WorldWideScience

Sample records for cellular deoxynucleoside triphosphates

  1. Analysis of the Endogenous Deoxynucleoside Triphosphate Pool in HIV-Positive and -Negative Individuals Receiving Tenofovir-Emtricitabine.

    Science.gov (United States)

    Chen, Xinhui; Castillo-Mancilla, Jose R; Seifert, Sharon M; McAllister, Kevin B; Zheng, Jia-Hua; Bushman, Lane R; MaWhinney, Samantha; Anderson, Peter L

    2016-09-01

    Tenofovir (TFV) disoproxil fumarate (TDF) and emtricitabine (FTC), two nucleos(t)ide analogs (NA), are coformulated as an anti-HIV combination tablet for treatment and preexposure prophylaxis (PrEP). TDF/FTC may have effects on the deoxynucleoside triphosphate (dNTP) pool due to their similar structures and similar metabolic pathways. We carried out a comprehensive clinical study to characterize the effects of TDF/FTC on the endogenous dNTP pool, from baseline to 30 days of TDF/FTC therapy, in both treatment-naive HIV-positive and HIV-negative individuals. dATP, dCTP, dGTP, and TTP were quantified in peripheral blood mononuclear cells (PBMC) with a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodology. Forty individuals (19 HIV-positive) were enrolled and underwent a baseline visit and then received TDF/FTC for at least 30 days. Longitudinal measurements were analyzed using mixed-model segmented linear regression analysis. The dNTPs were reduced by 14% to 37% relative to the baseline level within 3 days in both HIV-negative and HIV-positive individuals (P ≤ 0.003). These reductions persisted to various degrees at day 30. These findings indicate that dNTP pools are influenced by TDF/FTC therapy. This may alter cellular homeostasis and could increase the antiviral effect through a more favorable analog/dNTP ratio. Further work is needed to elucidate mechanisms, to evaluate the clinical significance of these findings, and to further probe differences between HIV-negative and HIV-positive individuals. (This study has been registered at ClinicalTrials.gov under identifier NCT01040091.). PMID:27353267

  2. Cross-linked polymeric nanogel formulations of 5'-triphosphates of nucleoside analogues: role of the cellular membrane in drug release.

    Science.gov (United States)

    Vinogradov, Serguei V; Kohli, Ekta; Zeman, Arin D

    2005-01-01

    Activation of cytotoxic nucleoside analogues in vivo depends primarily on their cell-specific phosphorylation. Anticancer chemotherapy using nucleoside analogues may be significantly enhanced by intracellular administration of active phosphorylated drugs. However, the cellular transport of anionic compounds is very ineffective and restricted by many drug efflux transporters. Recently developed cationic nanogel carriers can encapsulate large amounts of nucleoside 5'-triphosphates that form polyionic complexes with protonated amino groups on the polyethylenimine backbone of the nanogels. In this paper, the 5'-triphosphate of an antiviral nucleoside analogue, 3'-azido-2',3'-dideoxythymidine (AZT), was efficiently synthesized and its complexes with nanogels were obtained and evaluated as potential cytotoxic drug formulations for treatment of human breast carcinoma cells. A selective phosphorylating reagent, tris-imidazolylphosphate, was used to convert AZT into the nucleoside analogue 5'-triphosphate using a one-pot procedure. The corresponding 3'-azido-2',3'-dideoxythymidine 5'-triphosphate (AZTTP) was isolated with high yield (75%). Nanogels encapsulated up to 30% of AZTTP by weight by mixing solutions of the carrier and the drug. The AZTTP/nanogel formulation showed enhanced cytotoxicity in two breast cancer cell lines, MCF-7 and MDA-MB-231, demonstrating IC50 values 130-200 times lower than those values for AZT alone. The exact mechanism of drug release from nanogels remains unclear. One mechanism could involve interaction with negatively charged counterions. A high affinity of nanogels to isolated cellular membranes has been observed, especially for nanogels made of amphiphilic block copolymer, Pluronic P85. Cellular trafficking of nanogel particles, contrasted by polyethylenimine-coordinated copper(II) ions, was studied by transmission electron microscopy (TEM), which revealed membranotropic properties of nanogels. A substantial release of encapsulated drug was

  3. HIV-1 Reverse Transcriptase based assay to determine cellular dNTP concentrations

    Science.gov (United States)

    Hollenbaugh, Joseph A.; Kim, Baek

    2016-01-01

    Summary Deoxynucleoside triphosphates (dNTPs) are the building blocks of DNA and their biosynthesis are tightly regulated in the cell. HPLC-MS and enzyme-based methods are currently employed to determine dNTP concentrations from cellular extracts. Here, we describe a highly efficient, HIV-1 reverse transcriptase (RT)-based assay to quantitate dNTP concentrations. The assay is based on the ability of HIV-1 RT to function at very low dNTP concentrations, thus providing for the high sensitivity of detection. PMID:26714705

  4. Calcium and adenosine triphosphate control of cellular pathology: asparaginase-induced pancreatitis elicited via protease-activated receptor 2.

    Science.gov (United States)

    Peng, Shuang; Gerasimenko, Julia V; Tsugorka, Tatiana; Gryshchenko, Oleksiy; Samarasinghe, Sujith; Petersen, Ole H; Gerasimenko, Oleg V

    2016-08-01

    Exocytotic secretion of digestive enzymes from pancreatic acinar cells is elicited by physiological cytosolic Ca(2+) signals, occurring as repetitive short-lasting spikes largely confined to the secretory granule region, that stimulate mitochondrial adenosine triphosphate (ATP) production. By contrast, sustained global cytosolic Ca(2+) elevations decrease ATP levels and cause necrosis, leading to the disease acute pancreatitis (AP). Toxic Ca(2+) signals can be evoked by products of alcohol and fatty acids as well as bile acids. Here, we have investigated the mechanism by which l-asparaginase evokes AP. Asparaginase is an essential element in the successful treatment of acute lymphoblastic leukaemia, the most common type of cancer affecting children, but AP is a side-effect occurring in about 5-10% of cases. Like other pancreatitis-inducing agents, asparaginase evoked intracellular Ca(2+) release followed by Ca(2+) entry and also substantially reduced Ca(2+) extrusion because of decreased intracellular ATP levels. The toxic Ca(2+) signals caused extensive necrosis. The asparaginase-induced pathology depended on protease-activated receptor 2 and its inhibition prevented the toxic Ca(2+) signals and necrosis. We tested the effects of inhibiting the Ca(2+) release-activated Ca(2+) entry by the Ca(2+) channel inhibitor GSK-7975A. This markedly reduced asparaginase-induced Ca(2+) entry and also protected effectively against the development of necrosis.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377732

  5. Calcium and adenosine triphosphate control of cellular pathology: asparaginase-induced pancreatitis elicited via protease-activated receptor 2

    Science.gov (United States)

    Peng, Shuang; Gerasimenko, Julia V.; Tsugorka, Tatiana; Gryshchenko, Oleksiy; Samarasinghe, Sujith; Gerasimenko, Oleg V.

    2016-01-01

    Exocytotic secretion of digestive enzymes from pancreatic acinar cells is elicited by physiological cytosolic Ca2+ signals, occurring as repetitive short-lasting spikes largely confined to the secretory granule region, that stimulate mitochondrial adenosine triphosphate (ATP) production. By contrast, sustained global cytosolic Ca2+ elevations decrease ATP levels and cause necrosis, leading to the disease acute pancreatitis (AP). Toxic Ca2+ signals can be evoked by products of alcohol and fatty acids as well as bile acids. Here, we have investigated the mechanism by which l-asparaginase evokes AP. Asparaginase is an essential element in the successful treatment of acute lymphoblastic leukaemia, the most common type of cancer affecting children, but AP is a side-effect occurring in about 5–10% of cases. Like other pancreatitis-inducing agents, asparaginase evoked intracellular Ca2+ release followed by Ca2+ entry and also substantially reduced Ca2+ extrusion because of decreased intracellular ATP levels. The toxic Ca2+ signals caused extensive necrosis. The asparaginase-induced pathology depended on protease-activated receptor 2 and its inhibition prevented the toxic Ca2+ signals and necrosis. We tested the effects of inhibiting the Ca2+ release-activated Ca2+ entry by the Ca2+ channel inhibitor GSK-7975A. This markedly reduced asparaginase-induced Ca2+ entry and also protected effectively against the development of necrosis. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’. PMID:27377732

  6. Macroscopic and Fluorescent Discrimination of Adenosine Triphosphate via Selective Metallo-hydrogel Formation: A Visual, Practical, and Reliable Rehearsal toward Cellular Imaging.

    Science.gov (United States)

    Fang, Weiwei; Liu, Cong; Yu, Fabiao; Liu, Yaoqi; Li, Zhenhua; Chen, Lingxin; Bao, Xiaoling; Tu, Tao

    2016-08-17

    With use of simple terpyridine zinc nitrate complexes, intriguing visual recognition of adenosine triphosphate (ATP) via selective coordination assembly leading to two-component metallo-hydrogel formation has been realized. With intensive fluorescent study and density functional theory calculations, it may be inferred, besides the selective metal-ligand interaction between Zn center and phosphate groups, the intramolecular π-stacking between the planar nucleobases of ATP and the metal-hybrid aromatic ring of pincer complex strongly affected the geometry of the coordinated adducts and possible molecular self-assembly process, which constitute a completely new sensing strategy in comparison with the conventional approaches. Furthermore, in light of extreme sensitivity of pincer zinc complexes toward ATP at micromolar scale (1.85 μM) and remarkable fluorescent enhancement (ca. 44-fold) upon ATP addition, the feasibility of the low cytotoxicity pincer zinc complexes in monitoring ATP in HeLa cells has been fulfilled with confocal fluorescence microscopy. PMID:27420773

  7. Imaging Adenosine Triphosphate (ATP).

    Science.gov (United States)

    Rajendran, Megha; Dane, Eric; Conley, Jason; Tantama, Mathew

    2016-08-01

    Adenosine triphosphate (ATP) is a universal mediator of metabolism and signaling across unicellular and multicellular species. There is a fundamental interdependence between the dynamics of ATP and the physiology that occurs inside and outside the cell. Characterizing and understanding ATP dynamics provide valuable mechanistic insight into processes that range from neurotransmission to the chemotaxis of immune cells. Therefore, we require the methodology to interrogate both temporal and spatial components of ATP dynamics from the subcellular to the organismal levels in live specimens. Over the last several decades, a number of molecular probes that are specific to ATP have been developed. These probes have been combined with imaging approaches, particularly optical microscopy, to enable qualitative and quantitative detection of this critical molecule. In this review, we survey current examples of technologies available for visualizing ATP in living cells, and identify areas where new tools and approaches are needed to expand our capabilities.

  8. Synthesis of 4'-Methoxy 2'-Deoxynucleoside Phosphoramidites for Incorporation into Oligonucleotides.

    Science.gov (United States)

    Petrová, Magdalena; Rosenberg, Ivan

    2016-01-01

    This unit contains detailed synthetic protocols for the preparation of 4'-methoxy 2'-deoxynucleoside phosphoramidite monomers for A, G, C, T, and U. First, 3'-silyl-protected 2'-deoxynucleosides (dNs) are converted in two steps to 4',5'-enol acetates as the key starting compounds. Next, 4'-methoxy dNs are prepared by a one-pot procedure comprising N-iodosuccinimide-promoted methoxylation, hydrolysis, and reduction of the formed intermediates. Finally, 3'-phosphoramidites of 4'-methoxy dNs are obtained by a routine three-step procedure. Title phosphoramidite monomers are suitable for the synthesis of oligonucleotides on solid phase according to conventional amidite chemistry. 4'-Methoxy substitution represents a simple modification of the sugar part of dNs, where β-D-erythro epimers preferentially adopt N-type (C3'-endo, RNA-like) conformation. Moreover, it imparts superior chemical stability, nuclease resistance, and excellent hybridization properties to modified 4'-methoxyoligodeoxynucleotides. The strong tendency toward RNA-selective hybridization suggests its potential utilization in antisense and/or RNAi technologies. © 2016 by John Wiley & Sons, Inc. PMID:27584701

  9. Solar and UVC-induced mutation in human cells and inhibition by deoxynucleosides

    International Nuclear Information System (INIS)

    Optimum conditions were established for quantitating the induction of hypoxanthine guanine phosphoribosyl transferase-deficient (HGPRT-mutants in HeLa cells and a human amelanotic melanoma cell line (MM96L). Compared at a fluence of equal toxicity, noon sunlight in summer was slightly more mutagenic in MM96L than in HeLa cells. UVC exhibited similar mutagenicity as equitoxic sunlight in HeLa but was 8-fold more effective in MM96L than equitoxic sunlight. Addition of a mixture of deoxyguanosine, deoxyadenosine, deoxycytidine and thymidine to the culture medium during the 7-day expression period following irradiation gave a 3-fold reduction in the UVC-induced mutation frequency of MM96L but not HeLa cells. The results suggest that these melanocytic cells are highly susceptible to mutagenesis by short wavelength UV, in a mechanism sensitive to deoxynucleosides. (author). 21 refs.; 3 figs.; 1 tab

  10. Life on the salvage path: the deoxynucleoside kinase of Lactobacillus acidophilus R-26.

    Science.gov (United States)

    Ives, D H; Ikeda, S

    1998-01-01

    In Lactobacillus acidophilus R-26, the synthesis of DNA precursor deoxynucleotides occurs exclusively by salvage of deoxynucleosides, beginning with phosphorylation by four deoxynucleoside kinases. Subunits bearing three of these activities are uniquely organized into two heterodimers, deoxyadenosine/deoxycytidine kinase (dAK/dCK) and deoxyadenosine/deoxyguanosine kinase (dAK/dGK), which, along with a distinct deoxythymidine kinase (TK), catalyze the parallel first committed steps of dNTP biosynthesis. Whereas TK is common to most prokaryotes (and eukaryotes), the other three activities that are the emphasis of this review are quite unusual in bacteria. Each activity is regulated in cis by its homologous end-product (dNTP) which is understood to act as a multisubstrate inhibitor capable of binding to both nucleoside and phosphate subsites. Conversely, the inactive dAK subunit is progressively activated by 1) association with a dGK or dCK subunit and 2) the conformationally driven heterotropic affect of dGuo or dCyd bound to the opposing subunit. Limited proteolysis has proven to be a powerful probe of conformational states. Further indication of conformational or structural differences between dAK and dGK (or dCK) is that the former follows an ordered kinetic path, while dGK or dCK exhibits rapid-equilibrium random kinetics. The multi-substrate behavior of end-product binding provides a convenient new diagnostic tool for distinguishing kinetic mechanisms. Tandem dak-dgk genes have been cloned from Lactobacillus DNA and expressed in Escherichia coli as dAK/dGK, utilizing the associated promoter. Sequence alignments reveal 65% identity in their DNA and 61% in their derived amino acid sequences. Encoded N-terminal sequences are identical for the first 18 residues, and both subunits share conserved sequences in common with adenylate kinase and viral TK. A more unusual conserved element, which appears to play a role in the activation of dAK, resembles the G2 loop of p21

  11. Optical Aptasensors for Adenosine Triphosphate

    Science.gov (United States)

    Ng, Stella; Lim, Hui Si; Ma, Qian; Gao, Zhiqiang

    2016-01-01

    Nucleic acids are among the most researched and applied biomolecules. Their diverse two- and three-dimensional structures in conjunction with their robust chemistry and ease of manipulation provide a rare opportunity for sensor applications. Moreover, their high biocompatibility has seen them being used in the construction of in vivo assays. Various nucleic acid-based devices have been extensively studied as either the principal element in discrete molecule-like sensors or as the main component in the fabrication of sensing devices. The use of aptamers in sensors - aptasensors, in particular, has led to improvements in sensitivity, selectivity, and multiplexing capacity for a wide verity of analytes like proteins, nucleic acids, as well as small biomolecules such as glucose and adenosine triphosphate (ATP). This article reviews the progress in the use of aptamers as the principal component in sensors for optical detection of ATP with an emphasis on sensing mechanism, performance, and applications with some discussion on challenges and perspectives. PMID:27446501

  12. Adenosine triphosphate inhibition of yeast trehalase.

    Science.gov (United States)

    Panek, A D

    1969-09-01

    Yeast trehalase has been found to be inhibited non-competitively by adenosine triphosphate. Such a biological control could explain the accumulation of trehalose during the stationary phase of the growth curve. PMID:5370287

  13. Alkylation of 2'-deoxynucleosides and DNA by quinone methides derived from 2,6-di-tert-butyl-4-methylphenol.

    Science.gov (United States)

    Lewis, M A; Yoerg, D G; Bolton, J L; Thompson, J A

    1996-12-01

    4-Alkylphenols, such as the antioxidant 2, 6-di-tert-butyl-4-methylphenol (BHT), exhibit toxicities that appear to be mediated by their oxidative metabolism to electrophilic quinone methides. Reactions of these Michael acceptors with simple nucleophiles and proteins have been reported, but little information is available on quinone methide binding to the competing nucleophilic sites in DNA. In the present investigation, 2'-deoxynucleoside adducts generated in vitro with two BHT-derived quinone methides, 2,6-di-tert-butyl-4-methylenecyclohexa-2,5-dienone and 6-tert-butyl-2- (2'-hydroxy-1',1'-dimethylethyl)-4-methylenecyclohexa-2,5-dieno ne (BHTOH-QM) were isolated and identified. Both quinone methides produced adducts at the 1- and N2-positions of deoxyguanosine (dG) and the N6-position of deoxyadenosine (dA). In addition, a labile adduct formed at the 7-position of dG, which degraded to the corresponding 7-alkylguanine derivative. Additional work was conducted with BHTOH-QM, the more reactive of the two quinone methides. This species also formed stable adducts at the N4-position of deoxycytosine (dC) and the 3-position of thymidine and formed a labile adduct at the 3-position of dC that underwent hydrolytic cleavage to regenerate dC. In mixtures of deoxynucleosides treated with [14C]BHTOH-QM, alkylation occurred primarily at the N2- and 7-positions of dG and the N6-position of dA and occurred secondarily at the 1-position of dG. Treatment of calf thymus DNA with this quinone methide yielded N6-dA and N2-dG adducts with the former predominating. The unstable 7-dG adduct was detected by analysis of the 7-alkylguanine product from depurination. These results demonstrate that quinone methides are most likely to damage DNA through alkylation of the exocyclic amino groups of purine residues and possibly also by attack at the 7-position of dG followed by depurination. PMID:8951242

  14. Chemoelectrical energy conversion of adenosine triphosphate

    Science.gov (United States)

    Sundaresan, Vishnu Baba; Sarles, Stephen Andrew; Leo, Donald J.

    2007-04-01

    Plant and animal cell membranes transport charged species, neutral molecules and water through ion pumps and channels. The energy required for moving species against established concentration and charge gradients is provided by the biological fuel - adenosine triphosphate (ATP) -synthesized within the cell. The adenosine triphosphatase (ATPases) in a plant cell membrane hydrolyze ATP in the cell cytoplasm to pump protons across the cell membrane. This establishes a proton gradient across the membrane from the cell exterior into the cell cytoplasm. This proton motive force stimulates ion channels that transport nutrients and other species into the cell. This article discusses a device that converts the chemical energy stored in adenosine triphosphate into electrical power using a transporter protein, ATPase. The V-type ATPase proteins used in our prototype are extracted from red beet(Beta vulgaris) tonoplast membranes and reconstituted in a bilayer lipid membrane or BLM formed from POPC and POPS lipids. A pH7 medium that can support ATP hydrolysis is provided on both sides of the membrane and ATP is dissolved in the pH7 buffer on one side of the membrane. Hydrolysis of ATP results in the formation of a phosphate ion and adenosine diphosphate. The energy from the reaction activates ATPase in the BLM and moves a proton across the membrane. The charge gradient established across the BLM due to the reaction and ion transport is converted into electrical current by half-cell reference electrodes. The prototype ATPase cell with an effective BLM area of 4.15 mm2 carrying 15 μl of ATPase proteins was observed to develop a steady state peak power output of 70 nW, which corresponds to a specific power of 1.69 μW/cm2 and a current density of 43.4 μA/cm2 of membrane area.

  15. An Effector of Hemoglobin Structure: The Guanosine 3', 5'-Triphosphate

    OpenAIRE

    Rezaei-Zarchi, Saeed; Imani, Saber; Soufian, Safieh; Panahi, Yunes; Saboury, Ali Akbar; Arefi, Mohammad Reza

    2012-01-01

    The effect of guanosine 3', 5'-triphosphate (GTP) on the hemoglobin structure was studied by UV-visible, fluorescence and circular dichroism (CD) spectroscopies, and cyclic voltammetry. UV-visible absorption spectra showed an increase in absorbance in the regions of 420 nm and 280 nm. Fluorescence spectra showed that the Trp fluorescence intensity increased upon excitation at 280 nm, when guanosine 3', 5'-triphosphate concentration was increased in hemoglobin solution. Along with the increase...

  16. 21 CFR 864.7040 - Adenosine triphosphate release assay.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Adenosine triphosphate release assay. 864.7040 Section 864.7040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... disorders. (b) Classification. Class I (general controls)....

  17. Synthesis and Enzymatic Incorporation of Modified Deoxyuridine Triphosphates

    Directory of Open Access Journals (Sweden)

    Erkai Liu

    2015-07-01

    Full Text Available To expand the chemical functionality of DNAzymes and aptamers, several new modified deoxyuridine triphosphates have been synthesized. An important precursor that enables this aim is 5-aminomethyl dUTP, whereby the pendent amine serves as a handle for further synthetic functionalization. Five functional groups were conjugated to 5-aminomethyl dUTP. Incorporation assays were performed on several templates that demand 2–5 sequential incorporation events using several commercially available DNA polymerases. It was found that Vent (exo- DNA polymerase efficiently incorporates all five modified dUTPs. In addition, all nucleoside triphosphates were capable of supporting a double-stranded exponential PCR amplification. Modified PCR amplicons were PCR amplified into unmodified DNA and sequenced to verify that genetic information was conserved through incorporation, amplification, and reamplification. Overall these modified dUTPs represent new candidate substrates for use in selections using modified nucleotide libraries.

  18. Modified Nucleoside Triphosphates for in-vitro Selection Techniques

    Science.gov (United States)

    Iribarren, Adolfo; Dellafiore, María; Montserrat, Javier

    2016-05-01

    The development of SELEX (Selective Enhancement of Ligands by Exponential Enrichment) provides a powerful tool for the search of functional oligonucleotides with the ability to bind ligands with high affinity and selectivity (aptamers) and for the discovery of nucleic acid sequences with diverse enzymatic activities (ribozymes and DNAzymes). This technique has been extensively applied to the selection of natural DNA or RNA molecules but, in order to improve chemical and structural diversity as well as for particular applications where further chemical or biological stability is necessary, the extension of this strategy to modified oligonucleotides is desirable. Taking into account these needs, this review intends to collect the research carried out during the past years, focusing mainly on the use of modified nucleotides in SELEX and the development of mutant enzymes for broadening nucleoside triphosphates acceptance. In addition, comments regarding the synthesis of modified nucleoside triphosphate will be briefly discussed.

  19. Application of Adenosine Triphosphate Affinity Probe and Scheduled Multiple-Reaction Monitoring Analysis for Profiling Global Kinome in Human Cells in Response to Arsenite Treatment

    OpenAIRE

    Guo, Lei; Xiao, Yongsheng; Wang, Yinsheng

    2014-01-01

    Phosphorylation of cellular components catalyzed by kinases plays important roles in cell signaling and proliferation. Quantitative assessment of perturbation in global kinome may provide crucial knowledge for elucidating the mechanisms underlying the cytotoxic effects of environmental toxicants. Here, we utilized an adenosine triphosphate (ATP) affinity probe coupled with stable isotope labeling by amino acids in cell culture (SILAC) to assess quantitatively the arsenite-induced alteration o...

  20. Product ion studies of diastereomeric benzo[ghi]fluoranthene-2'-deoxynucleoside adducts by electrospray ionization and quadrupole ion trap mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Li Linge [Department of Chemistry, Loyola University, Chicago, IL 60626 (United States); Chang, H.-F. [Department of Biomedical Sciences, University of Rhode Island, Kingston, RI 02881 (United States); Olsen, Kenneth W. [Department of Chemistry, Loyola University, Chicago, IL 60626 (United States); Cho, Bongsup P. [Department of Biomedical Sciences, University of Rhode Island, Kingston, RI 02881 (United States); Chiarelli, M. Paul [Department of Chemistry, Loyola University, Chicago, IL 60626 (United States)]. E-mail: mchiare@luc.edu

    2006-01-31

    The product ion formation characteristics of the protonated molecule ions generated from 10 different deoxynucleoside adducts of benzo[ghi]fluoranthene (B[ghi]F) have been studied using electrospray ionization (ESI) and quadrupole ion trap mass spectrometry to gain a better understanding of the fragmentation mechanisms that govern structure-specific fragmentation. The reaction of the syn- and anti-diastereomers of trans-3,4-dihydroxy-5,5a-tetrahydrobenzo[ghi]fluoranthene with DNA produce four deoxyguanosine, four deoxyadenosine, and two deoxycytidine adducts whose structures differ based on the cis/trans arrangement of the hydroxyl groups and nucleic acids bound to B[ghi]F. Those adducts that have structures where the nucleic acid and 3'-hydroxyl group of B[ghi]F are cis with respect to each other undergo extensive water loss whereas those isomers where the nucleic acid and 3'-hydroxyl group are trans do not. These results are consistent with a mechanism of water loss initiated by a hydrogen-bonding interaction between the charge-bearing proton on a heterocyclic nitrogen atom on the nucleic acid and the 3'-hydroxyl oxygen on the PAH. The dG and dC adducts are observed to undergo more extensive water loss than the dA adducts. Molecular modeling indicates that the larger relative abundances of the product ions formed by water loss for the dG and dC relative to dA are due to stronger hydrogen-bonding interactions prior to fragmentation and the greater stability of the carbocations formed at the C3' carbon after fragmentation.

  1. Polyadenylation inhibition by the triphosphates of deoxyadenosine analogues

    OpenAIRE

    Chen, Lisa S.; Plunkett, William; Gandhi, Varsha

    2008-01-01

    The nucleotide substrate specificity of yeast poly(A) polymerase (yPAP) was examined with various ATP analogues of clinical relevance. The triphosphate derivatives of cladribine (2-Cl-dATP), clofarabine (Cl-F-ara-ATP), fludarabine (F-ara-ATP), and related derivatives were incubated with yPAP and 32P-radiolabeled RNA oligonucleotide primers in the absence of ATP to assay polyadenylation. While 2-Cl-ATP resulted in primer elongation, ara-ATP and F-ara-ATP were poor substrates for yPAP. In contr...

  2. Cellular and biophysical evidence for interactions between adenosine triphosphate and P-glycoprotein substrates

    DEFF Research Database (Denmark)

    Abraham, E H; Shrivastav, B; Salikhova, A Y;

    2001-01-01

    P-glycoprotein is involved with the removal of drugs, most of them cations, from the plasma membrane and cytoplasm. Pgp is also associated with movement of ATP, an anion, from the cytoplasm to the extracellular space. The central question of this study is whether drug and ATP transport associated...... with the expression of Pgp are in any way coupled. We have measured the stoichiometry of transport coupling between drug and ATP release. The drug and ATP transport that is inhibitable by the sulfonylurea compound, glyburide (P. E. Golstein, A. Boom, J. van Geffel, P. Jacobs, B. Masereel, and R. Beauwens, Pfluger...

  3. Treatment of paroxysmal supraventricular tachycardia with intravenous injection of adenosine triphosphate.

    OpenAIRE

    Saito, D.; Ueeda, M; Abe, Y.; Tani, H; Nakatsu, T.; Yoshida, H.; Haraoka, S; Nagashima, H

    1986-01-01

    Intravenous adenosine triphosphate rapidly terminated all 11 episodes of paroxysmal supraventricular tachycardia in 10 patients. Eight patients reported side effects but these resolved within 20 seconds and did not require treatment. Adenosine triphosphate is a suitable agent for the rapid termination of paroxysmal supraventricular tachycardia.

  4. Autophagy occurs within an hour of adenosine triphosphate treatment after nerve cell damage:the neuroprotective effects of adenosine triphosphate against apoptosis

    Institute of Scientific and Technical Information of China (English)

    Na Lu; Baoying Wang; Xiaohui Deng; Honggang Zhao; Yong Wang; Dongliang Li

    2014-01-01

    After hypoxia, ischemia, or inlfammatory injuries to the central nervous system, the damaged cells release a large amount of adenosine triphosphate, which may cause secondary neuronal death. Autophagy is a form of cell death that also has neuroprotective effects. Cell Counting Kit assay, monodansylcadaverine staining, lfow cytometry, western blotting, and real-time PCR were used to determine the effects of exogenous adenosine triphosphate treatment at different concentrations (2, 4, 6, 8, 10 mmol/L) over time (1, 2, 3, and 6 hours) on the apoptosis and autophagy of SH-SY5Y cells. High concentrations of extracellular adenosine triphosphate induced autophagy and apoptosis of SH-SY5Y cells. The enhanced autophagy ifrst appeared, and peaked at 1 hour after treatment with adenosine triphosphate. Cell apoptosis peaked at 3 hours, and persisted through 6 hours. With prolonged exposure to the adenosine triphosphate treatment, the fraction of apoptotic cells increased. These data suggest that the SH-SY5Y neural cells initiated autophagy against apoptosis within an hour of adenosine triphosphate treatment to protect themselves against injury.

  5. Laboratory procedures manual for the firefly luciferase assay for adenosine triphosphate (ATP)

    Science.gov (United States)

    Chappelle, E. W.; Picciolo, G. L.; Curtis, C. A.; Knust, E. A.; Nibley, D. A.; Vance, R. B.

    1975-01-01

    A manual on the procedures and instruments developed for the adenosine triphosphate (ATP) luciferase assay is presented. Data cover, laboratory maintenance, maintenance of bacterial cultures, bacteria measurement, reagents, luciferase procedures, and determination of microbal susceptibility to antibiotics.

  6. Cellular automata

    CERN Document Server

    Codd, E F

    1968-01-01

    Cellular Automata presents the fundamental principles of homogeneous cellular systems. This book discusses the possibility of biochemical computers with self-reproducing capability.Organized into eight chapters, this book begins with an overview of some theorems dealing with conditions under which universal computation and construction can be exhibited in cellular spaces. This text then presents a design for a machine embedded in a cellular space or a machine that can compute all computable functions and construct a replica of itself in any accessible and sufficiently large region of t

  7. Cyclization of the phosphate side chain of adenosine triphosphate: formation of monoadenosine 5'-trimetaphosphate.

    Science.gov (United States)

    Glonek, T; Kleps, R A; Myers, T C

    1974-07-26

    Monoadenosine 5'-trimetaphosphate has been prepared from adeno-sine 5'-triphosphate by a carbodiimide-mediated condensation. The molecule was characterized by (3l)P nuclear magnetic resonance, and its (31)P spectrum was simulated through the assumption of a three-phosphorus spin system. The molecule is highly reactive and is rapidly converted to adenosine triphosphate upon contact with water. PMID:4834364

  8. Association of Thymidylate Synthase Gene Polymorphisms with Stavudine Triphosphate Intracellular Levels and Lipodystrophy▿

    OpenAIRE

    Domingo, Pere (Domingo Pedrol); Cabeza, M. Carmen; Pruvost, Alain; Torres, Ferran; Salazar, Juliana; del Mar Gutierrez, M.; Mateo, M. Gracia; Fontanet, Angels; Fernandez, Irene; Domingo, Joan C.; Villarroya, Francesc; Vidal, Francesc; Baiget, Montserrat

    2011-01-01

    The antiviral activity and toxicity of stavudine (d4T) depend on its triphosphate metabolite, stavudine triphosphate (d4T-TP). Therefore, modifications in intracellular levels of d4T-TP may change the toxicity profile of stavudine. d4T-TP intracellular levels in peripheral blood mononuclear cells were determined with a prominence liquid chromatograph connected to a triple-quadruple mass spectrometer. Polymorphisms in the thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), ...

  9. Adenosine triphosphate inhibits melatonin synthesis in the rat pineal gland.

    Science.gov (United States)

    Souza-Teodoro, Luis Henrique; Dargenio-Garcia, Letícia; Petrilli-Lapa, Camila Lopes; Souza, Ewerton da Silva; Fernandes, Pedro A C M; Markus, Regina P; Ferreira, Zulma S

    2016-03-01

    Adenosine triphosphate (ATP) is released onto the pinealocyte, along with noradrenaline, from sympathetic neurons and triggers P2Y1 receptors that enhance β-adrenergic-induced N-acetylserotonin (NAS) synthesis. Nevertheless, the biotransformation of NAS into melatonin, which occurs due to the subsequent methylation by acetylserotonin O-methyltransferase (ASMT; EC 2.1.1.4), has not yet been evaluated in the presence of purinergic stimulation. We therefore evaluated the effects of purinergic signaling on melatonin synthesis induced by β-adrenergic stimulation. ATP increased NAS levels, but, surprisingly, inhibited melatonin synthesis in an inverse, concentration-dependent manner. Our results demonstrate that enhanced NAS levels, which depend on phospholipase C (PLC) activity (but not the induction of gene transcription), are a post-translational effect. By contrast, melatonin reduction is related to an ASMT inhibition of expression at both the gene transcription and protein levels. These results were independent of nuclear factor-kappa B (NF-kB) translocation. Neither the P2Y1 receptor activation nor the PLC-mediated pathway was involved in the decrease in melatonin, indicating that ATP regulates pineal metabolism through different mechanisms. Taken together, our data demonstrate that purinergic signaling differentially modulates NAS and melatonin synthesis and point to a regulatory role for ATP as a cotransmitter in the control of ASMT, the rate-limiting enzyme in melatonin synthesis. The endogenous production of melatonin regulates defense responses; therefore, understanding the mechanisms involving ASMT regulation might provide novel insights into the development and progression of neurological disorders since melatonin presents anti-inflammatory, neuroprotective, and neurogenic effects. PMID:26732366

  10. Behavior and stability of adenosine triphosphate (ATP) during chlorine disinfection.

    Science.gov (United States)

    Nescerecka, Alina; Juhna, Talis; Hammes, Frederik

    2016-09-15

    Adenosine triphosphate (ATP) analysis is a cultivation-independent alternative method for the determination of bacterial viability in both chlorinated and non-chlorinated water. Here we investigated the behavior and stability of ATP during chlorination in detail. Different sodium hypochlorite doses (0-22.4 mg-Cl2 L(-1); 5 min exposure) were applied to an Escherichia coli pure culture suspended in filtered river water. We observed decreasing intracellular ATP with increasing chlorine concentrations, but extracellular ATP concentrations only increased when the chlorine dose exceeded 0.35 mg L(-1). The release of ATP from chlorine-damaged bacteria coincided with severe membrane damage detected with flow cytometry (FCM). The stability of extracellular ATP was subsequently studied in different water matrixes, and we found that extracellular ATP was stable in sterile deionized water and also in chlorinated water until extremely high chlorine doses (≤11.2 mg-Cl2 L(-1); 5 min exposure). In contrast, ATP decreased relatively slowly (k = 0.145 h(-1)) in 0.1 μm filtered river water, presumably due to degradation by either extracellular enzymes or the fraction of bacteria that were able to pass through the filter. Extracellular ATP decreased considerably faster (k = 0.368 h(-1)) during batch growth of a river water bacterial community. A series of growth potential tests showed that extracellular ATP molecules were utilized as a phosphorus source during bacteria proliferation. From the combined data we conclude that ATP released from bacteria at high chlorine doses could promote bacteria regrowth, contributing to biological instability in drinking water distribution systems. PMID:27295623

  11. Behavior and stability of adenosine triphosphate (ATP) during chlorine disinfection.

    Science.gov (United States)

    Nescerecka, Alina; Juhna, Talis; Hammes, Frederik

    2016-09-15

    Adenosine triphosphate (ATP) analysis is a cultivation-independent alternative method for the determination of bacterial viability in both chlorinated and non-chlorinated water. Here we investigated the behavior and stability of ATP during chlorination in detail. Different sodium hypochlorite doses (0-22.4 mg-Cl2 L(-1); 5 min exposure) were applied to an Escherichia coli pure culture suspended in filtered river water. We observed decreasing intracellular ATP with increasing chlorine concentrations, but extracellular ATP concentrations only increased when the chlorine dose exceeded 0.35 mg L(-1). The release of ATP from chlorine-damaged bacteria coincided with severe membrane damage detected with flow cytometry (FCM). The stability of extracellular ATP was subsequently studied in different water matrixes, and we found that extracellular ATP was stable in sterile deionized water and also in chlorinated water until extremely high chlorine doses (≤11.2 mg-Cl2 L(-1); 5 min exposure). In contrast, ATP decreased relatively slowly (k = 0.145 h(-1)) in 0.1 μm filtered river water, presumably due to degradation by either extracellular enzymes or the fraction of bacteria that were able to pass through the filter. Extracellular ATP decreased considerably faster (k = 0.368 h(-1)) during batch growth of a river water bacterial community. A series of growth potential tests showed that extracellular ATP molecules were utilized as a phosphorus source during bacteria proliferation. From the combined data we conclude that ATP released from bacteria at high chlorine doses could promote bacteria regrowth, contributing to biological instability in drinking water distribution systems.

  12. CaMKII Regulation of Cardiac Ryanodine Receptors and Inositol Triphosphate Receptors

    Directory of Open Access Journals (Sweden)

    Emmanuel eCamors

    2014-05-01

    Full Text Available Ryanodine receptors (RyRs and inositol triphosphate receptors (InsP3Rs are structurally related intracellular calcium release channels that participate in multiple primary or secondary amplified Ca2+ signals, triggering muscle contraction and oscillatory Ca2+ waves, or activating transcription factors. In the heart, RyRs play an indisputable role in the process of excitation-contraction coupling as the main pathway for Ca2+ release from sarcoplasmic reticulum (SR, and a less prominent role in the process of excitation-transcription coupling. Conversely, InsP3Rs are believed to contribute in subtle ways, only, to contraction of the heart, and in more important ways to regulation of transcription factors. Because uncontrolled activity of either RyRs or InsP3Rs may elicit life-threatening arrhythmogenic and/or remodeling Ca2+ signals, regulation of their activity is of paramount importance for normal cardiac function. Due to their structural similarity, many regulatory factors, accessory proteins, and posttranslational processes are equivalent for RyRs and InsP3Rs. Here we discuss regulation of RyRs and InsP3Rs by CaMKII phosphorylation, but touch on other kinases whenever appropriate. CaMKII is emerging as a powerful modulator of RyR and InsP3R activity but interestingly, some of the complexities and controversies surrounding phosphorylation of RyRs also apply to InsP3Rs, and a clear-cut effect of CaMKII on either channel eludes investigators for now. Nevertheless, some effects of CaMKII on global cellular activity, such as SR Ca2+ leak or force-frequency potentiation, appear clear now, and this constrains the limits of the controversies and permits a more tractable approach to elucidate the effects of phosphorylation at the single channel level.

  13. Effect of calcium triphosphate cement on proximal humeral fracture osteosynthesis: a finite element analysis.

    Science.gov (United States)

    Kennedy, Jim; Feerick, Emer; McGarry, Patrick; FitzPatrick, David; Mullett, Hannan

    2013-08-01

    PURPOSE. To measure the effect of void-filling calcium triphosphate cement on the loads at the implant-bone interface of a proximal humeral fracture osteosynthesis using a finite element analysis. METHODS. Finite element models of a 3-part proximal humeral fracture fixed with a plate with and without calcium triphosphate cement augmentation were generated from a quantitative computed tomography dataset of an intact proximal humerus. Material properties were assigned to bone fragments using published expressions relating Young's modulus to local Hounsfield number. Boundary conditions were then applied to the model to replicate the physiological loads. The effect of void-filling calcium triphosphate cement was analysed. RESULTS. When the void was filled with calcium triphosphate cement, the pressure gradient of the bone surrounding the screws in the medial fracture fragment decreased 97% from up to 21.41 to 0.66 MPa. Peak pressure of the fracture planes decreased 95% from 6.10 to 0.30 MPa and occurred along the medial aspect. The mean stress in the screw locking mechanisms decreased 78% from 71.23 to 15.92 MPa. The angled proximal metaphyseal screw had the highest stress. CONCLUSION. Augmentation with calcium triphosphate cement improves initial stability and reduces stress on the implant-bone interface. PMID:24014777

  14. Cellular Telephone

    Institute of Scientific and Technical Information of China (English)

    杨周

    1996-01-01

    Cellular phones, used in automobiles, airliners, and passenger trains, are basically low-power radiotelephones. Calls go through radio transmitters that are located within small geographical units called cells. Because each cell’s signals are too weak to interfere with those of other cells operating on the same fre-

  15. Fluorometric determination of 2'-beta-fluoro-2',3'-dideoxyadenosine 5'-triphosphate, the active metabolite of a new anti-human immunodeficiency virus drug, in human lymphocytes.

    Science.gov (United States)

    Dai, F; Kelley, J A; Zhang, H; Malinowski, N; Kavlick, M F; Lietzau, J; Welles, L; Yarchoan, R; Ford, H

    2001-01-01

    A sensitive precolumn derivatization method has been developed to measure the 5'-triphosphate of 2'-beta-fluoro-2',3'-dideoxyadenosine (F-ddA, lodenosine), a new anti-HIV drug, in human lymphocytes by HPLC using fluorescence detection. Reaction of chloroacetaldehyde with F-ddA triphosphate in extracts from human lymphocytes produces a highly fluorescent etheno adduct. This derivative is then separated and quantitated by reverse-phase paired-ion chromatography. Degradation of natural nucleic acid ribosides, such as ATP, using periodate oxidation simplifies the chromatogram and minimizes interference with detection of the target analyte. This method, modeled using cultured MOLT-4 T-lymphocytes, achieves a linear detector response for peak area measurements over the range 2.5 to 22.5 pmol (50-450 nM using 50 microl sample). Analyte recovery is greater than 90%, and the method achieves a limit of detection and limit of quantitation of 1.4 and 2.5 pmol per HPLC injection (50 microl sample containing cellular extract from 2.5 x 10(6) cells), respectively. Application of this method to measure F-ddATP in peripheral blood mononuclear cells from HIV-infected patients treated with F-ddA at 3.2 mg/kg twice daily for 22 days shows F-ddATP levels which range from 1.5 to 3.5 pmol/10(6) cells. PMID:11141306

  16. Unexpected Discovery of Dichloroacetate Derived Adenosine Triphosphate Competitors Targeting Pyruvate Dehydrogenase Kinase To Inhibit Cancer Proliferation.

    Science.gov (United States)

    Zhang, Shao-Lin; Hu, Xiaohui; Zhang, Wen; Tam, Kin Yip

    2016-04-14

    Pyruvate dehydrogenase kinases (PDKs) have recently emerged as an attractive target for cancer therapy. Herein, we prepared a series of compounds derived from dichloroacetate (DCA) which inhibited cancer cells proliferation. For the first time, we have successfully developed DCA derived inhibitors that preferentially bind to the adenosine triphosphate (ATP) pocket of PDK isoform 1 (PDK1).

  17. Increased deoxythymidine triphosphate levels is a feature of relative cognitive decline

    DEFF Research Database (Denmark)

    Madsen, Claus Desler; Frederiksen, Jane H; Olsen, Maria Nathalie Angleys;

    2015-01-01

    PBMC content of deoxythymidine-triphosphate (dTTP) (20%), but not mitochondrial bioenergetics parameters measured in this study or mitochondrial ROS. Levels of dTTP in PBMCs are indicators of relative cognitive change suggesting a role of deoxyribonucleotides in the etiology of AD....

  18. Guanosine triphosphate cyclohydrolase 1 promoter deletion causes dopa-responsive dystonia

    NARCIS (Netherlands)

    Theuns, Jessie; Crosiers, David; Debaene, Luc; Nuytemans, Karen; Meeus, Bram; Sleegers, Kristel; Goossens, Dirk; Corsmit, Ellen; Elinck, Ellen; Peeters, Karin; Mattheijssens, Maria; Pickut, Barbara; Del-Favero, Jurgen; Engelborghs, Sebastiaan; De Deyn, Peter Paul; Cras, Patrick; Van Broeckhoven, Christine

    2012-01-01

    Background: Autosomal dominant dopa-responsive dystonia (AD-DRD) is caused by a biochemical defect primarily resulting from guanosine triphosphate cyclohydrolase 1 gene (GCH1) mutations. Few families have been reported without mutations in GCH1. Methods: Genome-wide linkage analysis and positional c

  19. Inhibition of DNA replication, DNA repair synthesis, and DNA polymerases α and δ by butylphenyl deoxyguanosine triphosphate

    International Nuclear Information System (INIS)

    Semiconservative DNA replication in growing mammalian cells and ultraviolet (UV)-induced DNA repair synthesis in nongrowing mammalian cells are mediated by one or both of the aphidicolin-sensitive DNA polymerases, α and/or δ. They have studied the inhibition of replication and repair synthesis in permeable human cells by N2 (p-n-butylphenyl)-2'-deoxyguanosine-5'-triphosphate (BuPh dGTP), an agent which inhibits polymerase α strongly and polymerase δ weakly. Both processes are inhibited by BuPh-dGTP in competition with dGTP. The K/sub i/'s are, for replication, 2-3 μM and, for repair synthesis, 3-4 μM, consistent with the involvement of the same DNA polymerase in both processes. Inhibition of isolated human polymerase α by BuPh-dGTP is also competitive with dGTP, but the K/sub i/ is approximately 10 nM, several hundred-fold lower than the K/sub i/'s of replication and repair synthesis. Isolated polymerase δ is inhibited by BuPh-dGTP at doses similar to those which inhibit replication and repair synthesis, however, attempts to determine the K/sub i/ of polymerase δ were hampered by the finding that the dependence of δ activity on deoxyribunucleotide concentration is parabolic at low doses. This behavior differs from the behavior of polymerase α and of cellular DNA replication and repair synthesis, all of which show a simple, hyperbolic relationship between activity and deoxyribonucleotide concentration. Thus, inhibition of DNA replication and UV induced DNA repair synthesis by BuPh dGTP is quantitatively similar to DNA polymerase δ, but some other characteristics of the cellular processes are more similar to those of polymerase α

  20. Simultaneous alteration of de novo and salvage pathway to the deoxynucleoside thriphosphate pool by (E)-2'-deoxy-(fluoromethylene)cytidine (FMDC) and zidovudine (AZT) results in increased radiosensitivity in vitro.

    OpenAIRE

    Coucke, Philippe; Cottin, Eliane; Laurent, A.; Decosterd, A.

    2007-01-01

    Abstract To test whether a thymidine analog zidovudine (=AZT), is able to modify the radiosensitizing effects of (E)-2'-Deoxy-(fluoromethylene)cytidine (FMdC). A human colon cancer cell line Widr was exposed for 48 hours prior to irradiation to FMdC. Zidovudine was added at various concentrations immediately before irradiation. We measured cell survival and the effect of FMdC, AZT and FMdC + AZT on deoxynucleotide triphosphate pool. FMdC results in a significant increase of radiosensitivit...

  1. Purification, crystallization and preliminary crystallographic analysis of deoxyuridine triphosphate nucleotidohydrolase from Arabidopsis thaliana

    Energy Technology Data Exchange (ETDEWEB)

    Bajaj, Mamta [School of Biological Sciences, University of Nebraska-Lincoln, Manter Hall, Lincoln, Nebraska 68588-0304 (United States); Moriyama, Hideaki, E-mail: hmoriyama2@unl.edu [Department of Chemistry, e-Toxicology and Biotechnology, University of Nebraska-Lincoln, Hamilton Hall, Lincoln, Nebraska 68588-0304 (United States); School of Biological Sciences, University of Nebraska-Lincoln, Manter Hall, Lincoln, Nebraska 68588-0304 (United States)

    2007-05-01

    The first crystallization of deoxyuridine triphosphate nucleotidohydrolase from plant, Arabidopsis thaliana, has been performed. An additive, taurine, was effective in producing the single crystal. The deoxyuridine triphosphate nucleotidohydrolase gene from Arabidopsis thaliana was expressed and the gene product was purified. Crystallization was performed by the hanging-drop vapour-diffusion method at 298 K using 2 M ammonium sulfate as the precipitant. X-ray diffraction data were collected to 2.2 Å resolution using Cu Kα radiation. The crystal belongs to the orthorhombic space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 69.90, b = 70.86 Å, c = 75.55 Å. Assuming the presence of a trimer in the asymmetric unit, the solvent content was 30%, with a V{sub M} of 1.8 Å{sup 3} Da{sup −1}.

