK/delta gNa).

  7. The regulation of transient receptor potential canonical 4 (TRPC4) channel by phosphodiesterase 5 inhibitor via the cyclic guanosine 3'5'-monophosphate.

    PubMed

    Wie, Jinhong; Jeong, SeungJoo; Kwak, Misun; Myeong, Jongyun; Chae, MeeRee; Park, Jong Kwan; Lee, Sung Won; So, Insuk

    2017-06-01

    The transient receptor potential (TRP) protein superfamily consists of a diverse group of cation channels that bear structural similarities to the fruit fly Drosophila TRP. The TRP superfamily is distinct from other groups of ion channels in displaying a large diversity in ion selectivity, modes of activation, and physiological functions. Classical TRP (transient receptor potential canonical (TRPC)) channels are activated by stimulation of Gq-PLC-coupled receptors and modulated by phosphorylation. The cyclic guanosine monophosphate (cGMP)-PKG pathway is involved in the regulation of TRPC3 and TRPC6 channels. Phosphodiesterase (PDE) 5 inhibitor induced muscle relaxation in corporal smooth muscle cells and was used to treat erectile dysfunction by inhibiting cGMP degradation. Here, we report the functional relationship between TRPC4 and cGMP. In human embryonic kidney (HEK) 293 cells overexpressing TRPC4, cGMP selectively activated TRPC4 channels and increased cytosolic calcium level through TRPC4 channel. We investigated phosphorylation sites in TRPC4 channels and identified S688 as an important phosphorylation site for the cGMP-PKG pathway. Cyclic GMP also activated TRPC4-like current with doubly rectifying current-voltage relationship in prostate smooth muscle cell lines. Taken together, these results show that TRPC4 is phosphorylated by the cGMP-PKG pathway and might be an important target for modulating prostate function by PDE5 inhibitors.

  8. Stressor states and the cation crossroads.

    PubMed

    Weber, Karl T; Bhattacharya, Syamal K; Newman, Kevin P; Soberman, Judith E; Ramanathan, Kodangudi B; McGee, Jesse E; Malik, Kafait U; Hickerson, William L

    2010-12-01

    Neurohormonal activation involving the hypothalamic-pituitary-adrenal axis and adrenergic nervous and renin-angiotensin-aldosterone systems is integral to stressor state-mediated homeostatic responses. The levels of effector hormones, depending upon the degree of stress, orchestrate the concordant appearance of hypokalemia, ionized hypocalcemia and hypomagnesemia, hypozincemia, and hyposelenemia. Seemingly contradictory to homeostatic responses wherein the constancy of extracellular fluid would be preserved, upregulation of cognate-binding proteins promotes coordinated translocation of cations to injured tissues, where they participate in wound healing. Associated catecholamine-mediated intracellular cation shifts regulate the equilibrium between pro-oxidants and antioxidant defenses, a critical determinant of cell survival. These acute and chronic stressor-induced iterations in extracellular and intracellular cations are collectively referred to as the cation crossroads. Intracellular cation shifts, particularly excessive accumulation of Ca2+, converge on mitochondria to induce oxidative stress and raise the opening potential of their inner membrane permeability transition pores (mPTPs). The ensuing loss of cationic homeostasis and adenosine triphosphate (ATP) production, together with osmotic swelling, leads to organellar degeneration and cellular necrosis. The overall impact of iterations in extracellular and intracellular cations and their influence on cardiac redox state, cardiomyocyte survival, and myocardial structure and function are addressed herein.

  9. Structural and energetic study of cation-π-cation interactions in proteins.

    PubMed

    Pinheiro, Silvana; Soteras, Ignacio; Gelpí, Josep Lluis; Dehez, François; Chipot, Christophe; Luque, F Javier; Curutchet, Carles

    2017-04-12

    Cation-π interactions of aromatic rings and positively charged groups are among the most important interactions in structural biology. The role and energetic characteristics of these interactions are well established. However, the occurrence of cation-π-cation interactions is an unexpected motif, which raises intriguing questions about its functional role in proteins. We present a statistical analysis of the occurrence, composition and geometrical preferences of cation-π-cation interactions identified in a set of non-redundant protein structures taken from the Protein Data Bank. Our results demonstrate that this structural motif is observed at a small, albeit non-negligible frequency in proteins, and suggest a preference to establish cation-π-cation motifs with Trp, followed by Tyr and Phe. Furthermore, we have found that cation-π-cation interactions tend to be highly conserved, which supports their structural or functional role. Finally, we have performed an energetic analysis of a representative subset of cation-π-cation complexes combining quantum-chemical and continuum solvation calculations. Our results point out that the protein environment can strongly screen the cation-cation repulsion, leading to an attractive interaction in 64% of the complexes analyzed. Together with the high degree of conservation observed, these results suggest a potential stabilizing role in the protein fold, as demonstrated recently for a miniature protein (Craven et al., J. Am. Chem. Soc. 2016, 138, 1543). From a computational point of view, the significant contribution of non-additive three-body terms challenges the suitability of standard additive force fields for describing cation-π-cation motifs in molecular simulations.

  10. cGMP and cyclic nucleotide-gated channels participate in mouse sperm capacitation.

    PubMed

    Cisneros-Mejorado, Abraham; Sánchez Herrera, Daniel P

    2012-01-20

    During capacitation of mammalian sperm intracellular [Ca(2+)] and cyclic nucleotides increase, suggesting that CNG channels play a role in the physiology of sperm. Here we study the effect of capacitation, 8Br-cAMP (8-bromoadenosine 3',5'-cyclic monophosphate) and 8Br-cGMP (8-bromoguanosine 3',5'-cyclic monophosphate) on the macroscopic ionic currents of mouse sperm, finding the existence of different populations of sperm, in terms of the recorded current and its response to cyclic nucleotides. Our results show that capacitation and cyclic nucleotides increase the ionic current, having a differential sensitivity to cGMP (cyclic guanosine monophosphate) and cAMP (cyclic adenosine monophosphate). Using a specific inhibitor we determine the contribution of CNG channels to macroscopic current and capacitation. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  11. In search of novel highly active mitochondria-targeted antioxidants: thymoquinone and its cationic derivatives.

    PubMed

    Severina, Inna I; Severin, Fedor F; Korshunova, Galina A; Sumbatyan, Natalya V; Ilyasova, Tatyana M; Simonyan, Ruben A; Rogov, Anton G; Trendeleva, Tatyana A; Zvyagilskaya, Renata A; Dugina, Vera B; Domnina, Lidia V; Fetisova, Elena K; Lyamzaev, Konstantin G; Vyssokikh, Mikhail Yu; Chernyak, Boris V; Skulachev, Maxim V; Skulachev, Vladimir P; Sadovnichii, Viktor A

    2013-06-27

    Since the times of the Bible, an extract of black cumin seeds was used as a medicine to treat many human pathologies. Thymoquinone (2-demethylplastoquinone derivative) was identified as an active antioxidant component of this extract. Recently, it was shown that conjugates of plastoquinone and penetrating cations are potent mitochondria-targeted antioxidants effective in treating a large number of age-related pathologies. This review summarizes new data on the antioxidant and some other properties of membrane-penetrating cationic compounds where 2-demethylplastoquinone substitutes for plastoquinone. It was found that such a substitution significantly increases a window between anti- and prooxidant concentrations of the conjugates. Like the original plastoquinone derivatives, the novel compounds are easily reduced by the respiratory chain, penetrate through model and natural membranes, specifically accumulate in mitochondria in an electrophoretic fashion, and strongly inhibit H2O2-induced apoptosis at pico- and nanomolar concentrations in cell cultures. At present, cationic demethylplastoquinone derivatives appear to be the most promising mitochondria-targeted drugs of the quinone series. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  12. The influence of natural organic matter and cations on the rejection of endocrine disrupting and pharmaceutically active compounds by nanofiltration.

    PubMed

    Comerton, Anna M; Andrews, Robert C; Bagley, David M

    2009-02-01

    The impact of natural organic matter (NOM) and cations on the rejection of five endocrine disrupting compounds (EDCs) and pharmaceutically active compounds (PhACs) (acetaminophen, carbamazepine, estrone, gemfibrozil, oxybenzone) by nanofiltration (NF) was examined. The water matrices included membrane bioreactor (MBR) effluent, Lake Ontario water and laboratory-prepared waters modelled to represent the characteristics of the Lake Ontario water. The impact of cations in natural waters on compound rejection was also examined by doubling the natural cation concentration (calcium, magnesium, sodium) in both the Lake Ontario water and the MBR effluent. The presence of Suwannee River NOM spiked into laboratory-grade water was found to cause an increase in compound NF rejection. In addition, the presence of cations alone in laboratory-grade water did not have a significant impact on rejection with the exception of the polar compound gemfibrozil. However, when cation concentration in natural waters was increased, a significant decrease in the rejection of EDCs and PhACs was observed. This suggests that the presence of cations may result in a reduction in the association of EDCs and PhACs with NOM.

  13. Cations Form Sequence Selective Motifs within DNA Grooves via a Combination of Cation-Pi and Ion-Dipole/Hydrogen Bond Interactions

    PubMed Central

    Stewart, Mikaela; Dunlap, Tori; Dourlain, Elizabeth; Grant, Bryce; McFail-Isom, Lori

    2013-01-01

    The fine conformational subtleties of DNA structure modulate many fundamental cellular processes including gene activation/repression, cellular division, and DNA repair. Most of these cellular processes rely on the conformational heterogeneity of specific DNA sequences. Factors including those structural characteristics inherent in the particular base sequence as well as those induced through interaction with solvent components combine to produce fine DNA structural variation including helical flexibility and conformation. Cation-pi interactions between solvent cations or their first hydration shell waters and the faces of DNA bases form sequence selectively and contribute to DNA structural heterogeneity. In this paper, we detect and characterize the binding patterns found in cation-pi interactions between solvent cations and DNA bases in a set of high resolution x-ray crystal structures. Specifically, we found that monovalent cations (Tl+) and the polarized first hydration shell waters of divalent cations (Mg2+, Ca2+) form cation-pi interactions with DNA bases stabilizing unstacked conformations. When these cation-pi interactions are combined with electrostatic interactions a pattern of specific binding motifs is formed within the grooves. PMID:23940752

  14. Cations form sequence selective motifs within DNA grooves via a combination of cation-pi and ion-dipole/hydrogen bond interactions.

    PubMed

    Stewart, Mikaela; Dunlap, Tori; Dourlain, Elizabeth; Grant, Bryce; McFail-Isom, Lori

    2013-01-01

    The fine conformational subtleties of DNA structure modulate many fundamental cellular processes including gene activation/repression, cellular division, and DNA repair. Most of these cellular processes rely on the conformational heterogeneity of specific DNA sequences. Factors including those structural characteristics inherent in the particular base sequence as well as those induced through interaction with solvent components combine to produce fine DNA structural variation including helical flexibility and conformation. Cation-pi interactions between solvent cations or their first hydration shell waters and the faces of DNA bases form sequence selectively and contribute to DNA structural heterogeneity. In this paper, we detect and characterize the binding patterns found in cation-pi interactions between solvent cations and DNA bases in a set of high resolution x-ray crystal structures. Specifically, we found that monovalent cations (Tl⁺) and the polarized first hydration shell waters of divalent cations (Mg²⁺, Ca²⁺) form cation-pi interactions with DNA bases stabilizing unstacked conformations. When these cation-pi interactions are combined with electrostatic interactions a pattern of specific binding motifs is formed within the grooves.

  15. Movement of gating machinery during the activation of rod cyclic nucleotide-gated channels.

    PubMed Central

    Brown, R L; Snow, S D; Haley, T L

    1998-01-01

    In the visual and olfactory systems, cyclic nucleotide-gated (CNG) ion channels convert stimulus-induced changes in the internal concentrations of cGMP and cAMP into changes in membrane potential. Although it is known that significant activation of these channels requires the binding of three or more molecules of ligand, the detailed molecular mechanism remains obscure. We have probed the structural changes that occur during channel activation by using sulfhydryl-reactive methanethiosulfonate (MTS) reagents and N-ethylmaleimide (NEM). When expressed in Xenopus oocytes, the alpha-subunit of the bovine retinal channel forms homomultimeric channels that are activated by cGMP with a K1/2 of approximately 100 microM. Cyclic AMP, on the other hand, is a very poor activator; a saturating concentration elicits only 1% of the maximum current produced by cGMP. Treatment of excised patches with MTS-ethyltrimethylamine (MTSET) or NEM dramatically potentiated the channel's response to both cyclic nucleotides. After MTSET treatment, the dose-response relation for cGMP was shifted by over two orders of magnitude to lower concentrations. The effect on channel activation by cAMP was even more striking. After modification, the channels were fully activated by cAMP with a K1/2 of approximately 60 microM. This potentiation was abolished by conversion of Cys481 to a nonreactive alanine residue. Potentiation occurred more rapidly in the presence of saturating cGMP, indicating that this region of the channel is more accessible when the channel is open. Cys481 is located in a linker region between the transmembrane and cGMP-binding domains of the channel. These results suggest that this region of the channel undergoes significant movement during the activation process and is critical for coupling ligand binding to pore opening. Potentiation, however, is not mediated by the recently reported interaction between the amino- and carboxy-terminal regions of the alpha-subunit. Deletion of the

  16. M‐Atrial Natriuretic Peptide and Nitroglycerin in a Canine Model of Experimental Acute Hypertensive Heart Failure: Differential Actions of 2 cGMP Activating Therapeutics

    PubMed Central

    McKie, Paul M.; Cataliotti, Alessandro; Ichiki, Tomoko; Sangaralingham, S. Jeson; Chen, Horng H.; Burnett, John C.

    2014-01-01

    Background Systemic hypertension is a common characteristic in acute heart failure (HF). This increasingly recognized phenotype is commonly associated with renal dysfunction and there is an unmet need for renal enhancing therapies. In a canine model of HF and acute vasoconstrictive hypertension we characterized and compared the cardiorenal actions of M‐atrial natriuretic peptide (M‐ANP), a novel particulate guanylyl cyclase (pGC) activator, and nitroglycerin, a soluble guanylyl cyclase (sGC) activator. Methods and Results HF was induced by rapid RV pacing (180 beats per minute) for 10 days. On day 11, hypertension was induced by continuous angiotensin II infusion. We characterized the cardiorenal and humoral actions prior to, during, and following intravenous M‐ANP (n=7), nitroglycerin (n=7), and vehicle (n=7) infusion. Mean arterial pressure (MAP) was reduced by M‐ANP (139±4 to 118±3 mm Hg, P<0.05) and nitroglycerin (137±3 to 116±4 mm Hg, P<0.05); similar findings were recorded for pulmonary wedge pressure (PCWP) with M‐ANP (12±2 to 6±2 mm Hg, P<0.05) and nitroglycerin (12±1 to 6±1 mm Hg, P<0.05). M‐ANP enhanced renal function with significant increases (P<0.05) in glomerular filtration rate (38±4 to 53±5 mL/min), renal blood flow (132±18 to 236±23 mL/min), and natriuresis (11±4 to 689±37 mEq/min) and also inhibited aldosterone activation (32±3 to 23±2 ng/dL, P<0.05), whereas nitroglycerin had no significant (P>0.05) effects on these renal parameters or aldosterone activation. Conclusions Our results advance the differential cardiorenal actions of pGC (M‐ANP) and sGC (nitroglycerin) mediated cGMP activation. These distinct renal and aldosterone modulating actions make M‐ANP an attractive therapeutic for HF with concomitant hypertension, where renal protection is a key therapeutic goal. PMID:24385449

  17. M-atrial natriuretic peptide and nitroglycerin in a canine model of experimental acute hypertensive heart failure: differential actions of 2 cGMP activating therapeutics.

    PubMed

    McKie, Paul M; Cataliotti, Alessandro; Ichiki, Tomoko; Sangaralingham, S Jeson; Chen, Horng H; Burnett, John C

    2014-01-02

    Systemic hypertension is a common characteristic in acute heart failure (HF). This increasingly recognized phenotype is commonly associated with renal dysfunction and there is an unmet need for renal enhancing therapies. In a canine model of HF and acute vasoconstrictive hypertension we characterized and compared the cardiorenal actions of M-atrial natriuretic peptide (M-ANP), a novel particulate guanylyl cyclase (pGC) activator, and nitroglycerin, a soluble guanylyl cyclase (sGC) activator. HF was induced by rapid RV pacing (180 beats per minute) for 10 days. On day 11, hypertension was induced by continuous angiotensin II infusion. We characterized the cardiorenal and humoral actions prior to, during, and following intravenous M-ANP (n=7), nitroglycerin (n=7), and vehicle (n=7) infusion. Mean arterial pressure (MAP) was reduced by M-ANP (139 ± 4 to 118 ± 3 mm Hg, P<0.05) and nitroglycerin (137 ± 3 to 116 ± 4 mm Hg, P<0.05); similar findings were recorded for pulmonary wedge pressure (PCWP) with M-ANP (12 ± 2 to 6 ± 2 mm Hg, P<0.05) and nitroglycerin (12 ± 1 to 6 ± 1 mm Hg, P<0.05). M-ANP enhanced renal function with significant increases (P<0.05) in glomerular filtration rate (38 ± 4 to 53 ± 5 mL/min), renal blood flow (132 ± 18 to 236 ± 23 mL/min), and natriuresis (11 ± 4 to 689 ± 37 mEq/min) and also inhibited aldosterone activation (32 ± 3 to 23 ± 2 ng/dL, P<0.05), whereas nitroglycerin had no significant (P>0.05) effects on these renal parameters or aldosterone activation. Our results advance the differential cardiorenal actions of pGC (M-ANP) and sGC (nitroglycerin) mediated cGMP activation. These distinct renal and aldosterone modulating actions make M-ANP an attractive therapeutic for HF with concomitant hypertension, where renal protection is a key therapeutic goal.

  18. Gating by Cyclic Gmp and Voltage in the α Subunit of the Cyclic Gmp–Gated Channel from Rod Photoreceptors

    PubMed Central

    Benndorf, Klaus; Koopmann, Rolf; Eismann, Elisabeth; Kaupp, U. Benjamin

    1999-01-01

    Gating by cGMP and voltage of the α subunit of the cGMP-gated channel from rod photoreceptor was examined with a patch-clamp technique. The channels were expressed in Xenopus oocytes. At low [cGMP] (<20 μM), the current displayed strong outward rectification. At low and high (700 μM) [cGMP], the channel activity was dominated by only one conductance level. Therefore, the outward rectification at low [cGMP] results solely from an increase in the open probability, P o. Kinetic analysis of single-channel openings revealed two exponential distributions. At low [cGMP], the larger P o at positive voltages with respect to negative voltages is caused by an increased frequency of openings in both components of the open-time distribution. In macroscopic currents, depolarizing voltage steps, starting from −100 mV, generated a time-dependent current that increased with the step size (activation). At low [cGMP] (20 μM), the degree of activation was large and the time course was slow, whereas at saturating [cGMP] (7 mM) the respective changes were small and fast. The dose–response relation at −100 mV was shifted to the right and saturated at significantly lower P o values with respect to that at +100 mV (0.77 vs. 0.96). P o was determined as function of the [cGMP] (at +100 and −100 mV) and voltage (at 20, 70, and 700 μM, and 7 mM cGMP). Both relations could be fitted with an allosteric state model consisting of four independent cGMP-binding reactions and one voltage-dependent allosteric opening reaction. At saturating [cGMP] (7 mM), the activation time course was monoexponential, which allowed us to determine the individual rate constants for the allosteric reaction. For the rapid rate constants of cGMP binding and unbinding, lower limits are determined. It is concluded that an allosteric model consisting of four independent cGMP-binding reactions and one voltage-dependent allosteric reaction, describes the cGMP- and voltage-dependent gating of cGMP-gated channels

  19. Ceruloplasmin ferroxidase activity stimulates cellular iron uptake by a trivalent cation-specific transport mechanism

    NASA Technical Reports Server (NTRS)

    Attieh, Z. K.; Mukhopadhyay, C. K.; Seshadri, V.; Tripoulas, N. A.; Fox, P. L.

    1999-01-01

    The balance required to maintain appropriate cellular and tissue iron levels has led to the evolution of multiple mechanisms to precisely regulate iron uptake from transferrin and low molecular weight iron chelates. A role for ceruloplasmin (Cp) in vertebrate iron metabolism is suggested by its potent ferroxidase activity catalyzing conversion of Fe2+ to Fe3+, by identification of yeast copper oxidases homologous to Cp that facilitate high affinity iron uptake, and by studies of "aceruloplasminemic" patients who have extensive iron deposits in multiple tissues. We have recently shown that Cp increases iron uptake by cultured HepG2 cells. In this report, we investigated the mechanism by which Cp stimulates cellular iron uptake. Cp stimulated the rate of non-transferrin 55Fe uptake by iron-deficient K562 cells by 2-3-fold, using a transferrin receptor-independent pathway. Induction of Cp-stimulated iron uptake by iron deficiency was blocked by actinomycin D and cycloheximide, consistent with a transcriptionally induced or regulated transporter. Cp-stimulated iron uptake was completely blocked by unlabeled Fe3+ and by other trivalent cations including Al3+, Ga3+, and Cr3+, but not by divalent cations. These results indicate that Cp utilizes a trivalent cation-specific transporter. Cp ferroxidase activity was required for iron uptake as shown by the ineffectiveness of two ferroxidase-deficient Cp preparations, copper-deficient Cp and thiomolybdate-treated Cp. We propose a model in which iron reduction and subsequent re-oxidation by Cp are essential for an iron uptake pathway with high ion specificity.

  20. Defining Specificity Determinants of cGMP Mediated Gustatory Sensory Transduction in Caenorhabditis elegans

    PubMed Central

    Smith, Heidi K.; Luo, Linjiao; O’Halloran, Damien; Guo, Dagang; Huang, Xin-Yun; Samuel, Aravinthan D. T.; Hobert, Oliver

    2013-01-01

    Cyclic guanosine monophosphate (cGMP) is a key secondary messenger used in signal transduction in various types of sensory neurons. The importance of cGMP in the ASE gustatory receptor neurons of the nematode Caenorhabditis elegans was deduced by the observation that multiple receptor-type guanylyl cyclases (rGCs), encoded by the gcy genes, and two presently known cyclic nucleotide-gated ion channel subunits, encoded by the tax-2 and tax-4 genes, are essential for ASE-mediated gustatory behavior. We describe here specific mechanistic features of cGMP-mediated signal transduction in the ASE neurons. First, we assess the specificity of the sensory functions of individual rGC proteins. We have previously shown that multiple rGC proteins are expressed in a left/right asymmetric manner in the functionally lateralized ASE neurons and are required to sense distinct salt cues. Through domain swap experiments among three different rGC proteins, we show here that the specificity of individual rGC proteins lies in their extracellular domains and not in their intracellular, signal-transducing domains. Furthermore, we find that rGC proteins are also sufficient to confer salt sensory responses to other neurons. Both findings support the hypothesis that rGC proteins are salt receptor proteins. Second, we identify a novel, likely downstream effector of the rGC proteins in gustatory signal transduction, a previously uncharacterized cyclic nucleotide-gated (CNG) ion channel, encoded by the che-6 locus. che-6 mutants show defects in gustatory sensory transduction that are similar to defects observed in animals lacking the tax-2 and tax-4 CNG channels. In contrast, thermosensory signal transduction, which also requires tax-2 and tax-4, does not require che-6, but requires another CNG, cng-3. We propose that CHE-6 may form together with two other CNG subunits, TAX-2 and TAX-4, a gustatory neuron-specific heteromeric CNG channel complex. PMID:23695300

  1. Sorption of the organic cation metoprolol on silica gel from its aqueous solution considering the competition of inorganic cations.

    PubMed

    Kutzner, Susann; Schaffer, Mario; Börnick, Hilmar; Licha, Tobias; Worch, Eckhard

    2014-05-01

    Systematic batch experiments with the organic monovalent cation metoprolol as sorbate and the synthetic material silica gel as sorbent were conducted with the aim of characterizing the sorption of organic cations onto charged surfaces. Sorption isotherms for metoprolol (>99% protonated in the tested pH of around 6) in competition with mono- and divalent inorganic cations (Na(+), NH4(+), Ca(2+), and Mg(2+)) were determined in order to assess their influence on cation exchange processes and to identify the role of further sorptive interactions. The obtained sorption isotherms could be described well by an exponential function (Freundlich isotherm model) with consistent exponents (about 0.8). In general, a decreasing sorption of metoprolol with increasing concentrations in inorganic cations was observed. Competing ions of the same valence showed similar effects. A significant sorption affinity of metoprolol with ion type dependent Freundlich coefficients KF,0.77 between 234.42 and 426.58 (L/kg)(0.77) could still be observed even at very high concentrations of competing inorganic cations. Additional column experiments confirm this behavior, which suggests the existence of further relevant interactions beside cation exchange. In subsequent batch experiments, the influence of mixtures with more than one competing ion and the effect of a reduced negative surface charge at a pH below the point of zero charge (pHPZC ≈ 2.5) were also investigated. Finally, the study demonstrates that cation exchange is the most relevant but not the sole mechanism for the sorption of metoprolol on silica gel. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Divalent cation shrinks DNA but inhibits its compaction with trivalent cation.

    PubMed

    Tongu, Chika; Kenmotsu, Takahiro; Yoshikawa, Yuko; Zinchenko, Anatoly; Chen, Ning; Yoshikawa, Kenichi

    2016-05-28

    Our observation reveals the effects of divalent and trivalent cations on the higher-order structure of giant DNA (T4 DNA 166 kbp) by fluorescence microscopy. It was found that divalent cations, Mg(2+) and Ca(2+), inhibit DNA compaction induced by a trivalent cation, spermidine (SPD(3+)). On the other hand, in the absence of SPD(3+), divalent cations cause the shrinkage of DNA. As the control experiment, we have confirmed the minimum effect of monovalent cation, Na(+) on the DNA higher-order structure. We interpret the competition between 2+ and 3+ cations in terms of the change in the translational entropy of the counterions. For the compaction with SPD(3+), we consider the increase in translational entropy due to the ion-exchange of the intrinsic monovalent cations condensing on a highly charged polyelectrolyte, double-stranded DNA, by the 3+ cations. In contrast, the presence of 2+ cation decreases the gain of entropy contribution by the ion-exchange between monovalent and 3+ ions.

  3. The tetravalent organic cation spermine causes the gating of the IRK1 channel expressed in murine fibroblast cells.

    PubMed Central

    Ishihara, K; Hiraoka, M; Ochi, R

    1996-01-01

    1. The activation kinetics of the IRK1 channel stably expressed in L cells (a murine fibroblast cell line) were studied under the whole-cell voltage clamp. Without polyamines or Mg2+ in the pipettes, inward currents showed an exponential activation on hyperpolarization. The steep inward rectification of the currents around the reversal potential (Erev) could be described by the open-close transition of the channel with first-order kinetics. 2. When the tetravalent organic cation spermine (Spm) was added in the pipettes, the activation kinetics changed; this was explicable by the increase in the closing rate constant. The activation of the currents observed without Spm or Mg2+ in the pipettes was ascribed to the unblocking of the 'endogenous-Spm block'. 3. In the presence of the divalent cation putrescine (Put) or of Mg2+ in the pipettes, a different non-conductive state suppressed the outward currents on depolarization; the channels instantaneously changed to the open state on repolarization. As the depolarization was prolonged, this non-conductive state was replaced by the non-conductive state that shows an exponential activation on repolarization. This phenomenon was attributed to the redistribution of the channels from the Put- or Mg(2+)-blocked state to the 'endogenous Spm-blocked state' during depolarization. 4. In the presence of the trivalent cation spermidine (Spd) in the pipettes, two different non-conductive states occurred, showing a faster and a slower activation on repolarization. The rectification around Erev was mainly due to the non-conductive state showing a faster activation, which appeared to be the Spd-blocked state. During depolarization, redistribution of the channels to the 'endogenous Spm-blocked state' also occurred. 5. In the presence of Spd, Put or Mg2+ in the pipettes, the voltage dependence of the activation time constant reflecting the unblocking of the 'endogenous Spm' was shifted in the hyperpolarizing direction. 6. Our results

  4. Activation of particulate guanylyl cyclase by endothelins in cultured SV-40 transformed cat iris sphincter smooth muscle cells.

    PubMed

    Ding, K H; Latimer, A J; Abdel-Latif, A A

    1999-01-01

    We investigated the effects of endothelins (ETs) on cGMP production in cultured SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells. ET-3 increased cGMP formation in a concentration-dependent manner (EC50 = 98nM), which was 2.5 times higher than that of ET-1. The ET(B)receptor agonists sarafotoxin-S6c and IRL 1620 also increased cGMP production, mimicking the effects of the ETs. The ET(B) receptor antagonist BQ 788, but not the ET(A) receptor antagonist BQ610, dose-dependently blocked ET-3-stimulated cGMP formation (IC50=10nM). The phorbol ester, Phorbol 12, 13-dibutyrate (PDBu), which inhibits particulate guanylyl cyclase in smooth muscle, dose-dependently inhibited ET-3-stimulated cGMP accumulation (IC50=66nM). LY83583 and ODQ, inhibitors of soluble guanylyl cyclases, as well as inhibitors of the nitric oxide cascade and of intracellular Ca2+ elevation had no appreciable effect on ET-3-induced cGMP production. ET-3 markedly inhibited carbachol-induced intracellular Ca2+ mobilization. We conclude that ET-3 increases intracellular cGMP levels in SV-CISM-2 cells through activation of the ET(B) receptor subtype and subsequent stimulation of the membrane-bound guanylyl cyclase. Elevation of cGMP by ET and the subsequent inhibition of muscarinic stimulation of intracellular Ca2+ mobilization by the cyclic nucleotide could serve to modulate the contractile effects of Ca2+-mobilizing agonists in the iris sphincter smooth muscle.

  5. Structural and functional characterization of a calcium-activated cation channel from Tsukamurella paurometabola

    NASA Astrophysics Data System (ADS)

    Dhakshnamoorthy, Balasundaresan; Rohaim, Ahmed; Rui, Huan; Blachowicz, Lydia; Roux, Benoît

    2016-09-01

    The selectivity filter is an essential functional element of K+ channels that is highly conserved both in terms of its primary sequence and its three-dimensional structure. Here, we investigate the properties of an ion channel from the Gram-positive bacterium Tsukamurella paurometabola with a selectivity filter formed by an uncommon proline-rich sequence. Electrophysiological recordings show that it is a non-selective cation channel and that its activity depends on Ca2+ concentration. In the crystal structure, the selectivity filter adopts a novel conformation with Ca2+ ions bound within the filter near the pore helix where they are coordinated by backbone oxygen atoms, a recurrent motif found in multiple proteins. The binding of Ca2+ ion in the selectivity filter controls the widening of the pore as shown in crystal structures and in molecular dynamics simulations. The structural, functional and computational data provide a characterization of this calcium-gated cationic channel.

  6. Effect of A-Site Cation Ordering on Chemical Stability, Oxygen Stoichiometry and Electrical Conductivity in Layered LaBaCo2O5+δ Double Perovskite

    PubMed Central

    Bernuy-Lopez, Carlos; Høydalsvik, Kristin; Einarsrud, Mari-Ann; Grande, Tor

    2016-01-01

    The effect of the A-site cation ordering on the chemical stability, oxygen stoichiometry and electrical conductivity in layered LaBaCo2O5+δ double perovskite was studied as a function of temperature and partial pressure of oxygen. Tetragonal A-site cation ordered layered LaBaCo2O5+δ double perovskite was obtained by annealing cubic A-site cation disordered La0.5Ba0.5CoO3-δ perovskite at 1100 °C in N2. High temperature X-ray diffraction between room temperature (RT) and 800 °C revealed that LaBaCo2O5+δ remains tetragonal during heating in oxidizing atmosphere, but goes through two phase transitions in N2 and between 450 °C and 675 °C from tetragonal P4/mmm to orthorhombic Pmmm and back to P4/mmm due to oxygen vacancy ordering followed by disordering of the oxygen vacancies. An anisotropic chemical and thermal expansion of LaBaCo2O5+δ was demonstrated. La0.5Ba0.5CoO3-δ remained cubic at the studied temperature irrespective of partial pressure of oxygen. LaBaCo2O5+δ is metastable with respect to La0.5Ba0.5CoO3-δ at oxidizing conditions inferred from the thermal evolution of the oxygen deficiency and oxidation state of Co in the two materials. The oxidation state of Co is higher in La0.5Ba0.5CoO3-δ resulting in a higher electrical conductivity relative to LaBaCo2O5+δ. The conductivity in both materials was reduced with decreasing partial pressure of oxygen pointing to a p-type semiconducting behavior. PMID:28773279

  7. The type II cGMP dependent protein kinase regulates GluA1 levels at the plasma membrane of developing cerebellar granule cells

    PubMed Central

    Incontro, Salvatore; Ciruela, Francisco; Ziff, Edward; Hofmann, Franz; Sánchez-Prieto, José; Torres, Magdalena

    2014-01-01

    Trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is regulated by specific interactions with other proteins and by post-translational mechanisms, such as phosphorylation. We have found that the type II cGMP-dependent protein kinase (cGKII) phosphorylates GluA1 (formerly GluR1) at S845, augmenting the surface expression of AMPARs at both synaptic and extrasynaptic sites. Activation of cGKII by 8-Br-cGMP enhances the surface expression of GluA1, whereas its inhibition or suppression effectively diminished the expression of this protein at the cell surface. In granule cells, NMDA receptor activation (NMDAR) stimulates nitric oxide and cGMP production, which in turn activates cGKII and induces the phosphorylation of GluA1, promoting its accumulation in the plasma membrane. GluA1 is mainly incorporated into calcium permeable AMPARs as exposure to 8-Br-cGMP or NMDA activation enhanced AMPA-elicited calcium responses that are sensitive to NASPM inhibition. We summarize evidence for an increase of calcium permeable AMPA receptors downstream of NMDA receptor activation that might be relevant for granule cell development and plasticity. PMID:23545413

  8. Does the cation really matter? The effect of modifying an ionic liquid cation on an SN2 process.

    PubMed

    Tanner, Eden E L; Yau, Hon Man; Hawker, Rebecca R; Croft, Anna K; Harper, Jason B

    2013-09-28

    The rate of reaction of a Menschutkin process in a range of ionic liquids with different cations was investigated, with temperature-dependent kinetic data giving access to activation parameters for the process in each solvent. These data, along with molecular dynamics simulations, demonstrate the importance of accessibility of the charged centre on the cation and that the key interactions are of a generalised electrostatic nature.

  9. Evaluation of the antibacterial activity of a cationic polymer in aqueous solution with a convenient electrochemical method.

    PubMed

    Wang, Yihong; Guo, Qing; Wang, Huafu; Qian, Kun; Tian, Liang; Yao, Chen; Song, Wei; Shu, Weixia; Chen, Ping; Qi, Jinxu

    2017-02-01

    Quaternized chitosan is a cationic biopolymer with good antibacterial activity, biocompatibility, and biodegradability, and it has been widely applied in many fields. We have developed a convenient method to evaluate the antibacterial activity of hydroxypropyltrimethylammonium chloride chitosan (HACC) with a nonionic surfactant poloxamer in aqueous solution by monitoring the change of the oxidation peak current in cyclic voltammetry. Increasing values of the oxidation peak current were positively correlated with the antibacterial activity of HACC-poloxamer solutions. Optical microscope images, the zeta potential, and fluorescence spectroscopy showed that the aggregation state of HACC-poloxamer was related to the ratio of the two polymers and also to the antibacterial activity and oxidation peak current. At an HACC-to-poloxamer ratio of 1:0.75, the maximum surface charge density and the smooth edge of HACC-poloxamer aggregates can accelerate diffusion in aqueous solution. It is expected that this convenient method can be applied for a quick evaluation of the antibacterial activity of cationic biopolymers in aqueous solution. Graphical Abstract The cyclic voltammograms of MB in HACC/poloxamer solution, and the antibacterial efficiency against S. aureus after incubated with HACC (a) and 1/0.75 of HACC/poloxamer (b).

  10. Synthesis and antibacterial evaluation of novel cationic chalcone derivatives possessing broad spectrum antibacterial activity.

    PubMed

    Chu, Wen-Chao; Bai, Peng-Yan; Yang, Zhao-Qing; Cui, De-Yun; Hua, Yong-Gang; Yang, Yi; Yang, Qian-Qian; Zhang, En; Qin, Shangshang

    2018-01-01

    There is an urgent need to identify new antibiotics with novel mechanisms that combat antibiotic resistant bacteria. Herein, a series of chalcone derivatives that mimic the essential properties of cationic antimicrobial peptides were designed and synthesized. Antibacterial activities against drug-sensitive bacteria, including Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Salmonella enterica, as well as clinical multiple drug resistant isolates of methicillin-resistant S. aureus (MRSA), KPC-2-producing and NDM-1-producing Carbapenem-resistant Enterobacteriaceae were evaluated. Representative compounds 5a (MIC: 1 μg/mL against S. aureus, 0.5 μg/mL against MRSA) and 5g (MIC: 0.5 μg/mL against S. aureus, 0.25 μg/mL against MRSA) showed good bactericidal activity against both Gram-positive and Gram-negative bacteria, including the drug-resistant species MRSA, KPC and NDM. These membrane-active antibacterial compounds were demonstrated to reduce the viable cell counts in bacterial biofilms effectively and do not induce the development of resistance in bacteria. Additionally, these representative molecules exhibited negligible toxicity toward mammalian cells at a suitable concentration. The combined results indicate that this series of cationic chalcone derivatives have potential therapeutic effects against bacterial infections. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Lysine-containing cationic liposomes activate the NLRP3 inflammasome: Effect of a spacer between the head group and the hydrophobic moieties of the lipids.

    PubMed

    Li, Tianshu; He, Jieyan; Horvath, Gabor; Próchnicki, Tomasz; Latz, Eicke; Takeoka, Shinji

    2018-02-01

    Cationic lipids containing lysine head groups and ditetradecyl, dihexadecyl or dioctadecyl glutamate hydrophobic moieties with/without propyl, pentyl or heptyl spacers were applied for the preparation of cationic liposomes using a simple bath type-sonicator. The size distribution, zeta potential, cellular internalization, and cytotoxicity of the liposomes were characterized, and the innate immune stimulation, e.g., the NLRP3 inflammasome activation of human macrophages and THP-1 cells, was evaluated by the detection of IL-1β release. Comparatively, L3C14 and L5C14 liposomes, made from the lipids bearing lysine head groups, ditetradecyl hydrophobic chains and propyl or pentyl spacers, respectively, were the most potent to activate the NLRP3 inflammasome. The possible mechanism includes endocytosis of the cationic liposomes and subsequent lysosome rupture without significant inducement of reactive oxygen species production. In summary, we first disclosed the structural effect of cationic liposomes on the NLRP3 inflammasome activation, which gives an insight into the application of nanoparticles for improved immune response. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Immune complexes with cationic antibodies deposit in glomeruli more effectively than cationic antibodies alone.

    PubMed

    Mannik, M; Gauthier, V J; Stapleton, S A; Agodoa, L Y

    1987-06-15

    In previously published studies, highly cationized antibodies alone and in immune complexes bound to glomeruli by charge-charge interaction, but only immune complexes persisted in glomeruli. Because normal IgG does not deposit in glomeruli, studies were conducted to determine whether cationized antibodies can be prepared which deposit in glomeruli when bound to antigen but not when free in circulation. A series of cationized rabbit antiHSA was prepared with the number of added amino groups ranging from 13.3 to 60.2 per antibody molecule. Antibodies alone or in preformed soluble immune complexes, prepared at fivefold or 50-fold antigen excess, were administered to mice. With the injection of a fixed dose of 100 micrograms per mouse, antibodies alone did not deposit in glomeruli with less than 29.6 added amino groups by immunofluorescence microscopy. In contrast, 100 micrograms of antibodies with 23.5 added amino groups in immune complexes, made at fivefold antigen excess, formed immune deposits in glomeruli. With selected preparations of cationized, radiolabeled antibodies, deposition in glomeruli was quantified by isolation of mouse glomeruli. These quantitative data were in good agreement with the results of immunofluorescence microscopy. Immune complexes made at 50-fold antigen excess, containing only small-latticed immune complexes with no more than two antibody molecules per complex, deposited in glomeruli similar to antibodies alone. Selected cationized antibodies alone or in immune complexes were administered to mice in varying doses. In these experiments, glomerular deposition of immune complexes, made at fivefold antigen excess, was detected with five- to 10-fold smaller doses than the deposition of the same antibodies alone. These studies demonstrate that antibody molecules in immune complexes are more likely to deposit in glomeruli by charge-charge interactions than antibodies alone.

  13. Alternating-current conductivity and dielectric relaxation of bulk iodoargentate

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Duan, Hai-Bao, E-mail: duanhaibao4660@163.com; Yu, Shan-Shan; Zhou, Hong

    Graphical abstract: The electric modulus shows single dielectric relaxation process in the measured frequency range. - Highlights: • The conduction mechanism is described by quantum mechanical tunneling model. • The applications of dielectric modulus give a simple method for evaluating the activation energy of the dielectric relaxation. • The [Ag{sub 2}I{sub 4}]{sup 2−}1-D chain and [Cu(en){sub 2}]{sup 2+} cation column form the layered stacks by hydrogen bond interactions. - Abstract: An inorganic-organic hybrid compound Cu(en){sub 2}Ag{sub 2}I{sub 4} (en = ethylenediamine) (1) was synthesized and single crystal structurally characterized. Along the [001] direction, the inorganic parts form an infinite 1-Dmore » chain and [Cu(en){sub 2}]{sup 2+} cations are separated by inorganic chain. The electrical conductivity and dielectric properties of 1 have been investigated over wide ranges of frequency. The alternating-current conductivities have been fitted to the Almond–West type power law expression with use of a single value of S. It is found that S values for 1 are nearly temperature-independent, which indicates that the conduction mechanism could be quantum mechanical tunneling (QMT) model. The dielectric loss and electric modulus show single dielectric relaxation process. The activation energy obtained from temperature-dependent electric modulus compare with the calculated from the dc conductivity plots.« less

  14. Viscosity, conductivity, and electrochemical property of dicyanamide ionic liquids

    NASA Astrophysics Data System (ADS)

    Yuan, Wen-Li; Yang, Xiao; He, Ling; Xue, Ying; Qin, Song; Tao, Guo-Hong

    2018-03-01

    The instructive structure-property relationships of ionic liquids (ILs) can be put to task-specific design of new functionalized ILs. The dicyanamide (DCA) ILs are typical CHN type ILs which are halogen free, chemical stable, low-viscous and fuel-rich. The transport properties of DCA ionic liquids are significant for their applications as solvents, electrolytes and hypergolic propellants. This work systematically investigates several important transport properties of four DCA ILs ([C4mim][N(CN)2], [C4m2im][N(CN)2], N4442[N(CN)2], and N8444[N(CN)2]) including viscosity, conductivity, and electrochemical property at different temperatures. The melting points, temperature-dependent viscosities and conductivities reveal the structure-activity relationship of four DCA ILs. From the Walden plots, the imidazolium cations exhibit stronger cation–anion attraction than the ammonium cations. DCA ILs have relatively high values of electrochemical windows (EWs), which indicates that the DCA ILs are potential candidates for electrolytes in electrochemical applications. The cyclic voltammograms of Eu(III) in these DCA ILs at GC working electrode at various temperatures 303–333 K consists of quasi-reversible waves. The electrochemical properties of the DCA ILs are also dominated by the cationic structures. The current intensity (ip), the diffusion coefficients (Do), the charge transfer rate constants (ks) of Eu(III) in DCA ILs all increased with the molar conductivities increased. The cationic structure-transport property relationships of DCA ILs were constructed for designing novel functionalized ILs to fulfill specific demands.

  15. Viscosity, Conductivity, and Electrochemical Property of Dicyanamide Ionic Liquids

    PubMed Central

    Yuan, Wen-Li; Yang, Xiao; He, Ling; Xue, Ying; Qin, Song; Tao, Guo-Hong

    2018-01-01

    The instructive structure-property relationships of ionic liquids (ILs) can be put to task-specific design of new functionalized ILs. The dicyanamide (DCA) ILs are typical CHN type ILs which are halogen free, chemical stable, low-viscous, and fuel-rich. The transport properties of DCA ionic liquids are significant for their applications as solvents, electrolytes, and hypergolic propellants. This work systematically investigates several important transport properties of four DCA ILs ([C4mim][N(CN)2], [C4m2im][N(CN)2], N4442[N(CN)2], and N8444[N(CN)2]) including viscosity, conductivity, and electrochemical property at different temperatures. The melting points, temperature-dependent viscosities and conductivities reveal the structure-activity relationship of four DCA ILs. From the Walden plots, the imidazolium cations exhibit stronger cation–anion attraction than the ammonium cations. DCA ILs have relatively high values of electrochemical windows (EWs), which indicates that the DCA ILs are potential candidates for electrolytes in electrochemical applications. The cyclic voltammograms of Eu(III) in these DCA ILs at GC working electrode at various temperatures 303–333 K consists of quasi-reversible waves. The electrochemical properties of the DCA ILs are also dominated by the cationic structures. The current intensity (ip), the diffusion coefficients (Do), the charge transfer rate constants (ks) of Eu(III) in DCA ILs all increased with the molar conductivities increased. The cationic structure-transport property relationships of DCA ILs were constructed for designing novel functionalized ILs to fulfill specific demands. PMID:29600245

  16. Cationic uremic toxins affect human renal proximal tubule cell functioning through interaction with the organic cation transporter.

    PubMed

    Schophuizen, Carolien M S; Wilmer, Martijn J; Jansen, Jitske; Gustavsson, Lena; Hilgendorf, Constanze; Hoenderop, Joost G J; van den Heuvel, Lambert P; Masereeuw, Rosalinde

    2013-12-01

    Several organic cations, such as guanidino compounds and polyamines, have been found to accumulate in plasma of patients with kidney failure due to inadequate renal clearance. Here, we studied the interaction of cationic uremic toxins with renal organic cation transport in a conditionally immortalized human proximal tubule epithelial cell line (ciPTEC). Transporter activity was measured and validated in cell suspensions by studying uptake of the fluorescent substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium-iodide (ASP(+)). Subsequently, the inhibitory potencies of the cationic uremic toxins, cadaverine, putrescine, spermine and spermidine (polyamines), acrolein (polyamine breakdown product), guanidine, and methylguanidine (guanidino compounds) were determined. Concentration-dependent inhibition of ASP(+) uptake by TPA, cimetidine, quinidine, and metformin confirmed functional endogenous organic cation transporter 2 (OCT2) expression in ciPTEC. All uremic toxins tested inhibited ASP(+) uptake, of which acrolein required the lowest concentration to provoke a half-maximal inhibition (IC50 = 44 ± 2 μM). A Dixon plot was constructed for acrolein using three independent inhibition curves with 10, 20, or 30 μM ASP(+), which demonstrated competitive or mixed type of interaction (K i = 93 ± 16 μM). Exposing the cells to a mixture of cationic uremic toxins resulted in a more potent and biphasic inhibitory response curve, indicating complex interactions between the toxins and ASP(+) uptake. In conclusion, ciPTEC proves a suitable model to study cationic xenobiotic interactions. Inhibition of cellular uptake transport was demonstrated for several uremic toxins, which might indicate a possible role in kidney disease progression during uremia.

  17. Measurement of cation exchange capacity (CEC) on natural zeolite by percolation method

    NASA Astrophysics Data System (ADS)

    Wiyantoko, Bayu; Rahmah, Nafisa

    2017-12-01

    The cation exchange capacity (CEC)measurement has been carried out in natural zeolite by percolation method. The natural zeolite samples used for cation exchange capacity measurement were activated beforehand with physical activation and chemical activation. The physically activated zeolite was done by calcination process at 600 °C for 4 hours. The natural zeolite was activated chemically by using sodium hydroxide by refluxing process at 60-80 °C for 3 hours. In summary, cation exchange capacity (CEC) determination was performed by percolation, distillation and titration processes. Based on the measurement that has been done, the exchange rate results from physical activated and chemical activated of natural zeolite were 181.90cmol (+)/kg and 901.49cmol (+)/kg respectively.

  18. Small Water Cluster Cations

    NASA Astrophysics Data System (ADS)

    Novakovskaya, Yu. V.; Stepanov, N. F.

    Structures of water cluster cations (H_{2}O)^{+}_{n} with n ≤ 5 are optimized at the unrestricted Hartree-Fock level with the 4 - 31 + +G** basis set. Energetic characteristics of the cations are then estimated taking into account the second order perturbation corrections (MP2). After the electron detachment from a neutral cluster, the structure of the latter substantially changes, so that OH and H3O+ fragments can be distinguished in it. In some cations H3O+ is so strongly bonded to water molecules that it is reasonable to speak of the [H2n-1On-1]+ fragments. According to the position of OH, the structures form two groups. In one group, OH acts exclusively as the proton acceptor in H-bonds with water molecules, thus being terminal in the chain-like structures; in the other group it is directly bonded to H3O and, as a proton donor, forms an H-bond with water molecule. Cluster cations do not tend to dissociate into the fragments. However, an external influence of ≤ 0.4 eV is sufficient for the cations of the first group to dissociate into a free OH radical and a protonated cluster H+(H2O)n-1. Extrapolation of the calculated adiabatic ionization potentials of the water clusters to n → ∞ provides a value of 8.6 eV, which can be considered as an estimation of the electron work function of water. This value is close to the experimental photoelectric thresholds of amorphous ice (8.7 ± 0.1 eV) and water (9.39 ± 0.3 eV). Solvation of the electron lowers the value, and an energy of 7 eV can be sufficient for initiating conductivity. This prediction is in accord with the experiment: irradiating ice with ultraviolet light of the photon energy 6.5-6.8 eV initiates photoconductivity, and hydrogen peroxide and H3O+ ions are observed.

  19. Studies on ocular and parenteral application potentials of azithromycin- loaded anionic, cationic and neutral-charged emulsions.

    PubMed

    Tamilvanan, Shunmugaperumal; Khanum, Ramona; Senthilkumar, Sudalimuthu Ramachandran; Muthuraman, Marimuthu; Rajasekharan, Thenrajan

    2013-10-01

    Ocular and parenteral application potentials of azithromycin-containing, non-phospholipid-based cationic nanosized emulsion in comparison to the phospholipid-based anionic and neutral-charged nanosized emulsions were investigated. Various physical, chemical, nonclinical toxicity and antimicrobial activity studies (mean droplet diameter, surface charge, creaming index, entrapment efficiency, accelerated, long-term and freeze-thaw cycling stabilities, TLC study, modified hen's egg chorioallantoic membrane (HET-CAM) test, in vitro hemolysis test, in vitro and in vivo myotoxicity, and in vitro antimicrobial activity) were conducted for assessing the potentials of these three types of emulsions. Following autoclave sterilization, all of these emulsions exhibited a nanometer range mean particle diameter (200 ± 29 to 434 ± 13 nm). While the anionic and cationic emulsions did show high negative (-34.2 ± 1.23 mV) and positive zeta potential (42.6 ± 1.45 mV) values, the neutral-charged emulsion did not. Even with 5 freeze-thaw cycles, the cationic emulsion remained stable whereas other two emulsions underwent phase-separation. The hen's egg chorioallantoic membrane test revealed an irritation score value that was higher for the anionic emulsion than for cationic or neutral-charged emulsion. A significantly higher % hemolysis value was also noticed for the anionic emulsion when compared to the % hemolysis value of cationic emulsion (ANOVA, P ‹ 0.05). However, all of the emulsions showed a lesser intracellular creatine kinase (CK) release/plasma CK level in comparison to the positive control (phenytoin) indicating their lesser myotoxicity at the injection site . When compared to anionic and neutral-charged emulsions, the possible controlled drug release from cationic emulsion delayed the in vitro antimicrobial action against H.influenzae and S.pneumoniae.

  20. Structure-Antibacterial Activity Relationships of Imidazolium-Type Ionic Liquid Monomers, Poly(ionic liquids) and Poly(ionic liquid) Membranes: Effect of Alkyl Chain Length and Cations.

    PubMed

    Zheng, Zhiqiang; Xu, Qiming; Guo, Jiangna; Qin, Jing; Mao, Hailei; Wang, Bin; Yan, Feng

    2016-05-25

    The structure-antibacterial activity relationship between the small molecular compounds and polymers are still elusive. Here, imidazolium-type ionic liquid (IL) monomers and their corresponding poly(ionic liquids) (PILs) and poly(ionic liquid) membranes were synthesized. The effect of chemical structure, including carbon chain length of substitution at the N3 position and charge density of cations (mono- or bis-imidazolium) on the antimicrobial activities against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was investigated by determination of minimum inhibitory concentration (MIC). The antibacterial activities of both ILs and PILs were improved with the increase of the alkyl chain length and higher charge density (bis-cations) of imidazolium cations. Moreover, PILs exhibited lower MIC values relative to the IL monomers. However, the antibacterial activities of PIL membranes showed no correlation to those of their analogous small molecule IL monomers and PILs, which increased with the charge density (bis-cations) while decreasing with the increase of alkyl chain length. The results indicated that antibacterial property studies on small molecules and homopolymers may not provide a solid basis for evaluating that in corresponding polymer membranes.

  1. Investigations of the ex situ ionic conductivities at 30 degrees C of metal-cation-free quaternary ammonium alkaline anion-exchange membranes in static atmospheres of different relative humidities.

    PubMed

    Varcoe, John R

    2007-03-28

    This article presents the first systematic study of the effect of Relative Humidity (RH) on the water content and hydroxide ion conductivity of quaternary ammonium-based Alkaline Anion-Exchange Membranes (AAEMs). These AAEMs have been developed specifically for application in alkaline membrane fuel cells, where conductivities of >0.01 S cm(-1) are mandatory. When fully hydrated, an ETFE-based radiation-grafted AAEM exhibited a hydroxide ion conductivity of 0.030 +/- 0.005 S cm(-1) at 30 degrees C without additional incorporation of metal hydroxide salts; this is contrary to the previous wisdom that anion-exchange membranes are very low in ionic conductivity and represents a significant breakthrough for metal-cation-free alkaline ionomers. Desirably, this AAEM also showed increased dimensional stability on full hydration compared to a Nafion-115 proton-exchange membrane; this dimensional stability is further improved (with no concomitant reduction in ionic conductivity) with a commercial AAEM of similar density but containing additional cross-linking. However, all of the AAEMs evaluated in this study demonstrated unacceptably low conductivities when the humidity of the surrounding static atmospheres was reduced (RH = 33-91%); this highlights the requirement for continued AAEM development for operation in H(2)/air fuel cells with low humidity gas supplies. Preliminary investigations indicate that the activation energies for OH(-) conduction in these quaternary ammonium-based solid polymer electrolytes are typically 2-3 times higher than for H(+) conduction in acidic Nafion-115 at all humidities.