  2. Description of a novel eukaryotic deoxyuridine 5'-triphosphate nucleotidohydrolase in Leishmania major

    DEFF Research Database (Denmark)

    Camacho, A; Arrebola, R; Pena Diaz, Javier;

    1997-01-01

    . None of the characteristic motifs were readily identifiable and the sequence encoded a larger polypeptide. However, the products of the reaction were dUMP and PPi, competition experiments with other deoxyribonucleoside triphosphates showed that the reaction is specific for dUTP, and the protozoan gene...... of recombinant enzyme in large quantities will now permit detailed mechanistic and structural studies, which might contribute to a rational design of specifically targeted inhibitors against dUTPase from L. major....

  3. Possible regulation of the Salmonella typhimurium histidine operon by adenosine triphosphate phosphoribosyltransferase: large metabolic effects.

    OpenAIRE

    Goitein, R K; Parsons, S. M.

    1980-01-01

    An effort to find growth conditions leading to conditional regulation of the histidine operon of Salmonella typhimurium by the allosteric first enzyme of the pathway, adenosine triphosphate phosphoribosyltransferase (EC 2.4.2.17), is reported. A strain deleting the enzyme, TR3343, behaved simply and predictably under all growth conditions, whereas histidine auxotrophs containing active enzyme behaved in complicated ways dependent upon the location of the histidine pathway lesion. hisE strains...

  4. Randomized clinical trial of adenosine 5'-triphosphate in patients with advanced non-small-cell lung cancer

    NARCIS (Netherlands)

    H.J. Agteresch; P.C. Dagnelie (Pieter); A. van der Gaast (Ate); Th. Stijnen (Theo); J.H.P. Wilson (Paul)

    2000-01-01

    textabstractBACKGROUND: Extracellular adenosine 5'-triphosphate (ATP) is involved in the regulation of a variety of biologic processes, including neurotransmission, muscle contraction, and liver glucose metabolism, via purinergic receptors. In nonrandomized studies invo

  5. Regulation of adenosine triphosphate-sensitive potassium channels suppresses the toxic effects of amyloid-beta peptide (25-35)

    Institute of Scientific and Technical Information of China (English)

    Min Kong; Maowen Ba; Hui Liang; Peng Shao; Tianxia Yu; Ying Wang

    2013-01-01

    In this study, we treated PC12 cells with 0-20 μM amyloid-β peptide (25-35) for 24 hours to induce cytotoxicity, and found that 5-20 μM amyloid-β peptide (25-35) decreased PC12 cell viability, but adenosine triphosphate-sensitive potassium channel activator diazoxide suppressed the decrease reactive oxygen species levels. These protective effects were reversed by the selective mitochondrial adenosine triphosphate-sensitive potassium channel blocker 5-hydroxydecanoate. An inducible nitric oxide synthase inhibitor, Nω-nitro-L-arginine, also protected PC12 cells from intracellular reactive oxygen species levels. However, the H2O2-degrading enzyme catalase could that the increases in both mitochondrial membrane potential and reactive oxygen species levels adenosine triphosphate-sensitive potassium channels and nitric oxide. Regulation of adenosine triphosphate-sensitive potassium channels suppresses PC12 cell cytotoxicity induced by amyloid-β

  6. Fluorescent Structural DNA Nanoballs Functionalized With Phosphate-Linked Nucleotide Triphosphates

    Science.gov (United States)

    Anderson, Jon P.; Reynolds, Bambi L.; Baum, Kristin; Williams, John G.

    2010-01-01

    Highly labeled DNA nanoballs functionalized with phosphate-linked nucleotide triphosphates (dNTPs) were developed as a source of dNTPs for DNA polymerase. The particles were prepared by strand-displacement polymerization from a self-complementary circular template. Imaged by atomic force microscopy, these functionalized particles appear as condensed fuzzy balls with diameters between 50–150 nm. They emit a bright fluorescent signal, detected in 2 msec exposures with a signal-to-noise of 25 when imaged using a TIR fluorescence microscope. PMID:20158249

  7. Synthesis of Nucleoside Triphosphates from 2'-3'-Protected Nucleosides Using Trimetaphosphate.

    Science.gov (United States)

    Mohamady, Samy; Taylor, Scott D

    2016-02-01

    Chemists have been attempting to triphosphorylate nucleosides and other alcohols using trimetaphosphate (TriMP) since the 1960s. However, this route appears to have been abandoned due to poor yields. The first practical syntheses of nucleoside triphosphates (NTPs) are reported using TriMP as the key reagent. This was achieved by reacting the tetrabutylammonium salt of TriMP with mesitylenesulfonyl chloride in the presence of DABCO in pyridine followed by the addition of an appropriately protected nucleoside and phthalimide. Quenching the reaction with aqueous buffer followed by hydrolysis of the OH protecting groups gave the NTPs in good yield. PMID:26759914

  8. Chloride permeability of rat brain membrane vesicles correlates with thiamine triphosphate content.

    Science.gov (United States)

    Bettendorff, L; Hennuy, B; De Clerck, A; Wins, P

    1994-07-25

    Incubation of rat brain homogenates with thiamine or thiamine diphosphate (TDP) leads to a synthesis of thiamine triphosphate (TTP). In membrane vesicles subsequently prepared from the homogenates, increased TTP content correlates with increased 36Cl- uptake. A hyperbolic relationship was obtained with a K0.5 of 0.27 nmol TTP/mg protein. In crude mitochondrial fractions from the brains of animals previously treated with thiamine or sulbutiamine, a positive correlation between 36Cl- uptake and TTP content was found. These results, together with other results previously obtained with the patch-clamp technique, suggest that TTP is an activator of chloride channels having a large unit conductance. PMID:7953714

  9. Scope and Limitations of Typical Copper-Free Bioorthogonal Reactions with DNA: Reactive 2'-Deoxyuridine Triphosphates for Postsynthetic Labeling.

    Science.gov (United States)

    Merkel, Marcus; Arndt, Stefanie; Ploschik, Damian; Cserép, Gergely B; Wenge, Ulrike; Kele, Péter; Wagenknecht, Hans-Achim

    2016-09-01

    Four triphosphates of 2'-deoxyuridine that carried the following bioorthogonally reactive groups were synthesized by organic-chemical methods. Two triphosphates with tetrazines and one with a cyclopropene moiety were designed for Diels-Alder reactions with inverse electron demand, and one triphosphate with a tetrazole core was designed for the "photoclick" cycloaddition. These triphosphates were not only successfully applied for oligonucleotide preparation by standard DNA polymerases, including Hemo KlenTaq, Vent, and Deep Vent, but also bypassed for full length primer extension products. Fluorescent labeling of the primer extension products was achieved by fluorophores with reactive counterparts and analyzed by polyacrylamide gel electrophoresis mobility shifts. The tetrazine-oligonucleotide conjugates were reacted with carboxymethylmonobenzocyclooctyne- and bicyclononyne-modified fluorophores. The yield of these postsynthetic reactions could significantly be improved by a more stable but still reactive nicotinic acid-derived tetrazine and by changing the key experimental conditions, mainly the pH of 7.2 and the temperature of 45-55 °C. The cyclopropene-oligonucleotide conjugate could be successfully labeled with a tetrazine-modified rhodamine in very good yields. The "photoclick" cycloaddition between tetrazole-oligonucleotide conjugates and a maleimide-modified dye worked quantitatively. The combination of primer extension, bypass, and bioorthogonal modification works also for double and triple labeling using the cyclopropene-modified 2'-deoxyuridine triphosphate. PMID:27513089

  10. Influence of hydrodynamic conditions on quantitative cellular assays in microfluidic systems.

    Science.gov (United States)

    Yin, Huabing; Zhang, Xunli; Pattrick, Nicola; Klauke, Norbert; Cordingley, Hayley C; Haswell, Stephen J; Cooper, Jonathan M

    2007-09-15

    This study demonstrates the importance of the hydrodynamic environment in microfluidic systems in quantitative cellular assays using live cells. Commonly applied flow conditions used in microfluidics were evaluated using the quantitative intracellular Ca2+ analysis of Chinese hamster ovary (CHO) cells as a model system. Above certain thresholds of shear stress, hydrodynamically induced intracellular Ca2+ fluxes were observed which mimic the responses induced by chemical stimuli, such as the agonist uridine 5'-triphosphate tris salt (UTP). This effect is of significance given the increasing application of microfluidic devices in high-throughput cellular analysis for biophysical applications and pharmacological screening.

  11. Cellular: Toward personal communications

    Science.gov (United States)

    Heffernan, Stuart

    1991-09-01

    The cellular industry is one of the fastest growing segment of the telecommunications industry. With an estimated penetration rate of 20 percent in the near future, cellular is becoming an ubiquitous telecommunications service in the U.S. In this paper we will examine the major advancements in the cellular industry: customer equipment, cellular networks, engineering tools, customer support, and nationwide seamless service.

  12. Adenosine triphosphate concentration in relation to microbial biomass in aquatic systems

    Energy Technology Data Exchange (ETDEWEB)

    Cunningham, H.W. Jr.

    1977-01-01

    Analyses of adenosine triphosphate (ATP) extracted from a sediment community of an aquatic ecosystem by the sulfuric acid method are complicated by inhibitions from inorganic and organic compounds. Inhibitions by inorganic compounds are reversible while those by organic compounds are irreversible. The primary inhibition by organic compounds results by complexing with acid-soluble fulvic acids which will prevent the detection of as much as 80% of the ATP present in a sample by the luciferin-luciferase reaction. Analytical techniques were developed to partially circumvent such interferences. Biomass interpretations from ATP concentrations in aquatic systems are complicated by the diversity of the microbiota and by the variability in the carbon to ATP ratio caused by environmental conditions. However, when levels of ATP are considered as a physiological condition of a sedimentary community, this data provides a means to interpret community metabolism not available hitherto.

  13. Interaction of Divalent Metal Ions with the Adenosine Triphosphate Measured Using Nuclear Magnetic Resonance

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The interaction of adenosine triphosphate with divalent metal ions is important in biochemical functions. The effects of pH and metal ions Mg2+, Ca2+, Zn2+, Mn2+, and Co2+ on the chemical shift of the phosphate group of ATP have been studied using Nuclear Magnetic Resonance. The chemical shift of the β-phosphate of ATP is the most sensitive to pH. Ca2+ and Mg2+ bind with the α- and β-phosphate groups of ATP. Zn2+ binds to the adenosine ring hydrogen as well as to phosphate. The paramagnetic ions Mn2+ and Co2+ do not cause chemical shifts of the phosphate or proton peak. Mn2+ and Co2+ broaden the resonance peak only.

  14. Genetics and complementation of Haemophilus influenzae mutants deficient in adenosine 5'-triphosphate-dependent nuclease

    Energy Technology Data Exchange (ETDEWEB)

    Kooistra, J.; Small, G.D.; Setlow, J.K.; Shapanka, R.

    1976-04-01

    Eight different mutations in Haemophilus influenzae leading to deficiency in adenosine 5'-triphosphate (ATP)-dependent nuclease have been investigated in strains in which the mutations of the originally mutagenized strains have been transferred into the wild type. Sensitivity to mitomycin C and deoxycholate and complementation between extracts and deoxyribonucleic acid (DNA)-dependent ATPase activity have been measured. Genetic crosses have provided information on the relative position of the mutations on the genome. There are three complementation groups, corresponding to three genetic groups. The strains most sensitive to mitomycin and deoxycholate, derived from mutants originally selected on the basis of sensitivity to mitomycin C or methyl methanesulfonate, are in one group. Apparently all these sensitive strains lack DNA-dependent ATPase activity, as does a strain intermediate in sensitivity to deoxycholate, which is the sole representative of another group. There are four strains that are relatively resistant to deoxycholate and mitomycin C, and all of these contain the ATPase activity.

  15. A sensitive LC-MS/MS method for quantifying clofarabine triphosphate concentrations in human peripheral blood mononuclear cells.

    Science.gov (United States)

    Tu, Xiaowei; Lu, Youming; Zhong, Dafang; Zhang, Yifan; Chen, Xiaoyan

    2014-08-01

    Clofarabine triphosphate is an intracellular active metabolite of clofarabine. In the present study, we developed and validated a rapid, sensitive, and selective liquid chromatography-tandem mass spectrometry method (LC-MS/MS) for quantifying clofarabine triphosphate concentrations in human peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from blood using the Ficoll gradient centrifugation method. Chromatographic separation was performed on a CN column using an isocratic mobile phase comprising acetonitrile/5mM ammonium acetate with 0.001% ammonium hydroxide (20/80, v/v) at a flow rate of 0.60 mL/min. Detection was carried out by MS/MS in the multiple reaction monitoring mode using a negative electrospray ionization interface. The method was validated in concentration ranges of 1.25-100 ng/10(7) cells with acceptable accuracy and precision using 50 μL of cell extract. Clofarabine triphosphate was stable in a series of stability studies with bench-top, auto-sampler, and repeated freeze-thaw cycles. The validated method was successfully used to measure the concentrations of clofarabine triphosphate in PBMCs from cancer patients treated with clofarabine. PMID:24529342

  16. Activation of guanine-{beta}-D-arabinofuranoside and deoxyguanosine to triphosphates by a common pathway blocks T lymphoblasts at different checkpoints

    Energy Technology Data Exchange (ETDEWEB)

    Leanza, Luigi; Miazzi, Cristina; Ferraro, Paola; Reichard, Peter; Bianchi, Vera, E-mail: vbianchi@bio.unipd.it

    2010-12-10

    The deoxyguanosine (GdR) analog guanine-ss-D-arabinofuranoside (araG) has a specific toxicity for T lymphocytes. Also GdR is toxic for T lymphocytes, provided its degradation by purine nucleoside phosphorylase (PNP) is prevented, by genetic loss of PNP or by enzyme inhibitors. The toxicity of both nucleosides requires their phosphorylation to triphosphates, indicating involvement of DNA replication. In cultured cells we found by isotope-flow experiments with labeled araG a rapid accumulation and turnover of araG phosphates regulated by cytosolic and mitochondrial kinases and deoxynucleotidases. At equilibrium their partition between cytosol and mitochondria depended on the substrate saturation kinetics and cellular abundance of the kinases leading to higher araGTP concentrations in mitochondria. dGTP interfered with the allosteric regulation of ribonucleotide reduction, led to highly imbalanced dNTP pools with gradual inhibition of DNA synthesis and cell-cycle arrest at the G1-S boundary. AraGTP had no effect on ribonucleotide reduction. AraG was in minute amounts incorporated into nuclear DNA and stopped DNA synthesis arresting cells in S-phase. Both nucleosides eventually induced caspases and led to apoptosis. We used high, clinically relevant concentrations of araG, toxic for nuclear DNA synthesis. Our experiments do not exclude an effect on mitochondrial DNA at low araG concentrations when phosphorylation occurs mainly in mitochondria.

  17. Detection of adenosine triphosphate through polymerization-induced aggregation of actin-conjugated gold/silver nanorods

    Science.gov (United States)

    Liao, Yu-Ju; Shiang, Yen-Chun; Chen, Li-Yi; Hsu, Chia-Lun; Huang, Chih-Ching; Chang, Huan-Tsung

    2013-11-01

    We have developed a simple and selective nanosensor for the optical detection of adenosine triphosphate (ATP) using globular actin-conjugated gold/silver nanorods (G-actin-Au/Ag NRs). By simply mixing G-actin and Au/Ag NRs (length ˜56 nm and diameter ˜12 nm), G-actin-Au/Ag NRs were prepared which were stable in physiological solutions (25 mM Tris-HCl, 150 mM NaCl, 5.0 mM KCl, 3.0 mM MgCl2 and 1.0 mM CaCl2; pH 7.4). Introduction of ATP into the G-actin-Au/Ag NR solutions in the presence of excess G-actin induced the formation of filamentous actin-conjugated Au/Ag NR aggregates through ATP-induced polymerization of G-actin. When compared to G-actin-modified spherical Au nanoparticles having a size of 13 nm or 56 nm, G-actin-Au/Ag NRs provided better sensitivity for ATP, mainly because the longitudinal surface plasmon absorbance of the Au/Ag NR has a more sensitive response to aggregation. This G-actin-Au/Ag NR probe provided high sensitivity (limit of detection 25 nM) for ATP with remarkable selectivity (>10-fold) over other adenine nucleotides (adenosine, adenosine monophosphate and adenosine diphosphate) and nucleoside triphosphates (guanosine triphosphate, cytidine triphosphate and uridine triphosphate). It also allowed the determination of ATP concentrations in plasma samples without conducting tedious sample pretreatments; the only necessary step was simple dilution. Our experimental results are in good agreement with those obtained from a commercial luciferin-luciferase bioluminescence assay. Our simple, sensitive and selective approach appears to have a practical potential for the clinical diagnosis of diseases (e.g. cystic fibrosis) associated with changes in ATP concentrations.

  18. ATM Couples Replication Stress and Metabolic Reprogramming during Cellular Senescence

    Directory of Open Access Journals (Sweden)

    Katherine M. Aird

    2015-05-01

    Full Text Available Replication stress induced by nucleotide deficiency plays an important role in cancer initiation. Replication stress in primary cells typically activates the cellular senescence tumor-suppression mechanism. Senescence bypass correlates with development of cancer, a disease characterized by metabolic reprogramming. However, the role of metabolic reprogramming in the cellular response to replication stress has been little explored. Here, we report that ataxia telangiectasia mutated (ATM plays a central role in regulating the cellular response to replication stress by shifting cellular metabolism. ATM inactivation bypasses senescence induced by replication stress triggered by nucleotide deficiency. This was due to restoration of deoxyribonucleotide triphosphate (dNTP levels through both upregulation of the pentose phosphate pathway via increased glucose-6-phosphate dehydrogenase (G6PD activity and enhanced glucose and glutamine consumption. These phenotypes were mediated by a coordinated suppression of p53 and upregulation of c-MYC downstream of ATM inactivation. Our data indicate that ATM status couples replication stress and metabolic reprogramming during senescence.

  19. Hybrid integrated biological-solid-state system powered with adenosine triphosphate

    Science.gov (United States)

    Roseman, Jared M.; Lin, Jianxun; Ramakrishnan, Siddharth; Rosenstein, Jacob K.; Shepard, Kenneth L.

    2015-12-01

    There is enormous potential in combining the capabilities of the biological and the solid state to create hybrid engineered systems. While there have been recent efforts to harness power from naturally occurring potentials in living systems in plants and animals to power complementary metal-oxide-semiconductor integrated circuits, here we report the first successful effort to isolate the energetics of an electrogenic ion pump in an engineered in vitro environment to power such an artificial system. An integrated circuit is powered by adenosine triphosphate through the action of Na+/K+ adenosine triphosphatases in an integrated in vitro lipid bilayer membrane. The ion pumps (active in the membrane at numbers exceeding 2 × 106 mm-2) are able to sustain a short-circuit current of 32.6 pA mm-2 and an open-circuit voltage of 78 mV, providing for a maximum power transfer of 1.27 pW mm-2 from a single bilayer. Two series-stacked bilayers provide a voltage sufficient to operate an integrated circuit with a conversion efficiency of chemical to electrical energy of 14.9%.

  20. Five putative nucleoside triphosphate diphosphohydrolase genes are expressed in Trichomonas vaginalis.

    Science.gov (United States)

    Frasson, Amanda Piccoli; Dos Santos, Odelta; Meirelles, Lúcia Collares; Macedo, Alexandre José; Tasca, Tiana

    2016-01-01

    Trichomonas vaginalis is a protozoan that parasitizes the human urogenital tract causing trichomoniasis, the most common non-viral sexually transmitted disease. The parasite has unique genomic characteristics such as a large genome size and expanded gene families. Ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) is an enzyme responsible for hydrolyzing nucleoside tri- and diphosphates and has already been biochemically characterized in T. vaginalis. Considering the important role of this enzyme in the production of extracellular adenosine for parasite uptake, we evaluated the gene expression of five putative NTPDases in T. vaginalis. We showed that all five putative TvNTPDase genes (TvNTPDase1-5) were expressed by both fresh clinical and long-term grown isolates. The amino acid alignment predicted the presence of the five crucial apyrase conserved regions, transmembrane domains, signal peptides, phosphorylation and catalytic sites. Moreover, a phylogenetic analysis showed that TvNTPDase sequences make up a clade with NTPDases intracellularly located. Biochemical NTPDase activity (ATP and ADP hydrolysis) is responsive to the serum-restrictive conditions and the gene expression of TvNTPDases was mostly increased, mainly TvNTPDase2 and TvNTPDase4, although there was not a clear pattern of expression among them. In summary, the present report demonstrates the gene expression patterns of predicted NTPDases in T. vaginalis.

  1. A Graphene and Aptamer Based Liquid Gated FET-Like Electrochemical Biosensor to Detect Adenosine Triphosphate.

    Science.gov (United States)

    Mukherjee, Souvik; Meshik, Xenia; Choi, Min; Farid, Sidra; Datta, Debopam; Lan, Yi; Poduri, Shripriya; Sarkar, Ketaki; Baterdene, Undarmaa; Huang, Ching-En; Wang, Yung Yu; Burke, Peter; Dutta, Mitra; Stroscio, Michael A

    2015-12-01

    Here we report successful demonstration of a FET-like electrochemical nano-biosensor to accurately detect ultralow concentrations of adenosine triphosphate. As a 2D material, graphene is a promising candidate due to its large surface area, biocompatibility, and demonstrated surface binding chemistries and has been employed as the conducting channel. A short 20-base DNA aptamer is used as the sensing element to ensure that the interaction between the analyte and the aptamer occurs within the Debye length of the electrolyte (PBS). Significant increase in the drain current with progressive addition of ATP is observed whereas for control experiments, no distinct change in the drain current occurs. The sensor is found to be highly sensitive in the nanomolar (nM) to micromolar ( μM) range with a high sensitivity of 2.55 μA (mM) (-1), a detection limit as low as 10 pM, and it has potential application in medical and biological settings to detect low traces of ATP. This simplistic design strategy can be further extended to efficiently detect a broad range of other target analytes.

  2. Leptin suppresses adenosine triphosphate-induced impairment of spinal cord astrocytes.

    Science.gov (United States)

    Li, Baoman; Qi, Shuang; Sun, Guangfeng; Yang, Li; Han, Jidong; Zhu, Yue; Xia, Maosheng

    2016-10-01

    Spinal cord injury (SCI) causes long-term disability and has no clinically effective treatment. After SCI, adenosine triphosphate (ATP) may be released from neuronal cells and astrocytes in large amounts. Our previous studies have shown that the extracellular release of ATP increases the phosphorylation of cytosolic phospholipase A2 (cPLA2 ) and triggers the rapid release of arachidonic acid (AA) and prostaglandin E2 (PGE2) via the stimulation of epidermal growth factor receptor (EGFR) and the downstream phosphorylation of extracellular-regulated protein kinases 1 and 2. Leptin, a glycoprotein, induces the activation of the Janus kinase (JAK2)/signal transducers and activators of transcription-3 (Stat3) pathway via the leptin receptor. In this study, we found that 1) prolonged leptin treatment suppressed the ATP-stimulated release of AA and PGE2 from cultured spinal cord astrocytes; 2) leptin elevated the expression of caveolin-1 (Cav-1) via the JAK2/Stat3 signaling pathway; 3) Cav-1 blocked the interaction between Src and EGFR, thereby inhibiting the phosphorylation of EGFR and cPLA2 and attenuating the release of AA or PGE2; 4) pretreatment with leptin decreased ;he level of apoptosis and the release of interleukin-6 from cocultured neurons and astrocytes; and 5) leptin improved the recovery of locomotion in mice after SCI. Our results highlight leptin as a promising therapeutic agent for SCI. © 2016 Wiley Periodicals, Inc. PMID:27316329

  3. The clinical value of adenosine triphosphate stress myocardial perfusion tomography for detecting coronary artery disease

    International Nuclear Information System (INIS)

    Objective: To study the clinical value of adenosine triphosphate stress myocardial perfusion tomography imaging (ATP-MPI) in detection of coronary artery disease (CAD). Methods: There were 278 patients underwent ATP-MPI, 51 patients of them also underwent coronary angiography (CAG). Seventy-three patients underwent stress-rest myocardial perfusion tomography imaging with multi-stage submaximal exercise test (ST-MPI) and CAG serving as control group. Results: 1) Side effects: there were 11 different symptoms and atrioventricular conduction block (10 patients), sinoatrial conduction block (2 patients) occurred during ATP stress. Allopathy or interruption of ATP stress did not happen. 2) The sensitivity and specificity of ATP-MPI in detection of CAD were 97.1% and 82.4%, respectively, and those in detection of ≥50% narrowing coronary artery were 91.0% and 94.7%, respectively. 3) In patients without myocardial infarction, the sensitivity and specificity of ATP-MPI in detection of myocardial ischemia were comparable to those of ST-MPI. Conclusion: ATP-MPI is an accurate, safe modality and is comparable to ST-MPI in the detection of CAD

  4. Measurement and interpretation of microbial adenosine tri-phosphate (ATP) in aquatic environments.

    Science.gov (United States)

    Hammes, Frederik; Goldschmidt, Felix; Vital, Marius; Wang, Yingying; Egli, Thomas

    2010-07-01

    There is a widespread need for cultivation-free methods to quantify viability of natural microbial communities in aquatic environments. Adenosine tri-phosphate (ATP) is the energy currency of all living cells, and therefore a useful indicator of viability. A luminescence-based ATP kit/protocol was optimised in order to detect ATP concentrations as low as 0.0001 nM with a standard deviation of water samples from a variety of aquatic environments (drinking water, groundwater, bottled water, river water, lake water and wastewater effluent) were analysed for extracellular ATP and microbial ATP in comparison with flow-cytometric (FCM) parameters. Microbial ATP concentrations ranged between 3% and 97% of total ATP concentrations, and correlated well (R(2)=0.8) with the concentrations of intact microbial cells (after staining with propidium iodide). From this correlation, we calculated an average ATP-per-cell value of 1.75x10(-10)nmol/cell. An even better correlation (R(2)=0.88) was observed between intact biovolume (derived from FCM scatter data) and microbial ATP concentrations, and an average ATP-per-biovolume value of 2.95x10(-9)nmol/microm(3) was calculated. These results support the use of ATP analysis for both routine monitoring and research purposes, and contribute towards a better interpretation of ATP data. PMID:20605621

  5. INHIBITORY EFFECTS OF ADENOSINE 5' -TRIPHOSPHATE ON COCHLEAR FUNCTION OF GUINEA PIG

    Institute of Scientific and Technical Information of China (English)

    杨军; 李吉平; 钱敏飞; 徐秀玲; 王家东; 丁大连

    2005-01-01

    Objective To study effects of adenosine 5'-triphosphate (ATP) on cochlear function of guinea pig. Methods After perfusion of ATP into perilymphatic spaces of the guinea pig cochlea, summating potential (SP), cochlear microphonic (CM) , auditory nerve compound action potential ( CAP ) , distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) were measured. Results The results showed concentration-dependent effect of ATP on the response alterations of bioelectric activity in cochlea. Administration of lmmol/L ATP caused an increase both in the amplitude of the SP and in the threshold of ABR, a decrease in amplitude of the CAP and DPOAE. In addition, response alterations of the CAP and DPOAE showed in an intensity- and frequency-dependent manner, respectively. At levels of 20 -70dB nHL sound intensity, lmmol/L ATP caused a significant decrease in the CAP amplitude, while at moderate and high frequency ranges of 2 -8kHz it reduced DPOAE amplitude significantly. 330μmol/L ATP also increased the threshold of ABR. Conclusion ATP through perilymphatic perfusion could inhibit cochlear function of guinea pig.

  6. Electroacupuncture improves neuropathic pain Adenosine,adenosine 5'-triphosphate disodium and their receptors perhaps change simultaneously

    Institute of Scientific and Technical Information of China (English)

    Wen Ren; Wenzhan Tu; Songhe Jiang; Ruidong Cheng; Yaping Du

    2012-01-01

    Applying a stimulating current to acupoints through acupuncture needles-known as electroacupuncture-has the potential to produce analgesic effects in human subjects and experimental animals.When acupuncture was applied in a rat model,adenosine 5'-triphosphate disodium in the extracellular space was broken down into adenosine,which in turn inhibited pain transmission by means of an adenosine A1 receptor-dependent process.Direct injection of an adenosine A1 receptor agonist enhanced the analgesic effect of acupuncture.The analgesic effect of acupuncture appears to be mediated by activation of A1 receptors located on ascending nerves.In neuropathic pain,there is upregulation of P2X purinoceptor 3(P2X3)receptor expression in dorsal root ganglion neurons.Conversely,the onset of mechanical hyperalgesia was diminished and established hyperalgesia was significantly reversed when P2X3 receptor expression was downregulated.The pathways upon which electroacupuncture appear to act are interwoven with pain pathways,and electroacupuncture stimuli converge with impulses originating from painful areas.Electroacupuncture may act via purinergic A1 and P2X3 receptors simultaneously to induce an analgesic effect on neuropathic pain.

  7. Comparison of the novel vasodilator uridine triphosphate and adenosine for the measurement of fractional flow reserve

    DEFF Research Database (Denmark)

    Sivertsen, Jacob; Jensen, Jan Skov; Galatius, Søren;

    2014-01-01

    AIM: Examination of the fractional flow reserve (FFR) responses of intravenous (IV) adenosine with increasing doses of intracoronary (IC) adenosine versus IC uridine triphosphate (UTP) in patients with coronary artery disease. METHODS AND RESULTS: We measured FFR in 25 patients during continuous IV...... and IC infusion (using a microcatheter in the coronary ostium). Standard IV adenosine infusion (140 μg/kg/min) was compared to 8 equimolar incremental doses of IC UTP and IC adenosine (20, 40, 60, 80, 160, 240, 320 and 640 μg/min) in a randomized order. Across all doses, ΔFFR[IC UTP - IC adenosine......] was -0.038 ± 0.008, Pdose of IC UTP, FFR was significantly lower (FFR[IC UTP] = 0.62 ± 0.04) than during IV adenosine (FFR[IV adenosine] = 0.72 ± 0.05; P=.02) and IC adenosine (FFR[IC adenosine] = 0.68 ± 0.05; P=.03). Furthermore, UTP had significantly fewer side effects compared...

  8. Age-associated repression of type 1 inositol 1, 4, 5-triphosphate receptor impairs muscle regeneration

    Science.gov (United States)

    Lee, Bora; Lee, Seung-Min; Bahn, Young Jae; Lee, Kwang-Pyo; Kang, Moonkyung; Kim, Yeon-Soo; Woo, Sun-Hee; Lim, Jae-Young; Kim, Eunhee; Kwon, Ki-Sun

    2016-01-01

    Skeletal muscle mass and power decrease with age, leading to impairment of mobility and metabolism in the elderly. Ca2+ signaling is crucial for myoblast differentiation as well as muscle contraction through activation of transcription factors and Ca2+-dependent kinases and phosphatases. Ca2+ channels, such as dihydropyridine receptor (DHPR), two-pore channel (TPC) and inositol 1,4,5-triphosphate receptor (ITPR), function to maintain Ca2+ homeostasis in myoblasts. Here, we observed a significant decrease in expression of type 1 IP3 receptor (ITPR1), but not types 2 and 3, in aged mice skeletal muscle and isolated myoblasts, compared with those of young mice. ITPR1 knockdown using shRNA-expressing viruses in C2C12 myoblasts and tibialis anterior muscle of mice inhibited myotube formation and muscle regeneration after injury, respectively, a typical phenotype of aged muscle. This aging phenotype was associated with repression of muscle-specific genes and activation of the epidermal growth factor receptor (EGFR)-Ras-extracellular signal-regulated kinase (ERK) pathway. ERK inhibition by U0126 not only induced recovery of myotube formation in old myoblasts but also facilitated muscle regeneration after injury in aged muscle. The conserved decline in ITPR1 expression in aged human skeletal muscle suggests utility as a potential therapeutic target for sarcopenia, which can be treated using ERK inhibition strategies. PMID:27658230

  9. Bond cleavages of adenosine 5'-triphosphate induced by monochromatic soft X-rays

    International Nuclear Information System (INIS)

    To investigate which type of bond is likely to be cleaved by soft X-ray exposure to an adenosine 5'-triphosphate (ATP), we observed spectral changes in X-ray absorption near edge structure (XANES) around nitrogen and oxygen K-edge of an ATP film by soft X-ray irradiation. Experiments were performed at a synchrotron soft X-ray beamline at SPring-8, Japan. The XANES spectra around the nitrogen and oxygen .K-edge slightly varied by exposure to 560 eV soft X-rays. These changes are originated from the cleavage of C-N bonds between a sugar and a nucleobase site and of C-O, P-O or O-H bond of sugar and phosphate site. From the comparison between the change in XANES intensity of σ* peak at nitrogen and that at oxygen K-edges, it is inferred that the C-O, P-O or O-H bond of sugar and phosphate is much efficiently cleaved than the C-N of N-glycoside bond by the exposure of 560 eV soft X-ray to ATP film.

  10. Identification of an Alternative Nucleoside Triphosphate: 5′-Deoxyadenosylcobinamide Phosphate Nucleotidyltransferase in Methanobacterium thermoautotrophicum ΔH

    OpenAIRE

    Michael G Thomas; Escalante-Semerena, Jorge C.

    2000-01-01

    Computer analysis of the archaeal genome databases failed to identify orthologues of all of the bacterial cobamide biosynthetic enzymes. Of particular interest was the lack of an orthologue of the bifunctional nucleoside triphosphate (NTP):5′-deoxyadenosylcobinamide kinase/GTP:adenosylcobinamide-phosphate guanylyltransferase enzyme (CobU in Salmonella enterica). This paper reports the identification of an archaeal gene encoding a new nucleotidyltransferase, which is proposed to be the nonorth...

  11. HPLC–MS/MS method for the intracellular determination of ribavirin monophosphate and ribavirin triphosphate in CEMss cells

    OpenAIRE

    Meléndez, Margarita; Rosario, Osvaldo; Zayas, Beatriz; Rodríguez, José F.

    2009-01-01

    A sensitive and specific method using high performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) for the determination of ribavirin monophosphate (RBV-MP) and ribavirin triphosphate (RBV-TP) in cells has been developed and validated. In this method, ribavirin phosphorylated metabolites were extracted and separated by anion exchange solid phase extraction (SPE). The RBV-MP and RBV-TP fractions were dephosphorylated using acid phosphatase and further purified by phenyl boronat...

  12. Diastolic Dysfunction Induced by a High-Fat Diet Is Associated with Mitochondrial Abnormality and Adenosine Triphosphate Levels in Rats

    OpenAIRE

    Kang, Ki-Woon; Kim, Ok-Soon; Chin, Jung Yeon; Kim, Won Ho; Park, Sang Hyun; Choi, Yu Jeong; Shin, Jong Ho; Jung, Kyung Tae; Lim, Do-Seon; Lee, Seong-Kyu

    2015-01-01

    Background Obesity is well-known as a risk factor for heart failure, including diastolic dysfunction. However, this mechanism in high-fat diet (HFD)-induced obese rats remain controversial. The purpose of this study was to investigate whether cardiac dysfunction develops when rats are fed with a HFD for 10 weeks; additionally, we sought to investigate the association between mitochondrial abnormalities, adenosine triphosphate (ATP) levels and cardiac dysfunction. Methods We examined myocardia...

  13. Assays To Detect the Formation of Triphosphates of Unnatural Nucleotides: Application to Escherichia coli Nucleoside Diphosphate Kinase.

    Science.gov (United States)

    Matsuura, Mariko F; Shaw, Ryan W; Moses, Jennifer D; Kim, Hyo-Joong; Kim, Myong-Jung; Kim, Myong-Sang; Hoshika, Shuichi; Karalkar, Nilesh; Benner, Steven A

    2016-03-18

    One frontier in synthetic biology seeks to move artificially expanded genetic information systems (AEGIS) into natural living cells and to arrange the metabolism of those cells to allow them to replicate plasmids built from these unnatural genetic systems. In addition to requiring polymerases that replicate AEGIS oligonucleotides, such cells require metabolic pathways that biosynthesize the triphosphates of AEGIS nucleosides, the substrates for those polymerases. Such pathways generally require nucleoside and nucleotide kinases to phosphorylate AEGIS nucleosides and nucleotides on the path to these triphosphates. Thus, constructing such pathways focuses on engineering natural nucleoside and nucleotide kinases, which often do not accept the unnatural AEGIS biosynthetic intermediates. This, in turn, requires assays that allow the enzyme engineer to follow the kinase reaction, assays that are easily confused by ATPase and other spurious activities that might arise through "site-directed damage" of the natural kinases being engineered. This article introduces three assays that can detect the formation of both natural and unnatural deoxyribonucleoside triphosphates, assessing their value as polymerase substrates at the same time as monitoring the progress of kinase engineering. Here, we focus on two complementary AEGIS nucleoside diphosphates, 6-amino-5-nitro-3-(1'-β-D-2'-deoxyribofuranosyl)-2(1H)-pyridone and 2-amino-8-(1'-β-D-2'-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one. These assays provide new ways to detect the formation of unnatural deoxyribonucleoside triphosphates in vitro and to confirm their incorporation into DNA. Thus, these assays can be used with other unnatural nucleotides. PMID:26829203

  14. Modelling cellular behaviour

    Science.gov (United States)

    Endy, Drew; Brent, Roger

    2001-01-01

    Representations of cellular processes that can be used to compute their future behaviour would be of general scientific and practical value. But past attempts to construct such representations have been disappointing. This is now changing. Increases in biological understanding combined with advances in computational methods and in computer power make it possible to foresee construction of useful and predictive simulations of cellular processes.

  15. Reversible quantum cellular automata

    CERN Document Server

    Schumacher, B

    2004-01-01

    We define quantum cellular automata as infinite quantum lattice systems with discrete time dynamics, such that the time step commutes with lattice translations and has strictly finite propagation speed. In contrast to earlier definitions this allows us to give an explicit characterization of all local rules generating such automata. The same local rules also generate the global time step for automata with periodic boundary conditions. Our main structure theorem asserts that any quantum cellular automaton is structurally reversible, i.e., that it can be obtained by applying two blockwise unitary operations in a generalized Margolus partitioning scheme. This implies that, in contrast to the classical case, the inverse of a nearest neighbor quantum cellular automaton is again a nearest neighbor automaton. We present several construction methods for quantum cellular automata, based on unitaries commuting with their translates, on the quantization of (arbitrary) reversible classical cellular automata, on quantum c...

  16. Identification of an alternative nucleoside triphosphate: 5'-deoxyadenosylcobinamide phosphate nucleotidyltransferase in Methanobacterium thermoautotrophicum delta H.

    Science.gov (United States)

    Thomas, M G; Escalante-Semerena, J C

    2000-08-01

    Computer analysis of the archaeal genome databases failed to identify orthologues of all of the bacterial cobamide biosynthetic enzymes. Of particular interest was the lack of an orthologue of the bifunctional nucleoside triphosphate (NTP):5'-deoxyadenosylcobinamide kinase/GTP:adenosylcobinamide-phosphate guanylyltransferase enzyme (CobU in Salmonella enterica). This paper reports the identification of an archaeal gene encoding a new nucleotidyltransferase, which is proposed to be the nonorthologous replacement of the S. enterica cobU gene. The gene encoding this nucleotidyltransferase was identified using comparative genome analysis of the sequenced archaeal genomes. Orthologues of the gene encoding this activity are limited at present to members of the domain Archaea. The corresponding ORF open reading frame from Methanobacterium thermoautotrophicum Delta H (MTH1152; referred to as cobY) was amplified and cloned, and the CobY protein was expressed and purified from Escherichia coli as a hexahistidine-tagged fusion protein. This enzyme had GTP:adenosylcobinamide-phosphate guanylyltransferase activity but did not have the NTP:AdoCbi kinase activity associated with the CobU enzyme of S. enterica. NTP:adenosylcobinamide kinase activity was not detected in M. thermoautotrophicum Delta H cell extract, suggesting that this organism may not have this activity. The cobY gene complemented a cobU mutant of S. enterica grown under anaerobic conditions where growth of the cell depended on de novo adenosylcobalamin biosynthesis. cobY, however, failed to restore adenosylcobalamin biosynthesis in cobU mutants grown under aerobic conditions where de novo synthesis of this coenzyme was blocked, and growth of the cell depended on the assimilation of exogenous cobinamide. These data strongly support the proposal that the relevant cobinamide intermediates during de novo adenosylcobalamin biosynthesis are adenosylcobinamide-phosphate and adenosylcobinamide-GDP, not adenosylcobinamide

  17. Amperometric biosensor system for simultaneous determination of adenosine-5'-triphosphate and glucose.

    Science.gov (United States)

    Kucherenko, Ivan S; Didukh, Daria Yu; Soldatkin, Oleksandr O; Soldatkin, Alexei P

    2014-06-01

    The majority of biosensors for adenosine-5'-triphosphate (ATP) determination are based on cascades of enzymatic reactions; therefore, they are sensitive to glucose or glycerol (depending on the enzymatic system) as well as to ATP. The presence of unknown concentrations of these substances in the sample greatly complicates the determination of ATP. To overcome this disadvantage of known biosensors, we developed a biosensor system consisting of two biosensors: the first one is based on glucose oxidase and is intended for measuring glucose concentration, and the second one is based on glucose oxidase and hexokinase and is sensitive toward both glucose and ATP. Using glucose concentration measured by the first biosensor, we can analyze the total response to glucose and ATP obtained by the second biosensor. Platinum disc electrodes were used as amperometric transducers. The polyphenilenediamine membrane was deposited onto the surface of platinum electrodes to avoid the response to electroactive substances. The effect of glucose concentration on biosensor determination of ATP was studied. The reproducibility of biosensor responses to glucose and ATP during a day was tested (relative standard deviation, RSD, of responses to glucose was 3-6% and to ATP was 8-12%) as well as storage stability of the biosensors (no decrease of glucose responses and 43% drop of ATP responses during 50 days). The measurements of ATP and glucose in pharmaceutical vials (including mixtures of ATP and glucose) were carried out. It was shown that the developed biosensor system can be used for simultaneous analysis of glucose and ATP concentrations in water solutions. PMID:24810180

  18. Coxsackievirus cloverleaf RNA containing a 5' triphosphate triggers an antiviral response via RIG-I activation.

    Science.gov (United States)

    Feng, Qian; Langereis, Martijn A; Olagnier, David; Chiang, Cindy; van de Winkel, Roel; van Essen, Peter; Zoll, Jan; Hiscott, John; van Kuppeveld, Frank J M

    2014-01-01

    Upon viral infections, pattern recognition receptors (PRRs) recognize pathogen-associated molecular patterns (PAMPs) and stimulate an antiviral state associated with the production of type I interferons (IFNs) and inflammatory markers. Type I IFNs play crucial roles in innate antiviral responses by inducing expression of interferon-stimulated genes and by activating components of the adaptive immune system. Although pegylated IFNs have been used to treat hepatitis B and C virus infections for decades, they exert substantial side effects that limit their use. Current efforts are directed toward the use of PRR agonists as an alternative approach to elicit host antiviral responses in a manner similar to that achieved in a natural infection. RIG-I is a cytosolic PRR that recognizes 5' triphosphate (5'ppp)-containing RNA ligands. Due to its ubiquitous expression profile, induction of the RIG-I pathway provides a promising platform for the development of novel antiviral agents and vaccine adjuvants. In this study, we investigated whether structured RNA elements in the genome of coxsackievirus B3 (CVB3), a picornavirus that is recognized by MDA5 during infection, could activate RIG-I when supplied with 5'ppp. We show here that a 5'ppp-containing cloverleaf (CL) RNA structure is a potent RIG-I inducer that elicits an extensive antiviral response that includes induction of classical interferon-stimulated genes, as well as type III IFNs and proinflammatory cytokines and chemokines. In addition, we show that prophylactic treatment with CVB3 CL provides protection against various viral infections including dengue virus, vesicular stomatitis virus and enterovirus 71, demonstrating the antiviral efficacy of this RNA ligand. PMID:24759703

  19. Adenosine 5′-Triphosphate Flux Through the North Inlet Marsh System †

    Science.gov (United States)

    Chrzanowski, Thomas H.; Stevenson, L. Harold; Kjerfve, Bjorn

    1979-01-01

    The distribution, fluctuation, and short-term transport of total microbial biomass (measured as adenosine 5′-triphosphate [ATP]) was investigated in a large salt marsh creek. Hourly samples were collected synoptically for 25 h from 10 boats positioned across the 320-m width of the creek. Samples were collected from three depths ranging from 0.2 to 8.0 m. Hourly data obtained from each station were graphed, plotting depth against ATP. Subsequently, interpolated ATP values were generated for every one-tenth depth from the surface to the bottom with the use of an 11-point proportional divider. A total of 2,750 values were generated, and a mean value of 0.865 mg of ATP per m3 was determined. Maximum levels of ATP were found at high tide and minimal values were found at low tide. The distribution of ATP concentrations was found to be complex, with no suggestion of vertical stratification; however, horizontal divisions were apparent. ATP values corrected for direction of flow or velocity indicated two ebb-directed channels; however, when considered in total, there was a net import of ATP through the interface. The total import of ATP for this 25-h sampling period was calculated to be 3.58 kg, corresponding to a net transport of 39.8 mg of ATP per s through the cross section. Results suggest that detailed characterization of a creek transect in terms of ATP or any similar parameter requires the simultaneous measurements of both the concentration of the parameter in question and the velocity at the time and point from which the sample was taken. PMID:16345382

  20. Coxsackievirus cloverleaf RNA containing a 5' triphosphate triggers an antiviral response via RIG-I activation.

    Directory of Open Access Journals (Sweden)

    Qian Feng

    Full Text Available Upon viral infections, pattern recognition receptors (PRRs recognize pathogen-associated molecular patterns (PAMPs and stimulate an antiviral state associated with the production of type I interferons (IFNs and inflammatory markers. Type I IFNs play crucial roles in innate antiviral responses by inducing expression of interferon-stimulated genes and by activating components of the adaptive immune system. Although pegylated IFNs have been used to treat hepatitis B and C virus infections for decades, they exert substantial side effects that limit their use. Current efforts are directed toward the use of PRR agonists as an alternative approach to elicit host antiviral responses in a manner similar to that achieved in a natural infection. RIG-I is a cytosolic PRR that recognizes 5' triphosphate (5'ppp-containing RNA ligands. Due to its ubiquitous expression profile, induction of the RIG-I pathway provides a promising platform for the development of novel antiviral agents and vaccine adjuvants. In this study, we investigated whether structured RNA elements in the genome of coxsackievirus B3 (CVB3, a picornavirus that is recognized by MDA5 during infection, could activate RIG-I when supplied with 5'ppp. We show here that a 5'ppp-containing cloverleaf (CL RNA structure is a potent RIG-I inducer that elicits an extensive antiviral response that includes induction of classical interferon-stimulated genes, as well as type III IFNs and proinflammatory cytokines and chemokines. In addition, we show that prophylactic treatment with CVB3 CL provides protection against various viral infections including dengue virus, vesicular stomatitis virus and enterovirus 71, demonstrating the antiviral efficacy of this RNA ligand.

  1. Adenosine-5'-triphosphate release by Mannheimia haemolytica, lipopolysaccharide, and interleukin-1 stimulated bovine pulmonary epithelial cells.

    Science.gov (United States)

    Craddick, Michael; Patel, Rakhi; Lower, Amanda; Highlander, Sarah; Ackermann, Mark; McClenahan, David

    2012-09-15

    Mannheimia haemolytica, one of the agents associated with bovine respiratory disease complex, can cause severe lung pathology including the leakage of vascular products into the airways and alveoli. Previous work by this laboratory has demonstrated that bovine lung endothelial and epithelial cells undergo dramatic permeability increases when exposed to adenosine-5'-triphosphate (ATP). Therefore, we wanted to determine if ATP levels were elevated in bronchoalveolar lavage (BAL) samples from calves experimentally infected with M. haemolytica. In addition, cultured bovine pulmonary epithelial (BPE) cells were stimulated with heat-killed and live M. haemolytica bacteria, lipopolysaccharide (LPS), lipoteichoic acid (LTA), interleukin-1 (IL-1), and zymosan activated plasma (ZAP) to determine whether they might release extracellular ATP during in vitro infection. Calves experimentally exposed to M. haemolytica had an approximately 2-fold higher level of ATP in their BAL samples compared to control. BPE cells exposed to increasing numbers of heat-killed or live M. haemolytica had significantly increased levels of ATP release as compared to time-matched controls. Finally, BPE cells treated with several concentrations of LPS and IL-1 had increases in ATP release as compared to time-matched controls. This increase appeared to be a result of active ATP secretion by the cells, as cell viability was similar between treated and non-treated cells. Neither ZAP nor LTA induced any ATP release by the cells. In conclusion, ATP levels are elevated in lung secretions from calves infected with M. haemolytica. In addition, lung epithelial cells can actively release ATP when exposed to heat-killed or live M. haemolytica, LPS or IL-1. PMID:22771196

  2. Construction of deletion mutants in the phosphotransferase transport system and adenosine triphosphate-binding cassette transporters in Listeria monocytogenes and analysis of their growth under different stress conditions

    Directory of Open Access Journals (Sweden)

    Marina Ceruso

    2013-10-01

    Full Text Available Functional genomics approaches enable us to investigate the biochemical, cellular, and physiological properties of each gene product and are nowadays applied to enhance food safety by understanding microbial stress responses in food and host-pathogen interactions. Listeria monocytogenes is a food-borne pathogen that causes listeriosis and is difficult to eliminate this pathogen since it can survive under multiple stress conditions such as low pH and low temperature. Detailed studies are needed to determine its mode of action and to understand the mechanisms that protect the pathogen when it is subjected to stress. In this study, deletion mutants of phosphotransferase transport system genes (PTS and adenosine triphosphate(ATP-binding cassette transporters (ABC of Listeria monocytogenes F2365 were created using molecular techniques. These mutants and the wild-type were tested under different stress conditions, such as in solutions with different NaCl concentration, pH value and for nisin resistance. Results demonstrate that the behaviour of these deletion mutants is different from the wild type. In particular, deleted genes may be involved in L. monocytogenes resistance to nisin and to acid and salt concentrations. Functional genomics research on L. monocytogenes allows a better understanding of the genes related to stress responses and this knowledge may help in intervention strategies to control this food-borne pathogen. Furthermore, specific gene markers can be used to identify and subtype L. monocytogenes. Thus, future development of this study will focus on additional functional analyses of important stress response-related genes, as well as on methods for rapid and sensitive detection of L. monocytogenes such as using DNA microarrays.

  3. Heterogeneous cellular networks

    CERN Document Server

    Hu, Rose Qingyang

    2013-01-01

    A timely publication providing coverage of radio resource management, mobility management and standardization in heterogeneous cellular networks The topic of heterogeneous cellular networks has gained momentum in industry and the research community, attracting the attention of standardization bodies such as 3GPP LTE and IEEE 802.16j, whose objectives are looking into increasing the capacity and coverage of the cellular networks. This book focuses on recent progresses,  covering the related topics including scenarios of heterogeneous network deployment, interference management i

  4. Nanostructured cellular networks.

    Science.gov (United States)

    Moriarty, P; Taylor, M D R; Brust, M

    2002-12-01

    Au nanocrystals spin-coated onto silicon from toluene form cellular networks. A quantitative statistical crystallography analysis shows that intercellular correlations drive the networks far from statistical equilibrium. Spin-coating from hexane does not produce cellular structure, yet a strong correlation is retained in the positions of nanocrystal aggregates. Mechanisms based on Marangoni convection alone cannot account for the variety of patterns observed, and we argue that spinodal decomposition plays an important role in foam formation.

  5. Cellular Cardiomyoplasty: Clinical Application

    OpenAIRE

    Chachques, J. (J.); Acar, C; J. Herreros; Trainini, J. (Jorge); Prosper, F.; D’Attellis, N. (N.); Fabiani, J. N.; Carpentier, A

    2004-01-01

    Myocardial regeneration can be induced with the implantation of a variety of myogenic and angiogenic cell types. More than 150 patients have been treated with cellular cardiomyoplasty worldwide, 18 patients have been treated by our group. Cellular cardiomyoplasty seems to reduce the size and fibrosis of infarct scars, limit postischemic remodelling, and restore regional myocardial contractility. Techniques for skeletal myoblasts culture and ex vivo expansion using auto...

  6. Clinical significance of high-density lipoproteins and the development of atherosclerosis: focus on the role of the adenosine triphosphate-binding cassette protein A1 transporter.

    Science.gov (United States)

    Brewer, H Bryan; Santamarina-Fojo, Silvia

    2003-08-21

    Low levels of high-density lipoprotein (HDL) cholesterol constitute a risk factor for coronary artery disease, and there is evidence that increasing HDL cholesterol levels reduces cardiovascular risk. The phenotype of low HDL cholesterol with or without elevated triglycerides is at least as common in patients hospitalized for cardiovascular disease as is hypercholesterolemia, and it is characteristic of diabetes and the metabolic syndrome, conditions associated with increased cardiovascular risk. Recent studies have elucidated mechanisms by which HDL acts to reduce cardiovascular risk, bolstering the rationale for targeting of HDL in lipid-modifying therapy. In particular, HDL (1) carries excess cholesterol from peripheral cells to the liver for removal in the process termed reverse cholesterol transport, (2) reduces oxidative modification of low-density lipoproteins (LDL), and (3) inhibits cytokine-induced expression of cellular adhesion molecules on endothelial cells. Studies of the newly described adenosine triphosphate-binding cassette protein A1 (ABCA1) transporter have established a crucial role for this transporter in modulating the levels of plasma HDL and intracellular cholesterol in the liver as well as in peripheral cells. Elevated levels of intracellular cholesterol stimulate the liver X receptor pathway, enhancing the expression of ABCA1, which increases intracellular trafficking of excess cholesterol to the cell surface for interaction with lipid-poor apolipoprotein A-I to form nascent HDL. Nascent HDL facilitates the removal of additional excess cellular cholesterol, which is esterified by lecithin-cholesterol acyltransferase with conversion of the nascent HDL to mature spherical HDL. Overexpression of ABCA1 in mice on a regular chow or Western diet results in a marked increase in plasma HDL, increased LDL, and increased transport of cholesterol to the liver. On a high cholesterol/cholate diet, transgenic mice overexpressing ABCA1 have increased HDL

  7. Ecto-nucleoside triphosphate diphosphohydrolase 3 in the ventral and lateral hypothalamic area of female rats: morphological characterization and functional implications

    Directory of Open Access Journals (Sweden)

    Kiss David S

    2009-04-01

    Full Text Available Abstract Background Based on its distribution in the brain, ecto-nucleoside triphosphate diphosphohydrolase 3 (NTPDase3 may play a role in the hypothalamic regulation of homeostatic systems, including feeding, sleep-wake behavior and reproduction. To further characterize the morphological attributes of NTPDase3-immunoreactive (IR hypothalamic structures in the rat brain, here we investigated: 1. The cellular and subcellular localization of NTPDase3; 2. The effects of 17β-estradiol on the expression level of hypothalamic NTPDase3; and 3. The effects of NTPDase inhibition in hypothalamic synaptosomal preparations. Methods Combined light- and electron microscopic analyses were carried out to characterize the cellular and subcellular localization of NTPDase3-immunoreactivity. The effects of estrogen on hypothalamic NTPDase3 expression was studied by western blot technique. Finally, the effects of NTPDase inhibition on mitochondrial respiration were investigated using a Clark-type oxygen electrode. Results Combined light- and electron microscopic analysis of immunostained hypothalamic slices revealed that NTPDase3-IR is linked to ribosomes and mitochondria, is predominantly present in excitatory axon terminals and in distinct segments of the perikaryal plasma membrane. Immunohistochemical labeling of NTPDase3 and glutamic acid decarboxylase (GAD indicated that γ-amino-butyric-acid- (GABA ergic hypothalamic neurons do not express NTPDase3, further suggesting that in the hypothalamus, NTPDase3 is predominantly present in excitatory neurons. We also investigated whether estrogen influences the expression level of NTPDase3 in the ventrobasal and lateral hypothalamus. A single subcutaneous injection of estrogen differentially increased NTPDase3 expression in the medial and lateral parts of the hypothalamus, indicating that this enzyme likely plays region-specific roles in estrogen-dependent hypothalamic regulatory mechanisms. Determination of

  8. Probing the ATP Site of GRP78 with Nucleotide Triphosphate Analogs.

    Directory of Open Access Journals (Sweden)

    Scott J Hughes

    Full Text Available GRP78, a member of the ER stress protein family, can relocate to the surface of cancer cells, playing key roles in promoting cell proliferation and metastasis. GRP78 consists of two major functional domains: the ATPase and protein/peptide-binding domains. The protein/peptide-binding domain of cell-surface GRP78 has served as a novel functional receptor for delivering cytotoxic agents (e.g., a apoptosis-inducing peptide or taxol across the cell membrane. Here, we report our study on the ATPase domain of GRP78 (GRP78ATPase, whose potential as a transmembrane delivery system of cytotoxic agents (e.g., ATP-based nucleotide triphosphate analogs remains unexploited. As the binding of ligands (ATP analogs to a receptor (GRP78ATPase is a pre-requisite for internalization, we determined the binding affinities and modes of GRP78ATPase for ADP, ATP and several ATP analogs using surface plasmon resonance and x-ray crystallography. The tested ATP analogs contain one of the following modifications: the nitrogen at the adenine ring 7-position to a carbon atom (7-deazaATP, the oxygen at the β-γ bridge position to a carbon atom (AMPPCP, or the removal of the 2'-OH group (2'-deoxyATP. We found that 7-deazaATP displays an affinity and a binding mode that resemble those of ATP regardless of magnesium ion (Mg++ concentration, suggesting that GRP78 is tolerant to modifications at the 7-position. By comparison, AMPPCP's binding affinity was lower than ATP and Mg++-dependent, as the removal of Mg++ nearly abolished binding to GRP78ATPase. The AMPPCP-Mg++ structure showed evidence for the critical role of Mg++ in AMPPCP binding affinity, suggesting that while GRP78 is sensitive to modifications at the β-γ bridge position, these can be tolerated in the presence of Mg++. Furthermore, 2'-deoxyATP's binding affinity was significantly lower than those for all other nucleotides tested, even in the presence of Mg++. The 2'-deoxyATP structure showed the conformation of the

  9. Probing the ATP Site of GRP78 with Nucleotide Triphosphate Analogs.

    Science.gov (United States)

    Hughes, Scott J; Antoshchenko, Tetyana; Chen, Yun; Lu, Hua; Pizarro, Juan C; Park, Hee-Won

    2016-01-01

    GRP78, a member of the ER stress protein family, can relocate to the surface of cancer cells, playing key roles in promoting cell proliferation and metastasis. GRP78 consists of two major functional domains: the ATPase and protein/peptide-binding domains. The protein/peptide-binding domain of cell-surface GRP78 has served as a novel functional receptor for delivering cytotoxic agents (e.g., a apoptosis-inducing peptide or taxol) across the cell membrane. Here, we report our study on the ATPase domain of GRP78 (GRP78ATPase), whose potential as a transmembrane delivery system of cytotoxic agents (e.g., ATP-based nucleotide triphosphate analogs) remains unexploited. As the binding of ligands (ATP analogs) to a receptor (GRP78ATPase) is a pre-requisite for internalization, we determined the binding affinities and modes of GRP78ATPase for ADP, ATP and several ATP analogs using surface plasmon resonance and x-ray crystallography. The tested ATP analogs contain one of the following modifications: the nitrogen at the adenine ring 7-position to a carbon atom (7-deazaATP), the oxygen at the β-γ bridge position to a carbon atom (AMPPCP), or the removal of the 2'-OH group (2'-deoxyATP). We found that 7-deazaATP displays an affinity and a binding mode that resemble those of ATP regardless of magnesium ion (Mg++) concentration, suggesting that GRP78 is tolerant to modifications at the 7-position. By comparison, AMPPCP's binding affinity was lower than ATP and Mg++-dependent, as the removal of Mg++ nearly abolished binding to GRP78ATPase. The AMPPCP-Mg++ structure showed evidence for the critical role of Mg++ in AMPPCP binding affinity, suggesting that while GRP78 is sensitive to modifications at the β-γ bridge position, these can be tolerated in the presence of Mg++. Furthermore, 2'-deoxyATP's binding affinity was significantly lower than those for all other nucleotides tested, even in the presence of Mg++. The 2'-deoxyATP structure showed the conformation of the bound

  10. Molecular structure of tetraaqua adenosine 5'-triphosphate aluminium(III) complex: A study involving Raman spectroscopy, theoretical DFT and potentiometry

    Science.gov (United States)

    Tenório, Thaís; Silva, Andréa M.; Ramos, Joanna Maria; Buarque, Camilla D.; Felcman, Judith

    2013-03-01

    The Alzheimer's disease is one of the most common neurodegenerative diseases that affect elderly population, due to the formation of β-amyloid protein aggregate and several symptoms, especially progressive cognitive decline. The result is a decrease in capture of glucose by cells leading to obliteration, meddling in the Krebs cycle, the principal biochemical route to the energy production leading to a decline in the levels of adenosine 5'-triphosphate. Aluminium(III) is connected to Alzheimer's and its ion provides raise fluidity of the plasma membrane, decrease cell viability and aggregation of amyloid plaques. Studies reveal that AlATP complex promotes the formation of reactive fibrils of β-amyloid protein and independent amyloidogenic peptides, suggesting the action of the complex as a chaperone in the role pathogenic process. In this research, one of complexes formed by Al(III) and adenosine 5'-triphosphate in aqueous solution is analyzed by potentiometry, Raman spectroscopy and ab initio calculations. The value of the log KAlATP found was 9.21 ± 0.01 and adenosine 5'-triphosphate should act as a bidentate ligand in the complex. Raman spectroscopy and potentiometry indicate that donor atoms are the oxygen of the phosphate β and the oxygen of the phosphate γ, the terminal phosphates. Computational calculations using Density Functional Theory, with hybrid functions B3LYP and 6-311++G(d,p) basis set regarding water solvent effects, have confirmed the results. Frontier molecular orbitals, electrostatic potential contour surface, electrostatic potential mapped and Mulliken charges of the title molecule were also investigated.

  11. Molecular structure of tetraaqua adenosine 5'-triphosphate aluminium(III) complex: a study involving Raman spectroscopy, theoretical DFT and potentiometry.

    Science.gov (United States)

    Tenório, Thaís; Silva, Andréa M; Ramos, Joanna Maria; Buarque, Camilla D; Felcman, Judith

    2013-03-15

    The Alzheimer's disease is one of the most common neurodegenerative diseases that affect elderly population, due to the formation of β-amyloid protein aggregate and several symptoms, especially progressive cognitive decline. The result is a decrease in capture of glucose by cells leading to obliteration, meddling in the Krebs cycle, the principal biochemical route to the energy production leading to a decline in the levels of adenosine 5'-triphosphate. Aluminium(III) is connected to Alzheimer's and its ion provides raise fluidity of the plasma membrane, decrease cell viability and aggregation of amyloid plaques. Studies reveal that AlATP complex promotes the formation of reactive fibrils of β-amyloid protein and independent amyloidogenic peptides, suggesting the action of the complex as a chaperone in the role pathogenic process. In this research, one of complexes formed by Al(III) and adenosine 5'-triphosphate in aqueous solution is analyzed by potentiometry, Raman spectroscopy and ab initio calculations. The value of the logK(AlATP) found was 9.21±0.01 and adenosine 5'-triphosphate should act as a bidentate ligand in the complex. Raman spectroscopy and potentiometry indicate that donor atoms are the oxygen of the phosphate β and the oxygen of the phosphate γ, the terminal phosphates. Computational calculations using Density Functional Theory, with hybrid functions B3LYP and 6-311++G(d,p) basis set regarding water solvent effects, have confirmed the results. Frontier molecular orbitals, electrostatic potential contour surface, electrostatic potential mapped and Mulliken charges of the title molecule were also investigated.

  12. Enzymatic Recognition of 2′‐Modified Ribonucleoside 5′‐Triphosphates: Towards the Evolution of Versatile Aptamers

    DEFF Research Database (Denmark)

    Lauridsen, Lasse Holm; Rothnagel, Joseph A.; Veedu, Rakesh N.

    2012-01-01

    The quest for effective, selective and nontoxic nucleic‐acid‐based drugs has led to designing modifications of naturally occurring nucleosides. A number of modified nucleic acids have been made in the past decades in the hope that they would prove useful in target‐validation studies and therapeutic...... of aptamers containing naturally occurring nucleotides, chemically modified nucleotides have to be used. In order to apply modified nucleotides in aptamer drug development, their enzyme‐recognition capabilities must be understood. For this purpose, several modified nucleoside 5′‐triphosphates were synthesized...

  13. Epigenetics and Cellular Metabolism

    Science.gov (United States)

    Xu, Wenyi; Wang, Fengzhong; Yu, Zhongsheng; Xin, Fengjiao

    2016-01-01

    Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well. PMID:27695375

  14. Architected Cellular Materials

    Science.gov (United States)

    Schaedler, Tobias A.; Carter, William B.

    2016-07-01

    Additive manufacturing enables fabrication of materials with intricate cellular architecture, whereby progress in 3D printing techniques is increasing the possible configurations of voids and solids ad infinitum. Examples are microlattices with graded porosity and truss structures optimized for specific loading conditions. The cellular architecture determines the mechanical properties and density of these materials and can influence a wide range of other properties, e.g., acoustic, thermal, and biological properties. By combining optimized cellular architectures with high-performance metals and ceramics, several lightweight materials that exhibit strength and stiffness previously unachievable at low densities were recently demonstrated. This review introduces the field of architected materials; summarizes the most common fabrication methods, with an emphasis on additive manufacturing; and discusses recent progress in the development of architected materials. The review also discusses important applications, including lightweight structures, energy absorption, metamaterials, thermal management, and bioscaffolds.

  15. Epigenetics and Cellular Metabolism

    Science.gov (United States)

    Xu, Wenyi; Wang, Fengzhong; Yu, Zhongsheng; Xin, Fengjiao

    2016-01-01

    Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well.

  16. Daily magnesium fluxes regulate cellular timekeeping and energy balance.

    Science.gov (United States)

    Feeney, Kevin A; Hansen, Louise L; Putker, Marrit; Olivares-Yañez, Consuelo; Day, Jason; Eades, Lorna J; Larrondo, Luis F; Hoyle, Nathaniel P; O'Neill, John S; van Ooijen, Gerben

    2016-04-21

    Circadian clocks are fundamental to the biology of most eukaryotes, coordinating behaviour and physiology to resonate with the environmental cycle of day and night through complex networks of clock-controlled genes. A fundamental knowledge gap exists, however, between circadian gene expression cycles and the biochemical mechanisms that ultimately facilitate circadian regulation of cell biology. Here we report circadian rhythms in the intracellular concentration of magnesium ions, [Mg(2+)]i, which act as a cell-autonomous timekeeping component to determine key clock properties both in a human cell line and in a unicellular alga that diverged from each other more than 1 billion years ago. Given the essential role of Mg(2+) as a cofactor for ATP, a functional consequence of [Mg(2+)]i oscillations is dynamic regulation of cellular energy expenditure over the daily cycle. Mechanistically, we find that these rhythms provide bilateral feedback linking rhythmic metabolism to clock-controlled gene expression. The global regulation of nucleotide triphosphate turnover by intracellular Mg(2+) availability has potential to impact upon many of the cell's more than 600 MgATP-dependent enzymes and every cellular system where MgNTP hydrolysis becomes rate limiting. Indeed, we find that circadian control of translation by mTOR is regulated through [Mg(2+)]i oscillations. It will now be important to identify which additional biological processes are subject to this form of regulation in tissues of multicellular organisms such as plants and humans, in the context of health and disease.

  17. Characterization of nucleoside triphosphate diphosphohydrolase activity in Trichomonas gallinae and the influence of penicillin and streptomycin in extracellular nucleotide hydrolysis.

    Science.gov (United States)

    Borges, Fernanda Pires; de Brum Vieira, Patrícia; Wiltuschnig, Renata C M; Tasca, Tiana; De Carli, Geraldo Attilio; Bonan, Carla Denise

    2008-06-01

    Here we described an nucleoside triphosphate diphosphohydrolase (NTPDase) activity in living trophozoites of Trichomonas gallinae. The enzyme hydrolyzes a variety of purine and pyrimidine nucleoside di- and triphosphates in an optimum pH range of 6.0-8.0. This enzyme activity was activated by high concentrations of divalent cations, such as calcium and magnesium. Contaminant activities were ruled out because the enzyme was not inhibited by classical inhibitors of ATPases (ouabain, 5.0 mM sodium azide, oligomycin) and alkaline phosphatases (levamisole). A significant inhibition of ATP hydrolysis (38%) was observed in the presence of 20 mM sodium azide. Sodium orthovanadate inhibited ATP and ADP hydrolysis (24% and 78%), respectively. The apparent K(M) (Michaelis constant) values were 667.62+/-13 microM for ATP and 125+/-5.3 microM for ADP. V(max) (maximum velocity) values were 0.44+/-0.007 nmol Pi min(-1) per 10(6) trichomonads and 0.91+/-0.12 nmol Pi min(-1) per 10(6) trichomonads for ATP and ADP, respectively. Moreover, we showed a marked decrease in ATP, ADP and AMP hydrolysis when the parasites were grown in the presence of penicillin and streptomycin. The existence of an NTPDase activity in T. gallinae may be involved in pathogenicity, protecting the parasite from the cytolytic effects of the extracellular nucleotides. PMID:18422631

  18. Ecto-nucleoside triphosphate diphosphohydrolase 2 modulates local ATP-induced calcium signaling in human HaCaT keratinocytes.

    Directory of Open Access Journals (Sweden)

    Chia-Lin Ho

    Full Text Available Keratinocytes are the major building blocks of the human epidermis. In many physiological and pathophysiological conditions, keratinocytes release adenosine triphosphate (ATP as an autocrine/paracrine mediator that regulates cell proliferation, differentiation, and migration. ATP receptors have been identified in various epidermal cell types; therefore, extracellular ATP homeostasis likely determines its long-term, trophic effects on skin health. We investigated the possibility that human keratinocytes express surface-located enzymes that modulate ATP concentration, as well as the corresponding receptor activation, in the pericellular microenvironment. We observed that the human keratinocyte cell line HaCaT released ATP and hydrolyzed extracellular ATP. Interestingly, ATP hydrolysis resulted in adenosine diphosphate (ADP accumulation in the extracellular space. Pharmacological inhibition by ARL 67156 or gene silencing of the endogenous ecto-nucleoside triphosphate diphosphohydrolase (NTPDase isoform 2 resulted in a 25% reduction in both ATP hydrolysis and ADP formation. Using intracellular calcium as a reporter, we found that although NTPDase2 hydrolyzed ATP and generated sustainable ADP levels, only ATP contributed to increased intracellular calcium via P2Y2 receptor activation. Furthermore, knocking down NTPDase2 potentiated the nanomolar ATP-induced intracellular calcium increase, suggesting that NTPDase2 globally attenuates nucleotide concentration in the pericellular microenvironment as well as locally shields receptors in the vicinity from being activated by extracellular ATP. Our findings reveal an important role of human keratinocyte NTPDase2 in modulating nucleotide signaling in the extracellular milieu of human epidermis.

  19. Crystallization and preliminary X-ray structural analysis of nucleoside triphosphate hydrolases from Neospora caninum and Toxoplasma gondii

    International Nuclear Information System (INIS)

    Recombinant nucleoside triphosphate hydrolases from N. caninum and T. gondii have been purified and crystallized for X-ray structure analysis. The nucleoside triphosphate hydrolases that are produced by Neospora caninum (NcNTPase) and Toxoplasma gondii (TgNTPase-I) have a different physiological function from the ubiquitous ecto-ATPases. The recombinant enzymes were crystallized at 293 K using polyethylene glycol 3350 as a precipitant and X-ray diffraction data sets were collected for NcNTPase (to 2.8 Å resolution) and TgNTPase-I (to 3.1 Å resolution) at 100 K using synchrotron radiation. The crystals of NcNTPase and TgNTPase-I belonged to the orthorhombic space group I222 (unit-cell parameters a = 93.6, b = 140.8, c = 301.1 Å) and the monoclinic space group P21 (unit-cell parameters a = 87.1, b = 123.5, c = 120.2 Å, β = 96.6°), respectively, with two NcNTPase (VM = 3.7 Å3 Da−1) and four TgNTPase-I (VM = 2.7 Å3 Da−1) molecules per asymmetric unit. SAD phasing trials using a data set (λ = 0.97904 Å) collected from a crystal of selenomethionylated NcNTPase gave an initial electron-density map of sufficient quality to build a molecular model of NcNTPase

  20. Cellular Response to Irradiation

    Institute of Scientific and Technical Information of China (English)

    LIU Bo; YAN Shi-Wei

    2011-01-01

    To explore the nonlinear activities of the cellular signaling system composed of one transcriptional arm and one protein-interaction arm, we use an irradiation-response module to study the dynamics of stochastic interactions.It is shown that the oscillatory behavior could be described in a unified way when the radiation-derived signal and noise are incorporated.

  1. The New Cellular Immunology

    Science.gov (United States)

    Claman, Henry N.

    1973-01-01

    Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)

  2. The nucleotidohydrolases DCTPP1 and dUTPase are involved in the cellular response to decitabine.

    Science.gov (United States)

    Requena, Cristina E; Pérez-Moreno, Guiomar; Horváth, András; Vértessy, Beáta G; Ruiz-Pérez, Luis M; González-Pacanowska, Dolores; Vidal, Antonio E

    2016-09-01

    Decitabine (5-aza-2'-deoxycytidine, aza-dCyd) is an anti-cancer drug used clinically for the treatment of myelodysplastic syndromes and acute myeloid leukaemia that can act as a DNA-demethylating or genotoxic agent in a dose-dependent manner. On the other hand, DCTPP1 (dCTP pyrophosphatase 1) and dUTPase are two 'house-cleaning' nucleotidohydrolases involved in the elimination of non-canonical nucleotides. In the present study, we show that exposure of HeLa cells to decitabine up-regulates the expression of several pyrimidine metabolic enzymes including DCTPP1, dUTPase, dCMP deaminase and thymidylate synthase, thus suggesting their contribution to the cellular response to this anti-cancer nucleoside. We present several lines of evidence supporting that, in addition to the formation of aza-dCTP (5-aza-2'-deoxycytidine-5'-triphosphate), an alternative cytotoxic mechanism for decitabine may involve the formation of aza-dUMP, a potential thymidylate synthase inhibitor. Indeed, dUTPase or DCTPP1 down-regulation enhanced the cytotoxic effect of decitabine producing an accumulation of nucleoside triphosphates containing uracil as well as uracil misincorporation and double-strand breaks in genomic DNA. Moreover, DCTPP1 hydrolyses the triphosphate form of decitabine with similar kinetic efficiency to its natural substrate dCTP and prevents decitabine-induced global DNA demethylation. The data suggest that the nucleotidohydrolases DCTPP1 and dUTPase are factors involved in the mode of action of decitabine with potential value as enzymatic targets to improve decitabine-based chemotherapy.

  3. Molecular and Cellular Signaling

    CERN Document Server

    Beckerman, Martin

    2005-01-01

    A small number of signaling pathways, no more than a dozen or so, form a control layer that is responsible for all signaling in and between cells of the human body. The signaling proteins belonging to the control layer determine what kinds of cells are made during development and how they function during adult life. Malfunctions in the proteins belonging to the control layer are responsible for a host of human diseases ranging from neurological disorders to cancers. Most drugs target components in the control layer, and difficulties in drug design are intimately related to the architecture of the control layer. Molecular and Cellular Signaling provides an introduction to molecular and cellular signaling in biological systems with an emphasis on the underlying physical principles. The text is aimed at upper-level undergraduates, graduate students and individuals in medicine and pharmacology interested in broadening their understanding of how cells regulate and coordinate their core activities and how diseases ...

  4. Magnetic Cellular Switches

    OpenAIRE

    Overby, Darryl R.; Alenghat, Francis J.; Montoya-Zavala, Martín; Bei, HuCheng; Oh, Philmo; Karavitis, John; Ingber, Donald E.

    2004-01-01

    This paper focuses on the development of magnetic cellular switches to enable magnetic control of intracellular functions in living mammalian cells, including receptor signal transduction and gene transcription. Our approach takes advantage of the mechanosensitivity of adenosine 3′,5′-monophosphate (cAMP) induction and downstream transcription controlled by the cAMP regulatory element (CRE) to engineer gene constructs that optically report gene expression in living cells. We activate transcri...

  5. Cellular therapy in Tuberculosis

    Directory of Open Access Journals (Sweden)

    Shreemanta K. Parida

    2015-03-01

    Full Text Available Cellular therapy now offer promise of potential adjunct therapeutic options for treatment of drug-resistant tuberculosis (TB. We review here the role of Mesenchymal stromal cells, (MSCs, as well as other immune effector cells in the therapy of infectious diseases with a focus on TB. MSCs represent a population of tissue-resident non-hematopoietic adult progenitor cells which home into injured tissues increase the proliferative potential of broncho-alveolar stem cells and restore lung epithelium. MSCs have been shown to be immune-modulatory and anti-inflammatory mediated via cell-cell contacts as well as soluble factors. We discuss the functional profile of MSCs and their potential use for adjunct cellular therapy of multi-drug resistant TB, with the aim of limiting tissue damage, and to convert unproductive inflammatory responses into effective anti-pathogen directed immune responses. Adjunct cellular therapy could potentially offer salvage therapy options for patients with drug-resistant TB, increase clinically relevant anti-M.tuberculosis directed immune responses and possibly shorten the duration of anti-TB therapy.

  6. Environment Aware Cellular Networks

    KAUST Repository

    Ghazzai, Hakim

    2015-02-01

    The unprecedented rise of mobile user demand over the years have led to an enormous growth of the energy consumption of wireless networks as well as the greenhouse gas emissions which are estimated currently to be around 70 million tons per year. This significant growth of energy consumption impels network companies to pay huge bills which represent around half of their operating expenditures. Therefore, many service providers, including mobile operators, are looking for new and modern green solutions to help reduce their expenses as well as the level of their CO2 emissions. Base stations are the most power greedy element in cellular networks: they drain around 80% of the total network energy consumption even during low traffic periods. Thus, there is a growing need to develop more energy-efficient techniques to enhance the green performance of future 4G/5G cellular networks. Due to the problem of traffic load fluctuations in cellular networks during different periods of the day and between different areas (shopping or business districts and residential areas), the base station sleeping strategy has been one of the main popular research topics in green communications. In this presentation, we present several practical green techniques that provide significant gains for mobile operators. Indeed, combined with the base station sleeping strategy, these techniques achieve not only a minimization of the fossil fuel consumption but also an enhancement of mobile operator profits. We start with an optimized cell planning method that considers varying spatial and temporal user densities. We then use the optimal transport theory in order to define the cell boundaries such that the network total transmit power is reduced. Afterwards, we exploit the features of the modern electrical grid, the smart grid, as a new tool of power management for cellular networks and we optimize the energy procurement from multiple energy retailers characterized by different prices and pollutant

  7. An Escherichia coli strain deficient for both exonuclease V and deoxycytidine triphosphate deaminase shows enhanced sensitivity to ionizing radiation.

    Science.gov (United States)

    Estèvenon, A M; Kooistra, J; Sicard, N

    1995-02-20

    An Escherichia coli mutant lacking deoxycytidine triphosphate deaminase (Dcd) activity and an unknown function encoded by a gene designated ior exhibits sensitivity to ionizing radiation whereas dcd mutants themselves are not sensitive. A DNA fragment from an E. coli genomic library that restores the wild type level of UV and gamma ray resistance to this mutant has been cloned in the multicopy vector pBR322. Comparison of its restriction map with the physical map of the E. coli chromosome revealed complete identity to the recBD genes. ior affects ATP-dependent exonuclease activity, suggesting that it is an allele of recB. This mutation alone does not confer sensitivity to UV and gamma radiation, indicating that lack of Dcd activity is also required for expression of radiation sensitivity.

  8. Crystal Structure of a Legionella pneumophila Ecto -Triphosphate Diphosphohydrolase, A Structural and Functional Homolog of the Eukaryotic NTPDases

    Energy Technology Data Exchange (ETDEWEB)

    Vivian, Julian P.; Riedmaier, Patrice; Ge, Honghua; Le Nours, Jérôme; Sansom, Fiona M.; Wilce, Matthew C.J.; Byres, Emma; Dias, Manisha; Schmidberger, Jason W.; Cowan, Peter J.; d' Apice, Anthony J.F.; Hartland, Elizabeth L.; Rossjohn, Jamie; Beddoe, Travis (Monash); (Melbourne)

    2010-04-19

    Many pathogenic bacteria have sophisticated mechanisms to interfere with the mammalian immune response. These include the disruption of host extracellular ATP levels that, in humans, is tightly regulated by the nucleoside triphosphate diphosphohydrolase family (NTPDases). NTPDases are found almost exclusively in eukaryotes, the notable exception being their presence in some pathogenic prokaryotes. To address the function of bacterial NTPDases, we describe the structures of an NTPDase from the pathogen Legionella pneumophila (Lpg1905/Lp1NTPDase) in its apo state and in complex with the ATP analog AMPPNP and the subtype-specific NTPDase inhibitor ARL 67156. Lp1NTPDase is structurally and catalytically related to eukaryotic NTPDases and the structure provides a basis for NTPDase-specific inhibition. Furthermore, we demonstrate that the activity of Lp1NTPDase correlates directly with intracellular replication of Legionella within macrophages. Collectively, these findings provide insight into the mechanism of this enzyme and highlight its role in host-pathogen interactions.

  9. A rapid method for the determination of microbial susceptibility using the firefly luciferase assay for adenosine triphosphate (ATP)

    Science.gov (United States)

    Vellend, H.; Tuttle, S. A.; Barza, M.; Weinstein, L.; Picciolo, G. L.; Chappelle, E. W.

    1975-01-01

    Luciferase assay for adenosine triphosphate (ATP) was optimized for pure bacteria in broth in order to evaluate if changes in bacterial ATP content could be used as a rapid measure of antibiotic effect on microorganisms. Broth cultures of log phase bacteria were incubated at 310 K (37 C) for 2.5 hours at antimicrobial concentrations which resulted in the best discrimination between sensitive and resistant strains. Eighty-seven strains of 11 bacterial species were studied for their susceptibility to 12 commonly used antimicrobial agents: ampicillin, Penicillin G, nafcillin, carbenicillin, cephalothin, tetracycline, erythromycin, clindamycin, gentamicin, nitrofurantoin, colistin, and chloramplenicol. The major advantage of the ATP system over existing methods of rapid microbial susceptibility testing is that the assay can be made specific for bacterial ATP.

  10. An improved red blood cell additive solution maintains 2,3-diphosphoglycerate and adenosine triphosphate levels by an enhancing effect on phosphofructokinase activity during cold storage

    NARCIS (Netherlands)

    P. Burger; H. Korsten; D. de Korte; E. Rombout; R. van Bruggen; A.J. Verhoeven

    2010-01-01

    BACKGROUND: Current additive solutions (ASs) for red blood cells (RBCs) do not maintain constant 2,3-diphosphoglycerate (DPG) and adenosine triphosphate (ATP) levels during cold storage We have previously shown that with a new AS called phosphate-adenine-glucose-guanosine-gluconate-mannitol (PAGGGM)

  11. Plaque retention by self-ligating vs elastomeric orthodontic brackets: quantitative comparison of oral bacteria and detection with adenosine triphosphate-driven bioluminescence.

    NARCIS (Netherlands)

    Pellegrini, P.; Sauerwein, R.W.; Finlayson, T.; McLeod, J.; Covell, D.A.; Maier, T.; Machida, C.A.

    2009-01-01

    INTRODUCTION: Enamel decalcification is a common problem in orthodontics. The objectives of this randomized clinical study were to enumerate and compare plaque bacteria surrounding 2 bracket types, self-ligating (SL) vs elastomeric ligating (E), and to determine whether adenosine triphosphate (ATP)-

  12. AN ESCHERICHIA-COLI STRAIN DEFICIENT FOR BOTH EXONUCLEASE-V AND DEOXYCYTIDINE TRIPHOSPHATE DEAMINASE SHOWS ENHANCED SENSITIVITY TO IONIZING-RADIATION

    NARCIS (Netherlands)

    ESTEVENON, AM; KOOISTRA, J; SICARD, N

    1995-01-01

    An Escherichia coli mutant lacking deoxycytidine triphosphate deaminase (Dcd) activity and an unknown function encoded by a gene designated ior exhibits sensitivity to ionizing radiation whereas dcd mutants themselves are not sensitive. A DNA fragment from an E. coli genomic library that restores th

  13. Sterol transporter adenosine triphosphate-binding cassette transporter G8, gallstones, and biliary cancer in 62,000 individuals from the general population

    DEFF Research Database (Denmark)

    Stender, Stefan; Frikke-Schmidt, Ruth; Nordestgaard, Børge G;

    2011-01-01

    Gallstone disease, a risk factor for biliary cancer, has a strong heritable component, but the underlying genes are largely unknown. To test the hypothesis that ABCG8 (adenosine triphosphate-binding cassette transporter G8) Asp19His (D19H) genotype predicted risk of gallstones and biliary cancer ...

  14. Adenosine 5 '-triphosphate (ATP) supplements are not orally bioavailable: a randomized, placebo-controlled cross-over trial in healthy humans

    NARCIS (Netherlands)

    Arts, I.C.W.; Coolen, E.J.C.M.; Bours, M.J.L.; Huyghebaert, N.; Cohen Stuart, M.A.; Bast, A.; Dagnelie, P.C.

    2012-01-01

    Background: Nutritional supplements designed to increase adenosine 5'-triphosphate (ATP) concentrations are commonly used by athletes as ergogenic aids. ATP is the primary source of energy for the cells, and supplementation may enhance the ability to maintain high ATP turnover during high-intensity

  15. Engineering Cellular Metabolism

    DEFF Research Database (Denmark)

    Nielsen, Jens; Keasling, Jay

    2016-01-01

    of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation.......Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds...

  16. Evidence that a major portion of cellular potassium is bound

    International Nuclear Information System (INIS)

    In this report we briefly review recent evidence which shows that a substantial proportion of intracellular K+ is bound or perturbed from the physicochemical properties expected in dilute aqueous solutions. In addition, we present evidence from electron probe x-ray microanalysis of thin cryosections of cells which indicates that the binding of K+ to anionic groups either carboxyl groups (HCO2) on proteins or to phosphate groups in creatine phosphate (CrP), in adenosine triphosphate, (ATP), in protein and in nucleic acids, are the main determinants of the maintenance of (as differentiated from the generated of) the well known intra- to extracellular K+ concentration difference. The collective evidence suggests that much of cellular K+ is reduced in its mobility and in its chemical activity due to association with negative charge groups (e.g. carboxyl and phosphates). This fact forces abandonment of the misleading assumption that the majority of intracellular K+ and other inorganic ions are as free as would be expected under ideal solution conditions. This realization should have far reaching consequences toward understanding transmembrane movement of water and solutes in cells. 41 references

  17. Integrated cellular systems

    Science.gov (United States)

    Harper, Jason C.

    The generation of new three-dimensional (3D) matrices that enable integration of biomolecular components and whole cells into device architectures, without adversely altering their morphology or activity, continues to be an expanding and challenging field of research. This research is driven by the promise that encapsulated biomolecules and cells can significantly impact areas as diverse as biocatalysis, controlled delivery of therapeutics, environmental and industrial process monitoring, early warning of warfare agents, bioelectronics, photonics, smart prosthetics, advanced physiological sensors, portable medical diagnostic devices, and tissue/organ replacement. This work focuses on the development of a fundamental understanding of the biochemical and nanomaterial mechanisms that govern the cell directed assembly and integration process. It was shown that this integration process relies on the ability of cells to actively develop a pH gradient in response to evaporation induced osmotic stress, which catalyzes silica condensation within a thin 3D volume surrounding the cells, creating a functional bio/nano interface. The mechanism responsible for introducing functional foreign membrane-bound proteins via proteoliposome addition to the silica-lipid-cell matrix was also determined. Utilizing this new understanding, 3D cellular immobilization capabilities were extended using sol-gel matrices endowed with glycerol, trehalose, and media components. The effects of these additives, and the metabolic phase of encapsulated S. cerivisiase cells, on long-term viability and the rate of inducible gene expression was studied. This enabled the entrapment of cells within a novel microfluidic platform capable of simultaneous colorimetric, fluorescent, and electrochemical detection of a single analyte, significantly improving confidence in the biosensor output. As a complementary approach, multiphoton protein lithography was utilized to engineer 3D protein matrices in which to

  18. Multiuser Cellular Network

    CERN Document Server

    Bao, Yi; Chen, Ming

    2011-01-01

    Modern radio communication is faced with a problem about how to distribute restricted frequency to users in a certain space. Since our task is to minimize the number of repeaters, a natural idea is enlarging coverage area. However, coverage has restrictions. First, service area has to be divided economically as repeater's coverage is limited. In this paper, our fundamental method is to adopt seamless cellular network division. Second, underlying physics content in frequency distribution problem is interference between two close frequencies. Consequently, we choose a proper frequency width of 0.1MHz and a relevantly reliable setting to apply one frequency several times. We make a few general assumptions to simplify real situation. For instance, immobile users yield to homogenous distribution; repeaters can receive and transmit information in any given frequency in duplex operation; coverage is mainly decided by antenna height. Two models are built up to solve 1000 users and 10000 users situations respectively....

  19. Efficient and Stereoselective Synthesis of C-(β-2'-Deoxynucleosides)

    Institute of Scientific and Technical Information of China (English)

    WU,Qin-Pei; REES,B.Colin

    2004-01-01

    @@ The formation of triplex DNA is, in principle, an effective way of regulating the expression of selected genes.[1]Many cytosine mimics were investigated to form triplex DNA, e.g., 2-amino-(2'-deoxy-β-D-ribofuranosyl)pyridine (9)was proved to have some effectiveness in stabilizing triplex DNA under neutral conditions.[2] Stereoselective synthesis of 9 was achieved starting from 2-deoxyribose.

  20. Evidence for a "metabolically inactive" inorganic phosphate pool in adenosine triphosphate synthase reaction using localized 31P saturation transfer magnetic resonance spectroscopy in the rat brain at 11.7 T.

    Science.gov (United States)

    Tiret, Brice; Brouillet, Emmanuel; Valette, Julien

    2016-09-01

    With the increased spectral resolution made possible at high fields, a second, smaller inorganic phosphate resonance can be resolved on (31)P magnetic resonance spectra in the rat brain. Saturation transfer was used to estimate de novo adenosine triphosphate synthesis reaction rate. While the main inorganic phosphate pool is used by adenosine triphosphate synthase, the second pool is inactive for this reaction. Accounting for this new pool may not only help us understand (31)P magnetic resonance spectroscopy metabolic profiles better but also better quantify adenosine triphosphate synthesis.

  1. Insights into the molecular mechanism of inhibition and drug resistance for HIV-1 RT with carbovir triphosphate.

    Science.gov (United States)

    Ray, Adrian S; Yang, Zhenjun; Shi, Junxing; Hobbs, Ann; Schinazi, Raymond F; Chu, Chung K; Anderson, Karen S

    2002-04-23

    Abacavir (1592U89, or Ziagen) is a powerful and selective inhibitor of HIV-1 viral replication that has been approved by the FDA for treatment of acquired immunodeficiency syndrome. Abacavir is metabolized to the active compound carbovir triphosphate (CBVTP). This compound is a guanosine analogue containing a 2',3'-unsaturation in its planar carbocyclic deoxyribose ring that acts on HIV-1 reverse transcriptase (RT(WT)) as a molecular target, resulting in chain termination of DNA synthesis. A single amino acid change from methionine 184 to valine in HIV-1 RT (RT(M184V)) has been observed clinically in response to abacavir treatment. The ability of the natural substrate, dGTP, or CBVTP to be utilized during DNA- and RNA-directed polymerization by RT(WT) and RT(M184V) was defined by pre-steady-state kinetic parameters. In the case of RT(WT), CBVTP was found to be a surprisingly poor substrate relative to dGTP. In both DNA- and RNA-directed polymerization, a decrease in the efficiency of CBVTP utilization with respect to dGTP was found with RT(M184V), suggesting that this mutation confers resistance at the level of CBVMP incorporation. The relatively low incorporation efficiency for RT(WT) was unanticipated considering earlier studies showing that the triphosphate form of a thymidine nucleoside analogue containing a planar 2',3'-unsaturated ribose ring, D4TTP, was incorporated with high efficiency relative to the natural substrate, dTTP. The difference may be related to the isosteric replacement of oxygen in the deoxyribose ring with carbon. This hypothesis was tested by synthesizing and evaluating D4GTP (the planar 2',3'-unsaturated deoxyribose guanosine analogue that is complementary to D4TTP). In contrast to CBVTP, D4GTP was found to be an excellent substrate for RT(WT) and no resistance was conferred by the M184V mutation, thus providing novel insight into structure-activity relationships for nucleoside-based inhibitors. In this work, we illustrate how an

  2. Leishmania infantum ecto-nucleoside triphosphate diphosphohydrolase-2 is an apyrase involved in macrophage infection and expressed in infected dogs.

    Directory of Open Access Journals (Sweden)

    Raphael De Souza Vasconcellos

    2014-11-01

    Full Text Available Visceral leishmaniasis is an important tropical disease, and Leishmania infantum chagasi (synonym of Leishmania infantum is the main pathogenic agent of visceral leishmaniasis in the New World. Recently, ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases were identified as enablers of infection and virulence factors in many pathogens. Two putative E-NTPDases (∼70 kDa and ∼45 kDa have been found in the L. infantum genome. Here, we studied the ∼45 kDa E-NTPDase from L. infantum chagasi to describe its natural occurrence, biochemical characteristics and influence on macrophage infection.We used live L. infantum chagasi to demonstrate its natural ecto-nucleotidase activity. We then isolated, cloned and expressed recombinant rLicNTPDase-2 in bacterial system. The recombinant rLicNTPDase-2 hydrolyzed a wide variety of triphosphate and diphosphate nucleotides (GTP> GDP  =  UDP> ADP> UTP  =  ATP in the presence of calcium or magnesium. In addition, rLicNTPDase-2 showed stable activity over a pH range of 6.0 to 9.0 and was partially inhibited by ARL67156 and suramin. Microscopic analyses revealed the presence of this protein on cell surfaces, vesicles, flagellae, flagellar pockets, kinetoplasts, mitochondria and nuclei. The blockade of E-NTPDases using antibodies and competition led to lower levels of parasite adhesion and infection of macrophages. Furthermore, immunohistochemistry showed the expression of E-NTPDases in amastigotes in the lymph nodes of naturally infected dogs from an area of endemic visceral leishmaniasis.In this work, we cloned, expressed and characterized the NTPDase-2 from L. infantum chagasi and demonstrated that it functions as a genuine enzyme from the E-NTPDase/CD39 family. We showed that E-NTPDases are present on the surface of promastigotes and in other intracellular locations. We showed, for the first time, the broad expression of LicNTPDases in naturally infected dogs. Additionally, the blockade of

  3. Never-ageing cellular senescence

    OpenAIRE

    Ogrunc, Müge; d’Adda di Fagagna, Fabrizio

    2011-01-01

    Cellular senescence was historically discovered as a form of cellular ageing of in vitro cultured cells. It has been under the spotlight following the evidence of oncogene-induced senescence in vivo and its role as a potent tumour suppressor mechanism. Presently, a PubMed search using keywords ‘cellular senescence and cancer’ reveals 8398 number of references (by April 2011) showing that while our knowledge of senescence keeps expanding, the complexity of the phenomenon keeps us – researchers...