  2. Antimicrobial particles from cationic lipid and polyelectrolytes.

    PubMed

    Melo, Letícia D; Mamizuka, Elsa M; Carmona-Ribeiro, Ana M

    2010-07-20

    Hybrid nanoparticles from cationic lipid and polymers were prepared and characterized regarding physical properties and antimicrobial activity. Carboxymethylcellulose (CMC) and polydiallyldimethylammonium chloride (PDDA) were sequentially added to cationic bilayer fragments (BF) prepared from ultrasonic dispersion in water of the synthetic and cationic lipid dioctadecyldimethylammonium bromide (DODAB). Particles thus obtained were characterized by dynamic light-scattering for determination of z-average diameter (Dz) and zeta-potential (zeta). Antimicrobial activity of the DODAB BF/CMC/PDDA particles against Pseudomonas aeruginosa or Staphylococcus aureus was determined by plating and CFU counting over a range of particle compositions. DODAB BF/CMC/PDDA particles exhibited sizes and zeta-potentials strictly dependent on DODAB, CMC, and PDDA concentrations. At 0.1 mM DODAB, 0.1 mg/mL CMC, and 0.1 mg/mL PDDA, small cationic particles with Dz = 100 nm and zeta = 30 mV were obtained. At 0.5 mM DODAB, 0.5 mg/mL CMC and 0.5 mg/mL PDDA, large cationic particles with Dz = 470 nm and zeta = 50 mV were obtained. Both particulates were highly reproducible regarding physical properties and yielded 0% of P. aeruginosa viability (10(7) CFU/mL) at 1 or 2 microg/mL PDDA dissolved in solution or in form of particles, respectively. 99% of S. aureus cells died at 10 microg/mL PDDA alone or in small or large DODAB BF/CMC/PDDA particles. The antimicrobial effect was dependent on the amount of positive charge on particles and independent of particle size. A high microbicide potency for PDDA over a range of nanomolar concentrations was disclosed. P. aeruginosa was more sensitive to all cationic assemblies than S. aureus.

  3. Simultaneous anionic and cationic redox

    NASA Astrophysics Data System (ADS)

    Jung, Sung-Kyun; Kang, Kisuk

    2017-12-01

    It is challenging to unlock anionic redox activity, accompanied by full utilization of available cationic redox process, to boost capacity of battery cathodes. Now, material design by tuning the metal-oxygen interaction is shown to be a promising solution.

  4. Mechanosensitive cation channels in human leukaemia cells: calcium permeation and blocking effect

    PubMed Central

    Staruschenko, Alexandr V; Vedernikova, Elena A

    2002-01-01

    Cell-attached and inside-out patch-clamp methods were employed to identify and characterize mechanosensitive (MS) ionic channels in the plasma membrane of human myeloid leukaemia K562 cells. A reversible activation of gadolinium-blockable mechanogated currents in response to negative pressure application was found in 58 % of stable patches (n = 317). I-V relationships measured with a sodium-containing pipette solution showed slight inward rectification. Data analysis revealed the presence of two different populations of channels that were distinguishable by their conductance properties (17.2 ± 0.3 pS and 24.5 ± 0.5 pS), but were indistinguishable with regard to their selective and pharmacological properties. Ion-substitution experiments indicated that MS channels in leukaemia cells were permeable to cations but not to anions and do not discriminate between Na+ and K+. The channels were fully impermeable to large organic cations such as Tris+ and N-methyl-d-glucamine ions (NMDG+). Ca2+ permeation and blockade of MS channels were examined using pipettes containing different concentrations of Ca2+. In the presence of 2 mm CaCl2, when other cations were impermeant, both outward and inward single-channel currents were observed; the I-V relationship showed a unitary conductance of 7.7 ± 1.0 pS. The relative permeability value, PCa/PK, was equal to 0.75, as estimated at physiological Ca2+ concentrations. Partial or full inhibition of inward Ca2+ currents through MS channels was observed at higher concentrations of external Ca2+ (10 or 20 mm). No MS channels were activated when using a pipette containing 90 mm CaCl2. Monovalent mechanogated currents were not significantly affected by extracellular Ca2+ at concentrations within the physiological range (0-2 mm), and at some higher Ca2+ concentrations. PMID:12015421

  5. Structure-activity relationship of carbamate-linked cationic lipids bearing hydroxyethyl headgroup for gene delivery.

    PubMed

    Zhi, Defu; Zhang, Shubiao; Qureshi, Farooq; Zhao, Yinan; Cui, Shaohui; Wang, Bing; Chen, Huiying; Yang, Baoling; Zhao, Defeng

    2013-12-01

    A novel series of carbamate-linked cationic lipids containing hydroxyl headgroup were synthesized and included in formulations for transfection assays. The DNA-lipid complexes were characterized for their ability to bind DNA, their size, ζ-potential and cytotoxicity. Compared with our previously reported cationic transfection lipid DDCDMA lacking the hydroxyl group and the commercially available, these cationic liposomes exhibited relatively higher transfection efficiency. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Gas-phase reactivity of lanthanide cations with fluorocarbons: C-F versus C-H and C-C bond activation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cornehl, H.H.; Hornung, G.; Schwarz, H.

    1996-10-16

    The gas-phase reactivity of the fluorinated hydrocarbons CF{sub 4}, CHF{sub 3}, CH{sub 3}F, C{sub 2}F{sub 6}, 1,1-C{sub 2}H{sub 4}F{sub 2}, and C{sub 6}F{sub 6} with the lanthanide cations Ce{sup +}, Pr{sup +}, Sm{sup +}, Ho{sup +}, Tm{sup +}, and Yb{sup +} and the reactivity of C{sub 6}H{sub 5}F with all lanthanide cations Ln{sup +} (Ln = La-Lu, with the exception of Pm{sup +}) have been examined by Fourier-transform ion cyclotron resonance mass spectrometry. The perfluorinated compounds tetrafluoromethane and hexafluoroethane as well as trifluoromethane do not react with any lanthanide cation. Selective activation of the strong C-F bonds in fluoromethane, 1,1-difluoroethane,more » hexafluorobenzene, and fluorobenzene appears as a general reaction scheme along the 4f row. Experimental evidence is given for a `harpoon`-like mechanism for the F atom abstraction process which operates via an initial electron transfer from the lanthanide cation to the fluorinated substrate in the encounter complex Ln{sup +}RF. The most reactive lanthanides La{sup +}, Ce{sup +}, Gd{sup +}, and Tb{sup +} and also the formal closed-shell species Lu{sup +} exhibit additional C-H and C-C bond activation pathways in the reaction with fluorobenzene, namely dehydrohalogenation as well as loss of a neutral acetylene molecule. In the case of Tm{sup +} and Yb{sup +} the formation of neutral LnF{sub 3} is observed in a multistep process via C-C coupling and charge transfer. 17 refs., 2 figs., 2 tabs.« less

  7. Comparison of the effects of divalent cations on the noradrenaline-evoked cation current in rabbit portal vein smooth muscle cells

    PubMed Central

    Aromolaran, A S; Large, W A

    1999-01-01

    The facilitatory effects of external Ca2+, Sr2+ and Ba2+ (Cao2+, Sro2+ and Bao2+) on the noradrenaline-evoked non-selective cation current (Icat) were compared in rabbit portal vein smooth muscle cells using patch pipette techniques. All divalent cations tested potentiated the amplitude of Icat and the potency sequence was Cao2+ > Sro2+ > Bao2+. Cao2+ and Sro2+ increased the amplitude of Icat by about eight times whereas Bao2+ produced only a threefold facilitation. The current-voltage relationship of Icat was not changed by Cao2+, Sro2+ or Bao2+. From noise analysis the single channel conductance (γ) was approximately 10 pS in divalent cation-free solution but was about 20 pS with Cao2+, Sro2+ and Bao2+. From noise and voltage-jump experiments it was apparent that at least three kinetically resolvable channel states are associated with Icat in divalent cation-free solution. Cao2+ and Sro2+ produced marked changes in the characteristics of the power spectrum and relaxations of Icat in response to voltage steps, consistent with a shift in the equilibrium between the channel states, whereas Bao2+ produced minimal effects. The data show that Cao2+, Sro2+ and Bao2+ increase the amplitude of Icat, which results in part from an increase in the single channel conductance. In addition the results suggest that Cao2+ and Sro2+ alter the kinetic behaviour of the single channels whereas Bao2+ has little effect on the equilibrium between the channel states. PMID:10545143

  8. Differential Inhibition of Water and Ion Channel Activities of Mammalian Aquaporin-1 by Two Structurally Related Bacopaside Compounds Derived from the Medicinal Plant Bacopa monnieri.

    PubMed

    Pei, Jinxin V; Kourghi, Mohamad; De Ieso, Michael L; Campbell, Ewan M; Dorward, Hilary S; Hardingham, Jennifer E; Yool, Andrea J

    2016-10-01

    Aquaporin-1 (AQP1) is a major intrinsic protein that facilitates flux of water and other small solutes across cell membranes. In addition to its function as a water channel in maintaining fluid homeostasis, AQP1 also acts as a nonselective cation channel gated by cGMP, a property shown previously to facilitate rapid cell migration in a AQP1-expressing colon cancer cell line. Here we report two new modulators of AQP1 channels, bacopaside I and bacopaside II, isolated from the medicinal plant Bacopa monnieri Screening was conducted in the Xenopus oocyte expression system, using quantitative swelling and two-electrode voltage clamp techniques. Results showed bacopaside I blocked both the water (IC50 117 μM) and ion channel activities of AQP1 but did not alter AQP4 activity, whereas bacopaside II selectively blocked the AQP1 water channel (IC50 18 μM) without impairing the ionic conductance. These results fit with predictions from in silico molecular modeling. Both bacopasides were tested in migration assays using HT29 and SW480 colon cancer cell lines, with high and low levels of AQP1 expression, respectively. Bacopaside I (IC50 48 μM) and bacopaside II (IC50 14 μM) impaired migration of HT29 cells but had minimal effect on SW480 cell migration. Our results are the first to identify differential AQP1 modulators isolated from a medicinal plant. Bacopasides could serve as novel lead compounds for pharmaceutic development of selective aquaporin modulators. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  9. The cation-π interaction.

    PubMed

    Dougherty, Dennis A

    2013-04-16

    The chemistry community now recognizes the cation-π interaction as a major force for molecular recognition, joining the hydrophobic effect, the hydrogen bond, and the ion pair in determining macromolecular structure and drug-receptor interactions. This Account provides the author's perspective on the intellectual origins and fundamental nature of the cation-π interaction. Early studies on cyclophanes established that water-soluble, cationic molecules would forego aqueous solvation to enter a hydrophobic cavity if that cavity was lined with π systems. Important gas phase studies established the fundamental nature of the cation-π interaction. The strength of the cation-π interaction (Li(+) binds to benzene with 38 kcal/mol of binding energy; NH4(+) with 19 kcal/mol) distinguishes it from the weaker polar-π interactions observed in the benzene dimer or water-benzene complexes. In addition to the substantial intrinsic strength of the cation-π interaction in gas phase studies, the cation-π interaction remains energetically significant in aqueous media and under biological conditions. Many studies have shown that cation-π interactions can enhance binding energies by 2-5 kcal/mol, making them competitive with hydrogen bonds and ion pairs in drug-receptor and protein-protein interactions. As with other noncovalent interactions involving aromatic systems, the cation-π interaction includes a substantial electrostatic component. The six (four) C(δ-)-H(δ+) bond dipoles of a molecule like benzene (ethylene) combine to produce a region of negative electrostatic potential on the face of the π system. Simple electrostatics facilitate a natural attraction of cations to the surface. The trend for (gas phase) binding energies is Li(+) > Na(+) > K(+) > Rb(+): as the ion gets larger the charge is dispersed over a larger sphere and binding interactions weaken, a classical electrostatic effect. On other hand, polarizability does not define these interactions. Cyclohexane is

  10. Diketonylpyridinium Cations as a Support of New Ionic Liquid Crystals and Ion-Conductive Materials: Analysis of Counter-Ion Effects.

    PubMed

    Pastor, María Jesús; Cuerva, Cristián; Campo, José A; Schmidt, Rainer; Torres, María Rosario; Cano, Mercedes

    2016-05-12

    Ionic liquid crystals (ILCs) allow the combination of the high ionic conductivity of ionic liquids (ILs) with the supramolecular organization of liquid crystals (LCs). ILCs salts were obtained by the assembly of long-chained diketonylpyridinium cations of the type [HOO R(n)pyH ]⁺ and BF₄ - , ReO₄ - , NO₃ - , CF₃SO₃ - , CuCl₄ 2- counter-ions. We have studied the thermal behavior of five series of compounds by differential scanning calorimetry (DSC) and hot stage polarized light optical microscopy (POM). All materials show thermotropic mesomorphism as well as crystalline polymorphism. X-ray diffraction of the [HOO R(12)pyH ][ReO₄] crystal reveals a layered structure with alternating polar and apolar sublayers. The mesophases also exhibit a lamellar arrangement detected by variable temperature powder X-ray diffraction. The CuCl₄ 2- salts exhibit the best LC properties followed by the ReO₄ - ones due to low melting temperature and wide range of existence. The conductivity was probed for the mesophases in one species each from the ReO₄ - , and CuCl₄ 2- families, and for the solid phase in one of the non-mesomorphic Cl - salts. The highest ionic conductivity was found for the smectic mesophase of the ReO₄ - containing salt, whereas the solid phases of all salts were dominated by electronic contributions. The ionic conductivity may be favored by the mesophase lamellar structure.

  11. Block by Extracellular Divalent Cations of Drosophila Big Brain Channels Expressed in Xenopus Oocytes

    PubMed Central

    Yanochko, Gina M.; Yool, Andrea J.

    2004-01-01

    Drosophila Big Brain (BIB) is a transmembrane protein encoded by the neurogenic gene big brain (bib), which is important for early development of the fly nervous system. BIB expressed in Xenopus oocytes is a monovalent cation channel modulated by tyrosine kinase signaling. Results here demonstrate that the BIB conductance shows voltage- and dose-dependent block by extracellular divalent cations Ca2+ and Ba2+ but not by Mg2+ in wild-type channels. Site-directed mutagenesis of negatively charged glutamate (Glu274) and aspartate (Asp253) residues had no effect on divalent cation block. However, mutation of a conserved glutamate at position 71 (Glu71) in the first transmembrane domain (M1) altered channel properties. Mutation of Glu71 to Asp introduced a new sensitivity to block by extracellular Mg2+; substitutions with asparagine or glutamine decreased whole-cell conductance; and substitution with lysine compromised plasma membrane expression. Block by divalent cations is important in other ion channels for voltage-dependent function, enhanced signal resolution, and feedback regulation. Our data show that the wild-type BIB conductance is attenuated by external Ca2+, suggesting that endogenous divalent cation block might be relevant for enhancing signal resolution or voltage dependence for the native signaling process in neuronal cell fate determination. PMID:14990474

  12. CATION TRANSPORT AND PARTITIONING DURING A FIELD TEST OF ELECTROOSMOSIS

    EPA Science Inventory

    Field experiments were conducted to evaluate the effects of soil properties, such as the cation exchange capacity and mineral content, on pH, soluble ion concentrations, and electrical conductivity during electroosmosis in a silty clay soil. The soil is composed mainly of quartz ...

  13. The effect of various electrolyte cations on electrochemical performance of polypyrrole/RGO based supercapacitors.

    PubMed

    Zhu, Jianbo; Xu, Youlong; Wang, Jie; Lin, Jun; Sun, Xiaofei; Mao, Shengchun

    2015-11-21

    In this work, polypyrrole/graphene doped by p-toluenesulfonic is prepared as an active material for supercapacitors, and its capacitance performance is investigated in various aqueous electrolytes including HCl, LiCl, NaCl, and KCl with a concentration of 3 M, respectively. A rising trend of capacitance is observed according to the cationic mobility (Li(+) < Na(+) < K(+) < H(+)), which is due to its effect on the ionic conductivity, efficient ion/charge diffusion/exchange and relaxation time. On the other hand, long-term cycling stability is in the following order: KCl < NaCl < LiCl < HCl, corresponding to the decreasing tendency of cation size (K(+) > Na(+) > Li(+) > H(+)). The reason can be attributed to the fact that the insertion/de-insertion of large size cation brings a significant doping level decrease and an over-oxidation increase during the charging-discharging cycles. Hence, we not only obtain good capacitance performance (280.3 F g(-1) at 5 mV s(-1)), superior rate capability (225.8 F g(-1) at 500 mV s(-1)) and high cycling stability (92.0% capacitance retention after 10,000 cycles at 1 A g(-1)) by employing 3 M HCl as an electrolyte, but also reveal that the electrolyte cations have a significant effect on the supercapacitors' electrochemical performance.

  14. The Cation-π Interaction

    PubMed Central

    DOUGHERTY, DENNIS A.

    2014-01-01

    CONSPECTUS The chemistry community now recognizes the cation-π interaction as a major force for molecular recognition, joining the hydrophobic effect, the hydrogen bond, and the ion pair in determining macromolecular structure and drug-receptor interactions. This Account provides the author’s perspective on the intellectual origins and fundamental nature of the cation-π interaction. Early studies on cyclophanes established that water-soluble, cationic molecules would forgo aqueous solvation to enter a hydrophobic cavity if that cavity was lined with π systems. Important gas phase studies established the fundamental nature of the cation-π interaction. The strength of the cation-π interaction – Li+ binds to benzene with 38 kcal/mol of binding energy; NH4+ with 19 kcal/mol– distinguishes it from the weaker polar-π interactions observed in the benzene dimer or water-benzene complexes. In addition to the substantial intrinsic strength of the cation-π interaction in gas phase studies, the cation-π interaction remains energetically significant in aqueous media and under biological conditions. Many studies have shown that cation-π interactions can enhance binding energies by 2 – 5 kcal/mol, making them competitive with hydrogen bonds and ion pairs in drug-receptor and protein-protein interactions. As with other noncovalent interactions involving aromatic systems, the cation-π interaction includes a substantial electrostatic component. The six (four) Cδ−–Hδ+ bond dipoles of a molecule like benzene (ethylene) combine to produce a region of negative electrostatic potential on the face of the π system. Simple electrostatics facilitate a natural attraction of cations to the surface. The trend for (gas phase) binding energies is Li+>Na+>K+>Rb+: as the ion gets larger the charge is dispersed over a larger sphere and binding interactions weaken, a classical electrostatic effect. On other hand, polarizability does not define these interactions. Cyclohexane

  15. Interactions of divalent cations with calcium binding sites of BK channels reveal independent motions within the gating ring.

    PubMed

    Miranda, Pablo; Giraldez, Teresa; Holmgren, Miguel

    2016-12-06

    Large-conductance voltage- and calcium-activated K + (BK) channels are key physiological players in muscle, nerve, and endocrine function by integrating intracellular Ca 2+ and membrane voltage signals. The open probability of BK channels is regulated by the intracellular concentration of divalent cations sensed by a large structure in the BK channel called the "gating ring," which is formed by four tandems of regulator of conductance for K + (RCK1 and RCK2) domains. In contrast to Ca 2+ that binds to both RCK domains, Mg 2+ , Cd 2+ , or Ba 2+ interact preferentially with either one or the other. Interaction of cations with their binding sites causes molecular rearrangements of the gating ring, but how these motions occur remains elusive. We have assessed the separate contributions of each RCK domain to the cation-induced gating-ring structural rearrangements, using patch-clamp fluorometry. Here we show that Mg 2+ and Ba 2+ selectively induce structural movement of the RCK2 domain, whereas Cd 2+ causes motions of RCK1, in all cases substantially smaller than those elicited by Ca 2+ By combining divalent species interacting with unique sites, we demonstrate that RCK1 and RCK2 domains move independently when their specific binding sites are occupied. Moreover, binding of chemically distinct cations to both RCK domains is additive, emulating the effect of fully occupied Ca 2+ binding sites.

  16. Guanylate cyclase-activating protein 2 contributes to phototransduction and light adaptation in mouse cone photoreceptors.

    PubMed

    Vinberg, Frans; Peshenko, Igor V; Chen, Jeannie; Dizhoor, Alexander M; Kefalov, Vladimir J

    2018-05-11

    Light adaptation of photoreceptor cells is mediated by Ca 2+ -dependent mechanisms. In darkness, Ca 2+ influx through cGMP-gated channels into the outer segment of photoreceptors is balanced by Ca 2+ extrusion via Na + /Ca 2+ , K + exchangers (NCKXs). Light activates a G protein signaling cascade, which closes cGMP-gated channels and decreases Ca 2+ levels in photoreceptor outer segment because of continuing Ca 2+ extrusion by NCKXs. Guanylate cyclase-activating proteins (GCAPs) then up-regulate cGMP synthesis by activating retinal membrane guanylate cyclases (RetGCs) in low Ca 2+ This activation of RetGC accelerates photoresponse recovery and critically contributes to light adaptation of the nighttime rod and daytime cone photoreceptors. In mouse rod photoreceptors, GCAP1 and GCAP2 both contribute to the Ca 2+ -feedback mechanism. In contrast, only GCAP1 appears to modulate RetGC activity in mouse cones because evidence of GCAP2 expression in cones is lacking. Surprisingly, we found that GCAP2 is expressed in cones and can regulate light sensitivity and response kinetics as well as light adaptation of GCAP1-deficient mouse cones. Furthermore, we show that GCAP2 promotes cGMP synthesis and cGMP-gated channel opening in mouse cones exposed to low Ca 2+ Our biochemical model and experiments indicate that GCAP2 significantly contributes to the activation of RetGC1 at low Ca 2+ when GCAP1 is not present. Of note, in WT mouse cones, GCAP1 dominates the regulation of cGMP synthesis. We conclude that, under normal physiological conditions, GCAP1 dominates the regulation of cGMP synthesis in mouse cones, but if its function becomes compromised, GCAP2 contributes to the regulation of phototransduction and light adaptation of cones. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Monovalent Cation Permeation through the Connexin40 Gap Junction Channel

    PubMed Central

    Beblo, Dolores A.; Veenstra, Richard D.

    1997-01-01

    The unitary conductances and permeability sequences of the rat connexin40 (rCx40) gap junction channels to seven monovalent cations and anions were studied in rCx40-transfected neuroblastoma 2A (N2A) cell pairs using the dual whole cell recording technique. Chloride salt cation substitutions (115 mM principal salt) resulted in the following junctional maximal single channel current-voltage relationship slope conductances (γj in pS): CsCl (153), RbCl (148), KCl (142), NaCl (115), LiCl (86), TMACl (71), TEACl (63). Reversible block of the rCx40 channel was observed with TBA. Potassium anion salt γj are: Kglutamate (160), Kacetate (160), Kaspartate (158), KNO3 (157), KF (148), KCl (142), and KBr (132). Ion selectivity was verified by measuring reversal potentials for current in rCx40 gap junction channels with asymmetric salt solutions in the two electrodes and using the Goldman-Hodgkin-Katz equation to calculate relative permeabilities. The permeabilities relative to Li+ are: Cs+ (1.38), Rb+ (1.32), K+ (1.31), Na+ (1.16), TMA+ (0.53), TEA+ (0.45), TBA+ (0.03), Cl− (0.19), glutamate− (0.04), and NO3− (0.14), assuming that the monovalent anions permeate the channel by forming ion pairs with permeant monovalent cations within the pore thereby causing proportionate decreases in the channel conductance. This hypothesis can account for why the predicted increasing conductances with increasing ion mobilities in an essentially aqueous channel were not observed for anions in the rCx40 channel. The rCx40 effective channel radius is estimated to be 6.6 Å from a theoretical fit of the relationship of relative permeability and cation radius. PMID:9101408

  18. Bicarbonate Modulates Photoreceptor Guanylate Cyclase (ROS-GC) Catalytic Activity*

    PubMed Central

    Duda, Teresa; Wen, Xiao-Hong; Isayama, Tomoki; Sharma, Rameshwar K.; Makino, Clint L.

    2015-01-01

    By generating the second messenger cGMP in retinal rods and cones, ROS-GC plays a central role in visual transduction. Guanylate cyclase-activating proteins (GCAPs) link cGMP synthesis to the light-induced fall in [Ca2+]i to help set absolute sensitivity and assure prompt recovery of the response to light. The present report discloses a surprising feature of this system: ROS-GC is a sensor of bicarbonate. Recombinant ROS-GCs synthesized cGMP from GTP at faster rates in the presence of bicarbonate with an ED50 of 27 mm for ROS-GC1 and 39 mm for ROS-GC2. The effect required neither Ca2+ nor use of the GCAPs domains; however, stimulation of ROS-GC1 was more powerful in the presence of GCAP1 or GCAP2 at low [Ca2+]. When applied to retinal photoreceptors, bicarbonate enhanced the circulating current, decreased sensitivity to flashes, and accelerated flash response kinetics. Bicarbonate was effective when applied either to the outer or inner segment of red-sensitive cones. In contrast, bicarbonate exerted an effect when applied to the inner segment of rods but had little efficacy when applied to the outer segment. The findings define a new regulatory mechanism of the ROS-GC system that affects visual transduction and is likely to affect the course of retinal diseases caused by cGMP toxicity. PMID:25767116

  19. Diketonylpyridinium Cations as a Support of New Ionic Liquid Crystals and Ion-Conductive Materials: Analysis of Counter-Ion Effects

    PubMed Central

    Pastor, María Jesús; Cuerva, Cristián; Campo, José A.; Schmidt, Rainer; Torres, María Rosario; Cano, Mercedes

    2016-01-01

    Ionic liquid crystals (ILCs) allow the combination of the high ionic conductivity of ionic liquids (ILs) with the supramolecular organization of liquid crystals (LCs). ILCs salts were obtained by the assembly of long-chained diketonylpyridinium cations of the type [HOOR(n)pyH]+ and BF4−, ReO4−, NO3−, CF3SO3−, CuCl42− counter-ions. We have studied the thermal behavior of five series of compounds by differential scanning calorimetry (DSC) and hot stage polarized light optical microscopy (POM). All materials show thermotropic mesomorphism as well as crystalline polymorphism. X-ray diffraction of the [HOOR(12)pyH][ReO4] crystal reveals a layered structure with alternating polar and apolar sublayers. The mesophases also exhibit a lamellar arrangement detected by variable temperature powder X-ray diffraction. The CuCl42− salts exhibit the best LC properties followed by the ReO4− ones due to low melting temperature and wide range of existence. The conductivity was probed for the mesophases in one species each from the ReO4−, and CuCl42− families, and for the solid phase in one of the non-mesomorphic Cl− salts. The highest ionic conductivity was found for the smectic mesophase of the ReO4− containing salt, whereas the solid phases of all salts were dominated by electronic contributions. The ionic conductivity may be favored by the mesophase lamellar structure. PMID:28773485

  20. Fluconazole affects the alkali-metal-cation homeostasis and susceptibility to cationic toxic compounds of Candida glabrata.

    PubMed

    Elicharova, Hana; Sychrova, Hana

    2014-08-01

    Candida glabrata is a salt-tolerant and fluconazole (FLC)-resistant yeast species. Here, we analyse the contribution of plasma-membrane alkali-metal-cation exporters, a cation/proton antiporter and a cation ATPase to cation homeostasis and the maintenance of membrane potential (ΔΨ). Using a series of single and double mutants lacking CNH1 and/or ENA1 genes we show that the inability to export potassium and toxic alkali-metal cations leads to a slight hyperpolarization of the plasma membrane of C. glabrata cells; this hyperpolarization drives more cations into the cells and affects cation homeostasis. Surprisingly, a much higher hyperpolarization of C. glabrata plasma membrane was produced by incubating cells with subinhibitory concentrations of FLC. FLC treatment resulted in a substantially increased sensitivity of cells to various cationic drugs and toxic cations that are driven into the cell by negative-inside plasma-membrane potential. The effect of the combination of FLC plus cationic drug treatment was enhanced by the malfunction of alkali-metal-cation transporters that contribute to the regulation of membrane potential and cation homeostasis. In summary, we show that the combination of subinhibitory concentrations of FLC and cationic drugs strongly affects the growth of C. glabrata cells. © 2014 The Authors.

  1. Retinal Cyclic Nucleotide-Gated Channels: From Pathophysiology to Therapy.

    PubMed

    Michalakis, Stylianos; Becirovic, Elvir; Biel, Martin

    2018-03-07

    The first step in vision is the absorption of photons by the photopigments in cone and rod photoreceptors. After initial amplification within the phototransduction cascade the signal is translated into an electrical signal by the action of cyclic nucleotide-gated (CNG) channels. CNG channels are ligand-gated ion channels that are activated by the binding of cyclic guanosine monophosphate (cGMP) or cyclic adenosine monophosphate (cAMP). Retinal CNG channels transduce changes in intracellular concentrations of cGMP into changes of the membrane potential and the Ca 2+ concentration. Structurally, the CNG channels belong to the superfamily of pore-loop cation channels and share a common gross structure with hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and voltage-gated potassium channels (KCN). In this review, we provide an overview on the molecular properties of CNG channels and describe their physiological role in the phototransduction pathways. We also discuss insights into the pathophysiological role of CNG channel proteins that have emerged from the analysis of CNG channel-deficient animal models and human CNG channelopathies. Finally, we summarize recent gene therapy activities and provide an outlook for future clinical application.

  2. Retinal Cyclic Nucleotide-Gated Channels: From Pathophysiology to Therapy

    PubMed Central

    Biel, Martin

    2018-01-01

    The first step in vision is the absorption of photons by the photopigments in cone and rod photoreceptors. After initial amplification within the phototransduction cascade the signal is translated into an electrical signal by the action of cyclic nucleotide-gated (CNG) channels. CNG channels are ligand-gated ion channels that are activated by the binding of cyclic guanosine monophosphate (cGMP) or cyclic adenosine monophosphate (cAMP). Retinal CNG channels transduce changes in intracellular concentrations of cGMP into changes of the membrane potential and the Ca2+ concentration. Structurally, the CNG channels belong to the superfamily of pore-loop cation channels and share a common gross structure with hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and voltage-gated potassium channels (KCN). In this review, we provide an overview on the molecular properties of CNG channels and describe their physiological role in the phototransduction pathways. We also discuss insights into the pathophysiological role of CNG channel proteins that have emerged from the analysis of CNG channel-deficient animal models and human CNG channelopathies. Finally, we summarize recent gene therapy activities and provide an outlook for future clinical application. PMID:29518895

  3. Pressure-induced cation-cation bonding in V 2 O 3

    DOE PAGES

    Bai, Ligang; Li, Quan; Corr, Serena A.; ...

    2015-10-09

    A pressure-induced phase transition, associated with the formation of cation-cation bonding, occurs in V 2O 3 by combining synchroton x-ray diffraction in a diamond anvil cell and ab initio evolutionary calculations. The high-pressure phase has a monoclinic structure with a C2/c space group, and it is both energetically and dynamically stable at pressures above 47 GPa to at least 105 GPa. this phase transition can be viewed as a two-dimensional Peierls-like distortion, where the cation-cation dimer chains are connected along the c axis of the monoclinic cell. In conclusion, this finding provides insights into the interplay of electron correlation andmore » lattice distortion in V 2O 3, and it may also help to understand novel properties of other early transition-metal oxides.« less

  4. Understanding conductivity anomalies in Cu(I)-based delafossite transparent conducting oxides: Theoretical insights.

    PubMed

    Scanlon, David O; Godinho, Kate G; Morgan, Benjamin J; Watson, Graeme W

    2010-01-14

    The Cu(I)-based delafossite structure, Cu(I)M(III)O(2), can accommodate a wide range of rare earth and transition metal cations on the M(III) site. Substitutional doping of divalent ions for these trivalent metals is known to produce higher p-type conductivity than that occurring in the undoped materials. However, an explanation of the conductivity anomalies observed in these p-type materials, as the trivalent metal is varied, is still lacking. In this article, we examine the electronic structure of Cu(I)M(III)O(2) (M(III)=Al,Cr,Sc,Y) using density functional theory corrected for on-site Coulomb interactions in strongly correlated systems (GGA+U) and discuss the unusual experimental trends. The importance of covalent interactions between the M(III) cation and oxygen for improving conductivity in the delafossite structure is highlighted, with the covalency trends found to perfectly match the conductivity trends. We also show that calculating the natural band offsets and the effective masses of the valence band maxima is not an ideal method to classify the conduction properties of these ternary materials.

  5. Ab-Initio Calculation of Electronic Structure of Lead Halide Perovskites with Formamidinium Cation as an Active Material for Perovskite Solar Cells

    NASA Astrophysics Data System (ADS)

    Indari, E. D.; Wungu, T. D. K.; Hidayat, R.

    2017-07-01

    Organic lead halide perovskite material based solar cells show impressive power conversion efficiencies, which can reach above 19 percent for perovskite solar cell with methyl-ammonium cations. These efficiencies are originated from efficient photoexcitation and charge carrier transport and not observed in conventional perovskite crystals. In this preliminary research work, we therefore performed Density Functional Theory (DFT) calculation of formamidinium lead iodide (FAPI), an alternative to methyl-ammonium lead iodide (MAPI), to predict their electronic structure and density of state (DOS). The calculation result at the most stable lattice parameters show a good agreement with the experiment results. The obtained band gap energy is 1.307 eV. The valence band is dominantly formed by the 5p orbitals of I- anions, while the conduction band is dominantly formed by the 6p orbitals of Pb2+ cations. The DOS of valence band of this perovskite seems smaller compared to the case of methyl-ammonium lead iodide perovskite, which then may explain the observation of smaller power conversion efficiencies in perovskite solar cells with this formamidinium cations.

  6. Atrial natriuretic peptide degradation by CPA47 cells: evidence for a divalent cation-independent cell-surface proteolytic activity.

    PubMed

    Frost, S J; Chen, Y M; Whitson, P A

    1992-11-23

    Atrial natriuretic peptide (ANP) is rapidly cleared and degraded in vivo. Nonguanylate-cyclase receptors (C-ANPR) and a metalloproteinase, neutral endopeptidase (EC 3.4.24.11) (NEP 24.11), are thought to be responsible for its metabolism. We investigated the mechanisms of ANP degradation by an endothelial-derived cell line, CPA47. CPA47 cells degraded 88% of 125I-ANP after 1 h at 37 degrees C as determined by HPLC. Medium preconditioned by these cells degraded 41% of the 125I-ANP, and this activity was inhibited by a divalent cation chelator, EDTA. Furthermore, a cell-surface proteolytic activity degraded 125I-ANP in the presence of EDTA when receptor-mediated endocytosis was inhibited either by low temperature (4 degrees C) or by hyperosmolarity at 37 degrees C. The metalloproteinase, NEP 24.11, is unlikely to be the cell-surface peptidase because 125I-ANP is degraded by CPA47 cells at 4 degrees C in the presence of 5 mM EDTA. These data indicate that CPA47 cells can degrade ANP by a novel divalent cation-independent cell-surface proteolytic activity.

  7. Atrial natriuretic peptide degradation by CPA47 cells - Evidence for a divalent cation-independent cell-surface proteolytic activity

    NASA Technical Reports Server (NTRS)

    Frost, S. J.; Chen, Y. M.; Whitson, P. A.

    1992-01-01

    Atrial natriuretic peptide (ANP) is rapidly cleared and degraded in vivo. Nonguanylate-cyclase receptors (C-ANPR) and a metalloproteinase, neutral endopeptidase (EC 3.4.24.11) (NEP 24.11), are thought to be responsible for its metabolism. We investigated the mechanisms of ANP degradation by an endothelial-derived cell line, CPA47. CPA47 cells degraded 88 percent of 125I-ANP after 1 h at 37 degrees C as determined by HPLC. Medium preconditioned by these cells degraded 41 percent of the 125I-ANP, and this activity was inhibited by a divalent cation chelator, EDTA. Furthermore, a cell-surface proteolytic activity degraded 125I-ANP in the presence of EDTA when receptor-mediated endocytosis was inhibited either by low temperature (4 degrees C) or by hyperosmolarity at 37 degrees C. The metalloproteinase, NEP 24.11, is unlikely to be the cell-surface peptidase because 125I-ANP is degraded by CPA47 cells at 4 degrees C in the presence of 5 mM EDTA. These data indicate that CPA47 cells can degrade ANP by a novel divalent cation-independent cell-surface proteolytic activity.

  8. Effect of Structure on Transport Properties (Viscosity, Ionic Conductivity, and Self-Diffusion Coefficient) of Aprotic Heterocyclic Anion (AHA) Room Temperature Ionic Liquids. 2. Variation of Alkyl Chain Length in the Phosphonium Cation.

    PubMed

    Sun, Liyuan; Morales-Collazo, Oscar; Xia, Han; Brennecke, Joan F

    2016-06-30

    A series of room-temperature ionic liquids (ILs) composed of triethyl(alkyl)phosphonium cations paired with three different aprotic heterocyclic anions (AHAs) (alkyl = butyl ([P2224](+)) and octyl ([P2228](+))) were prepared to investigate the effect of cationic alkyl chain length on transport properties. The transport properties and density of these ILs were measured from 283.15 to 343.15 K at ambient pressure. The dependence of the transport properties (viscosity, ionic conductivity, diffusivity, and molar conductivity) on temperature can be described by the Vogel-Fulcher-Tamman (VFT) equation. The ratio of the molar conductivity obtained from the molar concentration and ionic conductivity measurements to that calculated from self-diffusion coefficients (measured by pulsed gradient spin-echo nuclear magnetic resonance spectroscopy) using the Nernst-Einstein equation was used to quantify the ionicity of these ILs. The molar conductivity ratio decreases with increasing number of carbon atoms in the alkyl chain, indicating that the reduced Coulombic interactions resulting from lower density are more than balanced by the increased van der Waals interactions between the alkyl chains. The results of this study may provide insight into the design of ILs with enhanced dynamics that may be suitable as electrolytes in lithium ion batteries and other electrochemical applications.

  9. Cation activation of the pig kidney sodium pump: transmembrane allosteric effects of sodium.

    PubMed Central

    Karlish, S J; Stein, W D

    1985-01-01

    We have studied activation by Na or Rb ions of different transport modes of the Na-K pump, using phospholipid vesicles reconstituted with pig kidney Na-K-ATPase. The shape of the activation curves, sigmoid or quasi-hyperbolic, depends on the nature of the cation at the opposite surface and not on the specific mode of transport. ATP-dependent Na uptake into K-containing vesicles (Na-K exchange) is activated by cytoplasmic Na along a highly sigmoid curve in the absence of extracellular Na (Hill number, nH = 1.9). Activation displays progressively less-sigmoid curves as extracellular Na is raised to 150 mM (nH = 1.2). The maximal rate of the Na-K exchange is not affected. Na is not transported from the extracellular face by the pump in the presence of excess extracellular K, and the transmembrane effects of the extracellular Na are therefore 'allosteric' in nature. ATP-dependent Na-Na exchange (Lee & Blostein, 1980) and classical ATP-plus-ADP-dependent Na-Na exchange are activated by cytoplasmic Na along hyperbolic curves. ATP-dependent Na uptake into Tris-containing vesicles is activated by cytoplasmic Na along a somewhat sigmoidal curve. (ATP + Pi)-dependent Rb-Rb exchange is activated by cytoplasmic and extracellular Rb along strictly hyperbolic curves. The same applies for Rb-Rb exchange in the presence or absence of ATP or Pi alone. The presence of a high concentration of extracellular Na together with extracellular Rb induces a sigmoidal activation by cytoplasmic Rb of (ATP + Pi)-dependent Rb-Rb exchange (nH = 1.45) but does not affect the maximal rate of exchange. Slow passive Rb fluxes through the pump observed in the absence of other pump ligands (see Karlish & Stein, 1982 alpha) are activated by cytoplasmic Rb along a strictly hyperbolic curve with extracellular Rb, nH = 1.0 (Rb-Rb exchange), along a strongly sigmoid curve with extracellular Na, nH = 1.5 (Rb-Na exchange), and along less-sigmoid curves with extracellular Tris, nH = 1.24 (net Rb flux) or

  10. NMR studies of cation transport across membranes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shochet, N.R.

    1985-01-01

    /sup 23/Na NMR Studies of cation transport across membranes were conducted both on model and biological membranes. Two ionophores, the carrier monensin and the channel-former gramicidin, were chosen to induce cation transport in large unilamellar phosphatidylcholine vesicles. The distinction between the NMR signals arising from the two sides of the membrane was achieved by the addition of an anionic paramagnetic shift reagent to the outer solution. The kinetics of the cation transport across the membrane was observed simultaneously monitoring the changes in the /sup 23/Na NMR signals of both compartments. Two mathematical models were developed for the estimation of themore » transport parameters of the monensin- and gramicidin-induced cation transport. The models were able to fit the experimental data very well. A new method for the estimation of the volume trapped inside the vesicles was developed. The method uses the relative areas of the intra- and extravesicular NMR signals arising from a suspension of vesicles bathed in the same medium they contain, as a measure for the relative volumes of these compartments. Sodium transport across biological membranes was studied by /sup 23/ NMR, using suspensions of cultured nerve cells. The sodium influx through voltage-gated channels was studied using the channel modifier batrachotoxin in combination with scorpion toxin.« less

  11. Physical properties of ionic liquids consisting of the 1-butyl-3-methylimidazolium cation with various anions and the bis(trifluoromethylsulfonyl)imide anion with various cations.

    PubMed

    Jin, Hui; O'Hare, Bernie; Dong, Jing; Arzhantsev, Sergei; Baker, Gary A; Wishart, James F; Benesi, Alan J; Maroncelli, Mark

    2008-01-10

    Physical properties of 4 room-temperature ionic liquids consisting of the 1-butyl-3-methylimidazolium cation with various perfluorinated anions and the bis(trifluoromethylsulfonyl)imide (Tf2N-) anion with 12 pyrrolidinium-, ammonium-, and hydroxyl-containing cations are reported. Electronic structure methods are used to calculate properties related to the size, shape, and dipole moment of individual ions. Experimental measurements of phase-transition temperatures, densities, refractive indices, surface tensions, solvatochromic polarities based on absorption of Nile Red, 19F chemical shifts of the Tf2N- anion, temperature-dependent viscosities, conductivities, and cation diffusion coefficients are reported. Correlations among the measured quantities as well as the use of surface tension and molar volume for estimating Hildebrand solubility parameters of ionic liquids are also discussed.

  12. A simple model for metal cation-phosphate interactions in nucleic acids in the gas phase: alkali metal cations and trimethyl phosphate.

    PubMed

    Ruan, Chunhai; Huang, Hai; Rodgers, M T

    2008-02-01

    Threshold collision-induced dissociation techniques are employed to determine the bond dissociation energies (BDEs) of complexes of alkali metal cations to trimethyl phosphate, TMP. Endothermic loss of the intact TMP ligand is the only dissociation pathway observed for all complexes. Theoretical calculations at the B3LYP/6-31G* level of theory are used to determine the structures, vibrational frequencies, and rotational constants of neutral TMP and the M+(TMP) complexes. Theoretical BDEs are determined from single point energy calculations at the B3LYP/6-311+G(2d,2p) level using the B3LYP/6-31G* optimized geometries. The agreement between theory and experiment is reasonably good for all complexes except Li+(TMP). The absolute M+-(TMP) BDEs are found to decrease monotonically as the size of the alkali metal cation increases. No activated dissociation was observed for alkali metal cation binding to TMP. The binding of alkali metal cations to TMP is compared with that to acetone and methanol.

  13. A chimeric protein of aluminum-activated malate transporter generated from wheat and Arabidopsis shows enhanced response to trivalent cations.

    PubMed

    Sasaki, Takayuki; Tsuchiya, Yoshiyuki; Ariyoshi, Michiyo; Ryan, Peter R; Yamamoto, Yoko

    2016-07-01

    TaALMT1 from wheat (Triticum aestivum) and AtALMT1 from Arabidopsis thaliana encode aluminum (Al)-activated malate transporters, which confer acid-soil tolerance by releasing malate from roots. Chimeric proteins from TaALMT1 and AtALMT1 (Ta::At, At::Ta) were previously analyzed in Xenopus laevis oocytes. Those studies showed that Al could activate malate efflux from the Ta::At chimera but not from At::Ta. Here, functions of TaALMT1, AtALMT1 and the chimeric protein Ta::At were compared in cultured tobacco BY-2 cells. We focused on the sensitivity and specificity of their activation by trivalent cations. The activation of malate efflux by Al was at least two-fold greater in the chimera than the native proteins. All proteins were also activated by lanthanides (erbium, ytterbium, gadolinium, and lanthanum), but the chimera again released more malate than TaALMT1 or AtALMT1. In Xenopus oocytes, Al, ytterbium, and erbium activated inward currents from the native TaALMT1 and the chimeric protein, but gadolinium only activated currents from the chimera. Lanthanum inhibited currents from both proteins. These results demonstrated that function of the chimera protein was altered compared to the native proteins and was more responsive to a range of trivalent cations when expressed in plant cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. A conserved π-cation and an electrostatic bridge are essential for 11R-lipoxygenase catalysis and structural stability.

    PubMed

    Eek, Priit; Piht, Mari-Ann; Rätsep, Margus; Freiberg, Arvi; Järving, Ivar; Samel, Nigulas

    2015-10-01

    Lipoxygenases (LOXs) are lipid-peroxidizing enzymes that consist of a regulatory calcium- and membrane-binding PLAT (polycystin-1, lipoxygenase, α-toxin) domain and a catalytic domain. In a previous study, the crystal structure of an 11R-LOX revealed a conserved π-cation bridge connecting these two domains which could mediate the regulatory effect of the PLAT domain to the active site. Here we analyzed the role of residues Trp107 and Lys172 that constitute the π-cation bridge in 11R-LOX along with Arg106 and Asp173-a potential salt bridge, which could also contribute to the inter-domain communication. According to our kinetic assays and protein unfolding experiments conducted using differential scanning fluorimetry and circular dichroism spectroscopy, mutants with a disrupted link display diminished catalytic activity alongside reduced stability of the protein fold. The results demonstrate that both these bridges contribute to the two-domain interface, and are important for proper enzyme activation. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. A solid phase extraction-ion chromatography with conductivity detection procedure for determining cationic surfactants in surface water samples.

    PubMed

    Olkowska, Ewa; Polkowska, Żaneta; Namieśnik, Jacek

    2013-11-15

    A new analytical procedure for the simultaneous determination of individual cationic surfactants (alkyl benzyl dimethyl ammonium chlorides) in surface water samples has been developed. We describe this methodology for the first time: it involves the application of solid phase extraction (SPE-for sample preparation) coupled with ion chromatography-conductivity detection (IC-CD-for the final determination). Mean recoveries of analytes between 79% and 93%, and overall method quantification limits in the range from 0.0018 to 0.038 μg/mL for surface water and CRM samples were achieved. The methodology was applied to the determination of individual alkyl benzyl quaternary ammonium compounds in environmental samples (reservoir water) and enables their presence in such types of waters to be confirmed. In addition, it is a simpler, less time-consuming, labour-intensive, avoiding use of toxic chloroform and significantly less expensive methodology than previously described approaches (liquid-liquid extraction coupled with liquid chromatography-mass spectrometry). Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Structure-biocompatibility and transfection activity relationships of cationic polyaspartamides with (dialkylamino)alkyl and alkyl or hydroxyalkyl side groups.

    PubMed

    Salakhieva, Diana; Shevchenko, Vesta; Németh, Csaba; Gyarmati, Benjámin; Szilágyi, András; Abdullin, Timur

    2017-01-30

    A series of 14 cationic derivatives of poly(aspartic acid) i.e. cationic polyaspartamides with different (dialkylamino)alkyl and alkyl or hydroxyalkyl side groups was synthesized by nucleophilic addition on polysuccinimide. The resulting polyaspartamides have moderate amphiphilic properties. Relationships between the structure and ratio of side groups and in vitro properties of polyaspartamides, including their cytotoxic and membrane-damaging activity towards human cell lines, primary skin fibroblasts and erythrocytes, were established and discussed. Cationic polyaspartamides vary in their DNA-binding, condensing and nuclease-protecting characteristics depending on the concentration ratio of (dialkylamino)alkyl and alkyl or hydroxyalkyl side groups. Effective cell transfection was achieved upon polyaspartamide-mediated plasmid DNA delivery in serum-free medium in the presence of chloroquine. Effect of serum proteins adsorption onto polyaspartamide based polyplexes, and the role of concentration of polyplexes in culture medium in their colloidal stability and transfection process were demonstrated. Synthesized polyaspartamides are biocompatible and long-acting gene carriers, which are applied to cells after dilution and without washing, thus providing transfection level comparable to that of commercial transfection reagent. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Characterization and production of multifunctional cationic peptides derived from rice proteins.

    PubMed

    Taniguchi, Masayuki; Ochiai, Akihito

    2017-04-01

    Food proteins have been identified as a source of bioactive peptides. These peptides are inactive within the sequence of the parent protein and must be released during gastrointestinal digestion, fermentation, or food processing. Of bioactive peptides, multifunctional cationic peptides are more useful than other peptides that have specific activity in promotion of health and/or the treatment of diseases. We have identified and characterized cationic peptides from rice enzymes and proteins that possess multiple functions, including antimicrobial, endotoxin-neutralizing, arginine gingipain-inhibitory, and/or angiogenic activities. In particular, we have elucidated the contribution of cationic amino acids (arginine and lysine) in the peptides to their bioactivities. Further, we have discussed the critical parameters, particularly proteinase preparations and fractionation or purification, in the enzymatic hydrolysis process for producing bioactive peptides from food proteins. Using an ampholyte-free isoelectric focusing (autofocusing) technique as a tool for fractionation, we successfully prepared fractions containing cationic peptides with multiple functions.

  18. Binding symmetry of extracellular divalent cations to conduction pore studied using tandem dimers of a CNG channel.

    PubMed

    Kwon, Ryuk-Jun; Ha, Tal Soo; Kim, Wonjae; Park, Chul-Seung

    2002-11-08

    Cyclic nucleotide-gated (CNG) channels are composed of the tetramer of alpha-subunit alone or alpha- and beta-subunits. The alpha-subunits of these channels have a conserved glutamate (Glu) residue within the pore-forming region and the residue determines the selectivity as well as the affinity for the extracellular divalent cations. Using the high-affinity mutant (E363D) of bovine retinal CNG channel in which the Glu at position 363 was replaced to Asp, we constructed tandem dimers and investigated the binding characteristics of divalent cations to the site. The gating and permeation characteristics of individual homomeric tandem dimers are indistinguishable to those of homo-tetramers formed by parental monomers. The heteromeric tandem dimers showed the binding affinity for Sr(2+) identical to the geometric mean of the affinities for two parent channels, indicating the energy additive and thus the simultaneous interaction. On the other hand, the binding affinity for Mg(2+) followed the harmonic mean of those parent channels indicating that Mg(2+) interacts more strongly with the subunit bearing Asp residue at the position. Thus the results strongly suggest that the Glu363 residues in the CNG channel pore be flexible enough to adapt different binding symmetries for different divalent cations. Moreover, the simultaneous interaction between the four Glu residues and Sr(2+) provides an important structural constraint to the CNG channel outer vestibule of unknown structure.

  19. Bicarbonate Modulates Photoreceptor Guanylate Cyclase (ROS-GC) Catalytic Activity.

    PubMed

    Duda, Teresa; Wen, Xiao-Hong; Isayama, Tomoki; Sharma, Rameshwar K; Makino, Clint L

    2015-04-24

    By generating the second messenger cGMP in retinal rods and cones, ROS-GC plays a central role in visual transduction. Guanylate cyclase-activating proteins (GCAPs) link cGMP synthesis to the light-induced fall in [Ca(2+)]i to help set absolute sensitivity and assure prompt recovery of the response to light. The present report discloses a surprising feature of this system: ROS-GC is a sensor of bicarbonate. Recombinant ROS-GCs synthesized cGMP from GTP at faster rates in the presence of bicarbonate with an ED50 of 27 mM for ROS-GC1 and 39 mM for ROS-GC2. The effect required neither Ca(2+) nor use of the GCAPs domains; however, stimulation of ROS-GC1 was more powerful in the presence of GCAP1 or GCAP2 at low [Ca(2+)]. When applied to retinal photoreceptors, bicarbonate enhanced the circulating current, decreased sensitivity to flashes, and accelerated flash response kinetics. Bicarbonate was effective when applied either to the outer or inner segment of red-sensitive cones. In contrast, bicarbonate exerted an effect when applied to the inner segment of rods but had little efficacy when applied to the outer segment. The findings define a new regulatory mechanism of the ROS-GC system that affects visual transduction and is likely to affect the course of retinal diseases caused by cGMP toxicity. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Conserved Aromatic Residue Confers Cation Selectivity in Claudin-2 and Claudin-10b*

    PubMed Central

    Li, Jiahua; Zhuo, Min; Pei, Lei; Yu, Alan S. L.