  4. The State of Cellular Probes

    OpenAIRE

    Yim, Youngbin

    2003-01-01

    Cellular probe technology is one of several potentially promising technologies for obtaining accurate travel time information. In 1996, the Federal Communications Commission (FCC) mandated E911 requirements that cellular location be provided when 911 emergency calls come in to emergency management authorities. The E911 requirements allow 50 -300 meters from the emergency call location, depending on the type of cellular phone technology used and whether handset-based or network-based solutions...

  5. Cellular bioluminescence imaging.

    Science.gov (United States)

    Welsh, David K; Noguchi, Takako

    2012-08-01

    Bioluminescence imaging of live cells has recently been recognized as an important alternative to fluorescence imaging. Fluorescent probes are much brighter than bioluminescent probes (luciferase enzymes) and, therefore, provide much better spatial and temporal resolution and much better contrast for delineating cell structure. However, with bioluminescence imaging there is virtually no background or toxicity. As a result, bioluminescence can be superior to fluorescence for detecting and quantifying molecules and their interactions in living cells, particularly in long-term studies. Structurally diverse luciferases from beetle and marine species have been used for a wide variety of applications, including tracking cells in vivo, detecting protein-protein interactions, measuring levels of calcium and other signaling molecules, detecting protease activity, and reporting circadian clock gene expression. Such applications can be optimized by the use of brighter and variously colored luciferases, brighter microscope optics, and ultrasensitive, low-noise cameras. This article presents a review of how bioluminescence differs from fluorescence, its applications to cellular imaging, and available probes, optics, and detectors. It also gives practical suggestions for optimal bioluminescence imaging of single cells.

  6. Utilization of adenosine triphosphate in rat mast cells during histamine release induced by the ionophore A23187

    DEFF Research Database (Denmark)

    Johansen, Torben

    1979-01-01

    The role of endogenous adenosine triphosphate (ATP) in histamine release from rat mast cells induced by the ionophore A23187 in vitro has been studied. 2 The amount of histamine released by calcium from rat mast cells primed with the ionophore A23187 was dependent on the ATP content of the mast c...... cells. 3 In aerobic experiments a drastic reduction in mast cell ATP content was found during the time when histamine release induced by A23187 takes place. 4 Anaerobic experiments were performed with metabolic inhibitors (antimycin A, oligomycin, and carbonyl cyanide p......-trifluorometroxyphenylnydrazone), which are known to block the energy-dependent calcium uptake by isolated mitochondria. The mast cell ATP content was reduced during A23187-induced histamine release under anaerobic conditions in the presence of glucose. This indicates an increased utilization of ATP during the release process. 5...... The observations are consistent with the view that energy requiring processes are involved in ionophore-induced histamine release from rat mast cells although part of the ATP reduction in the aerobic experiments may be due to an uncoupling effect of calcium on the oxidative phosphorylation....

  7. Diagnostic value of adenosine-triphosphate radionuclide ventriculography in coronary artery disease. Comparison with conventional exercise stress method

    International Nuclear Information System (INIS)

    The purpose of this study was to assess the effect of adenosine-triphosphate (ATP) on hemodynamics and left ventricular (LV) function, and to examine the value of ATP radionuclide-ventriculography (RNVG) for detecting coronary artery disease (CAD) in comparison with standard exercise RNVG. Thirty-eight consecutive patients with suspected CAD underwent ATP (0.18 mg/Kg/min) RNVG and symptom-limited exercise RNVG. Coronary angiography revealed 27 patients with CAD (Group S) and 11 without CAD (Group N). In group S, exercise induced an increase in LV end-diastolic volume (LVEDV) and LV end-systolic volume (LVESV), and a decrease in LV ejection fraction (LVEF). In contrast, ATP infusion caused LVESV to decrease in both groups, improving LVEF. Only 14 of 39 segments whose wall motion was deteriorated by exercise showed worsening regional wall motion during ATP infusion. The sensitivity and specificity of ATP RNVG for detecting CAD were 22. 2% and 100%, while those of exercise RNVG were 77.8% and 81.8%, respectively. Although ATP induced a depression of peak filling rate in group S as compared with group N, the deterioration of systolic function was not apparent with this method. ATP RNVG was not adequate for detecting CAD because of its lower sensitivity compared with exercise RNVG. (author)

  8. Campylobacter jejuni adenosine triphosphate phosphoribosyltransferase is an active hexamer that is allosterically controlled by the twisting of a regulatory tail.

    Science.gov (United States)

    Mittelstädt, Gerd; Moggré, Gert-Jan; Panjikar, Santosh; Nazmi, Ali Reza; Parker, Emily J

    2016-08-01

    Adenosine triphosphate phosphoribosyltransferase (ATP-PRT) catalyzes the first committed step of the histidine biosynthesis in plants and microorganisms. Here, we present the functional and structural characterization of the ATP-PRT from the pathogenic ε-proteobacteria Campylobacter jejuni (CjeATP-PRT). This enzyme is a member of the long form (HisGL ) ATP-PRT and is allosterically inhibited by histidine, which binds to a remote regulatory domain, and competitively inhibited by AMP. In the crystalline form, CjeATP-PRT was found to adopt two distinctly different hexameric conformations, with an open homohexameric structure observed in the presence of substrate ATP, and a more compact closed form present when inhibitor histidine is bound. CjeATP-PRT was observed to adopt only a hexameric quaternary structure in solution, contradicting previous hypotheses favoring an allosteric mechanism driven by an oligomer equilibrium. Instead, this study supports the conclusion that the ATP-PRT long form hexamer is the active species; the tightening of this structure in response to remote histidine binding results in an inhibited enzyme. PMID:27191057

  9. Influence of Thromboxane A2 on the Regulation of Adenosine Triphosphate-Sensitive Potassium Channels in Mouse Ventricular Myocytes

    Science.gov (United States)

    Jeong, In Seok; Cho, Hwa Jin; Cho, Jeong Gwan; Kim, Sang Hyung; Na, Kook Joo

    2016-01-01

    Background and Objectives Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels play an important role in myocardial protection. We examined the effects of thromboxane A2 on the regulation of KATP channel activity in single ventricular myocytes. Subjects and Methods Single ventricular myocytes were isolated from the hearts of adult Institute of Cancer Research (ICR) mice by enzymatic digestion. Single channel activity was recorded by excised inside-out and cell-attached patch clamp configurations at −60 mV holding potential during the perfusion of an ATP-free K-5 solution. Results In the excised inside-out patches, the thromboxane A2 analog, U46619, decreased the KATP channel activity in a dose-dependent manner; however, the thromboxane A2 receptor antagonist, SQ29548, did not significantly attenuate the inhibitory effect of U46619. In the cell-attached patches, U46619 inhibited dinitrophenol (DNP)-induced KATP channel activity in a dose-dependent manner, and SQ29548 attenuated the inhibitory effects of U46619 on DNP-induced KATP channel activity. Conclusion Thromboxane A2 may inhibit KATP channel activity, and may have a harmful effect on ischemic myocardium. PMID:27482267

  10. Serine-324 of myosin's heavy chain is photoaffinity-labeled by 3'(2')-O-(4-benzoylbenzoyl)adenosine triphosphate

    International Nuclear Information System (INIS)

    A portion of the active site of rabbit skeletal myosin near the ribose ring of ATP can be labeled by the photoaffinity analogue 3'(2')-O-(4-benzoylbenzoyl)adenosine triphosphate (Bz2ATP). The specificity of the photolabeling was assured by first trapping [14C]Bz2ATP at the active site by use of thiol cross-linking agents. Five radioactive peptides were isolated by high-performance liquid chromatography after extensive trypsin and subtilisin digestion of photolabeled myosin subfragment 1. Four of these peptides were sequenced by Edman techniques, and all originated from a region with the sequence Gly-Glu-Ile-Thr-Val-Pro-Ser-Ile-Asp-Asp-Gln, which corresponds to rabbit myosin heavy chain residues 312-328. The fifth labeled peptide had an amino acid composition appropriate for residues 312-328. Amino acid composition, radiochemical analysis, and sequence data indicate that Ser-324 is the major amino acid residue photolabeled by Bz2ATP. Spectrophotometric evidence indicates that the benzophenone carbonyl group has inserted into a C-H bond from either the α- or β-carbon of serine. These results place Ser-324 at a distance of 6-7 angstrom from the 3'(2') ribose oxygens of ATP bound at the active site of myosin

  11. Upregulation of nucleoside triphosphate diphosphohydrolase-1 and ecto-5'-nucleotidase in rat hippocampus after repeated low-dose dexamethasone administration.

    Science.gov (United States)

    Drakulić, Dunja; Stanojlović, Miloš; Nedeljković, Nadežda; Grković, Ivana; Veličković, Nataša; Guševac, Ivana; Mitrović, Nataša; Buzadžić, Ivana; Horvat, Anica

    2015-04-01

    Although dexamethasone (DEX), a synthetic glucocorticoid receptor (GR) analog with profound effects on energy metabolism, immune system, and hypothalamic-pituitary-adrenal axis, is widely used therapeutically, its impact on the brain is poorly understood. The aim of the present study was to explore the effect of repeated low-dose DEX administration on the activity and expression of the ectonucleotidase enzymes which hydrolyze and therefore control extracellular ATP and adenosine concentrations in the synaptic cleft. Ectonucleotidases tested were ectonucleoside triphosphate diphosphohydrolase 1-3 (NTPDase1-3) and ecto-5'-nucleotidase (eN), whereas the effects were evaluated in two brain areas that show different sensitivity to glucocorticoid action, hippocampus, and cerebral cortex. In the hippocampus, but not in cerebral cortex, modest level of neurodegenerative changes as well as increase in ATP, ADP, and AMP hydrolysis and upregulation of NTPDase1 and eN mRNA expression ensued under the influence of DEX. The observed pattern of ectonucleotidase activation, which creates tissue volume with enhanced capacity for adenosine formation, is the hallmark of the response after different insults to the brain.

  12. Supplementation of exogenous adenosine 5'-triphosphate enhances mechanical properties of 3D cell-agarose constructs for cartilage tissue engineering.

    Science.gov (United States)

    Gadjanski, Ivana; Yodmuang, Supansa; Spiller, Kara; Bhumiratana, Sarindr; Vunjak-Novakovic, Gordana

    2013-10-01

    Formation of tissue-engineered cartilage is greatly enhanced by mechanical stimulation. However, direct mechanical stimulation is not always a suitable method, and the utilization of mechanisms underlying mechanotransduction might allow for a highly effective and less aggressive alternate means of stimulation. In particular, the purinergic, adenosine 5'-triphosphate (ATP)-mediated signaling pathway is strongly implicated in mechanotransduction within the articular cartilage. We investigated the effects of transient and continuous exogenous ATP supplementation on mechanical properties of cartilaginous constructs engineered using bovine chondrocytes and human mesenchymal stem cells (hMSCs) encapsulated in an agarose hydrogel. For both cell types, we have observed significant increases in equilibrium and dynamic compressive moduli after transient ATP treatment applied in the fourth week of cultivation. Continuous ATP treatment over 4 weeks of culture only slightly improved the mechanical properties of the constructs, without major changes in the total glycosaminoglycan (GAG) and collagen content. Structure-function analyses showed that transiently ATP-treated constructs, and in particular those based on hMSCs, had the highest level of correlation between compositional and mechanical properties. Transiently treated groups showed intense staining of the territorial matrix for GAGs and collagen type II. These results indicate that transient ATP treatment can improve functional mechanical properties of cartilaginous constructs based on chondrogenic cells and agarose hydrogels, possibly by improving the structural organization of the bulk phase and territorial extracellular matrix (ECM), that is, by increasing correlation slopes between the content of the ECM components (GAG, collagen) and mechanical properties of the construct.

  13. Light-driven artificial enzymes for selective oxidation of guanosine triphosphate using water-soluble POSS network polymers.

    Science.gov (United States)

    Jeon, Jong-Hwan; Tanaka, Kazuo; Chujo, Yoshiki

    2014-09-01

    The light-driven artificial enzymes were constructed to realize unnatural reactions concerning bio-significant molecules. In this manuscript, the guanosine triphosphate (GTP)-selective oxidation is reported using the network polymers composed of polyhedral oligomeric silsesquioxane (POSS). We synthesized the water-soluble POSS network polymer containing the naphthyridine ligands to capture GTP inside the networks and the ruthenium complexes to oxidize the captured GTP under light irradiation. Initially, the binding affinities of the guanosine nucleosides to the naphthyridine ligand inside the POSS network polymer were evaluated from the emission quenching experiments. Accordingly, it was observed that the naphthyridine ligand can form the stable complex only with GTP (K(a) = 5.5 × 10(6) M(-1)). These results indicate that only GTP can be captured by the network polymer. Next, the photo-catalytic activity of the ruthenium complex-modified POSS network polymer was investigated. Finally, it was revealed that the network polymer can decompose GTP efficiently under light irradiation. This is the first example, to the best of our knowledge, to offer not only the GTP-selective host polymers but also the light-driven artificial enzyme for GTP oxidation. PMID:25026217

  14. Adenosine triphosphate-competitive mTOR inhibitors: a new class of immunosuppressive agents that inhibit allograft rejection.

    Science.gov (United States)

    Rosborough, B R; Raïch-Regué, D; Liu, Q; Venkataramanan, R; Turnquist, H R; Thomson, A W

    2014-09-01

    The mechanistic/mammalian target of rapamycin (mTOR) is inhibited clinically to suppress T cell function and prevent allograft rejection. mTOR is the kinase subunit of two mTOR-containing complexes, mTOR complex (mTORC) 1 and 2. Although mTORC1 is inhibited by the macrolide immunosuppressant rapamycin (RAPA), its efficacy may be limited by its inability to block mTORC1 completely and its limited effect on mTORC2. Adenosine triphosphate (ATP)-competitive mTOR inhibitors are an emerging class of mTOR inhibitors that compete with ATP at the mTOR active site and inhibit any mTOR-containing complex. Since this class of compounds has not been investigated for their immunosuppressive potential, our goal was to determine the influence of a prototypic ATP-competitive mTOR inhibitor on allograft survival. AZD8055 proved to be a potent suppressor of T cell proliferation. Moreover, a short, 10-day course of the agent successfully prolonged murine MHC-mismatched, vascularized heart transplant survival. This therapeutic effect was associated with increased graft-infiltrating regulatory T cells and reduced CD4(+) and CD8(+) T cell interferon-γ production. These studies establish for the first time, that ATP-competitive mTOR inhibition can prolong organ allograft survival and warrant further investigation of this next generation mTOR inhibitors. PMID:25307040

  15. Binding of Mn-deoxyribonucleoside Triphosphates to the Active Site of the DNA Polymerase of Bacteriophage T7

    Energy Technology Data Exchange (ETDEWEB)

    B Akabayov; C Richardson

    2011-12-31

    Divalent metal ions are crucial as cofactors for a variety of intracellular enzymatic activities. Mg{sup 2+}, as an example, mediates binding of deoxyribonucleoside 5'-triphosphates followed by their hydrolysis in the active site of DNA polymerase. It is difficult to study the binding of Mg{sup 2+} to an active site because Mg{sup 2+} is spectroscopically silent and Mg{sup 2+} binds with low affinity to the active site of an enzyme. Therefore, we substituted Mg{sup 2+} with Mn{sup 2+}:Mn{sup 2+} that is not only visible spectroscopically but also provides full activity of the DNA polymerase of bacteriophage T7. In order to demonstrate that the majority of Mn{sup 2+} is bound to the enzyme, we have applied site-directed titration analysis of T7 DNA polymerase using X-ray near edge spectroscopy. Here we show how X-ray near edge spectroscopy can be used to distinguish between signal originating from Mn{sup 2+} that is free in solution and Mn{sup 2+} bound to the active site of T7 DNA polymerase. This method can be applied to other enzymes that use divalent metal ions as a cofactor.

  16. Leishmania (Viannia) braziliensis nucleoside triphosphate diphosphohydrolase (NTPDase 1): localization and in vitro inhibition of promastigotes growth by polyclonal antibodies.

    Science.gov (United States)

    Porcino, Gabriane Nascimento; Carvalho-Campos, Cristiane; Maia, Ana Carolina Ribeiro Gomes; Detoni, Michelle Lima; Faria-Pinto, Priscila; Coimbra, Elaine Soares; Marques, Marcos José; Juliano, Maria Aparecida; Juliano, Luiz; Diniz, Vanessa Álvaro; Corte-Real, Suzana; Vasconcelos, Eveline Gomes

    2012-10-01

    Nucleoside triphosphate diphosphohydrolase (NTPDase) activity was recently characterized in Leishmania (Viannia) braziliensis promastigotes (Lb), and an antigenic conserved domain (r82-121) from the specific NTPDase 1 isoform was identified. In this work, mouse polyclonal antibodies produced against two synthetic peptides derived from this domain (LbB1LJ, r82-103; LbB2LJ, r102-121) were used. The anti-LbB1LJ or anti-LbB2LJ antibodies were immobilized on protein A-sepharose and immunoprecipitated the NTPDase 1 of 48 kDa and depleted approximately 40% of the phosphohydrolytic activity from detergent-homogenized Lb preparation. Ultrastructural immunocytochemical microscopy identified the NTPDase 1 on the parasite surface and in its subcellular cytoplasmic vesicles, mitochondria, kinetoplast and nucleus. The ATPase and ADPase activities of detergent-homogenized Lb preparation were partially inhibited by anti-LbB1LJ antibody (43-79%), which was more effective than that inhibition (18-47%) by anti-LbB2LJ antibody. In addition, the immune serum anti-LbB1LJ (67%) or anti-LbB2LJ (33%) was cytotoxic, significantly reducing the promastigotes growth in vitro. The results appoint the conserved domain from the L. braziliensis NTPDase as an important target for inhibitor design and the potential application of these biomolecules in experimental protocols of disease control. PMID:22921497

  17. Adenosine 5 '-triphosphate (ATP) supplements are not orally bioavailable: a randomized, placebo-controlled cross-over trial in healthy humans

    OpenAIRE

    Arts Ilja CW; Coolen Erik JCM; Bours Martijn JL; Huyghebaert Nathalie; Stuart Martien A; Bast Aalt; Dagnelie Pieter C

    2012-01-01

    Abstract Background Nutritional supplements designed to increase adenosine 5′-triphosphate (ATP) concentrations are commonly used by athletes as ergogenic aids. ATP is the primary source of energy for the cells, and supplementation may enhance the ability to maintain high ATP turnover during high-intensity exercise. Oral ATP supplements have beneficial effects in some but not all studies examining physical performance. One of the remaining questions is whether orally administered ATP is bioav...

  18. Crystal structure of Escherichia coli cytidine triphosphate synthetase, a nucleotide-regulated glutamine amidotransferase/ATP-dependent amidoligase fusion protein and homologue of anticancer and antiparasitic drug targets.

    Science.gov (United States)

    Endrizzi, James A; Kim, Hanseong; Anderson, Paul M; Baldwin, Enoch P

    2004-06-01

    Cytidine triphosphate synthetases (CTPSs) produce CTP from UTP and glutamine, and regulate intracellular CTP levels through interactions with the four ribonucleotide triphosphates. We solved the 2.3-A resolution crystal structure of Escherichia coli CTPS using Hg-MAD phasing. The structure reveals a nearly symmetric 222 tetramer, in which each bifunctional monomer contains a dethiobiotin synthetase-like amidoligase N-terminal domain and a Type 1 glutamine amidotransferase C-terminal domain. For each amidoligase active site, essential ATP- and UTP-binding surfaces are contributed by three monomers, suggesting that activity requires tetramer formation, and that a nucleotide-dependent dimer-tetramer equilibrium contributes to the observed positive cooperativity. A gated channel that spans 25 A between the glutamine hydrolysis and amidoligase active sites provides a path for ammonia diffusion. The channel is accessible to solvent at the base of a cleft adjoining the glutamine hydrolysis active site, providing an entry point for exogenous ammonia. Guanine nucleotide binding sites of structurally related GTPases superimpose on this cleft, providing insights into allosteric regulation by GTP. Mutations that confer nucleoside drug resistance and release CTP inhibition map to a pocket that neighbors the UTP-binding site and can accommodate a pyrimidine ring. Its location suggests that competitive feedback inhibition is affected via a distinct product/drug binding site that overlaps the substrate triphosphate binding site. Overall, the E. coli structure provides a framework for homology modeling of other CTPSs and structure-based design of anti-CTPS therapeutics. PMID:15157079

  19. About Strongly Universal Cellular Automata

    Directory of Open Access Journals (Sweden)

    Maurice Margenstern

    2013-09-01

    Full Text Available In this paper, we construct a strongly universal cellular automaton on the line with 11 states and the standard neighbourhood. We embed this construction into several tilings of the hyperbolic plane and of the hyperbolic 3D space giving rise to strongly universal cellular automata with 10 states.

  20. Crystal Structure of Escherichia coli Cytidine Triphosphate Synthetase, a Nucleotide-Regulated Glutamine Amidotransferase/ATP-Dependent Amidoligase Fusion Protein and Homologue of Anticancer and Antiparasitic Drug Targets†,‡

    OpenAIRE

    Endrizzi, James A.; Kim, Hanseong; Anderson, Paul M; Baldwin, Enoch P.

    2004-01-01

    Cytidine triphosphate synthetases (CTPSs) produce CTP from UTP and glutamine, and regulate intracellular CTP levels through interactions with the four ribonucleotide triphosphates. We solved the 2.3-Å resolution crystal structure of Escherichia coli CTPS using Hg-MAD phasing. The structure reveals a nearly symmetric 222 tetramer, in which each bifunctional monomer contains a dethiobiotin synthetase-like amidoligase N-terminal domain and a Type 1 glutamine amidotransferase C-terminal domain. F...

  1. MIMO Communication for Cellular Networks

    CERN Document Server

    Huang, Howard; Venkatesan, Sivarama

    2012-01-01

    As the theoretical foundations of multiple-antenna techniques evolve and as these multiple-input multiple-output (MIMO) techniques become essential for providing high data rates in wireless systems, there is a growing need to understand the performance limits of MIMO in practical networks. To address this need, MIMO Communication for Cellular Networks presents a systematic description of MIMO technology classes and a framework for MIMO system design that takes into account the essential physical-layer features of practical cellular networks. In contrast to works that focus on the theoretical performance of abstract MIMO channels, MIMO Communication for Cellular Networks emphasizes the practical performance of realistic MIMO systems. A unified set of system simulation results highlights relative performance gains of different MIMO techniques and provides insights into how best to use multiple antennas in cellular networks under various conditions. MIMO Communication for Cellular Networks describes single-user,...

  2. Adenosine Triphosphate (ATP Is a Candidate Signaling Molecule in the Mitochondria-to-Nucleus Retrograde Response Pathway

    Directory of Open Access Journals (Sweden)

    Zhengchang Liu

    2013-03-01

    Full Text Available Intracellular communication from the mitochondria to the nucleus is achieved via the retrograde response. In budding yeast, the retrograde response, also known as the RTG pathway, is regulated positively by Rtg1, Rtg2, Rtg3 and Grr1 and negatively by Mks1, Lst8 and two 14-3-3 proteins, Bmh1/2. Activation of retrograde signaling leads to activation of Rtg1/3, two basic helix-loop-helix leucine zipper transcription factors. Rtg1/3 activation requires Rtg2, a cytoplasmic protein with an N-terminal adenosine triphosphate (ATP binding domain belonging to the actin/Hsp70/sugar kinase superfamily. The critical regulatory step of the retrograde response is the interaction between Rtg2 and Mks1. Rtg2 binds to and inactivates Mks1, allowing for activation of Rtg1/3 and the RTG pathway. When the pathway is inactive, Mks1 has dissociated from Rtg2 and bound to Bmh1/2, preventing activation of Rtg1/3. What signals association or disassociation of Mks1 and Rtg2 is unknown. Here, we show that ATP at physiological concentrations dissociates Mks1 from Rtg2 in a highly cooperative fashion. We report that ATP-mediated dissociation of Mks1 from Rtg2 is conserved in two other fungal species, K. lactis and K. waltii. Activation of Rtg1/3 upregulates expression of genes encoding enzymes catalyzing the first three reactions of the Krebs cycle, which is coupled to ATP synthesis through oxidative phosphorylation. Therefore, we propose that the retrograde response is an ATP homeostasis pathway coupling ATP production with ATP-mediated repression of the retrograde response by releasing Mks1 from Rtg2.

  3. Structural and functional insights into DR2231 protein, the MazG-like nucleoside triphosphate pyrophosphohydrolase from Deinococcus radiodurans.

    Science.gov (United States)

    Gonçalves, Ana Maria D; de Sanctis, Daniele; McSweeney, Sean M

    2011-09-01

    Deinococcus radiodurans is among the very few bacterial species extremely resistant to ionizing radiation, UV light, oxidizing agents, and cycles of prolonged desiccation. The proteome of D. radiodurans reflects the evolutionary pressure exerted by chronic exposure to (nonradioactive) forms of DNA and protein damage. A clear example of this adaptation is the overrepresentation of protein families involved in the removal of non-canonical nucleoside triphosphates (NTPs) whose incorporation into nascent DNA would promote mutagenesis and DNA damage. The three-dimensional structure of the DR2231 protein has been solved at 1.80 Å resolution. This protein had been classified as an all-α-helical MazG-like protein. The present study confirms that it holds the basic structural module characteristic of the MazG superfamily; two helices form a rigid domain, and two helices form a mobile domain and connecting loops. Contrary to what is known of MazG proteins, DR2231 protein shows a functional affinity with dUTPases. Enzymatic and isothermal calorimetry assays have demonstrated high specificity toward dUTP but an inability to hydrolyze dTTP, a typical feature of dUTPases. Co-crystallization with the product of hydrolysis, dUMP, in the presence of magnesium or manganese cations, suggests similarities with the dUTP/dUDP hydrolysis mechanism reported for dimeric dUTPases. The genome of D. radiodurans encodes for all enzymes required for dTTP synthesis from dCMP, thus bypassing the need of a dUTPase. We postulate that DR2231 protein is not essential to D. radiodurans and rather performs "house-cleaning" functions within the framework of oxidative stress response. We further propose DR2231 protein as an evolutionary precursor of dimeric dUTPases.

  4. A cascade amplification strategy based on rolling circle amplification and hydroxylamine amplified gold nanoparticles enables chemiluminescence detection of adenosine triphosphate.

    Science.gov (United States)

    Wang, Ping; Zhang, Tonghuan; Yang, Taoyi; Jin, Nan; Zhao, Yanjun; Fan, Aiping

    2014-08-01

    A highly sensitive and selective chemiluminescent (CL) biosensor for adenosine triphosphate (ATP) was developed by taking advantage of the ATP-dependent enzymatic reaction (ATP-DER), the powerful signal amplification capability of rolling circle amplification (RCA), and hydroxylamine-amplified gold nanoparticles (Au NPs). The strategy relies on the ability of ATP, a cofactor of T4 DNA ligase, to trigger the ligation-RCA reaction. In the presence of ATP, the T4 DNA ligase catalyzes the ligation reaction between the two ends of the padlock probe, producing a closed circular DNA template that initiates the RCA reaction with phi29 DNA polymerase and dNTP. Therein, many complementary copies of the circular template can be generated. The ATP-DER is eventually converted into a detectable CL signal after a series of processes, including gold probe hybridization, hydroxylamine amplification, and oxidative gold metal dissolution coupled with a simple and sensitive luminol CL reaction. The CL signal is directly proportional to the ATP level. The results showed that the detection limit of the assay is 100 pM of ATP, which compares favorably with those of other ATP detection techniques. In addition, by taking advantage of ATP-DER, the proposed CL sensing system exhibits extraordinary specificity towards ATP and could distinguish the target molecule ATP from its analogues. The proposed method provides a new and versatile platform for the design of novel DNA ligation reaction-based CL sensing systems for other cofactors. This novel ATP-DER based CL sensing system may find wide applications in clinical diagnosis as well as in environmental and biomedical fields.

  5. Magnetic nanoformulation of azidothymidine 5’-triphosphate for targeted delivery across the blood–brain barrier

    Directory of Open Access Journals (Sweden)

    Zainulabedin M Saiyed

    2010-03-01

    Full Text Available Zainulabedin M Saiyed, Nimisha H Gandhi, Madhavan PN Nair1Department of Immunology, College of Medicine, Florida International University, Miami, FL, USAAbstract: Despite significant advances in highly active antiretroviral therapy (HAART, the prevalence of neuroAIDS remains high. This is mainly attributed to inability of antiretroviral therapy (ART to cross the blood–brain barrier (BBB, thus resulting in insufficient drug concentration within the brain. Therefore, development of an active drug targeting system is an attractive strategy to increase the efficacy and delivery of ART to the brain. We report herein development of magnetic azidothymidine 5’-triphosphate (AZTTP liposomal nanoformulation and its ability to transmigrate across an in vitro BBB model by application of an external magnetic field. We hypothesize that this magnetically guided nanoformulation can transverse the BBB by direct transport or via monocyte-mediated transport. Magnetic AZTTP liposomes were prepared using a mixture of phosphatidyl choline and cholesterol. The average size of prepared liposomes was about 150 nm with maximum drug and magnetite loading efficiency of 54.5% and 45.3%, respectively. Further, magnetic AZTTP liposomes were checked for transmigration across an in vitro BBB model using direct or monocyte-mediated transport by application of an external magnetic field. The results show that apparent permeability of magnetic AZTTP liposomes was 3-fold higher than free AZTTP. Also, the magnetic AZTTP liposomes were efficiently taken up by monocytes and these magnetic monocytes showed enhanced transendothelial migration compared to normal/non-magnetic monocytes in presence of an external magnetic field. Thus, we anticipate that the developed magnetic nanoformulation can be used for targeting active nucleotide analog reverse transcriptase inhibitors to the brain by application of an external magnetic force and thereby eliminate the brain HIV reservoir and help

  6. Cellular systems biology profiling applied to cellular models of disease.

    Science.gov (United States)

    Giuliano, Kenneth A; Premkumar, Daniel R; Strock, Christopher J; Johnston, Patricia; Taylor, Lansing

    2009-11-01

    Building cellular models of disease based on the approach of Cellular Systems Biology (CSB) has the potential to improve the process of creating drugs as part of the continuum from early drug discovery through drug development and clinical trials and diagnostics. This paper focuses on the application of CSB to early drug discovery. We discuss the integration of protein-protein interaction biosensors with other multiplexed, functional biomarkers as an example in using CSB to optimize the identification of quality lead series compounds.

  7. Actual problems of cellular cardiomyoplasty

    Directory of Open Access Journals (Sweden)

    Bulat Kaupov

    2010-04-01

    Full Text Available The paper provides review of cellular technologies used incardiology, describes types of cellular preparations depending onsources of cells and types of compounding cells. The generalmechanisms of therapies with stem cells applications are described.Use of cellular preparations for treatment of cardiovascular diseasesand is improvement of the forecast at patients with heartinsufficiency of various genesis is considered as alternative topractice with organ transplantations. Efforts of biotechnologicallaboratories are directed on search of optimum population of cellsfor application in cardiology and studying of mechanisms andfactors regulating function of cardiac stem cells.

  8. Cellular mechanisms during vascular development

    OpenAIRE

    Blum, Yannick

    2012-01-01

    The vascular system is an essential organ in vertebrate animals and provides the organism with enough oxygen and nutrients. It is composed of an interconnected network of blood vessels, which form using a number of different morphogenetic mechanisms. Angiogenesis describes the formation of new blood vessels from preexisting vessels. A number of molecular pathways have been shown to be essential during angiogenesis. However, cellular architecture of blood vessels as well as cellular mechanisms...

  9. Cellular automaton for chimera states

    OpenAIRE

    García-Morales, Vladimir

    2016-01-01

    A minimalistic model for chimera states is presented. The model is a cellular automaton (CA) which depends on only one adjustable parameter, the range of the nonlocal coupling, and is built from elementary cellular automata and the majority (voting) rule. This suggests the universality of chimera-like behavior from a new point of view: Already simple CA rules based on the majority rule exhibit this behavior. After a short transient, we find chimera states for arbitrary initial conditions, the...

  10. Mathematical Modeling of Cellular Metabolism.

    Science.gov (United States)

    Berndt, Nikolaus; Holzhütter, Hermann-Georg

    2016-01-01

    Cellular metabolism basically consists of the conversion of chemical compounds taken up from the extracellular environment into energy (conserved in energy-rich bonds of organic phosphates) and a wide array of organic molecules serving as catalysts (enzymes), information carriers (nucleic acids), and building blocks for cellular structures such as membranes or ribosomes. Metabolic modeling aims at the construction of mathematical representations of the cellular metabolism that can be used to calculate the concentration of cellular molecules and the rates of their mutual chemical interconversion in response to varying external conditions as, for example, hormonal stimuli or supply of essential nutrients. Based on such calculations, it is possible to quantify complex cellular functions as cellular growth, detoxification of drugs and xenobiotic compounds or synthesis of exported molecules. Depending on the specific questions to metabolism addressed, the methodological expertise of the researcher, and available experimental information, different conceptual frameworks have been established, allowing the usage of computational methods to condense experimental information from various layers of organization into (self-) consistent models. Here, we briefly outline the main conceptual frameworks that are currently exploited in metabolism research.

  11. Comparison of plate counts, Petrifilm, dipslides, and adenosine triphosphate bioluminescence for monitoring bacteria in cooling-tower waters.

    Science.gov (United States)

    Mueller, Sherry A; Anderson, James E; Kim, Byung R; Ball, James C

    2009-04-01

    Effective bacterial control in cooling-tower systems requires accurate and timely methods to count bacteria. Plate-count methods are difficult to implement on-site, because they are time- and labor-intensive and require sterile techniques. Several field-applicable methods (dipslides, Petrifilm, and adenosine triphosphate [ATP] bioluminescence) were compared with the plate count for two sample matrices--phosphate-buffered saline solution containing a pure culture of Pseudomonas fluorescens and cooling-tower water containing an undefined mixed bacterial culture. For the pure culture, (1) counts determined on nutrient agar and plate-count agar (PCA) media and expressed as colony-forming units (CFU) per milliliter were equivalent to those on R2A medium (p = 1.0 and p = 1.0, respectively); (2) Petrifilm counts were not significantly different from R2A plate counts (p = 0.99); (3) the dipslide counts were up to 2 log units higher than R2A plate counts, but this discrepancy was not statistically significant (p = 0.06); and (4) a discernable correlation (r2 = 0.67) existed between ATP readings and plate counts. For cooling-tower water samples (n = 62), (1) bacterial counts using R2A medium were higher (but not significant; p = 0.63) than nutrient agar and significantly higher than tryptone-glucose yeast extract (TGE; p = 0.03) and PCA (p < 0.001); (2) Petrifilm counts were significantly lower than nutrient agar or R2A (p = 0.02 and p < 0.001, respectively), but not statistically different from TGE, PCA, and dipslides (p = 0.55, p = 0.69, and p = 0.91, respectively); (3) the dipslide method yielded bacteria counts 1 to 3 log units lower than nutrient agar and R2A (p < 0.001), but was not significantly different from Petrifilm (p = 0.91), PCA (p = 1.00) or TGE (p = 0.07); (4) the differences between dipslides and the other methods became greater with a 6-day incubation time; and (5) the correlation between ATP readings and plate counts varied from system to system, was poor

  12. Hierarchical Cellular Structures in High-Capacity Cellular Communication Systems

    CERN Document Server

    Jain, R K; Agrawal, N K

    2011-01-01

    In the prevailing cellular environment, it is important to provide the resources for the fluctuating traffic demand exactly in the place and at the time where and when they are needed. In this paper, we explored the ability of hierarchical cellular structures with inter layer reuse to increase the capacity of mobile communication network by applying total frequency hopping (T-FH) and adaptive frequency allocation (AFA) as a strategy to reuse the macro and micro cell resources without frequency planning in indoor pico cells [11]. The practical aspects for designing macro- micro cellular overlays in the existing big urban areas are also explained [4]. Femto cells are inducted in macro / micro / pico cells hierarchical structure to achieve the required QoS cost effectively.

  13. Sequencing, functional expression and characterization of rat NTPDase6, a nucleoside diphosphatase and novel member of the ecto-nucleoside triphosphate diphosphohydrolase family.

    Science.gov (United States)

    Braun, N; Fengler, S; Ebeling, C; Servos, J; Zimmermann, H

    2000-11-01

    We have isolated and characterized the cDNA encoding nucleoside triphosphate diphosphohydrolase 6 (NTPDase6), a novel member of the ecto-nucleoside triphosphate diphosphohydrolase family. The rat-brain-derived cDNA has an open reading frame of 1365 bp encoding a protein of 455 amino acid residues, a calculated molecular mass of 49971 Da and a predicted N-terminal hydrophobic sequence. It shares 86% sequence identity with the human CD39L2 sequence and 48% and 51% identity respectively with sequences of the two related human and murine nucleoside diphosphatases (CD39L4, NTPDase5/ER-UDPase). The mRNA was expressed in all tissues investigated, revealing two major transcripts with differing abundances. PCR analysis suggests a single open reading frame. A Myc-His-tagged NTPDase6 was expressed in Chinese hamster ovary (CHO) and PC12 cells for immunological analysis and protein isolation. The protein was contained in membrane fractions of transfected CHO cells and occurred in a soluble form in the cell culture supernatants. NTPDase6 preferentially hydrolysed nucleoside 5'-diphosphates. With different substrates the order of activity was GDP>IDP>UDP,CDP>ADP. Nucleoside 5'-triphosphates were hydrolysed only to a minor extent and no hydrolysis of nucleoside 5'-monophosphates was observed. The enzyme was strongly and equally activated by Ca(2+) and Mg(2+) and had a K(m) for GDP of 211 microM. The immunohistochemical analysis of transfected CHO and PC12 cells suggests that NTPDase6 is associated with the Golgi apparatus and to a small extent also with the plasma membrane. The enzyme might support glycosylation reactions in the Golgi apparatus and, when released from cells, might catalyse the hydrolysis of extracellular nucleotides. PMID:11042118

  14. Preferential binding of Escherichia coli RecF protein to gapped DNA in the presence of adenosine (gamma-thio) triphosphate.

    OpenAIRE

    Hegde, S P; Rajagopalan, M; Madiraju, M V

    1996-01-01

    Escherichia coli RecF protein binds, but does not hydrolyze, ATP. To determine the role that ATP binding to RecF plays in RecF protein-mediated DNA binding, we have determined the interaction between RecF protein and single-stranded (ss)DNA, double-stranded (ds)DNA, and dsDNA containing ssDNA regions (gapped [g]DNA) either alone or in various combinations both in the presence and in the absence of adenosine (gamma-thio) triphosphate, gamma-S-ATP, a nonhydrolyzable ATP analog. Protein-DNA comp...

  15. Dihydrothymidine and thymidine glycol triphosphates as substrates for DNA polymerases: differential recognition of thymine C5-C6 bond saturation and sequence specificity of incorporation.

    OpenAIRE

    Ide, H; Wallace, S. S.

    1988-01-01

    The ability of dihydrothymidine (DHdTTP) and thymidine glycol (dTTP-GLY) 5'-triphosphates to serve as substrates for different DNA polymerases was investigated. DHdTTP but not dTTP-GLY was used as a substrate by E. coli DNA polymerase I (Pol I). Within the detection limit of the assay used, neither T4 DNA polymerase nor avian myeloblastosis virus (AMV) reverse transcriptase used DHdTTP or dTTP-GLY as substrates. The ability of DHdTTP and dTTP-GLY to undergo enzyme-catalyzed turnover to the mo...

  16. Continuum representations of cellular solids

    Energy Technology Data Exchange (ETDEWEB)

    Neilsen, M.K.

    1993-09-01

    Cellular materials consist of interconnected struts or plates which form cells. The struts or plates are constructed from a variety of metals, polymers, ceramics and wood products. Cellular materials are often used in impact limiters for shipping containers to protect the contents from accidental impact events. These materials exhibit a variety of complex behavior when subjected to crushing loads. This research focuses on the development of continuum representations of cellular solids that can be used in the finite element analysis of shipping container accidents. A significant portion of this work is the development of a new methodology to relate localized deformations to appropriate constitutive descriptions. This methodology provides the insight needed to select constitutive descriptions for cellular solids that capture the localized deformations that are observed experimentally. Constitutive relations are developed for two different cellular materials, aluminum honeycomb and polyurethane foam. These constitutive relations are based on plasticity and continuum damage theories. Plasticity is used to describe the permanent deformation exhibited by both aluminum honeycomb and polyurethane foam. Continuum damage is needed to capture the change in elastic parameters due to cracking of the polyurethane cell wall materials. The new constitutive description of polyurethane foam is implemented in both static and dynamic finite element codes, and analytical and numerical predictions are compared with available experimental data.

  17. Prognosis of Different Cellular Generations

    Directory of Open Access Journals (Sweden)

    Preetish Ranjan

    2013-04-01

    Full Text Available Technological advancement in mobile telephony from 1G to 3G, 4G and 5G has a very axiomatic fact that made an entire world a global village. The cellular system employs a different design approach and technology that most commercial radio and television system use. In the cellular system, the service area is divided into cells and a transmitter is designed to serve an individual cell. The system seeks to make efficient use of available channels by using low-power transmitters to allow frequency reuse at a smaller distance. Maximizing the number of times each channel can be reused in a given geographical area is the key to an efficient cellular system design. During the past three decades, the world has seen significant changes in telecommunications industry. There have been some remarkable aspects to the rapid growth in wireless communications, as seen by the large expansion in mobile systems. This paper focuses on “Past, Present & Future of Cellular Telephony” and some light has been thrown upon the technologies of the cellular systems, namely 1G, 2G, 2.5G, 3G and future generations like 4G and 5G systems as well.

  18. Autophagy induced by HIF1α overexpression supports trophoblast invasion by supplying cellular energy.

    Directory of Open Access Journals (Sweden)

    Mikiko Yamanaka-Tatematsu

    Full Text Available Extravillous trophoblasts (EVTs characterize the invasion of the maternal decidua under low oxygen and poor nutrition at the early feto-maternal interface to establish a successful pregnancy. We previously reported that autophagy in EVTs was activated under 2% O2 in vitro, and autophagy activation was also observed in EVTs at the early feto-maternal interface in vivo. Here, we show that autophagy is an energy source for the invasion of EVTs. Cobalt chloride (CoCl2, which induces hypoxia inducible factor 1α (HIF1α overexpression, activated autophagy in HTR8/SVneo cells, an EVT cell line. The number of invading HTR8-ATG4B(C74A cells, an autophagy-deficient EVT cell line, was markedly reduced by 81 percent with the CoCl2 treatment through the suppression of MMP9 level, although CoCl2 did not affect the cellular invasion of HTR8-mStrawberry cells, a control cell line. HTR8-ATG4B(C74A cells treated with CoCl2 showed a decrease in cellular adenosine triphosphate (ATP levels and a compensatory increase in the expression of purinergic receptor P2X ligand-gated ion channel 7 (P2RX7, which is stimulated with ATP, whereas HTR8-mStrawberry cells maintained cellular ATP levels and did not affect P2RX7 expression. Furthermore, the decreased invasiveness of HTR8-ATG4B(C74A cells treated with CoCl2 was neutralized by ATP supplementation to the level of HTR8-ATG4B(C74A cells treated without CoCl2. These results suggest that autophagy plays a role in maintaining homeostasis by countervailing HIF1α-mediated cellular energy consumption in EVTs.

  19. Aging, cellular senescence, and cancer.

    Science.gov (United States)

    Campisi, Judith

    2013-01-01

    For most species, aging promotes a host of degenerative pathologies that are characterized by debilitating losses of tissue or cellular function. However, especially among vertebrates, aging also promotes hyperplastic pathologies, the most deadly of which is cancer. In contrast to the loss of function that characterizes degenerating cells and tissues, malignant (cancerous) cells must acquire new (albeit aberrant) functions that allow them to develop into a lethal tumor. This review discusses the idea that, despite seemingly opposite characteristics, the degenerative and hyperplastic pathologies of aging are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence. The senescence response is widely recognized as a potent tumor suppressive mechanism. However, recent evidence strengthens the idea that it also drives both degenerative and hyperplastic pathologies, most likely by promoting chronic inflammation. Thus, the senescence response may be the result of antagonistically pleiotropic gene action. PMID:23140366

  20. Adaptive stochastic cellular automata: Applications

    Science.gov (United States)

    Qian, S.; Lee, Y. C.; Jones, R. D.; Barnes, C. W.; Flake, G. W.; O'Rourke, M. K.; Lee, K.; Chen, H. H.; Sun, G. Z.; Zhang, Y. Q.; Chen, D.; Giles, C. L.

    1990-09-01

    The stochastic learning cellular automata model has been applied to the problem of controlling unstable systems. Two example unstable systems studied are controlled by an adaptive stochastic cellular automata algorithm with an adaptive critic. The reinforcement learning algorithm and the architecture of the stochastic CA controller are presented. Learning to balance a single pole is discussed in detail. Balancing an inverted double pendulum highlights the power of the stochastic CA approach. The stochastic CA model is compared to conventional adaptive control and artificial neural network approaches.

  1. Cellular automaton for chimera states

    Science.gov (United States)

    García-Morales, Vladimir

    2016-04-01

    A minimalistic model for chimera states is presented. The model is a cellular automaton (CA) which depends on only one adjustable parameter, the range of the nonlocal coupling, and is built from elementary cellular automata and the majority (voting) rule. This suggests the universality of chimera-like behavior from a new point of view: Already simple CA rules based on the majority rule exhibit this behavior. After a short transient, we find chimera states for arbitrary initial conditions, the system spontaneously splitting into stable domains separated by static boundaries, some synchronously oscillating and the others incoherent. When the coupling range is local, nontrivial coherent structures with different periodicities are formed.

  2. Cellular senescence in aging primates.

    Science.gov (United States)

    Herbig, Utz; Ferreira, Mark; Condel, Laura; Carey, Dee; Sedivy, John M

    2006-03-01

    The aging of organisms is characterized by a gradual functional decline of all organ systems. Mammalian somatic cells in culture display a limited proliferative life span, at the end of which they undergo an irreversible cell cycle arrest known as replicative senescence. Whether cellular senescence contributes to organismal aging has been controversial. We investigated telomere dysfunction, a recently discovered biomarker of cellular senescence, and found that the number of senescent fibroblasts increases exponentially in the skin of aging baboons, reaching >15% of all cells in very old individuals. In addition, the same cells contain activated ataxia-telangiectasia mutated kinase and heterochromatinized nuclei, confirming their senescent status. PMID:16456035

  3. Isolation of a gene encoding a developmentally regulated T cell-specific protein with a guanine nucleotide triphosphate-binding motif

    Energy Technology Data Exchange (ETDEWEB)

    Carlow, D.A.; Teh, H.S.; Marth, J. [Univ. of British Columbia, Vancouver (Canada)] [and others

    1995-02-15

    In this study, we describe a novel full length cDNA clone designated Tgtp that encodes a predicted 415-amino acid a T cell-specific guanine nucleotide triphosphate-binding protein (TGTP) bearing the characteristic motifs of a guanine nucleotide triphosphate (GTP) binding protein. Tgtp is expressed preferentially, if not exclusively, in T cells, and is up-regulated in both unfractionated and in purified CD4{sup +}8{sup +} thymocytes upon TCR cross-linking. In contrast, expression of Tgtp in peripheral T cells is maintained at relatively high levels and is not grossly affected by TCR cross-linking. Antiserum generated against synthetic peptides from the predicted TGTP amino acid sequence recognized a single protein with a molecular mass of {approx}50 kDa, corresponding well with the computed molecular mass of 47 kDa. The only known relative of Tgtp is MUSGTP, which is reportedly expressed in B cells and bears a GTP binding motif. Thus, the discovery of Tgtp resolves a subfamily of molecules with GTP binding motifs and apparent lymphoid lineage-restricted expression. Given the restricted expression pattern in T cells, the up-regulated expression observed in response to TCR signaling in immature thymocytes, and the presence of the motifs characteristic of GTP binding proteins, we suggest that TGTP may have an important function in T cell development and/or T cell activation. 51 refs., 6 figs.