    2013-01-01

    In tight junctions, both claudin-2 and claudin-10b form paracellular cation-selective pores by the interaction of the first ECL 1 with permeating ions. We hypothesized that a highly conserved aromatic residue near the pore selectivity filter of claudins contributes to cation selectivity by cation-π interaction with the permeating cation. To test this, we generated MDCK I Tet-off cells stably transfected with claudin-2 Tyr67 mutants. The Y67L mutant showed reduced cation selectivity compared with wild-type claudin-2 due to a decrease in Na+ permeability, without affecting the Cl− permeability. The Y67A mutant enlarged the pore size and further decreased the charge selectivity due to an increase in Cl− permeability. The Y67F mutant restored the Na+ permeability, Cl− permeability, and pore size back to wild-type. The accessibility of Y67C to methanethiosulfonate modification indicated that its side chain faces the lumen of the pore. In claudin-10b, the F66L mutant reduced cation selectivity, and the F66A mutant lost pore conductance. We conclude that the conserved aromatic residue near the cation pore domain of claudins contributes to cation selectivity by a dual role of cation-π interaction and a luminal steric effect. Our findings provide new insight into how ion selectivity is achieved in the paracellular pore. PMID:23760508

  1. TRPV2 Channels Contribute to Stretch-Activated Cation Currents and Myogenic Constriction in Retinal Arterioles.

    PubMed

    McGahon, Mary K; Fernández, José A; Dash, Durga P; McKee, Jon; Simpson, David A; Zholos, Alex V; McGeown, J Graham; Curtis, Tim M

    2016-10-01

    Activation of the transient receptor potential channels, TRPC6, TRPM4, and TRPP1 (PKD2), has been shown to contribute to the myogenic constriction of cerebral arteries. In the present study we sought to determine the potential role of various mechanosensitive TRP channels to myogenic signaling in arterioles of the rat retina. Rat retinal arterioles were isolated for RT-PCR, Fura-2 Ca2+ microfluorimetry, patch-clamp electrophysiology, and pressure myography studies. In some experiments, confocal immunolabeling of wholemount preparations was used to examine the localization of specific mechanosensitive TRP channels in retinal vascular smooth muscle cells (VSMCs). Reverse transcription-polymerase chain reaction analysis demonstrated mRNA expression for TRPC1, M7, V1, V2, V4, and P1, but not TRPC6 or M4, in isolated retinal arterioles. Immunolabeling revealed plasma membrane, cytosolic and nuclear expression of TRPC1, M7, V1, V2, V4, and P1 in retinal VSMCs. Hypoosmotic stretch-induced Ca2+ influx in retinal VSMCs was reversed by the TRPV2 inhibitor tranilast and the nonselective TRPP1/V2 antagonist amiloride. Inhibitors of TRPC1, M7, V1, and V4 had no effect. Hypoosmotic stretch-activated cation currents were similar in Na+ and Cs+ containing solutions suggesting no contribution by TRPP1 channels. Direct plasma membrane stretch triggered cation current activity that was blocked by tranilast and specific TRPV2 pore-blocking antibodies and mimicked by the TRPV2 activator, Δ9-tetrahydrocannabinol. Preincubation of retinal arterioles with TRPV2 blocking antibodies prevented the development of myogenic tone. Our results suggest that retinal VSMCs express a range of mechanosensitive TRP channels, but only TRPV2 appears to contribute to myogenic signaling in this vascular bed.

  2. Whole-cell and single channel monovalent cation currents through the novel rabbit epithelial Ca2+ channel ECaC

    PubMed Central

    Nilius, Bernd; Vennekens, Rudi; Prenen, Jean; Hoenderop, Joost G J; Bindels, René J M; Droogmans, Guy

    2000-01-01

    This study describes properties of monovalent cation currents through ECaC, a recently cloned epithelial Ca2+-permeable channel from rabbit. The kinetics of currents through ECaC was strongly modulated by divalent cations. Currents were inhibited in the presence of extracellular Ca2+. They showed an initial voltage-dependent decay in the presence of 1 mm Mg2+ at hyperpolarizing steps in Ca2+-free solutions, which represents a voltage-dependent Mg2+ block through binding of Mg2+ to a site localized in the electrical field of the membrane (δ = 0.31) and a voltage-dependent binding constant (at 0 mV 3.1 mm Ca2+, obtained from a Woodhull type analysis). Currents were only stable in the absence of divalent cations and showed under these conditions a small time- and voltage-dependent component of activation. Single channel currents in cell-attached and inside-out patches had a conductance of 77.5 ± 4.9 pS (n = 11) and reversed at +14.8 ± 1.6 mV (n = 9) in the absence of divalent cations. The permeation sequence for monovalent cations through ECaC was Na+ > Li+ > K+ > Cs+ > NMDG+ which is identical to the Eisenmann sequence X for a strong field-strength binding site. It is concluded that the permeation profile of ECaC for monovalent cations suggests a strong field-strength binding site that may be involved in Ca2+ permeation and Mg2+ block. PMID:10970426

  3. Sensitivity enhancement for nitrophenols using cationic surfactant-modified activated carbon for solid-phase extraction surface-assisted laser desorption/ionization mass spectrometry.

    PubMed

    Chen, Y C; Tsai, M F

    2000-01-01

    Previous work has demonstrated that a combination of solid-phase extraction with surface-assisted laser desorption/ionization (SPE-SALDI) mass spectrometry can be applied to the determination of trace nitrophenols in water. An improved method to lower the detection limit of this hyphenated technique is described in this present study. Activated carbon powder is used as both the SPE adsorbent and the SALDI solid in the analysis by SPE-SALDI. The surface of the activated carbon is modified by passing an aqueous solution of a cationic surfactant through the SPE cartridge. The results demonstrate that the sensitivity for nitrophenols in the analysis by SPE-SALDI can be improved by using cationic surfactants to modify the surface of the activated carbon. The detection limit for nitrophenols is about 25 ppt based on a signal-to-noise ratio of 3 by sampling from 100 mL of solution. Copyright 2000 John Wiley & Sons, Ltd.

  4. Ammonia vapor sensing properties of polyaniline-titanium(IV)phosphate cation exchange nanocomposite.

    PubMed

    Khan, Asif Ali; Baig, Umair; Khalid, Mohd

    2011-02-28

    In this study, the electrically conducting polyaniline-titanium(IV)phosphate (PANI-TiP) cation exchange nanocomposite was synthesized by sol-gel method. The cation exchange nanocomposite based sensor for detection of ammonia vapors was developed at room temperature. It was revealed that the sensor showed good reversible response towards ammonia vapors ranging from 3 to 6%. It was found that the sensor with p-toluene sulphonic acid (p-TSA) doped exhibited higher sensing response than hydrochloric acid doped. This sensor has detection limit ≤1% ammonia. The response of resistivity changes of the cation exchange nanocomposite on exposure to different concentrations of ammonia vapors shows its utility as a sensing material. These studies suggest that the cation exchange nanocomposite could be a good material for ammonia sensor at room temperature. Copyright © 2010 Elsevier B.V. All rights reserved.

  5. Structural basis for modulation and agonist specificity of HCN pacemaker channels.

    PubMed

    Zagotta, William N; Olivier, Nelson B; Black, Kevin D; Young, Edgar C; Olson, Rich; Gouaux, Eric

    2003-09-11

    The family of hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channels are crucial for a range of electrical signalling, including cardiac and neuronal pacemaker activity, setting resting membrane electrical properties and dendritic integration. These nonselective cation channels, underlying the I(f), I(h) and I(q) currents of heart and nerve cells, are activated by membrane hyperpolarization and modulated by the binding of cyclic nucleotides such as cAMP and cGMP. The cAMP-mediated enhancement of channel activity is largely responsible for the increase in heart rate caused by beta-adrenergic agonists. Here we have investigated the mechanism underlying this modulation by studying a carboxy-terminal fragment of HCN2 containing the cyclic nucleotide-binding domain (CNBD) and the C-linker region that connects the CNBD to the pore. X-ray crystallographic structures of this C-terminal fragment bound to cAMP or cGMP, together with equilibrium sedimentation analysis, identify a tetramerization domain and the mechanism for cyclic nucleotide specificity, and suggest a model for ligand-dependent channel modulation. On the basis of amino acid sequence similarity to HCN channels, the cyclic nucleotide-gated, and eag- and KAT1-related families of channels are probably related to HCN channels in structure and mechanism.

  6. Structure relationship of cationic lipids on gene transfection mediated by cationic liposomes.

    PubMed

    Paecharoenchai, Orapan; Niyomtham, Nattisa; Apirakaramwong, Auayporn; Ngawhirunpat, Tanasait; Rojanarata, Theerasak; Yingyongnarongkul, Boon-ek; Opanasopit, Praneet

    2012-12-01

    The aim of this study was to investigate the transfection efficiency of cationic liposomes formulated with phosphatidylcholine (PC) and novel synthesized diethanolamine-based cationic lipids at a molar ratio of 5:1 in comparison with Lipofectamine™ 2000. Factors affecting transfection efficiency and cell viability, including the chemical structure of the cationic lipids, such as different amine head group (diamine and polyamine; and non-spermine and spermine) and acyl chain lengths (C14, C16, and C18) and the weight ratio of liposomes to DNA were evaluated on a human cervical carcinoma cell line (HeLa cells) using the pDNA encoding green fluorescent protein (pEGFP-C2). Characterizations of these lipoplexes in terms of size and charge measurement and agarose gel electrophoresis were performed. The results from this study revealed that almost no transfection was observed in the liposome formulations composed of cationic lipids with a non-spermine head group. In addition, the transfection efficiency of these cationic liposomes was in the following order: spermine-C14 > spermine-C16 > spermine-C18. The highest transfection efficiency was observed in the formulation of spermine-C14 liposomes at a weight ratio of 25; furthermore, this formulation was safe for use in vitro. In conclusion, cationic liposomes containing spermine head groups demonstrated promising potential as gene carriers.

  7. Technological progress and challenges towards cGMP manufacturing of human pluripotent stem cells based therapeutic products for allogeneic and autologous cell therapies.

    PubMed

    Abbasalizadeh, Saeed; Baharvand, Hossein

    2013-12-01

    Recent technological advances in the generation, characterization, and bioprocessing of human pluripotent stem cells (hPSCs) have created new hope for their use as a source for production of cell-based therapeutic products. To date, a few clinical trials that have used therapeutic cells derived from hESCs have been approved by the Food and Drug Administration (FDA), but numerous new hPSC-based cell therapy products are under various stages of development in cell therapy-specialized companies and their future market is estimated to be very promising. However, the multitude of critical challenges regarding different aspects of hPSC-based therapeutic product manufacturing and their therapies have made progress for the introduction of new products and clinical applications very slow. These challenges include scientific, technological, clinical, policy, and financial aspects. The technological aspects of manufacturing hPSC-based therapeutic products for allogeneic and autologous cell therapies according to good manufacturing practice (cGMP) quality requirements is one of the most important challenging and emerging topics in the development of new hPSCs for clinical use. In this review, we describe main critical challenges and highlight a series of technological advances in all aspects of hPSC-based therapeutic product manufacturing including clinical grade cell line development, large-scale banking, upstream processing, downstream processing, and quality assessment of final cell therapeutic products that have brought hPSCs closer to clinical application and commercial cGMP manufacturing. © 2013.

  8. Ammonia-water cation and ammonia dimer cation.

    PubMed

    Kim, Hahn; Lee, Han Myoung

    2009-06-25

    We have investigated the structure, interaction energy, electronic properties, and IR spectra of the ammonia-water cation (NH(3)H(2)O)(+) using density functional theory (DFT) and high-level ab initio theory. The ammonia-water cation has three minimum-energy structures of (a) H(2)NH(+)...OH(2), (b) H(3)N(+)...OH(2), and (c) H(3)NH(+)...OH. The lowest-energy structure is (a), followed by (c) and (b). The ammonia dimer cation has two minimum-energy structures [the lowest H(3)NH(+)...NH(2) structure and the second lowest (H(3)N...NH(3))(+) structure]. The minimum transition barrier for the interconversion between (a), (b), and (c) is approximately 6 kcal/mol. Most DFT calculations with various functionals, except a few cases, overstabilize the N...O and N...N binding, predicting different structures from Moller-Plesset second-order perturbation (MP2) theory and the most reliable complete basis set (CBS) limit of coupled cluster theory with single, double, and perturbative triple excitations [CCSD(T)]. Thus, the validity test of the DFT functionals for these ionized molecular systems would be of importance.

  9. Liquid-like cationic sub-lattice in copper selenide clusters

    NASA Astrophysics Data System (ADS)

    White, Sarah L.; Banerjee, Progna; Jain, Prashant K.

    2017-02-01

    Super-ionic solids, which exhibit ion mobilities as high as those in liquids or molten salts, have been employed as solid-state electrolytes in batteries, improved thermoelectrics and fast-ion conductors in super-capacitors and fuel cells. Fast-ion transport in many of these solids is supported by a disordered, `liquid-like' sub-lattice of cations mobile within a rigid anionic sub-lattice, often achieved at high temperatures or pressures via a phase transition. Here we show that ultrasmall clusters of copper selenide exhibit a disordered cationic sub-lattice under ambient conditions unlike larger nanocrystals, where Cu+ ions and vacancies form an ordered super-structure similar to the bulk solid. The clusters exhibit an unusual cationic sub-lattice arrangement wherein octahedral sites, which serve as bridges for cation migration, are stabilized by compressive strain. The room-temperature liquid-like nature of the Cu+ sub-lattice combined with the actively tunable plasmonic properties of the Cu2Se clusters make them suitable as fast electro-optic switches.

  10. Electrical conductivity and dielectric behavior in sodium zinc divanadates

    NASA Astrophysics Data System (ADS)

    Sallemi, F.; Louati, B.; Guidara, K.

    2014-11-01

    The Na2ZnV2O7 compound was obtained by the conventional solid-state reaction. The sample was characterized by X-ray powder diffraction, Raman and impedance spectroscopy. The ac electrical conductivity and dielectric properties have been investigated in the frequency and temperature range of 200 Hz-1 MHz and 513 K-729 K, respectively. The direct current conductivity process is thermally activated. The frequency dependence of the conductivity is interpreted using the power law. The close values of activation energies obtained from the analysis of hopping frequency and dc conductivity implies that the transport is due to Na+ cation displacement parallel to (0 0 1) plane located between ZnO4 and VO4 tetrahedra. The evolution of the complex permittivity as a function of angular frequency was investigated. Several important parameters such as charge carrier concentration, ionic mobility and diffusion coefficient were determined. Thermodynamic parameters such as the free energy of activation ∆F, the enthalpy ∆H, and the change in entropy ∆S have been calculated.

  11. Adsorption of Cationic Peptides to Solid Surfaces of Glass and Plastic

    PubMed Central

    Kristensen, Kasper; Henriksen, Jonas R.; Andresen, Thomas L.

    2015-01-01

    Cationic membrane-active peptides have been studied for years in the hope of developing them into novel types of therapeutics. In this article, we investigate an effect that might have significant experimental implications for investigators who wish to study these peptides, namely, that the peptides adsorb to solid surfaces of glass and plastic. Specifically, we use analytical HPLC to systematically quantify the adsorption of the three cationic membrane-active peptides mastoparan X, melittin, and magainin 2 to the walls of commonly used glass and plastic sample containers. Our results show that, at typical experimental peptide concentrations, 90% or more of the peptides might be lost from solution due to rapid adsorption to the walls of the sample containers. Thus, our results emphasize that investigators should always keep these adsorption effects in mind when designing and interpreting experiments on cationic membrane-active peptides. We conclude the article by discussing different strategies for reducing the experimental impact of these adsorption effects. PMID:25932639

  12. Preparation of Cd/Pb Chalcogenide Heterostructured Janus Particles via Controllable Cation Exchange

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Jianbing; Chernomordik, Boris D.; Crisp, Ryan W.

    2015-07-28

    We developed a strategy for producing quasi-spherical nanocrystals of anisotropic heterostructures of Cd/Pb chalcogenides. The nanostructures are fabricated via a controlled cation exchange reaction where the Cd2+ cation is exchanged for the Pb2+ cation. The cation exchange reaction is thermally activated and can be controlled by adjusting the reaction temperature or time. We characterized the particles using TEM, XPS, PL, and absorption spectroscopy. With complete exchange, high quality Pb-chalcogenide quantum dots are produced. In addition to Cd2+, we also find suitable conditions for the exchange of Zn2+ cations for Pb2+ cations. The cation exchange is anisotropic starting at one edgemore » of the nanocrystals and proceeds along the <111> direction producing a sharp interface at a (111) crystallographic plane. Instead of spherical core/shell structures, we produced and studied quasi-spherical CdS/PbS and CdSe/PbSe Janus-type heterostructures. Nontrivial PL behavior was observed from the CdS(e)/PbS(e) heterostructures as the Pb:Cd ratio is increased.« less

  13. Preparation of Cd/Pb Chalcogenide Heterostructured Janus Particles via Controllable Cation Exchange.

    PubMed

    Zhang, Jianbing; Chernomordik, Boris D; Crisp, Ryan W; Kroupa, Daniel M; Luther, Joseph M; Miller, Elisa M; Gao, Jianbo; Beard, Matthew C

    2015-07-28

    We developed a strategy for producing quasi-spherical nanocrystals of anisotropic heterostructures of Cd/Pb chalcogenides. The nanostructures are fabricated via a controlled cation exchange reaction where the Cd(2+) cation is exchanged for the Pb(2+) cation. The cation exchange reaction is thermally activated and can be controlled by adjusting the reaction temperature or time. We characterized the particles using TEM, XPS, PL, and absorption spectroscopy. With complete exchange, high quality Pb-chalcogenide quantum dots are produced. In addition to Cd(2+), we also find suitable conditions for the exchange of Zn(2+) cations for Pb(2+) cations. The cation exchange is anisotropic starting at one edge of the nanocrystals and proceeds along the ⟨111⟩ direction producing a sharp interface at a (111) crystallographic plane. Instead of spherical core/shell structures, we produced and studied quasi-spherical CdS/PbS and CdSe/PbSe Janus-type heterostructures. Nontrivial PL behavior was observed from the CdS(e)/PbS(e) heterostructures as the Pb:Cd ratio is increased.

  14. Structural vs. intrinsic carriers: contrasting effects of cation chemistry and disorder on ionic conductivity in pyrochlores

    DOE PAGES

    Perriot, Romain; Uberuaga, Blas P.

    2015-04-21

    We use molecular dynamics simulations to investigate the role of cation disorder on oxygen diffusion in Gd 2Zr 2O 7 (GZO) and Gd 2Ti 2O 7 (GTO) pyrochlores, a class of complex oxides which contain a structural vacancy relative to the basic fluorite structure. The introduction of disorder has distinct effects depending on the chemistry of the material, increasing the mobility of structural carriers by up to four orders of magnitude in GZO. In contrast, in GTO, there is no mobility at zero or low disorder on the ns timescale, but higher disorder liberates the otherwise immobile carriers, allowing diffusionmore » with rates comparable to GZO for the fully disordered material. Here, we show that the cation disorder enhances the diffusivity by both increasing the concentration of mobile structural carriers and their individual mobility. The disorder also influences the diffusion in materials containing intrinsic carriers, such as additional vacancies VO or oxygen interstitials OI. And while in ordered GZO and GTO the contribution of the intrinsic carriers dominates the overall diffusion of oxygen, OI in GZO contributes along with structural carriers, and the total diffusion rate can be calculated by assuming simple additive contributions from the two sources. Although the disorder in the materials with intrinsic defects usually enhances the diffusivity as in the defect-free case, in low concentrations, cation antisites AB or BA, where A = Gd and B = Zr or Ti, can act as traps for fast intrinsic defects. The trapping results in a lowering of the diffusivity, and causes a non-monotonic behavior of the diffusivity with disorder. Conversely, in the case of slow intrinsic defects, the main effect of the disorder is to liberate the structural carriers, resulting in an increase of the diffusivity regardless of the defect trapping.« less

  15. Infrared Spectroscopy of the Mass 31 Cation: Protonated Formaldehyde VS. The Triplet Methoxy Cation

    NASA Astrophysics Data System (ADS)

    Mosley, J. D.; Cheng, T. C.; Duncan, M. A.

    2012-06-01

    The m/z=31 cation is produced by ionization and fragmentation of methanol, ethanol, dimethyl ether, etc. Two structures have been proposed, protonated formaldehyde (^1CH_2OH^+) and the triplet methoxy cation (^3CH_3O^+). The infrared spectrum of the mass 31 cation is obtained using infrared photodissociation spectroscopy with Ar tagging. The spectrum reveals the presence of two stable isomers, protonated formaldehyde (^1CH_2OH^+) and the triplet methoxy cation (^3CH_3O^+). The triplet methoxy cation has been studied extensively and is predicted to interconvert to protonated formaldehyde through an essentially barrierless process on a timescale much faster than our experiment (>100 μs). The presence of two structural isomers is verified by comparison of spectra from different precursors and spectra of different temperature ions from the same precursor.

  16. Predicting Organic Cation Sorption Coefficients: Accounting for Competition from Sorbed Inorganic Cations Using a Simple Probe Molecule.

    PubMed

    Jolin, William C; Goyetche, Reaha; Carter, Katherine; Medina, John; Vasudevan, Dharni; MacKay, Allison A

    2017-06-06

    With the increasing number of emerging contaminants that are cationic at environmentally relevant pH values, there is a need for robust predictive models of organic cation sorption coefficients (K d ). Current predictive models fail to account for the differences in the identity, abundance, and affinity of surface-associated inorganic exchange ions naturally present at negatively charged receptor sites on environmental solids. To better understand how organic cation sorption is influenced by surface-associated inorganic exchange ions, sorption coefficients of 10 organic cations (including eight pharmaceuticals and two simple probe organic amines) were determined for six homoionic forms of the aluminosilicate mineral, montmorillonite. Organic cation sorption coefficients exhibited consistent trends for all compounds across the various homoionic clays with sorption coefficients (K d ) decreasing as follows: K d Na + > K d NH 4 + ≥ K d K + > K d Ca 2+ ≥ K d Mg 2+ > K d Al 3+ . This trend for competition between organic cations and exchangeable inorganic cations is consistent with the inorganic cation selectivity sequence, determined for exchange between inorganic ions. Such consistent trends in competition between organic and inorganic cations suggested that a simple probe cation, such as phenyltrimethylammonium or benzylamine, could capture soil-to-soil variations in native inorganic cation identity and abundance for the prediction of organic cation sorption to soils and soil minerals. Indeed, sorption of two pharmaceutical compounds to 30 soils was better described by phenyltrimethylammonium sorption than by measures of benzylamine sorption, effective cation exchange capacity alone, or a model from the literature (Droge, S., and Goss, K. Environ. Sci. Technol. 2013, 47, 14224). A hybrid approach integrating structural scaling factors derived from this literature model of organic cation sorption, along with phenyltrimethylammonium K d values, allowed for

  17. Cationic antimicrobial polymers and their assemblies.

    PubMed

    Carmona-Ribeiro, Ana Maria; de Melo Carrasco, Letícia Dias

    2013-05-10

    Cationic compounds are promising candidates for development of antimicrobial agents. Positive charges attached to surfaces, particles, polymers, peptides or bilayers have been used as antimicrobial agents by themselves or in sophisticated formulations. The main positively charged moieties in these natural or synthetic structures are quaternary ammonium groups, resulting in quaternary ammonium compounds (QACs). The advantage of amphiphilic cationic polymers when compared to small amphiphilic molecules is their enhanced microbicidal activity. Besides, many of these polymeric structures also show low toxicity to human cells; a major requirement for biomedical applications. Determination of the specific elements in polymers, which affect their antimicrobial activity, has been previously difficult due to broad molecular weight distributions and random sequences characteristic of radical polymerization. With the advances in polymerization control, selection of well defined polymers and structures are allowing greater insight into their structure-antimicrobial activity relationship. On the other hand, antimicrobial polymers grafted or self-assembled to inert or non inert vehicles can yield hybrid antimicrobial nanostructures or films, which can act as antimicrobials by themselves or deliver bioactive molecules for a variety of applications, such as wound dressing, photodynamic antimicrobial therapy, food packing and preservation and antifouling applications.

  18. Cationic Antimicrobial Polymers and Their Assemblies

    PubMed Central

    Carmona-Ribeiro, Ana Maria; de Melo Carrasco, Letícia Dias

    2013-01-01

    Cationic compounds are promising candidates for development of antimicrobial agents. Positive charges attached to surfaces, particles, polymers, peptides or bilayers have been used as antimicrobial agents by themselves or in sophisticated formulations. The main positively charged moieties in these natural or synthetic structures are quaternary ammonium groups, resulting in quaternary ammonium compounds (QACs). The advantage of amphiphilic cationic polymers when compared to small amphiphilic molecules is their enhanced microbicidal activity. Besides, many of these polymeric structures also show low toxicity to human cells; a major requirement for biomedical applications. Determination of the specific elements in polymers, which affect their antimicrobial activity, has been previously difficult due to broad molecular weight distributions and random sequences characteristic of radical polymerization. With the advances in polymerization control, selection of well defined polymers and structures are allowing greater insight into their structure-antimicrobial activity relationship. On the other hand, antimicrobial polymers grafted or self-assembled to inert or non inert vehicles can yield hybrid antimicrobial nanostructures or films, which can act as antimicrobials by themselves or deliver bioactive molecules for a variety of applications, such as wound dressing, photodynamic antimicrobial therapy, food packing and preservation and antifouling applications. PMID:23665898

  19. Cationic antimicrobial peptides in penaeid shrimp.

    PubMed

    Tassanakajon, Anchalee; Amparyup, Piti; Somboonwiwat, Kunlaya; Supungul, Premruethai

    2011-08-01

    Penaeid shrimp aquaculture has been consistently affected worldwide by devastating diseases that cause a severe loss in production. To fight a variety of harmful microbes in the surrounding environment, particularly at high densities (of which intensive farming represents an extreme example), shrimps have evolved and use a diverse array of antimicrobial peptides (AMPs) as part of an important first-line response of the host defense system. Cationic AMPs in penaeid shrimps composed of penaeidins, crustins, and anti-lipopolysaccharide factors are comprised of multiple classes or isoforms and possess antibacterial and antifungal activities against different strains of bacteria and fungi. Shrimp AMPs are primarily expressed in circulating hemocytes, which is the main site of the immune response, and hemocytes expressing AMPs probably migrate to infection sites to fight against pathogen invasion. Indeed, most AMPs are produced as early as the nauplii developmental stage to protect shrimp larvae from infections. In this review, we discuss the sequence diversity, expression, gene structure, and antimicrobial activities of cationic AMPs in penaeid shrimps. The information available on antimicrobial activities indicates that these shrimp AMPs have potential therapeutic applications in the control of disease problems in aquaculture.

  20. Latent Ice Recrystallization Inhibition Activity in Nonantifreeze Proteins: Ca2+-Activated Plant Lectins and Cation-Activated Antimicrobial Peptides.

    PubMed

    Mitchell, Daniel E; Gibson, Matthew I

    2015-10-12

    Organisms living in polar regions have evolved a series of antifreeze (glyco) proteins (AFGPs) to enable them to survive by modulating the structure of ice. These proteins have huge potential for use in cellular cryopreservation, ice-resistant surfaces, frozen food, and cryosurgery, but they are limited by their relatively low availability and questions regarding their mode of action. This has triggered the search for biomimetic materials capable of reproducing this function. The identification of new structures and sequences capable of inhibiting ice growth is crucial to aid our understanding of these proteins. Here, we show that plant c-type lectins, which have similar biological function to human c-type lectins (glycan recognition) but no sequence homology to AFPs, display calcium-dependent ice recrystallization inhibition (IRI) activity. This IRI activity can be switched on/off by changing the Ca2+ concentration. To show that more (nonantifreeze) proteins may exist with the potential to display IRI, a second motif was considered, amphipathicity. All known AFPs have defined hydrophobic/hydrophilic domains, rationalizing this choice. The cheap, and widely used, antimicrobial Nisin was found to have cation-dependent IRI activity, controlled by either acid or addition of histidine-binding ions such as zinc or nickel, which promote its amphipathic structure. These results demonstrate a new approach in the identification of antifreeze protein mimetic macromolecules and may help in the development of synthetic mimics of AFPs.

  1. Theoretical study on the electronic, structural, properties and reactivity of a series of mono-, di-, tri- and tetrachlorothiophenes as well as corresponding radical cation forms as monomers for conducting polymers.

    PubMed

    Shirani Il Beigi, Hossein; Jameh-Bozorghi, Saeed

    2011-03-14

    In this paper, electrical and structural properties of mono-, di-, tri- and tetrachlorothiophenes and their radical cations have been studied using the density functional theory and B3LYP method with 6-311++G** basis set. The effects of the number and position of the substituent of chlorine atoms on the properties of the thiophene ring for all chlorothiophenes and their radical cations have been studied. Vibrational frequencies, nuclear chemical shielding constants, spin-density distribution, size and direction of dipole moment vector, ionization potential, electric polarizabilities and NICS values of these compounds have been calculated as well. The analysis of these data showed that double bonds in 3-chlorothiophene are more delocalized and it is the best possible candidate monomer among all chlorothiophenes for the synthesis of corresponding conducting polymers with modified characteristics.

  2. Cation-exchanged zeolites for the selective oxidation of methane to methanol

    DOE PAGES

    Kulkarni, Ambarish R.; Zhao, Zhi-Jian; Siahrostami, Samira; ...

    2017-10-19

    Motivated by the increasing availability of cheap natural gas resources, considerable experimental and computational research efforts have focused on identifying selective catalysts for the direct conversion of methane to methanol. One promising class of catalysts are cation-exchanged zeolites, which have steadily increased in popularity over the past decade. Here, in this article, we first present a broad overview of this field from a conceptual perspective, and highlight the role of theory in developing a molecular-level understanding of the reaction. Next, by performing and analyzing a large database of density functional theory (DFT) calculations for a wide range of transition metalmore » cations, zeolite topologies and active site motifs, we present a unifying picture of the methane activation process in terms of active site stability, C–H bond activation and methanol extraction. Based on the trade-offs of active site stability and reactivity, we propose a framework for identifying new, promising active site motifs in these systems. Further, we show that the high methanol selectivity arises due to the strong binding nature of the C–H activation products. Lastly, using the atomistic and mechanistic insight obtained from these analyses, we summarize the key challenges and future strategies for improving the performance of cation-exchanged zeolites for this industrially relevant conversion.« less

  3. Cation-exchanged zeolites for the selective oxidation of methane to methanol

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kulkarni, Ambarish R.; Zhao, Zhi-Jian; Siahrostami, Samira

    Motivated by the increasing availability of cheap natural gas resources, considerable experimental and computational research efforts have focused on identifying selective catalysts for the direct conversion of methane to methanol. One promising class of catalysts are cation-exchanged zeolites, which have steadily increased in popularity over the past decade. Here, in this article, we first present a broad overview of this field from a conceptual perspective, and highlight the role of theory in developing a molecular-level understanding of the reaction. Next, by performing and analyzing a large database of density functional theory (DFT) calculations for a wide range of transition metalmore » cations, zeolite topologies and active site motifs, we present a unifying picture of the methane activation process in terms of active site stability, C–H bond activation and methanol extraction. Based on the trade-offs of active site stability and reactivity, we propose a framework for identifying new, promising active site motifs in these systems. Further, we show that the high methanol selectivity arises due to the strong binding nature of the C–H activation products. Lastly, using the atomistic and mechanistic insight obtained from these analyses, we summarize the key challenges and future strategies for improving the performance of cation-exchanged zeolites for this industrially relevant conversion.« less

  4. Kinetic Monte Carlo Simulation of Cation Diffusion in Low-K Ceramics

    NASA Technical Reports Server (NTRS)

    Good, Brian

    2013-01-01

    Low thermal conductivity (low-K) ceramic materials are of interest to the aerospace community for use as the thermal barrier component of coating systems for turbine engine components. In particular, zirconia-based materials exhibit both low thermal conductivity and structural stability at high temperature, making them suitable for such applications. Because creep is one of the potential failure modes, and because diffusion is a mechanism by which creep takes place, we have performed computer simulations of cation diffusion in a variety of zirconia-based low-K materials. The kinetic Monte Carlo simulation method is an alternative to the more widely known molecular dynamics (MD) method. It is designed to study "infrequent-event" processes, such as diffusion, for which MD simulation can be highly inefficient. We describe the results of kinetic Monte Carlo computer simulations of cation diffusion in several zirconia-based materials, specifically, zirconia doped with Y, Gd, Nb and Yb. Diffusion paths are identified, and migration energy barriers are obtained from density functional calculations and from the literature. We present results on the temperature dependence of the diffusivity, and on the effects of the presence of oxygen vacancies in cation diffusion barrier complexes as well.

  5. Cation depletion by the sodium pump in red cells with pathologic cation leaks. Sickle cells and xerocytes.

    PubMed Central

    Joiner, C H; Platt, O S; Lux, S E

    1986-01-01

    The mechanism by which sickle cells and xerocytic red cells become depleted of cations in vivo has not been identified previously. Both types of cells exhibit elevated permeabilities to sodium and potassium, in the case of sickle cells, when deoxygenated. The ouabain-insensitive fluxes of sodium and potassium were equivalent, however, in both cell types under these conditions. When incubated 18 hours in vitro, sickle cells lost cations but only when deoxygenated. This cation depletion was blocked by ouabain, removal of external potassium, or pretreatment with 4,4'-diisothiocyanostilbene-2,2'-disulfonate, which blocks the increase in cation permeability induced by deoxygenation. The loss of cation exhibited by oxygenated xerocytes similarly incubated was also blocked by ouabain. These data support the hypothesis that the elevated "passive" cation fluxes of xerocytes and deoxygenated sickle cells are not directly responsible for cation depletion of these cells; rather, these pathologic leaks interact with the sodium pump to produce a net loss of cellular cation. PMID:2430999

  6. Cation depletion by the sodium pump in red cells with pathologic cation leaks. Sickle cells and xerocytes.

    PubMed

    Joiner, C H; Platt, O S; Lux, S E

    1986-12-01

    The mechanism by which sickle cells and xerocytic red cells become depleted of cations in vivo has not been identified previously. Both types of cells exhibit elevated permeabilities to sodium and potassium, in the case of sickle cells, when deoxygenated. The ouabain-insensitive fluxes of sodium and potassium were equivalent, however, in both cell types under these conditions. When incubated 18 hours in vitro, sickle cells lost cations but only when deoxygenated. This cation depletion was blocked by ouabain, removal of external potassium, or pretreatment with 4,4'-diisothiocyanostilbene-2,2'-disulfonate, which blocks the increase in cation permeability induced by deoxygenation. The loss of cation exhibited by oxygenated xerocytes similarly incubated was also blocked by ouabain. These data support the hypothesis that the elevated "passive" cation fluxes of xerocytes and deoxygenated sickle cells are not directly responsible for cation depletion of these cells; rather, these pathologic leaks interact with the sodium pump to produce a net loss of cellular cation.

  7. Effect of Cation Ordering on the Performance and Chemical Stability of Layered Double Perovskite Cathodes

    PubMed Central

    Bernuy-Lopez, Carlos; Rioja-Monllor, Laura; Nakamura, Takashi; Ricote, Sandrine; O’Hayre, Ryan; Amezawa, Koji; Einarsrud, Mari-Ann

    2018-01-01

    The effect of A-site cation ordering on the cathode performance and chemical stability of A-site cation ordered LaBaCo2O5+δ and disordered La0.5Ba0.5CoO3−δ materials are reported. Symmetric half-cells with a proton-conducting BaZr0.9Y0.1O3−δ electrolyte were prepared by ceramic processing, and good chemical compatibility of the materials was demonstrated. Both A-site ordered LaBaCo2O5+δ and A-site disordered La0.5Ba0.5CoO3−δ yield excellent cathode performance with Area Specific Resistances as low as 7.4 and 11.5 Ω·cm2 at 400 °C and 0.16 and 0.32 Ω·cm2 at 600 °C in 3% humidified synthetic air respectively. The oxygen vacancy concentration, electrical conductivity, basicity of cations and crystal structure were evaluated to rationalize the electrochemical performance of the two materials. The combination of high-basicity elements and high electrical conductivity as well as sufficient oxygen vacancy concentration explains the excellent performance of both LaBaCo2O5+δ and La0.5Ba0.5CoO3−δ materials at high temperatures. At lower temperatures, oxygen-deficiency in both materials is greatly reduced, leading to decreased performance despite the high basicity and electrical conductivity. A-site cation ordering leads to a higher oxygen vacancy concentration, which explains the better performance of LaBaCo2O5+δ. Finally, the more pronounced oxygen deficiency of the cation ordered polymorph and the lower chemical stability at reducing conditions were confirmed by coulometric titration. PMID:29373541

  8. Promising silicones modified with cationic biocides for the development of antimicrobial medical devices.

    PubMed

    Ghamrawi, Sarah; Bouchara, Jean-Philippe; Tarasyuk, Oksana; Rogalsky, Sergiy; Lyoshina, Lyudmila; Bulko, Olga; Bardeau, Jean-François

    2017-06-01

    We have tested silicones containing 2% or 5% of the cationic biocides polyhexamethylene guanidine dodecylbenzenesulfonate (PHMG-DBS), 1-octyl-3-methylimidazolium tetrafluoroborate (OMIM-BF 4 ) or 1-dodecyl-3-methylimidazolium tetrafluoroborate (DMIM-BF 4 ) against the major relevant bacterial and yeast species in health care-associated infections (HCAI). Study conducted according to the international standard ISO 22196 revealed that silicones containing 2% or 5% DMIM-BF 4 or 5% PHMG-DBS presented the highest antimicrobial activity, leading to a logarithmic growth reduction of 3.03 to 6.46 and 3.65 to 4.85 depending on the bacterial or fungal species. Heat-pretreated silicones containing 2% DMIM-BF 4 kept a high activity, with at least a 3-log reduction in bacterial growth, except against P. aeruginosa where there was only a 1.1-log reduction. After 33days, the release ratio of cationic biocide from silicone films containing 5% of DMIM-BF 4 was found to be 5.6% in pure water and 1.9% in physiological saline solution, respectively. No leaching of PHMG-DBS polymeric biocide was detected under the same conditions. These results demonstrate unambiguously that silicones containing 2% DMIM-BF 4 or 5% PHMG-DBS present high antimicrobial activity, as well as high leaching resistance and therefore may be good candidates for the development of safer medical devices. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Method for encapsulating and isolating hazardous cations, medium for encapsulating and isolating hazardous cations

    DOEpatents

    Wasserman, S.R.; Anderson, K.B.; Song, K.; Yuchs, S.E.; Marshall, C.L.

    1998-04-28

    A method for encapsulating hazardous cations is provided comprising supplying a pretreated substrate containing the cations; contacting the substrate with an organo-silane compound to form a coating on the substrate; and allowing the coating to cure. A medium for containing hazardous cations is also provided, comprising a substrate having ion-exchange capacity and a silane-containing coating on the substrate. 3 figs.

  10. Single mechanically-gated cation channel currents can trigger action potentials in neocortical and hippocampal pyramidal neurons.

    PubMed

    Nikolaev, Yury A; Dosen, Peter J; Laver, Derek R; van Helden, Dirk F; Hamill, Owen P

    2015-05-22

    The mammalian brain is a mechanosensitive organ that responds to different mechanical forces ranging from intrinsic forces implicated in brain morphogenesis to extrinsic forces that can cause concussion and traumatic brain injury. However, little is known of the mechanosensors that transduce these forces. In this study we use cell-attached patch recording to measure single mechanically-gated (MG) channel currents and their affects on spike activity in identified neurons in neonatal mouse brain slices. We demonstrate that both neocortical and hippocampal pyramidal neurons express stretch-activated MG cation channels that are activated by suctions of ~25mm Hg, have a single channel conductance for inward current of 50-70pS and show weak selectivity for alkali metal cations (i.e., Na(+)activated on the soma trigger spiking/action potentials in both neocortical and hippocampal pyramidal neurons. Not all neuron types studied here expressed MG channel currents. In particular, locus coeruleus and cerebellar Purkinje neurons showed no detectable MG channel activity. Moreover their robust rhythmic spike activity was resistant to mechanical modulation. Our observation that a single MG channel current can trigger spiking predicates the need for reassessment of the long held view that the impulse output of central neurons depends only upon their intrinsic voltage-gated channels and/or their integrated synaptic input. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. A Cation-containing Polymer Anion Exchange Membrane based on Poly(norbornene)

    NASA Astrophysics Data System (ADS)

    Beyer, Frederick; Price, Samuel; Ren, Xiaoming; Savage, Alice

    Cation-containing polymers are being studied widely for use as anion exchange membranes (AEMs) in alkaline fuel cells (AFCs) because AEMs offer a number of potential benefits including allowing a solid state device and elimination of the carbonate poisoning problem. The successful AEM will combine high performance from several orthogonal properties, having robust mechanical strength even when wet, high hydroxide conductivity, and the high chemical stability required for long device lifetimes. In this study, we have synthesized a model cationic polymer that combines three of the key advantages of Nafion. The polymer backbone based on semicrystalline atactic poly(norbornene) offers good mechanical properties. A flexible, ether-based tether between the backbone and fixed cation charged species (quaternary ammonium) should provide the low-Tg, hydrophilic environment required to facilitate OH- transport. Finally, methyl groups have been added at the beta position relative to the quaternary ammonium cation to prevent Hoffman elimination, one mechanism by which AEMs are neutralized in a high pH environment. In this poster, we will present our findings on mechanical properties, morphology, charge transport, and chemical stability of this material.

  12. A new model linking elastic properties and ionic conductivity of mixed network former glasses.

    PubMed

    Wang, Weimin; Christensen, Randilynn; Curtis, Brittany; Martin, Steve W; Kieffer, John

    2018-01-17

    Glasses are promising candidate materials for all-solid-state electrolytes for rechargeable batteries due to their outstanding mechanical stability, wide electrochemical stability range, and open structure for potentially high conductivity. Mechanical stiffness and ionic conductivity are two key parameters for solid-state electrolytes. In this study, we investigate two mixed-network former glass systems, sodium borosilicate 0.2Na 2 O + 0.8[xBO 1.5 + (1 - x)SiO 2 ] and sodium borogermanate 0.2Na 2 O + 0.8[xBO 1.5 + (1 - x)GeO 2 ] glasses. With mixed-network formers, the structure of the network changes while the network modifier mole fraction is kept constant, i.e., x = 0.2, which allows us to analyze the effect of the network structure on various properties, including ionic conductivity and elastic properties. Besides the non-linear, non-additive mixed glass former effect, we find that the longitudinal, shear and Young's moduli depend on the combined number density of tetrahedrally and octahedrally coordinated network former elements. These units provide connectivity in three dimensions, which is required for the networks to exhibit restoring forces in response to isotropic and shear deformations. Moreover, the activation energy for modifier cation, Na + , migration is strongly correlated with the bulk modulus, suggesting that the elastic strain energy associated with the passageway dilation for the sodium ions is governed by the bulk modulus of the glass. The detailed analysis provided here gives an estimate for the number of atoms in the vicinity of the migrating cation that are affected by elastic deformation during the activated process. The larger this number and the more compliant the glass network, the lower is the activation energy for the cation jump.

  13. Anion-Cation Permeability Correlates with Hydrated Counterion Size in Glycine Receptor Channels

    PubMed Central

    Sugiharto, Silas; Lewis, Trevor M.; Moorhouse, Andrew J.; Schofield, Peter R.; Barry, Peter H.

    2008-01-01

    The functional role of ligand-gated ion channels depends critically on whether they are predominantly permeable to cations or anions. However, these, and other ion channels, are not perfectly selective, allowing some counterions to also permeate. To address the mechanisms by which such counterion permeation occurs, we measured the anion-cation permeabilities of different alkali cations, Li+ Na+, and Cs+, relative to either Cl− or \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}{\\mathrm{NO}}_{3}^{-}\\end{equation*}\\end{document} anions in both a wild-type glycine receptor channel (GlyR) and a mutant GlyR with a wider pore diameter. We hypothesized and showed that counterion permeation in anionic channels correlated inversely with an equivalent or effective hydrated size of the cation relative to the channel pore radius, with larger counterion permeabilities being observed in the wider pore channel. We also showed that the anion component of conductance was independent of the nature of the cation. We suggest that anions and counterion cations can permeate through the pore as neutral ion pairs, to allow the cations to overcome the large energy barriers resulting from the positively charged selectivity filter in small GlyR channels, with the permeability of such ion pairs being dependent on the effective hydrated diameter of the ion pair relative to the pore diameter. PMID:18708455

  14. In vitro biopharmaceutical evaluation of ciprofloxacin/metal cation complexes for pulmonary administration.

    PubMed

    Brillault, J; Tewes, F; Couet, W; Olivier, J C

    2017-01-15

    Pulmonary delivery of fluoroquinolones (FQs) is an interesting approach to treat lung infections as it may lead to high local concentrations while minimizing systemic exposure. However, FQs have a rapid diffusion through the lung epithelium giving the pulmonary route no advantage compared to the oral route. Interactions between FQs and metal cations form complexes which limit the diffusion through the epithelial barrier and would reduce the absorption of FQs and maintain high concentrations in the lung. The effects of this complexation depend on the FQ and the metal cations and optimum partners should be selected through in vitro experiments prior to aerosol drug formulation. In this study, CIP was chosen as a representative FQ and 5 cations (Ca 2+ , Mg 2+ , Zn 2+ , Al 3+ , Cu 2+ ) were selected to study the complexation and its effects on permeability, antimicrobial efficacy and cell toxicity. The results showed that the apparent association constants between CIP and cations ranked with the descending order: Cu 2+ >Al 3+ >Zn 2+ >Mg 2+ >Ca 2+ . When a target of 80% complexation was reached with the adequate concentrations of cations, the CIP permeability through the Calu-3 lung epithelial cells was decreased of 50%. Toxicity of the CIP on the Calu-3 cells, with an EC50 evaluated at 7μM, was not significantly affected by the presence of the cations. The minimum inhibitory concentration of CIP for Pseudomonas aeruginosa was not affected or slightly increased in the range of cation concentrations tested, except for Mg 2+ . In conclusion, permeability was the main parameter that was affected by the metal cation complexation while cell toxicity and antimicrobial activity were not or slightly modified. Cu 2+ , with the highest apparent constant of association and with no effect on cell toxicity and antimicrobial activity of the CIP, appeared as a promising cation for the development of a controlled-permeability formulation of CIP for lung treatment. Copyright © 2016

  15. Novel polymeric LIT and divalent cation fast ion conducting materials

    NASA Astrophysics Data System (ADS)

    Angell, C. A.

    Solid state energy devices require a component which conducts electricity by ionic migration. The conductivity of this element of the system must be very high. Four types of materials show the promise to provide the necessary conductivity characteristics, while offering other desirable features such as the ability to distort in shape under mechanical stresses: (1) crystalline; (2) plastic crystal; (3) inorganic glassy; and (4) polymer salt solutions. This document reports on the following materials: lead halide-containing fast ion conducting glasses (LiF-PbF2-Al(PO3)3), mixed ionic electronic conduction (Na2O-V2O5-TeO2), alpha relaxation in ionic glasses, glass transition in P2O2, and conductivity transition between all-halide and all-oxide glasses.

  16. Cationic membrane-active peptides - anticancer and antifungal activity as well as penetration into human skin.

    PubMed

    Do, Nhung; Weindl, Günther; Grohmann, Lisa; Salwiczek, Mario; Koksch, Beate; Korting, Hans Christian; Schäfer-Korting, Monika

    2014-05-01

    Cationic antimicrobial peptides are ancient natural broad-spectrum antibiotics, and several compounds also exhibit anticancer activity. However, most applications pertain to bacterial infections, and treatment for skin cancer is less frequently considered. The cytotoxicity of melittin, cecropin A, protegrin-1 and histatin 5 against squamous skin cancer cell lines and normal human keratinocytes was evaluated and compared to established drugs. The results show that melittin clearly outperforms 5-fluorouracil regarding antitumor activity. Importantly, combined melittin and 5-fluorouracil enhanced cytotoxic effects on cancer cells and reduced toxicity on normal keratinocytes. Additionally, minimum inhibitory concentrations indicate that melittin also shows superior activity against clinical and laboratory strains of Candida albicans compared to amphotericin B. To evaluate its potential for topical applications, human skin penetration of melittin was investigated ex vivo and compared to two non-toxic cell-penetrating peptides (CPPs), low molecular weight protamine (LMWP) and penetratin. The stratum corneum prevents penetration into viable epidermis over 6 h; however, the peptides gain access to the viable skin after 24 h. Inhibition of digestive enzymes during skin penetration significantly enhances the availability of intact peptide. In conclusion, melittin may represent an innovative agent for non-melanoma skin cancer and infectious skin diseases. In order to develop a drug candidate, skin absorption and proteolytic digestion by skin enzymes need to be addressed. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Effect of cation ordering on oxygen vacancy diffusion pathways in double perovskites

    DOE PAGES

    Uberuaga, Blas Pedro; Pilania, Ghanshyam

    2015-07-08

    Perovskite structured oxides (ABO 3) are attractive for a number of technological applications, including as superionics because of the high oxygen conductivities they exhibit. Double perovskites (AA’BB’O 6) provide even more flexibility for tailoring properties. Using accelerated molecular dynamics, we examine the role of cation ordering on oxygen vacancy mobility in one model double perovskite SrLaTiAlO 6. We find that the mobility of the vacancy is very sensitive to the cation ordering, with a migration energy that varies from 0.6 to 2.7 eV. In the extreme cases, the mobility is both higher and lower than either of the two endmore » member single perovskites. Further, the nature of oxygen vacancy diffusion, whether one-dimensional, two-dimensional, or three-dimensional, also varies with cation ordering. We correlate the dependence of oxygen mobility on cation structure to the distribution of Ti 4+ cations, which provide unfavorable environments for the positively charged oxygen vacancy. The results demonstrate the potential of using tailored double perovskite structures to precisely control the behavior of oxygen vacancies in these materials.« less

  18. Cation–cation interactions and cation exchange in a series of isostructural framework uranyl tungstates

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Balboni, Enrica; Burns, Peter C., E-mail: pburns@nd.edu; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556

    2014-05-01

    The isotypical compounds (UO{sub 2}){sub 3}(WO{sub 6})(H{sub 2}O){sub 5} (1), Ag(UO{sub 2}){sub 3}(WO{sub 6})(OH)(H{sub 2}O){sub 3} (2), K(UO{sub 2}){sub 3}(WO{sub 6})OH(H{sub 2}O){sub 4} (3), Rb(UO{sub 2}){sub 3}(WO{sub 6})(OH)(H{sub 2}O){sub 3.5} (4), and Cs(UO{sub 2}){sub 3}(WO{sub 6})OH(H{sub 2}O){sub 3} (5) were synthesized, characterized, and their structures determined. Each crystallizes in space group Cc. (1): a=12.979 (3), b=10.238 (2), c=11.302 (2), β=102.044 (2); (2): a=13.148 (2), b=9.520 (1), c=11.083 (2), β=101.568 (2); (3): a=13.111 (8), b=9.930 (6), c=11.242 (7), β=101.024 (7); (4): a=12.940 (2), b=10.231 (2), c=11.259(2), β=102.205 (2); (5): a=12.983 (3), b=10.191 (3), c=11.263 (4), β=101.661 (4). Compounds 1–5 are amore » framework of uranyl and tungsten polyhedra containing cation–cation interactions. The framework has three symmetrically distinct U(VI) cations, one tungsten, sixteen to eighteen oxygen atoms, and in 2–5, one monovalent cation. Each atom occupies a general position. Each U(VI) cation is present as a typical (UO{sub 2}){sup 2+} uranyl ion in an overall pentagonal bipyramidal coordination environment. Each pentagonal bipyramid shares two equatorial edges with two other pentagonal bipyramids, forming a trimer. Trimers are connected into chains by edge-sharing with WO{sub 6} octahedra. Chains are linked through cation–cation interactions between two symmetrically independent uranyl ions. This yields a remarkably complex system of intersecting channels that extend along [0 0 1] and [−1 1 0]. The cation exchange properties of 2 and 3 were characterized at room temperature and at 140 °C. - Graphical abstract: Chains of uranium and tungsten polyhedra are connected into a three dimensional framework by cation–cation interactions occurring between two symmetrically independent uranyl pentagonal bipyramids. Monovalent cations present in channels within the structure can be exchanged by room temperature or mild

  19. Cationic niosomes an effective gene carrier composed of novel spermine-derivative cationic lipids: effect of central core structures.

    PubMed

    Opanasopit, Praneet; Leksantikul, Lalita; Niyomtham, Nattisa; Rojanarata, Theerasak; Ngawhirunpat, Tanasait; Yingyongnarongkul, Boon-Ek

    2017-05-01

    Cationic niosomes formulated from Span 20, cholesterol (Chol) and novel spermine-based cationic lipids of multiple central core structures (di(oxyethyl)amino, di(oxyethyl)amino carboxy, 3-amino-1,2-dioxypropyl and 2-amino-1,3-dioxypropyl) were successfully prepared for improving transfection efficiency in vitro. The niosomes composed of spermine cationic lipid with central core structure of di(oxyethyl)amino revealed the highest gene transfection efficiency. To investigate the factors affecting gene transfection and cell viability including differences in the central core structures of cationic lipids, the composition of vesicles, molar ratio of cationic lipids in formulations and the weight ratio of niosomes to DNA. Cationic niosomes composed of nonionic surfactants (Span20), cholesterol and spermine-based cationic lipids of multiple central core structures were formulated. Gene transfection and cell viability were evaluated on a human cervical carcinoma cell line (HeLa cells) using pDNA encoding green fluorescent protein (pEGFP-C2). The morphology, size and charge were also characterized. High transfection efficiency was obtained from cationic niosomes composed of Span20:Chol:cationic lipid at the molar ratio of 2.5:2.5:0.5 mM. Cationic lipids with di(oxyethyl)amino as a central core structure exhibited highest transfection efficiency. In addition, there was also no serum effect on transfection efficiency. These novel cationic niosomes may constitute a good alternative carrier for gene transfection.

  20. Study of the antimicrobial activity of cyclic cation-based ionic liquids via experimental and group contribution QSAR model.

    PubMed

    Ghanem, Ouahid Ben; Shah, Syed Nasir; Lévêque, Jean-Marc; Mutalib, M I Abdul; El-Harbawi, Mohanad; Khan, Amir Sada; Alnarabiji, Mohamad Sahban; Al-Absi, Hamada R H; Ullah, Zahoor

    2018-03-01

    Over the past decades, Ionic liquids (ILs) have gained considerable attention from the scientific community in reason of their versatility and performance in many fields. However, they nowadays remain mainly for laboratory scale use. The main barrier hampering their use in a larger scale is their questionable ecological toxicity. This study investigated the effect of hydrophobic and hydrophilic cyclic cation-based ILs against four pathogenic bacteria that infect humans. For that, cations, either of aromatic character (imidazolium or pyridinium) or of non-aromatic nature, (pyrrolidinium or piperidinium), were selected with different alkyl chain lengths and combined with both hydrophilic and hydrophobic anionic moieties. The results clearly demonstrated that introducing of hydrophobic anion namely bis((trifluoromethyl)sulfonyl)amide, [NTF 2 ] and the elongation of the cations substitutions dramatically affect ILs toxicity behaviour. The established toxicity data [50% effective concentration (EC 50 )] along with similar endpoint collected from previous work against Aeromonas hydrophila were combined to developed quantitative structure-activity relationship (QSAR) model for toxicity prediction. The model was developed and validated in the light of Organization for Economic Co-operation and Development (OECD) guidelines strategy, producing good correlation coefficient R 2 of 0.904 and small mean square error (MSE) of 0.095. The reliability of the QSAR model was further determined using k-fold cross validation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Enhancement of perchlorate removal from groundwater by cationic granular activated carbon: Effect of preparation protocol and surface properties.