  4. Pharmacogenetic research progress of inosine triphosphate pyrophosphatase%三磷酸肌苷焦磷酸酶药理遗传学的研究进展

    Institute of Scientific and Technical Information of China (English)

    李兴军

    2013-01-01

    嘌呤类药物主要用于治疗自身免疫性疾病、器官移植、急性淋巴细胞白血病等,其不良反应的发生率为15% ~28%,严重影响了药物在临床中的应用.三磷酸肌苷焦磷酸酶(inosine triphosphate pyrophosphatase,ITPA)存在个体间的差异,ITPA缺陷的患者在应用嘌呤类药物时会发生一定的不良反应,因此,有必要了解ITPA对嘌呤类药物临床应用的影响,该文综述了ⅡPA的药理遗传学方面的研究进展.%Purine drugs are for the treatment of autoimmune diseases,organ transplantation,acute lymphoblastic leukemia.The adverse reaction rate is 15% ~ 28%,which impacts on the clinical application in recent years.Studies have shown that inosine triphosphate pyrophosphatase (ITPA) are different between individuals,and there are adverse reactions in patients with defects of ITPA when purine drugs are used.This paper reviewes the ITPA pharmacogenetic research progresses.

  5. Simple, Fast and Selective Detection of Adenosine Triphosphate at Physiological pH Using Unmodified Gold Nanoparticles as Colorimetric Probes and Metal Ions as Cross-Linkers

    Directory of Open Access Journals (Sweden)

    Huan Pang

    2012-11-01

    Full Text Available We report a simple, fast and selective colorimetric assay of adenosine triphosphate (ATP using unmodified gold nanoparticles (AuNPs as probes and metal ions as cross-linkers. ATP can be assembled onto the surface of AuNPs through interaction between the electron-rich nitrogen atoms and the electron-deficient surface of AuNPs. Accordingly, Cu2+ ions induce a change in the color and UV/Vis absorbance of AuNPs by coordinating to the triphosphate groups and a ring nitrogen of ATP. A detection limit of 50 nM was achieved, which is comparable to or lower than that achievable by the currently used electrochemical, spectroscopic or chromatographic methods. The theoretical simplicity and high selectivity reported herein demonstrated that AuNPs-based colorimetric assay could be applied in a wide variety of fields by rationally designing the surface chemistry of AuNPs. In addition, our results indicate that ATP-modified AuNPs are less stable in Cu2+, Cd2+ or Zn2+-containing solutions due to the formation of the corresponding dimeric metal-ATP complexes.

  6. Radioimmunoassay for guanosin-5'-diphosphate-3'-diphosphate and adenosine-5'-triphosphate-3'-diphosphate

    Energy Technology Data Exchange (ETDEWEB)

    Hamagishi, Y.; Oki, T.; Tone, H.; Inui, T. (Sanraku-Ocean Co. Ltd., Fujisawa, Kanagawa (Japan). Central Research Lab.)

    1980-12-01

    A radioimmunoassay for guanosine-5'-diphosphate-3'-diphosphate (ppGpp) and adenosine-5'-triphosphate-3'-diphosphate (pppApp) has been developed. The assay method is based on competition of an unlabeled highly phosphorylated nucleotide with /sup 3/H-labeled highly phosphorylated nucleotide for binding sites on a specific antibody. Antibodies to ppGpp and pppApp were obtained by immunizing rabbits with the antigen prepared by conjugating ppGpp with human serum albumin using 1-ethyl-3-(3-dimethylaminoprophyl)carbodiimide, and with the antigen prepared by conjugating 8-(6-aminohexyl)amino-adenosine-5'-triphosphate-3'-diphosphate with human serum albumin using glutaraldehyde, respectively. Antibody-bound /sup 3/H-labeled highly phosphorylated nucleotides were separated from the free /sup 3/H-labeled highly phosphorylated nucleotides by selective adsorption on dextran-coated charcoal. Displacement plots were linear over a concentration range of 5 - 1,000 pmol/assay tube in a log-probit percentage plot. Application of this method to biological systems offers improved accuracy and convenience compared with the previous /sup 32/PO/sub 4/-labeling technique.

  7. Repaglinide at a cellular level

    DEFF Research Database (Denmark)

    Krogsgaard Thomsen, M; Bokvist, K; Høy, M;

    2002-01-01

    To investigate the hormonal and cellular selectivity of the prandial glucose regulators, we have undertaken a series of experiments, in which we characterised the effects of repaglinide and nateglinide on ATP-sensitive potassium ion (KATP) channel activity, membrane potential and exocytosis in ra...

  8. Analysis of cellular manufacturing systems

    NARCIS (Netherlands)

    Heragu, Sunderesh; Meng, Gang; Zijm, Henk; Ommeren, van Jan-Kees

    2001-01-01

    In this paper, we present an open queuing network modeling approach to estimate performance measures of a cellular manufacturing layout. It is assumed a layout and production data for a planning period of specified length are available. The production data takes into account, processing and handli

  9. Cellular uptake of metallated cobalamins

    DEFF Research Database (Denmark)

    Tran, MQT; Stürup, Stefan; Lambert, Ian H.;

    2016-01-01

    Cellular uptake of vitamin B12-cisplatin conjugates was estimated via detection of their metal constituents (Co, Pt, and Re) by inductively coupled plasma mass spectrometry (ICP-MS). Vitamin B12 (cyano-cob(iii)alamin) and aquo-cob(iii)alamin [Cbl-OH2](+), which differ in the β-axial ligands (CN(-...

  10. Adenosine 5'triphosphate transport and accumulation during the cold preservation of rat hepatocytes in University of Wisconsin solution

    Institute of Scientific and Technical Information of China (English)

    María E. Mamprin; Félix Vega; Joaquín V. Rodriguez

    2005-01-01

    AIM: We used isolated hepatocytes to investigate how different concentrations of ATP in the University of Wisconsin (UW) solution affected both cellular ATP content and cell viability during the cold storage and the rewarming step. The mechanism involved in ATP transport and accumulation in hypothermia was also determined.METHODS: The cells were preserved up to 72 h in different conditions: UW solution without ATP (a-group),UW+5 mmol/L ATP (b-group), and UW+10 mmol/L ATP (c-group). The ATP content and the cell viability (LDH release) were determined during the cold storage and the rewarming step. In the groups a and c, the respiratory function of the cells at rewarming was studied. In addition,the cell volume of hepatocytes and the mechanism involved in ATP transport and accumulation were assessed. The extracellular degradation of exogenous nucleotides during transport experiments was investigated by a HPLC technique.RESULTS: After three days of cold storage a loss of cellular ATP content was observed in hepatocytes preserved either without nucleotides (a-group) or with 5 mmol/L ATP (b-group). In contrast, 10 mmol/L ATP (c-group) was able to maintain a normal ATP cellular content, with only a 6% diminution after 72 h of cold storage. The respiratory function was significantly different in hepatocytes preserved with 10 mmol/L ATP than without ATP. No significant change was detected for the three groups in cellular volume during the cold storage. We also report that the time course accumulation of [3H]-ATP by cold stored hepatocytes is a rapid process that is completed after 180 s with linear dependence on the extracellular ATP concentration (linear fitting results in a slope of 0.5624±0.1179 mmol/L ATP intracell/mmol/L ATP extracell).CONCLUSION: Our results show that, during hypothermic storage in UW solution, hepatocytes are permeable to ATP by a diffusive mechanism. Also, we found that it is ATP the main extracellular nucleotide available for transport and it is

  11. Cellular solidification of transparent monotectics

    Science.gov (United States)

    Kaulker, W. F.

    1986-01-01

    Understanding how liquid phase particles are engulfed or pushed during freezing of a monotectic is addressed. The additional complication is that the solid-liquid interface is nonplanar due to constitutional undercooling. Some evidence of particle pushing where the particles are the liquid phase of the montectic was already observed. Cellular freezing of the succinonitrile-glycerol system also occurred. Only a few compositions were tested at that time. The starting materials were not especially pure so that cellular interface observed was likely due to the presence of unkown impurities, the major portion of which was water. Topics addressed include: the effort of modeling the particle pushing process using the computer, establishing an apparatus for the determination of phase diagrams, and the measurement of the temperature gradients with a specimen which will solidify on the temperature gradient microscope stage.

  12. Reversibly assembled cellular composite materials.

    Science.gov (United States)

    Cheung, Kenneth C; Gershenfeld, Neil

    2013-09-13

    We introduce composite materials made by reversibly assembling a three-dimensional lattice of mass-produced carbon fiber-reinforced polymer composite parts with integrated mechanical interlocking connections. The resulting cellular composite materials can respond as an elastic solid with an extremely large measured modulus for an ultralight material (12.3 megapascals at a density of 7.2 milligrams per cubic centimeter). These materials offer a hierarchical decomposition in modeling, with bulk properties that can be predicted from component measurements and deformation modes that can be determined by the placement of part types. Because site locations are locally constrained, structures can be produced in a relative assembly process that merges desirable features of fiber composites, cellular materials, and additive manufacturing.

  13. Analysis of cellular manufacturing systems

    OpenAIRE

    Heragu, Sunderesh; Meng, Gang; Zijm, Henk; Ommeren, van, J.C.

    2001-01-01

    In this paper, we present an open queuing network modeling approach to estimate performance measures of a cellular manufacturing layout. It is assumed a layout and production data for a planning period of specified length are available. The production data takes into account, processing and handling set-up times as well as transfer and process batch size information of multiple products that flow through the system. It is assumed that two sets of discrete material handling devices are used fo...

  14. Identification of Nonstationary Cellular Automata

    Institute of Scientific and Technical Information of China (English)

    AndrewI.Adamatzky

    1992-01-01

    The principal feature of nonstationary cellular automata(NCA) is that a local transitiol rule of each cell is changed at each time step depending on neighborhood configuration at previous time step.The identification problem for NCA is extraction of local transition rules and the establishment of mechanism for changing these rules using sequence of NCA configurations.We present serial and parallel algorithms for identification of NCA.

  15. The Origins of Cellular Life

    OpenAIRE

    Schrum, Jason P.; Zhu, Ting F.; SZOSTAK, JACK W.

    2010-01-01

    Understanding the origin of cellular life on Earth requires the discovery of plausible pathways for the transition from complex prebiotic chemistry to simple biology, defined as the emergence of chemical assemblies capable of Darwinian evolution. We have proposed that a simple primitive cell, or protocell, would consist of two key components: a protocell membrane that defines a spatially localized compartment, and an informational polymer that allows for the replication and inheritance of fun...

  16. Stochastic Nature in Cellular Processes

    Institute of Scientific and Technical Information of China (English)

    刘波; 刘圣君; 王祺; 晏世伟; 耿轶钊; SAKATA Fumihiko; GAO Xing-Fa

    2011-01-01

    The importance of stochasticity in cellular processes is increasingly recognized in both theoretical and experimental studies. General features of stochasticity in gene regulation and expression are briefly reviewed in this article, which include the main experimental phenomena, classification, quantization and regulation of noises. The correlation and transmission of noise in cascade networks are analyzed further and the stochastic simulation methods that can capture effects of intrinsic and extrinsic noise are described.

  17. CELLULAR FETAL MICROCHIMERISM IN PREECLAMPSIA

    OpenAIRE

    Gammill, Hilary S; Aydelotte, Tessa M.; Guthrie, Katherine A.; Nkwopara, Evangelyn C.; Nelson, J. Lee

    2013-01-01

    Previous studies have shown elevated concentrations of free fetal deoxyribonucleic acid and erythroblasts in maternal circulation in preeclampsia compared with normal pregnancy. Pluripotent and immunocompetent fetal cells also transfer to the maternal circulation during pregnancy, but whether concentrations of fetal mononuclear cells also differed in preeclampsia was unknown. We sought to quantify cellular fetal microchimerism in maternal circulation in women with preeclampsia and healthy con...

  18. Cellular reactions to patterned biointerfaces

    OpenAIRE

    Schulte, Vera Antonie

    2012-01-01

    The subject of this thesis is to study cellular reactions to topographically, mechanically and biochemically tunable polymeric biomaterials. Different aspects of in vitro cell-biomaterial interactions were systematically studied with the murine fibroblast cell line NIH L929 and primary human dermal fibroblasts (HDFs). Besides a general cytocompatibility assessment of the applied materials and the quantification of cell adhesion per se, cell morphological changes (e.g. cell spreading) and intr...

  19. CELLULAR INTERACTIONS MEDIATED BY GLYCONECTIDS

    OpenAIRE

    Popescu, O.; Sumanovski, L. T.; I. Checiu; Elisabeta Popescu; G. N. Misevic

    1999-01-01

    Cellular interactions involve many types of cell surface molecules and operate via homophilic and/or heterophilic protein-protein and protein-carbohydrate binding. Our investigations in different model-systems (marine invertebrates and mammals) have provided direct evidence that a novel class of primordial proteoglycans, named by us gliconectins, can mediate cell adhesion via a new alternative molecular mechanism of polyvalent carbohydrate-carbohydrate binding. Biochemical characterization of...

  20. Progress of cellular dedifferentiation research

    Institute of Scientific and Technical Information of China (English)

    LIU Hu-xian; HU Da-hai; JIA Chi-yu; FU Xiao-bing

    2006-01-01

    Differentiation, the stepwise specialization of cells, and transdifferentiation, the apparent switching of one cell type into another, capture much of the stem cell spotlight. But dedifferentiation, the developmental reversal of a cell before it reinvents itself, is an important process too. In multicellular organisms, cellular dedifferentiation is the major process underlying totipotency, regeneration and formation of new stem cell lineages. In humans,dedifferentiation is often associated with carcinogenesis.The study of cellular dedifferentiation in animals,particularly early events related to cell fate-switch and determination, is limited by the lack of a suitable,convenient experimental system. The classic example of dedifferentiation is limb and tail regeneration in urodele amphibians, such as salamanders. Recently, several investigators have shown that certain mammalian cell types can be induced to dedifferentiate to progenitor cells when stimulated with the appropriate signals or materials. These discoveries open the possibility that researchers might enhance the endogenous regenerative capacity of mammals by inducing cellular dedifferentiation in vivo.

  1. The insect cellular immune response

    Institute of Scientific and Technical Information of China (English)

    Michael R. Strand

    2008-01-01

    The innate immune system of insects is divided into humoral defenses that include the production of soluble effector molecules and cellular defenses like phagocytosis and encapsulation that are mediated by hemocytes. This review summarizes current understanding of the cellular immune response. Insects produce several terminally differentiated types of hemocytes that are distinguished by morphology, molecular and antigenic markers, and function. The differentiated hemocytes that circulate in larval or nymphal stage insects arise from two sources: progenitor cells produced during embryogenesis and mesodermally derived hematopoietic organs. Regulation of hematopoiesis and hemocyte differentiation also involves several different signaling pathways. Phagocytosis and encapsulation require that hemocytes first recognize a given target as foreign followed by activation of downstream signaling and effector responses. A number of humoral and cellular receptors have been identified that recognize different microbes and multicellular parasites. In turn, activation of these receptors stimulates a number of signaling pathways that regulate different hemocyte functions. Recent studies also identify hemocytes as important sources of a number of humoral effector molecules required for killing different foreign invaders.

  2. New structural and functional defects in polyphosphate deficient bacteria: A cellular and proteomic study

    Directory of Open Access Journals (Sweden)

    Chávez Francisco P

    2010-01-01

    Full Text Available Abstract Background Inorganic polyphosphate (polyP, a polymer of tens or hundreds of phosphate residues linked by ATP-like bonds, is found in all organisms and performs a wide variety of functions. PolyP is synthesized in bacterial cells by the actions of polyphosphate kinases (PPK1 and PPK2 and degraded by exopolyphosphatase (PPX. Bacterial cells with polyP deficiencies due to knocking out the ppk1 gene are affected in many structural and important cellular functions such as motility, quorum sensing, biofilm formation and virulence among others. The cause of this pleiotropy is not entirely understood. Results The overexpression of exopolyphosphatase in bacteria mimicked some pleitropic defects found in ppk1 mutants. By using this approach we found new structural and functional defects in the polyP-accumulating bacteria Pseudomonas sp. B4, which are most likely due to differences in the polyP-removal strategy. Colony morphology phenotype, lipopolysaccharide (LPS structure changes and cellular division malfunction were observed. Finally, we used comparative proteomics in order to elucidate the cellular adjustments that occurred during polyP deficiency in this bacterium and found some clues that helped to understand the structural and functional defects observed. Conclusions The results obtained suggest that during polyP deficiency energy metabolism and particularly nucleoside triphosphate (NTP formation were affected and that bacterial cells overcame this problem by increasing the flux of energy-generating metabolic pathways such as tricarboxilic acid (TCA cycle, β-oxidation and oxidative phosphorylation and by reducing energy-consuming ones such as active transporters and amino acid biosynthesis. Furthermore, our results suggest that a general stress response also took place in the cell during polyP deficiency.

  3. Cellular communications a comprehensive and practical guide

    CERN Document Server

    Tripathi, Nishith

    2014-01-01

    Even as newer cellular technologies and standards emerge, many of the fundamental principles and the components of the cellular network remain the same. Presenting a simple yet comprehensive view of cellular communications technologies, Cellular Communications provides an end-to-end perspective of cellular operations, ranging from physical layer details to call set-up and from the radio network to the core network. This self-contained source forpractitioners and students represents a comprehensive survey of the fundamentals of cellular communications and the landscape of commercially deployed

  4. Theoretical vibrational spectroscopy of intermediates and the reaction mechanism of the guanosine triphosphate hydrolysis by the protein complex Ras-GAP.

    Science.gov (United States)

    Khrenova, Maria G; Grigorenko, Bella L; Nemukhin, Alexander V

    2016-09-01

    The structures and vibrational spectra of the reacting species upon guanosine triphosphate (GTP) hydrolysis to guanosine diphosphate and inorganic phosphate (Pi) trapped inside the protein complex Ras-GAP were analyzed following the results of QM/MM simulations. The frequencies of the phosphate vibrations referring to the reactants and to Pi were compared to those observed in the experimental FTIR studies. A good correlation between the theoretical and experimental vibrational data provides a strong support to the reaction mechanism of GTP hydrolysis by the Ras-GAP enzyme system revealed by the recent QM/MM modeling. Evolution of the vibrational bands associated with the inorganic phosphate Pi during the elementary stages of GTP hydrolysis is predicted. PMID:27214270

  5. Theoretical vibrational spectroscopy of intermediates and the reaction mechanism of the guanosine triphosphate hydrolysis by the protein complex Ras-GAP

    Science.gov (United States)

    Khrenova, Maria G.; Grigorenko, Bella L.; Nemukhin, Alexander V.

    2016-09-01

    The structures and vibrational spectra of the reacting species upon guanosine triphosphate (GTP) hydrolysis to guanosine diphosphate and inorganic phosphate (Pi) trapped inside the protein complex Ras-GAP were analyzed following the results of QM/MM simulations. The frequencies of the phosphate vibrations referring to the reactants and to Pi were compared to those observed in the experimental FTIR studies. A good correlation between the theoretical and experimental vibrational data provides a strong support to the reaction mechanism of GTP hydrolysis by the Ras-GAP enzyme system revealed by the recent QM/MM modeling. Evolution of the vibrational bands associated with the inorganic phosphate Pi during the elementary stages of GTP hydrolysis is predicted.

  6. Variants of the inosine triphosphate pyrophosphatase gene are associated with reduced relapse risk following treatment for HCV genotype 2/3

    DEFF Research Database (Denmark)

    Rembeck, Karolina; Waldenström, Jesper; Hellstrand, Kristoffer;

    2014-01-01

    The present study evaluated the impact of variations in the inosine triphosphate pyrophosphatase (ITPase) gene (ITPA) on treatment outcome in patients with hepatitis C virus (HCV) genotype 2/3 infection receiving peginterferon-α2a and lower, conventional 800 mg daily dose of ribavirin. Previous...... naïve HCV genotype 2/3 infected patients, enrolled in a phase III trial (NORDynamIC), were genotyped for ITPA (rs1127354 and rs7270101). Homo- or heterozygosity at Ars1127354 or Crs7270101, entailing reduced ITPase activity, was observed in 37% of patients and was associated with increased likelihood...... duration arms, HCV genotype, fibrosis stage and IL28B genotype, and was not secondary to improved adherence to therapy or less pronounced anemia. Gene variants predicting reduced predicted ITPase activity also were associated with decreased risk of anemia (P

  7. Dielectric spectra broadening as a signature for dipole-matrix interaction. III. Water in adenosine monophosphate/adenosine-5'-triphosphate solutions.

    Science.gov (United States)

    Puzenko, Alexander; Levy, Evgeniya; Shendrik, Andrey; Talary, Mark S; Caduff, Andreas; Feldman, Yuri

    2012-11-21

    In this, the third part of our series on the dielectric spectrum symmetrical broadening of water, we consider the nucleotide aqueous solutions. Where in Parts I [E. Levy et al., J. Chem. Phys. 136, 114502 (2012)] and II [E. Levy et al., J. Chem. Phys. 136, 114503 (2012)], the dipole-dipole or ion-dipole interaction had a dominant feature, now the interplay between these two types of dipole-matrix interactions will be considered. We present the results of high frequency dielectric measurements of different concentrations of adenosine monophosphate/adenosine-5'-triphosphate aqueous solutions. We observed the Cole-Cole broadening of the main relaxation peak of the solvent in the solutions. Moreover, depending on the nucleotide concentration, we observed both types of dipole-matrix interaction. The 3D trajectory approach (described in detail in Part I) is applied in order to highlight the differences between the two types of interaction.

  8. Dielectric spectra broadening as a signature for dipole-matrix interaction. III. Water in adenosine monophosphate/adenosine-5'-triphosphate solutions.

    Science.gov (United States)

    Puzenko, Alexander; Levy, Evgeniya; Shendrik, Andrey; Talary, Mark S; Caduff, Andreas; Feldman, Yuri

    2012-11-21

    In this, the third part of our series on the dielectric spectrum symmetrical broadening of water, we consider the nucleotide aqueous solutions. Where in Parts I [E. Levy et al., J. Chem. Phys. 136, 114502 (2012)] and II [E. Levy et al., J. Chem. Phys. 136, 114503 (2012)], the dipole-dipole or ion-dipole interaction had a dominant feature, now the interplay between these two types of dipole-matrix interactions will be considered. We present the results of high frequency dielectric measurements of different concentrations of adenosine monophosphate/adenosine-5'-triphosphate aqueous solutions. We observed the Cole-Cole broadening of the main relaxation peak of the solvent in the solutions. Moreover, depending on the nucleotide concentration, we observed both types of dipole-matrix interaction. The 3D trajectory approach (described in detail in Part I) is applied in order to highlight the differences between the two types of interaction. PMID:23181321

  9. Simultaneous Analysis of Major Coenzymes of Cellular Redox Reactions and Energy Using ex Vivo (1)H NMR Spectroscopy.

    Science.gov (United States)

    Nagana Gowda, G A; Abell, Lauren; Lee, Chi Fung; Tian, Rong; Raftery, Daniel

    2016-05-01

    Coenzymes of cellular redox reactions and cellular energy mediate biochemical reactions fundamental to the functioning of all living cells. Despite their immense interest, no simple method exists to gain insights into their cellular concentrations in a single step. We show that a simple (1)H NMR experiment can simultaneously measure oxidized and reduced forms of nicotinamide adenine dinucleotide (NAD(+) and NADH), oxidized and reduced forms of nicotinamide adenine dinucleotide phosphate (NADP(+) and NADPH), and adenosine triphosphate (ATP) and its precursors, adenosine diphosphate (ADP) and adenosine monophosphate (AMP), using mouse heart, kidney, brain, liver, and skeletal muscle tissue extracts as examples. Combining 1D/2D NMR experiments, chemical shift libraries, and authentic compound data, reliable peak identities for these coenzymes have been established. To assess this methodology, cardiac NADH and NAD(+) ratios/pool sizes were measured using mouse models with a cardiac-specific knockout of the mitochondrial Complex I Ndufs4 gene (cKO) and cardiac-specific overexpression of nicotinamide phosphoribosyltransferase (cNAMPT) as examples. Sensitivity of NAD(+) and NADH to cKO or cNAMPT was observed, as anticipated. Time-dependent investigations showed that the levels of NADH and NADPH diminish by up to ∼50% within 24 h; concomitantly, NAD(+) and NADP(+) increase proportionately; however, degassing the sample and flushing the sample tubes with helium gas halted such changes. The analysis protocol along with the annotated characteristic fingerprints for each coenzyme is provided for easy identification and absolute quantification using a single internal reference for routine use. The ability to visualize the ubiquitous coenzymes fundamental to cellular functions, simultaneously and reliably, offers a new avenue to interrogate the mechanistic details of cellular function in health and disease. PMID:27043450

  10. Interaction of Beta-Hydroxy-Beta-Methylbutyrate Free Acid and Adenosine Triphosphate on Muscle Mass, Strength, and Power in Resistance Trained Individuals.

    Science.gov (United States)

    Lowery, Ryan P; Joy, Jordan M; Rathmacher, John A; Baier, Shawn M; Fuller, John C; Shelley, Mack C; Jäger, Ralf; Purpura, Martin; Wilson, Stephanie M C; Wilson, Jacob M

    2016-07-01

    Lowery, RP, Joy, JM, Rathmacher, JA, Baier, SM, Fuller, JC Jr, Shelley, MC II, Jäger, R, Purpura, M, Wilson, SMC, and Wilson, JM. Interaction of beta-hydroxy-beta-methylbutyrate free acid and adenosine triphosphate on muscle mass, strength, and power in resistance trained individuals. J Strength Cond Res 30(7): 1843-1854, 2016-Adenosine-5'-triphosphate (ATP) supplementation helps maintain performance under high fatiguing contractions and with greater fatigue recovery demands also increase. Current evidence suggests that the free acid form of β-hydroxy-β-methylbutyrate (HMB-FA) acts by speeding regenerative capacity of skeletal muscle after high-intensity or prolonged exercise. Therefore, we investigated the effects of 12 weeks of HMB-FA (3 g) and ATP (400 mg) administration on lean body mass (LBM), strength, and power in trained individuals. A 3-phase double-blind, placebo-, and diet-controlled study was conducted. Phases consisted of an 8-week periodized resistance training program (phase 1), followed by a 2-week overreaching cycle (phase 2), and a 2-week taper (phase 3). Lean body mass was increased by a combination of HMB-FA/ATP by 12.7% (p power were increased in the HMB-FA/ATP-supplemented group compared with the placebo-supplemented group, and the 12-week increases were 21.5 and 23.7%, respectively. During the overreaching cycle, strength and power declined in the placebo group (4.3-5.7%), whereas supplementation with HMB-FA/ATP resulted in continued strength gains (1.3%). In conclusion, HMB-FA and ATP in combination with resistance exercise training enhanced LBM, power, and strength. In addition, HMB-FA plus ATP blunted the typical response to overreaching, resulting in a further increase in strength during that period. It seems that the combination of HMB-FA/ATP could benefit those who continuously train at high levels such as elite athletes or military personnel.

  11. Cellular host responses to gliomas.

    Directory of Open Access Journals (Sweden)

    Joseph Najbauer

    Full Text Available BACKGROUND: Glioblastoma multiforme (GBM is the most aggressive type of malignant primary brain tumors in adults. Molecular and genetic analysis has advanced our understanding of glioma biology, however mapping the cellular composition of the tumor microenvironment is crucial for understanding the pathology of this dreaded brain cancer. In this study we identified major cell populations attracted by glioma using orthotopic rodent models of human glioma xenografts. Marker-specific, anatomical and morphological analyses revealed a robust influx of host cells into the main tumor bed and tumor satellites. METHODOLOGY/PRINCIPAL FINDINGS: Human glioma cell lines and glioma spheroid orthotopic implants were used in rodents. In both models, the xenografts recruited large numbers of host nestin-expressing cells, which formed a 'network' with glioma. The host nestin-expressing cells appeared to originate in the subventricular zone ipsilateral to the tumor, and were clearly distinguishable from pericytes that expressed smooth muscle actin. These distinct cell populations established close physical contact in a 'pair-wise' manner and migrated together to the deeper layers of tumor satellites and gave rise to tumor vasculature. The GBM biopsy xenografts displayed two different phenotypes: (a low-generation tumors (first in vivo passage in rats were highly invasive and non-angiogenic, and host nestin-positive cells that infiltrated into these tumors displayed astrocytic or elongated bipolar morphology; (b high-generation xenografts (fifth passage had pronounced cellularity, were angiogenic with 'glomerulus-like' microvascular proliferations that contained host nestin-positive cells. Stromal cell-derived factor-1 and its receptor CXCR4 were highly expressed in and around glioma xenografts, suggesting their role in glioma progression and invasion. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate a robust migration of nestin-expressing host cells to glioma, which

  12. Estimation in Cellular Radio Systems

    OpenAIRE

    Blom, Jonas; Gunnarsson, Fredrik; Gustafsson, Fredrik

    1999-01-01

    The problem to track time-varying parameters in cellular radio systems is studied, and the focus is on estimation based only on the signals that are readily available. Previous work have demonstrated very good performance, but were relying on analog measurement that are not available. Most of the information is lost due to quantization and sampling at a rate that might be as low as 2 Hz (GSM case). For that matter a maximum likelihood estimator have been designed and exemplified in the case o...

  13. Cellular immune responses to HIV

    Science.gov (United States)

    McMichael, Andrew J.; Rowland-Jones, Sarah L.

    2001-04-01

    The cellular immune response to the human immunodeficiency virus, mediated by T lymphocytes, seems strong but fails to control the infection completely. In most virus infections, T cells either eliminate the virus or suppress it indefinitely as a harmless, persisting infection. But the human immunodeficiency virus undermines this control by infecting key immune cells, thereby impairing the response of both the infected CD4+ T cells and the uninfected CD8+ T cells. The failure of the latter to function efficiently facilitates the escape of virus from immune control and the collapse of the whole immune system.

  14. Cellular automata a parallel model

    CERN Document Server

    Mazoyer, J

    1999-01-01

    Cellular automata can be viewed both as computational models and modelling systems of real processes. This volume emphasises the first aspect. In articles written by leading researchers, sophisticated massive parallel algorithms (firing squad, life, Fischer's primes recognition) are treated. Their computational power and the specific complexity classes they determine are surveyed, while some recent results in relation to chaos from a new dynamic systems point of view are also presented. Audience: This book will be of interest to specialists of theoretical computer science and the parallelism challenge.

  15. Game of Life Cellular Automata

    CERN Document Server

    Adamatzky, Andrew

    2010-01-01

    In the late 1960s, British mathematician John Conway invented a virtual mathematical machine that operates on a two-dimensional array of square cell. Each cell takes two states, live and dead. The cells' states are updated simultaneously and in discrete time. A dead cell comes to life if it has exactly three live neighbours. A live cell remains alive if two or three of its neighbours are alive, otherwise the cell dies. Conway's Game of Life became the most programmed solitary game and the most known cellular automaton. The book brings together results of forty years of study into computational

  16. Protein accounting in the cellular economy

    Science.gov (United States)

    Vázquez-Laslop, Nora; Mankin, Alexander S.

    2014-01-01

    Knowing the copy number of cellular proteins is critical for understanding cell physiology. By being able to measure the absolute synthesis rates of the majority of cellular proteins, Li et al. (2014) gain insights into key aspects of translation regulation and fundamental principles of cellular strategies to adjust protein synthesis according to the needs. PMID:24766801

  17. Cellular uptake of metallated cobalamins.

    Science.gov (United States)

    Tran, Mai Thanh Quynh; Stürup, Stefan; Lambert, Ian Henry; Gammelgaard, Bente; Furger, Evelyne; Alberto, Roger

    2016-03-01

    Cellular uptake of vitamin B12-cisplatin conjugates was estimated via detection of their metal constituents (Co, Pt, and Re) by inductively coupled plasma mass spectrometry (ICP-MS). Vitamin B12 (cyano-cob(iii)alamin) and aquo-cob(iii)alamin [Cbl-OH2](+), which differ in the β-axial ligands (CN(-) and H2O, respectively), were included as control samples. The results indicated that B12 derivatives delivered cisplatin to both cellular cytosol and nuclei with an efficiency of one third compared to the uptake of free cisplatin cis-[Pt(II)Cl2(NH3)2]. In addition, uptake of charged B12 derivatives including [Cbl-OH2](+), [{Co}-CN-{cis-PtCl(NH3)2}](+), [{Re}-{Co}-CN-{cis-PtCl(NH3)2}](+), and [{Co}-CN-{trans-Pt(Cyt)(NH3)2}](2+) (Cyt = cytarabin) was high compared to neutral B12, which implied the existence of an additional internalization pathway for charged B12 vitamin analogs. The affinities of the charged B12 derivatives to the B12 transporters HC, IF and TC were similar to that of native vitamin B12. PMID:26739575

  18. Cellular Therapy for Heart Failure.

    Science.gov (United States)

    Psaltis, Peter J; Schwarz, Nisha; Toledo-Flores, Deborah; Nicholls, Stephen J

    2016-01-01

    The pathogenesis of cardiomyopathy and heart failure (HF) is underpinned by complex changes at subcellular, cellular and extracellular levels in the ventricular myocardium. For all of the gains that conventional treatments for HF have brought to mortality and morbidity, they do not adequately address the loss of cardiomyocyte numbers in the remodeling ventricle. Originally conceived to address this problem, cellular transplantation for HF has already gone through several stages of evolution over the past two decades. Various cell types and delivery routes have been implemented to positive effect in preclinical models of ischemic and nonischemic cardiomyopathy, with pleiotropic benefits observed in terms of myocardial remodeling, systolic and diastolic performance, perfusion, fibrosis, inflammation, metabolism and electrophysiology. To a large extent, these salubrious effects are now attributed to the indirect, paracrine capacity of transplanted stem cells to facilitate endogenous cardiac repair processes. Promising results have also followed in early phase human studies, although these have been relatively modest and somewhat inconsistent. This review details the preclinical and clinical evidence currently available regarding the use of pluripotent stem cells and adult-derived progenitor cells for cardiomyopathy and HF. It outlines the important lessons that have been learned to this point in time, and balances the promise of this exciting field against the key challenges and questions that still need to be addressed at all levels of research, to ensure that cell therapy realizes its full potential by adding to the armamentarium of HF management. PMID:27280304

  19. Cellular automata modelling of SEIRS

    Institute of Scientific and Technical Information of China (English)

    Liu Quan-Xing; Jin Zhen

    2005-01-01

    In this paper the SEIRS epidemic spread is analysed, and a two-dimensional probability cellular automata model for SEIRS is presented. Each cellular automation cell represents a part of the population that may be found in one of five states of individuals: susceptible, exposed (or latency), infected, immunized (or recovered) and death. Here studied are the effects of two cases on the epidemic spread. i.e. the effects of non-segregation and segregation on the latency and the infected of population. The conclusion is reached that the epidemic will persist in the case of non-segregation but it will decrease in the case of segregation. The proposed model can serve as a basis for the development of algorithms to simulate real epidemics based on real data. Last we find the density series of the exposed and the infected will fluctuate near a positive equilibrium point, when the constant for the immunized is less than its corresponding constant τ0. Our theoretical results are verified by numerical simulations.

  20. Cellular functions of the microprocessor.

    Science.gov (United States)

    Macias, Sara; Cordiner, Ross A; Cáceres, Javier F

    2013-08-01

    The microprocessor is a complex comprising the RNase III enzyme Drosha and the double-stranded RNA-binding protein DGCR8 (DiGeorge syndrome critical region 8 gene) that catalyses the nuclear step of miRNA (microRNA) biogenesis. DGCR8 recognizes the RNA substrate, whereas Drosha functions as an endonuclease. Recent global analyses of microprocessor and Dicer proteins have suggested novel functions for these components independent of their role in miRNA biogenesis. A HITS-CLIP (high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation) experiment designed to identify novel substrates of the microprocessor revealed that this complex binds and regulates a large variety of cellular RNAs. The microprocessor-mediated cleavage of several classes of RNAs not only regulates transcript levels, but also modulates alternative splicing events, independently of miRNA function. Importantly, DGCR8 can also associate with other nucleases, suggesting the existence of alternative DGCR8 complexes that may regulate the fate of a subset of cellular RNAs. The aim of the present review is to provide an overview of the diverse functional roles of the microprocessor.

  1. Universal map for cellular automata

    Energy Technology Data Exchange (ETDEWEB)

    García-Morales, V., E-mail: vmorales@ph.tum.de [Institute for Advanced Study – Technische Universität München, Lichtenbergstr. 2a, D-85748 Garching (Germany)

    2012-08-20

    A universal map is derived for all deterministic 1D cellular automata (CAs) containing no freely adjustable parameters and valid for any alphabet size and any neighborhood range (including non-symmetrical neighborhoods). The map can be extended to an arbitrary number of dimensions and topologies and to arbitrary order in time. Specific CA maps for the famous Conway's Game of Life and Wolfram's 256 elementary CAs are given. An induction method for CAs, based in the universal map, allows mathematical expressions for the orbits of a wide variety of elementary CAs to be systematically derived. -- Highlights: ► A universal map is derived for all deterministic 1D cellular automata (CA). ► The map is generalized to 2D for Von Neumann, Moore and hexagonal neighborhoods. ► A map for all Wolfram's 256 elementary CAs is derived. ► A map for Conway's “Game of Life” is obtained.

  2. Melanoma screening with cellular phones.

    Directory of Open Access Journals (Sweden)

    Cesare Massone

    Full Text Available BACKGROUND: Mobile teledermatology has recently been shown to be suitable for teledermatology despite limitations in image definition in preliminary studies. The unique aspect of mobile teledermatology is that this system represents a filtering or triage system, allowing a sensitive approach for the management of patients with emergent skin diseases. METHODOLOGY/PRINCIPAL FINDINGS: In this study we investigated the feasibility of teleconsultation using a new generation of cellular phones in pigmented skin lesions. 18 patients were selected consecutively in the Pigmented Skin Lesions Clinic of the Department of Dermatology, Medical University of Graz, Graz (Austria. Clinical and dermoscopic images were acquired using a Sony Ericsson with a built-in two-megapixel camera. Two teleconsultants reviewed the images on a specific web application (http://www.dermahandy.net/default.asp where images had been uploaded in JPEG format. Compared to the face-to-face diagnoses, the two teleconsultants obtained a score of correct telediagnoses of 89% and of 91.5% reporting the clinical and dermoscopic images, respectively. CONCLUSIONS/SIGNIFICANCE: The present work is the first study performing mobile teledermoscopy using cellular phones. Mobile teledermatology has the potential to become an easy applicable tool for everyone and a new approach for enhanced self-monitoring for skin cancer screening in the spirit of the eHealth program of the European Commission Information for Society and Media.

  3. Suppression of the E. coli SOS response by dNTP pool changes.

    Science.gov (United States)

    Maslowska, Katarzyna H; Makiela-Dzbenska, Karolina; Fijalkowska, Iwona J; Schaaper, Roel M

    2015-04-30

    The Escherichia coli SOS system is a well-established model for the cellular response to DNA damage. Control of SOS depends largely on the RecA protein. When RecA is activated by single-stranded DNA in the presence of a nucleotide triphosphate cofactor, it mediates cleavage of the LexA repressor, leading to expression of the 30(+)-member SOS regulon. RecA activation generally requires the introduction of DNA damage. However, certain recA mutants, like recA730, bypass this requirement and display constitutive SOS expression as well as a spontaneous (SOS) mutator effect. Presently, we investigated the possible interaction between SOS and the cellular deoxynucleoside triphosphate (dNTP) pools. We found that dNTP pool changes caused by deficiencies in the ndk or dcd genes, encoding nucleoside diphosphate kinase and dCTP deaminase, respectively, had a strongly suppressive effect on constitutive SOS expression in recA730 strains. The suppression of the recA730 mutator effect was alleviated in a lexA-deficient background. Overall, the findings suggest a model in which the dNTP alterations in the ndk and dcd strains interfere with the activation of RecA, thereby preventing LexA cleavage and SOS induction.

  4. The Cellular Prion Protein Prevents Copper-Induced Inhibition of P2X4 Receptors

    Directory of Open Access Journals (Sweden)

    Ramón A. Lorca

    2011-01-01

    Full Text Available Although the physiological function of the cellular prion protein (PrPC remains unknown, several evidences support the notion of its role in copper homeostasis. PrPC binds Cu2+ through a domain composed by four to five repeats of eight amino acids. Previously, we have shown that the perfusion of this domain prevents and reverses the inhibition by Cu2+ of the adenosine triphosphate (ATP-evoked currents in the P2X4 receptor subtype, highlighting a modulatory role for PrPC in synaptic transmission through regulation of Cu2+ levels. Here, we study the effect of full-length PrPC in Cu2+ inhibition of P2X4 receptor when both are coexpressed. PrPC expression does not significantly change the ATP concentration-response curve in oocytes expressing P2X4 receptors. However, the presence of PrPC reduces the inhibition by Cu2+ of the ATP-elicited currents in these oocytes, confirming our previous observations with the Cu2+ binding domain. Thus, our observations suggest a role for PrPC in modulating synaptic activity through binding of extracellular Cu2+.

  5. Small molecule inhibition of phosphatidylinositol-3,4,5-triphosphate (PIP3) binding to pleckstrin homology domains

    Science.gov (United States)

    Miao, Benchun; Skidan, Igor; Yang, Jinsheng; Lugovskoy, Alexey; Reibarkh, Mikhail; Long, Kai; Brazell, Tres; Durugkar, Kulbhushan A.; Maki, Jenny; Ramana, C. V.; Schaffhausen, Brian; Wagner, Gerhard; Torchilin, Vladimir; Yuan, Junying; Degterev, Alexei

    2010-01-01

    The PI3-kinase (PI3K) pathway regulates many cellular processes, especially cell metabolism, cell survival, and apoptosis. Phosphatidylinositol-3,4,5-trisphosphate (PIP3), the product of PI3K activity and a key signaling molecule, acts by recruiting pleckstrin-homology (PH) domain-containing proteins to cell membranes. Here, we describe a new structural class of nonphosphoinositide small molecule antagonists (PITenins, PITs) of PIP3–PH domain interactions (IC50 ranges from 13.4 to 31 μM in PIP3/Akt PH domain binding assay). PITs inhibit interactions of a number of PIP3-binding PH domains, including those of Akt and PDK1, without affecting several PIP2-selective PH domains. As a result, PITs suppress the PI3K-PDK1-Akt pathway and trigger metabolic stress and apoptosis. A PIT-1 analog displayed significant antitumor activity in vivo, including inhibition of tumor growth and induction of apoptosis. Overall, our studies demonstrate the feasibility of developing specific small molecule antagonists of PIP3 signaling. PMID:21041639

  6. Running out of time: the decline of channel activity and nucleotide activation in adenosine triphosphate-sensitive K-channels.

    Science.gov (United States)

    Proks, Peter; Puljung, Michael C; Vedovato, Natascia; Sachse, Gregor; Mulvaney, Rachel; Ashcroft, Frances M

    2016-08-01

    KATP channels act as key regulators of electrical excitability by coupling metabolic cues-mainly intracellular adenine nucleotide concentrations-to cellular potassium ion efflux. However, their study has been hindered by their rapid loss of activity in excised membrane patches (rundown), and by a second phenomenon, the decline of activation by Mg-nucleotides (DAMN). Degradation of PI(4,5)P2 and other phosphoinositides is the strongest candidate for the molecular cause of rundown. Broad evidence indicates that most other determinants of rundown (e.g. phosphorylation, intracellular calcium, channel mutations that affect rundown) also act by influencing KATP channel regulation by phosphoinositides. Unfortunately, experimental conditions that reproducibly prevent rundown have remained elusive, necessitating post hoc data compensation. Rundown is clearly distinct from DAMN. While the former is associated with pore-forming Kir6.2 subunits, DAMN is generally a slower process involving the regulatory sulfonylurea receptor (SUR) subunits. We speculate that it arises when SUR subunits enter non-physiological conformational states associated with the loss of SUR nucleotide-binding domain dimerization following prolonged exposure to nucleotide-free conditions. This review presents new information on both rundown and DAMN, summarizes our current understanding of these processes and considers their physiological roles.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377720

  7. Potassium and sodium ions in the glycerinated skeletal muscle. Distribution changes induced by adenosine triphosphate and nondissociable anesthetic substances.

    Science.gov (United States)

    Dragomir, C T; Barbier, A; Ungureanu, D; Ionescu, V; Pausescu, E; Chirvasie, R; Ghitescu, D; Filipescu, G

    1975-01-01

    Investigation of the ionic behavior of glycerinated muscle fibers showed that the residual structures of this biologic cellular material, lacking functional membranes, are able to discriminate between alkaline ions. The characteristics of the ionic selectivity of the glycerinated fibers change with their functional state and with the presence in the medium of certain nonionic substances. Among the more important features of ionic distribution between the membrane-free fibers and the medium are the following: (1) There is evident adsorption of potassium on the fibers, in the absence of ATP. (2) This adsorption increases in contraction and decreases in relaxation. (3) At high ionic concentrations, in contrast to what occurs at low potassium concentrations, the glycerinated muscle prefers sodium to potassium, but even under these conditions both ions are accumulated in the fibers to far greater levels than in the medium. This strongly suggests a Donnan ionic equilibrium developing parallel to the adsorption process. (4) Nonionic substances of the general anesthetic group markedly alter the ionic selectivity of the glycerinated fibers, probably by their action on the water's physical state. A mechanism is proposed for the observed ionic adsorption specific of the muscle-a mechanism in which actin-myosin coupling plays the cardinal adsorption role. In the general interpretation of the data a synthetic concept is advanced according to which an entire set of processes and factors concurs with the distribution of ions between the muscle and the medium.

  8. Cellular Delivery of RNA Nanoparticles.

    Science.gov (United States)

    Parlea, Lorena; Puri, Anu; Kasprzak, Wojciech; Bindewald, Eckart; Zakrevsky, Paul; Satterwhite, Emily; Joseph, Kenya; Afonin, Kirill A; Shapiro, Bruce A

    2016-09-12

    RNA nanostructures can be programmed to exhibit defined sizes, shapes and stoichiometries from naturally occurring or de novo designed RNA motifs. These constructs can be used as scaffolds to attach functional moieties, such as ligand binding motifs or gene expression regulators, for nanobiology applications. This review is focused on four areas of importance to RNA nanotechnology: the types of RNAs of particular interest for nanobiology, the assembly of RNA nanoconstructs, the challenges of cellular delivery of RNAs in vivo, and the delivery carriers that aid in the matter. The available strategies for the design of nucleic acid nanostructures, as well as for formulation of their carriers, make RNA nanotechnology an important tool in both basic research and applied biomedical science. PMID:27509068

  9. Discrete geodesics and cellular automata

    CERN Document Server

    Arrighi, Pablo

    2015-01-01

    This paper proposes a dynamical notion of discrete geodesics, understood as straightest trajectories in discretized curved spacetime. The notion is generic, as it is formulated in terms of a general deviation function, but readily specializes to metric spaces such as discretized pseudo-riemannian manifolds. It is effective: an algorithm for computing these geodesics naturally follows, which allows numerical validation---as shown by computing the perihelion shift of a Mercury-like planet. It is consistent, in the continuum limit, with the standard notion of timelike geodesics in a pseudo-riemannian manifold. Whether the algorithm fits within the framework of cellular automata is discussed at length. KEYWORDS: Discrete connection, parallel transport, general relativity, Regge calculus.