    PubMed

    Hou, Pin; Yan, Zhe; Cannon, Fred S; Yue, Ye; Byrne, Timothy; Nieto-Delgado, Cesar

    2018-06-01

    In order to obtain a high adsorption capacity for perchlorate, the epoxide-forming quaternary ammonium (EQA) compounds were chemically bonded onto granular activated carbon (GAC) surface by cationic reaction. The optimum preparation condition of the cationic GAC was achieved while applying softwood-based Gran C as the parent GAC, dosing EQA first at a pH of 12, preparation time of 48 h, preparation temperature of 50 °C, and mole ratio of EQA/oxygen groups of 2.5. The most favorable cationic GAC that had the QUAB360 pre-anchored exhibited the highest perchlorate adsorption capacity of 24.7 mg/g, and presented the longest bed volumes (3000 BV) to 2 ppb breakthrough during rapid small scale column tests (RSSCTs), which was 150 times higher than that for the pristine Gran C. This was attributed to its higher nitrogen amount (1.53 At%) and higher positive surface charge (0.036 mmol/g) at pH 7.5. Also, there was no leaching of the quaternary ammonium detected in the effluent of the RSSCTs, indicating there was no secondary pollution occurring during the perchlorate removal process. Overall, this study provides an effective and environmental-friendly technology for improving GAC perchlorate adsorption capacity for groundwater treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Cationic nanoemulsions as potential carriers for intracellular delivery

    PubMed Central

    Khachane, P.V.; Jain, A.S.; Dhawan, V.V.; Joshi, G.V.; Date, A.A.; Mulherkar, R.; Nagarsenker, M.S.

    2014-01-01

    Successful cytosolic delivery enables opportunities for improved treatment of various genetic disorders, infectious diseases and cancer. Cationic nanoemulsions were designed using alternative excipients and evaluated for particle size, charge, effect of sterilization on its stability, DNA condensation potential and cellular uptake efficiency. Various concentrations of non-ionic and ionic stabilizers were evaluated to design formula for colloidally stable cationic nanoemulsion. The nanoemulsion comprised of 5% Capmul MCM, 0.5% didodecyldimethylammonium bromide (DDAB), 1% phospholipid, 1% Poloxamer 188 and 2.25% glycerol and possessed particle size of 81.6 ± 3.56 nm and 137.1 ± 1.57 nm before and after steam sterilization, respectively. DNA condensation studies were carried out at various nanoemulsion: DNA ratios ranging from 1:1 to 10:1. Cell uptake studies were conducted on human embryonic kidney (HEK) cell lines which are widely reported for transfection studies. The nanoemulsions showed excellent cellular uptake as evaluated by fluorescence microscopy and flow cytometry. Overall, a colloidally stable cationic nanoemulsion with good DNA condensation ability was successfully fabricated for efficient cytosolic delivery and potential for in vivo effectiveness. PMID:25972740

  3. [Effect of univalent cations on the glutamate dehydrogenase of chlorella].

    PubMed

    Shatilov, V R; Kasparova, M A; Kretovich, V L

    1976-09-01

    Effect of univalent cations (Li+, K+, Na+ and Cs+) on the activity and some kinetic properties of the constitutive and the inducible glutamate dehydrogenases (GDH) of Chlorella pyrenoidosa Pringsheim 82T has been studied. All the cations used activate the inducible GDH and produced no such effect on the constitutive GDH. From the analysis of the kinetic behaviour in the presence of K+ the conclusion was made that K+ promotes and stabilyzes a catalitically advantagenous conformation of the inducible GDH. This phenomenon appears to have a physiological meaning, because of a higher K+ concentration in Chlorella cells (about 0.1 M) and its important role in metabolism.

  4. Latent Ice Recrystallization Inhibition Activity in Nonantifreeze Proteins: Ca2+-Activated Plant Lectins and Cation-Activated Antimicrobial Peptides

    PubMed Central

    2015-01-01

    Organisms living in polar regions have evolved a series of antifreeze (glyco) proteins (AFGPs) to enable them to survive by modulating the structure of ice. These proteins have huge potential for use in cellular cryopreservation, ice-resistant surfaces, frozen food, and cryosurgery, but they are limited by their relatively low availability and questions regarding their mode of action. This has triggered the search for biomimetic materials capable of reproducing this function. The identification of new structures and sequences capable of inhibiting ice growth is crucial to aid our understanding of these proteins. Here, we show that plant c-type lectins, which have similar biological function to human c-type lectins (glycan recognition) but no sequence homology to AFPs, display calcium-dependent ice recrystallization inhibition (IRI) activity. This IRI activity can be switched on/off by changing the Ca2+ concentration. To show that more (nonantifreeze) proteins may exist with the potential to display IRI, a second motif was considered, amphipathicity. All known AFPs have defined hydrophobic/hydrophilic domains, rationalizing this choice. The cheap, and widely used, antimicrobial Nisin was found to have cation-dependent IRI activity, controlled by either acid or addition of histidine-binding ions such as zinc or nickel, which promote its amphipathic structure. These results demonstrate a new approach in the identification of antifreeze protein mimetic macromolecules and may help in the development of synthetic mimics of AFPs. PMID:26407233

  5. Cation distribution, magnetic properties and cubic-perovskite phase transition in bismuth-doped nickel ferrite

    NASA Astrophysics Data System (ADS)

    Gore, Shyam K.; Jadhav, Santosh S.; Tumberphale, Umakant B.; Shaikh, Shoyeb M.; Naushad, Mu; Mane, Rajaram S.

    2017-12-01

    The phase transition of bismuth-substituted nickel ferrite, synthesized by using a simple sol-gel autocombustion method, from cubic to perovskite is confirmed from the X-ray diffraction spectrums. The changes in isomer shift, hyperfine field and cation distribution are obtained from the Mossbauer spectroscopy analysis. The cation distribution demonstrates Ni2+ cations occupy tetrahedral sites, while Fe3+ and Bi3+ occupy both tetrahedral as well as octahedral sites. For higher concentrations of bismuth, saturation magnetization is increased whereas, coercivity is decreased which is related to phase change. The variations of dielectric constant, tangent loss and conductivity (ac) with frequency (10 Hz-5 MHz) have been explored with Bi3+-doping i.e. 'x'. According to Maxwell-Wagener model, there is an involvement of electron hopping kinetics as both dielectric constant and tangent loss are decreased with increasing frequency. Increase of conductivity with frequency (measured at room temperature, 27 °C) is attributed to increase of number of carriers and mobility.

  6. Cation Coordination Alters the Conformation of a Thrombin-Binding G-Quadruplex DNA Aptamer That Affects Inhibition of Thrombin.

    PubMed

    Zavyalova, Elena; Tagiltsev, Grigory; Reshetnikov, Roman; Arutyunyan, Alexander; Kopylov, Alexey

    2016-10-01

    Thrombin-binding aptamers are promising anticoagulants. HD1 is a monomolecular antiparallel G-quadruplex with two G-quartets linked by three loops. Aptamer-thrombin interactions are mediated with two TT-loops that bind thrombin exosite I. Several cations were shown to be coordinated inside the G-quadruplex, including K + , Na + , NH 4 + , Ba 2+ , and Sr 2+ ; on the contrary, Mn 2+ was coordinated in the grooves, outside the G-quadruplex. K + or Na + coordination provides aptamer functional activity. The effect of other cations on aptamer functional activity has not yet been described, because of a lack of relevant tests. Interactions between aptamer HD1 and a series of cations were studied. A previously developed enzymatic method was applied to evaluate aptamer inhibitory activity. The structure-function correlation was studied using the characterization of G-quadruplex conformation by circular dichroism spectroscopy. K + coordination provided the well-known high inhibitory activity of the aptamer, whereas Na + coordination supported low activity. Although NH 4 + coordination yielded a typical antiparallel G-quadruplex, no inhibitory activity was shown; a similar effect was observed for Ba 2+ and Sr 2+ coordination. Mn 2+ coordination destabilized the G-quadruplex that drastically diminished aptamer inhibitory activity. Therefore, G-quadruplex existence per se is insufficient for aptamer inhibitory activity. To elicit the nature of these effects, we thoroughly analyzed nuclear magnetic resonance (NMR) and X-ray data on the structure of the HD1 G-quadruplex with various cations. The most reasonable explanation is that cation coordination changes the conformation of TT-loops, affecting thrombin binding and inhibition. HD1 counterparts, aptamers 31-TBA and NU172, behaved similarly with some distinctions. In 31-TBA, an additional duplex module stabilized antiparallel G-quadruplex conformation at high concentrations of divalent cations; whereas in NU172, a different

  7. Nitric oxide enhances angiogenesis via the synthesis of vascular endothelial growth factor and cGMP after stroke in the rat.

    PubMed

    Zhang, Ruilan; Wang, Lei; Zhang, Li; Chen, Jieli; Zhu, Zhenping; Zhang, Zhenggang; Chopp, Michael

    2003-02-21

    We investigated the effects of NO on angiogenesis and the synthesis of vascular endothelial growth factor (VEGF) in a model of focal embolic cerebral ischemia in the rat. Compared with control rats, systemic administration of an NO donor, DETANONOate, to rats 24 hours after stroke significantly enlarged vascular perimeters and increased the number of proliferated cerebral endothelial cells and the numbers of newly generated vessels in the ischemic boundary regions, as evaluated by 3-dimensional laser scanning confocal microscopy. Treatment with DETANONOate significantly increased VEGF levels in the ischemic boundary regions as measured by ELISA. A capillary-like tube formation assay was used to investigate whether DETANONOate increases angiogenesis in ischemic brain via activation of soluble guanylate cyclase. DETANONOate-induced capillary-like tube formation was completely inhibited by a soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ). Blocking VEGF activity by a neutralized antibody against VEGF receptor 2 significantly attenuated DETANONOate-induced capillary-like tube formation. Moreover, systemic administration of a phosphodiesterase type 5 inhibitor (Sildenafil) to rats 24 hours after stroke significantly increased angiogenesis in the ischemic boundary regions. Sildenafil and an analog of cyclic guanosine monophosphate (cGMP) also induced capillary-like tube formation. These findings suggest that exogenous NO enhances angiogenesis in ischemic brain, which is mediated by the NO/cGMP pathway. Furthermore, our data suggest that NO, in part via VEGF, may enhance angiogenesis in ischemic brain.

  8. The Flocculating Cationic Polypetide from Moringa oleifera Seeds Damages Bacterial Cell Membranes by Causing Membrane Fusion.

    PubMed

    Shebek, Kevin; Schantz, Allen B; Sines, Ian; Lauser, Kathleen; Velegol, Stephanie; Kumar, Manish

    2015-04-21

    A cationic protein isolated from the seeds of the Moringa oleifera tree has been extensively studied for use in water treatment in developing countries and has been proposed for use in antimicrobial and therapeutic applications. However, the molecular basis for the antimicrobial action of this peptide, Moringa oleifera cationic protein (MOCP), has not been previously elucidated. We demonstrate here that a dominant mechanism of MOCP antimicrobial activity is membrane fusion. We used a combination of cryogenic electron microscopy (cryo-EM) and fluorescence assays to observe and study the kinetics of fusion of membranes in liposomes representing model microbial cells. We also conducted cryo-EM experiments on E. coli cells where MOCP was seen to fuse the inner and outer membranes. Coarse-grained molecular dynamics simulations of membrane vesicles with MOCP molecules were used to elucidate steps in peptide adsorption, stalk formation, and fusion between membranes.

  9. Formation of Stable Cationic Lipid/DNA Complexes for Gene Transfer

    NASA Astrophysics Data System (ADS)

    Hofland, Hans E. J.; Shephard, Lee; Sullivan, Sean M.

    1996-07-01

    Stable cationic lipid/DNA complexes were formed by solubilizing cationic liposomes with 1% octylglucoside and complexing a DNA plasmid with the lipid in the presence of detergent. Removal of the detergent by dialysis yielded a lipid/DNA suspension that was able to transfect tissue culture cells up to 90 days after formation with no loss in activity. Similar levels of gene transfer were obtained by mixing the cationic lipid in a liposome form with DNA just prior to cell addition. However, expression was completely lost 24 hr after mixing. The transfection efficiency of the stable complex in 15% fetal calf serum was 30% of that obtained in the absence of serum, whereas the transient complex was completely inactivated with 2% fetal calf serum. A 90-day stability study comparing various storage conditions showed that the stable complex could be stored frozen or as a suspension at 4 degrees C with no loss in transfection efficiency. Centrifugation of the stable complex produced a pellet that contained approximately 90% of the DNA and 10% of the lipid. Transfection of cells with the resuspended pellet and the supernatant showed that the majority of the transfection activity was in the pellet and all the toxicity was in the supernatant. Formation of a stable cationic lipid/DNA complex has produced a transfection vehicle that can be stored indefinitely, can be concentrated with no loss in transfection efficiency, and the toxicity levels can be greatly reduced when the active complex is isolated from the uncomplexed lipid.

  10. Carbamate-linked cationic lipids with different hydrocarbon chains for gene delivery.

    PubMed

    Shi, Jia; Yu, Shijun; Zhu, Jie; Zhi, Defu; Zhao, Yinan; Cui, Shaohui; Zhang, Shubiao

    2016-05-01

    A series of carbamate-linked cationic lipids containing saturated or unsaturated hydrocarbon chains and quaternary ammonium head were designed and synthesized. After recrystallization, carbamate-linked cationic lipids with high purity (over 95%) were obtained. The structures of these lipids were proved by IR spectrum, HR-ESI-MS, HPLC, (1)H NMR and (13)C NMR. The liposomes were prepared by using these cationic lipids and neutral lipid DOPE. Particle size and zeta-potential were studied to show that they were suitable for gene transfection. The DNA-bonding ability of C12:0, C14:0 and C18:1 cationic liposomes was much better than others. The results of transfection showed that hydrophobic chains of these lipids have great effects on their transfection activity. The lipids bearing C12:0, C14:0 saturated chains or C18:1 unsaturated chain showed relatively higher transfection efficiency and lower cytotoxicity. So these cationic lipids could be used as non-viral gene carriers for further studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Purified anthocyanin supplementation improves endothelial function via NO-cGMP activation in hypercholesterolemic individuals.

    PubMed

    Zhu, Yanna; Xia, Min; Yang, Yan; Liu, Fengqiong; Li, Zhongxia; Hao, Yuantao; Mi, Mantian; Jin, Tianru; Ling, Wenhua

    2011-11-01

    Anthocyanins have been shown to improve endothelial function in animal models. However, whether these compounds have similar beneficial effects in humans is largely unknown. In a short-term crossover study, 12 hypercholesterolemic individuals were given oral anthocyanins (320 mg) isolated from berries or placebo. Brachial artery flow-mediated dilation (FMD) was assessed before and after the intervention. In a long-term intervention trial (12 weeks), 150 hypercholesterolemic individuals were given anthocyanins (320 mg/day, n = 75) or placebo (n = 75), after which we measured FMD, plasma cGMP, and other serum biomarkers. Another short-term intervention was conducted in the presence of NO-cGMP inhibitors in 6 people and in a rat aortic ring model (n = 8). Significant increases of FMD from 8.3% (0.6%) at baseline to 11.0% (0.8%) at 1 h and 10.1% (0.9%) at 2 h were observed after short-term anthocyanin consumption, concomitantly with increases of plasma anthocyanin concentrations (P < 0.05). In the study participants who received long-term anthocyanin intervention, compared with the control group, we observed significant increases in the FMD (28.4% vs 2.2%), cGMP (12.6% vs -1.2%), and HDL-cholesterol concentrations, but decreases in the serum soluble vascular adhesion molecule-1 and LDL cholesterol concentrations (P < 0.05). The changes in the cGMP and HDL cholesterol concentrations positively correlated with FMD in the anthocyanin group (P < 0.05). In the presence of NO-cGMP inhibitors, the effects of anthocyanin on endothelial function were abolished in human participants and in a rat aortic ring model. Anthocyanin supplementation improves endothelium-dependent vasodilation in hypercholesterolemic individuals. This effect involves activation of the NO-cGMP signaling pathway, improvements in the serum lipid profile, and decreased inflammation.

  12. A human intermediate conductance calcium-activated potassium channel.

    PubMed

    Ishii, T M; Silvia, C; Hirschberg, B; Bond, C T; Adelman, J P; Maylie, J

    1997-10-14

    An intermediate conductance calcium-activated potassium channel, hIK1, was cloned from human pancreas. The predicted amino acid sequence is related to, but distinct from, the small conductance calcium-activated potassium channel subfamily, which is approximately 50% conserved. hIK1 mRNA was detected in peripheral tissues but not in brain. Expression of hIK1 in Xenopus oocytes gave rise to inwardly rectifying potassium currents, which were activated by submicromolar concentrations of intracellular calcium (K0.5 = 0.3 microM). Although the K0.5 for calcium was similar to that of small conductance calcium-activated potassium channels, the slope factor derived from the Hill equation was significantly reduced (1.7 vs. 3. 5). Single-channel current amplitudes reflected the macroscopic inward rectification and revealed a conductance level of 39 pS in the inward direction. hIK1 currents were reversibly blocked by charybdotoxin (Ki = 2.5 nM) and clotrimazole (Ki = 24.8 nM) but were minimally affected by apamin (100 nM), iberiotoxin (50 nM), or ketoconazole (10 microM). These biophysical and pharmacological properties are consistent with native intermediate conductance calcium-activated potassium channels, including the erythrocyte Gardos channel.

  13. A hydrophobic filter confers the cation selectivity of Zygosaccharomyces rouxii plasma-membrane Na+/H+ antiporter.

    PubMed

    Kinclova-Zimmermannova, Olga; Falson, Pierre; Cmunt, Denis; Sychrova, Hana

    2015-04-24

    Na(+)/H(+) antiporters may recognize all alkali-metal cations as substrates but may transport them selectively. Plasma-membrane Zygosaccharomyces rouxii Sod2-22 antiporter exports Na(+) and Li(+), but not K(+). The molecular basis of this selectivity is unknown. We combined protein structure modeling, site-directed mutagenesis, phenotype analysis and cation efflux measurements to localize and characterize the cation selectivity region. A three-dimensional model of the ZrSod2-22 transmembrane domain was generated based on the X-ray structure of the Escherichia coli NhaA antiporter and primary sequence alignments with homologous yeast antiporters. The model suggested a close proximity of Thr141, Ala179 and Val375 from transmembrane segments 4, 5 and 11, respectively, forming a hydrophobic hole in the putative cation pathway's core. A series of mutagenesis experiments verified the model and showed that structural modifications of the hole resulted in altered cation selectivity and transport activity. The triple ZrSod2-22 mutant T141S-A179T-V375I gained K(+) transport capacity. The point mutation A179T restricted the antiporter substrate specificity to Li(+) and reduced its transport activity, while serine at this position preserved the native cation selectivity. The negative effect of the A179T mutation can be eliminated by introducing a second mutation, T141S or T141A, in the preceding transmembrane domain. Our experimental results confirm that the three residues found through modeling play a central role in the determination of cation selectivity and transport activity in Z. rouxii Na(+)/H(+) antiporter and that the cation selectivity can be modulated by repositioning a single local methyl group. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Highly Stable, Anion Conductive, Comb-Shaped Copolymers for Alkaline Fuel Cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, NW; Leng, YJ; Hickner, MA

    2013-07-10

    To produce an anion-conductive and durable polymer electrolyte for alkaline fuel cell applications, a series of quaternized poly(2,6-dimethyl phenylene oxide)s containing long alkyl side chains pendant to the nitrogen-centered cation were synthesized using a Menshutkin reaction to form comb-shaped structures. The pendant alkyl chains were responsible for the development of highly conductive ionic domains, as confirmed by small-angle X-ray scattering (SAXS). The comb-shaped polymers having one alkyl side chain showed higher hydroxide conductivities than those with benzyltrimethyl ammonium moieties or structures with more than one alkyl side chain per cationic site. The highest conductivity was observed for comb-shaped polymers withmore » benzyldimethylhexadecyl ammonium cations. The chemical stabilities of the comb-shaped membranes were evaluated under severe, accelerated-aging conditions, and degradation was observed by measuring IEC and ion conductivity changes during aging. The comb-shaped membranes retained their high ion conductivity in 1 M NaOH at 80 degrees C for 2000 h. These cationic polymers were employed as ionomers in catalyst layers for alkaline fuel cells. The results indicated that the C-16 alkyl side chain ionomer had a slightly better initial performance, despite its low IEC value, but very poor durability in the fuel cell. In contrast, 90% of the initial performance was retained for the alkaline fuel cell with electrodes containing the C-6 side chain after 60 h of fuel cell operation.« less

  15. Self-assembly of cationic multidomain peptide hydrogels: supramolecular nanostructure and rheological properties dictate antimicrobial activity

    NASA Astrophysics Data System (ADS)

    Jiang, Linhai; Xu, Dawei; Sellati, Timothy J.; Dong, He

    2015-11-01

    Hydrogels are an important class of biomaterials that have been widely utilized for a variety of biomedical/medical applications. The biological performance of hydrogels, particularly those used as wound dressing could be greatly advanced if imbued with inherent antimicrobial activity capable of staving off colonization of the wound site by opportunistic bacterial pathogens. Possessing such antimicrobial properties would also protect the hydrogel itself from being adversely affected by microbial attachment to its surface. We have previously demonstrated the broad-spectrum antimicrobial activity of supramolecular assemblies of cationic multi-domain peptides (MDPs) in solution. Here, we extend the 1-D soluble supramolecular assembly to 3-D hydrogels to investigate the effect of the supramolecular nanostructure and its rheological properties on the antimicrobial activity of self-assembled hydrogels. Among designed MDPs, the bactericidal activity of peptide hydrogels was found to follow an opposite trend to that in solution. Improved antimicrobial activity of self-assembled peptide hydrogels is dictated by the combined effect of supramolecular surface chemistry and storage modulus of the bulk materials, rather than the ability of individual peptides/peptide assemblies to penetrate bacterial cell membrane as observed in solution. The structure-property-activity relationship developed through this study will provide important guidelines for designing biocompatible peptide hydrogels with built-in antimicrobial activity for various biomedical applications.Hydrogels are an important class of biomaterials that have been widely utilized for a variety of biomedical/medical applications. The biological performance of hydrogels, particularly those used as wound dressing could be greatly advanced if imbued with inherent antimicrobial activity capable of staving off colonization of the wound site by opportunistic bacterial pathogens. Possessing such antimicrobial properties would

  16. What Hinders Electron Transfer Dissociation (ETD) of DNA Cations?

    NASA Astrophysics Data System (ADS)

    Hari, Yvonne; Leumann, Christian J.; Schürch, Stefan

    2017-12-01

    Radical activation methods, such as electron transfer dissociation (ETD), produce structural information complementary to collision-induced dissociation. Herein, electron transfer dissociation of 3-fold protonated DNA hexamers was studied to gain insight into the fragmentation mechanism. The fragmentation patterns of a large set of DNA hexamers confirm cytosine as the primary target of electron transfer. The reported data reveal backbone cleavage by internal electron transfer from the nucleobase to the phosphate linker leading either to a•/ w or d/ z• ion pairs. This reaction pathway contrasts with previous findings on the dissociation processes after electron capture by DNA cations, suggesting multiple, parallel dissociation channels. However, all these channels merely result in partial fragmentation of the precursor ion because the charge-reduced DNA radical cations are quite stable. Two hypotheses are put forward to explain the low dissociation yield of DNA radical cations: it is either attributed to non-covalent interactions between complementary fragments or to the stabilization of the unpaired electron in stacked nucleobases. MS3 experiments suggest that the charge-reduced species is the intact oligonucleotide. Moreover, introducing abasic sites significantly increases the dissociation yield of DNA cations. Consequently, the stabilization of the unpaired electron by π-π-stacking provides an appropriate rationale for the high intensity of DNA radical cations after electron transfer. [Figure not available: see fulltext.

  17. U(VI) uranyl cation-cation interactions in framework germanates.

    PubMed

    Morrison, Jessica M; Moore-Shay, Laura J; Burns, Peter C

    2011-03-21

    The isomorphous compounds NH(4)[(UO(6))(2)(UO(2))(9)(GeO(4))(GeO(3)(OH))] (1), K[(UO(6))(2)(UO(2))(9)(GeO(4))(GeO(3)(OH))] (2), Li(3)O[(UO(6))(2)(UO(2))(9)(GeO(4))(GeO(3)(OH))] (3), and Ba[(UO(6))(2)(UO(2))(9)(GeO(4))(2)] (4) were synthesized by hydrothermal reaction at 220 °C. The structures were determined using single crystal X-ray diffraction and refined to R(1) = 0.0349 (1), 0.0232 (2), 0.0236 (3), 0.0267 (4). Each are trigonal, P(3)1c. 1: a = 10.2525(5), c = 17.3972(13), V = 1583.69(16) Å(3), Z = 2; 2: a = 10.226(4), c = 17.150(9), V = 1553.1(12) Å(3), Z = 2; 3: a = 10.2668(5), c = 17.0558(11), V = 1556.94(15) Å(3), Z = 2; 4: a = 10.2012(5), c = 17.1570(12), V = 1546.23(15) Å(3), Z = 2. There are three symmetrically independent U sites in each structure, two of which correspond to typical (UO(2))(2+) uranyl ions and the other of which is octahedrally coordinated by six O atoms. One of the uranyl ions donates a cation-cation interaction, and accepts a different cation-cation interaction. The linkages between the U-centered polyhedra result in a relatively dense three-dimensional framework. Ge and low-valence sites are located within cavities in the framework of U-polyhedra. Chemical, thermal, and spectroscopic characterizations are provided.

  18. Heat shock factor-1 intertwines insulin/IGF-1, TGF-β and cGMP signaling to control development and aging.

    PubMed

    Barna, János; Princz, Andrea; Kosztelnik, Mónika; Hargitai, Balázs; Takács-Vellai, Krisztina; Vellai, Tibor

    2012-11-01

    Temperature affects virtually all cellular processes. A quick increase in temperature challenges the cells to undergo a heat shock response to maintain cellular homeostasis. Heat shock factor-1 (HSF-1) functions as a major player in this response as it activates the transcription of genes coding for molecular chaperones (also called heat shock proteins) that maintain structural integrity of proteins. However, the mechanisms by which HSF-1 adjusts fundamental cellular processes such as growth, proliferation, differentiation and aging to the ambient temperature remain largely unknown. We demonstrate here that in Caenorhabditis elegans HSF-1 represses the expression of daf-7 encoding a TGF-β (transforming growth factor-beta) ligand, to induce young larvae to enter the dauer stage, a developmentally arrested, non-feeding, highly stress-resistant, long-lived larval form triggered by crowding and starvation. Under favorable conditions, HSF-1 is inhibited by crowding pheromone-sensitive guanylate cyclase/cGMP (cyclic guanosine monophosphate) and systemic nutrient-sensing insulin/IGF-1 (insulin-like growth factor-1) signaling; loss of HSF-1 activity allows DAF-7 to promote reproductive growth. Thus, HSF-1 interconnects the insulin/IGF-1, TGF-β and cGMP neuroendocrine systems to control development and longevity in response to diverse environmental stimuli. Furthermore, HSF-1 upregulates another TGF-β pathway-interacting gene, daf-9/cytochrome P450, thereby fine-tuning the decision between normal growth and dauer formation. Together, these results provide mechanistic insight into how temperature, nutrient availability and population density coordinately influence development, lifespan, behavior and stress response through HSF-1.

  19. Structure of the S. aureus PI-specific phospholipase C reveals modulation of active site access by a titratable π-cation latched loop†

    PubMed Central

    Goldstein, Rebecca; Cheng, Jiongjia; Stec, Boguslaw; Roberts, Mary F.

    2012-01-01

    Staphylococcus aureus secretes a phosphatidylinositol-specific phospholipase C (PIPLC) as a virulence factor that is unusual in exhibiting higher activity at acidic pH values than other enzymes in this class. We have determined the crystal structure of this enzyme at pH 4.6 and pH 7.5. Under slightly basic conditions, the S. aureus PI-PLC structure closely follows the conformation of other bacterial PI-PLCs. However, when crystallized under acidic conditions, a large section of mobile loop at the αβ-barrel rim in the vicinity of the active site shows ~10 Å shift. This loop displacement at acidic pH is the result of a titratable intramolecular π-cation interaction between His258 and Phe249. This was verified by a structure of the mutant protein H258Y crystallized at pH 4.6, which does not exhibit the large loop shift. The intramolecular π-cation interaction for S. aureus PI-PLC provides an explanation for the activity of the enzyme at acid pH and also suggests how phosphatidylcholine, as a competitor for Phe249, may kinetically activate this enzyme. PMID:22390775

  20. Mercury release from deforested soils triggered by base cation enrichment.

    PubMed

    Farella, N; Lucotte, M; Davidson, R; Daigle, S

    2006-09-01

    The Brazilian Amazon has experienced considerable colonization in the last few decades. Family agriculture based on slash-and-burn enables millions of people to live in that region. However, the poor nutrient content of most Amazonian soils requires cation-rich ashes from the burning of the vegetation biomass for cultivation to be successful, which leads to forest ecosystem degradation, soil erosion and mercury contamination. While recent studies have suggested that mercury present in soils was transferred towards rivers upon deforestation, little is known about the dynamics between agricultural land-use and mercury leaching. In this context, the present study proposes an explanation that illustrates how agricultural land-use triggers mercury loss from soils. This explanation lies in the competition between base cations and mercury in soils which are characterized by a low adsorption capacity. Since these soils are naturally very poor in base cations, the burning of the forest biomass suddenly brings high quantities of base cations to soils, destabilizing the previous equilibrium amongst cations. Base cation enrichment triggers mobility in soil cations, rapidly dislocating mercury atoms. This conclusion comes from principal component analyses illustrating that agricultural land-use was associated with base cation enrichment and mercury depletion. The overall conclusions highlight a pernicious cycle: while soil nutrient enrichment actually occurs through biomass burning, although on a temporary basis, there is a loss in Hg content, which is leached to rivers, entering the aquatic chain, and posing a potential health threat to local populations. Data presented here reflects three decades of deforestation activities, but little is known about the long-term impact of such a disequilibrium. These findings may have repercussions on our understanding of the complex dynamics of deforestation and agriculture worldwide.

  1. Electrolyte Engineering: Optimizing High-Rate Double-Layer Capacitances of Micropore- and Mesopore-Rich Activated Carbon.

    PubMed

    Chen, Ting-Hao; Yang, Cheng-Hsien; Su, Ching-Yuan; Lee, Tai-Chou; Dong, Quan-Feng; Chang, Jeng-Kuei

    2017-09-22

    Various types of electrolyte cations as well as binary cations are used to optimize the capacitive performance of activated carbon (AC) with different pore structures. The high-rate capability of micropore-rich AC, governed by the mobility of desolvated cations, can outperform that of mesopore-rich AC, which essentially depends on the electrolyte conductivity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Penetrating cation/fatty acid anion pair as a mitochondria-targeted protonophore

    PubMed Central

    Severin, Fedor F.; Severina, Inna I.; Antonenko, Yury N.; Rokitskaya, Tatiana I.; Cherepanov, Dmitry A.; Mokhova, Elena N.; Vyssokikh, Mikhail Yu.; Pustovidko, Antonina V.; Markova, Olga V.; Yaguzhinsky, Lev S.; Korshunova, Galina A.; Sumbatyan, Nataliya V.; Skulachev, Maxim V.; Skulachev, Vladimir P.

    2010-01-01

    A unique phenomenon of mitochondria-targeted protonophores is described. It consists in a transmembrane H+-conducting fatty acid cycling mediated by penetrating cations such as 10-(6’-plastoquinonyl)decyltriphenylphosphonium (SkQ1) or dodecyltriphenylphosphonium (C12TPP). The phenomenon has been modeled by molecular dynamics and directly proved by experiments on bilayer planar phospholipid membrane, liposomes, isolated mitochondria, and yeast cells. In bilayer planar phospholipid membrane, the concerted action of penetrating cations and fatty acids is found to result in conversion of a pH gradient (ΔpH) to a membrane potential (Δψ) of the Nernstian value (about 60 mV Δψ at ΔpH = 1). A hydrophobic cation with localized charge (cetyltrimethylammonium) failed to substitute for hydrophobic cations with delocalized charge. In isolated mitochondria, SkQ1 and C12TPP, but not cetyltrimethylammonium, potentiated fatty acid-induced (i) uncoupling of respiration and phosphorylation, and (ii) inhibition of H2O2 formation. In intact yeast cells, C12TPP stimulated respiration regardless of the extracellular pH value, whereas a nontargeted protonophorous uncoupler (trifluoromethoxycarbonylcyanide phenylhydrazone) stimulated respiration at pH 5 but not at pH 3. Hydrophobic penetrating cations might be promising to treat obesity, senescence, and some kinds of cancer that require mitochondrial hyperpolarization. PMID:20080732

  3. 30 CFR 250.207 - What ancillary activities may I conduct?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 2 2011-07-01 2011-07-01 false What ancillary activities may I conduct? 250... and Information Ancillary Activities § 250.207 What ancillary activities may I conduct? Before or... the Regional Supervisor may direct you to conduct ancillary activities. Ancillary activities include...

  4. Sn Cation Valency Dependence in Cation Exchange Reactions Involving Cu2-xSe Nanocrystals

    PubMed Central

    2014-01-01

    We studied cation exchange reactions in colloidal Cu2-xSe nanocrystals (NCs) involving the replacement of Cu+ cations with either Sn2+ or Sn4+ cations. This is a model system in several aspects: first, the +2 and +4 oxidation states for tin are relatively stable; in addition, the phase of the Cu2-xSe NCs remains cubic regardless of the degree of copper deficiency (that is, “x”) in the NC lattice. Also, Sn4+ ions are comparable in size to the Cu+ ions, while Sn2+ ones are much larger. We show here that the valency of the entering Sn ions dictates the structure and composition not only of the final products but also of the intermediate steps of the exchange. When Sn4+ cations are used, alloyed Cu2–4ySnySe NCs (with y ≤ 0.33) are formed as intermediates, with almost no distortion of the anion framework, apart from a small contraction. In this exchange reaction the final stoichiometry of the NCs cannot go beyond Cu0.66Sn0.33Se (that is Cu2SnSe3), as any further replacement of Cu+ cations with Sn4+ cations would require a drastic reorganization of the anion framework, which is not possible at the reaction conditions of the experiments. When instead Sn2+ cations are employed, SnSe NCs are formed, mostly in the orthorhombic phase, with significant, albeit not drastic, distortion of the anion framework. Intermediate steps in this exchange reaction are represented by Janus-type Cu2-xSe/SnSe heterostructures, with no Cu–Sn–Se alloys. PMID:25340627

  5. Gadolinium and didymium (praseodymium/neodymium) cations as capture agents in lightmicroscopical histochemistry of acid and alkaline phosphatase.

    PubMed

    Halbhuber, K J; Zimmermann, N

    1987-01-01

    In previous papers, cerium and lanthanum based methods for light-microscopical detection of acid and alkaline phosphatase activity were proposed. In this paper, the usefulness of other lanthanide cations such as gadolinium and praseodymium/neodymium cations as capture agents in phosphatase histochemistry is tested. It is evident that phosphate ions were sufficiently trapped by these cations. According to the lead and silver multistep procedures earlier described it is possible to visualize alkaline phosphatase activity in the brush borders of the intestine or kidney as well as acid phosphatase activity in the lysosomes. These methods can be recommended.

  6. Gating current studies reveal both intra- and extracellular cation modulation of K+ channel deactivation

    PubMed Central

    Wang, Zhuren; Zhang, Xue; Fedida, David

    1999-01-01

    The presence of permeant ions can modulate the rate of gating charge return in wild-type human heart K+ (hKv1.5) channels. Here we employ gating current measurements in a non-conducting mutant, W472F, of the hKv1.5 channel to investigate how different cations can modulate charge return and whether the actions can be specifically localized at the internal as well as the external mouth of the channel pore. Intracellular cations were effective at accelerating charge return in the sequence Cs+ > Rb+ > K+ > Na+ > NMG+. Extracellular cations accelerated charge return with the selectivity sequence Cs+ > Rb+ > Na+ = NMG+. Intracellular and extracellular cation actions were of relatively low affinity. The Kd for preventing slowing of the time constant of the off-gating current decay (τoff) was 20.2 mM for intracellular Cs+ (Csi+) and 358 mM for extracellular Cs+ (Cso+). Both intracellular and extracellular cations can regulate the rate of charge return during deactivation of hKv1.5, but intracellular cations are more effective. We suggest that ion crystal radius is an important determinant of this action, with larger ions preventing slowing more effectively. Important parallels exist with cation-dependent modulation of slow inactivation of ionic currents in this channel. However, further experiments are required to understand the exact relationship between acceleration of charge return and the slowing of inactivation of ionic currents by cations. PMID:10050001

  7. Bumetanide hyperpolarizes madin-darby canine kidney cells and enhances cellular gentamicin uptake by elevating cytosolic Ca(2+) thus facilitating intermediate conductance Ca(2+)--activated potassium channels.

    PubMed

    Wang, Tian; Yang, Yu-Qin; Karasawa, Takatoshi; Wang, Qi; Phillips, Amanda; Guan, Bing-Cai; Ma, Ke-Tao; Jiang, Meiyan; Xie, Ding-Hua; Steyger, Peter S; Jiang, Zhi-Gen

    2013-04-01

    Loop diuretics such as bumetanide and furosemide enhance aminoglycoside ototoxicity when co-administered to patients and animal models. The underlying mechanism(s) is poorly understood. We investigated the effect of these diuretics on cellular uptake of aminoglycosides, using Texas Red-tagged gentamicin (GTTR), and intracellular/whole-cell recordings of Madin-Darby canine kidney (MDCK) cells. We found that bumetanide and furosemide dose-dependently enhanced cytoplasmic GTTR fluorescence by ~60 %. This enhancement was suppressed by La(3+), a non-selective cation channel (NSCC) blocker, and by K(+) channel blockers Ba(2+) and clotrimazole, but not by tetraethylammonium (TEA), 4-aminopyridine (4-AP) or glipizide, nor by Cl(-) channel blockers diphenylamine-2-carboxylic acid (DPC), niflumic acid (NFA), and CFTRinh-172. Bumetanide and furosemide hyperpolarized MDCK cells by ~14 mV, increased whole-cell I/V slope conductance; the bumetanide-induced net current I/V showed a reversal potential (V r) ~-80 mV. Bumetanide-induced hyperpolarization and I/V change was suppressed by Ba(2+) or clotrimazole, and absent in elevated [Ca(2+)]i, but was not affected by apamin, 4-AP, TEA, glipizide, DPC, NFA, or CFTRinh-172. Bumetanide and furosemide stimulated a surge of Fluo-4-indicated cytosolic Ca(2+). Ba(2+) and clotrimazole alone depolarized cells by ~18 mV and reduced I/V slope with a net current V r near -85 mV, and reduced GTTR uptake by ~20 %. La(3+) alone hyperpolarized the cells by ~-14 mV, reduced the I/V slope with a net current V r near -10 mV, and inhibited GTTR uptake by ~50 %. In the presence of La(3+), bumetanide-caused negligible change in potential or I/V. We conclude that NSCCs constitute a major cell entry pathway for cationic aminoglycosides; bumetanide enhances aminoglycoside uptake by hyperpolarizing cells that increases the cation influx driving force; and bumetanide-induced hyperpolarization is caused by elevating intracellular Ca(2+) and thus facilitating

  8. 30 CFR 250.207 - What ancillary activities may I conduct?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What ancillary activities may I conduct? 250... Activities § 250.207 What ancillary activities may I conduct? Before or after you submit an EP, DPP, or DOCD... direct you to conduct ancillary activities. Ancillary activities include: (a) Geological and geophysical...

  9. High-capacity cation-exchange column for enhanced resolution of adjacent peaks of cations in ion chromatography.

    PubMed

    Rey, M A

    2001-06-22

    One of the advantages of ion chromatography [Anal Chem. 47 (1975) 1801] as compared to other analytical techniques is that several ions may be analyzed simultaneously. One of the most important contributions of cation-exchange chromatography is its sensitivity to ammonium ion, which is difficult to analyze by other techniques [J. Weiss, in: E.L. Johnson (Ed.), Handbook of Ion Chromatography, Dionex, Sunnyvale, CA, USA]. The determination of low concentrations of ammonium ion in the presence of high concentrations of sodium poses a challenge in cation-exchange chromatography [J. Weiss, Ion Chromatography, VCH, 2nd Edition, Weinheim, 1995], as both cations have similar selectivities for the common stationary phases containing either sulfonate or carboxylate functional groups. The task was to develop a new cation-exchange stationary phase (for diverse concentration ratios of adjacent peaks) to overcome limitations experienced in previous trails. Various cation-exchange capacities and column body formats were investigated to optimize this application and others. The advantages and disadvantages of two carboxylic acid columns of different cation-exchange capacities and different column formats will be discussed.

  10. A human intermediate conductance calcium-activated potassium channel

    PubMed Central

    Ishii, Takahiro M.; Silvia, Christopher; Hirschberg, Birgit; Bond, Chris T.; Adelman, John P.; Maylie, James

    1997-01-01

    An intermediate conductance calcium-activated potassium channel, hIK1, was cloned from human pancreas. The predicted amino acid sequence is related to, but distinct from, the small conductance calcium-activated potassium channel subfamily, which is ≈50% conserved. hIK1 mRNA was detected in peripheral tissues but not in brain. Expression of hIK1 in Xenopus oocytes gave rise to inwardly rectifying potassium currents, which were activated by submicromolar concentrations of intracellular calcium (K0.5 = 0.3 μM). Although the K0.5 for calcium was similar to that of small conductance calcium-activated potassium channels, the slope factor derived from the Hill equation was significantly reduced (1.7 vs. 3.5). Single-channel current amplitudes reflected the macroscopic inward rectification and revealed a conductance level of 39 pS in the inward direction. hIK1 currents were reversibly blocked by charybdotoxin (Ki = 2.5 nM) and clotrimazole (Ki = 24.8 nM) but were minimally affected by apamin (100 nM), iberiotoxin (50 nM), or ketoconazole (10 μM). These biophysical and pharmacological properties are consistent with native intermediate conductance calcium-activated potassium channels, including the erythrocyte Gardos channel. PMID:9326665

  11. Natural zeolite reactivity towards ozone: the role of compensating cations.

    PubMed

    Valdés, Héctor; Alejandro, Serguei; Zaror, Claudio A

    2012-08-15

    Among indoor pollutants, ozone is recognised to pose a threat to human health. Recently, low cost natural zeolites have been applied as alternative materials for ozone abatement. In this work, the effect of compensating cation content of natural zeolite on ozone removal is studied. A Chilean natural zeolite is used here as starting material. The amount of compensating cations in the zeolite framework was modified by ion exchange using an ammonium sulphate solution (0.1 mol L(-1)). Characterisation of natural and modified zeolites were performed by X-ray powder diffraction (XRD), nitrogen adsorption at 77K, elemental analysis, X-ray fluorescence (XRF), thermogravimetric analysis coupled with mass spectroscopy (TGA-MS), and temperature-programmed desorption of ammonia (NH(3)-TPD). Ozone adsorption and/or decomposition on natural and modified zeolites were studied by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). Results show that the zeolite compensating cation content affects ozone interaction with zeolite active sites. Ammonium ion-exchange treatments followed by thermal out-gassing at 823 K, reduces ozone diffusion resistance inside the zeolite framework, increasing ozone abatement on zeolite surface active sites. Weak and strong Lewis acid sites of zeolite surface are identified here as the main active sites responsible of ozone removal. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Modulation of mechanosensitive calcium-selective cation channels by temperature

    NASA Technical Reports Server (NTRS)

    Ding, J. P.; Pickard, B. G.

    1993-01-01

    Gating of associations of mechanosensitive Ca(2+)-selective cation co-channels in the plasmalemma of onion epidermis has a strong and unusual temperature dependence. Tension-dependent activity rises steeply as temperature is lowered from 25 degrees C to about 6 degrees C, but drops to a low level at about 5 degrees C. Under the conditions tested (with Mg2+ and K+ at the cytosolic face of outside-out membrane patches), promotion results both from more bursting at all observed linkage levels and from longer duration of bursts of co-channels linked as quadruplets and quintuplets. Co-channel conductance decreases linearly, but only modestly, with declining temperature. It is proposed that these and related mechanosensitive channels may participate in a variety of responses to temperature, including thermonasty, thermotropism, hydrotropism, and both cold damage and cold acclimation.

  13. Hydration of cations: a key to understanding of specific cation effects on aggregation behaviors of PEO-PPO-PEO triblock copolymers.

    PubMed

    Lutter, Jacob C; Wu, Tsung-yu; Zhang, Yanjie

    2013-09-05

    This work reports results from the interactions of a series of monovalent and divalent cations with a triblock copolymer, poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-PPO-PEO). Phase transition temperatures of the polymer in the presence of chloride salts with six monovalent and eight divalent cations were measured using an automated melting point apparatus. The polymer undergoes a two-step phase transition, consisting of micellization of the polymer followed by aggregation of the micelles, in the presence of all the salts studied herein. The results suggest that hydration of cations plays a key role in determining the interactions between the cations and the polymer. The modulation of the phase transition temperature of the polymer by cations can be explained as a balance between three interactions: direct binding of cations to the oxygen in the polymer chains, cations sharing one water molecule with the polymer in their hydration layer, and cations interacting with the polymer via two water molecules. Monovalent cations Na(+), K(+), Rb(+), and Cs(+) do not bind to the polymer, while Li(+) and NH4(+) and all the divalent cations investigated including Mg(2+), Ca(2+), Sr(2+), Ba(2+), Co(2+), Ni(2+), Cu(2+), and Cd(2+) bind to the polymer. The effects of the cations correlate well with their hydration thermodynamic properties. Mechanisms for cation-polymer interactions are discussed.

  14. Alkali Metal Cation versus Proton and Methyl Cation Affinities: Structure and Bonding Mechanism

    PubMed Central

    Boughlala, Zakaria; Fonseca Guerra, Célia

    2016-01-01

    Abstract We have analyzed the structure and bonding of gas‐phase Cl−X and [HCl−X]+ complexes for X+= H+, CH3 +, Li+, and Na+, using relativistic density functional theory (DFT). We wish to establish a quantitative trend in affinities of the anionic and neutral Lewis bases Cl− and HCl for the various cations. The Cl−X bond becomes longer and weaker along X+ = H+, CH3 +, Li+, and Na+. Our main purpose is to understand the heterolytic bonding mechanism behind the intrinsic (i.e., in the absence of solvent) alkali metal cation affinities (AMCA) and how this compares with and differs from those of the proton affinity (PA) and methyl cation affinity (MCA). Our analyses are based on Kohn–Sham molecular orbital (KS‐MO) theory in combination with a quantitative energy decomposition analysis (EDA) that pinpoints the importance of the different features in the bonding mechanism. Orbital overlap appears to play an important role in determining the trend in cation affinities. PMID:27551660

  15. Investigation of Proton Conductivity of Cation-Exchanged, Sulfonated Poly(b-Styrene-b-Isobutylene-b-Styrene) Membranes

    DTIC Science & Technology

    2009-09-01

    solvents. Similar behavior was observed for Nafion -117 (also a polymer with ionic SO3H clusters) by other researchers (14). Results shown in this...pattern was only valid for ionic S-SIBS membranes exchanged with cations; neither acid form of SIBS-97-H nor Nafion -117 fell on this line. In order...10  vi INTENTIONALLY LEFT BLANK. 1 1. Introduction Research in ionic polymers has been gaining popularity in the scientific community

  16. A xanthine-based epithelium-dependent airway relaxant KMUP-3 (7-[2-[4-(4-nitrobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) increases respiratory performance and protects against tumor necrosis factor-alpha-induced tracheal contraction, involving nitric oxide release and expression of cGMP and protein kinase G.

    PubMed

    Lin, Rong-Jyh; Wu, Bin-Nan; Lo, Yi-Ching; An, Li-Mei; Dai, Zen-Kong; Lin, Young-Tso; Tang, Chao-Shun; Chen, Ing-Jun

    2006-02-01

    KMUP-3 (7-[2-[4-(4-nitrobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) was investigated in guinea pig tracheal smooth muscle. Intratracheal instillation of tumor necrosis factor (TNF)-alpha (0.01 mg/kg/300 microl) induced bronchoconstriction, increases of lung resistance, and decreases of dynamic lung compliance. Instillation of KMUP-3 (0.5-2.0 mg/kg) reversed this situation. In isolated trachea precontracted with carbachol, KMUP-3 (10-100 microM)-caused relaxations were attenuated by epithelium removal and by pretreatments with an inhibitor of K(+) channel, tetraethylammonium (10 mm); K(ATP) channel, glibenclamide (1 microM); voltage-dependent K(+) channel, 4-aminopyridine (100 microM); Ca(2+)-dependent K(+) channel, charybdotoxin (0.1 microM) or apamin (1 microM); soluble guanylate cyclase (sGC), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1one (ODQ, 1 microM); nitric-oxide (NO) synthase, N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM); and adenylate cyclase, SQ 22536 [9-(terahydro-2-furanyl)-9H-purin-6-amine] (100 microM). KMUP-3 (0.01-100 microM) induced increases of cGMP and cAMP in primary culture of tracheal smooth muscle cells (TSMCs). The increase in cGMP by KMUP-3 was reduced by ODQ and L-NAME; the increase in cAMP was reduced by SQ 22536. Western blot analysis indicated that KMUP-3 (1 microM) induced expression of protein kinase A (PKA)(ri) and protein kinase G (PKG)(1alpha 1beta) in TSMCs.SQ 22536 inhibited KMUP-3-induced expression of (PKA)(ri). On the contrary, ODQ inhibited KMUP-3-induced expression of PKG(1alpha 1beta) In epithelium-intact trachea, KMUP-3 increased the NO release. Activation of sGC, NO release, and inhibition of phosphodiesterases in TSMCs by KMUP-3 may result in increases of intracellular cGMP and cAMP, which subsequently activate PKG and PKA, efflux of K(+) ion, and associated reduction in Ca(2+) influx in vitro, indicating the action mechanism to protect against TNF-alpha-induced airway dysfunction in vivo.

  17. Electron Transfer Dissociation with Supplemental Activation to Differentiate Aspartic and Isoaspartic Residues in Doubly Charged Peptide Cations

    PubMed Central

    Chan, Wai Yi Kelly; Chan, T. W. Dominic; O’Connor, Peter B.

    2011-01-01

    Electron-transfer dissociation (ETD) with supplemental activation of the doubly charged deamidated tryptic digested peptide ions allows differentiation of isoaspartic acid and aspartic acid residues using c + 57 or z• − 57 peaks. The diagnostic peak clearly localizes and characterizes the isoaspartic acid residue. Supplemental activation in ETD of the doubly charged peptide ions involves resonant excitation of the charge reduced precursor radical cations and leads to further dissociation, including extra backbone cleavages and secondary fragmentation. Supplemental activation is essential to obtain a high quality ETD spectrum (especially for doubly charged peptide ions) with sequence information. Unfortunately, the low-resolution of the ion trap mass spectrometer makes detection of the diagnostic peak for the aspartic acid residue difficult due to interference with side-chain loss from arginine and glutamic acid residues. PMID:20304674

  18. Purine 3':5'-cyclic nucleotides with the nucleobase in a syn orientation: cAMP, cGMP and cIMP.

    PubMed

    Řlepokura, Katarzyna Anna

    2016-06-01

    Purine 3':5'-cyclic nucleotides are very well known for their role as the secondary messengers in hormone action and cellular signal transduction. Nonetheless, their solid-state conformational details still require investigation. Five crystals containing purine 3':5'-cyclic nucleotides have been obtained and structurally characterized, namely adenosine 3':5'-cyclic phosphate dihydrate, C10H12N5O6P·2H2O or cAMP·2H2O, (I), adenosine 3':5'-cyclic phosphate 0.3-hydrate, C10H12N5O6P·0.3H2O or cAMP·0.3H2O, (II), guanosine 3':5'-cyclic phosphate pentahydrate, C10H12N5O7P·5H2O or cGMP·5H2O, (III), sodium guanosine 3':5'-cyclic phosphate tetrahydrate, Na(+)·C10H11N5O7P(-)·4H2O or Na(cGMP)·4H2O, (IV), and sodium inosine 3':5'-cyclic phosphate tetrahydrate, Na(+)·C10H10N4O7P(-)·4H2O or Na(cIMP)·4H2O, (V). Most of the cyclic nucleotide zwitterions/anions [two from four cAMP present in total in (I) and (II), cGMP in (III), cGMP(-) in (IV) and cIMP(-) in (V)] are syn conformers about the N-glycosidic bond, and this nucleobase arrangement is accompanied by Crib-H...Npur hydrogen bonds (rib = ribose and pur = purine). The base orientation is tuned by the ribose pucker. An analysis of data obtained from the Cambridge Structural Database made in the context of syn-anti conformational preferences has revealed that among the syn conformers of various purine nucleotides, cyclic nucleotides and dinucleotides predominate significantly. The interactions stabilizing the syn conformation have been indicated. The inter-nucleotide contacts in (I)-(V) have been systematized in terms of the chemical groups involved. All five structures display three-dimensional hydrogen-bonded networks.

  19. A Spectral-SAR Model for the Anionic-Cationic Interaction in Ionic Liquids: Application to Vibrio fischeri Ecotoxicity

    PubMed Central

    Lacrămă, Ana-Maria; Putz, Mihai V.; Ostafe, Vasile

    2007-01-01

    Within the recently launched the spectral-structure activity relationship (S-SAR) analysis, the vectorial anionic-cationic model of a generic ionic liquid is proposed, along with the associated algebraic correlation factor in terms of the measured and predicted activity norms. The reliability of the present scheme is tested by assessing the Hansch factors, i.e. lipophylicity, polarizability and total energy, to predict the ecotoxicity endpoints of wide types of ionic liquids with ammonium, pyridinium, phosphonium, choline and imidazolium cations on the aquatic bacteria Vibrio fischeri. The results, while confirming the cationic dominant influence when only lipophylicity is considered, demonstrate that the anionic effect dominates all other more specific interactions. It was also proved that the S-SAR vectorial model predicts considerably higher activity for the ionic liquids than for its anionic and cationic subsystems separately, in all considered cases. Moreover, through applying the least norm-correlation path principle, the complete toxicological hierarchies are presented, unfolding the ecological rules of combined cationic and anionic influences in ionic liquid toxicity.

  20. Increased Degree of Unsaturation in the Lipid of Antifungal Cationic Amphiphiles Facilitates Selective Fungal Cell Disruption.

    PubMed

    Steinbuch, Kfir B; Benhamou, Raphael I; Levin, Lotan; Stein, Reuven; Fridman, Micha

    2018-05-11

    Antimicrobial cationic amphiphiles derived from aminoglycosides act through cell membrane permeabilization but have limited selectivity for microbial cell membranes. Herein, we report that an increased degree of unsaturation in the fatty acid segment of antifungal cationic amphiphiles derived from the aminoglycoside tobramycin significantly reduced toxicity to mammalian cells. A collection of tobramycin-derived cationic amphiphiles substituted with C 18 lipid chains varying in degree of unsaturation and double bond configuration were synthesized. All had potent activity against a panel of important fungal pathogens including strains with resistance to a variety of antifungal drugs. The tobramycin-derived cationic amphiphile substituted with linolenic acid with three cis double bonds (compound 6) was up to an order of magnitude less toxic to mammalian cells than cationic amphiphiles composed of lipids with a lower degree of unsaturation and than the fungal membrane disrupting drug amphotericin B. Compound 6 was 12-fold more selective (red blood cell hemolysis relative to antifungal activity) than compound 1, the derivative with a fully saturated lipid chain. Notably, compound 6 disrupted the membranes of fungal cells without affecting the viability of cocultured mammalian cells. This study demonstrates that the degree of unsaturation and the configuration of the double bond in lipids of cationic amphiphiles are important parameters that, if optimized, result in compounds with broad spectrum and potent antifungal activity as well as reduced toxicity toward mammalian cells.

  1. All-inorganic Germanium nanocrystal films by cationic ligand exchange

    DOE PAGES

    Wheeler, Lance M.; Nichols, Asa W.; Chernomordik, Boris D.; ...

    2016-01-21

    In this study, we introduce a new paradigm for group IV nanocrystal surface chemistry based on room temperature surface activation that enables ionic ligand exchange. Germanium nanocrystals synthesized in a gas-phase plasma reactor are functionalized with labile, cationic alkylammonium ligands rather than with traditional covalently bound groups. We employ Fourier transform infrared and 1H nuclear magnetic resonance spectroscopies to demonstrate the alkylammonium ligands are freely exchanged on the germanium nanocrystal surface with a variety of cationic ligands, including short inorganic ligands such as ammonium and alkali metal cations. This ionic ligand exchange chemistry is used to demonstrate enhanced transport inmore » germanium nanocrystal films following ligand exchange as well as the first photovoltaic device based on an all-inorganic germanium nanocrystal absorber layer cast from solution. This new ligand chemistry should accelerate progress in utilizing germanium and other group IV nanocrystals for optoelectronic applications.« less

  2. Cationic liposomes as vaccine adjuvants.

    PubMed

    Christensen, Dennis; Korsholm, Karen S; Rosenkrands, Ida; Lindenstrøm, Thomas; Andersen, Peter; Agger, Else Marie

    2007-10-01

    Cationic liposomes are lipid-bilayer vesicles with a positive surface charge that have re-emerged as a promising new adjuvant technology. Although there is some evidence that cationic liposomes themselves can improve the immune response against coadministered vaccine antigens, their main functions are to protect the antigens from clearance in the body and deliver the antigens to professional antigen-presenting cells. In addition, cationic liposomes can be used to introduce immunomodulators to enhance and modulate the immune response in a desirable direction and, thereby, represent an efficient tool when designing tailor-made adjuvants for specific disease targets. In this article we review the recent progress on cationic liposomes as vehicles, enhancing the effect of immunomodulators and the presentation of vaccine antigens.

  3. Efficacy of a novel water-soluble curcumin derivative versus sildenafil citrate in mediating erectile function.

    PubMed

    Zaahkouk, A M S; Abdel Aziz, M T; Rezq, A M; Atta, H M; Fouad, H H; Ahmed, H H; Sabry, D; Yehia, M H

    2015-01-01

    The present study was conducted to assess the efficacy of a novel curcumin derivative (NCD) versus sildenafil citrate in erectile signaling. The study was conducted on 10 control male rats and 50 diabetic male rats divided into the following groups: diabetic, curcumin, NCD, sildenafil and NCD combined with sildenafil. Cavernous tissue (CC) gene expression levels of heme oxygenase (HO)-1, Nrf2, NF-κβ and p38, enzyme activities of HO and nitric oxide synthase (NOS), cyclic guanosine monophosphate (cGMP) and intracavernosal pressure (ICP) were assessed. Results showed that 12 weeks after induction of diabetes, erectile dysfunction was confirmed by the significant decrease in ICP, a significant decrease in cGMP, NOS, HO enzyme activities, a significant decrease in HO-1 gene and a significant elevation of NF-κβ, p38 genes. Administration of all therapeutic interventions led to a significant elevation in ICP, cGMP levels, a significant increase in HO-1 and NOS enzymes, a significant increase in HO-1 and Nrf2 gene expression, and a significant decrease in NF-κβ, p38 gene expression. NCD or its combination with sildenafil showed significant efficacy and more prolonged duration of action. In conclusion, NCD could enhance erectile function with more efficacy and more prolonged duration of action.

  4. Ternary nylon-3 copolymers as host-defense peptide mimics: beyond hydrophobic and cationic subunits.

    PubMed

    Chakraborty, Saswata; Liu, Runhui; Hayouka, Zvi; Chen, Xinyu; Ehrhardt, Jeffrey; Lu, Qin; Burke, Eileen; Yang, Yiqing; Weisblum, Bernard; Wong, Gerard C L; Masters, Kristyn S; Gellman, Samuel H

    2014-10-15

    Host-defense peptides (HDPs) are produced by eukaryotes to defend against bacterial infection, and diverse synthetic polymers have recently been explored as mimics of these natural peptides. HDPs are rich in both hydrophobic and cationic amino acid residues, and most HDP-mimetic polymers have therefore contained binary combinations of hydrophobic and cationic subunits. However, HDP-mimetic polymers rarely duplicate the hydrophobic surface and cationic charge density found among HDPs ( Hu , K. ; et al. Macromolecules 2013 , 46 , 1908 ); the charge and hydrophobicity are generally higher among the polymers. Statistical analysis of HDP sequences ( Wang , G. ; et al. Nucleic Acids Res. 2009 , 37 , D933 ) has revealed that serine (polar but uncharged) is a very common HDP constituent and that glycine is more prevalent among HDPs than among proteins in general. These observations prompted us to prepare and evaluate ternary nylon-3 copolymers that contain a modestly polar but uncharged subunit, either serine-like or glycine-like, along with a hydrophobic subunit and a cationic subunit. Starting from binary hydrophobic-cationic copolymers that were previously shown to be highly active against bacteria but also highly hemolytic, we found that replacing a small proportion of the hydrophobic subunit with either of the polar, uncharged subunits can diminish the hemolytic activity with minimal impact on the antibacterial activity. These results indicate that the incorporation of polar, uncharged subunits may be generally useful for optimizing the biological activity profiles of antimicrobial polymers. In the context of HDP evolution, our findings suggest that there is a selective advantage to retaining polar, uncharged residues in natural antimicrobial peptides.

  5. Emission spectroscopy of divalent-cation-doped GaN photocatalysts

    NASA Astrophysics Data System (ADS)

    Hirai, Takeshi; Harada, Takashi; Ikeda, Shigeru; Matsumura, Michio; Saito, Nobuo; Nishiyama, Hiroshi; Inoue, Yasunobu; Harada, Yoshiyuki; Ohno, Nobuhito; Maeda, Kazuhiko; Kubota, Jun; Domen, Kazunari

    2011-12-01

    Photoluminescence (PL) and time-resolved photoluminescence (TRPL) spectra of GaN particles doped with divalent cations (Mg2+, Zn2+, and Be2+), which promote photocatalytic overall water splitting, were investigated. The PL and TRPL spectra were mainly attributed to donor-acceptor pair recombination between the divalent cation dopants and divalent anion impurities (O2- and S2-) unintentionally introduced from raw materials, which form acceptor and donor levels, respectively. These levels are likely to provide holes and electrons required for photocatalytic reactions, contributing to the photocatalytic activity of the GaN-based photocatalysts for overall water splitting.

  6. Optimization of ionic conductivity in doped ceria

    PubMed Central

    Andersson, David A.; Simak, Sergei I.; Skorodumova, Natalia V.; Abrikosov, Igor A.; Johansson, Börje

    2006-01-01

    Oxides with the cubic fluorite structure, e.g., ceria (CeO2), are known to be good solid electrolytes when they are doped with cations of lower valence than the host cations. The high ionic conductivity of doped ceria makes it an attractive electrolyte for solid oxide fuel cells, whose prospects as an environmentally friendly power source are very promising. In these electrolytes, the current is carried by oxygen ions that are transported by oxygen vacancies, present to compensate for the lower charge of the dopant cations. Ionic conductivity in ceria is closely related to oxygen-vacancy formation and migration properties. A clear physical picture of the connection between the choice of a dopant and the improvement of ionic conductivity in ceria is still lacking. Here we present a quantum-mechanical first-principles study of the influence of different trivalent impurities on these properties. Our results reveal a remarkable correspondence between vacancy properties at the atomic level and the macroscopic ionic conductivity. The key parameters comprise migration barriers for bulk diffusion and vacancy–dopant interactions, represented by association (binding) energies of vacancy–dopant clusters. The interactions can be divided into repulsive elastic and attractive electronic parts. In the optimal electrolyte, these parts should balance. This finding offers a simple and clear way to narrow the search for superior dopants and combinations of dopants. The ideal dopant should have an effective atomic number between 61 (Pm) and 62 (Sm), and we elaborate that combinations of Nd/Sm and Pr/Gd show enhanced ionic conductivity, as compared with that for each element separately. PMID:16478802

  7. Optimization of ionic conductivity in doped ceria.

    PubMed

    Andersson, David A; Simak, Sergei I; Skorodumova, Natalia V; Abrikosov, Igor A; Johansson, Börje

    2006-03-07

    Oxides with the cubic fluorite structure, e.g., ceria (CeO2), are known to be good solid electrolytes when they are doped with cations of lower valence than the host cations. The high ionic conductivity of doped ceria makes it an attractive electrolyte for solid oxide fuel cells, whose prospects as an environmentally friendly power source are very promising. In these electrolytes, the current is carried by oxygen ions that are transported by oxygen vacancies, present to compensate for the lower charge of the dopant cations. Ionic conductivity in ceria is closely related to oxygen-vacancy formation and migration properties. A clear physical picture of the connection between the choice of a dopant and the improvement of ionic conductivity in ceria is still lacking. Here we present a quantum-mechanical first-principles study of the influence of different trivalent impurities on these properties. Our results reveal a remarkable correspondence between vacancy properties at the atomic level and the macroscopic ionic conductivity. The key parameters comprise migration barriers for bulk diffusion and vacancy-dopant interactions, represented by association (binding) energies of vacancy-dopant clusters. The interactions can be divided into repulsive elastic and attractive electronic parts. In the optimal electrolyte, these parts should balance. This finding offers a simple and clear way to narrow the search for superior dopants and combinations of dopants. The ideal dopant should have an effective atomic number between 61 (Pm) and 62 (Sm), and we elaborate that combinations of Nd/Sm and Pr/Gd show enhanced ionic conductivity, as compared with that for each element separately.

  8. Cation Selectivity in Biological Cation Channels Using Experimental Structural Information and Statistical Mechanical Simulation.

    PubMed

    Finnerty, Justin John; Peyser, Alexander; Carloni, Paolo

    2015-01-01

    Cation selective channels constitute the gate for ion currents through the cell membrane. Here we present an improved statistical mechanical model based on atomistic structural information, cation hydration state and without tuned parameters that reproduces the selectivity of biological Na+ and Ca2+ ion channels. The importance of the inclusion of step-wise cation hydration in these results confirms the essential role partial dehydration plays in the bacterial Na+ channels. The model, proven reliable against experimental data, could be straightforwardly used for designing Na+ and Ca2+ selective nanopores.

  9. Cation Selectivity in Biological Cation Channels Using Experimental Structural Information and Statistical Mechanical Simulation

    PubMed Central

    Finnerty, Justin John

    2015-01-01

    Cation selective channels constitute the gate for ion currents through the cell membrane. Here we present an improved statistical mechanical model based on atomistic structural information, cation hydration state and without tuned parameters that reproduces the selectivity of biological Na+ and Ca2+ ion channels. The importance of the inclusion of step-wise cation hydration in these results confirms the essential role partial dehydration plays in the bacterial Na+ channels. The model, proven reliable against experimental data, could be straightforwardly used for designing Na+ and Ca2+ selective nanopores. PMID:26460827

  10. Nanostructure-thermal conductivity relationships in protic ionic liquids.

    PubMed

    Murphy, Thomas; Varela, Luis M; Webber, Grant B; Warr, Gregory G; Atkin, Rob

    2014-10-16

    The thermal conductivities of nine protic ionic liquids (ILs) have been investigated between 293 and 340 K. Within this range, the thermal conductivities are between 0.18 and 0.30 W · m(-1) · K(-1). These values are higher than those typically associated with oils and aprotic ILs, but lower than those of strongly hydrogen bonding solvents like water. Weak linear decreases in thermal conductivity with temperature are noted, with the exception of ethanolammonium nitrate (EtAN) where the thermal conductivity increases with temperature. The dependence of thermal conductivity on IL type is analyzed with use of the Bahe-Varela pseudolattice theory. This theory treats the bulk IL as an array of ordered domains with intervening domains of uncorrelated structure which enable and provide barriers to heat propagation (respectively) via allowed vibrational modes. For the protic ILs investigated, thermal conductivity depends strongly on the IL cation alkyl chain length. This is because the cation alkyl chain controls the dimensions of the IL bulk nanostructure, which consists of charged (ordered domains) and uncharged regions (disordered domains). As the cation alkyl chain controls the dimensions of the disordered domains, it thus limits the thermal conductivity. To test the generality of this interpretation, the thermal conductivities of propylammonium nitrate (PAN) and PAN-octanol mixtures were examined; water selectively swells the PAN charged domain, while octanol swells the uncharged regions. Up to a certain concentration, adding water increases thermal conduction and octanol decreases it, as expected. However, at high solute concentrations the IL nanostructure is broken. When additional solvent is added above this concentration the rate of change in thermal conductivity is greatly reduced. This is because, in the absence of nanostructure, the added solvent only serves to dilute the salt solution.

  11. [Noncovalent cation-π interactions--their role in nature].

    PubMed

    Fink, Krzysztof; Boratyński, Janusz

    2014-11-07

    Non-covalent interactions play an extremely important role in organisms. The main non-covalent interactions in nature are: ion-ion interactions, dipole-dipole interactions, hydrogen bonds, and van der Waals interactions. A new kind of intermolecular interactions--cation-π interactions--is gaining increasing attention. These interactions occur between a cation and a π system. The main contributors to cation-π interactions are electrostatic, polarization and, to a lesser extent, dispersion interactions. At first, cation-π interactions were studied in a gas phase, with metal cation-aromatic system complexes. The characteristics of these complexes are as follows: an increase of cation atomic number leads to a decrease of interaction energy, and an increase of cation charge leads to an increase of interaction energy. Aromatic amino acids bind with metal cations mainly through interactions with their main chain. Nevertheless, cation-π interaction with a hydrophobic side chain significantly enhances binding energy. In water solutions most cations preferentially interact with water molecules rather than aromatic systems. Cation-π interactions occur in environments with lower accessibility to a polar solvent. Cation-π interactions can have a stabilizing role on the secondary, tertiary and quaternary structure of proteins. These interactions play an important role in substrate or ligand binding sites in many proteins, which should be taken into consideration when the screening of effective inhibitors for these proteins is carried out. Cation-π interactions are abundant and play an important role in many biological processes.

  12. Cationic electrodepositable coating composition comprising lignin

    DOEpatents

    Fenn, David; Bowman, Mark P; Zawacky, Steven R; Van Buskirk, Ellor J; Kamarchik, Peter

    2013-07-30

    A cationic electrodepositable coating composition is disclosed. The present invention in directed to a cationic electrodepositable coating composition comprising a lignin-containing cationic salt resin, that comprises (A) the reaction product of: lignin, an amine, and a carbonyl compound; (B) the reaction product of lignin, epichlorohydrin, and an amine; or (C) combinations thereof.

  13. A theoretical study of complexes formed between cations and curved aromatic systems: electrostatics does not always control cation-π interaction.

    PubMed

    Carrazana-García, Jorge A; Cabaleiro-Lago, Enrique M; Rodríguez-Otero, Jesús

    2017-04-19

    The present work studies the interaction of two extended curved π-systems (corannulene and sumanene) with various cations (sodium, potassium, ammonium, tetramethylammonium, guanidinium and imidazolium). Polyatomic cations are models of groups found in important biomolecules in which cation-π interaction plays a fundamental role. The results indicate an important size effect: with extended π systems and cations of the size of potassium and larger, dispersion is much more important than has been generally recognized for cation-π interactions. In most of the systems studied here, the stability of the cation-π complexes is the result of a balanced combination of electrostatic, induction and dispersion contributions. None of the systems studied here owes its stability to the electrostatic interaction more than 42%. Induction dominates stabilization in complexes with sodium, and in some of the potassium and ammonium complexes. In complexes with large cations and with flat cations dispersion is the major stabilizing contribution and can provide more than 50% of the stabilization energy. This implies that theoretical studies of the cation-π interaction involving large or even medium-size fragments require a level of calculation capable of properly modelling dispersion. The separation between the cation and the π system is another important factor to take into account, especially when the fragments of the cation-π complex are bound (for example, to a protein backbone) and cannot interact at the most favourable distance.

  14. Effect of Divalent Cations on RED Performance and Cation Exchange Membrane Selection to Enhance Power Densities.

    PubMed

    Rijnaarts, Timon; Huerta, Elisa; van Baak, Willem; Nijmeijer, Kitty

    2017-11-07

    Reverse electrodialysis (RED) is a membrane-based renewable energy technology that can harvest energy from salinity gradients. The anticipated feed streams are natural river and seawater, both of which contain not only monovalent ions but also divalent ions. However, RED using feed streams containing divalent ions experiences lower power densities because of both uphill transport and increased membrane resistance. In this study, we investigate the effects of divalent cations (Mg 2+ and Ca 2+ ) on RED and demonstrate the mitigation of those effects using both novel and existing commercial cation exchange membranes (CEMs). Monovalent-selective Neosepta CMS is known to block divalent cations transport and can therefore mitigate reductions in stack voltage. The new multivalent-permeable Fuji T1 is able to transport divalent cations without a major increase in resistance. Both strategies significantly improve power densities compared to standard-grade CEMs when performing RED using streams containing divalent cations.

  15. HMGB1: a novel protein that induced platelets active and aggregation via Toll-like receptor-4, NF-κB and cGMP dependent mechanisms.

    PubMed

    Yang, Xinyu; Wang, Haichao; Zhang, Menmen; Liu, Jin; Lv, Ben; Chen, Fangping

    2015-08-06

    Thrombotic diseases are a group of prevalent and life-threatening diseases. Selective inhibition of pathological thrombosis holds the key to treat variety of thrombotic diseases. The pathological thrombosis can be induced by either tissue necrosis and deregulated inflammation. HMGB1, as an important proinflammatory cytokine and a late mediator, also involves on thrombosis disease. However, the underlying mechanisms are not fully understood. Immunofluorescence, ELISA assay, Platelet Aggregation, Thromboelastogram (TEG) analyzes. Flow cytometric analysis and Western blot analysis were used to investigated the role of HMGB1 in platelet aggregation and obtained following observations. By doing so, we obtained the following observations: i) Highly purified HMGB1 recombinant protein induces platelet aggregation and secretion in a dose-dependent manner in the presence of serum. ii) Low concentration of extracellular HMGB1 could synergistically promote subthreshold concentration of collagen or thrombin induced platelet aggregation. iii) Extracellular HMGB1 promoted platelet aggregation in a platelet-expressed GPIIb/IIIa-dependent manner. iv) We proposed that extracellular HMGB1 seems to promote the phosphorylation of GPIIb/IIIa and subsequent platelet aggregation via TLR4/NF-κB and cGMP pathway. In this study, we provide evidence for the hypothesis that HMGB1 interact with platelet might play an important role in the haemostasis and thrombotic diseases. Our research might be provide an interesting avenue for the treatment of thrombotic diseases in the future.

  16. Intervention effects of five cations and their correction on hemolytic activity of tentacle extract from the jellyfish Cyanea capillata

    PubMed Central

    2017-01-01

    Cations have generally been reported to prevent jellyfish venom-induced hemolysis through multiple mechanisms by spectrophotometry. Little attention has been paid to the potential interaction between cations and hemoglobin, potentially influencing the antagonistic effect of cations. Here, we explored the effects of five reported cations, La3+, Mn2+, Zn2+, Cu2+ and Fe2+, on a hemolytic test system and the absorbance of hemoglobin, which was further used to measure their effects on the hemolysis of tentacle extract (TE) from the jellyfish Cyanea capillata. All the cations displayed significant dose-dependent inhibitory effects on TE-induced hemolysis with various dissociation equilibrium constant (Kd) values as follows: La3+ 1.5 mM, Mn2+ 93.2 mM, Zn2+ 38.6 mM, Cu2+ 71.9 μM and Fe2+ 32.8 mM. The transparent non-selective pore blocker La3+ did not affect the absorbance of hemoglobin, while Mn2+ reduced it slightly. Other cations, including Zn2+, Cu2+ and Fe2+, greatly decreased the absorbance with Kd values of 35.9, 77.5 and 17.6 mM, respectively. After correction, the inhibitory Kd values were 1.4 mM, 45.8 mM, 128.5 μM and 53.1 mM for La3+, Zn2+, Cu2+ and Fe2+, respectively. Mn2+ did not inhibit TE-induced hemolysis. Moreover, the inhibitory extent at the maximal given dose of all cations except La3+ was also diminished. These corrected results from spectrophotometry were further confirmed by direct erythrocyte counting under microscopy. Our results indicate that the cations, except for La3+, can interfere with the absorbance of hemoglobin, which should be corrected when their inhibitory effects on hemolysis by jellyfish venoms are examined. The variation in the inhibitory effects of cations suggests that the hemolysis by jellyfish venom is mainly attributed to the formation of non-selective cation pore complexes over other potential mechanisms, such as phospholipases A2 (PLA2), polypeptides, protease and oxidation. Blocking the pore-forming complexes may be a

  17. Cholesterol derived cationic lipids as potential non-viral gene delivery vectors and their serum compatibility.

    PubMed

    Ju, Jia; Huan, Meng-Lei; Wan, Ning; Hou, Yi-Lin; Ma, Xi-Xi; Jia, Yi-Yang; Li, Chen; Zhou, Si-Yuan; Zhang, Bang-Le

    2016-05-15

    Cholesterol derivatives M1-M6 as synthetic cationic lipids were designed and the biological evaluation of the cationic liposomes based on them as non-viral gene delivery vectors were described. Plasmid pEGFP-N1, used as model gene, was transferred into 293T cells by cationic liposomes formed with M1-M6 and transfection efficiency and GFP expression were tested. Cationic liposomes prepared with cationic lipids M1-M6 exhibited good transfection activity, and the transfection activity was parallel (M2 and M4) or superior (M1 and M6) to that of DC-Chol derived from the same backbone. Among them, the transfection efficiency of cationic lipid M6 was parallel to that of the commercially available Lipofectamine2000. The optimal formulation of M1 and M6 were found to be at a mol ratio of 1:0.5 for cationic lipid/DOPE, and at a N/P charge mol ratio of 3:1 for liposome/DNA. Under optimized conditions, the efficiency of M1 and M6 is greater than that of all the tested commercial liposomes DC-Chol and Lipofectamine2000, even in the presence of serum. The results indicated that M1 and M6 exhibited low cytotoxicity, good serum compatibility and efficient transfection performance, having the potential of being excellent non-viral vectors for gene delivery. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Cationic nanoparticles induce nanoscale disruption in living cell plasma membranes.

    PubMed

    Chen, Jiumei; Hessler, Jessica A; Putchakayala, Krishna; Panama, Brian K; Khan, Damian P; Hong, Seungpyo; Mullen, Douglas G; Dimaggio, Stassi C; Som, Abhigyan; Tew, Gregory N; Lopatin, Anatoli N; Baker, James R; Holl, Mark M Banaszak; Orr, Bradford G

    2009-08-13

    It has long been recognized that cationic nanoparticles induce cell membrane permeability. Recently, it has been found that cationic nanoparticles induce the formation and/or growth of nanoscale holes in supported lipid bilayers. In this paper, we show that noncytotoxic concentrations of cationic nanoparticles induce 30-2000 pA currents in 293A (human embryonic kidney) and KB (human epidermoid carcinoma) cells, consistent with a nanoscale defect such as a single hole or group of holes in the cell membrane ranging from 1 to 350 nm(2) in total area. Other forms of nanoscale defects, including the nanoparticle porating agents adsorbing onto or intercalating into the lipid bilayer, are also consistent; although the size of the defect must increase to account for any reduction in ion conduction, as compared to a water channel. An individual defect forming event takes 1-100 ms, while membrane resealing may occur over tens of seconds. Patch-clamp data provide direct evidence for the formation of nanoscale defects in living cell membranes. The cationic polymer data are compared and contrasted with patch-clamp data obtained for an amphiphilic phenylene ethynylene antimicrobial oligomer (AMO-3), a small molecule that is proposed to make well-defined 3.4 nm holes in lipid bilayers. Here, we observe data that are consistent with AMO-3 making approximately 3 nm holes in living cell membranes.

  19. Sodium Fluxes through Nonselective Cation Channels in the Plasma Membrane of Protoplasts from Arabidopsis Roots1

    PubMed Central

    Demidchik, Vadim; Tester, Mark

    2002-01-01

    The aim of the present work was to characterize Na+ currents through nonselective cation channels (NSCCs) in protoplasts derived from root cells of Arabidopsis. The procedure of the protoplast isolation was modified to increase the stability of Arabidopsis root protoplasts in low external Ca2+ by digesting tissue in elevated Ca2+. Experiments in whole-cell and outside-out modes were carried out. We found that Na+ currents in Arabidopsis root protoplasts were mediated by cation channels that were insensitive to externally applied tetraethylammonium+ and verapamil, had no time-dependent activation (permanently opened or completely activated within 1–2 ms), were voltage independent, and were weakly selective for monovalent cations. The selectivity sequence was as follows: K+ (1.49) > NH4+ (1.24) > Rb+ (1.15) ≈ Cs+ (1.10) ≈ Na+ (1.00) > Li+ (0.73) > tetraethylammonium+ (0.47). Arabidopsis root NSCCs were blocked by H+ (pK ≈ 6.0), Ca2+ (K1/2 ≈ 0.1 mm), Ba2+, Zn2+, La3+, Gd3+, quinine, and the His modifier diethylpyrocarbonate. They were insensitive to most organic blockers (nifedipine, verapamil, flufenamate, and amiloride) and to the SH-group modifier p-chloromercuriphenyl sulfonic acid. Voltage-insensitive, Ca2+-sensitive single channels were also resolved. Properties of Arabidopsis root NSCCs are discussed and compared with characteristics of similar conductances studied previously in plants and animals. It is suggested that NSCCs present a distinct group of plant ion channels, mediating toxic Na+ influx to the cell and probably having other important roles in physiological processes of plants. PMID:11842142

  20. Photo-fragmentation spectroscopy of benzylium and 1-phenylethyl cations

    NASA Astrophysics Data System (ADS)

    Féraud, Géraldine; Dedonder-Lardeux, Claude; Soorkia, Satchin; Jouvet, Christophe

    2014-01-01

    The electronic spectra of cold benzylium (C6H5-CH2+) and 1-phenylethyl (C6H5-CH-CH3+) cations have been recorded via photofragment spectroscopy. Benzylium and 1-phenylethyl cations produced from electrosprayed benzylamine and phenylethylamine solutions, respectively, were stored in a cryogenically cooled quadrupole ion trap and photodissociated by an OPO laser, scanned in parts of the UV and visible regions (600-225 nm). The electronic states and active vibrational modes of the benzylium and 1-phenylethyl cations as well as those of their tropylium or methyl tropylium isomers have been calculated with ab initio methods for comparison with the spectra observed. Sharp vibrational progressions are observed in the visible region while the absorption features are much broader in the UV. The visible spectrum of the benzylium cation is similar to that obtained in an argon tagging experiment [V. Dryza, N. Chalyavi, J. A. Sanelli, and E. J. Bieske, J. Chem. Phys. 137, 204304 (2012)], with an additional splitting assigned to Fermi resonances. The visible spectrum of the 1-phenylethyl cation also shows vibrational progressions. For both cations, the second electronic transition is observed in the UV, around 33 000 cm-1 (4.1 eV) and shows a broadened vibrational progression. In both cases the S2 optimized geometry is non-planar. The third electronic transition observed around 40 000 cm-1 (5.0 eV) is even broader with no apparent vibrational structures, which is indicative of either a fast non-radiative process or a very large change in geometry between the excited and the ground states. The oscillator strengths calculated for tropylium and methyl tropylium are weak. Therefore, these isomeric structures are most likely not responsible for these absorption features. Finally, the fragmentation pattern changes in the second and third electronic states: C2H2 loss becomes predominant at higher excitation energies, for both cations.

  1. Photo-fragmentation spectroscopy of benzylium and 1-phenylethyl cations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Féraud, Géraldine; Dedonder-Lardeux, Claude; Jouvet, Christophe, E-mail: christophe.jouvet@univ-amu.fr

    The electronic spectra of cold benzylium (C{sub 6}H{sub 5}-CH{sub 2}{sup +}) and 1-phenylethyl (C{sub 6}H{sub 5}-CH-CH{sub 3}{sup +}) cations have been recorded via photofragment spectroscopy. Benzylium and 1-phenylethyl cations produced from electrosprayed benzylamine and phenylethylamine solutions, respectively, were stored in a cryogenically cooled quadrupole ion trap and photodissociated by an OPO laser, scanned in parts of the UV and visible regions (600–225 nm). The electronic states and active vibrational modes of the benzylium and 1-phenylethyl cations as well as those of their tropylium or methyl tropylium isomers have been calculated with ab initio methods for comparison with the spectra observed.more » Sharp vibrational progressions are observed in the visible region while the absorption features are much broader in the UV. The visible spectrum of the benzylium cation is similar to that obtained in an argon tagging experiment [V. Dryza, N. Chalyavi, J. A. Sanelli, and E. J. Bieske, J. Chem. Phys. 137, 204304 (2012)], with an additional splitting assigned to Fermi resonances. The visible spectrum of the 1-phenylethyl cation also shows vibrational progressions. For both cations, the second electronic transition is observed in the UV, around 33 000 cm{sup −1} (4.1 eV) and shows a broadened vibrational progression. In both cases the S{sub 2} optimized geometry is non-planar. The third electronic transition observed around 40 000 cm{sup −1} (5.0 eV) is even broader with no apparent vibrational structures, which is indicative of either a fast non-radiative process or a very large change in geometry between the excited and the ground states. The oscillator strengths calculated for tropylium and methyl tropylium are weak. Therefore, these isomeric structures are most likely not responsible for these absorption features. Finally, the fragmentation pattern changes in the second and third electronic states: C{sub 2}H{sub 2} loss becomes predominant at

  2. Structural and transport properties of lithium-conducting NASICON materials

    NASA Astrophysics Data System (ADS)

    Rossbach, Andreas; Tietz, Frank; Grieshammer, Steffen

    2018-07-01

    Lithium-containing NASICON-structured materials are a promising class of solid-state Li-ion conductors for application in electrochemical energy storage devices. Amongst the wide variety of possible compositions the highest conductivities are reported for materials according to the formula Li1+xMx(III) M2-x(IV) (PO4)3 , in which the substitution of tetravalent with trivalent metal cations leads to incorporation of additional lithium ions and a higher mobility of the charge carriers. For this study, we surveyed more than 300 research articles about Li-NASICON materials. The relations between composition, structure and conductivity are evaluated to give a comprehensive overview of published data on synthesized compositions. A special focus is laid on Li1+xAlxTi2-x (PO4)3 as the single most conductive and investigated material. The collected conductivities show a wide scattering in a range of 10-10 S cm-1 up to 10-3 S cm-1. The highest values are obtained for materials with M(III) to M(IV) cation ratios of x = 0.3-0.4. Further characteristics for high conductivity are evaluated and the rhombohedral structure as well as cation sizes of around 50-60 p.m. are identified as crucial prerequisites, favoring titanium-based compositions. Considering the evaluated data, selected compositions are suggested for further investigation to support future research.

  3. Crystal Structure of PKG I:cGMP Complex Reveals a cGMP-Mediated Dimeric Interface that Facilitates cGMP-Induced Activation.

    PubMed

    Kim, Jeong Joo; Lorenz, Robin; Arold, Stefan T; Reger, Albert S; Sankaran, Banumathi; Casteel, Darren E; Herberg, Friedrich W; Kim, Choel

    2016-05-03

    Cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is a key regulator of smooth muscle and vascular tone and represents an important drug target for treating hypertensive diseases and erectile dysfunction. Despite its importance, its activation mechanism is not fully understood. To understand the activation mechanism, we determined a 2.5 Å crystal structure of the PKG I regulatory (R) domain bound with cGMP, which represents the activated state. Although we used a monomeric domain for crystallization, the structure reveals that two R domains form a symmetric dimer where the cGMP bound at high-affinity pockets provide critical dimeric contacts. Small-angle X-ray scattering and mutagenesis support this dimer model, suggesting that the dimer interface modulates kinase activation. Finally, structural comparison with the homologous cyclic AMP-dependent protein kinase reveals that PKG is drastically different from protein kinase A in its active conformation, suggesting a novel activation mechanism for PKG. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Crystal Structure of PKG I:cGMP Complex Reveals a cGMP-Mediated Dimeric Interface that Facilitates cGMP-Induced Activation

    DOE PAGES

    Kim, Jeong Joo; Lorenz, Robin; Arold, Stefan T.; ...

    2016-04-07

    Cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is a key regulator of smooth muscle and vascular tone and represents an important drug target for treating hypertensive diseases and erectile dysfunction. Despite its importance, its activation mechanism is not fully understood. To understand the activation mechanism, we determined a 2.5 Å crystal structure of the PKG I regulatory (R) domain bound with cGMP, which represents the activated state. Here, although we used a monomeric domain for crystallization, the structure reveals that two R domains form a symmetric dimer where the cGMP bound at high-affinity pockets provide critical dimeric contacts. Small-angle X-raymore » scattering and mutagenesis support this dimer model, suggesting that the dimer interface modulates kinase activation. Finally, structural comparison with the homologous cyclic AMP-dependent protein kinase reveals that PKG is drastically different from protein kinase A in its active conformation, suggesting a novel activation mechanism for PKG.« less

  5. One-Step Cationic Grafting of 4-Hydroxy-TEMPO and its Application in a Hybrid Redox Flow Battery with a Crosslinked PBI Membrane.

    PubMed

    Chang, Zhenjun; Henkensmeier, Dirk; Chen, Ruiyong

    2017-08-24

    By using a one-step epoxide ring-opening reaction between 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (4-hydroxy-TEMPO) and glycidyltrimethylammonium cation (GTMA + ), we synthesized a cation-grafted TEMPO (g + -TEMPO) and studied its electrochemical performance against a Zn 2+ /Zn anode in a hybrid redox flow battery. To conduct Cl - counter anions, a crosslinked methylated polybenzimidazole (PBI) membrane was prepared and placed between the catholyte and anolyte. Compared to 4-hydroxy-TEMPO, the positively charged g + - TEMPO exhibits enhanced reaction kinetics. Moreover, flow battery tests with g + -TEMPO show improved Coulombic, voltage, and energy efficiencies and cycling stability over 140 cycles. Crossover of active species through the membrane was not detected. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. p53 Mutagenesis by Benzo[a]pyrene derived Radical Cations

    PubMed Central

    Sen, Sushmita; Bhojnagarwala, Pratik; Francey, Lauren; Lu, Ding; Jeffrey Field, Trevor M. Penning

    2013-01-01

    Benzo[a]pyrene (B[a]P), a major human carcinogen in combustion products such as cigarette smoke and diesel exhaust, is metabolically activated into DNA-reactive metabolites via three different enzymatic pathways. The pathways are the anti-(+)-benzo[a]pyrene 7,8-diol 9, 10-epoxide pathway (P450/ epoxide hydrolase catalyzed) (B[a]PDE), the benzo[a]pyrene o-quinone pathway (aldo ketose reductase (AKR) catalyzed) and the B[a]P radical cation pathway (P450 peroxidase catalyzed). We used a yeast p53 mutagenesis system to assess mutagenesis by B[a]P radical cations. Because radical cations are short-lived, they were generated in situ by reacting B[a]P with cumene hydroperoxide (CuOOH) and horse radish peroxidase (HRP) and then monitoring the generation of the more stable downstream products, B[a]P-1,6-dione and B[a]P-3,6-dione. Based on the B[a]P-1,6 and 3,6-dione formation, approximately 4µM of radical cation was generated. In the mutagenesis assays, the radical cations produced in situ showed a dose-dependent increase in mutagenicity from 0.25 µM to 10 µM B[a]P with no significant increase seen with further escalation to 50 µM B[a]P. However, mutagenesis was 200-fold less than with the AKR pathway derived B[a]P, 7–8 dione. Mutant p53 plasmids, which yield red colonies, were recovered from the yeast to study the pattern and spectrum of mutations. The mutation pattern observed was G to T (31%) > G to C (29%) > G to A (14%). The frequency of codons mutated by the B[a]P radical cations was essentially random and not enriched at known cancer hotspots. The quinone products of radical cations, B[a]P-1,6-dione and B[a]P-3,6-dione were more mutagenic than the radical cation reactions, but still less mutagenic than AKR derived B[a]P-7,8-dione. We conclude that B[a]P radical cations and their quinone products are weakly mutagenic in this yeast-based system compared to redox cycling PAH o-quinones. PMID:22768918

  7. Atomistic Modeling of Ion Conduction through the Voltage-Sensing Domain of the Shaker K+ Ion Channel.

    PubMed

    Wood, Mona L; Freites, J Alfredo; Tombola, Francesco; Tobias, Douglas J

    2017-04-20

    Voltage-sensing domains (VSDs) sense changes in the membrane electrostatic potential and, through conformational changes, regulate a specific function. The VSDs of wild-type voltage-dependent K + , Na + , and Ca 2+ channels do not conduct ions, but they can become ion-permeable through pathological mutations in the VSD. Relatively little is known about the underlying mechanisms of conduction through VSDs. The most detailed studies have been performed on Shaker K + channel variants in which ion conduction through the VSD is manifested in electrophysiology experiments as a voltage-dependent inward current, the so-called omega current, which appears when the VSDs are in their resting state conformation. Only monovalent cations appear to permeate the Shaker VSD via a pathway that is believed to be, at least in part, the same as that followed by the S4 basic side chains during voltage-dependent activation. We performed μs-time scale atomistic molecular dynamics simulations of a cation-conducting variant of the Shaker VSD under applied electric fields in an experimentally validated resting-state conformation, embedded in a lipid bilayer surrounded by solutions containing guanidinium chloride or potassium chloride. Our simulations provide insights into the Shaker VSD permeation pathway, the protein-ion interactions that control permeation kinetics, and the mechanism of voltage-dependent activation of voltage-gated ion channels.

  8. Adsorption of Cr(III) on ozonised activated carbon. Importance of Cpi-cation interactions.

    PubMed

    Rivera-Utrilla, J; Sánchez-Polo, M

    2003-08-01

    The adsorption of Cr(III) in aqueous solution was investigated on a series of ozonised activated carbons, analysing the effect of oxygenated surface groups on the adsorption process. A study was carried out to determine the adsorption isotherms and the influence of the pH on the adsorption of this metal. The adsorption capacity and affinity of the adsorbent for Cr(III) increased with the increase in oxygenated acid groups on the surface of the activated carbon. These findings imply that electrostatic-type interactions predominate in the adsorption process, although the adsorption of Cr(III) on the original (basic) carbon indicates that other forces also participate in the adsorption process. Thus, the ionic exchange of protons in the -Cpi-H3O(+) interaction for Cr(III) accounts for the adsorption of cationic species in basic carbons with positive charge density. Study of the influence of pH on the adsorption of Cr(III) showed that, in each system, the maximum adsorption occurred when the charge of the carbon surface was opposite that of the species of Cr(III) present at the pH of the experiment. These results confirmed that electrostatic interactions predominate in the adsorption process.

  9. Cation-π interaction of the univalent sodium cation with [2.2.2]paracyclophane: Experimental and theoretical study

    NASA Astrophysics Data System (ADS)

    Makrlík, Emanuel; Sýkora, David; Böhm, Stanislav; Vaňura, Petr

    2018-02-01

    By employing electrospray ionization mass spectrometry (ESI-MS), it was proven experimentally that the univalent sodium cation (Na+) forms with [2.2.2]paracyclophane (C24H24) the cationic complex [Na(C24H24)]+. Further, applying quantum chemical DFT calculations, the most probable structure of the [Na(C24H24)]+ complex was derived. In the resulting complex with a symmetry very close to C3, the "central" cation Na+, fully located in the cavity of the parent [2.2.2]paracyclophane ligand, is bound to all three benzene rings of [2.2.2]paracyclophane via cation-π interaction. Finally, the interaction energy, E(int), of the considered cation-π complex [Na(C24H24)]+ was found to be -267.3 kJ/mol, confirming the formation of this fascinating complex species as well.

  10. Acidic pH and divalent cation sensing by PhoQ are dispensable for systemic salmonellae virulence.

    PubMed

    Hicks, Kevin G; Delbecq, Scott P; Sancho-Vaello, Enea; Blanc, Marie-Pierre; Dove, Katja K; Prost, Lynne R; Daley, Margaret E; Zeth, Kornelius; Klevit, Rachel E; Miller, Samuel I

    2015-05-23

    Salmonella PhoQ is a histidine kinase with a periplasmic sensor domain (PD) that promotes virulence by detecting the macrophage phagosome. PhoQ activity is repressed by divalent cations and induced in environments of acidic pH, limited divalent cations, and cationic antimicrobial peptides (CAMP). Previously, it was unclear which signals are sensed by salmonellae to promote PhoQ-mediated virulence. We defined conformational changes produced in the PhoQ PD on exposure to acidic pH that indicate structural flexibility is induced in α-helices 4 and 5, suggesting this region contributes to pH sensing. Therefore, we engineered a disulfide bond between W104C and A128C in the PhoQ PD that restrains conformational flexibility in α-helices 4 and 5. PhoQ(W104C-A128C) is responsive to CAMP, but is inhibited for activation by acidic pH and divalent cation limitation. phoQ(W104C-A128C) Salmonella enterica Typhimurium is virulent in mice, indicating that acidic pH and divalent cation sensing by PhoQ are dispensable for virulence.

  11. Axial stretch-dependent cation entry in dystrophic cardiomyopathy: Involvement of several TRPs channels

    PubMed Central

    Krzesiak, A.; Lipskaia, L.; Adnot, S.; Hajjar, R.J.; Cognard, C.

    2016-01-01

    In Duchenne muscular dystrophy (DMD), deficiency of the cytoskeletal protein dystrophin leads to well-described defects in skeletal muscle but also to dilated cardiomyopathy (DCM). In cardiac cells, the subsarcolemmal localization of dystrophin is thought to protect the membrane from mechanical stress. The dystrophin deficiency leads to membrane instability and a high stress-induced Ca2+ influx due to dysregulation of sarcolemmal channels such as stretch-activated channels (SACs). In this work divalent cation entry has been explored in isolated ventricular Wild Type (WT) and mdx cardiomyocytes in two different conditions: at rest and during the application of an axial stretch. At rest, our results suggest that activation of TRPV2 channels participates to a constitutive basal cation entry in mdx cardiomyocytes.Using microcarbon fibres technique, an axial stretchwas applied to mimic effects of physiological conditions of ventricular filling and study on cation influx bythe Mn2+-quenching techniquedemonstrated a high stretch-dependentcationic influx in dystrophic cells, partially due to SACs. Involvement of TRPs channels in this excessive Ca2+ influx has been investigated using specific modulators and demonstratedboth sarcolemmal localization and an abnormal activity of TRPV2 channels. In conclusion, TRPV2 channels are demonstrated here to play a key role in cation influx and dysregulation in dystrophin deficient cardiomyocytes, enhanced in stretching conditions. PMID:26803937

  12. Alternative splice isoforms of small conductance calcium-activated SK2 channels differ in molecular interactions and surface levels

    PubMed Central

    Scholl, Elizabeth Storer; Pirone, Antonella; Cox, Daniel H; Duncan, R Keith; Jacob, Michele H

    2014-01-01

    Small conductance Ca2+-sensitive potassium (SK2) channels are voltage-independent, Ca2+-activated ion channels that conduct potassium cations and thereby modulate the intrinsic excitability and synaptic transmission of neurons and sensory hair cells. In the cochlea, SK2 channels are functionally coupled to the highly Ca2+ permeant α9/10-nicotinic acetylcholine receptors (nAChRs) at olivocochlear postsynaptic sites. SK2 activation leads to outer hair cell hyperpolarization and frequency-selective suppression of afferent sound transmission. These inhibitory responses are essential for normal regulation of sound sensitivity, frequency selectivity, and suppression of background noise. However, little is known about the molecular interactions of these key functional channels. Here we show that SK2 channels co-precipitate with α9/10-nAChRs and with the actin-binding protein α-actinin-1. SK2 alternative splicing, resulting in a 3 amino acid insertion in the intracellular 3′ terminus, modulates these interactions. Further, relative abundance of the SK2 splice variants changes during developmental stages of synapse maturation in both the avian cochlea and the mammalian forebrain. Using heterologous cell expression to separately study the 2 distinct isoforms, we show that the variants differ in protein interactions and surface expression levels, and that Ca2+ and Ca2+-bound calmodulin differentially regulate their protein interactions. Our findings suggest that the SK2 isoforms may be distinctly modulated by activity-induced Ca2+ influx. Alternative splicing of SK2 may serve as a novel mechanism to differentially regulate the maturation and function of olivocochlear and neuronal synapses. PMID:24394769

  13. The atypical cation-conduction and gating properties of ELIC underscore the marked functional versatility of the pentameric ligand-gated ion-channel fold

    PubMed Central

    Gonzalez-Gutierrez, Giovanni

    2015-01-01

    The superfamily of pentameric ligand-gated ion channels (pLGICs) is unique among ionotropic receptors in that the same overall structure has evolved to generate multiple members with different combinations of agonist specificities and permeant-ion charge selectivities. However, aside from these differences, pLGICs have been typically regarded as having several invariant functional properties. These include pore blockade by extracellular quaternary-ammonium cations in the micromolar-to-millimolar concentration range (in the case of the cation-selective members), and a gain-of-function phenotype, which manifests as a slower deactivation time course, as a result of mutations that reduce the hydrophobicity of the transmembrane pore lining. Here, we tested this notion on three distantly related cation-selective members of the pLGIC superfamily: the mouse muscle nicotinic acetylcholine receptor (nAChR), and the bacterial GLIC and ELIC channels. Remarkably, we found that, whereas low millimolar concentrations of TMA+ and TEA+ block the nAChR and GLIC, neither of these two quaternary-ammonium cations blocks ELIC at such concentrations; instead, both carry measurable inward currents when present as the only cations on the extracellular side. Also, we found that, whereas lidocaine binding speeds up the current-decay time courses of the nAChR and GLIC in the presence of saturating concentrations of agonists, the binding of lidocaine to ELIC slows this time course down. Furthermore, whereas mutations that reduce the hydrophobicity of the side chains at position 9′ of the M2 α-helices greatly slowed the deactivation time course of the nAChR and GLIC, these mutations had little effect—or even sped up deactivation—when engineered in ELIC. Our data indicate that caution should be exercised when generalizing results obtained with ELIC to the rest of the pLGICs, but more intriguingly, they hint at the possibility that ELIC is a representative of a novel branch of the

  14. Specificity in cationic interaction with poly(N-isopropylacrylamide).

    PubMed

    Du, Hongbo; Wickramasinghe, Sumith Ranil; Qian, Xianghong

    2013-05-02

    Classical molecular dynamics (MD) simulations were conducted for PNIPAM in 1 M monovalent alkali chloride salt solutions as well as in 0.5 M divalent Mg(2+) and Ca(2+) chloride salt solutions. It was found that the strength for the direct alkali ion-amide O binding is strongly correlated with the size of the ionic radius. The smallest Li(+) ion binds strongest to amide O, and the largest Cs(+) ion has the weakest interaction with the amide bond. For the divalent Mg(2+) and Ca(2+) ions, their interactions with the amide bond are weak and appear to be mediated by the water molecules, particularly in the case of Mg(2+), resulting from their strong hydration. The direct binding between the cations and amide O requires partial desovlation of the ions that is energetically unfavorable for Mg(2+) and also to a great extent for Ca(2+). The higher cation charge makes the electrostatic interaction more favorable but the dehydration process less favorable. This competition between electrostatic interaction and the dehydration process largely dictates whether the direct binding between the cation and amide O is energetically preferred or not. For monovalent alkali ions, it is energetically preferred to bind directly with the amide O. Moreover, Li(+) ion is also found to associate strongly with the hydrophobic residues on PNIPAM.

  15. Inhibition of trypanosome alternative oxidase without its N-terminal mitochondrial targeting signal (ΔMTS-TAO) by cationic and non-cationic 4-hydroxybenzoate and 4-alkoxybenzaldehyde derivatives active against T. brucei and T. congolense.

    PubMed

    Ebiloma, Godwin U; Ayuga, Teresa Díaz; Balogun, Emmanuel O; Gil, Lucía Abad; Donachie, Anne; Kaiser, Marcel; Herraiz, Tomás; Inaoka, Daniel K; Shiba, Tomoo; Harada, Shigeharu; Kita, Kiyoshi; de Koning, Harry P; Dardonville, Christophe

    2018-04-25

    African trypanosomiasis is a neglected parasitic disease that is still of great public health relevance, and a severe impediment to agriculture in endemic areas. The pathogens possess certain unique metabolic features that can be exploited for the development of new drugs. Notably, they rely on an essential, mitochondrially-localized enzyme, Trypanosome Alternative Oxidase (TAO) for their energy metabolism, which is absent in the mammalian hosts and therefore an attractive target for the design of safe drugs. In this study, we cloned, expressed and purified the physiologically relevant form of TAO, which lacks the N-terminal 25 amino acid mitochondrial targeting sequence (ΔMTS-TAO). A new class of 32 cationic and non-cationic 4-hydroxybenzoate and 4-alkoxybenzaldehyde inhibitors was designed and synthesized, enabling the first structure-activity relationship studies on ΔMTS-TAO. Remarkably, we obtained compounds with enzyme inhibition values (IC 50 ) as low as 2 nM, which were efficacious against wild type and multidrug-resistant strains of T. brucei and T. congolense. The inhibitors 13, 15, 16, 19, and 30, designed with a mitochondrion-targeting lipophilic cation tail, displayed trypanocidal potencies comparable to the reference drugs pentamidine and diminazene, and showed no cross-resistance with the critical diamidine and melaminophenyl arsenical classes of trypanocides. The cationic inhibitors 15, 16, 19, 20, and 30 were also much more selective (900 - 344,000) over human cells than the non-targeted neutral derivatives (selectivity >8-fold). A preliminary in vivo study showed that modest doses of 15 and 16 reduced parasitaemia of mice infected with T. b. rhodesiense (STIB900). These compounds represent a promising new class of potent and selective hits against African trypanosomes. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  16. Cationic PAMAM Dendrimers Aggressively Initiate Blood Clot Formation

    PubMed Central

    Jones, Clinton F.; Campbell, Robert A.; Brooks, Amanda E.; Assemi, Shoeleh; Tadjiki, Soheyl; Thiagarajan, Giridhar; Mulcock, Cheyanne; Weyrich, Andrew S.; Brooks, Benjamin D.; Ghandehari, Hamidreza; Grainger, David W.

    2012-01-01

    Poly(amidoamine) (PAMAM) dendrimers are increasingly studied as model nanoparticles for a variety of biomedical applications, notably in systemic administrations. However, with respect to blood contacting applications, amine-terminated dendrimers have recently been shown to activate platelets and cause a fatal, disseminated intravascular coagulation (DIC)-like condition in mice and rats. We here demonstrate that, upon addition to blood, cationic G7 PAMAM dendrimers induce fibrinogen aggregation, which may contribute to the in vivo DIC-like phenomenon. We demonstrate that amine-terminated dendrimers act directly on fibrinogen in a thrombin-independent manner to generate dense, high-molecular-weight fibrinogen aggregates with minimal fibrin fibril formation. In addition, we hypothesize this clot-like behavior is likely mediated through electrostatic interactions between the densely charged cationic dendrimer surface and negatively charged fibrinogen domains. Interestingly, cationic dendrimers also induced aggregation of albumin, suggesting that many negatively charged blood proteins may be affected by cationic dendrimers. To investigate this further, zebrafish embryos (ZFE) were employed to more specifically determine the speed of this phenomenon and the pathway- and dose-dependency of the resulting vascular occlusion phenotype. These novel findings show that G7 PAMAM dendrimers significantly and adversely impact many blood components to produce rapid coagulation and strongly suggest that these effects are independent of classic coagulation mechanisms. These results also strongly suggest the need to fully characterize amine-terminated PAMAM dendrimers in regards to their adverse effects on both coagulation and platelets, which may contribute to blood toxicity. PMID:23062017

  17. Ion Dynamics in a Mixed-Cation Alkoxy-Ammonium Ionic Liquid Electrolyte for Sodium Device Applications.

    PubMed

    Pope, Cameron R; Kar, Mega; MacFarlane, Douglas R; Armand, Michel; Forsyth, Maria; O'Dell, Luke A

    2016-10-18

    The ion dynamics in a novel sodium-containing room-temperature ionic liquid (IL) consisting of an ether-functionalised quaternary ammonium cation and bis(trifluoromethylsulfonyl)amide [NTf 2 ] anion with various concentrations of Na[NTf 2 ] have been characterised using differential scanning calorimetry, impedance spectroscopy, diffusometry and NMR relaxation measurements. The IL studied has been specifically designed to dissolve a relatively large concentration of Na[NTf 2 ] salt (over 2 mol kg -1 ) as this has been shown to improve ion transport and conductivity. Consistent with other studies, the measured ionic conductivity and diffusion coefficients show that the overall ionic mobility decreases with decreasing temperature and increasing salt content. NMR relaxation measurements provide evidence for correlated dynamics between the ether-functionalised ammonium and Na cations, possibly with the latter species acting as cross-links between multiple ammonium cations. Finally, preliminary cyclic voltammetry experiments show that this IL can undergo stable electrochemical cycling and could therefore be potentially useful as an electrolyte in a Na-based device. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Variational first hyperpolarizabilities of 2,3-naphtho-15-crown-5 ether derivatives with cation-complexing: a potential and selective cation detector.