  10. Cellular compartmentalization of secondary metabolism

    Directory of Open Access Journals (Sweden)

    H. Corby eKistler

    2015-02-01

    Full Text Available Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors shared with the most essential processes of the cell (e.g. amino acids, acetyl CoA, NADPH, enzymes for secondary metabolite synthesis are compartmentalized at conserved subcellular sites that position pathway enzymes to use these common biochemical precursors. Co-compartmentalization of secondary metabolism pathway enzymes also may function to channel precursors, promote pathway efficiency and sequester pathway intermediates and products from the rest of the cell. In this review we discuss the compartmentalization of three well-studied fungal secondary metabolite biosynthetic pathways for penicillin G, aflatoxin and deoxynivalenol, and summarize evidence used to infer subcellular localization. We also discuss how these metabolites potentially are trafficked within the cell and may be exported.

  11. Thermomechanical characterisation of cellular rubber

    Science.gov (United States)

    Seibert, H.; Scheffer, T.; Diebels, S.

    2016-09-01

    This contribution discusses an experimental possibility to characterise a cellular rubber in terms of the influence of multiaxiality, rate dependency under environmental temperature and its behaviour under hydrostatic pressure. In this context, a mixed open and closed cell rubber based on an ethylene propylene diene monomer is investigated exemplarily. The present article intends to give a general idea of the characterisation method and the considerable effects of this special type of material. The main focus lies on the experimental procedure and the used testing devices in combination with the analysis methods such as true three-dimensional digital image correlation. The structural compressibility is taken into account by an approach for a material model using the Theory of Porous Media with additional temperature dependence.

  12. Novel Materials for Cellular Nanosensors

    DEFF Research Database (Denmark)

    Sasso, Luigi

    modifications for electrochemical nanosensors for the detection of analytes released from cells. Two type of materials were investigated, each pertaining to the two different aspects of such devices: peptide nanostructures were studied for the creation of cellular sensing substrates that mimic in vivo surfaces......' functionalization with biomolecules, metal nanoparticles and chemical functional groups such as thiols, showing the versatility and flexibility of this material's applications. A technique for the patterning of these nanostructures using soft lithography was also developed and tested for suitable cell sensing....... An in vivo investigation also gave evidence of how the peptide nanowires can be used as surface modification in implantable electrodes for neurological measurements. Conducting polymers were utilized in electrode modifications for electrochemical sensor surfaces. Both chemical and electrochemical deposition...

  13. Identification of an mtDNA mutation hot spot in UV-induced mouse skin tumors producing altered cellular biochemistry.

    Science.gov (United States)

    Jandova, Jana; Eshaghian, Alex; Shi, Mingjian; Li, Meiling; King, Lloyd E; Janda, Jaroslav; Sligh, James E

    2012-02-01

    There is increasing awareness of the role of mtDNA alterations in the development of cancer, as mtDNA point mutations are found at high frequency in a variety of human tumors. To determine the biological effects of mtDNA mutations in UV-induced skin tumors, hairless mice were irradiated to produce tumors, and the tumor mtDNAs were screened for single-nucleotide changes using temperature gradient capillary electrophoresis (TGCE), followed by direct sequencing. A mutation hot spot (9821insA) in the mitochondrially encoded tRNA arginine (mt-Tr) locus (tRNA(Arg)) was discovered in approximately one-third of premalignant and malignant skin tumors. To determine the functional relevance of this particular mutation in vitro, cybrid cell lines containing different mt-Tr (tRNA(Arg)) alleles were generated. The resulting cybrid cell lines contained the same nuclear genotype and differed only in their mtDNAs. The biochemical analysis of the cybrids revealed that the mutant haplotype is associated with diminished levels of complex I protein (CI), resulting in lower levels of baseline oxygen consumption and lower cellular adenosine triphosphate (ATP) production. We hypothesize that this specific mtDNA mutation alters cellular biochemistry, supporting the development of keratinocyte neoplasia.

  14. Challenges and solutions in the bioanalysis of BMS-986094 and its metabolites including a highly polar, active nucleoside triphosphate in plasma and tissues using LC-MS/MS.

    Science.gov (United States)

    Liu, Ang; Lute, John; Gu, Huidong; Wang, Bonnie; Trouba, Kevin J; Arnold, Mark E; Aubry, Anne-Françoise; Wang, Jian

    2015-09-01

    BMS-986094, a nucleotide polymerase inhibitor of the hepatitis C virus, was withdrawn from clinical trials because of a serious safety issue. To investigate a potential association between drug/metabolite exposure and toxicity in evaluations conducted after the termination of the BMS-986094 development program, it was essential to determine the levels of BMS-986094 and its major metabolites INX-08032, INX-08144 and INX-09054 in circulation and the active nucleoside triphosphate INX-09114 in target and non-target tissues. However, there were many challenges in the bioanalysis of these compounds. The chromatography challenge for the extremely polar nucleoside triphosphate was solved by applying mixed-mode chromatography which combined anion exchange and reversed-phase interactions. The LC conditions provided adequate retention and good peak shape of the analyte and showed good robustness. A strategy using simultaneous extraction but separate LC analysis of the prodrug BMS-986094 and its major circulating metabolites was used to overcome a carryover issue of the hydrophobic prodrug while still achieving good chromatography of the polar metabolites. In addition, the nucleotide analytes were not stable in the presence of endogenous enzymes. Low pH and low temperature were required for blood collection and plasma sample processing. However, the use of phosphatase inhibitor and immediate homogenization and extraction were critical for the quantitative analysis of the active triphosphate, INX-09114, in tissue samples. To alleviate the bioanalytical complexity caused by multiple analytes, different matrices, and various species, a fit-for-purpose approach to assay validation was implemented based on the needs of drug safety assessment in non-clinical (GLP or non-GLP) studies. The assay for INX-08032 was fully validated in plasma of toxicology species. The lower limit of quantification was 1.00ng/mL and the linear curve range was 1.00-500.00ng/mL using a weighted (1/x(2

  15. Tween 20-stabilized gold nanoparticles combined with adenosine triphosphate-BODIPY conjugates for the fluorescence detection of adenosine with more than 1000-fold selectivity

    Energy Technology Data Exchange (ETDEWEB)

    Hung, Szu-Ying; Shih, Ya-Chen [Department of Chemistry, National Sun Yat-sen University, Taiwan (China); Tseng, Wei-Lung, E-mail: tsengwl@mail.nsysu.edu.tw [Department of Chemistry, National Sun Yat-sen University, Taiwan (China); School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Taiwan (China); Center for Nanoscience and Nanotechnology, National Sun Yat-sen University, Taiwan (China); Center for Stem Cell Research, Kaohsiung Medical University, Taiwan (China)

    2015-02-01

    Graphical abstract: A simple, enzyme-free, label-free, sensitive and selective system was developed for detecting adenosine based on the use of Tween 20-stabilized gold nanoparticles as an efficient quencher for boron dipyrromethene-conjugated adenosine 5′-triphosphate and as a recognition element for adenosine. - Highlights: • The proposed method can detect adenosine with more than 1000-fold selectivity. • The analysis of adenosine is rapid (∼6 min) using the proposed method. • This method provided better sensitivity for adenosine as compared to aptamer-based sensors. • This method can be applied for the determination of adenosine in urine. - Abstract: This study describes the development of a simple, enzyme-free, label-free, sensitive, and selective system for detecting adenosine based on the use of Tween 20-stabilized gold nanoparticles (Tween 20-AuNPs) as an efficient fluorescence quencher for boron dipyrromethene-conjugated adenosine 5′-triphosphate (BODIPY-ATP) and as a recognition element for adenosine. BODIPY-ATP can interact with Tween 20-AuNPs through the coordination between the adenine group of BODIPY-ATP and Au atoms on the NP surface, thereby causing the fluorescence quenching of BODIPY-ATP through the nanometal surface energy transfer (NSET) effect. When adenosine attaches to the NP surface, the attached adenosine exhibits additional electrostatic attraction to BODIPY-ATP. As a result, the presence of adenosine enhances the efficiency of AuNPs in fluorescence quenching of BODIPY-ATP. The AuNP-induced fluorescence quenching of BODIPY-ATP progressively increased with an increase in the concentration of adenosine; the detection limit at a signal-to-noise ratio of 3 for adenosine was determined to be 60 nM. The selectivity of the proposed system was more than 1000-fold for adenosine over any adenosine analogs and other nucleotides. The proposed system combined with a phenylboronic acid-containing column was successfully applied to the

  16. Cellular phones: are they detrimental?

    Science.gov (United States)

    Salama, Osama E; Abou El Naga, Randa M

    2004-01-01

    The issue of possible health effects of cellular phones is very much alive in the public's mind where the rapid increase in the number of the users of cell phones in the last decade has increased the exposure of people to the electromagnetic fields (EMFs). Health consequences of long term use of mobile phones are not known in detail but available data indicates the development of non specific annoying symptoms on acute exposure to mobile phone radiations. In an attempt to determine the prevalence of such cell phones associated health manifestations and the factors affecting their occurrence, a cross sectional study was conducted in five randomly selected faculties of Alexandria University. Where, 300 individuals including teaching staff, students and literate employee were equally allocated and randomly selected among the five faculties. Data about mobile phone's users and their medical history, their pattern of mobile usage and the possible deleterious health manifestations associated with cellular phone use was collected. The results revealed 68% prevalence of mobile phone usage, nearly three quarters of them (72.5%) were complainers of the health manifestations. They suffered from headache (43%), earache (38.3%), sense of fatigue (31.6%), sleep disturbance (29.5%), concentration difficulty (28.5%) and face burning sensation (19.2%). Both univariate and multivariate analysis were consistent in their findings. Symptomatic users were found to have significantly higher frequency of calls/day, longer call duration and longer total duration of mobile phone usage/day than non symptomatic users. For headache both call duration and frequency of calls/day were the significant predicting factors for its occurrence (chi2 = 18.208, p = 0.0001). For earache, in addition to call duration, the longer period of owning the mobile phone were significant predictors (chi2 = 16.996, p = 0.0002). Sense of fatigue was significantly affected by both call duration and age of the user

  17. Radiation, nitric oxide and cellular death

    International Nuclear Information System (INIS)

    The mechanisms of radiation induced cellular death constitute an objective of research ever since the first biological effects of radiation were first observed. The explosion of information produced in the last 20 years calls for a careful analysis due to the apparent contradictory data related to the cellular system studied and the range of doses used. This review focuses on the role of the active oxygen species, in particular the nitric oxides, in its relevance as potential mediator of radiation induced cellular death

  18. Autophagy and mitophagy in cellular damage control

    Directory of Open Access Journals (Sweden)

    Jianhua Zhang

    2013-01-01

    Full Text Available Autophagy and mitophagy are important cellular processes that are responsible for breaking down cellular contents, preserving energy and safeguarding against accumulation of damaged and aggregated biomolecules. This graphic review gives a broad summary of autophagy and discusses examples where autophagy is important in controlling protein degradation. In addition we highlight how autophagy and mitophagy are involved in the cellular responses to reactive species and mitochondrial dysfunction. The key signaling pathways for mitophagy are described in the context of bioenergetic dysfunction.

  19. Optimized Cellular Core for Rotorcraft Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Patz Materials and Technologies proposes to develop a unique structural cellular core material to improve mechanical performance, reduce platform weight and lower...

  20. Efficiency of cellular information processing

    CERN Document Server

    Barato, Andre C; Seifert, Udo

    2014-01-01

    We show that a rate of conditional Shannon entropy reduction, characterizing the learning of an internal process about an external process, is bounded by the thermodynamic entropy production. This approach allows for the definition of an informational efficiency that can be used to study cellular information processing. We analyze three models of increasing complexity inspired by the E. coli sensory network, where the external process is an external ligand concentration jumping between two values. We start with a simple model for which ATP must be consumed so that a protein inside the cell can learn about the external concentration. With a second model for a single receptor we show that the rate at which the receptor learns about the external environment can be nonzero even without any dissipation inside the cell since chemical work done by the external process compensates for this learning rate. The third model is more complete, also containing adaptation. For this model we show inter alia that a bacterium i...

  1. Adenosine triphosphate-sensitive potassium channel opener protects PC12 cells against hypoxia-induced apoptosis through PI3K/Akt and Bcl-2 signaling pathways

    Institute of Scientific and Technical Information of China (English)

    Hong Zhang; Chunhong Jia; Danyang Zhao; Yang Lu; Runling Wang; Jia Li

    2010-01-01

    Although previous studies have shown the neuroprotective effects of the adenosine triphosphate (ATP)-sensitive potassium (KATP) channel opener against ischemic neuronal damage, little is known about the mechanisms involved. Phosphatidylinositol-3 kinase (PI3K)/v-akt murine thy-moma viral oncogene homolog (Akt) and Bcl-2 are thought to be important factors that mediate neuroprotection. The present study investigated the effects of KATP openers on hypoxia-induced PC12 cell apoptosis, as well as mRNA and protein expression of Akt and Bcl-2. Results demon-strated that pretreatment of PC12 cells with pinacidil, a KATP opener, resulted in decreased PC12 cell apoptosis following hypoxia, as detected by Annexin-V fluorescein isothiocyanate/ propidium iodide double staining flow cytometry. In addition, mRNA and protein expression of phosphorylated Akt (p-Akt) and Bcl-2 increased, as detected by immunofluorescence, Western blot analysis, and reverse-transcription polymerase chain reaction. The protective effect of this preconditioning was attenuated by glipizide, a selective KATP blocker. These results demonstrate for the first time that the protective mechanisms of KATP openers on PC12 cell apoptosis following hypoxia could result from activation of the PI3K/Akt signaling pathway, which further activates expression of the downstream Bcl-2 gene.

  2. Characterization of the Deoxynucleotide Triphosphate Triphosphohydrolase (dNTPase) Activity of the EF1143 Protein from Enterococcus faecalis and Crystal Structure of the Activator-Substrate Complex

    Energy Technology Data Exchange (ETDEWEB)

    Vorontsov, Ivan I.; Minasov, George; Kiryukhina, Olga; Brunzelle, Joseph S.; Shuvalova, Ludmilla; Anderson, Wayne F. (NWU)

    2012-06-19

    The EF1143 protein from Enterococcus faecalis is a distant homolog of deoxynucleotide triphosphate triphosphohydrolases (dNTPases) from Escherichia coli and Thermus thermophilus. These dNTPases are important components in the regulation of the dNTP pool in bacteria. Biochemical assays of the EF1143 dNTPase activity demonstrated nonspecific hydrolysis of all canonical dNTPs in the presence of Mn{sup 2+}. In contrast, with Mg{sup 2+} hydrolysis required the presence of dGTP as an effector, activating the degradation of dATP and dCTP with dGTP also being consumed in the reaction with dATP. The crystal structure of EF1143 and dynamic light scattering measurements in solution revealed a tetrameric oligomer as the most probable biologically active unit. The tetramer contains four dGTP specific allosteric regulatory sites and four active sites. Examination of the active site with the dATP substrate suggests an in-line nucleophilic attack on the {alpha}-phosphate center as a possible mechanism of the hydrolysis and two highly conserved residues, His-129 and Glu-122, as an acid-base catalytic dyad. Structural differences between EF1143 apo and holo forms revealed mobility of the {alpha}3 helix that can regulate the size of the active site binding pocket and could be stabilized in the open conformation upon formation of the tetramer and dGTP effector binding.

  3. Fluorescence detection of adenosine-5'-triphosphate and alkaline phosphatase based on the generation of CdS quantum dots

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Siyu; Wang, Xinyan; Pang, Shu; Na, Weidan; Yan, Xu; Su, Xingguang, E-mail: suxg@jlu.edu.cn

    2014-05-01

    Highlights: • Cd²⁺ reacts with S²⁻ to generate fluorescent CdS QDs with ATP. • ATP can be hydrolyzed by the enzymatic dephosphorylation of ALP. • Fluorescent CdS QDs could not be generated in the presence of ALP. • The analysis system was successfully applied to assay ATP and ALP. Abstract: We have developed an analytical method to detect adenosine-5'-triphosphate (ATP) and alkaline phosphatase (ALP) based on the generation of CdS quantum dots (QDs). We demonstrated that Cd²⁺ cation reacts with S²⁻anion to generate fluorescent CdS QDs in the presence of some certain amount of ATP. With increase in the ATP concentration, the fluorescence intensity of CdS QDs was also enhanced. ATP can be converted into adenosine by the dephosphorylation of ALP, so that the generation of CdS QDs would be inhibited in the presence of ALP. Therefore, this novel analysis system could be applied to assay ATP and ALP based on the growth of fluorescent CdS QDs.

  4. Reduced rate of adenosine triphosphate synthesis by in vivo 31P nuclear magnetic resonance spectroscopy and downregulation of PGC-1beta in distal skeletal muscle following burn.

    Science.gov (United States)

    Tzika, A Aria; Mintzopoulos, Dionyssios; Padfield, Katie; Wilhelmy, Julie; Mindrinos, Michael N; Yu, Hongue; Cao, Haihui; Zhang, Qunhao; Astrakas, Loukas G; Zhang, Jiangwen; Yu, Yong-Ming; Rahme, Laurence G; Tompkins, Ronald G

    2008-02-01

    Using a mouse model of burn trauma, we tested the hypothesis that severe burn trauma corresponding to 30% of total body surface area (TBSA) causes reduction in adenosine triphosphate (ATP) synthesis in distal skeletal muscle. We employed in vivo 31P nuclear magnetic resonance (NMR) in intact mice to assess the rate of ATP synthesis, and characterized the concomitant gene expression patterns in skeletal muscle in burned (30% TBSA) versus control mice. Our NMR results showed a significantly reduced rate of ATP synthesis and were complemented by genomic results showing downregulation of the ATP synthase mitochondrial F1 F0 complex and PGC-1beta gene expression. Our findings suggest that inflammation and muscle atrophy in burns are due to a reduced ATP synthesis rate that may be regulated upstream by PGC-1beta. These findings implicate mitochondrial dysfunction in distal skeletal muscle following burn injury. That PGC-1beta is a highly inducible factor in most tissues and responds to common calcium and cyclic adenosine monophosphate (cAMP) signaling pathways strongly suggests that it may be possible to develop drugs that can induce PGC-1beta.

  5. Flow cytometry and adenosine tri-phosphate analysis: alternative possibilities to evaluate major bacteriological changes in drinking water treatment and distribution systems.

    Science.gov (United States)

    Vital, Marius; Dignum, Marco; Magic-Knezev, Aleksandra; Ross, Petra; Rietveld, Luuk; Hammes, Frederik

    2012-10-01

    An ever-growing need exists for rapid, quantitative and meaningful methods to quantify and characterize the effect of different treatment steps on the microbiological processes and events that occur during drinking water treatment and distribution. Here we compared cultivation-independent flow cytometry (FCM) and adenosine tri-phosphate (ATP) analysis with conventional cultivation-based microbiological methods, on water samples from two full-scale treatment and distribution systems. The two systems consist of nearly identical treatment trains, but their raw water quality and pre-treatment differed significantly. All of the drinking water treatment processes affected the microbiological content of the water considerably, but once treated, the finished water remained remarkably stable throughout the distribution system. Both the FCM and ATP data were able to describe the microbiology of the systems accurately, providing meaningful process data when combined with other parameters such as dissolved organic carbon analysis. Importantly, the results highlighted a complimentary value of the two independent methods: while similar trends were mostly observed, variations in ATP-per-cell values between water samples were adequately explained by differences in the FCM fingerprints of the samples. This work demonstrates the value of alternative microbial methods for process/system control, optimization and routine monitoring of the general microbial quality of water during treatment and distribution. PMID:22763289

  6. Use of a Sampling Area-Adjusted Adenosine Triphosphate Bioluminescence Assay Based on Digital Image Quantification to Assess the Cleanliness of Hospital Surfaces

    Science.gov (United States)

    Ho, Yu-Huai; Wang, Lih-Shinn; Jiang, Hui-Li; Chang, Chih-Hui; Hsieh, Chia-Jung; Chang, Dan-Chi; Tu, Hsin-Yu; Chiu, Tan-Yun; Chao, Huei-Jen; Tseng, Chun-Chieh

    2016-01-01

    Contaminated surfaces play an important role in the transmission of pathogens. We sought to establish a criterion that could indicate “cleanliness” using a sampling area–adjusted adenosine triphosphate (ATP) assay. In the first phase of the study, target surfaces were selected for swab sampling before and after daily cleaning; then, an aerobic colony count (ACC) plate assay of bacteria and antibiotic-resistant bacteria was conducted. ATP swabs were also tested, and the ATP readings were reported as relative light units (RLUs). The results of the ACC and ATP assays were adjusted according to the sampling area. During the second phase of the study, a new cleaning process employing sodium dichloroisocyanurate (NaDCC) was implemented for comparison. Using the criterion of 2.5 colony-forming units (CFU)/cm2, 45% of the sampled sites were successfully cleaned during phase one of the study. During phase two, the pass rates of the surface samples (64%) were significantly improved, except under stringent (5 RLU/cm2) and lax (500 RLU) ATP criteria. Using receiver-operating characteristic curve analysis, the best cut-off point for an area-adjusted ATP level was 7.34 RLU/cm2, which corresponded to culture-assay levels of <2.5 CFU/cm2. An area adjustment of the ATP assay improved the degree of correlation with the ACC-assay results from weak to moderate. PMID:27294944

  7. Proline modulates the effect of bisphosphonate on calcium levels and adenosine triphosphate production in cell lines derived from bovine Echinococcus granulosus protoscoleces.

    Science.gov (United States)

    Fuchs, A G; Echeverría, C I; Pérez Rojo, F G; Prieto González, E A; Roldán, E J A

    2014-12-01

    Bisphosphonates have been proposed as pharmacological agents against parasite and cancer cell growth. The effect of these compounds on helminthic cell viability and acellular compartment morphology, however, has not yet been studied. The effects of different types of bisphosphonates, namely etidronate (EHDP), pamidronate (APD), alendronate (ABP), ibandronate (IB) and olpadronate (OPD), and their interaction with amiloride, 1,25-dihydroxycholecalciferol (D3) and proline were evaluated on a cell line derived from bovine Echinococcus granulousus protoscoleces (EGPE) that forms cystic colonies in agarose. The EGPE cell line allowed testing the effect of bisphosphonates alone and in association with other compounds that could modulate calcium apposition/deposition, and were useful in measuring the impact of these compounds on cell growth, cystic colony formation and calcium storage. Decreased cell growth and cystic colony formation were found with EHDP, IB and OPD, and increased calcium storage with EHDP only. Calcium storage in EGPE cells appeared to be sensitive to the effect of amiloride, D3 and proline. Proline decreased calcium storage and increased colony formation. Changes in calcium storage may be associated with degenerative changes of the cysts, as shown in the in vitro colony model and linked to an adenosine triphosphate (ATP) decrease. In conclusion, bisphosphonates could be suitable tempering drugs to treat cestode infections.

  8. Use of a Sampling Area-Adjusted Adenosine Triphosphate Bioluminescence Assay Based on Digital Image Quantification to Assess the Cleanliness of Hospital Surfaces.

    Science.gov (United States)

    Ho, Yu-Huai; Wang, Lih-Shinn; Jiang, Hui-Li; Chang, Chih-Hui; Hsieh, Chia-Jung; Chang, Dan-Chi; Tu, Hsin-Yu; Chiu, Tan-Yun; Chao, Huei-Jen; Tseng, Chun-Chieh

    2016-01-01

    Contaminated surfaces play an important role in the transmission of pathogens. We sought to establish a criterion that could indicate "cleanliness" using a sampling area-adjusted adenosine triphosphate (ATP) assay. In the first phase of the study, target surfaces were selected for swab sampling before and after daily cleaning; then, an aerobic colony count (ACC) plate assay of bacteria and antibiotic-resistant bacteria was conducted. ATP swabs were also tested, and the ATP readings were reported as relative light units (RLUs). The results of the ACC and ATP assays were adjusted according to the sampling area. During the second phase of the study, a new cleaning process employing sodium dichloroisocyanurate (NaDCC) was implemented for comparison. Using the criterion of 2.5 colony-forming units (CFU)/cm², 45% of the sampled sites were successfully cleaned during phase one of the study. During phase two, the pass rates of the surface samples (64%) were significantly improved, except under stringent (5 RLU/cm²) and lax (500 RLU) ATP criteria. Using receiver-operating characteristic curve analysis, the best cut-off point for an area-adjusted ATP level was 7.34 RLU/cm², which corresponded to culture-assay levels of <2.5 CFU/cm². An area adjustment of the ATP assay improved the degree of correlation with the ACC-assay results from weak to moderate. PMID:27294944

  9. In Vitro Adenosine Triphosphate-Based Chemotherapy Response Assay as a Predictor of Clinical Response to Fluorouracil-Based Adjuvant Chemotherapy in Stage II Colorectal Cancer

    Science.gov (United States)

    Kwon, Hye Youn; Kim, Im-kyung; Kang, Jeonghyun; Sohn, Seung-Kook; Lee, Kang Young

    2016-01-01

    Purpose We evaluated the usefulness of the in vitro adenosine triphosphate-based chemotherapy response assay (ATP-CRA) for prediction of clinical response to fluorouracil-based adjuvant chemotherapy in stage II colorectal cancer. Materials and Methods Tumor specimens of 86 patients with pathologically confirmed stage II colorectal adenocarcinoma were tested for chemosensitivity to fluorouracil. Chemosensitivity was determined by cell death rate (CDR) of drug-exposed cells, calculated by comparing the intracellular ATP level with that of untreated controls. Results Among the 86 enrolled patients who underwent radical surgery followed by fluorouracil-based adjuvant chemotherapy, recurrence was found in 11 patients (12.7%). The CDR ≥ 20% group was associated with better disease-free survival than the CDR < 20% group (89.4% vs. 70.1%, p=0.027). Multivariate analysis showed that CDR < 20% and T4 stage were poor prognostic factors for disease-free survival after fluorouracil-based adjuvant chemotherapy. Conclusion In stage II colorectal cancer, the in vitro ATP-CRA may be useful in identifying patients likely to benefit from fluorouracil-based adjuvant chemotherapy. PMID:26511802

  10. Comparison of immunomagnetic separation/adenosine triphosphate rapid method to traditional culture-based method for E. coli and enterococci enumeration in wastewater.

    Science.gov (United States)

    Bushon, Rebecca N; Likirdopulos, Christina A; Brady, Amie M G

    2009-11-01

    Untreated wastewater samples from California, North Carolina, and Ohio were analyzed by the immunomagnetic separation/adenosine triphosphate (IMS/ATP) method and the traditional culture-based method for E. coli and enterococci concentrations. The IMS/ATP method concentrates target bacteria by immunomagnetic separation and then quantifies captured bacteria by measuring bioluminescence induced by release of ATP from the bacterial cells. Results from this method are available within 1h from the start of sample processing. Significant linear correlations were found between the IMS/ATP results and results from traditional culture-based methods for E. coli and enterococci enumeration for one location in California, two locations in North Carolina, and one location in Ohio (r values ranged from 0.87 to 0.97). No significant linear relation was found for a second location in California that treats a complex mixture of residential and industrial wastewater. With the exception of one location, IMS/ATP showed promise as a rapid method for the quantification of faecal-indicator organisms in wastewater.

  11. Comparison of immunomagnetic separation/adenosine triphosphate rapid method to traditional culture-based method for E. coli and enterococci enumeration in wastewater

    Science.gov (United States)

    Bushon, R.N.; Likirdopulos, C.A.; Brady, A.M.G.

    2009-01-01

    Untreated wastewater samples from California, North Carolina, and Ohio were analyzed by the immunomagnetic separation/adenosine triphosphate (IMS/ATP) method and the traditional culture-based method for E. coli and enterococci concentrations. The IMS/ATP method concentrates target bacteria by immunomagnetic separation and then quantifies captured bacteria by measuring bioluminescence induced by release of ATP from the bacterial cells. Results from this method are available within 1 h from the start of sample processing. Significant linear correlations were found between the IMS/ATP results and results from traditional culture-based methods for E. coli and enterococci enumeration for one location in California, two locations in North Carolina, and one location in Ohio (r??values ranged from 0.87 to 0.97). No significant linear relation was found for a second location in California that treats a complex mixture of residential and industrial wastewater. With the exception of one location, IMS/ATP showed promise as a rapid method for the quantification of faecal-indicator organisms in wastewater.

  12. An ultrasensitive quantum dots fluorescent polarization immunoassay based on the antibody modified Au nanoparticles amplifying for the detection of adenosine triphosphate.

    Science.gov (United States)

    He, Yanlong; Tian, Jianniao; Hu, Kun; Zhang, Juanni; Chen, Sheng; Jiang, Yixuan; Zhao, Yanchun; Zhao, Shulin

    2013-11-13

    In this work, an ultrasensitive fluorescent polarization immunoassay (FPIA) method based on the quantum dot/aptamer/antibody/gold nanoparticles ensemble has been developed for the detection of adenosine triphosphate (ATP). DNA hybridization is formed when ATP is present in the PBS solution containing the DNA-conjugated quantum dots (QDs) and antibody-AuNPs. The substantial sensitivity improvement of the antibody-AuNPs-enhanced method is mainly attributed to the slower rotation of fluorescent unit when QDs-labeled oligonucleotides hybridize with antibody modified the gold nanoparticle. As a result, the fluorescent polarization (FP) values of the system increase significantly. Under the optimal conditions, a linear response with ATP concentration is ranged from 8×10(-12) M to 2.40×10(-4) M. The detection limit reached as low as 1.8 pM. The developed work provides a sensitive and selective immunoassay protocol for ATP detection, which could be applied in more bioanalytical systems. PMID:24176506

  13. An ultrasensitive quantum dots fluorescent polarization immunoassay based on the antibody modified Au nanoparticles amplifying for the detection of adenosine triphosphate

    International Nuclear Information System (INIS)

    Graphical abstract: A new fluorescent polarization immunoassay (FPIA) method for ATP was structured. The fluorescence polarization method has ultrahigh sensitivity and good selectivity. The method could be applied for the ATP detection in bioanalysis. -- Highlights: •A new fluorescent polarization immunoassay (FPIA) method for ATP was structured. •The fluorescence polarization method has ultrahigh sensitivity and good selectivity. •The method could be applied for the ATP detection in bioanalysis. -- Abstract: In this work, an ultrasensitive fluorescent polarization immunoassay (FPIA) method based on the quantum dot/aptamer/antibody/gold nanoparticles ensemble has been developed for the detection of adenosine triphosphate (ATP). DNA hybridization is formed when ATP is present in the PBS solution containing the DNA-conjugated quantum dots (QDs) and antibody-AuNPs. The substantial sensitivity improvement of the antibody-AuNPs-enhanced method is mainly attributed to the slower rotation of fluorescent unit when QDs-labeled oligonucleotides hybridize with antibody modified the gold nanoparticle. As a result, the fluorescent polarization (FP) values of the system increase significantly. Under the optimal conditions, a linear response with ATP concentration is ranged from 8 × 10−12 M to 2.40 × 10−4 M. The detection limit reached as low as 1.8 pM. The developed work provides a sensitive and selective immunoassay protocol for ATP detection, which could be applied in more bioanalytical systems

  14. An ultrasensitive quantum dots fluorescent polarization immunoassay based on the antibody modified Au nanoparticles amplifying for the detection of adenosine triphosphate

    Energy Technology Data Exchange (ETDEWEB)

    He, Yanlong; Tian, Jianniao, E-mail: birdtjn@sina.com; Hu, Kun; Zhang, Juanni; Chen, Sheng; Jiang, Yixuan; Zhao, Yanchun, E-mail: yanchunzh@sina.com; Zhao, Shulin

    2013-11-13

    Graphical abstract: A new fluorescent polarization immunoassay (FPIA) method for ATP was structured. The fluorescence polarization method has ultrahigh sensitivity and good selectivity. The method could be applied for the ATP detection in bioanalysis. -- Highlights: •A new fluorescent polarization immunoassay (FPIA) method for ATP was structured. •The fluorescence polarization method has ultrahigh sensitivity and good selectivity. •The method could be applied for the ATP detection in bioanalysis. -- Abstract: In this work, an ultrasensitive fluorescent polarization immunoassay (FPIA) method based on the quantum dot/aptamer/antibody/gold nanoparticles ensemble has been developed for the detection of adenosine triphosphate (ATP). DNA hybridization is formed when ATP is present in the PBS solution containing the DNA-conjugated quantum dots (QDs) and antibody-AuNPs. The substantial sensitivity improvement of the antibody-AuNPs-enhanced method is mainly attributed to the slower rotation of fluorescent unit when QDs-labeled oligonucleotides hybridize with antibody modified the gold nanoparticle. As a result, the fluorescent polarization (FP) values of the system increase significantly. Under the optimal conditions, a linear response with ATP concentration is ranged from 8 × 10{sup −12} M to 2.40 × 10{sup −4} M. The detection limit reached as low as 1.8 pM. The developed work provides a sensitive and selective immunoassay protocol for ATP detection, which could be applied in more bioanalytical systems.

  15. Safety and feasibility of thallium-201 myocardial SPECT with intravenous infusion of disodium adenosine triphosphate (ATP) in the diagnosis of coronary artery disease

    International Nuclear Information System (INIS)

    ATP (adenosine triphosphate) is a potent coronary vasodilator with a rapid onset of action and a very short half-life. Myocardial perfusion scintigraphy with intravenous ATP has not yet bee sufficiently proven in the diagnosis, follow-up, and risk stratification of coronary artery disease. The purpose of this study was to evaluate the safety, feasibility and diagnostic accuracy of pharmacologic stress thallium-102 myocardial SPECT using an intravenous ATP infusion in patients with suspected coronary artery disease. Thallium-201 myocardial SPECT in 319 patients with suspected coronary artery disease were performed after the infusion of ATP (0.08 mg/min for 6 min). The adverse effects were carefully monitored. Coronary angiography was also performed within 3 weeks. Although 76.5% of he patients had some adverse effects, they were transient, mild, and well tolerated. In all patients, the ATP infusion protocol was completed and only 2 patients required aminophylline. The adverse effects were dyspnea in 63%, headache in 31%, flushing in 21%, chest pain in 14% and abdominal discomfort in 5% of the patients. The sensitivity and specificity were 80% and 90% respectively. Thallium-201 myocardial SPECT after 6 min-infusion of ATP at a rate of 0.08 mg/kg/min is safe and has a diagnostic value in detecting coronary artery disease

  16. Competitive adsorption of uranium(VI) and thorium(IV) ions from aqueous solution using triphosphate-crosslinked magnetic chitosan resins

    International Nuclear Information System (INIS)

    The triphosphate-crosslinked magnetic chitosan resins (TPP-MCR) with a diameter range of 200-350 nm were synthesized for the adsorption of U(VI) and Th(IV) ions from aqueous solutions. The adsorption experiments were conducted in both mono-component systems with pure actinide solution and bi-component systems with different U/Th mass ratios. The maximum adsorption capacities in mono-component systems determined by Langmuir model were 169.5 and 146.8 mg g-1 for U(VI) and Th(IV), respectively. In bi-component systems, U(VI) and Th(IV) adsorption capacities were reduced significantly, and the combined sorption capacities were substantially lower (almost halved) compared to those obtained by the addition of sorption capacities using mono-component solutions, indicating that U(VI) and Th(IV) compete for the same sorption sites. Adsorption-desorption experiments for five cycles illustrated the feasibility of the repeated use of TPP-MCR for the adsorption of U(VI) and Th(IV) ions. (author)

  17. Adenosine Triphosphate (ATP) Inhibits Voltage-Sensitive Potassium Currents in Isolated Hensen’s Cells and Nifedipine Protects Against Noise-Induced Hearing Loss in Guinea Pigs

    Science.gov (United States)

    Ye, Rui; Liu, Jun; Jia, Zhiying; Wang, Hongyang; Wang, YongAn; Sun, Wei; Wu, Xuan; Zhao, Zhifei; Niu, Baolong; Li, Xingqi; Dai, Guanghai; Li, Jianxiong

    2016-01-01

    Background There is increasing evidence that adenosine triphosphate (ATP), a well-known neurotransmitter and neuromodulator in the central nervous system, plays an important role as an extracellular chemical messenger in the cochlea. Material/Methods Using a whole-cell recording technique, we studied the effects of ATP on isolated Hensen’s cells, which are supporting cells in the cochlea, to determine if they are involved in the transduction of ions with hair cells. Results ATP (0.1–10 μM) reduced the potassium current (IK+) in the majority of the recorded Hensen’s cells (21 out of 25 cells). An inward current was also induced by high concentrations of ATP (100 μM to 10 mM), which was reversibly blocked by 100 μM suramin (a purinergic antagonist) and blocked by nifedipine (an L-type calcium channel blocker). After the cochleas were perfused with artificial perilymph solutions containing nifedipine and exposed to noise, the amplitude increase in the compound action potential (CAP) threshold and the reduction in cochlear microphonics was lower than when they were exposed to noise alone. Conclusions Our results suggest that ATP can block IK+ channels at a low concentration and induce an inward Ca2+ current at high concentrations, which is reversed by purinergic receptors. Nifedipine may have a partially protective effect on noise-induced hearing loss (NIHL). PMID:27292522

  18. Clinical Observation on Adenosine Triphosphate Treatment of Paroxysmal Supraventricular Tachycardia%三磷酸腺苷治疗阵发性室上心动过速的临床观察

    Institute of Scientific and Technical Information of China (English)

    王宝金

    2014-01-01

    目的:探讨三磷酸腺苷对于治疗阵发性室上心动过速的临床效果。方法将我院接受治疗的40例患有阵发性室上心动过速的患者通过肘静脉注射三磷酸腺苷药物进行治疗,观察疗效。结果通过一段时间治疗观察发现,三磷酸腺苷对患有阵发性室上心动过速有很好的治疗效果,第一次转复成功达到92.5%。第二次转复成功,达到66.7%。结论临床研究表明,三磷酸腺苷对于PSVT有较强的治疗作用。%Objective To explore the clinical efficacy of the treatment of Paroxysmal Supraventricular Tachycardi awith Adenosine Triphosphate. Method The patients were treated in our hospital on 40 patients suffering from Paroxysmal Supraventricular Tachycardia treated by intravenous Adenosine Triphosphate elbow drugs, observing the effective.Results Treatment period of observation by finding, Adenosine Triphosphate on the body with Paroxysmal Supraventricular Tachycardia have a good therapeutic effect for the first time a successful cardioversion,it has reached 92.5%.e second cardioversion success, it has reached 66.7%.Conclusion Clinical studies have shown that adenosine triphosphate for PSVT has a strong therapeutic effect.

  19. Pulsed feedback defers cellular differentiation.

    Directory of Open Access Journals (Sweden)

    Joe H Levine

    2012-01-01

    Full Text Available Environmental signals induce diverse cellular differentiation programs. In certain systems, cells defer differentiation for extended time periods after the signal appears, proliferating through multiple rounds of cell division before committing to a new fate. How can cells set a deferral time much longer than the cell cycle? Here we study Bacillus subtilis cells that respond to sudden nutrient limitation with multiple rounds of growth and division before differentiating into spores. A well-characterized genetic circuit controls the concentration and phosphorylation of the master regulator Spo0A, which rises to a critical concentration to initiate sporulation. However, it remains unclear how this circuit enables cells to defer sporulation for multiple cell cycles. Using quantitative time-lapse fluorescence microscopy of Spo0A dynamics in individual cells, we observed pulses of Spo0A phosphorylation at a characteristic cell cycle phase. Pulse amplitudes grew systematically and cell-autonomously over multiple cell cycles leading up to sporulation. This pulse growth required a key positive feedback loop involving the sporulation kinases, without which the deferral of sporulation became ultrasensitive to kinase expression. Thus, deferral is controlled by a pulsed positive feedback loop in which kinase expression is activated by pulses of Spo0A phosphorylation. This pulsed positive feedback architecture provides a more robust mechanism for setting deferral times than constitutive kinase expression. Finally, using mathematical modeling, we show how pulsing and time delays together enable "polyphasic" positive feedback, in which different parts of a feedback loop are active at different times. Polyphasic feedback can enable more accurate tuning of long deferral times. Together, these results suggest that Bacillus subtilis uses a pulsed positive feedback loop to implement a "timer" that operates over timescales much longer than a cell cycle.

  20. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to sugar-free chewing gum with pyro- and triphosphates and reduction of calculus formation (ID 1309) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    conclusions could be drawn for the scientific substantiation of a claim on the use of sugar-free chewing gum with pyro- and triphosphates and the reduction of calculus formation at sites which are most important for dental health (e.g. gingival margin or between teeth). On the basis of the data presented...... or directly from stakeholders. The food that is the subject of the health claim is sugar-free chewing gum with pyro- and triphosphates. The Panel considers that sugar-free chewing gum with pyro- and triphosphates is sufficiently characterised in relation to the claimed effect. The claimed effect is “contrasts......, the Panel concludes that a cause and effect relationship has not been established between the use of sugar-free chewing gum with pyro- and triphosphates and reduction of calculus formation at sites which are most important for dental health....

  1. From Cnn Dynamics to Cellular Wave Computers

    Science.gov (United States)

    Roska, Tamas

    2013-01-01

    Embedded in a historical overview, the development of the Cellular Wave Computing paradigm is presented, starting from the standard CNN dynamics. The theoretical aspects, the physical implementation, the innovation process, as well as the biological relevance are discussed in details. Finally, the latest developments, the physical versus virtual cellular machines, as well as some open questions are presented.

  2. Cellular encoding for interactive evolutionary robotics

    NARCIS (Netherlands)

    Gruau, F.C.; Quatramaran, K.

    1996-01-01

    This work reports experiments in interactive evolutionary robotics. The goal is to evolve an Artificial Neural Network (ANN) to control the locomotion of an 8-legged robot. The ANNs are encoded using a cellular developmental process called cellular encoding. In a previous work similar experiments ha

  3. Recent development of cellular manufacturing systems

    Indian Academy of Sciences (India)

    P K Arora; A Haleem; M K Singh

    2013-06-01

    Cellular manufacturing system has been proved a vital approach for batch and job shop production systems. Group technology has been an essential tool for developing a cellular manufacturing system. The paper aims to discuss various cell formation techniques and highlights the significant research work done in past over the years and attempts to points out the gap in research.

  4. The Universe as a Cellular System

    CERN Document Server

    Aragón-Calvo, Miguel A

    2014-01-01

    Cellular systems are observed everywhere in nature, from crystal domains in metals, soap froth and cucumber cells to the network of cosmological voids. Surprisingly, despite their disparate scale and origin all cellular systems follow certain scaling laws relating their geometry, topology and dynamics. Using a cosmological N-body simulation we found that the Cosmic Web, the largest known cellular system, follows the same scaling relations seen elsewhere in nature. Our results extend the validity of scaling relations in cellular systems by over 30 orders of magnitude in scale with respect to previous studies. The dynamics of cellular systems can be used to interpret local observations such as the local velocity anomaly as the result of a collapsing void in our cosmic backyard. Moreover, scaling relations depend on the curvature of space, providing an independent measure of geometry.

  5. A differential genome-wide transcriptome analysis: impact of cellular copper on complex biological processes like aging and development.

    Directory of Open Access Journals (Sweden)

    Jörg Servos

    Full Text Available The regulation of cellular copper homeostasis is crucial in biology. Impairments lead to severe dysfunctions and are known to affect aging and development. Previously, a loss-of-function mutation in the gene encoding the copper-sensing and copper-regulated transcription factor GRISEA of the filamentous fungus Podospora anserina was reported to lead to cellular copper depletion and a pleiotropic phenotype with hypopigmentation of the mycelium and the ascospores, affected fertility and increased lifespan by approximately 60% when compared to the wild type. This phenotype is linked to a switch from a copper-dependent standard to an alternative respiration leading to both a reduced generation of reactive oxygen species (ROS and of adenosine triphosphate (ATP. We performed a genome-wide comparative transcriptome analysis of a wild-type strain and the copper-depleted grisea mutant. We unambiguously assigned 9,700 sequences of the transcriptome in both strains to the more than 10,600 predicted and annotated open reading frames of the P. anserina genome indicating 90% coverage of the transcriptome. 4,752 of the transcripts differed significantly in abundance with 1,156 transcripts differing at least 3-fold. Selected genes were investigated by qRT-PCR analyses. Apart from this general characterization we analyzed the data with special emphasis on molecular pathways related to the grisea mutation taking advantage of the available complete genomic sequence of P. anserina. This analysis verified but also corrected conclusions from earlier data obtained by single gene analysis, identified new candidates of factors as part of the cellular copper homeostasis system including target genes of transcription factor GRISEA, and provides a rich reference source of quantitative data for further in detail investigations. Overall, the present study demonstrates the importance of systems biology approaches also in cases were mutations in single genes are analyzed to

  6. Markers of cellular senescence. Telomere shortening as a marker of cellular senescence.

    Science.gov (United States)

    Bernadotte, Alexandra; Mikhelson, Victor M; Spivak, Irina M

    2016-01-01

    The cellular senescence definition comes to the fact of cells irreversible proliferation disability. Besides the cell cycle arrest, senescent cells go through some morphological, biochemical, and functional changes which are the signs of cellular senescence. The senescent cells (including replicative senescence and stress-induced premature senescence) of all the tissues look alike. They are metabolically active and possess the set of characteristics in vitro and in vivo, which are known as biomarkers of aging and cellular senescence. Among biomarkers of cellular senescence telomere shortening is a rather elegant frequently used biomarker. Validity of telomere shortening as a marker for cellular senescence is based on theoretical and experimental data. PMID:26805432

  7. CELLULAR INTERACTIONS MEDIATED BY GLYCONECTIDS

    Directory of Open Access Journals (Sweden)

    O.Popescu

    1999-01-01

    Full Text Available Cellular interactions involve many types of cell surface molecules and operate via homophilic and/or heterophilic protein-protein and protein-carbohydrate binding. Our investigations in different model-systems (marine invertebrates and mammals have provided direct evidence that a novel class of primordial proteoglycans, named by us gliconectins, can mediate cell adhesion via a new alternative molecular mechanism of polyvalent carbohydrate-carbohydrate binding. Biochemical characterization of isolated and purified glyconectins revealed the presence of specific carbohydrate structures, acidic glycans, different from classical glycosaminoglycans. Such acidic glycans of high molecular weight containing fucose, glucuronic or galacturonic acids, and sulfate groups, originally found in sponges and sea urchin embryos, may represent a new class of carbohydrate carcino-embryonal antigens in mice and humans. Such interactions between biological macromolecules are usually investigated by kinetic binding studies, calorimetric methods, X-ray diffraction, nuclear magnetic resonance, and other spectroscopic analyses. However, these methods do not supply a direct estimation of the intermolecular binding forces that are fundamental for the function of the ligand-receptor association. Recently, we have introduced atomic force microscopy to quantify the binding strength between cell adhesion proteoglycans. Measurement of binding forces intrinsic to cell adhesion proteoglycans is necessary to assess their contribution to the maintenance of the anatomical integrity of multicellular organisms. As a model, we selected the glyconectin 1, a cell adhesion proteoglycan isolated from the marine sponge Microciona prolifera. This glyconectin mediates in vivo cell recognition and aggregation via homophilic, species-specific, polyvalent, and calcium ion-dependent carbohydrate-carbohydrate interactions. Under physiological conditions, an adhesive force of up to 400 piconewtons

  8. Macromolecular lesions and cellular radiation chemistry

    International Nuclear Information System (INIS)

    Our studies of the interaction of densely ionizing particles with macromolecules in the living cell may be divided into four parts: characterization of lesions to cellular DNA in the unmodified Bragg ionization curve; characterization of lesions to cellular DNA in the spread Bragg curve as used in radiation therapy; elucidation of the cellular radiation chemistry characteristic of high vs. low LET radiation qualities; and the introduction of novel techniques designed to give a better understanding of the fundamental properties of induction of lesions and their repair potentials in high LET radiation

  9. Cellular and molecular mechanisms in kidney fibrosis

    Science.gov (United States)

    Duffield, Jeremy S.