    PubMed

    Yu, Hai-Ling; Wang, Wen-Yong; Hong, Bo; Zong, Ying; Si, Yan-Ling; Hu, Zhong-Qiang

    2016-09-29

    Crown ethers, as a kind of heterocycle, have been the subject of great interest over recent decades due to their selective capability to bind to metal cations. The use of a constant crown ether, such as naphtho-15-crown-5 (N15C5), and varied metal cations (Li + , Na + , K + , Be 2+ , Mg 2+ , Ca 2+ , Co 2+ , Ni 2+ , Cu 2+ ) makes it possible to determine the contributions of the metal cations to nonlinear optical (NLO) responses and to design an appropriate NLO-based cation detector. N15C5 and its metal cation derivatives have been systematically investigated by density functional theory. It is found that the dependency of the first hyperpolarizability relies on the metal cation, especially for transition metals. The decrease of the first hyperpolarizabilities for alkali metal cation derivatives is due to their relatively low oscillator strengths, whereas the significant increase of the first hyperpolarizabilities for transition metal cation derivatives can be further illustrated by their low transition energies, large amplitudes and separate distributions of first hyperpolarizability density. Thus, the alkali metal and transition metal cations are distinguishable and the transition metal cations are easier to detect by utilizing the variations in NLO responses.

  19. Non-surface activity and micellization behavior of cationic amphiphilic block copolymer synthesized by reversible addition-fragmentation chain transfer process.

    PubMed

    Ghosh, Arjun; Yusa, Shin-ichi; Matsuoka, Hideki; Saruwatari, Yoshiyuki

    2011-08-02

    Cationic amphiphilic diblock copolymers of poly(n-butylacrylate)-b-poly(3-(methacryloylamino)propyl)trimethylammonium chloride) (PBA-b-PMAPTAC) with various hydrophobic and hydrophilic chain lengths were synthesized by a reversible addition-fragmentation chain transfer (RAFT) process. Their molecular characteristics such as surface activity/nonactivity were investigated by surface tension measurements and foam formation observation. Their micelle formation behavior and micelle structure were investigated by fluorescence probe technique, static and dynamic light scattering (SLS and DLS), etc., as a function of hydrophilic and hydrophobic chain lengths. The block copolymers were found to be non-surface active because the surface tension of the aqueous solutions did not change with increasing polymer concentration. Critical micelle concentration (cmc) of the polymers could be determined by fluorescence and SLS measurements, which means that these polymers form micelles in bulk solution, although they were non-surface active. Above the cmc, the large blue shift of the emission maximum of N-phenyl-1-naphthylamine (NPN) probe and the low micropolarity value of the pyrene probe in polymer solution indicate the core of the micelle is nonpolar in nature. Also, the high value of the relative intensity of the NPN probe and the fluorescence anisotropy of the 1,6-diphenyl-1,3,5-hexatriene (DPH) probe indicated that the core of the micelle is highly viscous in nature. DLS was used to measure the average hydrodynamic radii and size distribution of the copolymer micelles. The copolymer with the longest PBA block had the poorest water solubility and consequently formed micelles with larger size while having a lower cmc. The "non-surface activity" was confirmed for cationic amphiphilic diblock copolymers in addition to anionic ones studied previously, indicating the universality of non-surface activity nature.

  20. Ethanol extract of seeds of Oenothera odorata induces vasorelaxation via endothelium-dependent NO-cGMP signaling through activation of Akt-eNOS-sGC pathway.

    PubMed

    Kim, Hye Yoom; Oh, Hyuncheol; Li, Xiang; Cho, Kyung Woo; Kang, Dae Gill; Lee, Ho Sub

    2011-01-27

    The vasorelaxant effect of ethanol extract of seeds of Oenothera odorata (Onagraceae) (one species of evening primroses) (ESOO) and its mechanisms involved were defined. Changes in vascular tension, guanosine 3',5'-cyclic monophosphate (cGMP) levels, and Akt expression were measured in carotid arterial rings from rats. Seeds of Oenothera odorata were extracted with ethanol (94%) and the extract was filtered, concentrated and stored at -70°C. ESOO relaxed endothelium-intact, but not endothelium-denuded, carotid arterial rings in a concentration-dependent manner. Similarly, ESOO increased cGMP levels of the carotid arterial rings. Pretreatment of endothelium-intact arterial rings with L-NAME, an inhibitor of nitric oxide synthase (NOS), or ODQ, an inhibitor of soluble guanylyl cyclase (sGC), blocked the ESOO-induced vasorelaxation and increase in cGMP levels. Nominally Ca(2+)-free but not L-typed Ca(2+) channel inhibition attenuated the ESOO-induced vasorelaxation. Thapsigargin, Gd(3+), and 2-aminoethyl diphenylborinate, modulators of store-operated Ca(2+) entry (SOCE), significantly attenuated the ESOO-induced vasorelaxation and increase in cGMP levels. Further, wortmannin, an inhibitor of Akt, attenuated the ESOO-induced vasorelaxation and increases in cGMP levels and phosphorylated Akt2 expression. K(+) channel blockade with TEA, 4-aminopyridine, and glibenclamide attenuated the ESOO-induced vascular relaxation. Taken together, the present study demonstrates that ESOO relaxes vascular smooth muscle via endothelium-dependent NO-cGMP signaling through activation of the Akt-eNOS-sGC pathway. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  1. The special features of the crystal structure and properties of oxides with mixed conductivity based on lanthanum gallate

    NASA Astrophysics Data System (ADS)

    Politova, E. D.; Ivanov, S. A.; Kaleva, G. M.; Mosunov, A. V.; Rusakov, V. S.

    2008-10-01

    The paper presents a review of works on the synthesis, structural composition effects, phase transitions, and electrical conductivity properties of multicomponent solid solutions based on heterosubstituted lanthanum gallate (La,A)(Ga,M)O3 - y . High-temperature phase transitions and structural and charge ordering effects were studied. The presence of iron cations in different valence states was proved; the relative contents of these cations depended on the x parameter and nonstoichiometry parameter y of the base composition. For M = Fe, antiferromagnetic ordering was observed; its temperature interval was determined by the concentration of iron cations in the high-spin state. The total conductivity was found to increase as the concentration of transition metal cations grew because of an increase in the electronic conductivity component. The data on structural parameters and dc and ac conductivity substantiated the conclusion that the highest ionic conductivity and permeability to oxygen were characteristic of iron-containing oxides. The results obtained are evidence that crystal chemical factors play a determining role in the formation of the ion-conducting properties of anion-deficient perovskite-like oxides.

  2. Metal cation controls phosphate release in the myosin ATPase.

    PubMed

    Ge, Jinghua; Huang, Furong; Nesmelov, Yuri E

    2017-11-01

    Myosin is an enzyme that utilizes ATP to produce a conformational change generating a force. The kinetics of the myosin reverse recovery stroke depends on the metal cation complexed with ATP. The reverse recovery stroke is slow for MgATP and fast for MnATP. The metal ion coordinates the γ phosphate of ATP in the myosin active site. It is accepted that the reverse recovery stroke is correlated with the phosphate release; therefore, magnesium "holds" phosphate tighter than manganese. Magnesium and manganese are similar ions in terms of their chemical properties and the shell complexation; hence, we propose to use these ions to study the mechanism of the phosphate release. Analysis of octahedral complexes of magnesium and manganese show that the partial charge of magnesium is higher than that of manganese and the slightly larger size of manganese ion makes its ionic potential smaller. We hypothesize that electrostatics play a role in keeping and releasing the abstracted γ phosphate in the active site, and the stronger electric charge of magnesium ion holds γ phosphate tighter. We used stable myosin-nucleotide analog complex and Raman spectroscopy to examine the effect of the metal cation on the relative position of γ phosphate analog in the active site. We found that in the manganese complex, the γ phosphate analog is 0.01 nm further away from ADP than in the magnesium complex. We conclude that the ionic potential of the metal cation plays a role in the retention of the abstracted phosphate. © 2017 The Protein Society.

  3. Triphenylphosphonium cation: a valuable functional group for antimicrobial photodynamic therapy.

    PubMed

    Bresolí-Obach, Roger; Gispert, Ignacio; García Peña, Diego; Boga, Sonia; Gulias, Óscar; Agut, Montserrat; Vázquez, M Eugenio; Nonell, Santi

    2018-06-08

    Light-mediated killing of pathogens by cationic photosensitisers is a promising antimicrobial approach that avoids the development of resistance inherent to the use of antimicrobials. In this study, we demonstrate that modification of different photosensitisers with the triphenylphosphonium cation yields derivatives with excellent photoantimicrobial activity against Gram-positive bacteria (i.e., S. aureus and E. faecalis). Thus, the triphenylphosphonium functional group should be considered for the development of photoantimicrobials for the selective killing of Gram-positive bacteria in the presence of Gram-negative species. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  4. Cation radius effects on the helix-coil transition of DNA. Cryptates and other large cations.

    PubMed Central

    Trend, B L; Knoll, D A; Ueno, M; Evans, D F; Bloomfield, V A

    1990-01-01

    Most polyelectrolyte theories of the effect of ions on the thermal melting of DNA assume that the predominant influence of the cations comes through their charge. Ion size and structure are treated, for analytic convenience, as negligible variables. We have examined the validity of this assumption by measuring the melting temperature of calf thymus DNA as a function of salt concentration with four univalent cations of different hydrated radii. These are K+ (3.3 A), (n-Pr)4N+ (4.5 A), (EtOH)4N+ (4.5 A), and C222-K+ (5 A). C222-K+ is a complex of cryptand C222 with K+. With K+ as the sole cation, Tm varies linearly with the log of ionic strength over the range 0.001-0.1 M. With all the K+ sequestered by an equimolar amount of C222, Tm is depressed by 10-20 degrees C and the slope of Tm vs. ionic strength is lower. At low ionic strength, an even greater reduction in Tm is achieved with (n-Pr)4N+; but the similar-sized (EtOH)4N+ gives a curve more similar to K+. Theoretical modeling, taking into account cation size through the Poisson-Boltzmann equation for cylindrical polyelectrolytes, predicts that larger cations should be less effective in stabilizing the double helix; but the calculated effect is less than observed experimentally. These results show that valence, cation size, and specific solvation effects are all important in determining the stability of the double-helical form of DNA. PMID:2344467

  5. Adsorption of reovirus to clay minerals: effects of cation-exchange capacity, cation saturation, and surface area.

    PubMed Central

    Lipson, S M; Stotzky, G

    1983-01-01

    The adsorption of reovirus to clay minerals has been reported by several investigators, but the mechanisms defining this association have been studied only minimally. The purpose of this investigation was to elucidate the mechanisms involved with this interaction. More reovirus type 3 was adsorbed, in both distilled and synthetic estuarine water, by low concentrations of montmorillonite than by comparable concentrations of kaolinite containing a mixed complement of cations on the exchange complex. Adsorption to the clays was essentially immediate and was correlated with the cation-exchange capacity of the clays, indicating that adsorption was primarily to negatively charged sites on the clays. Adsorption was greater with low concentrations of clays in estuarine water than in distilled water, as the higher ionic strength of the estuarine water reduced the electrokinetic potential of both clay and virus particles. The addition of cations (as chloride salts) to distilled water enhanced adsorption, with divalent cations being more effective than monovalent cations and 10(-2) M resulting in more adsorption than 10(-3) M. Potassium ions suppressed reovirus adsorption to montmorillonite, probably by collapsing the clay lattices and preventing the expression of the interlayer-derived cation-exchange capacity. More virus was adsorbed by montmorillonite made homoionic to various mono-, di-, and trivalent cations (except by montmorillonite homoionic to potassium) than by comparable concentrations of kaolinite homoionic to the same cations. The sequence of the amount of adsorption to homoionic montmorillonite was Al greater than Ca greater than Mg greater than Na greater than K; the sequence of adsorption to kaolinite was Na greater than Al greater than Ca greater than Mg greater than K. The constant partition-type adsorption isotherms obtained when the clay concentration was maintained constant and the virus concentration was varied indicated that a fixed proportion of the

  6. Regulate axon branching by the cyclic GMP pathway via inhibition of glycogen synthase kinase 3 in dorsal root ganglion sensory neurons.

    PubMed

    Zhao, Zhen; Wang, Zheng; Gu, Ying; Feil, Robert; Hofmann, Franz; Ma, Le

    2009-02-04

    Cyclic GMP has been proposed to regulate axonal development, but the molecular and cellular mechanisms underlying the formation of axon branches are not well understood. Here, we report the use of rodent embryonic sensory neurons from the dorsal root ganglion (DRG) to demonstrate the role of cGMP signaling in axon branching and to identify the downstream molecular pathway mediating this novel regulation. Pharmacologically, a specific cGMP analog promotes DRG axon branching in culture, and this activity can be achieved by activating the endogenous soluble guanylyl cyclase that produces cGMP. At the molecular level, the cGMP-dependent protein kinase 1 (PrkG1) mediates this activity, as DRG neurons isolated from the kinase-deficient mouse fail to respond to cGMP activation to make branches, whereas overexpression of a PrkG1 mutant with a higher-than-normal basal kinase activity is sufficient to induce branching. In addition, cGMP activation in DRG neurons leads to phosphorylation of glycogen synthase kinase 3 (GSK3), a protein that normally suppresses branching. This interaction is direct, because PrkG1 binds GSK3 in heterologous cells and the purified kinase can phosphorylate GSK3 in vitro. More importantly, overexpression of a dominant active form of GSK3 suppresses cGMP-dependent branching in DRG neurons. Thus, our study establishes an intrinsic signaling cascade that links cGMP activation to GSK3 inhibition in controlling axon branching during sensory axon development.

  7. Active subthreshold dendritic conductances shape the local field potential

    PubMed Central

    Ness, Torbjørn V.; Remme, Michiel W. H.

    2016-01-01

    Key points The local field potential (LFP), the low‐frequency part of extracellular potentials recorded in neural tissue, is often used for probing neural circuit activity. Interpreting the LFP signal is difficult, however.While the cortical LFP is thought mainly to reflect synaptic inputs onto pyramidal neurons, little is known about the role of the various subthreshold active conductances in shaping the LFP.By means of biophysical modelling we obtain a comprehensive qualitative understanding of how the LFP generated by a single pyramidal neuron depends on the type and spatial distribution of active subthreshold currents.For pyramidal neurons, the h‐type channels probably play a key role and can cause a distinct resonance in the LFP power spectrum.Our results show that the LFP signal can give information about the active properties of neurons and imply that preferred frequencies in the LFP can result from those cellular properties instead of, for example, network dynamics. Abstract The main contribution to the local field potential (LFP) is thought to stem from synaptic input to neurons and the ensuing subthreshold dendritic processing. The role of active dendritic conductances in shaping the LFP has received little attention, even though such ion channels are known to affect the subthreshold neuron dynamics. Here we used a modelling approach to investigate the effects of subthreshold dendritic conductances on the LFP. Using a biophysically detailed, experimentally constrained model of a cortical pyramidal neuron, we identified conditions under which subthreshold active conductances are a major factor in shaping the LFP. We found that, in particular, the hyperpolarization‐activated inward current, I h, can have a sizable effect and cause a resonance in the LFP power spectral density. To get a general, qualitative understanding of how any subthreshold active dendritic conductance and its cellular distribution can affect the LFP, we next performed a systematic

  8. Infrared Spectroscopic and Theoretical Study of the HC_nO^+(N=5-12) Cations

    NASA Astrophysics Data System (ADS)

    Li, Wei; Jin, Jiaye; Wang, Guanjun; Zhou, Mingfei

    2017-06-01

    Carbon chains and derivatives are highly active species, which are widely existed as reactive intermediates in many chemical processes including atmospheric chemistry, hydrocarbon combustion, as well as interstellar chemistry. The carbon chain cations, HC_nO^+ (n = 5-12) are produced via pulsed laser vaporization of a graphite target in supersonic expansions containing carbon monoxide and hydrogen. The infrared spectra are measured via mass-selected infrared photodissociation spectroscopy of the CO "tagged" [HC_nO.CO] cation complexes in the 1600-3500 \\wn region. The geometries and electronic ground states of these cation complexes are determined by their infrared spectra in conjunction with theoretical calculations. All the HC_nO^+ (n = 5-12) core cations are characterized to be linear carbon chain derivatives terminated by hydrogen and oxygen. The HC_nO^+ cations with odd n have closed-shell singlet ground states with polyyne-like structures, while those with even n have triplet ground states with allene-like structures.

  9. ADSORPTION METHOD FOR SEPARATING METAL CATIONS

    DOEpatents

    Khym, J.X.

    1959-03-10

    The chromatographic separation of fission product cations is discussed. By use of this method a mixture of metal cations containing Zr, Cb, Ce, Y, Ba, and Sr may be separated from one another. Mentioned as preferred exchange adsorbents are resins containing free sulfonic acid groups. Various eluants, such as tartaric acid, HCl, and citric acid, used at various acidities, are employed to effect the selective elution and separation of the various fission product cations.

  10. Identification of a crucial histidine involved in metal transport activity in the Arabidopsis cation/H+ exchanger CAX1.

    PubMed

    Shigaki, Toshiro; Barkla, Bronwyn J; Miranda-Vergara, Maria Cristina; Zhao, Jian; Pantoja, Omar; Hirschi, Kendal D

    2005-08-26

    In plants, yeast, and bacteria, cation/H+ exchangers (CAXs) have been shown to translocate Ca2+ and other metal ions utilizing the H+ gradient. The best characterized of these related transporters is the plant vacuolar localized CAX1. We have used site-directed mutagenesis to assess the impact of altering the seven histidine residues to alanine within Arabidopsis CAX1. The mutants were expressed in a Saccharomyces cerevisiae strain that is sensitive to Ca2+ and other metals. By utilizing a yeast growth assay, the H338A mutant was the only mutation that appeared to alter Ca2+ transport activity. The CAX1 His338 residue is conserved among various CAX transporters and may be located within a filter for cation selection. We proceeded to mutate His338 to every other amino acid residue and utilized yeast growth assays to estimate the transport properties of the 19 CAX mutants. Expression of 16 of these His338 mutants could not rescue any of the metal sensitivities. However, expression of H338N, H338Q, and H338K allowed for some growth on media containing Ca2+. Most interestingly, H338N exhibited increased tolerance to Cd2+ and Zn2+. Endomembrane fractions from yeast cells were used to measure directly the transport of H338N. Although the H338N mutant demonstrated 25% of the wild type Ca2+/H+ transport, it showed an increase in transport for both Cd2+ and Zn2+ reflected in a decrease in the Km for these substrates. This study provides insights into the CAX cation filter and novel mechanisms by which metals may be partitioned across membranes.

  11. Low conductivity and sintering-resistant thermal barrier coatings

    NASA Technical Reports Server (NTRS)

    Zhu, Dongming (Inventor); Miller, Robert A. (Inventor)

    2007-01-01

    A thermal barrier coating composition is provided. The composition has a base oxide, a primary stabilizer, and at least two additional cationic oxide dopants. Preferably, a pair of group A and group B defect cluster-promoting oxides is used in conjunction with the base and primary stabilizer oxides. The new thermal barrier coating is found to have significantly lower thermal conductivity and better sintering resistance. In preferred embodiments, the base oxide is selected from zirconia and hafnia. The group A and group B cluster-promoting oxide dopants preferably are selected such that the group A dopant has a smaller cationic radius than the primary stabilizer oxide, and so that the primary stabilizer oxide has a small cationic radius than that of the group B dopant.

  12. Low conductivity and sintering-resistant thermal barrier coatings

    NASA Technical Reports Server (NTRS)

    Zhu, Dongming (Inventor); Miller, Robert A. (Inventor)

    2006-01-01

    A thermal barrier coating composition is provided. The composition has a base oxide, a primary stabilizer, and at least two additional cationic oxide dopants. Preferably, a pair of group A and group B defect cluster-promoting oxides is used in conjunction with the base and primary stabilizer oxides. The new thermal barrier coating is found to have significantly lower thermal conductivity and better sintering resistance. In preferred embodiments, the base oxide is selected from zirconia and hafnia. The group A and group B cluster-promoting oxide dopants preferably are selected such that the group A dopant has a smaller cationic radius than the primary stabilizer oxide, and so that the primary stabilizer oxide has a small cationic radius than that of the group B dopant.

  13. Gas phase chemistry of N-benzylbenzamides with silver(I) cations: characterization of benzylsilver cation.

    PubMed

    Sun, Hezhi; Jin, Zhe; Quan, Hong; Sun, Cuirong; Pan, Yuanjiang

    2015-03-07

    The benzylsilver cation which emerges from the collisional dissociation of silver(I)-N-benzylbenzamide complexes was characterized by deuterium-labeling experiments, theoretical calculations, breakdown curves and substituent effects. The nucleophilic attack of the carbonyl oxygen on an α-hydrogen results in the generation of the benzylsilver cation, which is competitive to the AgH loss with the α-hydrogen.

  14. Aversive Behavior in the Nematode C. elegans Is Modulated by cGMP and a Neuronal Gap Junction Network

    PubMed Central

    Krzyzanowski, Michelle C.; Wood, Jordan F.; Brueggemann, Chantal; Bowitch, Alexander; Bethke, Mary; L’Etoile, Noelle D.; Ferkey, Denise M.

    2016-01-01

    All animals rely on their ability to sense and respond to their environment to survive. However, the suitability of a behavioral response is context-dependent, and must reflect both an animal’s life history and its present internal state. Based on the integration of these variables, an animal’s needs can be prioritized to optimize survival strategies. Nociceptive sensory systems detect harmful stimuli and allow for the initiation of protective behavioral responses. The polymodal ASH sensory neurons are the primary nociceptors in C. elegans. We show here that the guanylyl cyclase ODR-1 functions non-cell-autonomously to downregulate ASH-mediated aversive behaviors and that ectopic cGMP generation in ASH is sufficient to dampen ASH sensitivity. We define a gap junction neural network that regulates nociception and propose that decentralized regulation of ASH signaling can allow for rapid correlation between an animal’s internal state and its behavioral output, lending modulatory flexibility to this hard-wired nociceptive neural circuit. PMID:27459302

  15. Aversive Behavior in the Nematode C. elegans Is Modulated by cGMP and a Neuronal Gap Junction Network.

    PubMed

    Krzyzanowski, Michelle C; Woldemariam, Sarah; Wood, Jordan F; Chaubey, Aditi H; Brueggemann, Chantal; Bowitch, Alexander; Bethke, Mary; L'Etoile, Noelle D; Ferkey, Denise M

    2016-07-01

    All animals rely on their ability to sense and respond to their environment to survive. However, the suitability of a behavioral response is context-dependent, and must reflect both an animal's life history and its present internal state. Based on the integration of these variables, an animal's needs can be prioritized to optimize survival strategies. Nociceptive sensory systems detect harmful stimuli and allow for the initiation of protective behavioral responses. The polymodal ASH sensory neurons are the primary nociceptors in C. elegans. We show here that the guanylyl cyclase ODR-1 functions non-cell-autonomously to downregulate ASH-mediated aversive behaviors and that ectopic cGMP generation in ASH is sufficient to dampen ASH sensitivity. We define a gap junction neural network that regulates nociception and propose that decentralized regulation of ASH signaling can allow for rapid correlation between an animal's internal state and its behavioral output, lending modulatory flexibility to this hard-wired nociceptive neural circuit.

  16. Influence of lithium cations on prolyl peptide bonds.

    PubMed

    Kunz, Claudia; Jahreis, Günther; Günther, Robert; Berger, Stefan; Fischer, Gunter; Hofmann, Hans-Jörg

    2012-06-01

    The influence of lithium cations on the cis/trans isomerization of prolyl peptide bonds was investigated in a quantitative manner in trifluoroethanol (TFE) and acetonitrile, employing NMR techniques. The focus was on various environmental and structural aspects, such as lithium cation and water concentrations, the type of the partner amino acid in the prolyl peptide bond, and the peptide sequence length. Comparison of the thermodynamic parameters of the isomerization in LiCl/TFE and TFE shows a lithium cation concentration dependence of the cis/trans ratio, which saturates at cation concentrations >200 mM. A pronounced increase in the cis isomer content in the presence of lithium cations occurs with the exception of peptides with Gly-Pro and Asp-Pro moieties. The cation effect appears already at the dipeptide level. The salt concentration can considerably be reduced in solvents with a lower number of nucleophilic centers like acetonitrile. The lithium cation effect decreases with small amounts of water and disappears at a water concentration of about 5%. The isomerization kinetics under the influence of lithium cations suggests a weak cation interaction with the carbonyl oxygen of the peptide bond. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.

  17. Hydrogen molecule defect in proton-conductive SrTiO3 Perovskite

    NASA Astrophysics Data System (ADS)

    Onishi, Taku

    2017-11-01

    In proton-conductive SrTiO3 perovskite, no hydrogen molecule defect ideally exists. However, the unforeseen chemical reaction is often observed after the use of fuel cell. From the viewpoint of battery safety, we have investigated the effect of hydrogen molecule defect by molecular orbital analysis. When counter cation vacancy exists, the activation energy for hydrogen molecule migration was 1.39 - 1.50 eV, which is much smaller than the dissociation energy of hydrogen molecule. It implies that hydrogen molecule may migrate without its dissociation.

  18. Electronic spectra of astrophysically interesting cations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Maier, John P., E-mail: j.p.maier@unibas.ch; Rice, Corey A., E-mail: j.p.maier@unibas.ch; Mazzotti, Fabio J., E-mail: j.p.maier@unibas.ch

    2015-01-22

    The electronic spectra of polyacetylene cations were recorded at 20K in the laboratory in an ion trap instrument. These can then be compared with diffuse interstellar band (DIB) absorptions. Examination of recently published data shows that the attribution of a weak DIB at ∼506.9 nm to diacetylene cation is not justified. Study of the higher excited electronic states of polyacetylene cations shows that their widths can still be sufficiently narrow for consideration as DIB carriers.

  19. How the cation-cation π-π stacking occurs: A theoretical investigation into ionic clusters of imidazolium.

    PubMed

    Gao, Wei; Tian, Yong; Xuan, Xiaopeng

    2015-07-01

    The cation-cation π-π stacking is uncommon but it is essential for the understanding of some supramolecular structures. We explore theoretically the nature of non-covalent interaction occurring in the stacked structure within modeled clusters of 1,3-dimethylimidazolium and halide. The evidences of the energy decomposition analysis (EDA) and reduced density gradient (RDG) approach are different from those of common π-π interaction. Isosurfaces with RDG also illustrate the strength of the titled π-π interaction and their region. Additionally, we find that the occurrence of this interaction is attributed to a few C-H···X interactions, as depicted using atom in molecule (AIM) method. This work presents a clear picture of the typical cation-cation π-π interaction and can serve to advance the understanding of this uncommon interaction. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Impact of monovalent cations on soil structure. Part I. Results of an Iranian soil

    NASA Astrophysics Data System (ADS)

    Farahani, Elham; Emami, Hojat; Keller, Thomas; Fotovat, Amir; Khorassani, Reza

    2018-01-01

    This study investigated the impact of monovalent cations on clay dispersion, aggregate stability, soil pore size distribution, and saturated hydraulic conductivity on agricultural soil in Iran. The soil was incubated with treatment solutions containing different concentrations (0-54.4 mmol l-1) of potassium and sodium cations. The treatment solutions included two levels of electrical conductivity (EC=3 or 6 dS m-1) and six K:Na ratios per electrical conductivity level. At both electrical conductivity levels, spontaneously dispersible clay increased with increasing K concentration, and with increasing K:Na ratio. A negative linear relationship between percentage of water-stable aggregates and spontaneously dispersible clay was observed. Clay dispersion generally reduced the mean pore size, presumably due to clogging of pores, resulting in increased water retention. At both electrical conductivity levels, hydraulic conductivity increased with increasing exchangeable potassium percentage at low exchangeable potassium percentage values, but decreased with further increases in exchangeable potassium percentage at higher exchangeable potassium percentage. This is in agreement with earlier studies, but seems in conflict with our data showing increasing spontaneously dispersible clay with increasing exchangeable potassium percentage. Our findings show that clay dispersion increased with increasing K concentration and increasing K:Na ratio, demonstrating that K can have negative impacts on soil structure.

  1. Cationized Carbohydrate Gas-Phase Fragmentation Chemistry

    NASA Astrophysics Data System (ADS)

    Bythell, Benjamin J.; Abutokaikah, Maha T.; Wagoner, Ashley R.; Guan, Shanshan; Rabus, Jordan M.

    2017-04-01

    We investigate the fragmentation chemistry of cationized carbohydrates using a combination of tandem mass spectrometry, regioselective labeling, and computational methods. Our model system is D-lactose. Barriers to the fundamental glyosidic bond cleavage reactions, neutral loss pathways, and structurally informative cross-ring cleavages are investigated. The most energetically favorable conformations of cationized D-lactose were found to be similar. In agreement with the literature, larger group I cations result in structures with increased cation coordination number which require greater collision energy to dissociate. In contrast with earlier proposals, the B n -Y m fragmentation pathways of both protonated and sodium-cationized analytes proceed via protonation of the glycosidic oxygen with concerted glycosidic bond cleavage. Additionally, for the sodiated congeners our calculations support sodiated 1,6-anhydrogalactose B n ion structures, unlike the preceding literature. This affects the subsequent propensity of formation and prediction of B n /Y m branching ratio. The nature of the anomeric center (α/β) affects the relative energies of these processes, but not the overall ranking. Low-energy cross-ring cleavages are observed for the metal-cationized analytes with a retro-aldol mechanism producing the 0,2 A 2 ion from the sodiated forms . Theory and experiment support the importance of consecutive fragmentation processes, particularly for the protonated congeners at higher collision energies.

  2. Functional involvement of the organic cation transporter 2 (rOct2) in the renal uptake of organic cations in rats.

    PubMed

    Umehara, K-I; Iwatsubo, T; Noguchi, K; Kamimura, H

    2008-01-01

    This study examined the contribution made by organic cation transporters (hOCT/rOct) to the saturable component of the renal uptake of 1-methyl-4-phenylpyridinium, tetraethylammonium (TEA), cimetidine and metformin into rOct2-expressing HEK293 cells and rat kidney slices. All the test compounds accumulated in the rat kidney slices in a carrier-mediated manner. The Michaelis- Menten constant (K(m)) values for saturable uptake of TEA, cimetidine and metformin into rat kidney slices were relatively comparable with those for the rOct2-expressing HEK293 cells. In addition, the relative uptake activity values of TEA, cimetidine and metformin in rat kidney slices were similar to those in rOct2-expressing HEK293 cells. This suggests that the saturable components involved in the renal uptake of TEA, cimetidine and metformin are mediated mainly by rOct2. The saturable uptake profile of cationic compounds into rat kidney can be evaluated in both cDNA-expressing cells and rat kidney slices, as well as the transporter expression pattern. This approach can also be used to estimate the saturable uptake mechanism of cationic compounds into the human kidney when human kidney slices and hOCT2-expressing cells are used.

  3. Ultrasound enhances in vivo tumor expression of plasmid DNA by PEG-introduced cationized dextran.

    PubMed

    Hosseinkhani, Hossein; Tabata, Yasuhiko

    2005-11-28

    This study is an investigation to experimentally confirm whether or not ultrasound (US) irradiation is effective in enhancing the in vivo gene expression of plasmid DNA in tumor. Dextran was cationized by introducing spermine to the hydroxyl groups to allow to polyionically complex with a plasmid DNA. The cationized dextran prepared was additionally modified with poly(ethylene glycol) (PEG) molecules which have an active ester and methoxy groups at each terminal, to obtain cationized dextran with different percentages of PEG introduced. Various cationized dextrans with or without PEG introduction were mixed with a plasmid DNA of LacZ to form cationized dextran-plasmid DNA complexes. Electrophoretical examination revealed that the plasmid DNA was complexed both with the cationized dextran and PEG-introduced cationized dextran, irrespective of the PEG introduction percentage, although the higher N/P ratio was needed for plasmid DNA complexation with the latter. By complexation with the cationized dextran, the zeta potential of plasmid DNA was changed to be positive. The charge of PEG-introduced cationized dextran-plasmid DNA complexes became close to 0 mV as their percentage of PEG introduced increased, although the molecular size was about 250 nm, irrespective of the PEG introduction. When cationized dextran-plasmid DNA complexes with or without PEG introduction were intravenously injected to mice carrying a subcutaneous Meth-AR-1 fibrosarcoma mass and the subsequent US irradiation to the tumor mass percutaneously, the PEG-introduced cationized dextran-plasmid DNA complex plus US irradiation enhanced the tumor level of gene expression to a significantly high extent compared with the cationized dextran-plasmid DNA complex and free plasmid DNA with or without US irradiation. The enhanced level depended on the time period and timing of US irradiation. Fluorescent microscopic studies revealed that the localization of plasmid DNA and the gene expression were observed in

  4. Electrical Conductivity in Transition Metals

    ERIC Educational Resources Information Center

    Talbot, Christopher; Vickneson, Kishanda

    2013-01-01

    The aim of this "Science Note" is to describe how to test the electron-sea model to determine whether it accurately predicts relative electrical conductivity for first-row transition metals. In the electron-sea model, a metal crystal is viewed as a three-dimensional array of metal cations immersed in a sea of delocalised valence…

  5. Discovery of the ammonium substrate site on glutamine synthetase, a third cation binding site.

    PubMed Central

    Liaw, S. H.; Kuo, I.; Eisenberg, D.

    1995-01-01

    Glutamine synthetase (GS) catalyzes the ATP-dependent condensation of ammonia and glutamate to yield glutamine, ADP, and inorganic phosphate in the presence of divalent cations. Bacterial GS is an enzyme of 12 identical subunits, arranged in two rings of 6, with the active site between each pair of subunits in a ring. In earlier work, we have reported the locations within the funnel-shaped active site of the substrates glutamate and ATP and of the two divalent cations, but the site for ammonia (or ammonium) has remained elusive. Here we report the discovery by X-ray crystallography of a binding site on GS for monovalent cations, Tl+ and Cs+, which is probably the binding site for the substrate ammonium ion. Fourier difference maps show the following. (1) Tl+ and Cs+ bind at essentially the same site, with ligands being Glu 212, Tyr 179, Asp 50', Ser 53' of the adjacent subunit, and the substrate glutamate. From its position adjacent to the substrate glutamate and the cofactor ADP, we propose that this monovalent cation site is the substrate ammonium ion binding site. This proposal is supported by enzyme kinetics. Our kinetic measurements show that Tl+, Cs+, and NH4+ are competitive inhibitors to NH2OH in the gamma-glutamyl transfer reaction. (2) GS is a trimetallic enzyme containing two divalent cation sites (n1, n2) and one monovalent cation site per subunit. These three closely spaced ions are all at the active site: the distance between n1 and n2 is 6 A, between n1 and Tl+ is 4 A, and between n2 and Tl+ is 7 A. Glu 212 and the substrate glutamate are bridging ligands for the n1 ion and Tl+. (3) The presence of a monovalent cation in this site may enhance the structural stability of GS, because of its effect of balancing the negative charges of the substrate glutamate and its ligands and because of strengthening the "side-to-side" intersubunit interaction through the cation-protein bonding. (4) The presence of the cofactor ADP increases the Tl+ binding to GS

  6. Cationic influences upon synaptic transmission at the hair cell-afferent fiber synapse of the frog

    NASA Technical Reports Server (NTRS)

    Cochran, S. L.

    1995-01-01

    The concentrations of inorganic cations (K+, Na+, and Ca2+) bathing the isolated frog labyrinth were varied in order to assess their role in influencing and mediating synaptic transmission at the hair cell-afferent fiber synapse. Experiments employed intracellular recordings of synaptic activity from VIIIth nerve afferents. Recordings were digitized continuously at 50 kHz, and excitatory postsynaptic potentials were detected and parameters quantified by computer algorithms. Particular attention was focused on cationic effects upon excitatory postsynaptic potential frequency of occurrence and excitatory postsynaptic potential amplitude, in order to discriminate between pre- and postsynaptic actions. Because the small size of afferents preclude long term stable recordings, alterations in cationic concentrations were applied transiently and their peak effects on synaptic activity were assessed. Increases in extracellular K+ concentration of a few millimolar produced a large increase in the frequency of occurrence of excitatory postsynaptic potentials with little change in amplitude, indicating that release of transmitter from the hair cell is tightly coupled to its membrane potential. Increasing extracellular Na+ concentration resulted in an increase in excitatory postsynaptic potential amplitude with no significant change in excitatory postsynaptic potential frequency of occurrence, suggesting that the transmitter-gated subsynaptic channel conducts Na+ ions. Decreases in extracellular Ca2+ concentration had little effect upon excitatory postsynaptic potential frequency, but increased excitatory postsynaptic potential frequency and amplitude. These findings suggest that at higher concentrations Ca2+ act presynaptically to prevent transmitter release and postsynaptically to prevent Na+ influx during the generation of the excitatory postsynaptic potential. The influences of these ions on synaptic activity at this synapse are remarkably similar to those reported at the

  7. Comparative analysis of cation/proton antiporter superfamily in plants.

    PubMed

    Ye, Chu-Yu; Yang, Xiaohan; Xia, Xinli; Yin, Weilun

    2013-06-01

    The cation/proton antiporter superfamily is associated with the transport of monovalent cations across membranes. This superfamily was annotated in the Arabidopsis genome and some members were functionally characterized. In the present study, a systematic analysis of the cation/proton antiporter genes in diverse plant species was reported. We identified 240 cation/proton antiporters in alga, moss, and angiosperm. A phylogenetic tree was constructed showing these 240 members are separated into three families, i.e., Na(+)/H(+) exchangers, K(+) efflux antiporters, and cation/H(+) exchangers. Our analysis revealed that tandem and/or segmental duplications contribute to the expansion of cation/H(+) exchangers in the examined angiosperm species. Sliding window analysis of the nonsynonymous/synonymous substitution ratios showed some differences in the evolutionary fate of cation/proton antiporter paralogs. Furthermore, we identified over-represented motifs among these 240 proteins and found most motifs are family specific, demonstrating diverse evolution of the cation/proton antiporters among three families. In addition, we investigated the co-expressed genes of the cation/proton antiporters in Arabidopsis thaliana. The results showed some biological processes are enriched in the co-expressed genes, suggesting the cation/proton antiporters may be involved in these biological processes. Taken together, this study furthers our knowledge on cation/proton antiporters in plants. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Molecular dynamics simulation of diffusion and electrical conductivity in montmorillonite interlayers

    DOE PAGES

    Greathouse, Jeffery A.; Cygan, Randall T.; Fredrich, Joanne T.; ...

    2016-01-20

    In this study, the diffusion of water and ions in the interlayer region of smectite clay minerals represents a direct probe of the type and strength of clay–fluid interactions. Interlayer diffusion also represents an important link between molecular simulation and macroscopic experiments. Here we use molecular dynamics simulation to investigate trends in cation and water diffusion in montmorillonite interlayers, looking specifically at the effects of layer charge, interlayer cation and cation charge (sodium or calcium), water content, and temperature. For Na-montmorillonite, the largest increase in ion and water diffusion coefficients occurs between the one-layer and two-layer hydrates, corresponding to themore » transition from inner-sphere to outer-sphere surface complexes. Calculated activation energies for ion and water diffusion in Na-montmorillonite are similar to each other and to the water hydrogen bond energy, suggesting the breaking of water–water and water–clay hydrogen bonds as a likely mechanism for interlayer diffusion. A comparison of interlayer diffusion with that of bulk electrolyte solutions reveals a clear trend of decreasing diffusion coefficient with increasing electrolyte concentration, and in most cases the interlayer diffusion results are nearly coincident with the corresponding bulk solutions. Trends in electrical conductivities computed from the ion diffusion coefficients are also compared.« less

  9. Dielectric relaxation and conduction mechanism studies of BNT-BT-BKT ceramics

    NASA Astrophysics Data System (ADS)

    Chandrasekhar, M.; Khatua, Dipak Kumar; Pattanayak, Ranjit; Kumar, P.

    2017-12-01

    Electrical properties of 0.884Bi0.5Na0.5TiO3-0.036BaTiO3-0.08Bi0.5K0.5TiO3 ceramic samples were investigated in 100Hz to 1 MHz frequency range and in 200-450 °C temperature range using impedance spectroscopy technique. Real part of impedance versus frequency plots in lower frequency region revealed its PTCR behavior and NTCR behaviors in higher frequency region. Impedance study also suggested the presence of non-Debye type relaxation mechanism. Cole-Cole plots suggested two relaxation regions, in which grain and grain, grain boundary effects were prominent in lower and high temperature regions, respectively. DC conductivity followed Arrhenius law with an activation energy of ∼0.79 and 1.2 eV, which suggested that the charge carrier were cation vacancies in lower temperature region whereas cation vacancies and oxygen vacancies in higher temperature region.

  10. Antimicrobial activity and interactions of cationic peptides derived from Galleria mellonella cecropin D-like peptide with model membranes.

    PubMed

    Oñate-Garzón, José; Manrique-Moreno, Marcela; Trier, Steven; Leidy, Chad; Torres, Rodrigo; Patiño, Edwin

    2017-03-01

    Antimicrobial peptides are effector molecules of the innate immune system against invading pathogens. The cationic charge in their structures has a strong correlation with antimicrobial activity, being responsible for the initial electrostatic interaction between peptides and the anionic microbial surface. This paper contains evidence that charge modification in the neutral peptide Gm cecropin D-like (WT) improved the antimicrobial activity of the modified peptides. Two cationic peptides derived from WT sequence named as ΔM1 and ΔM2, with net charge of +5 and +9, respectively, showed at least an eightfold increase in their antimicrobial activity in comparison to WT. The mechanism of action of these peptides was investigated using small unilamellar vesicles (SUVs) as model membranes. To study permeabilization effects of the peptides on cell membranes, entrapped calcein liposomes were used and the results showed that all peptides induced calcein release from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) SUVs, whereas in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), POPC/POPG and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE)/POPG SUVs, only ΔM1 and ΔM2 induced a notable permeabilization. In addition, interactions of these peptides with phospholipids at the level of the glycerol backbone and hydrophobic domain were studied through observed changes in generalized polarization and fluorescence anisotropy using probes such as Laurdan and DPH, respectively. The results suggest that peptides slightly ordered the bilayer structure at the level of glycerol backbone and on the hydrophobic core in 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) SUVs, whereas in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/DMPG SUVs, only ΔM1 and ΔM2 peptides increased the order of bilayers. Thus, peptides would be inducing clustering of phospholipids creating phospholipid domains with a higher phase transition temperature.

  11. Atrial natriuretic peptide induces acrosomal exocytosis in bovine spermatozoa.

    PubMed

    Zamir, N; Barkan, D; Keynan, N; Naor, Z; Breitbart, H

    1995-08-01

    The induction of acrosomal exocytosis in capacitated bull spermatozoa by atrial natriuretic peptide (ANP) was studied in vitro. ANP markedly stimulated acrosomal exocytosis in a calcium-dependent manner. Typically, ANP exerts its action via activation of the ANP receptor (ANPR-A), a particulate guanylyl cyclase-linked receptor, and subsequent formation of guanosine 3',5'-cyclic monophosphate (cGMP). We found that the ANP-induced acrosome reaction was inhibited by the competitive ANPR-A receptor antagonist-anantin, indicating a receptor-mediated effect. We could mimic the effect of ANP on the acrosome reaction by using 8-bromo-cGMP, suggesting that cGMP may serve as a signal transducer mediating the acrosome reaction. Indeed, the ANP-induced acrosome reaction was associated with elevation of cGMP levels. cGMP can also be formed by activation of the soluble form of guanylyl cyclase. Sodium nitroprusside (SNP) stimulated cGMP accumulation and acrosome reaction of capacitated spermatozoa. Thus ANP and the nitric oxide-releasing compound SNP, via activation of guanylyl cyclase (the former activating the particulate and the latter activating the soluble form of the enzyme), may play a significant role in the induction of the acrosome reaction.

  12. Oxidative cyclization reactions: controlling the course of a radical cation-derived reaction with the use of a second nucleophile.

    PubMed

    Redden, Alison; Perkins, Robert J; Moeller, Kevin D

    2013-12-02

    Construction of new ring systems: Oxidative cyclizations (see picture; RVC=reticulated vitreous carbon) have been conducted that use two separate intramolecular nucleophiles to trap an enol ether-derived radical cation intermediate. The reactions provide a means for rapidly trapping the radical cation intermediate in a manner that avoids competitive decomposition reactions. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Conductive hydrogel containing 3-ionene

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor); Yen, Shiao-Ping Siao (Inventor)

    1977-01-01

    Cationic polyelectrolytes formed by the polymerization in absence of oxygen of a monomer of the general formula: dispersed ##STR1## where x is 3 or more than 6 and Z is I, Br or Cl to form high charge density linear polymers are dispered in a water-soluble polymer such as polyvinyl alcohol to form a conductive hydrogel.

  14. Understanding the impact of the central atom on the ionic liquid behavior: phosphonium vs ammonium cations.

    PubMed

    Carvalho, Pedro J; Ventura, Sónia P M; Batista, Marta L S; Schröder, Bernd; Gonçalves, Fernando; Esperança, José; Mutelet, Fabrice; Coutinho, João A P

    2014-02-14

    The influence of the cation's central atom in the behavior of pairs of ammonium- and phosphonium-based ionic liquids was investigated through the measurement of densities, viscosities, melting temperatures, activity coefficients at infinite dilution, refractive indices, and toxicity against Vibrio fischeri. All the properties investigated are affected by the cation's central atom nature, with ammonium-based ionic liquids presenting higher densities, viscosities, melting temperatures, and enthalpies. Activity coefficients at infinite dilution show the ammonium-based ionic liquids to present slightly higher infinite dilution activity coefficients for non-polar solvents, becoming slightly lower for polar solvents, suggesting that the ammonium-based ionic liquids present somewhat higher polarities. In good agreement these compounds present lower toxicities than the phosphonium congeners. To explain this behavior quantum chemical gas phase DFT calculations were performed on isolated ion pairs at the BP-TZVP level of theory. Electronic density results were used to derive electrostatic potentials of the identified minimum conformers. Electrostatic potential-derived CHelpG and Natural Population Analysis charges show the P atom of the tetraalkylphosphonium-based ionic liquids cation to be more positively charged than the N atom in the tetraalkylammonium-based analogous IL cation, and a noticeable charge delocalization occurring in the tetraalkylammonium cation, when compared with the respective phosphonium congener. It is argued that this charge delocalization is responsible for the enhanced polarity observed on the ammonium based ionic liquids explaining the changes in the thermophysical properties observed.

  15. Understanding the impact of the central atom on the ionic liquid behavior: Phosphonium vs ammonium cations

    NASA Astrophysics Data System (ADS)

    Carvalho, Pedro J.; Ventura, Sónia P. M.; Batista, Marta L. S.; Schröder, Bernd; Gonçalves, Fernando; Esperança, José; Mutelet, Fabrice; Coutinho, João A. P.

    2014-02-01

    The influence of the cation's central atom in the behavior of pairs of ammonium- and phosphonium-based ionic liquids was investigated through the measurement of densities, viscosities, melting temperatures, activity coefficients at infinite dilution, refractive indices, and toxicity against Vibrio fischeri. All the properties investigated are affected by the cation's central atom nature, with ammonium-based ionic liquids presenting higher densities, viscosities, melting temperatures, and enthalpies. Activity coefficients at infinite dilution show the ammonium-based ionic liquids to present slightly higher infinite dilution activity coefficients for non-polar solvents, becoming slightly lower for polar solvents, suggesting that the ammonium-based ionic liquids present somewhat higher polarities. In good agreement these compounds present lower toxicities than the phosphonium congeners. To explain this behavior quantum chemical gas phase DFT calculations were performed on isolated ion pairs at the BP-TZVP level of theory. Electronic density results were used to derive electrostatic potentials of the identified minimum conformers. Electrostatic potential-derived CHelpG and Natural Population Analysis charges show the P atom of the tetraalkylphosphonium-based ionic liquids cation to be more positively charged than the N atom in the tetraalkylammonium-based analogous IL cation, and a noticeable charge delocalization occurring in the tetraalkylammonium cation, when compared with the respective phosphonium congener. It is argued that this charge delocalization is responsible for the enhanced polarity observed on the ammonium based ionic liquids explaining the changes in the thermophysical properties observed.

  16. Screening for High Conductivity/Low Viscosity Ionic Liquids Using Product Descriptors.

    PubMed

    Martin, Shawn; Pratt, Harry D; Anderson, Travis M

    2017-07-01

    We seek to optimize Ionic liquids (ILs) for application to redox flow batteries. As part of this effort, we have developed a computational method for suggesting ILs with high conductivity and low viscosity. Since ILs consist of cation-anion pairs, we consider a method for treating ILs as pairs using product descriptors for QSPRs, a concept borrowed from the prediction of protein-protein interactions in bioinformatics. We demonstrate the method by predicting electrical conductivity, viscosity, and melting point on a dataset taken from the ILThermo database on June 18 th , 2014. The dataset consists of 4,329 measurements taken from 165 ILs made up of 72 cations and 34 anions. We benchmark our QSPRs on the known values in the dataset then extend our predictions to screen all 2,448 possible cation-anion pairs in the dataset. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Screening for High Conductivity/Low Viscosity Ionic Liquids Using Product Descriptors

    DOE PAGES

    Martin, Shawn; Pratt, III, Harry D.; Anderson, Travis M.

    2017-02-21

    We seek to optimize Ionic liquids (ILs) for application to redox flow batteries. As part of this effort, we have developed a computational method for suggesting ILs with high conductivity and low viscosity. Since ILs consist of cation-anion pairs, we consider a method for treating ILs as pairs using product descriptors for QSPRs, a concept borrowed from the prediction of protein-protein interactions in bioinformatics. We demonstrate the method by predicting electrical conductivity, viscosity, and melting point on a dataset taken from the ILThermo database on June 18th, 2014. The dataset consists of 4,329 measurements taken from 165 ILs made upmore » of 72 cations and 34 anions. In conclusion, we benchmark our QSPRs on the known values in the dataset then extend our predictions to screen all 2,448 possible cation-anion pairs in the dataset.« less

  18. Screening for High Conductivity/Low Viscosity Ionic Liquids Using Product Descriptors

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Martin, Shawn; Pratt, III, Harry D.; Anderson, Travis M.

    We seek to optimize Ionic liquids (ILs) for application to redox flow batteries. As part of this effort, we have developed a computational method for suggesting ILs with high conductivity and low viscosity. Since ILs consist of cation-anion pairs, we consider a method for treating ILs as pairs using product descriptors for QSPRs, a concept borrowed from the prediction of protein-protein interactions in bioinformatics. We demonstrate the method by predicting electrical conductivity, viscosity, and melting point on a dataset taken from the ILThermo database on June 18th, 2014. The dataset consists of 4,329 measurements taken from 165 ILs made upmore » of 72 cations and 34 anions. In conclusion, we benchmark our QSPRs on the known values in the dataset then extend our predictions to screen all 2,448 possible cation-anion pairs in the dataset.« less

  19. Pentavalent neptunyl ([OΞNpΞO] +) cation–cation interactions in aqueous/polar organic mixed-solvent media

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Burn, Adam G.; Martin, Leigh R.; Nash, Kenneth L.

    Bonding interactions between polyvalent cations and oxo-anions are well known and characterized by predictably favorable Gibbs energies in solution-phase coordination chemistry. In contrast, interactions between ions of like charge are generally expected to be repulsive and strongly influenced by cation solvation. An exception to this instinctive rule is found in the existence of complexes resulting from interactions of pentavalent actinyl cations ([O≡An≡O] +) with selected polyvalent cations. Such cation–cation complexes have been known to exist since the 1960s, when they were first reported by Sullivan and co-workers. The weak actinyl cation–cation complex, resulting from a bonding interaction between a pentavalentmore » linear dioxo actinyl cation donor and hexavalent actinyl or trivalent/tetravalent metal cation acceptor, has been most commonly seen in media in which water activities are reduced, principally highly-salted aqueous media. Such interactions of pentavalent actinides are of relevance in ongoing research that focuses on advanced nuclear fuel processing systems based on the upper oxidation states of americium. This investigation focuses on exploring the thermodynamic stability of complexes between selected highly-charged metal cations (Al 3+, Sc 3+, Cr 3+, Fe 3+, In 3+ and UO 2+ 2) and the pentavalent neptunyl cation (NpO + 2, whose coordination chemistry is similar to that of AmO + 2 while exhibiting significantly greater oxidation state stability) in aqueous–polar organic mixed-solvents. As a result, the Gibbs energies for the cation–cation complexation reactions are correlated with general features of electrostatic bonding models; the NpO + 2 • Cr 3+ complex exhibits unexpectedly strong interactions that may indicate significant covalency in the cation–cation bonding interaction.« less

  20. Pentavalent neptunyl ([OΞNpΞO] +) cation–cation interactions in aqueous/polar organic mixed-solvent media

    DOE PAGES

    Burn, Adam G.; Martin, Leigh R.; Nash, Kenneth L.

    2017-06-17

    Bonding interactions between polyvalent cations and oxo-anions are well known and characterized by predictably favorable Gibbs energies in solution-phase coordination chemistry. In contrast, interactions between ions of like charge are generally expected to be repulsive and strongly influenced by cation solvation. An exception to this instinctive rule is found in the existence of complexes resulting from interactions of pentavalent actinyl cations ([O≡An≡O] +) with selected polyvalent cations. Such cation–cation complexes have been known to exist since the 1960s, when they were first reported by Sullivan and co-workers. The weak actinyl cation–cation complex, resulting from a bonding interaction between a pentavalentmore » linear dioxo actinyl cation donor and hexavalent actinyl or trivalent/tetravalent metal cation acceptor, has been most commonly seen in media in which water activities are reduced, principally highly-salted aqueous media. Such interactions of pentavalent actinides are of relevance in ongoing research that focuses on advanced nuclear fuel processing systems based on the upper oxidation states of americium. This investigation focuses on exploring the thermodynamic stability of complexes between selected highly-charged metal cations (Al 3+, Sc 3+, Cr 3+, Fe 3+, In 3+ and UO 2+ 2) and the pentavalent neptunyl cation (NpO + 2, whose coordination chemistry is similar to that of AmO + 2 while exhibiting significantly greater oxidation state stability) in aqueous–polar organic mixed-solvents. As a result, the Gibbs energies for the cation–cation complexation reactions are correlated with general features of electrostatic bonding models; the NpO + 2 • Cr 3+ complex exhibits unexpectedly strong interactions that may indicate significant covalency in the cation–cation bonding interaction.« less

  1. Vinpocetine regulates cation channel permeability of inner retinal neurons in the ischaemic retina.

    PubMed

    Nivison-Smith, Lisa; Acosta, Monica L; Misra, Stuti; O'Brien, Brendan J; Kalloniatis, Michael

    2014-01-01

    Vinpocetine is a natural drug which exerts neuroprotective effects in ischaemia of the brain through actions on cation channels, glutamate receptors and other pathways. This study investigated the effect of vinpocetine on cation channel permeability of inner retinal neurons after acute retinal metabolic insult. We focused on amacrine and ganglion cells immunoreactive for calretinin or parvalbumin due to their previously documented susceptibility to ischaemia. Using the probe, 1-amino-4-guanidobutane (AGB), we observed increased cation channel permeability across amacrine and ganglion cells under ischaemia and hypoglycaemia but not anoxia. Calretinin and parvalbumin immunoreactivity was also reduced during ischaemia and hypoglyacemia but not anoxia. Vinpocetine decreased AGB entry into ischaemic and hypoglycaemic ganglion cells indicating that the drug can modulate unregulated cation entry. In addition, vinpocetine prevented the loss of calretinin and parvalbumin immunoreactivity following ischaemia suggesting it may indirectly regulate intracellular calcium. Vinpocetine also reduced AGB permeability in selected amacrine and ganglion cell populations following N-methyl-D-aspartate (NMDA) but not kainate activation suggesting that vinpocetine's regulation of cation channel permeability may partly involve NMDA sensitive glutamate receptors. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. First Cationic Uranyl-Organic Framework with Anion-Exchange Capabilities.