    2014-01-01

    Fibrosis is a characteristic feature of all forms of chronic kidney disease. Deposition of pathological matrix in the interstitial space and within the walls of glomerular capillaries as well as the cellular processes resulting in this deposition are increasingly recognized as important factors amplifying kidney injury and accelerating nephron demise. Recent insights into the cellular and molecular mechanisms of fibrogenesis herald the promise of new therapies to slow kidney disease progression. This review focuses on new findings that enhance understanding of cellular and molecular mechanisms of fibrosis, the characteristics of myofibroblasts, their progenitors, and molecular pathways regulating both fibrogenesis and its resolution. PMID:24892703

  10. Cellular chain formation in Escherichia coli biofilms

    DEFF Research Database (Denmark)

    Vejborg, Rebecca Munk; Klemm, Per

    2009-01-01

    In this study we report on a novel structural phenotype in Escherichia coli biofilms: cellular chain formation. Biofilm chaining in E. coli K-12 was found to occur primarily by clonal expansion, but was not due to filamentous growth. Rather, chain formation was the result of intercellular......; type I fimbriae expression significantly reduced cellular chain formation, presumably by steric hindrance. Cellular chain formation did not appear to be specific to E coli K-12. Although many urinary tract infection (UTI) isolates were found to form rather homogeneous, flat biofilms, three isolates...

  11. Imaging in cellular and tissue engineering

    CERN Document Server

    Yu, Hanry

    2013-01-01

    Details on specific imaging modalities for different cellular and tissue engineering applications are scattered throughout articles and chapters in the literature. Gathering this information into a single reference, Imaging in Cellular and Tissue Engineering presents both the fundamentals and state of the art in imaging methods, approaches, and applications in regenerative medicine. The book underscores the broadening scope of imaging applications in cellular and tissue engineering. It covers a wide range of optical and biological applications, including the repair or replacement of whole tiss

  12. Cellular Signaling Pathways and Their Clinical Reflections

    Directory of Open Access Journals (Sweden)

    N. Ceren Sumer-Turanligil

    2010-06-01

    Full Text Available Cellular signaling pathways have important roles in cellular growth, differentiation, inflammatory response and apoptosis and in regulation of cellular responses under various chemical stimulators. Different proteins which belong to these pathways may be exposed to loss-of-function or gain-of-function mutations; this may lead to many clinical phenotypes including primarily cancer. In this review information about basic working principles of these pathways and diseases related to them are included. [Archives Medical Review Journal 2010; 19(3.000: 180-191

  13. Cellular Cell Bifurcation of Cylindrical Detonations

    Institute of Scientific and Technical Information of China (English)

    HAN Gui-Lai; JIANG Zong-Lin; WANG Chun; ZHANG Fan

    2008-01-01

    Cellular cell pattern evolution of cylindrically-diverging detonations is numerically simulated successfully by solving two-dimensional Euler equations implemented with an improved two-step chemical kinetic model. From the simulation, three cell bifurcation modes are observed during the evolution and referred to as concave front focusing, kinked and wrinkled wave front instability, and self-merging of cellular cells. Numerical research demonstrates that the wave front expansion resulted from detonation front diverging plays a major role in the cellular cell bifurcation, which can disturb the nonlinearly self-sustained mechanism of detonations and finally lead to cell bifurcations.

  14. Inactivation efficiency of Escherichia coli and autochthonous bacteria during ozonation of municipal wastewater effluents quantified with flow cytometry and adenosine tri-phosphate analyses.

    Science.gov (United States)

    Lee, Yunho; Imminger, Stefanie; Czekalski, Nadine; von Gunten, Urs; Hammes, Frederik

    2016-09-15

    Inactivation kinetics of autochthonous bacteria during ozonation of wastewater effluents were investigated using cultivation-independent flow cytometry (FCM) with total cell count (TCC) and intact cell count (ICC) and intracellular adenosine triphosphate (ATP) analysis. The principles of the methods including ozone inactivation kinetics were demonstrated with laboratory-cultured Escherichia coli spiked into filtered and sterilized wastewater effluent. Both intracellular ATP and ICC decreased with increasing ozone doses, with ICC being the more conservative parameter. The log-inactivation levels (-log(N/N0) of E. coli reached the method detection limits for FCM (∼3) and ATP (∼1.7) at specific ozone doses of ≥0.5 gO3/gDOC. During ozonation of four real wastewater effluents, the log-inactivation of autochthonous bacteria with FCM ICC was 0.3-1.0 for 0.25 gO3/gDOC and increased to 1.1-2.1 for 0.5 gO3/gDOC, but remained at a similar level of 1.5-2.8 for a further increase of the specific ozone doses to 1.0 and 1.5 gO3/gDOC. The FCM data also showed that autochthonous bacteria were composed of communities with high and low ozone reactivity. The inactivation levels measured with intracellular ATP were reasonably correlated to ICC (r(2) = 0.8). Overall, FCM and ATP measurements were demonstrated to be useful tools to monitor the inactivation of autochthonous bacteria during ozonation of municipal wastewater effluents. PMID:27322566

  15. Estimation of intracellular concentration of stavudine triphosphate in HIV-infected children given a reduced dose of 0.5 milligrams per kilogram twice daily.

    Science.gov (United States)

    Sy, Sherwin K B; Innes, Steve; Derendorf, Hartmut; Cotton, Mark F; Rosenkranz, Bernd

    2014-01-01

    The antiviral efficacy of stavudine depends on the trough concentration of its intracellular metabolite, stavudine-triphosphate (d4T-TP), while the degree of stavudine's mitochondrial toxicity depends on its peak concentration. Rates of mitochondrial toxicity are high when stavudine is used at the current standard pediatric dose (1 mg/kg twice daily [BID]). Evidence from adult work suggests that half of the original standard adult dose (i.e., 20 mg BID) may be equally effective, with markedly less mitochondrial toxicity. We present a population pharmacokinetic model to predict intracellular d4T-TP concentrations in pediatric HIV-infected patients administered a dose of 0.5 mg/kg BID. Our model predicted that the reduced pediatric dose would result in a trough intracellular d4T-TP concentration above that of the reduced 20-mg adult dose and a peak concentration below that of the 20-mg adult dose. The simulated pediatric intracellular d4T-TP at 0.5 mg/kg BID resulted in median peak and trough values of approximately 23.9 fmol/10(6) cells (95% prediction interval [PI], 14.2 to 41 fmol/10(6) cells) and 14.8 fmol/10(6) cells (95% PI, 7.2 to 31 fmol/10(6) cells), respectively. The peak and trough concentrations resulting from a 20-mg BID adult dose were 28.4 fmol/10(6) cells (95% PI, 17.3 to 45.5 fmol/10(6) cells) and 13 fmol/10(6) cells (95% PI, 6.8 to 28.6 fmol/10(6) cells), respectively. Halving the current standard pediatric dose should therefore not compromise antiviral efficacy, while markedly reducing mitochondrial toxicity.

  16. Using an Adenosine Triphosphate Bioluminescent Assay to Determine Effective Antibiotic Combinations against Carbapenem-Resistant Gram Negative Bacteria within 24 Hours.

    Directory of Open Access Journals (Sweden)

    Yiying Cai

    Full Text Available Current in vitro combination testing methods involve enumeration by bacterial plating, which is labor-intensive and time-consuming. Measurement of bioluminescence, released when bacterial adenosine triphosphate binds to firefly luciferin-luciferase, has been proposed as a surrogate for bacterial counts. We developed an ATP bioluminescent combination testing assay with a rapid turnaround time of 24h to determine effective antibiotic combinations.100 strains of carbapenem-resistant (CR GNB [30 Acinetobacter baumannii (AB, 30 Pseudomonas aeruginosa (PA and 40 Klebsiella pneumoniae (KP] were used. Bacterial suspensions (105 CFU/ml were added to 96-well plates containing clinically achievable concentrations of multiple single and two-antibiotic combinations. At 24h, the luminescence intensity of each well was measured. Receiver operator characteristic curves were plotted to determine optimal luminescence threshold (TRLU to discriminate between inhibitory/non-inhibitory combinations when compared to viable plating. The unweighted accuracy (UA [(sensitivity + specificity/2] of TRLU values was determined. External validation was further done using 50 additional CR-GNB.Predictive accuracies of TRLU were high for when all antibiotic combinations and species were collectively analyzed (TRLU = 0.81, UA = 89%. When individual thresholds for each species were determined, UA remained high. Predictive accuracy was highest for KP (TRLU = 0.81, UA = 91%, and lowest for AB (TRLU = 0.83, UA = 87%. Upon external validation, high overall accuracy (91% was observed. The assay distinguished inhibitory/non-inhibitory combinations with UA of 80%, 94% and 93% for AB, PA and KP respectively.We developed an assay that is robust at identifying useful combinations with a rapid turn-around time of 24h, and may be employed to guide the timely selection of effective antibiotic combinations.

  17. Colonic ornithine decarboxylase in inflammatory bowel disease: ileorectal activity gradient, guanosine triphosphate stimulation, and association with epithelial regeneration but not the degree of inflammation and clinical features.

    Science.gov (United States)

    Allgayer, Hubert; Roisch, Ulla; Zehnter, Elmar; Ziegenhagen, Dieter J; Dienes, Hans P; Kruis, Wolfgang

    2007-01-01

    The role of colonic mucosal ornithine decarboxylase (ODC) in inflammatory bowel disease (IBD) remains controversial. This study assessed mucosal ODC activity in IBD patients segment by segment with regard to patient characteristics, disease activity/duration, medication, degree of mucosal inflammation, and presence/absence of epithelial regeneration and guanosine triphosphate (GTP) stimulation. Mucosal ODC activity was determined in biopsy specimens from the terminal ileum, cecum/ascending, transverse, and descending colon, and the sigmoid/rectum of 35 patients with IBD (18 with Crohn's disease, 17 with ulcerative colitis) and 29 controls, using the amount of 14CO2 liberated from (carboxyl-14C)ornithine hydrochloride. GTP-stimulatable activity was expressed as the ratio of ODC activity in the presence and absence of GTP (70 micromol/L). Mucosal inflammation was assessed endoscopically/microscopically with previously described criteria. Presence/absence of mucosal regeneration also was determined by predefined criteria. Mucosal ODC-activity did not significantly differ in IBD patients and controls. There was a 4.4-fold activity gradient from the ileum to the rectum. Mucosal ODC activity was significantly higher in areas with epithelial regeneration compared to those without regeneration, and was stimulated by GTP by a factor of 1.42 in Crohn's disease and 1.19 in ulcerative colitis patients compared to controls (p < 0.004). On the other hand, there was no significant association/relationship of mucosal ODC activity with disease activity/duration and the endoscopic/histologic degree of mucosal inflammation. The observation of unchanged mucosal ODC activity in patients with IBD and the absence of a significant relationship with clinical and endoscopic/histologic disease characteristics speaks against a major role of ODC in IBD as a major disease marker. The role of the ileorectal gradient, the enhanced activity in areas with epithelial regeneration, and the GTP

  18. Effects of repetitive transcranial magnetic stimulation on adenosine triphosphate content and microtubule associated protein-2 expression after cerebral ischemia-reperfusion injury in rat brain

    Institute of Scientific and Technical Information of China (English)

    FENG Hong-lin; YAN Li; CUI Li-ying

    2008-01-01

    Background Repetitive transcranial magnetic stimulation (rTMS) research has mainly been focused on the therapeutic effect of psychiatric disorders and Parkinson's disease. A few studies have shown that rTMS might protect against delayed neuronal death induced by transient ischemia, enhance long-term potentiation in ischemic conditions and affect regional brain blood flow and metabolism. The aim of this study was to determine the effects of repetitive transcranial magnetic stimulation (rTMS) on adenosine triphosphate (ATP) content and microtubule associated protein-2 (MAP-2) expression in rat brain after middle cerebral artery occlusion (MCAO)/reperfusion.Methods To study the effects of different timecourses of rTMS on ATP content and MAP-2 expression, 90 rats were randomly divided into three groups (30 rats in each group). To study the effects of multiple rTMS parameters on ATP content and MAP-2 expression, the rats in each group were further divided into six subgroups (five rats each). The rats were sacrificr, 24-hour and 48-hour intervals after reperfusion, and the brain tissues were collected for the detection of ATP and MAP-2.Results rTMS could significantly increase ATP content and MAP-2 expression in the left brain following ischemic insult (P<0.01) and different rTMS parameters had different effects on the ATP level and the MAP-2 expression in the left striatum. A high-frequency rTMS played an important role in MAP-2 expression and ATP preservation.Conclusions This study revealed that rTMS induced significant increase of ATP content and MAP-2 expression in the injured area of the brain, suggesting that the regulation of both ATP and MAP-2 may be involved in the biological mechanism of the effect of rTMS on neural recovery. Therefore, rTMS may become a potential adjunctive therapy for ischemic cerebrovascular disease.

  19. Do Cyclosporine A, an IL-1 Receptor Antagonist, Uridine Triphosphate, Rebamipide, and/or Bimatoprost Regulate Human Meibomian Gland Epithelial Cells?

    Science.gov (United States)

    Kam, Wendy R.; Liu, Yang; Ding, Juan; Sullivan, David A.

    2016-01-01

    Purpose Researchers have hypothesized that treatment with cyclosporine A (CyA), interleukin-1 receptor antagonists (IL-1RA; e.g., anakinra), P2Y2 receptor agonists (e.g., uridine triphosphate; UTP), and rebamipide may alleviate human meibomian gland dysfunction (MGD) and/or dry eye disease. Investigators have also proposed that prostaglandin analogues (e.g., bimatoprost) may induce MGD. Our goal was to determine whether these compounds directly influence human meibomian gland epithelial cell (HMGEC) function. Methods Multiple concentrations of each compound were tested for effects on immortalized (I) HMGEC morphology and survival. Nontoxic dosages were used for our studies. Immortalized HMGEC were cultured in the presence of vehicle, CyA, IL-1RA, UTP, rebamipide, or bimatoprost for up to 6 days in various media. Experiments included positive controls for proliferation (epidermal growth factor and bovine pituitary extract), differentiation (azithromycin), and signaling pathway activation (insulin-like growth factor 1). Cells were analyzed for neutral lipid staining, lysosome accumulation, lipid composition, and phosphatidylinositol-3-kinase/Akt (AKT), phosphorylation. Results Our findings demonstrate that CyA, IL-1RA, UTP, rebamipide, and bimatoprost had no effect on the proliferation; neutral lipid content; lysosome number; or levels of free cholesterol, triglycerides, or phospholipids in IHMGECs. Cylosporine A, IL-1RA, rebamipide, and bimatoprost significantly reduced the phosphorylation of AKT, as compared to control. Of interest, tested doses of CyA above 8 nM killed the IHMGECs. Conclusions Our results show that CyA, IL-1RA, UTP, rebamipide, and bimatoprost do not influence the proliferation or differentiation of IHMGEC. However, with the exception of UTP, these compounds do decrease the activity of the AKT signaling pathway, which is known to promote cell survival. PMID:27552406

  20. Electrochemical oxidation of adenosine-5 Prime -triphosphate on a chitosan-graphene composite modified carbon ionic liquid electrode and its determination

    Energy Technology Data Exchange (ETDEWEB)

    Sun Wei, E-mail: swyy26@hotmail.com [College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou, 571158 (China); College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042 (China); Liu Jun; Wang Xiuzhen; Li Tongtong; Li Guangjiu; Wu Jie [College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042 (China); Zhang Liqi [State Key Laboratory of Coal Combustion, Huazhong University of Science and Technology, Wuhan 430074 (China)

    2012-10-01

    In this paper a new electrochemical method was proposed for the determination of adenosine-5 Prime -triphosphate (ATP) based on a chitosan (CTS) and graphene (GR) composite film modified carbon ionic liquid electrode (CTS-GR/CILE). CILE was fabricated by using ionic liquid 1-butyl-3-methylimidazolium dihydrogen phosphate ([BMIM]H{sub 2}PO{sub 4}) as the binder, which was further modified by GR and CTS composite. The modified electrode exhibited an excellent electrocatalytic activity toward the oxidation of ATP with the increase of the oxidation peak current and the decrease of the oxidation peak potential. The electrochemical parameters of ATP on CTS-GR/CILE were calculated with the electron transfer coefficient ({alpha}) as 0.329, the electron transfer number (n) as 2.15, the apparent heterogeneous electron transfer rate constant (ks) as 3.705 Multiplication-Sign 10{sup -5} s{sup -1} and the surface coverage ({Gamma}{sub T}) as 9.33 Multiplication-Sign 10{sup -10} mol cm{sup -2}. Under the optimal conditions the oxidation peak current was proportional to ATP concentration in the range from 1.0 Multiplication-Sign 10{sup -6} to 1.0 Multiplication-Sign 10{sup -3} M with the detection limit of 0.311 {mu}M (S/N = 3). The proposed electrode showed excellent reproducibility, stability, anti-interference ability and further successfully applied to the ATP injection sample detection. - Highlights: Black-Right-Pointing-Pointer Ionic liquid [BMIM]H{sub 2}PO{sub 4} based carbon ionic liquid electrode (CILE) was prepared. Black-Right-Pointing-Pointer Graphene modified CILE was fabricated for the sensitive electrochemical detection of ATP. Black-Right-Pointing-Pointer Good electrocatalytic ability to the ATP oxidation was achieved. Black-Right-Pointing-Pointer Detection of 5 Prime -ATP in commercial injection samples with satisfactory results.

  1. Densities and entropies in cellular automata

    CERN Document Server

    Guillon, Pierre

    2012-01-01

    Following work by Hochman and Meyerovitch on multidimensional SFT, we give computability-theoretic characterizations of the real numbers that can appear as the topological entropies of one-dimensional and two-dimensional cellular automata.

  2. A Matrix Construction of Cellular Algebras

    Institute of Scientific and Technical Information of China (English)

    Dajing Xiang

    2005-01-01

    In this paper, we give a concrete method to construct cellular algebras from matrix algebras by specifying certain fixed matrices for the data of inflations. In particular,orthogonal matrices can be chosen for such data.

  3. The role of sirtuins in cellular homeostasis.

    Science.gov (United States)

    Kupis, Wioleta; Pałyga, Jan; Tomal, Ewa; Niewiadomska, Ewa

    2016-09-01

    Sirtuins are evolutionarily conserved nicotinamide adenine dinucleotide (NAD(+))-dependent lysine deacylases or ADP-ribosyltransferases. These cellular enzymes are metabolic sensors sensitive to NAD(+) levels that maintain physiological homeostasis in the animal and plant cells. PMID:27154583

  4. Optimized Cellular Core for Rotorcraft Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Patz Materials and Technologies has developed, produced and tested, as part of the Phase-I SBIR, a new form of composite cellular core material, named Interply...

  5. Cellular Defect May Be Linked to Parkinson's

    Science.gov (United States)

    ... 160862.html Cellular Defect May Be Linked to Parkinson's: Study Abnormality might apply to all forms of ... that may be common to all forms of Parkinson's disease. The defect plays a major role in ...

  6. MILLIMETER-WAVE EMISSIVITY OF CELLULAR SYSTEMS

    Science.gov (United States)

    A general analysis has been presented of the millimeter-wave and farinfrared spectroscopic properties of in vivo cellular systems, and of the boson radiative equilibrium with steady-state nonequilibrium molecular systems. The frequency threshhold of spectroscopic properties assoc...

  7. Cellular Restriction Factors of Feline Immunodeficiency Virus

    OpenAIRE

    Carsten Münk; Jörg Zielonka

    2011-01-01

    Lentiviruses are known for their narrow cell- and species-tropisms, which are determined by cellular proteins whose absence or presence either support viral replication (dependency factors, cofactors) or inhibit viral replication (restriction factors). Similar to Human immunodeficiency virus type 1 (HIV-1), the cat lentivirus Feline immunodeficiency virus (FIV) is sensitive to recently discovered cellular restriction factors from non-host species that are able to stop viruses from replicating...

  8. Cellular and molecular mechanisms in kidney fibrosis

    OpenAIRE

    Duffield, Jeremy S.

    2014-01-01

    Fibrosis is a characteristic feature of all forms of chronic kidney disease. Deposition of pathological matrix in the interstitial space and within the walls of glomerular capillaries as well as the cellular processes resulting in this deposition are increasingly recognized as important factors amplifying kidney injury and accelerating nephron demise. Recent insights into the cellular and molecular mechanisms of fibrogenesis herald the promise of new therapies to slow kidney disease progressi...

  9. Apoptotic regulation of epithelial cellular extrusion

    OpenAIRE

    De Andrade, Daniel,; Rosenblatt, Jody

    2011-01-01

    Cellular extrusion is a mechanism that removes dying cells from epithelial tissues to prevent compromising their barrier function. Extrusion occurs in all observed epithelia in vivo and can be modeled in vitro by inducing apoptosis in cultured epithelial monolayers. We established that actin and myosin form a ring that contracts in the surrounding cells that drives cellular extrusion. It is not clear, however, if all apoptotic pathways lead to extrusion and how apoptosis and extrusion are mol...

  10. Cellularity of certain quantum endomorphism algebras

    DEFF Research Database (Denmark)

    Andersen, Henning Haahr; Lehrer, Gus; Zhang, Ruibin

    2015-01-01

    For any ring A˜ such that Z[q±1∕2]⊆A˜⊆Q(q1∕2), let ΔA˜(d) be an A˜-form of the Weyl module of highest weight d∈N of the quantised enveloping algebra UA˜ of sl2. For suitable A˜, we exhibit for all positive integers r an explicit cellular structure for EndUA˜(ΔA˜(d)⊗r). This algebra and its cellular...

  11. Cellular Hyperproliferation and Cancer as Evolutionary Variables

    OpenAIRE

    Alvarado, Alejandro Sánchez

    2012-01-01

    Technological advances in biology have begun to dramatically change the way we think about evolution, development, health and disease. The ability to sequence the genomes of many individuals within a population, and across multiple species, has opened the door to the possibility of answering some long-standing and perplexing questions about our own genetic heritage. One such question revolves around the nature of cellular hyperproliferation. This cellular behavior is used to effect wound heal...

  12. Building mathematics cellular phone learning communities

    OpenAIRE

    Wajeeh M. Daher

    2011-01-01

    Researchers emphasize the importance of maintaining learning communities and environments. This article describes the building and nourishment of a learning community, one comprised of middle school students who learned mathematics out-of-class using the cellular phone. The building of the learning community was led by three third year pre-service teachers majoring in mathematics and computers. The pre-service teachers selected thirty 8th grade students to learn mathematics with the cellular ...

  13. Understanding cisplatin resistance using cellular models.

    OpenAIRE

    STORDAL, BRITTA KRISTINA

    2007-01-01

    PUBLISHED Many mechanisms of cisplatin resistance have been proposed from studies of cellular models of resistance including changes in cellular drug accumulation, detoxification of the drug, inhibition of apoptosis and repair of the DNA adducts. A series of resistant models were developed from CCRF-CEM leukaemia cells with increasing doses of cisplatin from 100 ng/ml. This produced increasing resistance up to 7-fold with a treatment dose of 1.6 ?g/ml. Cisplatin resistance i...

  14. Understanding cisplatin resistance using cellular models

    OpenAIRE

    Stordal, Britta; Davey, Mary

    2007-01-01

    Many mechanisms of cisplatin resistance have been proposed from studies of cellular models of resistance including changes in cellular drug accumulation, detoxification of the drug, inhibition of apoptosis and repair of the DNA adducts. A series of resistant models were developed from CCRF-CEM leukaemia cells with increasing doses of cisplatin from 100 ng/ml. This produced increasing resistance up to 7-fold with a treatment dose of 1.6 microg/ml. Cisplatin resistance in these cells correlated...

  15. On the Behavior Characteristics of Cellular Automata

    Institute of Scientific and Technical Information of China (English)

    CHEN Jin-cai; ZHANG Jiang-ling; FENG Dan

    2005-01-01

    In this paper, the inherent relationships between the running regulations and behavior characteristics of cellular automata are presented; an imprecise taxonomy of such systems is put forward; the three extreme cases of stable systems are discussed; and the illogicalness of evolutional strategies of cellular automata is analyzed. The result is suitable for the emulation and prediction of behavior of discrete dynamics systems; especially it can be taken as an important analysis means of dynamic performance of complex networks.

  16. Cellular Scaling Rules of Insectivore Brains

    OpenAIRE

    Sarko, Diana K.; Catania, Kenneth C.; Leitch, Duncan B.; Kaas, Jon H.; Herculano-Houzel, Suzana

    2009-01-01

    Insectivores represent extremes in mammalian body size and brain size, retaining various “primitive” morphological characteristics, and some species of Insectivora are thought to share similarities with small-bodied ancestral eutherians. This raises the possibility that insectivore brains differ from other taxa, including rodents and primates, in cellular scaling properties. Here we examine the cellular scaling rules for insectivore brains and demonstrate that insectivore scaling rules overla...

  17. Cellular scaling rules of insectivore brains

    OpenAIRE

    Sarko, Diana K.; Catania, Kenneth C.; Leitch, Duncan B.; Kaas, Jon H.; Suzana Herculano-Houzel

    2009-01-01

    Insectivores represent extremes in mammalian body size and brain size, retaining various “primitive” morphological characteristics, and some species of Insectivora are thought to share similarities with small-bodied ancestral eutherians. This raises the possibility that insectivore brains differ from other taxa, including rodents and primates, in cellular scaling properties. Here we examine the cellular scaling rules for insectivore brains and demonstrate that insectivore scaling ...

  18. Cellular scaling rules for primate brains

    OpenAIRE

    Herculano-Houzel, Suzana; Collins, Christine E.; Wong, Peiyan; Kaas, Jon H.

    2007-01-01

    Primates are usually found to have richer behavioral repertoires and better cognitive abilities than rodents of similar brain size. This finding raises the possibility that primate brains differ from rodent brains in their cellular composition. Here we examine the cellular scaling rules for primate brains and show that brain size increases approximately isometrically as a function of cell numbers, such that an 11× larger brain is built with 10× more neurons and ≈12× more nonneuronal cells of ...

  19. Polymersomes containing quantum dots for cellular imaging

    Directory of Open Access Journals (Sweden)

    Camblin M

    2014-05-01

    Full Text Available Marine Camblin,1 Pascal Detampel,1 Helene Kettiger,1 Dalin Wu,2 Vimalkumar Balasubramanian,1,* Jörg Huwyler1,*1Division of Pharmaceutical Technology, 2Department of Chemistry, University of Basel, Basel, Switzerland*These authors contributed equally to this workAbstract: Quantum dots (QDs are highly fluorescent and stable probes for cellular and molecular imaging. However, poor intracellular delivery, stability, and toxicity of QDs in biological compartments hamper their use in cellular imaging. To overcome these limitations, we developed a simple and effective method to load QDs into polymersomes (Ps made of poly(dimethylsiloxane-poly(2-methyloxazoline (PDMS-PMOXA diblock copolymers without compromising the characteristics of the QDs. These Ps showed no cellular toxicity and QDs were successfully incorporated into the aqueous compartment of the Ps as confirmed by transmission electron microscopy, fluorescence spectroscopy, and fluorescence correlation spectroscopy. Ps containing QDs showed colloidal stability over a period of 6 weeks if stored in phosphate-buffered saline (PBS at physiological pH (7.4. Efficient intracellular delivery of Ps containing QDs was achieved in human liver carcinoma cells (HepG2 and was visualized by confocal laser scanning microscopy (CLSM. Ps containing QDs showed a time- and concentration-dependent uptake in HepG2 cells and exhibited better intracellular stability than liposomes. Our results suggest that Ps containing QDs can be used as nanoprobes for cellular imaging.Keywords: quantum dots, polymersomes, cellular imaging, cellular uptake

  20. Optimization of Inter Cellular Movement of Parts in Cellular Manufacturing System Using Genetic Algorithm

    OpenAIRE

    Siva Prasad Darla; C.D. Naiju; Polu Vidya Sagar; B. Venkat Likhit

    2014-01-01

    In the modern manufacturing environment, Cellular Manufacturing Systems (CMS) have gained greater importance in job shop or batch-type production to gain economic advantage similar to those of mass production. Successful implementation of CMS highly depends on the determination of part families; machine cells and minimizing inter cellular movement. This study considers machine component grouping problems namely inter-cellular movement and cell load variation by developing a mathematical model...

  1. Optimization of Inter Cellular Movement of Parts in Cellular Manufacturing System Using Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Siva Prasad Darla

    2014-01-01

    Full Text Available In the modern manufacturing environment, Cellular Manufacturing Systems (CMS have gained greater importance in job shop or batch-type production to gain economic advantage similar to those of mass production. Successful implementation of CMS highly depends on the determination of part families; machine cells and minimizing inter cellular movement. This study considers machine component grouping problems namely inter-cellular movement and cell load variation by developing a mathematical model and optimizing the solution using Genetic Algorithm to arrive at a cell formation to minimize the inter-cellular movement and cell load variation. The results are presented with a numerical example.

  2. The biochemical properties of the Arabidopsis ecto-nucleoside triphosphate diphosphohydrolase AtAPY1 contradict a direct role in purinergic signaling.

    Directory of Open Access Journals (Sweden)

    Carolin Massalski

    Full Text Available The Arabidopsis E-NTPDase (ecto-nucleoside triphosphate diphosphohydrolase AtAPY1 was previously shown to be involved in growth and development, pollen germination and stress responses. It was proposed to perform these functions through regulation of extracellular ATP signals. However, a GFP-tagged version was localized exclusively in the Golgi and did not hydrolyze ATP. In this study, AtAPY1 without the bulky GFP-tag was biochemically characterized with regard to its suggested role in purinergic signaling. Both the full-length protein and a soluble form without the transmembrane domain near the N-terminus were produced in HEK293 cells. Of the twelve nucleotide substrates tested, only three--GDP, IDP and UDP--were hydrolyzed, confirming that ATP was not a substrate of AtAPY1. In addition, the effects of pH, divalent metal ions, known E-NTPDase inhibitors and calmodulin on AtAPY1 activity were analyzed. AtAPY1-GFP extracted from transgenic Arabidopsis seedlings was included in the analyses. All three AtAPY1 versions exhibited very similar biochemical properties. Activity was detectable in a broad pH range, and Ca(2+, Mg(2+ and Mn(2+ were the three most efficient cofactors. Of the inhibitors tested, vanadate was the most potent one. Surprisingly, sulfonamide-based inhibitors shown to inhibit other E-NTPDases and presumed to inhibit AtAPY1 as well were not effective. Calmodulin stimulated the activity of the GFP-tagless membranous and soluble AtAPY1 forms about five-fold, but did not alter their substrate specificities. The apparent Km values obtained with AtAPY1-GFP indicate that AtAPY1 is primarily a GDPase. A putative three-dimensional structural model of the ecto-domain is presented, explaining the potent inhibitory potential of vanadate and predicting the binding mode of GDP. The found substrate specificity classifies AtAPY1 as a nucleoside diphosphatase typical of N-terminally anchored Golgi E-NTPDases and negates a direct function in

  3. Adenosine 5′-triphosphate (ATP supplements are not orally bioavailable: a randomized, placebo-controlled cross-over trial in healthy humans

    Directory of Open Access Journals (Sweden)

    Arts Ilja CW

    2012-04-01

    Full Text Available Abstract Background Nutritional supplements designed to increase adenosine 5′-triphosphate (ATP concentrations are commonly used by athletes as ergogenic aids. ATP is the primary source of energy for the cells, and supplementation may enhance the ability to maintain high ATP turnover during high-intensity exercise. Oral ATP supplements have beneficial effects in some but not all studies examining physical performance. One of the remaining questions is whether orally administered ATP is bioavailable. We investigated whether acute supplementation with oral ATP administered as enteric-coated pellets led to increased concentrations of ATP or its metabolites in the circulation. Methods Eight healthy volunteers participated in a cross-over study. Participants were given in random order single doses of 5000 mg ATP or placebo. To prevent degradation of ATP in the acidic environment of the stomach, the supplement was administered via two types of pH-sensitive, enteric-coated pellets (targeted at release in the proximal or distal small intestine, or via a naso-duodenal tube. Blood ATP and metabolite concentrations were monitored by HPLC for 4.5 h (naso-duodenal tube or 7 h (pellets post-administration. Areas under the concentration vs. time curve were calculated and compared by paired-samples t-tests. Results ATP concentrations in blood did not increase after ATP supplementation via enteric-coated pellets or naso-duodenal tube. In contrast, concentrations of the final catabolic product of ATP, uric acid, were significantly increased compared to placebo by ~50% after administration via proximal-release pellets (P = 0.003 and naso-duodenal tube (P = 0.001, but not after administration via distal-release pellets. Conclusions A single dose of orally administered ATP is not bioavailable, and this may explain why several studies did not find ergogenic effects of oral ATP supplementation. On the other hand, increases in uric acid after release of

  4. Quantitative circumferential strain analysis using adenosine triphosphate-stress/rest 3-T tagged magnetic resonance to evaluate regional contractile dysfunction in ischemic heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Masashi, E-mail: m.nakamura1230@gmail.com [Department of Radiology, Ehime University Graduate School of Medicine, Shitsukawa, Toon-city, Ehime 791-0295 (Japan); Kido, Tomoyuki [Department of Radiology, Saiseikai Matsuyama Hospital, Ehime 791-0295 (Japan); Kido, Teruhito; Tanabe, Yuki; Matsuda, Takuya; Nishiyama, Yoshiko; Miyagawa, Masao; Mochizuki, Teruhito [Department of Radiology, Ehime University Graduate School of Medicine, Shitsukawa, Toon-city, Ehime 791-0295 (Japan)

    2015-08-15

    Highlights: • Infarcted segments could be differentiated from non-ischemic and ischemic segments with high sensitivity and specificity under at rest conditions. • The time-to-peak circumferential strain values in infarcted segments were more significantly delayed than those in non-ischemic and ischemic segments. • Both circumferential strain and circumferential systolic strain rate values under ATP-stress conditions were significantly lower in ischemic segments than in non-ischemic segments. • Subtracting stress and rest circumferential strain had a higher diagnostic capability for ischemia relative to only utilizing rest or ATP-stress circumferential strain values. • A circumferential strain analysis using tagged MR can quantitatively assess contractile dysfunction in ischemic and infarcted myocardium. - Abstract: Purpose: We evaluated whether a quantitative circumferential strain (CS) analysis using adenosine triphosphate (ATP)-stress/rest 3-T tagged magnetic resonance (MR) imaging can depict myocardial ischemia as contractile dysfunction during stress in patients with suspected coronary artery disease (CAD). We evaluated whether it can differentiate between non-ischemia, myocardial ischemia, and infarction. We assessed its diagnostic performance in comparison with ATP-stress myocardial perfusion MR and late gadolinium enhancement (LGE)-MR imaging. Methods: In 38 patients suspected of having CAD, myocardial segments were categorized as non-ischemic (n = 485), ischemic (n = 74), or infarcted (n = 49) from the results of perfusion MR and LGE-MR. The peak negative CS value, peak circumferential systolic strain rate (CSR), and time-to-peak CS were measured in 16 segments. Results: A cutoff value of −12.0% for CS at rest allowed differentiation between infarcted and other segments with a sensitivity of 79%, specificity of 76%, accuracy of 76%, and an area under the curve (AUC) of 0.81. Additionally, a cutoff value of 477.3 ms for time-to-peak CS at rest

  5. Shape Memory Alloy-Based Periodic Cellular Structures Project

    Data.gov (United States)

    National Aeronautics and Space Administration — This SBIR Phase I effort will develop and demonstrate an innovative shape memory alloy (SMA) periodic cellular structural technology. Periodic cellular structures...

  6. Characterizing heterogeneous cellular responses to perturbations.

    Science.gov (United States)

    Slack, Michael D; Martinez, Elisabeth D; Wu, Lani F; Altschuler, Steven J

    2008-12-01

    Cellular populations have been widely observed to respond heterogeneously to perturbation. However, interpreting the observed heterogeneity is an extremely challenging problem because of the complexity of possible cellular phenotypes, the large dimension of potential perturbations, and the lack of methods for separating meaningful biological information from noise. Here, we develop an image-based approach to characterize cellular phenotypes based on patterns of signaling marker colocalization. Heterogeneous cellular populations are characterized as mixtures of phenotypically distinct subpopulations, and responses to perturbations are summarized succinctly as probabilistic redistributions of these mixtures. We apply our method to characterize the heterogeneous responses of cancer cells to a panel of drugs. We find that cells treated with drugs of (dis-)similar mechanism exhibit (dis-)similar patterns of heterogeneity. Despite the observed phenotypic diversity of cells observed within our data, low-complexity models of heterogeneity were sufficient to distinguish most classes of drug mechanism. Our approach offers a computational framework for assessing the complexity of cellular heterogeneity, investigating the degree to which perturbations induce redistributions of a limited, but nontrivial, repertoire of underlying states and revealing functional significance contained within distinct patterns of heterogeneous responses.

  7. Cellular Signaling in Health and Disease

    CERN Document Server

    Beckerman, Martin

    2009-01-01

    In today’s world, three great classes of non-infectious diseases – the metabolic syndromes (such as type 2 diabetes and atherosclerosis), the cancers, and the neurodegenerative disorders – have risen to the fore. These diseases, all associated with increasing age of an individual, have proven to be remarkably complex and difficult to treat. This is because, in large measure, when the cellular signaling pathways responsible for maintaining homeostasis and health of the body become dysregulated, they generate equally stable disease states. As a result the body may respond positively to a drug, but only for a while and then revert back to the disease state. Cellular Signaling in Health and Disease summarizes our current understanding of these regulatory networks in the healthy and diseased states, showing which molecular components might be prime targets for drug interventions. This is accomplished by presenting models that explain in mechanistic, molecular detail how a particular part of the cellular sign...

  8. Parametric study of double cellular detonation structure

    Science.gov (United States)

    Khasainov, B.; Virot, F.; Presles, H.-N.; Desbordes, D.

    2013-05-01

    A parametric numerical study is performed of a detonation cellular structure in a model gaseous explosive mixture whose decomposition occurs in two successive exothermic reaction steps with markedly different characteristic times. Kinetic and energetic parameters of both reactions are varied in a wide range in the case of one-dimensional steady and two-dimensional (2D) quasi-steady self-supported detonations. The range of governing parameters of both exothermic steps is defined where a "marked" double cellular structure exists. It is shown that the two-level cellular structure is completely governed by the kinetic parameters and the local overdrive ratio of the detonation front propagating inside large cells. Furthermore, since it is quite cumbersome to use detailed chemical kinetics in unsteady 2D case, the proposed work should help to identify the mixtures and the domain of their equivalence ratio where double detonation structure could be observed.

  9. Infrared image enhancement using Cellular Automata

    Science.gov (United States)

    Qi, Wei; Han, Jing; Zhang, Yi; Bai, Lian-fa

    2016-05-01

    Image enhancement is a crucial technique for infrared images. The clear image details are important for improving the quality of infrared images in computer vision. In this paper, we propose a new enhancement method based on two priors via Cellular Automata. First, we directly learn the gradient distribution prior from the images via Cellular Automata. Second, considering the importance of image details, we propose a new gradient distribution error to encode the structure information via Cellular Automata. Finally, an iterative method is applied to remap the original image based on two priors, further improving the quality of enhanced image. Our method is simple in implementation, easy to understand, extensible to accommodate other vision tasks, and produces more accurate results. Experiments show that the proposed method performs better than other methods using qualitative and quantitative measures.

  10. Spin Echo Studies on Cellular Water

    CERN Document Server

    Chang, D C; Nichols, B L; Rorschach, H E

    2014-01-01

    Previous studies indicated that the physical state of cellular water could be significantly different from pure liquid water. To experimentally investigate this possibility, we conducted a series of spin-echo NMR measurements on water protons in rat skeletal muscle. Our result indicated that the spin-lattice relaxation time and the spin-spin relaxation time of cellular water protons are both significantly shorter than that of pure water (by 4.3-fold and 34-fold, respectively). Furthermore, the spin diffusion coefficient of water proton is almost 1/2 of that of pure water. These data suggest that cellular water is in a more ordered state in comparison to pure water.

  11. Online isolation of defects in cellular nanocomputers

    Institute of Scientific and Technical Information of China (English)

    Teijiro Isokawa; Shin'ya Kowada; Ferdinand Peper; Naotake Kamiura; Nobuyuki Matsui

    2007-01-01

    Unreliability will be a major issue for computers built from components at nanometer scales.Thus,it's to be expected that such computers will need a high degree of defect-tolerance to overcome components' defects which have arisen during the process of manufacturing.This paper presents a novel approach to defect-tolerance that is especially geared towards nanocomputers based on asynchronous cellular automata.According to this approach,defective cells are detected and isolated by small configurations that move around randomly in cellular space.These configurations,called random flies,will attach to configurations that are static,which is typical for configurations that contain defective cells.On the other hand,dynamic configurations,like those that conduct computations,will not be isolated from the rest of the cellular space by the random flies,and will be able to continue their operations unaffectedly.

  12. Software-Defined Cellular Mobile Network Solutions

    Institute of Scientific and Technical Information of China (English)

    Jiandong Li; Peng Liu; Hongyan Li

    2014-01-01

    The emergency relating to software-defined networking (SDN), especially in terms of the prototype associated with OpenFlow, pro-vides new possibilities for innovating on network design. Researchers have started to extend SDN to cellular networks. Such new programmable architecture is beneficial to the evolution of mobile networks and allows operators to provide better services. The typical cellular network comprises radio access network (RAN) and core network (CN); hence, the technique roadmap diverges in two ways. In this paper, we investigate SoftRAN, the latest SDN solution for RAN, and SoftCell and MobileFlow, the latest solu-tions for CN. We also define a series of control functions for CROWD. Unlike in the other literature, we emphasize only software-defined cellular network solutions and specifications in order to provide possible research directions.

  13. Asymptotic Behavior of Excitable Cellular Automata

    CERN Document Server

    Durrett, R; Durrett, Richard; Griffeath, David

    1993-01-01

    Abstract: We study two families of excitable cellular automata known as the Greenberg-Hastings Model (GHM) and the Cyclic Cellular Automaton (CCA). Each family consists of local deterministic oscillating lattice dynamics, with parallel discrete-time updating, parametrized by the range of interaction, the "shape" of its neighbor set, threshold value for contact updating, and number of possible states per site. GHM and CCA are mathematically tractable prototypes for the spatially distributed periodic wave activity of so-called excitable media observed in diverse disciplines of experimental science. Earlier work by Fisch, Gravner, and Griffeath studied the ergodic behavior of these excitable cellular automata on Z^2, and identified two distinct (but closely-related) elaborate phase portraits as the parameters vary. In particular, they noted the emergence of asymptotic phase diagrams (and Euclidean dynamics) in a well-defined threshold-range scaling limit. In this study we present several rigorous results and som...

  14. Alleviate Cellular Congestion Through Opportunistic Trough Filling

    Directory of Open Access Journals (Sweden)

    Yichuan Wang

    2014-04-01

    Full Text Available The demand for cellular data service has been skyrocketing since the debut of data-intensive smart phones and touchpads. However, not all data are created equal. Many popular applications on mobile devices, such as email synchronization and social network updates, are delay tolerant. In addition, cellular load varies significantly in both large and small time scales. To alleviate network congestion and improve network performance, we present a set of opportunistic trough filling schemes that leverage the time-variation of network congestion and delay-tolerance of certain traffic in this paper. We consider average delay, deadline, and clearance time as the performance metrics. Simulation results show promising performance improvement over the standard schemes. The work shed lights on addressing the pressing issue of cellular overload.

  15. Cellular automatons applied to gas dynamic problems

    Science.gov (United States)

    Long, Lyle N.; Coopersmith, Robert M.; Mclachlan, B. G.

    1987-01-01

    This paper compares the results of a relatively new computational fluid dynamics method, cellular automatons, with experimental data and analytical results. This technique has been shown to qualitatively predict fluidlike behavior; however, there have been few published comparisons with experiment or other theories. Comparisons are made for a one-dimensional supersonic piston problem, Stokes first problem, and the flow past a normal flat plate. These comparisons are used to assess the ability of the method to accurately model fluid dynamic behavior and to point out its limitations. Reasonable results were obtained for all three test cases, but the fundamental limitations of cellular automatons are numerous. It may be misleading, at this time, to say that cellular automatons are a computationally efficient technique. Other methods, based on continuum or kinetic theory, would also be very efficient if as little of the physics were included.

  16. 运动与ATP-敏感型钾离子通道%Exercise and adenosine triphosphate-sensitive potassium channel

    Institute of Scientific and Technical Information of China (English)

    张如江; 宋永晶

    2014-01-01

    背景:在运动生理状态下,KATP 在调节冠状动脉张力、运动诱导心肌保护效应和延缓骨骼肌疲劳等多个方面具有重要作用。目的:对KATP在运动中的作用进行了综述和探讨,以期为深入了解运动调节机体代谢提供理论参考。方法:检索1991年1月至2014年6月 PubMed数据库及维普中文科技数据库文献。英文检索词为“KATP Channels;Adenosine Triphosphate;Sports;Myocardium;Ion Channels”,中文检索词为“KATP通道;三磷酸腺苷;运动;心肌;离子通道”。选择与KATP分子结构、生物学功能及调控相关,以及KATP与冠状动脉、心肌、骨骼肌疲劳及运动能力相关的文献42篇文献进行探讨。结果与结论:ATP敏感性钾离子通道可以偶联细胞内能量代谢和细胞膜兴奋性,在应对各种生理和病理应激时是保护心肌的效应器之一。长期的耐力训练则会增加骨骼肌和心肌KATP的表达,可能是心肌和骨骼肌对运动应激产生的一种适应性表现。KATP 可能参与冠状动脉血流量的调节。在运动诱导的减轻心肌缺血再灌注损伤的保护效应中,心肌KATP具有重要作用。当骨骼肌疲劳发生时,KATP的激活有利于防止ATP的过度消耗而造成肌纤维损伤和细胞死亡,有利于疲劳的快速恢复。关于KATP与运动能力的关系仍需进一步的研究。%BACKGROUND:In the condition of exercise physiology, adenosine triphosphate-sensitive potassium (KATP) channel plays an important role in many aspects, such as regulation of coronary artery tension, exercise-induced myocardial protection effect and delay of skeletal muscle fatigue. OBJECTIVE:To review and investigate the role of KATP in exercise in order to provide theoretical reference for understanding mechanism underlying exercise regulation of body’s metabolism. METHODS: A computer-based online search of PubMed and VIP databases was performed for articles

  17. Toxicology and cellular effect of manufactured nanomaterials

    Science.gov (United States)

    Chen, Fanqing

    2014-07-22

    The increasing use of nanotechnology in consumer products and medical applications underlies the importance of understanding its potential toxic effects to people and the environment. Herein are described methods and assays to predict and evaluate the cellular effects of nanomaterial exposure. Exposing cells to nanomaterials at cytotoxic doses induces cell cycle arrest and increases apoptosis/necrosis, activates genes involved in cellular transport, metabolism, cell cycle regulation, and stress response. Certain nanomaterials induce genes indicative of a strong immune and inflammatory response within skin fibroblasts. Furthermore, the described multiwall carbon nanoonions (MWCNOs) can be used as a therapeutic in the treatment of cancer due to its cytotoxicity.

  18. The cellular decision between apoptosis and autophagy

    Institute of Scientific and Technical Information of China (English)

    Yong-Jun Fan; Wei-Xing Zong

    2013-01-01

    Apoptosis and autophagy are important molecular processes that maintain organismal and cellular homeostasis,respectively.While apoptosis fulfills its role through dismantling damaged or unwanted cells,autophagy maintains cellular homeostasis through recycling selective intracellular organelles and molecules.Yet in some conditions,autophagy can lead to cell death.Apoptosis and autophagy can be stimulated by the same stresses.Emerging evidence indicates an interplay between the core proteins in both pathways,which underlies the molecular mechanism of the crosstalk between apoptosis and autophagy.This review summarizes recent literature on molecules that regulate both the apoptotic and autophagic processes.

  19. Rapid Cellular Turnover in Adipose Tissue

    OpenAIRE

    Alessandra Rigamonti; Kristen Brennand; Frank Lau; Cowan, Chad A.