    PubMed

    Bai, Zhuanling; Wang, Yanlong; Li, Yuxiang; Liu, Wei; Chen, Lanhua; Sheng, Daopeng; Diwu, Juan; Chai, Zhifang; Albrecht-Schmitt, Thomas E; Wang, Shuao

    2016-07-05

    By controlling the extent of hydrolysis during the self-assembly process of a zwitterionic-based ligand with uranyl cations, we observed a structural evolution from the neutral uranyl-organic framework [(UO2)2(TTTPC)(OH)O(COOH)]·1.5DMF·7H2O (SCU-6) to the first cationic uranyl-organic framework with the formula of [(UO2)(HTTTPC)(OH)]Br·1.5DMF·4H2O (SCU-7). The crystal structures of SCU-6 and SCU-7 are layers built with tetranuclear and dinuclear uranyl clusters, respectively. Exchangeable halide anions are present in the interlaminar spaces balancing the positive charge of layers in SCU-7. Therefore, SCU-7 is able to effectively remove perrhenate anions from aqueous solution. Meanwhile, the H2PO4(-)-exchanged SCU-7 material exhibits a moderate proton conductivity of 8.70 × 10(-5) S cm(-1) at 50 °C and 90% relative humidity, representing nearly 80 times enhancement compared to the original material.

  3. Mechanism of cAMP Partial Agonism in Protein Kinase G (PKG)*♦

    PubMed Central

    VanSchouwen, Bryan; Selvaratnam, Rajeevan; Giri, Rajanish; Lorenz, Robin; Herberg, Friedrich W.; Kim, Choel; Melacini, Giuseppe

    2015-01-01

    Protein kinase G (PKG) is a major receptor of cGMP and controls signaling pathways often distinct from those regulated by cAMP. Hence, the selective activation of PKG by cGMP versus cAMP is critical. However, the mechanism of cGMP-versus-cAMP selectivity is only limitedly understood. Although the C-terminal cyclic nucleotide-binding domain B of PKG binds cGMP with higher affinity than cAMP, the intracellular concentrations of cAMP are typically higher than those of cGMP, suggesting that the cGMP-versus-cAMP selectivity of PKG is not controlled uniquely through affinities. Here, we show that cAMP is a partial agonist for PKG, and we elucidate the mechanism for cAMP partial agonism through the comparative NMR analysis of the apo, cGMP-, and cAMP-bound forms of the PKG cyclic nucleotide-binding domain B. We show that although cGMP activation is adequately explained by a two-state conformational selection model, the partial agonism of cAMP arises from the sampling of a third, partially autoinhibited state. PMID:26370085

  4. Claudin-2-mediated cation and water transport share a common pore

    PubMed Central

    Rosenthal, Rita; Günzel, Dorothee; Krug, Susanne M.; Schulzke, Jörg-Dieter; Fromm, Michael; Yu, Alan S.L.

    2016-01-01

    Aim Claudin-2 is a tight junction protein typically located in “leaky” epithelia exhibiting large paracellular permeabilities like small intestine and proximal kidney tubule. Former studies revealed that claudin-2 forms paracellular channels for small cations like sodium and potassium and also paracellular channels for water. This study analyzes whether the diffusive transport of sodium and water occurs through a common pore of the claudin-2 channel. Methods Wild-type claudin-2 and different claudin-2 mutants were expressed in MDCK I kidney tubule cells using an inducible system. Ion and water permeability and the effect of blocking reagents on both were investigated on different clones of the mutants. Results Neutralization of a negatively charged cation interaction site in the pore with the mutation, D65N, decreased both, sodium permeability and water permeability. Claudin-2 mutants (I66C and S68C) with substitution of the pore-lining amino acids with cysteine were used to test the effect of steric blocking of the claudin-2 pore by thiol-reactive reagents. Addition of thiol-reactive reagents to these mutants simultaneously decreased conductance and water permeability. Remarkably, all experimental perturbations caused parallel changes in ion conductance and water permeability, disproving different or independent passage pathways. Conclusion Our results indicate that claudin-2-mediated cation and water transport are frictionally coupled and share a common pore. This pore is lined and determined in permeability by amino acid residues of the first extracellular loop of claudin-2. PMID:27359349

  5. Complex conductivity of oil-contaminated clayey soils

    NASA Astrophysics Data System (ADS)

    Deng, Y.; Revil, A.; Shi, X.

    2017-12-01

    Non-intrusive hydrogeophysical techniques have been wildly applied to detect organic contaminants because of the difference of electrical properties for contaminated soil. Among them, spectral induced polarization (SIP) has emerged as a promising tool for the identification of contamination due to its sensitivity to the chemistry of pore water, solid-fluid interfaces and fluid content. Previous works have investigated the influences of oil on the electrical signatures of porous media, which demonstrated the potentials of SIP in the detection of hydrocarbon contamination. However, few works have done on the SIP response of oil in clayey soils. In this study, we perform a set of SIP measurements on the clayey samples under different water saturations. These clayey soils are characterized by relatively high cation exchange capacity. The objective in this work is to test the empirical relationships between the three exponents, including the cementation exponent (m), the saturation exponent (n) and the quadrature conductivity exponent (p), which is expected to reduce the model parameters needed in geophysical and hydraulic properties predictions. Our results show that the complex conductivity are saturation dependent. The magnitude of both in-phase and quadrature conductivities generally decrease with decreasing water saturation. The shape of quadrature conductivity spectra slightly changes when water saturation decreases in some cases. The saturation exponent slightly increases with cation exchange capacity, specific surface area and clay content, with an average value around 2.05. Compared to saturation exponent, the quadrature conductivity exponent apparently increases with cation exchange capacity and specific surface area while has little to do with the clay content. Further, the results indicate that the quadrature conductivity exponent p does not strictly obey to p=n-1 as proposed by Vinegar and Waxman (1984). Instead, it mostly ranges between p=n-1.5 and p=n-0

  6. 78 FR 17215 - Agency Information Collection Activities: Proposed Collection; Comment Request; Current Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-20

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0242... (CGMP) for positron emission tomography (PET) drugs. DATES: Submit either electronic or written comments... product. FDA's CGMP regulations at 21 CFR part 212 are intended to ensure that PET drug products meet the...

  7. Heavy metal cations permeate the TRPV6 epithelial cation channel.

    PubMed

    Kovacs, Gergely; Danko, Tamas; Bergeron, Marc J; Balazs, Bernadett; Suzuki, Yoshiro; Zsembery, Akos; Hediger, Matthias A

    2011-01-01

    TRPV6 belongs to the vanilloid family of the transient receptor potential channel (TRP) superfamily. This calcium-selective channel is highly expressed in the duodenum and the placenta, being responsible for calcium absorption in the body and fetus. Previous observations have suggested that TRPV6 is not only permeable to calcium but also to other divalent cations in epithelial tissues. In this study, we tested whether TRPV6 is indeed also permeable to cations such as zinc and cadmium. We found that the basal intracellular calcium concentration was higher in HEK293 cells transfected with hTRPV6 than in non-transfected cells, and that this difference almost disappeared in nominally calcium-free solution. Live cell imaging experiments with Fura-2 and NewPort Green DCF showed that overexpression of human TRPV6 increased the permeability for Ca(2+), Ba(2+), Sr(2+), Mn(2+), Zn(2+), Cd(2+), and interestingly also for La(3+) and Gd(3+). These results were confirmed using the patch clamp technique. (45)Ca uptake experiments showed that cadmium, lanthanum and gadolinium were also highly efficient inhibitors of TRPV6-mediated calcium influx at higher micromolar concentrations. Our results suggest that TRPV6 is not only involved in calcium transport but also in the transport of other divalent cations, including heavy metal ions, which may have toxicological implications. Copyright © 2010 Elsevier Ltd. All rights reserved.

  8. The ferrous iron-responsive BqsRS two-component system activates genes that promote cationic stress tolerance.

    PubMed

    Kreamer, Naomi N; Costa, Flavia; Newman, Dianne K

    2015-02-24

    The physiological resistance of pathogens to antimicrobial treatment is a severe problem in the context of chronic infections. For example, the mucus-filled lungs of cystic fibrosis (CF) patients are readily colonized by diverse antibiotic-resistant microorganisms, including Pseudomonas aeruginosa. Previously, we showed that bioavailable ferrous iron [Fe(II)] is present in CF sputum at all stages of infection and constitutes a significant portion of the iron pool at advanced stages of lung function decline [R. C. Hunter et al., mBio 4(4):e00557-13, 2013]. P. aeruginosa, a dominant CF pathogen, senses Fe(II) using a two-component signal transduction system, BqsRS, which is transcriptionally active in CF sputum [R. C. Hunter et al., mBio 4(4):e00557-13, 2013; N. N. Kreamer, J. C. Wilks, J. J. Marlow, M. L. Coleman, and D. K. Newman, J Bacteriol 194:1195-1204, 2012]. Here, we show that an RExxE motif in BqsS is required for BqsRS activation. Once Fe(II) is sensed, BqsR binds a tandem repeat DNA sequence, activating transcription. The BqsR regulon--defined through iterative bioinformatic predictions and experimental validation--includes several genes whose products are known to drive antibiotic resistance to aminoglycosides and polymyxins. Among them are genes encoding predicted determinants of polyamine transport and biosynthesis. Compared to the wild type, bqsS and bqsR deletion mutants are sensitive to high levels of Fe(II), produce less spermidine in high Fe(II), and are more sensitive to tobramycin and polymyxin B but not arsenate, chromate, or cefsulodin. BqsRS thus mediates a physiological response to Fe(II) that guards the cell against positively charged molecules but not negatively charged stressors. These results suggest Fe(II) is an important environmental signal that, via BqsRS, bolsters tolerance of a variety of cationic stressors, including clinically important antimicrobial agents. Clearing chronic infections is challenging due to the physiological

  9. Case study II: application of the divalent cation bridging theory to improve biofloc properties and industrial activated sludge system performance-using alternatives to sodium-based chemicals.

    PubMed

    Higgins, Matthew J; Sobeck, David C; Owens, Steven J; Szabo, Lynn M

    2004-01-01

    The objective of this study was to investigate the application of the divalent cation bridging theory (DCBT) as a tool in the chemical selection process at an activated sludge plant to improve settling, dewatering, and effluent quality. According to the DCBT, to achieve improvements, the goal of chemical selection should be to reduce the ratio of monovalent-to-divalent (M/D) cations. A study was conducted to determine the effect of using magnesium hydroxide [Mg(OH)2] as an alternative to sodium hydroxide (NaOH) at a full-scale industrial wastewater treatment plant. Floc properties and treatment plant performance were measured for approximately one year during two periods of NaOH addition and Mg(OH)2 addition. A cost analysis of plant operation during NaOH and Mg(OH)2 use was also performed. During NaOH addition, the M/D ratio was 48, while, during Mg(OH)2 addition, this ratio was reduced to an average of approximately 0.1. During the Mg(OH)2 addition period, the sludge volume index, effluent total suspended solids, and effluent chemical oxygen demand were reduced by approximately 63, 31, and 50%, respectively, compared to the NaOH addition period. The alum and polymer dose used for clarification was reduced by approximately 50 and 60%, respectively, during Mg(OH)2 addition. The dewatering properties of the activated sludge improved dewatering as measured by decreased capillary suction time and specific resistance to filtration (SRF), along with an increase in cake solids from the SRF test. This corresponded to a reduction in the volume of solids thickened by centrifuges at the treatment plant, which reduced the disposal costs of solids. Considering the costs for chemicals and solids disposal, the annual cost of using Mg(OH)2 was approximately 30,000 dollars to 115,000 dollars less than using NaOH, depending on the pricing of NaOH. The results of this study confirm that the DCBT is a useful tool for assessing chemical-addition strategies and their potential effect

  10. On the permeation of large organic cations through the pore of ATP-gated P2X receptors

    PubMed Central

    Harkat, Mahboubi; Peverini, Laurie; Dunning, Kate; Beudez, Juline; Martz, Adeline; Calimet, Nicolas; Specht, Alexandre; Cecchini, Marco; Chataigneau, Thierry; Grutter, Thomas

    2017-01-01

    Pore dilation is thought to be a hallmark of purinergic P2X receptors. The most commonly held view of this unusual process posits that under prolonged ATP exposure the ion pore expands in a striking manner from an initial small-cation conductive state to a dilated state, which allows the passage of larger synthetic cations, such as N-methyl-d-glucamine (NMDG+). However, this mechanism is controversial, and the identity of the natural large permeating cations remains elusive. Here, we provide evidence that, contrary to the time-dependent pore dilation model, ATP binding opens an NMDG+-permeable channel within milliseconds, with a conductance that remains stable over time. We show that the time course of NMDG+ permeability superimposes that of Na+ and demonstrate that the molecular motions leading to the permeation of NMDG+ are very similar to those that drive Na+ flow. We found, however, that NMDG+ “percolates” 10 times slower than Na+ in the open state, likely due to a conformational and orientational selection of permeating molecules. We further uncover that several P2X receptors, including those able to desensitize, are permeable not only to NMDG+ but also to spermidine, a large natural cation involved in ion channel modulation, revealing a previously unrecognized P2X-mediated signaling. Altogether, our data do not support a time-dependent dilation of the pore on its own but rather reveal that the open pore of P2X receptors is wide enough to allow the permeation of large organic cations, including natural ones. This permeation mechanism has considerable physiological significance. PMID:28442564

  11. (4 + 3) Cycloadditions of Nitrogen-Stabilized Oxyallyl Cations

    PubMed Central

    Lohse, Andrew G.; Hsung, Richard P.

    2011-01-01

    The use of heteroatom-substituted oxyallyl cations in (4 + 3) cycloadditions has had a tremendous impact on the development of cycloaddition chemistry. Extensive efforts have been exerted toward investigating the effect of oxygen-, sulfur-, and halogen-substituents on the reactivity of oxyallyl cations. Most recently, the use of nitrogen-stabilized oxyallyl cations has gained prominence in the area of (4 + 3) cycloadditions. The following article will provide an overview of this concept utilizing nitrogen-stabilized oxyallyl cations. PMID:21384451

  12. The DEG/ENaC cation channel protein UNC-8 drives activity-dependent synapse removal in remodeling GABAergic neurons

    PubMed Central

    Miller-Fleming, Tyne W; Petersen, Sarah C; Manning, Laura; Matthewman, Cristina; Gornet, Megan; Beers, Allison; Hori, Sayaka; Mitani, Shohei; Bianchi, Laura; Richmond, Janet; Miller, David M

    2016-01-01

    Genetic programming and neural activity drive synaptic remodeling in developing neural circuits, but the molecular components that link these pathways are poorly understood. Here we show that the C. elegans Degenerin/Epithelial Sodium Channel (DEG/ENaC) protein, UNC-8, is transcriptionally controlled to function as a trigger in an activity-dependent mechanism that removes synapses in remodeling GABAergic neurons. UNC-8 cation channel activity promotes disassembly of presynaptic domains in DD type GABA neurons, but not in VD class GABA neurons where unc-8 expression is blocked by the COUP/TF transcription factor, UNC-55. We propose that the depolarizing effect of UNC-8-dependent sodium import elevates intracellular calcium in a positive feedback loop involving the voltage-gated calcium channel UNC-2 and the calcium-activated phosphatase TAX-6/calcineurin to initiate a caspase-dependent mechanism that disassembles the presynaptic apparatus. Thus, UNC-8 serves as a link between genetic and activity-dependent pathways that function together to promote the elimination of GABA synapses in remodeling neurons. DOI: http://dx.doi.org/10.7554/eLife.14599.001 PMID:27403890

  13. Plant rhamnogalacturonan II complexation of heavy metal cations

    DOEpatents

    O`Neill, M.A.; Pellerin, P.J.M.; Warrenfeltz, D.; Vidal, S.; Darvill, A.G.; Albersheim, P.

    1999-03-02

    The present invention provides rhamnogalacturonan-II (RG-II) and relates to its ability to complex specific multivalent heavy metal cations. In the presence of boric acid, RG-II monomers form dimers that are cross-linked by a borate ester. The yield of such borate ester cross-linked dimers of RG-II is enhanced in the presence of specific heavy metal cations. The present invention further relates to the utility of RG-II in assays for the detection of specific heavy metal contamination; as a reagent useful in the removal of specific heavy metal cations contaminating foods and liquids, for example, fish, wines, etc.; as a pharmaceutical composition useful as an antidote in specific heavy metal cation poisoning; as a treatment for the detoxification of specific heavy metal cations from blood and/or tissues; and in a method of remediation of waters and soils contaminated with specific heavy metal cations. 15 figs.

  14. Plant rhamnogalacturonan II complexation of heavy metal cations

    DOEpatents

    O'Neill, Malcolm A.; Pellerin, Patrice J. M.; Warrenfeltz, Dennis; Vidal, Stephane; Darvill, Alan G.; Albersheim, Peter

    1999-01-01

    The present invention provides rhamnogalacturonan-II (RG-II) and relates to its ability to complex specific multivalent heavy metal cations. In the presence of boric acid, RG-II monomers form dimers that are cross-linked by a borate ester. The yield of such borate ester cross-linked dimers of RG-II is enhanced in the presence of specific heavy metal cations. The present invention further relates to the utility of RG-II in assays for the detection of specific heavy metal contamination; as a reagent useful in the removal of specific heavy metal cations contaminating foods and liquids, for example, fish, wines, etc.; as a pharmaceutical composition useful as an antidote in specific heavy metal cation poisoning; as a treatment for the detoxification of specific heavy metal cations from blood and/or tissues; and in a method of remediation of waters and soils contaminated with specific heavy metal cations.

  15. Membrane stress increases cation permeability in red cells.

    PubMed

    Johnson, R M

    1994-11-01

    The human red cell is known to increase its cation permeability when deformed by mechanical forces. Light-scattering measurements were used to quantitate the cell deformation, as ellipticity under shear. Permeability to sodium and potassium was not proportional to the cell deformation. An ellipticity of 0.75 was required to increase the permeability of the membrane to cations, and flux thereafter increased rapidly as the limits of cell extension were reached. Induction of membrane curvature by chemical agents also did not increase cation permeability. These results indicate that membrane deformation per se does not increase permeability, and that membrane tension is the effector for increased cation permeability. This may be relevant to some cation permeabilities observed by patch clamping.

  16. Anomalous frequency-dependent ionic conductivity of lesion-laden human-brain tissue

    NASA Astrophysics Data System (ADS)

    Emin, David; Akhtari, Massoud; Fallah, Aria; Vinters, Harry V.; Mathern, Gary W.

    2017-10-01

    We study the effect of lesions on our four-electrode measurements of the ionic conductivity of (˜1 cm3) samples of human brain excised from patients undergoing pediatric epilepsy surgery. For most (˜94%) samples, the low-frequency ionic conductivity rises upon increasing the applied frequency. We attributed this behavior to the long-range (˜0.4 mm) diffusion of solvated sodium cations before encountering intrinsic impenetrable blockages such as cell membranes, blood vessels, and cell walls. By contrast, the low-frequency ionic conductivity of some (˜6%) brain-tissue samples falls with increasing applied frequency. We attribute this unusual frequency-dependence to the electric-field induced liberation of sodium cations from traps introduced by the unusually severe pathology observed in samples from these patients. Thus, the anomalous frequency-dependence of the ionic conductivity indicates trap-producing brain lesions.

  17. Cationic Phosphorus Dendrimer Enhances Photodynamic Activity of Rose Bengal against Basal Cell Carcinoma Cell Lines.

    PubMed

    Dabrzalska, Monika; Janaszewska, Anna; Zablocka, Maria; Mignani, Serge; Majoral, Jean Pierre; Klajnert-Maculewicz, Barbara

    2017-05-01

    In the last couple of decades, photodynamic therapy emerged as a useful tool in the treatment of basal cell carcinoma. However, it still meets limitations due to unfavorable properties of photosensitizers such as poor solubility or lack of selectivity. Dendrimers, polymers widely studied in biomedical field, may play a role as photosensitizer carriers and improve the efficacy of photodynamic treatment. Here, we describe the evaluation of an electrostatic complex of cationic phosphorus dendrimer and rose bengal in such aspects as singlet oxygen production, cellular uptake, and phototoxicity against three basal cell carcinoma cell lines. Rose bengal-cationic dendrimer complex in molar ratio 5:1 was compared to free rose bengal. Obtained results showed that the singlet oxygen production in aqueous medium was significantly higher for the complex than for free rose bengal. The cellular uptake of the complex was 2-7-fold higher compared to a free photosensitizer. Importantly, rose bengal, rose bengal-dendrimer complex, and dendrimer itself showed no dark toxicity against all three cell lines. Moreover, we observed that phototoxicity of the complex was remarkably enhanced presumably due to high cellular uptake. On the basis of the obtained results, we conclude that rose bengal-cationic dendrimer complex has a potential in photodynamic treatment of basal cell carcinoma.

  18. Ionization behavior of amino lipids for siRNA delivery: determination of ionization constants, SAR, and the impact of lipid pKa on cationic lipid-biomembrane interactions.

    PubMed

    Zhang, Jingtao; Fan, Haihong; Levorse, Dorothy A; Crocker, Louis S

    2011-03-01

    Ionizable amino lipids are being pursued as an important class of materials for delivering small interfering RNA (siRNA) therapeutics, and research is being conducted to elucidate the structure-activity relationships (SAR) of these lipids. The pK(a) of cationic lipid headgroups is one of the critical physiochemical properties of interest due to the strong impact of lipid ionization on the assembly and performance of these lipids. This research focused on developing approaches that permit the rapid determination of the relevant pK(a) of the ionizable amino lipids. Two distinct approaches were investigated: (1) potentiometric titration of amino lipids dissolved in neutral surfactant micelles; and (2) pH-dependent partitioning of a fluorescent dye to cationic liposomes formulated from amino lipids. Using the approaches developed here, the pK(a) values of cationic lipids with distinct headgroups were measured and found to be significantly lower than calculated values. It was also found that lipid-lipid interaction has a strong impact on the pK(a) values of lipids. Lysis of model biomembranes by cationic lipids was used to evaluate the impact of lipid pK(a) on the interaction between cationic lipids and cell membranes. It was found that cationic lipid-biomembrane interaction depends strongly on lipid pK(a) and solution pH, and this interaction is much stronger when amino lipids are highly charged. The presence of an optimal pK(a) range of ionizable amino lipids for siRNA delivery was suggested based on these results. The pK(a) methods reported here can be used to support the SAR screen of cationic lipids for siRNA delivery, and the information revealed through studying the impact of pK(a) on the interaction between cationic lipids and cell membranes will contribute significantly to the design of more efficient siRNA delivery vehicles.

  19. The lightest organic radical cation for charge storage in redox flow batteries

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Huang, Jinhua; Pan, Baofei; Duan, Wentao

    2016-08-25

    Electrochemically reversible fluids of high energy density are promising materials for capturing the electrical energy generated from intermittent sources like solar and wind. To meet this technological challenge there is a need to understand the fundamental limits and interplay of electrochemical potential, stability and solubility in “lean” derivatives of redox-active molecules. Here we describe the process of molecular pruning, illustrated for 2,5-di-tert-butyl-1,4-bis(2-methoxyethoxy)benzene, a molecule known to produce a persistently stable, high-potential radical cation. By systematically shedding molecular fragments considered important for radical cation steric stabilization, we discovered a minimalistic structure that retains long-term stability in its oxidized form. Interestingly, wemore » find the tert-butyl groups are unnecessary; high stability of the radical cation and high solubility are both realized in derivatives having appropriately positioned arene methyl groups. These stability trends are rationalized by mechanistic considerations of the postulated decomposition pathways. We suggest that the molecular pruning approach will uncover lean redox active derivatives for electrochemical energy storage leading to materials with long-term stability and high intrinsic capacity.« less

  20. 75 FR 9442 - Lonza, Inc., Riverside Plant, Lonza Exclusive Synthesis Section, Custom Manufacturing Division...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-02

    ... competitive with cGMP intermediates and Active Pharmaceutical Ingredients from the subject facility to a..., Conshohocken, Pennsylvania, who are engaged in employment related to the production of cGMP intermediates and...GMP intermediates and Active Pharmaceutical Ingredients, who became totally or partially separated...

  1. Erionite-Na upon heating: dehydration dynamics and exchangeable cations mobility

    NASA Astrophysics Data System (ADS)

    Ballirano, Paolo; Pacella, Alessandro

    2016-03-01

    Erionite is a fibrous zeolite significantly more tumorigenic than crocidolite asbestos upon inhalation. In recent years, several papers have been published aimed at characterizing from the crystal-chemical point of view erionite fibres. As their toxicity has been ascribed to Fe acquired within the human body, studies aimed at characterizing the iron topochemistry have also been published, suggesting a possible important role played by the ionic exchange properties and cations mobility of this zeolite on developing carcinogenicity. Here we report the analysis results of the thermal behaviour of erionite-Na, which has been found to deviate significantly from that of erionite-K. This result is in contrast with the current scientific view that differences in weighted ionic potential, Si/Al ratio and size of exchangeable cations result in significantly different thermal behaviours, all those parameters being nearly identical or very similar in both species. The different mobility of the extraframework cations observed in erionite samples with dissimilar chemistry is of particular interest within the frame of the hypothesis that their biological activity could depend, apart from surface interactions, also on bulk effects.

  2. On the Structural Basis for Size-selective Permeation of Organic Cations through the Voltage-gated Sodium Channel

    PubMed Central

    Sun, Ye-Ming; Favre, Isabelle; Schild, Laurent; Moczydlowski, Edward

    1997-01-01

    (II), and Lys(III) residues and the dependence on molecular size suggests that relative permeability of organic cations is a complex function of the size, charge, and polarity of these residues and cation substrates. As judged by effects on macroscopic conductance, charged residues of the DEKA locus also appear to play a role in the mechanisms of block by external Ca2+ and H+, but are not essential for the positive shift in activation voltage that is produced by these ions. PMID:9382897

  3. Examination of the effect of the annealing cation on higher order structures containing guanine or isoguanine repeats

    PubMed Central

    Pierce, Sarah E.; Wang, Junmei; Jayawickramarajah, Janarthanan; Hamilton, Andrew D.; Brodbelt, Jennifer S.

    2010-01-01

    Isoguanine (2-oxo-6-amino-guanine), a natural but non-standard base, exhibits unique self-association properties compared to its isomer, guanine, and results in formation of different higher order DNA structures. In this work, the higher order structures formed by oligonucleotides containing guanine repeats or isoguanine repeats after annealing in solutions containing various cations are evaluated by electrospray ionization mass spectrometry (ESI-MS) and circular dichroism (CD) spectroscopy. The guanine-containing strand (G9) consistently formed quadruplexes upon annealing, whereas the isoguanine strand (Ig9) formed both pentaplexes and quadruplexes depending on the annealing cation. Quadruplex formation with G9 showed some dependence on the identity of the cation present during annealing with high relative quadruplex formation detected with six of ten cations. Analogous annealing experiments with Ig9 resulted in complex formation with all ten cations, and the majority of the resulting complexes were pentaplexes. CD results indicated most of the original complexes survived the desalting process necessary for ESI-MS analysis. In addition, several complexes, especially the pentaplexes, were found to be capable of cation exchange with ammonium ions. Ab initio calculations were conducted for isoguanine tetrads and pentads coordinated with all ten cations to predict the most energetically stable structures of the complexes in the gas phase. The observed preference of forming quadruplexes versus pentaplexes as a function of the coordinated cation can be interpreted by the calculated reaction energies of both the tetrads and pentads in combination with the distortion energies of tetrads. PMID:19746468

  4. Functional role of hCngb3 in regulation of human cone cng channel: effect of rod monochromacy-associated mutations in hCNGB3 on channel function.

    PubMed

    Okada, Akira; Ueyama, Hisao; Toyoda, Futoshi; Oda, Sanae; Ding, Wei-Guang; Tanabe, Shoko; Yamade, Shinichi; Matsuura, Hiroshi; Ohkubo, Iwao; Kani, Kazutaka

    2004-07-01

    The human cone photoreceptor cyclic nucleotide-gated (CNG) channel comprises alpha- and beta-subunits, which are respectively encoded by hCNGA3 and hCNGB3. The purpose was to examine the functional role of hCNGB3 in modulation of human cone CNG channels and to characterize functional consequences of rod monochromacy-associated mutations in hCNGB3 (S435F and D633G). Macroscopic patch currents were recorded from human embryonic kidney (HEK) 293 cells expressing homomeric (hCNGA3 and hCNGB3) and heteromeric (hCNGA3/hCNGB3, hCNGA3/hCNGB3-S435F, and hCNGA3/hCNGB3-D633G) channels using inside-out patch-clamp technique. Both hCNGA3 homomeric and hCNGA3/hCNGB3 heteromeric channels were activated by cGMP, with half-maximally activating concentration (K(1/2)) of 11.1 +/- 1.0 and 26.2 +/- 1.9 micro M, respectively. The hCNGA3 channels appeared to be more sensitive to inhibition by extracellular Ca(2+) compared with hCNGA3/hCNGB3 channels, when assessed by the degree of outward rectification. Coexpression of either of rod monochromacy-associated mutants of hCNGB3 with hCNGA3 significantly reduced K(1/2) value for cGMP but little affected the sensitivity to extracellular Ca(2+), compared with wild-type heteromeric channels. The selectivity of hCNGA3, hCNGA3/hCNGB3, hCNGA3/hCNGB3-S435F, and hCNGA3/hCNGB3-D633G channels for monovalent cations were largely similar. Immunoprecipitation experiments showed association of hCNGA3 subunit with both of wild-type and mutant hCNGB3 subunits. The hCNGB3 plays an important modulatory role in the function of human cone CNG channels with respect to cGMP and extracellular Ca(2+) sensitivities. The rod monochromacy-associated S435F and D633G mutations in hCNGB3 evokes a significant increase in the apparent affinity for cGMP, which should alter cone function and thereby contribute at least partly to pathogenesis of the disease.

  5. Bumetanide hyperpolarizes Madin-Darby canine kidney cells and enhances cellular gentamicin uptake via elevating cytosolic Ca2+ thus facilitating intermediate conductance Ca2+-activated potassium channels

    PubMed Central

    Wang, Tian; Yang, Yu-qin; Karasawa, Takatoshi; Wang, Qi; Phillips, Amanda; Guan, Bing-Cai; Ma, Ke-Tao; Jiang, Meiyan; Xie, Ding-Hua; Steyger, Peter S.; Jiang, Zhi-Gen

    2012-01-01

    Loop diuretics such as bumetanide and furosemide enhance aminoglycoside ototoxicity when co-administered to patients and animal models. The underlying mechanism(s) is poorly understood. We investigated the effect of these diuretics on cellular uptake of aminoglycosides, using Texas Red-tagged gentamicin (GTTR), and intracellular/whole-cell recordings of Madin-Darby Canine kidney (MDCK) cells. We found that bumetanide and furosemide concentration-dependently enhanced cytoplasmic GTTR fluorescence by ~60%. This enhancement was suppressed by La3+, a non-selective cation channel (NSCC) blocker, and by K+ channel blockers Ba2+ and clotrimazole, but not by tetraethylammonium (TEA), 4-aminopyridine (4-AP) or glipizide, nor by Cl− channel blockers diphenylamine-2-carboxylic acid (DPC), niflumic acid (NFA), and CFTRinh-172. Bumetanide and furosemide hyperpolarized MDCK cells by ~14 mV, increased whole-cell I/V slope conductance; the bumetanide-induced net current I/V showed a reversal potential (Vr) ~−80 mV. Bumetanide-induced hyperpolarization and I/V change was suppressed by Ba2+ or clotrimazole, and absent in elevated [Ca2+]i, but not affected by apamin, 4-AP, TEA, glipizide, DPC, NFA or CFTRinh-172. Bumetanide and furosemide stimulated a surge of Fluo-4-indicated cytosolic Ca2+. Ba2+ and clotrimazole alone depolarized cells by ~18 mV and reduced I/V slope with a net current Vr near −85 mV, and reduced GTTR uptake by ~20%. La3+ alone hyperpolarized the cells by ~−14 mV, reduced the I/V slope with a net current Vr near −10 mV, and inhibited GTTR uptake by ~50%. In the presence of La3+, bumetanide caused negligible potential or I/V change. We conclude that NSCCs constitute a major cell entry pathway for cationic aminoglycosides; bumetanide enhances aminoglycoside uptake by hyperpolarizing cells that increases cation influx driving force; and bumetanide-induced hyperpolarization is caused by elevating the intracellular Ca2+ and thus a facilitation of the

  6. Abnormal cation transport in uremia. Mechanisms in adipocytes and skeletal muscle from uremic rats.

    PubMed

    Druml, W; Kelly, R A; May, R C; Mitch, W E

    1988-04-01

    The cause of the abnormal active cation transport in erythrocytes of some uremic patients is unknown. In isolated adipocytes and skeletal muscle from chronically uremic chronic renal failure rats, basal sodium pump activity was decreased by 36 and 30%, and intracellular sodium was increased by 90 and 50%, respectively, compared with pair-fed control rats; insulin-stimulated sodium pump activity was preserved in both tissues. Lower basal NaK-ATPase activity in adipocytes was due to a proportionate decline in [3H]ouabain binding, while in muscle, [3H]ouabain binding was not changed, indicating that the NaK-ATPase turnover rate was decreased. Normal muscle, but not normal adipocytes, acquired defective Na pump activity when incubated in uremic sera. Thus, the mechanism for defective active cation transport in CRF is multifactorial and tissue specific. Sodium-dependent amino acid transport in adipocytes closely paralleled diminished Na pump activity (r = 0.91), indicating the importance of this defect to abnormal cellular metabolism in uremia.

  7. Abnormal cation transport in uremia. Mechanisms in adipocytes and skeletal muscle from uremic rats.

    PubMed Central

    Druml, W; Kelly, R A; May, R C; Mitch, W E

    1988-01-01

    The cause of the abnormal active cation transport in erythrocytes of some uremic patients is unknown. In isolated adipocytes and skeletal muscle from chronically uremic chronic renal failure rats, basal sodium pump activity was decreased by 36 and 30%, and intracellular sodium was increased by 90 and 50%, respectively, compared with pair-fed control rats; insulin-stimulated sodium pump activity was preserved in both tissues. Lower basal NaK-ATPase activity in adipocytes was due to a proportionate decline in [3H]ouabain binding, while in muscle, [3H]ouabain binding was not changed, indicating that the NaK-ATPase turnover rate was decreased. Normal muscle, but not normal adipocytes, acquired defective Na pump activity when incubated in uremic sera. Thus, the mechanism for defective active cation transport in CRF is multifactorial and tissue specific. Sodium-dependent amino acid transport in adipocytes closely paralleled diminished Na pump activity (r = 0.91), indicating the importance of this defect to abnormal cellular metabolism in uremia. PMID:2832446

  8. Saxagliptin and Tadalafil Differentially Alter Cyclic Guanosine Monophosphate (cGMP) Signaling and Left Ventricular Function in Aortic-Banded Mini-Swine.

    PubMed

    Hiemstra, Jessica A; Lee, Dong I; Chakir, Khalid; Gutiérrez-Aguilar, Manuel; Marshall, Kurt D; Zgoda, Pamela J; Cruz Rivera, Noelany; Dozier, Daniel G; Ferguson, Brian S; Heublein, Denise M; Burnett, John C; Scherf, Carolin; Ivey, Jan R; Minervini, Gianmaria; McDonald, Kerry S; Baines, Christopher P; Krenz, Maike; Domeier, Timothy L; Emter, Craig A

    2016-04-20

    Cyclic guanosine monophosphate-protein kinase G-phosphodiesterase 5 signaling may be disturbed in heart failure (HF) with preserved ejection fraction, contributing to cardiac remodeling and dysfunction. The purpose of this study was to manipulate cyclic guanosine monophosphate signaling using the dipeptidyl-peptidase 4 inhibitor saxagliptin and phosphodiesterase 5 inhibitor tadalafil. We hypothesized that preservation of cyclic guanosine monophosphate cGMP signaling would attenuate pathological cardiac remodeling and improve left ventricular (LV) function. We assessed LV hypertrophy and function at the organ and cellular level in aortic-banded pigs. Concentric hypertrophy was equal in all groups, but LV collagen deposition was increased in only HF animals. Prevention of fibrotic remodeling by saxagliptin and tadalafil was correlated with neuropeptide Y plasma levels. Saxagliptin better preserved integrated LV systolic and diastolic function by maintaining normal LV chamber volumes and contractility (end-systolic pressure-volume relationship, preload recruitable SW) while preventing changes to early/late diastolic longitudinal strain rate. Function was similar to the HF group in tadalafil-treated animals including increased LV contractility, reduced chamber volume, and decreased longitudinal, circumferential, and radial mechanics. Saxagliptin and tadalafil prevented a negative cardiomyocyte shortening-frequency relationship observed in HF animals. Saxagliptin increased phosphodiesterase 5 activity while tadalafil increased cyclic guanosine monophosphate levels; however, neither drug increased downstream PKG activity. Early mitochondrial dysfunction, evident as decreased calcium-retention capacity and Complex II-dependent respiratory control, was present in both HF and tadalafil-treated animals. Both saxagliptin and tadalafil prevented increased LV collagen deposition in a manner related to the attenuation of increased plasma neuropeptide Y levels. Saxagliptin

  9. Photodynamic inactivation of Candida albicans sensitized by tri- and tetra-cationic porphyrin derivatives.

    PubMed

    Cormick, M Paula; Alvarez, M Gabriela; Rovera, Marisa; Durantini, Edgardo N

    2009-04-01

    The photodynamic action of 5-(4-trifluorophenyl)-10,15,20-tris(4-trimethylammoniumphenyl)porphyrin iodide (TFAP(3+)) and 5,10,15,20-tetra(4-N,N,N-trimethylammonium phenyl)porphyrin p-tosylate (TMAP(4+)) has been studied in vitro on Candida albicans. The results of these cationic porphyrins were compared with those of 5,10,15,20-tetra(4-sulphonatophenyl)porphyrin (TPPS(4-)), which characterizes an anionic sensitizer. In vitro investigations show that these cationic porphyrins are rapidly bound to C. albicans cells, reaching a value of approximately 1.4 nmol/10(6) cells, when the cellular suspensions were incubated with 5 microM sensitizer for 30 min. In contrast, TPPS(4-) is poorly uptaken by yeast cells. The fluorescence spectra of these sensitizers into the cells confirm this behaviour. The amount of porphyrin binds to cells is dependent on both sensitizer concentrations (1-5 microM) and cells densities (10(6)-10(8) cells/mL). Photosensitized inactivation of C. albicans cellular suspensions increases with sensitizer concentration, causing a approximately 5 log decrease of cell survival, when the cultures are treated with 5 microM of cationic porphyrin and irradiated for 30 min. However, the photocytotoxicity decreases with an increase in the cell density, according to its low binding to cells. Under these conditions, the photodynamic activity of TFAP(3+) is quite similar to that produced by TMAP(4+), whereas no important inactivation effect was found for TPPS(4)(-). The high photodynamic activity of cationic porphyrins was confirmed by growth delay experiments. Thus, C. albicans cell growth was not detected in the presence of 5 microM TFAP(3+). Photodynamic inactivation capacities of these sensitizers were also evaluated on C. albicans cells growing in colonies on agar surfaces. Cationic porphyrins produce a growth delay of C. albicans colonies and viability of cells was not observed after 3 h irradiation, indicating a complete inactivation of yeast cells

  10. Characterisation of a cell swelling-activated K+-selective conductance of Ehrlich mouse ascites tumour cells

    PubMed Central

    Niemeyer, María Isabel; Hougaard, Charlotte; Hoffmann, Else K; Jørgensen, Finn; Stutzin, Andrés; Sepúlveda, Francisco V

    2000-01-01

    The K+ and Cl− currents activated by hypotonic cell swelling were studied in Ehrlich ascites tumour cells using the whole-cell recording mode of the patch-clamp technique. Currents were measured in the absence of added intracellular Ca2+ and with strong buffering of Ca2+. K+ current activated by cell swelling was measured as outward current at the Cl− equilibrium potential (ECl) under quasi-physiological gradients. It could be abolished by replacing extracellular Na+ with K+, thereby cancelling the driving force. Replacement with other cations suggested a selectivity sequence of K+ > Rb+ > NH4≈ Na+≈ Li+; Cs+ appeared to be inhibitory. The current-voltage relationship of the volume-sensitive K+ current was well fitted with the Goldman-Hodgkin-Katz current equation between -130 and +20 mV with a permeability coefficient of around 10−6 cm s−1 with both physiological and high-K+ extracellular solutions. The class III antiarrhythmic drug clofilium blocked the volume-sensitive K+ current in a voltage-independent manner with an IC50 of 32 μM. Clofilium was also found to be a strong inhibitor of the regulatory volume decrease response of Ehrlich cells. Cell swelling-activated K+ currents of Ehrlich cells are voltage and calcium insensitive and are resistant to a range of K+ channel inhibitors. These characteristics are similar to those of the so-called background K+ channels. Noise analysis of whole-cell current was consistent with a unitary conductance of 5.5 pS for the single channels underlying the K+ current evoked by cell swelling, measured at 0 mV under a quasi-physiological K+ gradient. PMID:10790156

  11. Methane Activation Mediated by a Series of Cerium-Vanadium Bimetallic Oxide Cluster Cations: Tuning Reactivity by Doping.

    PubMed

    Ma, Jia-Bi; Meng, Jing-Heng; He, Sheng-Gui

    2016-04-18

    The reactions of cerium-vanadium cluster cations Cex Vy Oz (+) with CH4 are investigated by time-of-flight mass spectrometry and density functional theory calculations. (CeO2 )m (V2 O5 )n (+) clusters (m=1,2, n=1-5; m=3, n=1-4) with dimensions up to nanosize can abstract one hydrogen atom from CH4 . The theoretical study indicates that there are two types of active species in (CeO2 )m (V2 O5 )n (+) , V[(Ot )2 ](.) and [(Ob )2 CeOt ](.) (Ot and Ob represent terminal and bridging oxygen atoms, respectively); the former is less reactive than the latter. The experimentally observed size-dependent reactivities can be rationalized by considering the different active species and mechanisms. Interestingly, the reactivity of the (CeO2 )m (V2 O5 )n (+) clusters falls between those of (CeO2 )2-4 (+) and (V2 O5 )1-5 (+) in terms of C-H bond activation, thus the nature of the active species and the cluster reactivity can be effectively tuned by doping. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Effects of divalent cations and La3+ on contractility and ecto-ATPase activity in the guinea-pig urinary bladder.

    PubMed Central

    Ziganshin, A U; Ziganshina, L E; Hoyle, C H; Burnstock, G

    1995-01-01

    1. Several cations (Ba2+, Cd2+, Co2+, Cu2+, Mn2+, Ni2+, Zn2+ and La3+, all as chloride salts, 1-1000 microM) were tested in the guinea-pig urinary bladder for their ability to: (i) modify contractile responses to electrical field stimulation (EFS), ATP, alpha,beta-methylene ATP (alpha,beta-meATP), carbachol (CCh), and KCl; (ii) affect ecto-ATPase activity. 2. Ba2+ (10-1000 microM) concentration-dependently potentiated contractile responses evoked by EFS (4-16 Hz), ATP (100 microM), alpha,beta-meATP (1 microM), CCh (0.5 microM), and KCl (30 mM). Ni2+ at concentrations of 1-100 microM also potentiated contractility of the urinary bladder, but at concentrations tested its effect was not concentration-dependent. Cu2+ at a concentration of 10 microM and Cd2+ at a concentration of 1 microM potentiated responses to all stimuli, except KCl. Ni2+ at a concentration of 1000 microM and Cd2+ at a concentration of 100 microM inhibited contractions evoked by all stimuli, and at a concentration of 1000 microM Cd2+ abolished any contractions. Responses to ATP and alpha,beta-meATP were selectively inhibited by Cu2+, Zn2+ or La3+, each at a concentration of 1 mM. 3. Cu2+, Ni2+, Zn2+ and La3+ (100-1000 microM) concentration-dependently inhibited ecto-ATPase activity in the urinary bladder smooth muscle preparations, while Ba2+ and Mn2+ were without effect, and Cd2+ and Co2+ caused significant inhibition only at a concentration of 1000 microM. 4. There was no correlation between the extent of ecto-ATPase inhibition and the effect on contractile activity of any of the cations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7735690

  13. Ionophores and receptors using cation-pi interactions: collarenes.

    PubMed

    Choi, H S; Suh, S B; Cho, S J; Kim, K S

    1998-10-13

    Cation-pi interactions are important forces in molecular recognition by biological receptors, enzyme catalysis, and crystal engineering. We have harnessed these interactions in designing molecular systems with circular arrangement of benzene units that are capable of acting as ionophores and models for biological receptors. [n]Collarenes are promising candidates with high selectivity for a specific cation, depending on n, because of their structural rigidity and well-defined cavity size. The interaction energies of [n]collarenes with cations have been evaluated by using ab initio calculations. The selectivity of these [n]collarenes in aqueous solution was revealed by using statistical perturbation theory in conjunction with Monte Carlo and molecular dynamics simulations. It has been observed that in [n]collarenes the ratio of the interaction energies of a cation with it and the cation with the basic building unit (benzene) can be correlated to its ion selectivity. We find that collarenes are excellent and efficient ionophores that bind cations through cation-pi interactions. [6]Collarene is found to be a selective host for Li+ and Mg2+, [8]collarene for K+ and Sr2+, and [10]collarene for Cs+ and Ba2+. This finding indicates that [10]collarene and [8]collarene could be used for effective separation of highly radioactive isotopes, 137Cs and 90Sr, which are major constituents of nuclear wastes. More interestingly, collarenes of larger cavity size can be useful in capturing organic cations. [12]Collarene exhibits a pronounced affinity for tetramethylammonium cation and acetylcholine, which implies that it could serve as a model for acetylcholinestrase. Thus, collarenes can prove to be novel and effective ionophores/model-receptors capable of heralding a new direction in molecular recognition and host-guest chemistry.

  14. The C4H7+ cation. A theoretical investigation

    NASA Technical Reports Server (NTRS)

    Koch, W.; Liu, B.; DeFrees, D. J.

    1988-01-01

    The potential energy surface of the C4H7+ cation has been investigated with ab initio quantum chemical theory. Extended basis set calculations, including electronic correlation, show that cyclobutyl and cyclopropylcarbinyl cation are equally stable isomers. The saddle point connecting these isomers lies 0.6 kcal/mol above the minima. The global C4H7+ minimum corresponds to the 1-methylallyl cation, which is 9.0 kcal/mol more stable than the cyclobutyl and the cyclopropylcarbinyl cation and 9.5 kcal/mol below the 2-methylallyl cation. These results are in excellent agreement with experimental data.

  15. Structure-activity correlation in transfection promoted by pyridinium cationic lipids.

    PubMed

    Parvizi-Bahktar, P; Mendez-Campos, J; Raju, L; Khalique, N A; Jubeli, E; Larsen, H; Nicholson, D; Pungente, M D; Fyles, T M

    2016-03-21

    The efficiency of the transfection of a plasmid DNA encoding a galactosidase promoted by a series of pyridinium lipids in mixtures with other cationic lipids and neutral lipids was assessed in CHO-K1 cells. We identify key molecular parameters of the lipids in the mixture - clog P, lipid length, partial molar volume - to predict the morphology of the lipid-DNA lipoplex and then correlate these same parameters with transfection efficiency in an in vitro assay. We define a Transfection Index that provides a linear correlation with normalized transfection efficiency over a series of 90 different lipoplex compositions. We also explore the influence of the same set of molecular parameters on the cytotoxicity of the formulations.

  16. Cation and anion dependence of stable geometries and stabilization energies of alkali metal cation complexes with FSA(-), FTA(-), and TFSA(-) anions: relationship with physicochemical properties of molten salts.

    PubMed

    Tsuzuki, Seiji; Kubota, Keigo; Matsumoto, Hajime

    2013-12-19

    Stable geometries and stabilization energies (Eform) of the alkali metal complexes with bis(fluorosulfonyl)amide, (fluorosulfonyl)(trifluoromethylslufonyl)amide and bis(trifluoromethylsulfonyl)amide (FSA(-), FTA(-) and TFSA(-)) were studied by ab initio molecular orbital calculations. The FSA(-) complexes prefer the bidentate structures in which two oxygen atoms of two SO2 groups have contact with the metal cation. The FTA(-) and TFSA(-) complexes with Li(+) and Na(+) prefer the bidentate structures, while the FTA(-) and TFSA(-) complexes with Cs(+) prefer tridentate structures in which the metal cation has contact with two oxygen atoms of an SO2 group and one oxygen atom of another SO2 group. The two structures are nearly isoenergetic in the FTA(-) and TFSA(-) complexes with K(+) and Rb(+). The magnitude of Eform depends on the alkali metal cation significantly. The Eform calculated for the most stable TFSA(-) complexes with Li(+), Na(+), K(+), Rb(+) and Cs(+) cations at the MP2/6-311G** level are -137.2, -110.5, -101.1, -89.6, and -84.1 kcal/mol, respectively. The viscosity and ionic conductivity of the alkali TFSA molten salts have strong correlation with the magnitude of the attraction. The viscosity increases and the ionic conductivity decreases with the increase of the attraction. The melting points of the alkali TFSA and alkali BETA molten salts also have correlation with the magnitude of the Eform, which strongly suggests that the magnitude of the attraction play important roles in determining the melting points of these molten salts. The anion dependence of the Eform calculated for the complexes is small (less than 2.9 kcal/mol). This shows that the magnitude of the attraction is not the cause of the low melting points of alkali FTA molten salts compared with those of corresponding alkali TFSA molten salts. The electrostatic interactions are the major source of the attraction in the complexes. The electrostatic energies for the most stable TFSA

  17. Cationic nanocarriers induce cell necrosis through impairment of Na+/K+-ATPase and cause subsequent inflammatory response

    PubMed Central

    Wei, Xiawei; Shao, Bin; He, Zhiyao; Ye, Tinghong; Luo, Min; Sang, Yaxiong; Liang, Xiao; Wang, Wei; Luo, Shuntao; Yang, Shengyong; Zhang, Shuang; Gong, Changyang; Gou, Maling; Deng, Hongxing; Zhao, Yinglan; Yang, Hanshuo; Deng, Senyi; Zhao, Chengjian; Yang, Li; Qian, Zhiyong; Li, Jiong; Sun, Xun; Han, Jiahuai; Jiang, Chengyu; Wu, Min; Zhang, Zhirong

    2015-01-01

    Nanocarriers with positive surface charges are known for their toxicity which has limited their clinical applications. The mechanism underlying their toxicity, such as the induction of inflammatory response, remains largely unknown. In the present study we found that injection of cationic nanocarriers, including cationic liposomes, PEI, and chitosan, led to the rapid appearance of necrotic cells. Cell necrosis induced by cationic nanocarriers is dependent on their positive surface charges, but does not require RIP1 and Mlkl. Instead, intracellular Na+ overload was found to accompany the cell death. Depletion of Na+ in culture medium or pretreatment of cells with the Na+/K+-ATPase cation-binding site inhibitor ouabain, protected cells from cell necrosis. Moreover, treatment with cationic nanocarriers inhibited Na+/K+-ATPase activity both in vitro and in vivo. The computational simulation showed that cationic carriers could interact with cation-binding site of Na+/K+-ATPase. Mice pretreated with a small dose of ouabain showed improved survival after injection of a lethal dose of cationic nanocarriers. Further analyses suggest that cell necrosis induced by cationic nanocarriers and the resulting leakage of mitochondrial DNA could trigger severe inflammation in vivo, which is mediated by a pathway involving TLR9 and MyD88 signaling. Taken together, our results reveal a novel mechanism whereby cationic nanocarriers induce acute cell necrosis through the interaction with Na+/K+-ATPase, with the subsequent exposure of mitochondrial damage-associated molecular patterns as a key event that mediates the inflammatory responses. Our study has important implications for evaluating the biocompatibility of nanocarriers and designing better and safer ones for drug delivery. PMID:25613571

  18. 21 CFR 872.3480 - Polyacrylamide polymer (modified cationic) denture adhesive.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Polyacrylamide polymer (modified cationic) denture... polymer (modified cationic) denture adhesive. (a) Identification. A polyacrylamide polymer (modified cationic) denture adhesive is a device composed of polyacrylamide polymer (modified cationic) intended to...

  19. 21 CFR 872.3480 - Polyacrylamide polymer (modified cationic) denture adhesive.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Polyacrylamide polymer (modified cationic) denture... polymer (modified cationic) denture adhesive. (a) Identification. A polyacrylamide polymer (modified cationic) denture adhesive is a device composed of polyacrylamide polymer (modified cationic) intended to...

  20. 21 CFR 872.3480 - Polyacrylamide polymer (modified cationic) denture adhesive.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Polyacrylamide polymer (modified cationic) denture... polymer (modified cationic) denture adhesive. (a) Identification. A polyacrylamide polymer (modified cationic) denture adhesive is a device composed of polyacrylamide polymer (modified cationic) intended to...

  1. 21 CFR 872.3480 - Polyacrylamide polymer (modified cationic) denture adhesive.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Polyacrylamide polymer (modified cationic) denture... polymer (modified cationic) denture adhesive. (a) Identification. A polyacrylamide polymer (modified cationic) denture adhesive is a device composed of polyacrylamide polymer (modified cationic) intended to...

  2. 21 CFR 872.3480 - Polyacrylamide polymer (modified cationic) denture adhesive.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Polyacrylamide polymer (modified cationic) denture... polymer (modified cationic) denture adhesive. (a) Identification. A polyacrylamide polymer (modified cationic) denture adhesive is a device composed of polyacrylamide polymer (modified cationic) intended to...

  3. Isomerization and fragmentation reactions of gaseous phenylarsane radical cations and phenylarsanyl cations. A study by tandem mass spectrometry and theoretical calculations.

    PubMed

    Letzel, Matthias; Kirchhoff, Dirk; Grützmacher, Hans-Friedrich; Stein, Daniel; Grützmacher, Hansjörg

    2006-04-28

    The unimolecular reactions of radical cations and cations derived from phenylarsane, C6H5AsH2 (1) and dideutero phenylarsane, C6H5AsD2 (1-d2), were investigated by methods of tandem mass spectrometry and theoretical calculations. The mass spectrometric experiments reveal that the molecular ion of phenylarsane, 1*+, exhibits different reactivity at low and high internal excess energy. Only at low internal energy the observed fragmentations are as expected, that is the molecular ion 1*+ decomposes almost exclusively by loss of an H atom. The deuterated derivative 1-d2 with an AsD2 group eliminates selectively a D atom under these conditions. The resulting phenylarsenium ion [C6H5AsH]+, 2+, decomposes rather easily by loss of the As atom to give the benzene radical cation [C6H6]*+ and is therefore of low abundance in the 70 eV EI mass spectrum. At high internal excess energy, the ion 1*+ decomposes very differently either by elimination of an H2 molecule, or by release of the As atom, or by loss of an AsH fragment. Final products of these reactions are either the benzoarsenium ion 4*+, or the benzonium ion [C6H7]+, or the benzene radical cation, [C6H6]*+. As key-steps, these fragmentations contain reductive eliminations from the central As atom under H-H or C-H bond formation. Labeling experiments show that H/D exchange reactions precede these fragmentations and, specifically, that complete positional exchange of the H atoms in 1*+ occurs. Computations at the UMP2/6-311+G(d)//UHF/6-311+G(d) level agree best with the experimental results and suggest: (i) 1*+ rearranges (activation enthalpy of 93 kJ mol(-1)) to a distinctly more stable (DeltaH(r)(298) = -64 kJ mol(-1)) isomer 1 sigma*+ with a structure best represented as a distonic radical cation sigma complex between AsH and benzene. (ii) The six H atoms of the benzene moiety of 1 sigma*+ become equivalent by a fast ring walk of the AsH group. (iii) A reversible isomerization 1+<==>1 sigma*+ scrambles eventually all H

  4. Equilibrium Acidities and Homolytic Bond Dissociation Enthalpies of the Acidic C-H Bonds in P-(Para-substituted benzyl)triphenylphosphonium Cations and Related Cations.

    PubMed

    Zhang, Xian-Man; Fry, Albert J.; Bordwell, Frederick G.

    1996-06-14

    Equilibrium acidities (pK(HA)) of six P-(para-substituted benzyl)triphenylphosphonium (p-GC(6)H(4)CH(2)PPh(3)(+)) cations, P-allyltriphenylphosphonium cation, P-cinnamyltriphenylphosphonium cation, and As-(p-cyanobenzyl)triphenylarsonium cation, together with the oxidation potentials [E(ox)(A(-))] of their conjugate anions (ylides) have been measured in dimethyl sulfoxide (DMSO) solution. The acidifying effects of the alpha-triphenylphosphonium groups on the acidic C-H bonds in toluene and propene were found to be ca 25 pK(HA) units (34 kcal/mol). Introduction of an electron-withdrawing group such as 4-NO(2), 4-CN, or 4-Br into the para position of the benzyl ring in p-GC(6)H(4)CH(2)PPh(3)(+) cations resulted in an additional acidity increase, but introduction of the 4-OEt electron-donating group decreases the acidity. The equilibrium acidities of p-GC(6)H(4)CH(2)PPh(3)(+) cations were nicely linearly correlated with the Hammett sigma(-) constants of the substituents (G) with a slope of 4.78 pK(HA) units (R(2) = 0.992) (Figure 1). Reversible oxidation potentials of the P-(para-substituted benzyl)triphenylphosphonium ylides were obtained by fast scan cyclic voltammetry. The homolytic bond dissociation enthalpies (BDEs) of the acidic C-H bonds in these cations, estimated by combining their equilibrium acidities with the oxidation potentials of their corresponding conjugate anions, showed that the alpha-Ph(3)P(+) groups have negligible stabilizing or destabilizing effects on the adjacent radicals. The equilibrium acidity of As-(p-cyanobenzyl)triphenylarsonium cation is 4 pK(HA) units weaker than that of P-(p-cyanobenzyl)triphenylphosphonium cation, but the BDE of the acidic C-H bond in As-(p-cyanobenzyl)triphenylarsonium cation is ca 2 kcal/mol higher than that in P-(p-cyanobenzyl)triphenylphosphonium cation.

  5. The [C{sub 6}H{sub 10}]{sup {sm{underscore}bullet}+} hypersurface: The parent radical cation Diels-Alder reaction

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hoffmann, M.; Schaefer, H.F. III

    1999-07-21

    Various possible reaction pathways between ethene and butadiene radical cation (cis- and trans-), have been investigated at different levels of theory up to UCCSD(T)/DZP/UMP2(fc)/DZP and with density functional theory at B3LYP/DZP. A stepwise addition involving open chain intermediates and leading to the Diels-Alder product, the cyclohexene radical cation, was found to have a total activation barrier {Delta}G{sup 298{ne}} = 6.3 kcal mol{sup {minus}1} and a change in free Gibbs energy, {Delta}G{sup 298}, of {minus}33.5 kcal mol{sup {minus}1}. On the E{degree} potential energy surface, all transition states are lower in energy than separated ethene and butadiene, the exothermicity {Delta}E = -45.6more » kcal mol{sup {minus}1}. A more direct path could be characterized as stepwise with one intermediate only at the SCF level but not at electron-correlated levels and hence might actually be a concerted strongly asynchronous addition with a very small or no activation barrier (UCCSD(T)/DZP/UHF/6-31G* gives a {Delta}G{sup 298{ne}} of 0.8 kcal mol{sup {minus}1}). The critical step for another alternative, the cyclobutanation-vinylcyclobutane/cyclohexene rearrangement, is a 1,3-alkyl shift which involves a barrier ({Delta}G{sup 298{ne}}) only 1.7 kcal mol{sup {minus}1} higher than that of stop use addition for both cis-, and trans-butadiene radical cation. However, from the (ethene and trans-butadiene) reactions, ring expansion of the vinylcyclobutane radical cation intermediate, to a methylene cyclopentane radical cation, requires an activation only 1.3 kcal mol{sup {minus}1} larger than for (trans-butadiene radical). While cis/trans isomerization of free butadiene radical cation requires a high activation (24.9 kcal mol{sup {minus}1}), a reaction sequence involving addition of ethene (to stepwise give an open chain intermediate and vinyl cyclobutane radical cation) has a barrier of only 3.5 kcal mol{sup {minus}1} ({Delta}G{sup 298{ne}}). This sequence also makes ethene

  6. Neutron diffraction reveals hydrogen bonds critical for cGMP-selective activation: Insights for cGMP-dependent protein kinase agonist design

    DOE PAGES

    Huang, Gilbert Y.; Gerlits, Oksana O.; Blakeley, Matthew P.; ...

    2014-10-01

    High selectivity of cyclic-nucleotide binding (CNB) domains for cAMP and cGMP are required for segregating signaling pathways; however, the mechanism of selectivity remains unclear. To investigate the mechanism of high selectivity in cGMP-dependent protein kinase (PKG), we determined a room-temperature joint X-ray/neutron (XN) structure of PKG Iβ CNB-B, a domain 200-fold selective for cGMP over cAMP, bound to cGMP (2.2 Å), and a low-temperature X-ray structure of CNB-B with cAMP (1.3 Å). Finally, the XN structure directly describes the hydrogen bonding interactions that modulate high selectivity for cGMP, while the structure with cAMP reveals that all these contacts are disrupted,more » explaining its low affinity for cAMP.« less

  7. Nucleophilic addition of nitrogen to aryl cations: mimicking Titan chemistry.

    PubMed

    Li, Anyin; Jjunju, Fred P M; Cooks, R Graham

    2013-11-01

    The reactivity of aryl cations toward molecular nitrogen is studied systematically in an ion trap mass spectrometer at 10(2) Pascal of nitrogen, the pressure of the Titan main haze layer. Nucleophilic addition of dinitrogen occurs and the nature of aryl group has a significant influence on the reactivity, through inductive effects and by changing the ground state spin multiplicity. The products of nitrogen activation, aryldiazonium ions, react with typical nitriles, aromatic amines, and alkynes (compounds that are relevant as possible Titan atmosphere constituents) to form covalently bonded heterocyclic products. Theoretical calculations at the level [DFT(B3LYP)/6-311++G(d,p)] indicate that the N2 addition reaction is exothermic for the singlet aryl cations but endothermic for their triplet spin isomers. The -OH and -NH2 substituted aryl ions are calculated to have triplet ground states, which is consistent with their decreased nitrogen addition reactivity. The energy needed for the generation of the aryl cations from their protonated precursors (ca. 340 kJ/mol starting with protonated aniline) is far less than that required to directly activate the nitrogen triple bond (the lowest energy excited state of N2 lies ca. 600 kJ/mol above the ground state). The formation of aza-aromatics via arene ionization and subsequent reactions provide a conceivable route to the genesis of nitrogen-containing organic molecules in the interstellar medium and Titan haze layers.

  8. Mechanistic insights into allosteric regulation of the A 2A adenosine G protein-coupled receptor by physiological cations

    DOE PAGES

    Ye, Libin; Neale, Chris Andrew; Sljoka, Adnan; ...

    2018-04-10

    Cations play key roles in regulating G-protein-coupled receptors (GPCRs), although their mechanisms are poorly understood. Here, 19F NMR is used to delineate the effects of cations on functional states of the adenosine A 2A GPCR. While Na + reinforces an inactive ensemble and a partial-agonist stabilized state, Ca 2+ and Mg 2+ shift the equilibrium toward active states. Positive allosteric effects of divalent cations are more pronounced with agonist and a G-protein-derived peptide. In cell membranes, divalent cations enhance both the affinity and fraction of the high affinity agonist-bound state. Molecular dynamics simulations suggest high concentrations of divalent cations bridgemore » specific extracellular acidic residues, bringing TM5 and TM6 together at the extracellular surface and allosterically driving open the G-protein-binding cleft as shown by rigidity-transmission allostery theory. Lastly, an understanding of cation allostery should enable the design of allosteric agents and enhance our understanding of GPCR regulation in the cellular milieu.« less

  9. Mechanistic insights into allosteric regulation of the A 2A adenosine G protein-coupled receptor by physiological cations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ye, Libin; Neale, Chris Andrew; Sljoka, Adnan

    Cations play key roles in regulating G-protein-coupled receptors (GPCRs), although their mechanisms are poorly understood. Here, 19F NMR is used to delineate the effects of cations on functional states of the adenosine A 2A GPCR. While Na + reinforces an inactive ensemble and a partial-agonist stabilized state, Ca 2+ and Mg 2+ shift the equilibrium toward active states. Positive allosteric effects of divalent cations are more pronounced with agonist and a G-protein-derived peptide. In cell membranes, divalent cations enhance both the affinity and fraction of the high affinity agonist-bound state. Molecular dynamics simulations suggest high concentrations of divalent cations bridgemore » specific extracellular acidic residues, bringing TM5 and TM6 together at the extracellular surface and allosterically driving open the G-protein-binding cleft as shown by rigidity-transmission allostery theory. Lastly, an understanding of cation allostery should enable the design of allosteric agents and enhance our understanding of GPCR regulation in the cellular milieu.« less

  10. A novel route to recognizing quaternary ammonium cations using electrospray mass spectrometry.

    PubMed

    Shackman, Holly M; Ding, Wei; Bolgar, Mark S

    2015-01-01

    Characterizing and elucidating structures is a commonplace and necessary activity in the pharmaceutical industry with mass spectrometry and NMR being the primary tools for analysis. Although many functional groups are readily identifiable, quaternary ammonium cations have proven to be difficult to unequivocally identify using these techniques. Due to the lack of an N-H bond, quaternary ammonium groups can only be detected in the (1)H NMR spectra by weak signals generated from long-range (14)N-H coupling, which by themselves are inconclusive evidence of a quaternary ammonium functional group. Due to their low intensity, these signals are frequently not detected. Additionally, ions cannot be differentiated in a mass spectrum as an M(+) or [M + H](+) ion without prior knowledge of the compound's structure. In order to utilize mass spectrometry as a tool for determining this functionality, ion cluster formation of quaternary ammonium cations and non-quaternary amines was studied using electrospray ionization. Several mobile phase modifiers were compared; however, the addition of small amounts of trifluoroacetic acid proved superior in producing characteristic and intense [M +2TFA](-) clusters for compounds containing quaternary ammonium cations when using negative electrospray. By fragmenting this characteristic ion using CID, nearly all compounds studied could be unambiguously identified as containing a quaternary ammonium cation or a non-quaternary amine attributable to the presence (non-quaternary amine) or absence (quaternary ammonium cation) of the resulting [2TFA + H](-) ion in the product spectra. This method of analysis provides a rapid, novel, and reliable technique for indicating the presence of quaternary ammonium cations in order to aid in structural elucidation.

  11. Process and apparatus for the production of BI-213 cations

    DOEpatents

    Horwitz, E. Philip; Hines, John J.; Chiarizia, Renato; Dietz, Mark

    1998-01-01

    A process for producing substantially impurity-free Bi-213 cations is disclosed. An aqueous acid feed solution containing Ac-225 cations is contacted with an ion exchange medium to bind the Ac-225 cations and form an Ac-225-laden ion exchange medium. The bound Ac-225 incubates on the ion exchange medium to form Bi-213 cations by radioactive decay. The Bi-213 cations are then recovered from the Ac-225-laden ion exchange medium to form a substantially impurity-free aqueous Bi-213 cation acid solution. An apparatus for carrying out this process is also disclosed.

  12. Process and apparatus for the production of Bi-213 cations

    DOEpatents

    Horwitz, E.P.; Hines, J.J.; Chiarizia, R.; Dietz, M.

    1998-12-29

    A process for producing substantially impurity-free Bi-213 cations is disclosed. An aqueous acid feed solution containing Ac-225 cations is contacted with an ion exchange medium to bind the Ac-225 cations and form an Ac-225-laden ion exchange medium. The bound Ac-225 incubates on the ion exchange medium to form Bi-213 cations by radioactive decay. The Bi-213 cations are then recovered from the Ac-225-laden ion exchange medium to form a substantially impurity-free aqueous Bi-213 cation acid solution. An apparatus for carrying out this process is also disclosed. 7 figs.

  13. Covalent Incorporation of Ionic Liquid into Ion-Conductive Networks via Thiol-Ene Photopolymerization.

    PubMed

    Tibbits, Andrew C; Yan, Yushan S; Kloxin, Christopher J

    2017-07-01

    Ene-functionalized ionic liquids with a range of different cationic groups and counteranions react stoichiometrically within a tetrathiol-divinyl ether formulation within 20 minutes to form thiol-ene polymers with measurable ionic conductivities via a photoinitiated polymerization and crosslinking reaction. Dynamic mechanical analysis indicates that these networks are more spatially heterogeneous and possess higher glass transition temperatures (T g ) compared with thiol-ene formulations without charge. While tuning the molar content of ionic liquid monomer is one method for adjusting the crosslink and charge densities of the thiol-ene polymeric ionic liquid networks, the presence of cation-anion interactions also plays a critical role in dictating the thermomechanical and conductive properties. Particularly, while cationic structure effects are not significant on the polymer properties, the use of a weakly coordinating hydrophobic anion (bistriflimide) instead of bromide-based networks results in an apparent decrease in hydrated ion conductivity (7.4 to 1.5 mS cm -1 ) and T g (-9.6 to -17.8 °C). © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Ion channel-mediated uptake of cationic vital dyes into live cells: a potential source of error when assessing cell viability.

    PubMed

    Bukhari, Maurish; Burm, Hayley; Samways, Damien S K

    2016-10-01

    Ionic "vital dyes" are commonly used to assess cell viability based on the idea that their permeation is contingent on a loss of membrane integrity. However, the possibility that dye entry is conducted into live cells by endogenous membrane transporters must be recognized and controlled for. Several cation-selective plasma membrane-localized ion channels, including the adenosine 5'-triphosphate (ATP)-gated P2X receptors, have been reported to conduct entry of the DNA-binding fluorescence dye, YO-PRO-1, into live cells. Extracellular ATP often becomes elevated as a result of release from dying cells, and so it is possible that activation of P2X channels on neighboring live cells could lead to exaggerated estimation of cytotoxicity. Here, we screened a number of fluorescent vital dyes for ion channel-mediated uptake in HEK293 cells expressing recombinant P2X2, P2X7, or TRPV1 channels. Our data shows that activation of all three channels caused substantial uptake and nuclear accumulation of YO-PRO-1, 4',6-diamidino-2-phenylindole (DAPI), and Hoechst 33258 into transfected cells and did so well within the time period usually used for incubation of cells with vital dyes. In contrast, channel activation in the presence of propidium iodide and SYTOX Green caused no measurable uptake and accumulation during a 20-min exposure, suggesting that these dyes are not likely to exhibit measurable uptake through these particular ion channels during a conventional cell viability assay. Caution is encouraged when choosing and employing cationic dyes for the purpose of cell viability assessment, particularly when there is a likelihood of cells expressing ion channels permeable to large ions.

  15. Novel polymer electrolytes based on cationic polyurethane with different alkyl chain length

    NASA Astrophysics Data System (ADS)

    Liu, Libin; Wu, Xiwen; Li, Tianduo

    2014-03-01

    A series of comb-like cationic polyurethanes (PUs) were synthesized by quaternizing different bromoalkane (C2H5Br, C8H17Br, and C14H29Br) with polyurethane. Solid polymer electrolytes were prepared by complexes cationic PUs with different content of LiClO4. All the solid polymer electrolytes had sufficient thermal stability as confirmed by TGA and exhibited a single-phase behavior evidenced by DSC results. For these electrolytes, FT-IR spectra indicated the formation of polymer-ion complexes. The ac impedance spectra show that the conductivity of the electrolytes follow the Arrhenius behavior, and ionic conductivity is associated with both the charge migration of ions between coordination sites and transmission between aggregates, as confirmed by FT-IR and SEM. Alkyl quaternary ammonium salts in the polymer backbone are recognized as inherent plasticizers, which make the electrolytes exhibit liquid-like behavior. The plasticizing effect of PU-C8 and PU-C14 electrolytes are more effective than that of PU-C2 electrolyte. Maximum ionic conductivity at room temperature for PU-C8 electrolytes containing 50 wt% LiClO4 reached 1.1 × 10-4 S cm-1. This work provides a new research clue that alkyl quaternary ammonium salts could be used as inherent plasticizers and hence make the system behave like a liquid with high ionic conductivity, while preserving the dimensional stability of the solids.

  16. B-Site Metal Cation Exchange in Halide Perovskites

    DOE PAGES

    Eperon, Giles E.; Ginger, David S.

    2017-05-02

    Here, we demonstrate exchange of the B-site metal cation in hybrid organic-inorganic halide perovskite thin films. We exchange tin in formamidinium tin triiodide (NH 2) 2SnI 3' or FASnI 3) with lead at controllable levels, forming (CH- (NH 2) 2SnI xPB 1-xI 3 alloys with partial substitution and fully converting the film to CH(NH 2) 2PbI 3 with a large excess of Pb 2+. We observe no evidence for phase segregation or bilayered films, indicating that conversion is uniform throughout the film. This facile technique provides a new way to control composition independently from the crystallization processes, allowing formation ofmore » the black phase of CH(NH 2) 2PbI 3 at much lower temperatures than those previously reported while also opening the door to new morphology-composition combinations. The surprising observation that the B-site metal cations are mobile may also provide insight into the nature of transient processes in these materials, suggesting that they may be involved in ionic conduction, and will be a critical consideration for long-term stability.« less

  17. B-Site Metal Cation Exchange in Halide Perovskites

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Eperon, Giles E.; Ginger, David S.

    Here, we demonstrate exchange of the B-site metal cation in hybrid organic-inorganic halide perovskite thin films. We exchange tin in formamidinium tin triiodide (NH 2) 2SnI 3' or FASnI 3) with lead at controllable levels, forming (CH- (NH 2) 2SnI xPB 1-xI 3 alloys with partial substitution and fully converting the film to CH(NH 2) 2PbI 3 with a large excess of Pb 2+. We observe no evidence for phase segregation or bilayered films, indicating that conversion is uniform throughout the film. This facile technique provides a new way to control composition independently from the crystallization processes, allowing formation ofmore » the black phase of CH(NH 2) 2PbI 3 at much lower temperatures than those previously reported while also opening the door to new morphology-composition combinations. The surprising observation that the B-site metal cations are mobile may also provide insight into the nature of transient processes in these materials, suggesting that they may be involved in ionic conduction, and will be a critical consideration for long-term stability.« less

  18. Current scenario of peptide-based drugs: the key roles of cationic antitumor and antiviral peptides

    PubMed Central

    Mulder, Kelly C. L.; Lima, Loiane A.; Miranda, Vivian J.; Dias, Simoni C.; Franco, Octávio L.

    2013-01-01

    Cationic antimicrobial peptides (AMPs) and host defense peptides (HDPs) show vast potential as peptide-based drugs. Great effort has been made in order to exploit their mechanisms of action, aiming to identify their targets as well as to enhance their activity and bioavailability. In this review, we will focus on both naturally occurring and designed antiviral and antitumor cationic peptides, including those here called promiscuous, in which multiple targets are associated with a single peptide structure. Emphasis will be given to their biochemical features, selectivity against extra targets, and molecular mechanisms. Peptides which possess antitumor activity against different cancer cell lines will be discussed, as well as peptides which inhibit virus replication, focusing on their applications for human health, animal health and agriculture, and their potential as new therapeutic drugs. Moreover, the current scenario for production and the use of nanotechnology as delivery tool for both classes of cationic peptides, as well as the perspectives on improving them is considered. PMID:24198814

  19. Ablation of the Kell/Xk complex alters erythrocyte divalent cation homeostasis

    PubMed Central

    Rivera, Alicia; Kam, Siok Yuen; Ho, Mengfatt; Romero, Jose R.; Lee, Soohee

    2012-01-01

    XK is a putative transporter of unknown function that is ubiquitously expressed and linked through disulfide bonds to Kell protein, an endothelin-3 (ET-3)-converting enzyme. We generated three knockout (KO) mice that lacked either Xk, Kell or both proteins and characterized erythrocyte cation levels, transport and hematological parameters. Absence of Xk or Kell was accompanied by changes in erythrocyte K+, Mg2+, Na+ and Ca2+ transport that were associated with changes in mean cellular volume and corpuscular hemoglobin concentration mean. Baseline Ca2+-ATPase activity was undetected in erythrocytes from all three mouse types but was restored upon pre-incubation with ET-3. Consistent with these alterations in Ca2+ handling, we observed increased Gardos channel activity in Kel and Xk KO mice. In addition Kel deletion was associated with increased Mg2+ permeability while Xk deletion blocked Na/Mg exchanger activity. Our results provide evidence that cellular divalent cation regulation is functionally coupled to the Kell/XK system in erythrocytes and loss of this complex may contribute to acanthocytosis formation in McLeod syndrome. PMID:23122227

  20. Calcineurin Regulates Homologous Desensitization of Natriuretic Peptide Receptor-A and Inhibits ANP-Induced Testosterone Production in MA-10 Cells

    PubMed Central

    Henesy, Michelle B.; Britain, Andrea L.; Zhu, Bing; Amable, Lauren; Honkanen, Richard E.; Corbin, Jackie D.; Francis, Sharron H.; Rich, Thomas C.

    2012-01-01

    Receptor desensitization is a ubiquitous regulatory mechanism that defines the activatable pool of receptors, and thus, the ability of cells to respond to environmental stimuli. In recent years, the molecular mechanisms controlling the desensitization of a variety of receptors have been established. However, little is known about the molecular mechanisms that underlie desensitization of natriuretic peptide receptors, including natriuretic peptide receptor-A (NPR-A). Here we report that calcineurin (protein phosphatase 2B, PP2B, PPP3C) regulates homologous desensitization of NPR-A in murine Leydig tumor (MA-10) cells. We demonstrate that both pharmacological inhibition of calcineurin activity and siRNA-mediated suppression of calcineurin expression potentiate atrial natriuretic peptide (ANP)-induced cGMP synthesis. Treatment of MA-10 cells with inhibitors of other phosphoprotein phosphatases had little or no effect on ANP-induced cGMP accumulation. In addition, overexpression of calcineurin blunts ANP-induced cGMP synthesis. We also present data indicating that the inhibition of calcineurin potentiates ANP-induced testosterone production. To better understand the contribution of calcineurin in the regulation of NPR-A activity, we examined the kinetics of ANP-induced cGMP signals. We observed transient ANP-induced cGMP signals, even in the presence of phosphodiesterase inhibitors. Inhibition of both calcineurin and phosphodiesterase dramatically slowed the decay in the response. These observations are consistent with a model in which calcineurin mediated dephosphorylation and desensitization of NPR-A is associated with significant inhibition of cGMP synthesis. PDE activity hydrolyzes cGMP, thus lowering intracellular cGMP toward the basal level. Taken together, these data suggest that calcineurin plays a previously unrecognized role in the desensitization of NPR-A and, thereby, inhibits ANP-mediated increases in testosterone production. PMID:22876290

  1. Light and dark-activated biocidal activity of conjugated polyelectrolytes.

    PubMed

    Ji, Eunkyung; Corbitt, Thomas S; Parthasarathy, Anand; Schanze, Kirk S; Whitten, David G

    2011-08-01

    This Spotlight on Applications provides an overview of a research program that has focused on the development and mechanistic study of cationic conjugated polyelectrolytes (CPEs) that function as light- and dark-active biocidal agents. Investigation has centered on poly-(phenylene ethynylene) (PPE) type conjugated polymers that are functionalized with cationic quaternary ammonium solubilizing groups. These polymers are found to interact strongly with Gram-positive and Gram-negative bacteria, and upon illumination with near-UV and visible light act to rapidly kill the bacteria. Mechanistic studies suggest that the cationic PPE-type polymers efficiently sensitize singlet oxygen ((1)O(2)), and this cytotoxic agent is responsible for initiating the sequence of events that lead to light-activated bacterial killing. Specific CPEs also exhibit dark-active antimicrobial activity, and this is believed to arise due to interactions between the cationic/lipophilic polymers and the negatively charged outer membrane characteristic of Gram-negative bacteria. Specific results are shown where a cationic CPE with a degree of polymerization of 49 exhibits pronounced light-activated killing of E. coli when present in the cell suspension at a concentration of 1 μg mL(-1).

  2. Compliant glass–polymer hybrid single ion-conducting electrolytes for lithium batteries

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Villaluenga, Irune; Wujcik, Kevin H.; Tong, Wei

    2015-12-22

    Despite high ionic conductivities, current inorganic solid electrolytes cannot be used in lithium batteries because of a lack of compliance and adhesion to active particles in battery electrodes as they are discharged and charged. Here, we have successfully developed a compliant, nonflammable, hybrid single ion-conducting electrolyte comprising inorganic sulfide glass particles covalently bonded to a perfluoropolyether polymer. The hybrid with 23 wt% perfluoropolyether exhibits low shear modulus relative to neat glass electrolytes, ionic conductivity of 10 -4 S/cm at room temperature, a cation transference number close to unity, and an electrochemical stability window up to 5 V relative to Limore » +/Li. X-ray absorption spectroscopy indicates that the hybrid electrolyte limits lithium polysulfide dissolution and is, thus, ideally suited for Li-S cells. Our work opens a previously unidentified route for developing compliant solid electrolytes that will address the challenges of lithium batteries.« less

  3. Compliant glass–polymer hybrid single ion-conducting electrolytes for lithium batteries

    PubMed Central

    Villaluenga, Irune; Wujcik, Kevin H.; Tong, Wei; Devaux, Didier; Wong, Dominica H. C.; DeSimone, Joseph M.; Balsara, Nitash P.

    2016-01-01

    Despite high ionic conductivities, current inorganic solid electrolytes cannot be used in lithium batteries because of a lack of compliance and adhesion to active particles in battery electrodes as they are discharged and charged. We have successfully developed a compliant, nonflammable, hybrid single ion-conducting electrolyte comprising inorganic sulfide glass particles covalently bonded to a perfluoropolyether polymer. The hybrid with 23 wt% perfluoropolyether exhibits low shear modulus relative to neat glass electrolytes, ionic conductivity of 10−4 S/cm at room temperature, a cation transference number close to unity, and an electrochemical stability window up to 5 V relative to Li+/Li. X-ray absorption spectroscopy indicates that the hybrid electrolyte limits lithium polysulfide dissolution and is, thus, ideally suited for Li-S cells. Our work opens a previously unidentified route for developing compliant solid electrolytes that will address the challenges of lithium batteries. PMID:26699512

  4. Development of a novel device to trap heavy metal cations: application of the specific interaction between heavy metal cation and mismatch DNA base pair.

    PubMed

    Torigoe, Hidetaka; Miyakawa, Yukako; Fukushi, Miyako; Ono, Akira; Kozasa, Tetsuo

    2009-01-01

    We have already found that Hg(II) cation specifically binds to T:T mismatch base pair in heteroduplex DNA, which increases the melting temperature of heteroduplex DNA involving T:T mismatch base pair by about 4 degrees C. We have also found that Ag(I) cation specifically binds to C:C mismatch base pair in heteroduplex DNA, which increases the melting temperature of heteroduplex DNA involving C:C mismatch base pair by about 4 degrees C. Using the specific interaction, we developed a novel device to trap each of Hg(II) and Ag(I) cation. The device is composed of 5'-biotinylated T-rich or C-rich DNA oligonucleotides, BIO-T20: 5'-Bio-T(20)-3' or BIO-C20: 5'-Bio-C(20)-3' (Bio is a biotin), immobilized on streptavidin-coated polystylene beads. When the BIO-T20-immobilized beads were added to a solution containing Hg(II) cation, and the beads trapping Hg(II) cation were collected by centrifugation, almost all of Hg(II) cation were removed from the solution. Also, when the BIO-C20-immobilized beads were added to a solution containing Ag(I) cation, and the beads trapping Ag(I) cation were collected by centrifugation, almost all of Ag(I) cation were removed from the solution. We conclude that, using the novel device developed in this study, Hg(II) and Ag(I) cation can be effectively removed from the solution.

  5. High-performance cation-exchange chromatofocusing of proteins.

    PubMed

    Kang, Xuezhen; Frey, Douglas D

    2003-03-28

    Chromatofocusing using high-performance cation-exchange column packings, as opposed to the more commonly used anion-exchange column packings, is investigated with regard to the performance achieved and the range of applications possible. Linear or convex gradients in the range from pH 2.6 to 9 were formed using a variety of commercially available column packings that provide a buffering capacity in different pH ranges, and either polyampholytes or simple mixtures having a small number (three or fewer) of buffering species as the elution buffer. The resolutions achieved using cation-exchange or anion-exchange chromatofocusing were in general comparable, although for certain pairs of proteins better resolution could be achieved using one type of packing as compared to the other, evidently due to the way electrostatic charges are distributed on the protein surface. Several chromatofocusing methods were investigated that take advantage of the acid-base properties of commercially available cation-exchange column packings. These include the use of gradients with a composite shape, the use of very low pH ranges, and the use of elution buffers containing a single buffering species. The advantages of chromatofocusing over ion-exchange chromatography using a salt gradient at constant pH were illustrated by employing the former method and a cation-exchange column packing to separate beta-lactoglobulins A and B, which is a separation reported to be impossible using the latter method and a cation-exchange column packing. Trends in the apparent isoelectric points determined using cation- and anion-exchange chromatofocusing were interpreted using applicable theories. Results of this study indicate that cation-exchange chromatofocusing is a useful technique which is complementary to anion-exchange chromatofocusing and isoelectric focusing for separating proteins at both the analytical and preparative scales.

  6. Structural, Chemical, and Dynamical Frustration: Origins of Superionic Conductivity in closo -Borate Solid Electrolytes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kweon, Kyoung E.; Varley, Joel B.; Shea, Patrick

    Li 2B 12H 12, Na 2B 12H 12, and their closo-borate relatives exhibit unusually high ionic conductivity, making them attractive as a new class of candidate electrolytes in solid-state Li- and Na-ion batteries. However, further optimization of these materials requires a deeper understanding of the fundamental mechanisms underlying ultrafast ion conduction. To this end, we use ab initio molecular dynamics simulations and density-functional calculations to explore the motivations for cation diffusion. We find that superionic behavior in Li 2B 12H 12 and Na 2B 12H 12 results from a combination of key structural, chemical, and dynamical factors that introduce intrinsicmore » frustration and disorder. A statistical metric is used to show that the structures exhibit a high density of accessible interstitial sites and site types, which correlates with the flatness of the energy landscape and the observed cation mobility. Furthermore, cations are found to dock to specific anion sites, leading to a competition between the geometric symmetry of the anion and the symmetry of the lattice itself, which can facilitate cation hopping. Finally, facile anion reorientations and other low-frequency thermal vibrations lead to fluctuations in the local potential that enhance cation mobility by creating a local driving force for hopping. In conclusion, we discuss the relevance of each factor for developing new ionic conductivity descriptors that can be used for discovery and optimization of closo-borate solid electrolytes, as well as superionic conductors more generally.« less

  7. Structural, Chemical, and Dynamical Frustration: Origins of Superionic Conductivity in closo -Borate Solid Electrolytes

    DOE PAGES

    Kweon, Kyoung E.; Varley, Joel B.; Shea, Patrick; ...

    2017-10-11

    Li 2B 12H 12, Na 2B 12H 12, and their closo-borate relatives exhibit unusually high ionic conductivity, making them attractive as a new class of candidate electrolytes in solid-state Li- and Na-ion batteries. However, further optimization of these materials requires a deeper understanding of the fundamental mechanisms underlying ultrafast ion conduction. To this end, we use ab initio molecular dynamics simulations and density-functional calculations to explore the motivations for cation diffusion. We find that superionic behavior in Li 2B 12H 12 and Na 2B 12H 12 results from a combination of key structural, chemical, and dynamical factors that introduce intrinsicmore » frustration and disorder. A statistical metric is used to show that the structures exhibit a high density of accessible interstitial sites and site types, which correlates with the flatness of the energy landscape and the observed cation mobility. Furthermore, cations are found to dock to specific anion sites, leading to a competition between the geometric symmetry of the anion and the symmetry of the lattice itself, which can facilitate cation hopping. Finally, facile anion reorientations and other low-frequency thermal vibrations lead to fluctuations in the local potential that enhance cation mobility by creating a local driving force for hopping. In conclusion, we discuss the relevance of each factor for developing new ionic conductivity descriptors that can be used for discovery and optimization of closo-borate solid electrolytes, as well as superionic conductors more generally.« less

  8. On the mechanisms of cation injection in conducting bridge memories: The case of HfO{sub 2} in contact with noble metal anodes (Au, Cu, Ag)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Saadi, M.; CNRS, LTM, F-38000 Grenoble; El Manar University, LMOP, 2092 Tunis

    Resistance switching is studied in HfO{sub 2} as a function of the anode metal (Au, Cu, and Ag) in view of its application to resistive memories (resistive random access memories, RRAM). Current-voltage (I-V) and current-time (I-t) characteristics are presented. For Au anodes, resistance transition is controlled by oxygen vacancies (oxygen-based resistive random access memory, OxRRAM). For Ag anodes, resistance switching is governed by cation injection (Conducting Bridge random access memory, CBRAM). Cu anodes lead to an intermediate case. I-t experiments are shown to be a valuable tool to distinguish between OxRRAM and CBRAM behaviors. A model is proposed to explainmore » the high-to-low resistance transition in CBRAMs. The model is based on the theory of low-temperature oxidation of metals (Cabrera-Mott theory). Upon electron injection, oxygen vacancies and oxygen ions are generated in the oxide. Oxygen ions are drifted to the anode, and an interfacial oxide is formed at the HfO{sub 2}/anode interface. If oxygen ion mobility is low in the interfacial oxide, a negative space charge builds-up at the HfO{sub 2}/oxide interface. This negative space charge is the source of a strong electric field across the interfacial oxide thickness, which pulls out cations from the anode (CBRAM case). Inversely, if oxygen ions migration through the interfacial oxide is important (or if the anode does not oxidize such as Au), bulk oxygen vacancies govern resistance transition (OxRRAM case).« less

  9. Lithium ion conducting ionic electrolytes

    DOEpatents

    Angell, C.A.; Xu, K.; Liu, C.

    1996-01-16

    A liquid, predominantly lithium-conducting, ionic electrolyte is described which has exceptionally high conductivity at temperatures of 100 C or lower, including room temperature. It comprises molten lithium salts or salt mixtures in which a small amount of an anionic polymer lithium salt is dissolved to stabilize the liquid against recrystallization. Further, a liquid ionic electrolyte which has been rubberized by addition of an extra proportion of anionic polymer, and which has good chemical and electrochemical stability, is described. This presents an attractive alternative to conventional salt-in-polymer electrolytes which are not cationic conductors. 4 figs.

  10. Lithium ion conducting ionic electrolytes

    DOEpatents

    Angell, C. Austen; Xu, Kang; Liu, Changle

    1996-01-01

    A liquid, predominantly lithium-conducting, ionic electrolyte is described which has exceptionally high conductivity at temperatures of 100.degree. C. or lower, including room temperature. It comprises molten lithium salts or salt mixtures in which a small amount of an anionic polymer lithium salt is dissolved to stabilize the liquid against recrystallization. Further, a liquid ionic electrolyte which has been rubberized by addition of an extra proportion of anionic polymer, and which has good chemical and electrochemical stability, is described. This presents an attractive alternative to conventional salt-in-polymer electrolytes which are not cationic conductors.

  11. A Lys-Trp cation-π interaction mediates the dimerization and function of the chloride intracellular channel protein 1 transmembrane domain.

    PubMed

    Peter, Bradley; Polyansky, Anton A; Fanucchi, Sylvia; Dirr, Heini W

    2014-01-14

    Chloride intracellular channel protein 1 (CLIC1) is a dual-state protein that can exist either as a soluble monomer or in an integral membrane form. The oligomerization of the transmembrane domain (TMD) remains speculative despite it being implicated in pore formation. The extent to which electrostatic and van der Waals interactions drive folding and association of the dimorphic TMD is unknown and is complicated by the requirement of interactions favorable in both aqueous and membrane environments. Here we report a putative Lys37-Trp35 cation-π interaction and show that it stabilizes the dimeric form of the CLIC1 TMD in membranes. A synthetic 30-mer peptide comprising a K37M TMD mutant was examined in 2,2,2-trifluoroethanol, sodium dodecyl sulfate micelles, and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine liposomes using far-ultraviolet (UV) circular dichroism, fluorescence, and UV absorbance spectroscopy. Our data suggest that Lys37 is not implicated in the folding, stability, or membrane insertion of the TMD peptide. However, removal of this residue impairs the formation of dimers and higher-order oligomers. This is accompanied by a 30-fold loss of chloride influx activity, suggesting that dimerization modulates the rate of chloride conductance. We propose that, within membranes, individual TMD helices associate via a Lys37-mediated cation-π interaction to form active dimers. The latter findings are also supported by results of modeling a putative TMD dimer conformation in which Lys37 and Trp35 form cation-π pairs at the dimer interface. Dimeric helix bundles may then associate to form fully active ion channels. Thus, within a membrane-like environment, aromatic interactions involving a polar lysine side chain provide a thermodynamic driving force for helix-helix association.

  12. Polyamines control of cation transport across plant membranes: implications for ion homeostasis and abiotic stress signaling.

    PubMed

    Pottosin, Igor; Shabala, Sergey

    2014-01-01

    Polyamines are unique polycationic metabolites, controlling a variety of vital functions in plants, including growth and stress responses. Over the last two decades a bulk of data was accumulated providing explicit evidence that polyamines play an essential role in regulating plant membrane transport. The most straightforward example is a blockage of the two major vacuolar cation channels, namely slow (SV) and fast (FV) activating ones, by the micromolar concentrations of polyamines. This effect is direct and fully reversible, with a potency descending in a sequence Spm(4+) > Spd(3+) > Put(2+). On the contrary, effects of polyamines on the plasma membrane (PM) cation and K(+)-selective channels are hardly dependent on polyamine species, display a relatively low affinity, and are likely to be indirect. Polyamines also affect vacuolar and PM H(+) pumps and Ca(2+) pump of the PM. On the other hand, catabolization of polyamines generates H2O2 and other reactive oxygen species (ROS), including hydroxyl radicals. Export of polyamines to the apoplast and their oxidation there by available amine oxidases results in the induction of a novel ion conductance and confers Ca(2+) influx across the PM. This mechanism, initially established for plant responses to pathogen attack (including a hypersensitive response), has been recently shown to mediate plant responses to a variety of abiotic stresses. In this review we summarize the effects of polyamines and their catabolites on cation transport in plants and discuss the implications of these effects for ion homeostasis, signaling, and plant adaptive responses to environment.

  13. Polyamines control of cation transport across plant membranes: implications for ion homeostasis and abiotic stress signaling

    PubMed Central

    Pottosin, Igor; Shabala, Sergey

    2014-01-01

    Polyamines are unique polycationic metabolites, controlling a variety of vital functions in plants, including growth and stress responses. Over the last two decades a bulk of data was accumulated providing explicit evidence that polyamines play an essential role in regulating plant membrane transport. The most straightforward example is a blockage of the two major vacuolar cation channels, namely slow (SV) and fast (FV) activating ones, by the micromolar concentrations of polyamines. This effect is direct and fully reversible, with a potency descending in a sequence Spm4+ > Spd3+ > Put2+. On the contrary, effects of polyamines on the plasma membrane (PM) cation and K+-selective channels are hardly dependent on polyamine species, display a relatively low affinity, and are likely to be indirect. Polyamines also affect vacuolar and PM H+ pumps and Ca2+ pump of the PM. On the other hand, catabolization of polyamines generates H2O2 and other reactive oxygen species (ROS), including hydroxyl radicals. Export of polyamines to the apoplast and their oxidation there by available amine oxidases results in the induction of a novel ion conductance and confers Ca2+ influx across the PM. This mechanism, initially established for plant responses to pathogen attack (including a hypersensitive response), has been recently shown to mediate plant responses to a variety of abiotic stresses. In this review we summarize the effects of polyamines and their catabolites on cation transport in plants and discuss the implications of these effects for ion homeostasis, signaling, and plant adaptive responses to environment. PMID:24795739

  14. Characterization of a C-type natriuretic peptide (CNP-39)-formed cation-selective channel from platypus (Ornithorhynchus anatinus) venom

    PubMed Central

    Kourie, Joseph I

    1999-01-01

    The lipid bilayer technique is used to characterize the biophysical and pharmacological properties of a novel, fast, cation-selective channel formed by incorporating platypus (Ornithorhynchus anatinus) venom (OaV) into lipid membranes.A synthetic C-type natriuretic peptide OaCNP-39, which is identical to that present in platypus venom, mimics the conductance, kinetics, selectivity and pharmacological properties of the OaV-formed fast cation-selective channel. The N-terminal fragment containing residues 1-17, i.e. OaCNP-39(1-17), induces the channel activity.The current amplitude of the TEACl-insensitive fast cation-selective channel is dependent on cytoplasmic K+, [K+]cis. The increase in the current amplitude, as a function of increasing [K+]cis, is non-linear and can be described by the Michaelis-Menten equation. At +140 mV, the values of γmax and KS are 63·1 pS and 169 mM, respectively, whereas at 0 mV the values of γmax and KS are 21·1 pS and 307 mM, respectively. γmax and KS are maximal single channel conductance and concentration for half-maximal γ, respectively. The calculated permeability ratios, PK:PRb:PNa: PCs:PLi, were 1:0·76:0·21:0·09:0·03, respectively.The probability of the fast channel being open, Po, increases from 0·15 at 0 mV to 0·75 at +140 mV. In contrast, the channel frequency, Fo, decreases from 400 to 180 events per second for voltages between 0 mV and +140. The mean open time, To, increases as the bilayer is made more positive, between 0 and +140 mV. The mean values of the voltage-dependent kinetic parameters, Po, Fo, To and mean closed time (Tc), are independent of [KCl]cis between 50 and 750 mM (P > 0·05).It is proposed that some of the symptoms of envenomation by platypus venom may be caused partly by changes in cellular functions mediated via the OaCNP-39-formed fast cation-selective channel, which affects signal transduction. PMID:10381585

  15. Differential Cationization of Fatty Acids with Monovalent Cations Studied by ESI-MS/MS and Computational Approach.

    PubMed

    Sudarshana Reddy, B; Pavankumar, P; Sridhar, L; Saha, Soumen; Narahari Sastry, G; Prabhakar, S

    2018-04-24

    The intercellular and intracellular transport of charged species (Na + /K + ) entail interaction of the ions with neutral organic molecules and formation of adduct ions. The rate of transport of the ions across the cell membrane(s) may depend on the stability of the adduct ions, which in turn rely on structural aspects of the organic molecules that interact with the ions. Positive ion ESI mass spectra were recorded for the solutions containing fatty acids (FAs) and monovalent cations (X=Li + , Na + , K + , Rb + and Cs + ). Product ion spectra of the [FA+X] + ions were recorded at different collision energies. Theoretical studies were exploited under both gas phase and solvent phase to investigate the structural effects of the fatty acids during cationization. Stability of [FA+X] + adduct ions were further estimated by means of AIM topological analyses and interaction energy (IE) values. Positive ion ESI-MS analyses of the solution of FAs and X + ions showed preferential binding of the K + ions to FAs. The K + ion binding increased with the increase in number of double bonds of FAs, while decreased with increase in the number of carbons of FAs. Dissociation curves of [FA+X] + ions indicated the relative stability order of the [FA+X] + ions and it was in line with the observed trends in ESI-MS. The solvent phase computational studies divulged the mode of binding and the binding efficiencies of different FAs with monovalent cations. Among the studied monovalent cations, the cationization of FAs follow the order K + >Na + >Li + >Rb + >Cs + . The docosahexaenoic acid showed high efficiency in binding with K + ion. The K + ion binding efficiency of FAs depends on the number of double bonds in unsaturated FAs and the carbon chain length in saturated FAs. The cationization trends of FAs obtained from the ESI-MS, ESI-MS/MS analyses were in good agreement with solvent phase computational studies. This article is protected by copyright. All rights reserved.

  16. Cyclic GMP is involved in auxin signalling during Arabidopsis root growth and development.

    PubMed

    Nan, Wenbin; Wang, Xiaomin; Yang, Lei; Hu, Yanfeng; Wei, Yuantao; Liang, Xiaolei; Mao, Lina; Bi, Yurong

    2014-04-01

    The second messenger cyclic guanosine 3',5'-monophosphate (cGMP) plays an important role in plant development and responses to stress. Recent studies indicated that cGMP is a secondary signal generated in response to auxin stimulation. cGMP also mediates auxin-induced adventitious root formation in mung bean and gravitropic bending in soybean. Nonetheless, the mechanism of the participation of cGMP in auxin signalling to affect these growth and developmental processes is largely unknown. In this report we provide evidence that indole-3-acetic acid (IAA) induces cGMP accumulation in Arabidopsis roots through modulation of the guanylate cyclase activity. Application of 8-bromo-cGMP (a cell-permeable cGMP derivative) increases auxin-dependent lateral root formation, root hair development, primary root growth, and gene expression. In contrast, inhibitors of endogenous cGMP synthesis block these processes induced by auxin. Data also showed that 8-bromo-cGMP enhances auxin-induced degradation of Aux/IAA protein modulated by the SCF(TIR1) ubiquitin-proteasome pathway. Furthermore, it was found that 8-bromo-cGMP is unable to directly influence the auxin-dependent TIR1-Aux/IAA interaction as evidenced by pull-down and yeast two-hybrid assays. In addition, we provide evidence for cGMP-mediated modulation of auxin signalling through cGMP-dependent protein kinase (PKG). Our results suggest that cGMP acts as a mediator to participate in auxin signalling and may govern this process by PKG activity via its influence on auxin-regulated gene expression and auxin/IAA degradation.

  17. Increased oxidative/nitrosative stress and decreased antioxidant enzyme activities in prostate cancer.

    PubMed

    Arsova-Sarafinovska, Zorica; Eken, Ayse; Matevska, Nadica; Erdem, Onur; Sayal, Ahmet; Savaser, Ayhan; Banev, Saso; Petrovski, Daniel; Dzikova, Sonja; Georgiev, Vladimir; Sikole, Aleksandar; Ozgök, Yaşar; Suturkova, Ljubica; Dimovski, Aleksandar J; Aydin, Ahmet

    2009-08-01

    The study was aimed to evaluate the oxidative/nitrosative stress status in prostate cancer (CaP) and benign prostatic hyperplasia (BPH). 312 men from two different populations were included: 163 men from Macedonia (73 CaP patients, 67 BPH patients and 23 control subjects) and 149 men from Turkey (34 prostate cancer patients, 100 BPH patients and 15 control subjects). We measured erythrocyte malondialdehyde (MDA) levels, erythrocyte activities of superoxide dismutase (CuZn-SOD), glutathione peroxidase (GPX) and catalase (CAT); plasma nitrite/nitrate (NO(2)(-)/NO(3)(-)), cGMP and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. A similar pattern of alteration in the oxidative/nitrosative stress-related parameters was found in both, Macedonian and Turkish studied samples: higher MDA concentrations with lower GPX and CuZn-SOD activities in CaP patients versus controls and BPH groups. The CAT activity was decreased in the CaP patients versus controls in the Turkish studied sample. Furthermore, CaP patients had increased plasma NO(2)(-)/NO(3)(-) and cGMP levels versus controls and BPH groups in both studied samples. This study has confirmed an imbalance in the oxidative stress/antioxidant status and revealed an altered nitrosative status in prostate cancer patients.

  18. Polymerized Paired Ions as Polymeric Ionic Liquid-Proton Conductivity.

    PubMed

    Gu, Hong; Yan, Feng; Texter, John

    2016-07-01

    A new polymerized ionic liquid has been derived by photopolymerization of a stimuli-responsive ionic liquid surfactant, ILAMPS, which is composed of polymerizable, paired ions. The cation is 1-methyl-3-[11-(acryloyloxy)undecyl] imidazolium (IL), and the anion is 2-acrylamido-2-methyl-1-propanesulfonate (AMPS). This ion combination is a new ionic liquid. The resulting hygroscopic resins are highly polarizable, suitable for sensor design and for ultracapacitor fabrication and proton conducting. Interactions of imidazolium with anions provide basis for stimuli-responsiveness, and are used to promote proton transport. Doping with one equivalent of HPF6 at 0% relative humidity produces a 100-fold increase in proton conductivity at 100-125 °C and activation energies for proton transport lower than those of Nafion at water loadings less than 5 per sulfonate. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. A computational study of anion-modulated cation-π interactions.

    PubMed

    Carrazana-García, Jorge A; Rodríguez-Otero, Jesús; Cabaleiro-Lago, Enrique M

    2012-05-24

    The interaction of anions with cation-π complexes formed by the guanidinium cation and benzene was thoroughly studied by means of computational methods. Potential energy surface scans were performed in order to evaluate the effect of the anion coming closer to the cation-π pair. Several structures of guanidinium-benzene complexes and anion approaching directions were examined. Supermolecule calculations were performed on ternary complexes formed by guanidinium, benzene, and one anion and the interaction energy was decomposed into its different two- and three-body contributions. The interaction energies were further dissected into their electrostatic, exchange, repulsion, polarization and dispersion contributions by means of local molecular orbital energy decomposition analysis. The results confirm that, besides the electrostatic cation-anion attraction, the effect of the anion over the cation-π interaction is mainly due to polarization and can be rationalized following the changes in the anion-π and the nonadditive (three-body) terms of the interaction. When the cation and the anion are on the same side of the π system, the three-body interaction is anticooperative, but when the anion and the cation are on opposite sides of the π system, the three-body interaction is cooperative. As far as we know, this is the first study where this kind of analysis is carried out with a structured cation as guanidinium with a significant biological interest.

  20. PEGylation enhances tumor targeting of plasmid DNA by an artificial cationized protein with repeated RGD sequences, Pronectin.

    PubMed

    Hosseinkhani, Hossein; Tabata, Yasuhiko

    2004-05-31

    The objective of this study is to investigate feasibility of a non-viral gene carrier with repeated RGD sequences (Pronectin F+) in tumor targeting for gene expression. The Pronectin F+ was cationized by introducing spermine (Sm) to the hydroxyl groups to allow to polyionically complex with plasmid DNA. The cationized Pronectin F+ prepared was additionally modified with poly(ethylene glycol) (PEG) molecules which have active ester and methoxy groups at the terminal, to form various PEG-introduced cationized Pronectin F+. The cationized Pronectin F+ with or without PEGylation at different extents was mixed with a plasmid DNA of LacZ to form respective cationized Pronectin F+-plasmid DNA complexes. The plasmid DNA was electrophoretically complexed with cationized Pronectin F+ and PEG-introduced cationized Pronectin F+, irrespective of the PEGylation extent, although the higher N/P ratio of complexes was needed for complexation with the latter Pronectin F+. The molecular size and zeta potential measurements revealed that the plasmid DNA was reduced in size to about 250 nm and the charge was changed to be positive by the complexation with cationized Pronectin F+. For the complexation with PEG-introduced cationized Pronectin F+, the charge of complex became neutral being almost 0 mV with the increasing PEGylation extents, while the molecular size was similar to that of cationized Pronectin F+. When cationized Pronectin F+-plasmid DNA complexes with or without PEGylation were intravenously injected to mice carrying a subcutaneous Meth-AR-1 fibrosarcoma mass, the PEG-introduced cationized Pronectin F+-plasmid DNA complex specifically enhanced the level of gene expression in the tumor, to a significantly high extent compared with the cationized Pronectin F+-plasmid DNA complexes and free plasmid DNA. The enhanced level of gene expression depended on the percentage of PEG introduced, the N/P ratio, and the plasmid DNA dose. A fluorescent microscopic study revealed that the