    2011-01-01

    It was recently shown that cellular turnover occurs within the human adipocyte population. Through three independent experimental approaches — dilution of an inducible histone 2B-green fluorescent protein (H2BGFP), labeling with the cell cycle marker Ki67 and incorporation of BrdU — we characterized the degree of cellular turnover in murine adipose tissue. We observed rapid turnover of the adipocyte population, finding that 4.8% of preadipocytes are replicating at any time and that between 1–...

  20. Chaotic behavior in the disorder cellular automata

    International Nuclear Information System (INIS)

    Disordered cellular automata (DCA) represent an intermediate class between elementary cellular automata and the Kauffman network. Recently, Rule 126 of DCA has been explicated: the system can be accurately described by a discrete probability function. However, a means of extending to other rules has not been developed. In this investigation, a density map of the dynamical behavior of DCA is formulated based on Rule 22 and other totalistic rules. The numerical results reveal excellent agreement between the model and original automata. Furthermore, the inhomogeneous situation is also discussed

  1. PHYSIOLOGY AND ENDOCRINOLOGY SYMPOSIUM: Cellular and molecular mechanisms of heat stress related to bovine ovarian function.

    Science.gov (United States)

    Roth, Z

    2015-05-01

    In light of the intensive genetic selection for high milk production and the onset of global warming, it seems that the reduced fertility of lactating cows during the summer will worsen in coming years. Although not entirely clear, the mechanism appears to be multifactorial in nature. It includes alterations in follicular development, depression of follicular dominance, and impairment of steroidogenesis and gonadotropin secretion. Heat-induced perturbations in the physiology of the follicle-enclosed oocyte have also been documented, expressed by impaired cleavage rate and reduced developmental competence. With respect to the oocyte, alterations include an increase in PUFA in the membrane, reactive oxygen species, ceramide formation and caspase activity, and induction of apoptosis via the sphingomyelin and/or mitochondrial pathways. New insight into cellular and molecular alterations has revealed that heat induces perturbations in both nuclear and cytoplasmic maturation events, such as resumption of meiosis, metaphase II plate formation, cytoskeleton rearrangement, and translocation of cortical granules. Alterations in mitochondrial distribution (i.e., low proportion of category I mitochondria) and function (i.e., low membrane potential) have recently been reported for oocytes collected during the summer. These were associated with impaired expression of both nuclear (succinate dehydrogenase subunit [SDHD], adenosine triphosphate [ATP] synthase subunit beta [ATP5B]), mitochondrially NADH dehydrogenase subunit 2 (ND2), and mitochondiral (cytochrome c oxidase subunit II [MT-CO2] and cytochrome b [MT-CYB]) genes that are crucial in the mitochondrial respiratory chain. In addition, season-induced alteration in the stored maternal mRNA has been documented, expressed by reduced transcript levels (oocyte maturation factor MOS [C-MOS], growth differentiation factor 9 [GDF9], POU domain class 5 transcription factor 1 [POU5F1], and glyceraldehyde-3-phosphate dehydrogenase

  2. Green Cellular - Optimizing the Cellular Network for Minimal Emission from Mobile Stations

    CERN Document Server

    Ezri, Doron

    2009-01-01

    Wireless systems, which include cellular phones, have become an essential part of the modern life. However the mounting evidence that cellular radiation might adversely affect the health of its users, leads to a growing concern among authorities and the general public. Radiating antennas in the proximity of the user, such as antennas of mobile phones are of special interest for this matter. In this paper we suggest a new architecture for wireless networks, aiming at minimal emission from mobile stations, without any additional radiation sources. The new architecture, dubbed Green Cellular, abandons the classical transceiver base station design and suggests the augmentation of transceiver base stations with receive only devices. These devices, dubbed Green Antennas, are not aiming at coverage extension but rather at minimizing the emission from mobile stations. We discuss the implications of the Green Cellular architecture on 3G and 4G cellular technologies. We conclude by showing that employing the Green Cell...

  3. Construction of deletion mutants in the phosphotransferase transport system and adenosine triphosphate-binding cassette transporters in Listeria monocytogenes and analysis of their growth under different stress conditions

    OpenAIRE

    Marina Ceruso; Pina Fratamico; Claudia Chirollo; Rosanna Taglialatela; Maria Luisa Cortesi; Tiziana Pepe

    2013-01-01

    Functional genomics approaches enable us to investigate the biochemical, cellular, and physiological properties of each gene product and are nowadays applied to enhance food safety by understanding microbial stress responses in food and host-pathogen interactions. Listeria monocytogenes is a food-borne pathogen that causes listeriosis and is difficult to eliminate this pathogen since it can survive under multiple stress conditions such as low pH and low temperature. Detailed studies are neede...

  4. On reversibility of cellular automata with periodic boundary conditions

    Energy Technology Data Exchange (ETDEWEB)

    Nobe, Atsushi [Graduate School of Engineering Science, Osaka University, Machikaneyama-cho 1-3, Toyonaka, Osaka 560-8531 (Japan); Yura, Fumitaka [Imai Quantum Computing and Information Project, ERATO, JST, Daini Hongo White Bldg 201, 5-28-3 Hongo, Bunkyo, Tokyo 113-0033 (Japan)

    2004-06-04

    Reversibility of one-dimensional cellular automata with periodic boundary conditions is discussed. It is shown that there exist exactly 16 reversible elementary cellular automaton rules for infinitely many cell sizes by means of a correspondence between elementary cellular automaton and the de Bruijn graph. In addition, a sufficient condition for reversibility of three-valued and two-neighbour cellular automaton is given.

  5. Cellular Automata Rules and Linear Numbers

    OpenAIRE

    Nayak, Birendra Kumar; Sahoo, Sudhakar; Biswal, Sagarika

    2012-01-01

    In this paper, linear Cellular Automta (CA) rules are recursively generated using a binary tree rooted at "0". Some mathematical results on linear as well as non-linear CA rules are derived. Integers associated with linear CA rules are defined as linear numbers and the properties of these linear numbers are studied.

  6. Virtual cellular manufacturing : Configuring routing flexibility

    NARCIS (Netherlands)

    Nomden, G.; van der Zee, D.J.

    2008-01-01

    Virtual cellular manufacturing (VCM) creates groups of products and machines in the production planning and control system. Similar groupings may help to reduce set-up times. Starting from two industrial cases, we study parallel machine shops assuming the implementation of VCM. We address the way mi

  7. Determining lineage pathways from cellular barcoding experiments

    NARCIS (Netherlands)

    Perié, Leïla; Hodgkin, Philip D; Naik, Shalin H; Schumacher, Ton N; de Boer, Rob J; Duffy, Ken R

    2014-01-01

    Cellular barcoding and other single-cell lineage-tracing strategies form experimental methodologies for analysis of in vivo cell fate that have been instrumental in several significant recent discoveries. Due to the highly nonlinear nature of proliferation and differentiation, interrogation of the r

  8. Building mathematics cellular phone learning communities

    Directory of Open Access Journals (Sweden)

    Wajeeh M. Daher

    2011-04-01

    Full Text Available Researchers emphasize the importance of maintaining learning communities and environments. This article describes the building and nourishment of a learning community, one comprised of middle school students who learned mathematics out-of-class using the cellular phone. The building of the learning community was led by three third year pre-service teachers majoring in mathematics and computers. The pre-service teachers selected thirty 8th grade students to learn mathematics with the cellular phone and be part of a learning community experimenting with this learning. To analyze the building and development stages of the cellular phone learning community, two models of community building stages were used; first the team development model developed by Tuckman (1965, second the life cycle model of a virtual learning community developed by Garber (2004. The research findings indicate that a learning community which is centered on a new technology has five 'life' phases of development: Pre-birth, birth, formation, performing, and maturity. Further, the research finding indicate that the norms that were encouraged by the preservice teachers who initiated the cellular phone learning community resulted in a community which developed, nourished and matured to be similar to a community of experienced applied mathematicians who use mathematical formulae to study everyday phenomena.

  9. Cellular grafts in management of leucoderma

    Directory of Open Access Journals (Sweden)

    Mysore Venkataram

    2009-01-01

    Full Text Available Cellular grafting methods constitute important advances in the surgical management of leucoderma. Different methods such as noncultured epidermal suspensions, melanocyte cultures, and melanocyte-keratinocyte cultures have all been shown to be effective. This article reviews these methods.

  10. Cellular telephone use and cancer risk

    DEFF Research Database (Denmark)

    2006-01-01

    expected in the Danish population. RESULTS: A total of 14,249 cancers were observed (SIR = 0.95; 95% confidence interval [CI] = 0.93 to 0.97) for men and women combined. Cellular telephone use was not associated with increased risk for brain tumors (SIR = 0.97), acoustic neuromas (SIR = 0.73), salivary...

  11. Cellular basis of memory for addiction.

    Science.gov (United States)

    Nestler, Eric J

    2013-12-01

    DESPITE THE IMPORTANCE OF NUMEROUS PSYCHOSOCIAL FACTORS, AT ITS CORE, DRUG ADDICTION INVOLVES A BIOLOGICAL PROCESS: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. Here, we review the types of molecular and cellular adaptations that occur in specific brain regions to mediate addiction-associated behavioral abnormalities. These include alterations in gene expression achieved in part via epigenetic mechanisms, plasticity in the neurophysiological functioning of neurons and synapses, and associated plasticity in neuronal and synaptic morphology mediated in part by altered neurotrophic factor signaling. Each of these types of drug-induced modifications can be viewed as a form of "cellular or molecular memory." Moreover, it is striking that most addiction-related forms of plasticity are very similar to the types of plasticity that have been associated with more classic forms of "behavioral memory," perhaps reflecting the finite repertoire of adaptive mechanisms available to neurons when faced with environmental challenges. Finally, addiction-related molecular and cellular adaptations involve most of the same brain regions that mediate more classic forms of memory, consistent with the view that abnormal memories are important drivers of addiction syndromes. The goal of these studies which aim to explicate the molecular and cellular basis of drug addiction is to eventually develop biologically based diagnostic tests, as well as more effective treatments for addiction disorders. PMID:24459410

  12. Klotho-Dependent Cellular Transport Regulation.

    Science.gov (United States)

    Sopjani, M; Dërmaku-Sopjani, M

    2016-01-01

    Klotho is a transmembrane protein that in humans is encoded by the hKL gene. This protein is known to have aging suppressor effects and is predominantly expressed in the distal convoluted tubule of the kidney, parathyroid glands, and choroid plexus of the brain. The Klotho protein exists in both full-length membrane form and a soluble secreted form, which exerts numerous distinct functions. The extracellular domain of Klotho can be enzymatically cleaved off and released into the systemic circulation where it functions as β-glucuronidase and a hormone. Soluble Klotho is a multifunction protein present in the biological fluids including blood, urine, and cerebrospinal fluid of mammals. Klotho deficiency leads to multiple organ failure accompanied by early appearance of multiple age-related disorders and early death, whereas overexpression of Klotho results in the opposite effects. Klotho, an enzyme and hormone, has been reported to participate in the regulation of cellular transport processes across the plasma membrane either indirectly through inhibiting calcitriol (1,25(OH)2D3) formation or other mechanism, or by directly affecting transporter proteins, including ion channels, cellular carriers, and Na(+)/K(+)-ATPase. Accordingly, Klotho protein serves as a powerful regulator of cellular transport across the plasma membrane. Importantly, Klotho-dependent cellular transport regulation implies stimulatory or inhibitory effects. Klotho has been shown to play a key role in the regulation of multiple calcium and potassium ion channels, and various cellular carriers including the Na(+)-coupled cotransporters such as NaPi-IIa, NaPi-IIb, EAAT3, and EAAT4, CreaT1 as well as Na(+)/K(+)-ATPase. These regulations are parts of the antiaging function of Klotho, which will be discussing throughout this chapter. Clearly, further experimental efforts are required to investigate the effect of Klotho on other transport proteins and underlying molecular mechanisms by which Klotho

  13. Comparison of the Immunomagnetic Separation/Adenosine Triphosphate Rapid Method and the Modified mTEC Membrane-Filtration Method for Enumeration of Escherichia coli

    Science.gov (United States)

    Brady, Amie M.G.; Bushon, Rebecca N.; Bertke, Erin E.

    2009-01-01

    Water quality at beaches is monitored for fecal indicator bacteria by traditional, culture-based methods that can take 18 to 24 hours to obtain results. A rapid detection method that provides estimated concentrations of fecal indicator bacteria within 1 hour from the start of sample processing would allow beach managers to post advisories or close the beach when the conditions are actually considered unsafe instead of a day later, when conditions may have changed. A rapid method that couples immunomagnetic separation with adenosine triphosphate detection (IMS/ATP rapid method) was evaluated through monitoring of Escherichia coli (E. coli) at three Lake Erie beaches in Ohio (Edgewater and Villa Angela in Cleveland and Huntington in Bay Village). Beach water samples were collected between 4 and 5 days per week during the recreational seasons (May through September) of 2006 and 2007. Composite samples were created in the lab from two point samples collected at each beach and were shown to be comparable substitutes for analysis of two individual samples. E. coli concentrations in composite samples, as determined by the culture-based method, ranged from 4 to 24,000 colony-forming units per 100 milliliters during this study across all beaches. Turbidity also was measured for each sample and ranged from 0.8 to 260 neophelometric turbidity ratio units. Environmental variables were noted at the time of sampling, including number of birds at the beach and wave height. Rainfall amounts were measured at National Weather Service stations at local airports. Turbidity, rainfall, and wave height were significantly related to the culture-based method results each year and for both years combined at each beach. The number of birds at the beach was significantly related to the culture-based method results only at Edgewater during 2006 and during both years combined. Results of the IMS/ATP method were compared to results of the culture-based method for samples by year for each beach

  14. Cellular Dynamic Simulator: An Event Driven Molecular Simulation Environment for Cellular Physiology

    OpenAIRE

    Byrne, Michael J.; Waxham, M. Neal; Kubota, Yoshihisa

    2010-01-01

    In this paper, we present the Cellular Dynamic Simulator (CDS) for simulating diffusion and chemical reactions within crowded molecular environments. CDS is based on a novel event driven algorithm specifically designed for precise calculation of the timing of collisions, reactions and other events for each individual molecule in the environment. Generic mesh based compartments allow the creation / importation of very simple or detailed cellular structures that exist in a 3D environment. Multi...

  15. G-protein-coupled Receptor Kinase-interacting Proteins Inhibit Apoptosis by Inositol 1,4,5-Triphosphate Receptor-mediated Ca2+ Signal Regulation*

    OpenAIRE

    Zhang, Songbai; Hisatsune, Chihiro; Matsu-ura, Toru; Mikoshiba, Katsuhiko

    2009-01-01

    The inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) is an intracellular IP3-gated calcium (Ca2+) release channel and plays important roles in regulation of numerous Ca2+-dependent cellular responses. Many intracellular modulators and IP3R-binding proteins regulate the IP3R channel function. Here we identified G-protein-coupled receptor kinase-interacting proteins (GIT), GIT1 and GIT2, as novel IP3R-binding proteins. We found that both GIT1 and GIT2 directly bind to all three subtypes of IP...

  16. Mobile Node Localization in Cellular Networks

    Directory of Open Access Journals (Sweden)

    Yasir Malik

    2012-01-01

    Full Text Available Location information is the major component in location based applications. This information is used in different safety and service oriented applications to provide users with services according to their Geolocation. There are many approaches to locate mobile nodes in indoor and outdoor environments. In thispaper, we are interested in outdoor localization particularly in cellular networks of mobile nodes andpresented a localization method based on cell and user location information. Our localization method is based on hello message delay (sending and receiving time and coordinate information of Base Transceiver Station (BTSs. To validate our method across cellular network, we implemented and simulated our method in two scenarios i.e. maintaining database of base stations in centralize and distributed system. Simulation results show the effectiveness of our approach and its implementation applicability in telecommunication systems.

  17. External insulation with cellular plastic materials

    DEFF Research Database (Denmark)

    Sørensen, Lars Schiøtt; Nielsen, Anker

    2014-01-01

    External thermal insulation composite systems (ETICS) can be used as extra insulation of existing buildings. The system can be made of cellular plastic materials or mineral wool. There is a European Technical guideline, ETAG 004, that describe the tests that shall be conducted on such systems....... This paper gives a comparison of systems with mineral wool and cellular plastic, based on experience from practice and literature. It is important to look at the details in the system and at long time stability of the properties such as thermal insulation, moisture and fire. Investigation of fire properties...... must be done before utilisation of the system, including the risk of fire spread from one storey to the next for practical solutions. An elaboration of fire spread risks require thermo physic knowledge about ignition temperatures, critical radiation, upward flame spread velocities etc. of the actual...

  18. Designing beauty the art of cellular automata

    CERN Document Server

    Martínez, Genaro

    2016-01-01

    This fascinating, colourful book offers in-depth insights and first-hand working experiences in the production of art works, using simple computational models with rich morphological behaviour, at the edge of mathematics, computer science, physics and biology. It organically combines ground breaking scientific discoveries in the theory of computation and complex systems with artistic representations of the research results. In this appealing book mathematicians, computer scientists, physicists, and engineers brought together marvelous and esoteric patterns generated by cellular automata, which are arrays of simple machines with complex behavior. Configurations produced by cellular automata uncover mechanics of dynamic patterns formation, their propagation and interaction in natural systems: heart pacemaker, bacterial membrane proteins, chemical rectors, water permeation in soil, compressed gas, cell division, population dynamics, reaction-diffusion media and self-organisation. The book inspires artists to tak...

  19. Astrobiological Complexity with Probabilistic Cellular Automata

    CERN Document Server

    Vukotić, B

    2012-01-01

    Search for extraterrestrial life and intelligence constitutes one of the major endeavors in science, but has yet been quantitatively modeled only rarely and in a cursory and superficial fashion. We argue that probabilistic cellular automata (PCA) represent the best quantitative framework for modeling astrobiological history of the Milky Way and its Galactic Habitable Zone. The relevant astrobiological parameters are to be modeled as the elements of the input probability matrix for the PCA kernel. With the underlying simplicity of the cellular automata constructs, this approach enables a quick analysis of large and ambiguous input parameters' space. We perform a simple clustering analysis of typical astrobiological histories and discuss the relevant boundary conditions of practical importance for planning and guiding actual empirical astrobiological and SETI projects. In addition to showing how the present framework is adaptable to more complex situations and updated observational databases from current and ne...

  20. Molecular kinesis in cellular function and plasticity.

    Science.gov (United States)

    Tiedge, H; Bloom, F E; Richter, D

    2001-06-19

    Intracellular transport and localization of cellular components are essential for the functional organization and plasticity of eukaryotic cells. Although the elucidation of protein transport mechanisms has made impressive progress in recent years, intracellular transport of RNA remains less well understood. The National Academy of Sciences Colloquium on Molecular Kinesis in Cellular Function and Plasticity therefore was devised as an interdisciplinary platform for participants to discuss intracellular molecular transport from a variety of different perspectives. Topics covered at the meeting included RNA metabolism and transport, mechanisms of protein synthesis and localization, the formation of complex interactive protein ensembles, and the relevance of such mechanisms for activity-dependent regulation and synaptic plasticity in neurons. It was the overall objective of the colloquium to generate momentum and cohesion for the emerging research field of molecular kinesis.

  1. Cellular and Molecular Mechanisms of AKI.

    Science.gov (United States)

    Agarwal, Anupam; Dong, Zheng; Harris, Raymond; Murray, Patrick; Parikh, Samir M; Rosner, Mitchell H; Kellum, John A; Ronco, Claudio

    2016-05-01

    In this article, we review the current evidence for the cellular and molecular mechanisms of AKI, focusing on epithelial cell pathobiology and related cell-cell interactions, using ischemic AKI as a model. Highlighted are the clinical relevance of cellular and molecular targets that have been investigated in experimental models of ischemic AKI and how such models might be improved to optimize translation into successful clinical trials. In particular, development of more context-specific animal models with greater relevance to human AKI is urgently needed. Comorbidities that could alter patient susceptibility to AKI, such as underlying diabetes, aging, obesity, cancer, and CKD, should also be considered in developing these models. Finally, harmonization between academia and industry for more clinically relevant preclinical testing of potential therapeutic targets and better translational clinical trial design is also needed to achieve the goal of developing effective interventions for AKI. PMID:26860342

  2. Cellular and molecular introduction to brain development.

    Science.gov (United States)

    Jiang, Xiangning; Nardelli, Jeannette

    2016-08-01

    Advances in the study of brain development over the last decades, especially recent findings regarding the evolutionary expansion of the human neocortex, and large-scale analyses of the proteome/transcriptome in the human brain, have offered novel insights into the molecular mechanisms guiding neural maturation, and the pathophysiology of multiple forms of neurological disorders. As a preamble to reviews of this issue, we provide an overview of the cellular, molecular and genetic bases of brain development with an emphasis on the major mechanisms associated with landmarks of normal neural development in the embryonic stage and early postnatal life, including neural stem/progenitor cell proliferation, cortical neuronal migration, evolution and folding of the cerebral cortex, synaptogenesis and neural circuit development, gliogenesis and myelination. We will only briefly depict developmental disorders that result from perturbations of these cellular or molecular mechanisms, and the most common perinatal brain injuries that could disturb normal brain development. PMID:26184894

  3. Cellularity of certain quantum endomorphism algebras

    DEFF Research Database (Denmark)

    Andersen, Henning Haahr; Lehrer, G. I.; Zhang, R.

    Let $\\tA=\\Z[q^{\\pm \\frac{1}{2}}][([d]!)\\inv]$ and let $\\Delta_{\\tA}(d)$ be an integral form of the Weyl module of highest weight $d \\in \\N$ of the quantised enveloping algebra $\\U_{\\tA}$ of $\\fsl_2$. We exhibit for all positive integers $r$ an explicit cellular structure for $\\End_{\\U_{\\tA}}(\\Del......Let $\\tA=\\Z[q^{\\pm \\frac{1}{2}}][([d]!)\\inv]$ and let $\\Delta_{\\tA}(d)$ be an integral form of the Weyl module of highest weight $d \\in \\N$ of the quantised enveloping algebra $\\U_{\\tA}$ of $\\fsl_2$. We exhibit for all positive integers $r$ an explicit cellular structure for $\\End...

  4. Cellular automata in image processing and geometry

    CERN Document Server

    Adamatzky, Andrew; Sun, Xianfang

    2014-01-01

    The book presents findings, views and ideas on what exact problems of image processing, pattern recognition and generation can be efficiently solved by cellular automata architectures. This volume provides a convenient collection in this area, in which publications are otherwise widely scattered throughout the literature. The topics covered include image compression and resizing; skeletonization, erosion and dilation; convex hull computation, edge detection and segmentation; forgery detection and content based retrieval; and pattern generation. The book advances the theory of image processing, pattern recognition and generation as well as the design of efficient algorithms and hardware for parallel image processing and analysis. It is aimed at computer scientists, software programmers, electronic engineers, mathematicians and physicists, and at everyone who studies or develops cellular automaton algorithms and tools for image processing and analysis, or develops novel architectures and implementations of mass...

  5. Cellular and molecular basis of cerebellar development

    Science.gov (United States)

    Martinez, Salvador; Andreu, Abraham; Mecklenburg, Nora; Echevarria, Diego

    2013-01-01

    Historically, the molecular and cellular mechanisms of cerebellar development were investigated through structural descriptions and studying spontaneous mutations in animal models and humans. Advances in experimental embryology, genetic engineering, and neuroimaging techniques render today the possibility to approach the analysis of molecular mechanisms underlying histogenesis and morphogenesis of the cerebellum by experimental designs. Several genes and molecules were identified to be involved in the cerebellar plate regionalization, specification, and differentiation of cerebellar neurons, as well as the establishment of cellular migratory routes and the subsequent neuronal connectivity. Indeed, pattern formation of the cerebellum requires the adequate orchestration of both key morphogenetic signals, arising from distinct brain regions, and local expression of specific transcription factors. Thus, the present review wants to revisit and discuss these morphogenetic and molecular mechanisms taking place during cerebellar development in order to understand causal processes regulating cerebellar cytoarchitecture, its highly topographically ordered circuitry and its role in brain function. PMID:23805080

  6. Cellular and Molecular Basis of Cerebellar Development

    Directory of Open Access Journals (Sweden)

    Salvador eMartinez

    2013-06-01

    Full Text Available Historically, the molecular and cellular mechanisms of cerebellar development were investigated through structural descriptions and studying spontaneous mutations in animal models and humans. Advances in experimental embryology, genetic engineering and neuroimaging techniques render today the possibility to approach the analysis of molecular mechanisms underlying histogenesis and morphogenesis of the cerebellum by experimental designs. Several genes and molecules were identified to be involved in the cerebellar plate regionalization, specification and differentiation of cerebellar neurons, as well as the establishment of cellular migratory routes and the subsequent neuronal connectivity. Indeed, pattern formation of the cerebellum requires the adequate orchestration of both key morphogenetic signals, arising from distinct brain regions, and local expression of specific transcription factors. Thus, the present review wants to revisit and discuss these morphogenetic and molecular mechanisms taking place during cerebellar development in order to understand causal processes regulating cerebellar cytoarchitecture, its highly topographically ordered circuitry and its role in brain function.

  7. WD40 proteins propel cellular networks.

    Science.gov (United States)

    Stirnimann, Christian U; Petsalaki, Evangelia; Russell, Robert B; Müller, Christoph W

    2010-10-01

    Recent findings indicate that WD40 domains play central roles in biological processes by acting as hubs in cellular networks; however, they have been studied less intensely than other common domains, such as the kinase, PDZ or SH3 domains. As suggested by various interactome studies, they are among the most promiscuous interactors. Structural studies suggest that this property stems from their ability, as scaffolds, to interact with diverse proteins, peptides or nucleic acids using multiple surfaces or modes of interaction. A general scaffolding role is supported by the fact that no WD40 domain has been found with intrinsic enzymatic activity despite often being part of large molecular machines. We discuss the WD40 domain distributions in protein networks and structures of WD40-containing assemblies to demonstrate their versatility in mediating critical cellular functions.

  8. Quantum features of natural cellular automata

    CERN Document Server

    Elze, Hans-Thomas

    2016-01-01

    Cellular automata can show well known features of quantum mechanics, such as a linear rule according to which they evolve and which resembles a discretized version of the Schroedinger equation. This includes corresponding conservation laws. The class of "natural" Hamiltonian cellular automata is based exclusively on integer-valued variables and couplings and their dynamics derives from an Action Principle. They can be mapped reversibly to continuum models by applying Sampling Theory. Thus, "deformed" quantum mechanical models with a finite discreteness scale $l$ are obtained, which for $l\\rightarrow 0$ reproduce familiar continuum results. We have recently demonstrated that such automata can form "multipartite" systems consistently with the tensor product structures of nonrelativistic many-body quantum mechanics, while interacting and maintaining the linear evolution. Consequently, the Superposition Principle fully applies for such primitive discrete deterministic automata and their composites and can produce...

  9. A cellular glass substrate solar concentrator

    Science.gov (United States)

    Bedard, R.; Bell, D.

    1980-01-01

    The design of a second generation point focusing solar concentration is discussed. The design is based on reflective gores fabricated of thin glass mirror bonded continuously to a contoured substrate of cellular glass. The concentrator aperture and structural stiffness was optimized for minimum concentrator cost given the performance requirement of delivering 56 kWth to a 22 cm diameter receiver aperture with a direct normal insolation of 845 watts sq m and an operating wind of 50 kmph. The reflective panel, support structure, drives, foundation and instrumentation and control subsystem designs, optimized for minimum cost, are summarized. The use of cellular glass as a reflective panel substrate material is shown to offer significant weight and cost advantages compared to existing technology materials.

  10. SELF-ORGANIZED CRITICALITY AND CELLULAR AUTOMATA

    Energy Technology Data Exchange (ETDEWEB)

    CREUTZ,M.

    2007-01-01

    Cellular automata provide a fascinating class of dynamical systems based on very simple rules of evolution yet capable of displaying highly complex behavior. These include simplified models for many phenomena seen in nature. Among other things, they provide insight into self-organized criticality, wherein dissipative systems naturally drive themselves to a critical state with important phenomena occurring over a wide range of length and the scales. This article begins with an overview of self-organized criticality. This is followed by a discussion of a few examples of simple cellular automaton systems, some of which may exhibit critical behavior. Finally, some of the fascinating exact mathematical properties of the Bak-Tang-Wiesenfeld sand-pile model [1] are discussed.

  11. A Modified Sensitive Driving Cellular Automaton Model

    Institute of Scientific and Technical Information of China (English)

    GE Hong-Xia; DAI Shi-Qiang; DONG Li-Yun; LEI Li

    2005-01-01

    A modified cellular automaton model for traffic flow on highway is proposed with a novel concept about the variable security gap. The concept is first introduced into the original Nagel-Schreckenberg model, which is called the non-sensitive driving cellular automaton model. And then it is incorporated with a sensitive driving NaSch model,in which the randomization brake is arranged before the deterministic deceleration. A parameter related to the variable security gap is determined through simulation. Comparison of the simulation results indicates that the variable security gap has different influence on the two models. The fundamental diagram obtained by simulation with the modified sensitive driving NaSch model shows that the maximumflow are in good agreement with the observed data, indicating that the presented model is more reasonable and realistic.

  12. Cellular and molecular basis of mammary microcalcifications

    OpenAIRE

    Cox, Rachel

    2011-01-01

    Mammary microcalcifications represent one of the most reliable mammographic features of non-palpable breast cancer and are often the sole indicator of the disease. However, it is unknown whether these microcalcifications are a sign of degeneration or an active cellular process. The aims of this project were to establish and characterise an in vitro model of mammary mineralisation in monolayer, 3D scaffolds and in vivo and to investigate the molecular mechanisms involved in this process, focus...

  13. Exponential Stability for Delayed Cellular Neural Networks

    Institute of Scientific and Technical Information of China (English)

    YANG Jin-xiang; ZHONG Shou-ming; YAN Ke-yu

    2005-01-01

    The exponential stability of the delayed cellular neural networks (DCNN's) is investigated. By dividing the network state variables into some parts according to the characters of the neural networks, some new sufficient conditions of exponential stability are derived via constructing a Liapunov function. It is shown that the conditions differ from previous ones. The new conditions, which are associated with some initial value, are represented by some blocks of the interconnection matrix.

  14. Light weight cellular structures based on aluminium

    Energy Technology Data Exchange (ETDEWEB)

    Prakash, O. [Indian Inst. of Tech., Kanpur (India); Embury, J.D.; Sinclair, C. [McMaster Univ., Hamilton, ON (Canada); Sang, H. [Queen`s Univ., Kingston, ON (Canada); Silvetti, P. [Cordoba Univ. Nacional (Argentina). Facultad de Ciencias Exactas, Fisicas y Naturales

    1997-02-01

    An interesting form of lightweight material which has emerged in the past 2 decades is metallic foam. This paper deals with the basic concepts of making metallic foams and a detailed study of foams produced from Al-SiC. In addition, some aspects of cellular solids based on honeycomb structures are outlined including the concept of producing both two-phase foams and foams with composite walls.

  15. Animal and cellular models of human disease

    OpenAIRE

    Arends, Mark; White, Eric; Whitelaw, Christopher

    2016-01-01

    In this eighteenth (2016) Annual Review Issue of The Journal of Pathology, we present a collection of 19 invited review articles that cover different aspects of cellular and animal models of disease. These include genetically-engineered models, chemically-induced models, naturally-occurring models, and combinations thereof, with the focus on recent methodological and conceptual developments across a wide range of human diseases.

  16. Cellular immune findings in Lyme disease.

    Science.gov (United States)

    Sigal, L. H.; Moffat, C. M.; Steere, A. C.; Dwyer, J. M.

    1984-01-01

    From 1981 through 1983, we did the first testing of cellular immunity in Lyme disease. Active established Lyme disease was often associated with lymphopenia, less spontaneous suppressor cell activity than normal, and a heightened response of lymphocytes to phytohemagglutinin and Lyme spirochetal antigens. Thus, a major feature of the immune response during active disease seems to be a lessening of suppression, but it is not yet known whether this response plays a role in the pathophysiology of the disease. PMID:6240164

  17. Spectrum sharing for future mobile cellular systems

    OpenAIRE

    Bennis, M

    2009-01-01

    Abstract Spectrum sharing has become a high priority research area over the past few years. The motivation behind this lies in the fact that the limited spectrum is currently inefficiently utilized. As recognized by the World radio communication conference (WRC)-07, the amount of identified spectrum is not large enough to support large bandwidths for a substantial number of operators. Therefore, it is paramount for future mobile cellular systems to share the frequency spectrum and coexist ...

  18. Cellular factors required for papillomavirus DNA replication.

    OpenAIRE

    Melendy, T; Sedman, J; Stenlund, A

    1995-01-01

    In vitro replication of papillomavirus DNA has been carried out with a combination of purified proteins and partially purified extracts made from human cells. DNA synthesis requires the viral E1 protein and the papillomavirus origin of replication. The E2 protein stimulates DNA synthesis in a binding site-independent manner. Papillomavirus DNA replication is also dependent on the cellular factors replication protein A, replication factor C, and proliferating-cell nuclear antigen as well as a ...

  19. Clinical applications of cellular therapy products

    OpenAIRE

    Serpil Yanbakan

    2015-01-01

    Adult stem cells have the potential to differentiate into multiple cell types and have usage about lots of regenerative medicine research fields. Especially bone marrow-derived mesenchymal stem cells have a wide range of case presentation. New discoveries about stem cell biology will progress new options about cellular therapy products and isolation of different stem cell types will increase hope for treatment of important illness such as Parkinson’s disease, diabetes, malign brain tumors. It...

  20. Sumo and the cellular stress response

    OpenAIRE

    Enserink, Jorrit M.

    2015-01-01

    The ubiquitin family member Sumo has important functions in many cellular processes including DNA repair, transcription and cell division. Numerous studies have shown that Sumo is essential for maintaining cell homeostasis when the cell encounters endogenous or environmental stress, such as osmotic stress, hypoxia, heat shock, genotoxic stress, and nutrient stress. Regulation of transcription is a key component of the Sumo stress response, and multiple mechanisms have been described by which ...

  1. The flow of forces through cellular materials

    OpenAIRE

    Berger, Mitchell A.

    2012-01-01

    Describing and measuring the elastic properties of cellular materials such as honeycombs and foams can be a difficult problem when the cell structure is disordered. This paper suggests that tracking the flow of forces through the material can help in visualizing and understanding how the geometry of the cell structure affects the elastic behaviour. The mean strain tensor for a sample of material can be calculated by summing over the force paths, weighted by the strengths of the paths. This me...

  2. Imaging cellular and molecular biological functions

    Energy Technology Data Exchange (ETDEWEB)

    Shorte, S.L. [Institut Pasteur, 75 - Paris (France). Plateforme d' Imagerie Dynamique PFID-Imagopole; Frischknecht, F. (eds.) [Heidelberg Univ. Medical School (Germany). Dept. of Parasitology

    2007-07-01

    'Imaging cellular and molecular biological function' provides a unique selection of essays by leading experts, aiming at scientist and student alike who are interested in all aspects of modern imaging, from its application and up-scaling to its development. Indeed the philosophy of this volume is to provide student, researcher, PI, professional or provost the means to enter this applications field with confidence, and to construct the means to answer their own specific questions. (orig.)

  3. Cellular and synaptic network defects in autism

    OpenAIRE

    Peça, João; Feng, Guoping

    2012-01-01

    Many candidate genes are now thought to confer susceptibility to autism spectrum disorders (ASDs). Here we review four interrelated complexes, each composed of multiple families of genes that functionally coalesce on common cellular pathways. We illustrate a common thread in the organization of glutamatergic synapses and suggest a link between genes involved in Tuberous Sclerosis Complex, Fragile X syndrome, Angelman syndrome and several synaptic ASD candidate genes. When viewed in this conte...

  4. Cellular events and biomarkers of wound healing

    OpenAIRE

    Shah Jumaat Mohd Yussof; Effat Omar; Pai, Dinker R.; Suneet Sood

    2012-01-01

    Researchers have identified several of the cellular events associated with wound healing. Platelets, neutrophils, macrophages, and fibroblasts primarily contribute to the process. They release cytokines including interleukins (ILs) and TNF-α, and growth factors, of which platelet-derived growth factor (PDGF) is perhaps the most important. The cytokines and growth factors manipulate the inflammatory phase of healing. Cytokines are chemotactic for white cells and fibroblasts, while the growth f...

  5. Oxidative stress action in cellular aging

    OpenAIRE

    Monique Cristine de Oliveira; João Paulo Ferreira Schoffen

    2010-01-01

    Various theories try to explain the biological aging by changing the functions and structure of organic systems and cells. During lifetime, free radicals in the oxidative stress lead to lipid peroxidation of cellular membranes, homeostasis imbalance, chemical residues formation, gene mutations in DNA, dysfunction of certain organelles, and the arise of diseases due to cell death and/or injury. This review describes the action of oxidative stress in the cells aging process, emphasizing the fac...

  6. Cellular immune findings in Lyme disease.

    OpenAIRE

    Sigal, L. H.; Moffat, C. M.; Steere, A. C.; Dwyer, J. M.

    1984-01-01

    From 1981 through 1983, we did the first testing of cellular immunity in Lyme disease. Active established Lyme disease was often associated with lymphopenia, less spontaneous suppressor cell activity than normal, and a heightened response of lymphocytes to phytohemagglutinin and Lyme spirochetal antigens. Thus, a major feature of the immune response during active disease seems to be a lessening of suppression, but it is not yet known whether this response plays a role in the pathophysiology o...

  7. Introduction to Tissular and Cellular Engineering

    Institute of Scientific and Technical Information of China (English)

    JF; STOLTZ

    2005-01-01

    Most human tissues do not regenerate spontaneously, which is why cellular therapies and tissular engineering are promising alternatives. The principle is simple: cells are sampled in a patient and introduced in the damaged tissue or in a tridimentional porous support and cultivated in a bioreactor in which the physico-chemical and mechanical parameters are controlled. Once the tissues (or the cells) are mature they may be implanted. In parallel, the development of biotherapies with stem cells is a field of ...

  8. Empirical multiscale networks of cellular regulation.

    Directory of Open Access Journals (Sweden)

    Benjamin de Bivort

    2007-10-01

    Full Text Available Grouping genes by similarity of expression across multiple cellular conditions enables the identification of cellular modules. The known functions of genes enable the characterization of the aggregate biological functions of these modules. In this paper, we use a high-throughput approach to identify the effective mutual regulatory interactions between modules composed of mouse genes from the Alliance for Cell Signaling (AfCS murine B-lymphocyte database which tracks the response of approximately 15,000 genes following chemokine perturbation. This analysis reveals principles of cellular organization that we discuss along four conceptual axes. (1 Regulatory implications: the derived collection of influences between any two modules quantifies intuitive as well as unexpected regulatory interactions. (2 Behavior across scales: trends across global networks of varying resolution (composed of various numbers of modules reveal principles of assembly of high-level behaviors from smaller components. (3 Temporal behavior: tracking the mutual module influences over different time intervals provides features of regulation dynamics such as duration, persistence, and periodicity. (4 Gene Ontology correspondence: the association of modules to known biological roles of individual genes describes the organization of functions within coexpressed modules of various sizes. We present key specific results in each of these four areas, as well as derive general principles of cellular organization. At the coarsest scale, the entire transcriptional network contains five divisions: two divisions devoted to ATP production/biosynthesis and DNA replication that activate all other divisions, an "extracellular interaction" division that represses all other divisions, and two divisions (proliferation/differentiation and membrane infrastructure that activate and repress other divisions in specific ways consistent with cell cycle control.

  9. Cellular responses to environmental DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    1994-08-01

    This volume contains the proceedings of the conference entitled Cellular Responses to Environmental DNA Damage held in Banff,Alberta December 1--6, 1991. The conference addresses various aspects of DNA repair in sessions titled DNA repair; Basic Mechanisms; Lesions; Systems; Inducible Responses; Mutagenesis; Human Population Response Heterogeneity; Intragenomic DNA Repair Heterogeneity; DNA Repair Gene Cloning; Aging; Human Genetic Disease; and Carcinogenesis. Individual papers are represented as abstracts of about one page in length.

  10. Stability of Stochastic Neutral Cellular Neural Networks

    Science.gov (United States)

    Chen, Ling; Zhao, Hongyong

    In this paper, we study a class of stochastic neutral cellular neural networks. By constructing a suitable Lyapunov functional and employing the nonnegative semi-martingale convergence theorem we give some sufficient conditions ensuring the almost sure exponential stability of the networks. The results obtained are helpful to design stability of networks when stochastic noise is taken into consideration. Finally, two examples are provided to show the correctness of our analysis.

  11. Cellular Signaling in the Bovine Antral Follicles

    OpenAIRE

    Juan F. Vásquez - Cano; Martha Olivera - A.

    2010-01-01

    Antral follicle development in the ovary of female cattle is the product of a complex of endocrine, paracrine and autocrine relationships. The interactions of the pituitary gonadotropins over granulosa and theca cells prepare the follicle to produce estradiol and for the final stages of maturation of the oocyte and its potencial ovulation or atresia inside subordinate follicles. It is a dynamic event where cellular signaling patterns changes sequentiallyand quickly at different stages of foll...

  12. Cellular Automation of Galactic Habitable Zone

    CERN Document Server

    Vukotic, Branislav

    2010-01-01

    We present a preliminary results of our Galactic Habitable Zone (GHZ) 2D probabilistic cellular automata models. The relevant time-scales (emergence of life, it's diversification and evolution influenced with the global risk function) are modeled as the probability matrix elements and are chosen in accordance with the Copernican principle to be well-represented by the data inferred from the Earth's fossil record. With Fermi's paradox as a main boundary condition the resulting histories of astrobiological landscape are discussed.

  13. Cognitive resource management for heterogeneous cellular networks

    CERN Document Server

    Liu, Yongkang

    2014-01-01

    This Springer Brief focuses on cognitive resource management in heterogeneous cellular networks (Het Net) with small cell deployment for the LTE-Advanced system. It introduces the Het Net features, presents practical approaches using cognitive radio technology in accommodating small cell data relay and optimizing resource allocation and examines the effectiveness of resource management among small cells given limited coordination bandwidth and wireless channel uncertainty. The authors introduce different network characteristics of small cell, investigate the mesh of small cell access points in

  14. Important cellular targets for antimicrobial photodynamic therapy.

    Science.gov (United States)

    Awad, Mariam M; Tovmasyan, Artak; Craik, James D; Batinic-Haberle, Ines; Benov, Ludmil T

    2016-09-01

    The persistent problem of antibiotic resistance has created a strong demand for new methods for therapy and disinfection. Photodynamic inactivation (PDI) of microbes has demonstrated promising results for eradication of antibiotic-resistant strains. PDI is based on the use of a photosensitive compound (photosensitizer, PS), which upon illumination with visible light generates reactive species capable of damaging and killing microorganisms. Since photogenerated reactive species are short lived, damage is limited to close proximity of the PS. It is reasonable to expect that the larger the number of damaged targets is and the greater their variety is, the higher the efficiency of PDI is and the lower the chances for development of resistance are. Exact molecular mechanisms and specific targets whose damage is essential for microbial inactivation have not been unequivocally established. Two main cellular components, DNA and plasma membrane, are regarded as the most important PDI targets. Using Zn porphyrin-based PSs and Escherichia coli as a model Gram-negative microorganism, we demonstrate that efficient photoinactivation of bacteria can be achieved without detectable DNA modification. Among the cellular components which are modified early during illumination and constitute key PDI targets are cytosolic enzymes, membrane-bound protein complexes, and the plasma membrane. As a result, membrane barrier function is lost, and energy and reducing equivalent production is disrupted, which in turn compromises cell defense mechanisms, thus augmenting the photoinduced oxidative injury. In conclusion, high PDI antimicrobial effectiveness does not necessarily require impairment of a specific critical cellular component and can be achieved by inducing damage to multiple cellular targets. PMID:27221289

  15. Investigation of proton affinities and gas phase vibrational spectra of protonated nucleosides, deoxynucleosides, and their analogs

    NARCIS (Netherlands)

    H.U. Ung; K.T. Huynh; J.C. Poutsma; J. Oomens; G. Berden; T.H. Morton

    2015-01-01

    DNA nucleobases make use of hydrogen bonding, whether in associating to form the Watson-Crick double-helix or in producing alternative structures such as the G-quadruplex or the i-motif. Nucleoside proton-bound dimers provide an avenue for investigating characteristics that they possess within the i

  16. Cellular Kinetics of Perivascular MSC Precursors

    Directory of Open Access Journals (Sweden)

    William C. W. Chen

    2013-01-01

    Full Text Available Mesenchymal stem/stromal cells (MSCs and MSC-like multipotent stem/progenitor cells have been widely investigated for regenerative medicine and deemed promising in clinical applications. In order to further improve MSC-based stem cell therapeutics, it is important to understand the cellular kinetics and functional roles of MSCs in the dynamic regenerative processes. However, due to the heterogeneous nature of typical MSC cultures, their native identity and anatomical localization in the body have remained unclear, making it difficult to decipher the existence of distinct cell subsets within the MSC entity. Recent studies have shown that several blood-vessel-derived precursor cell populations, purified by flow cytometry from multiple human organs, give rise to bona fide MSCs, suggesting that the vasculature serves as a systemic reservoir of MSC-like stem/progenitor cells. Using individually purified MSC-like precursor cell subsets, we and other researchers have been able to investigate the differential phenotypes and regenerative capacities of these contributing cellular constituents in the MSC pool. In this review, we will discuss the identification and characterization of perivascular MSC precursors, including pericytes and adventitial cells, and focus on their cellular kinetics: cell adhesion, migration, engraftment, homing, and intercellular cross-talk during tissue repair and regeneration.

  17. HDACi: cellular effects, opportunities for restorative dentistry.

    LENUS (Irish Health Repository)

    Duncan, H F

    2011-12-01

    Acetylation of histone and non-histone proteins alters gene expression and induces a host of cellular effects. The acetylation process is homeostatically balanced by two groups of cellular enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). HAT activity relaxes the structure of the human chromatin, rendering it transcriptionally active, thereby increasing gene expression. In contrast, HDAC activity leads to gene silencing. The enzymatic balance can be \\'tipped\\' by histone deacetylase inhibitors (HDACi), leading to an accumulation of acetylated proteins, which subsequently modify cellular processes including stem cell differentiation, cell cycle, apoptosis, gene expression, and angiogenesis. There is a variety of natural and synthetic HDACi available, and their pleiotropic effects have contributed to diverse clinical applications, not only in cancer but also in non-cancer areas, such as chronic inflammatory disease, bone engineering, and neurodegenerative disease. Indeed, it appears that HDACi-modulated effects may differ between \\'normal\\' and transformed cells, particularly with regard to reactive oxygen species accumulation, apoptosis, proliferation, and cell cycle arrest. The potential beneficial effects of HDACi for health, resulting from their ability to regulate global gene expression by epigenetic modification of DNA-associated proteins, also offer potential for application within restorative dentistry, where they may promote dental tissue regeneration following pulpal damage.

  18. Dynamic Channel Allocation in Sectored Cellular Systems

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    It is known that dynamic channel assignment(DCA) strategy outperforms the fixed channel assignment(FCA) strategy in omni-directional antenna cellular systems. One of the most important methods used in DCA was channel borrowing. But with the emergence of cell sectorization and spatial division multiple access(SDMA) which are used to increase the capacity of cellular systems, the channel assignment faces a series of new problems. In this paper, a dynamic channel allocation scheme based on sectored cellular systems is proposed. By introducing intra-cell channel borrowing (borrowing channels from neighboring sectors) and inter-cell channel borrowing (borrowing channels from neighboring cells) methods, previous DCA strategies, including compact pattern based channel borrowing(CPCB) and greedy based dynamic channel assignment(GDCA) schemes proposed by the author, are improved significantly. The computer simulation shows that either intra-cell borrowing scheme or inter-cell borrowing scheme is efficient enough to uniform and non-uniform traffic service distributions.

  19. Influence of electric field on cellular migration

    Science.gov (United States)

    Guido, Isabella; Bodenschatz, Eberhard

    Cells have the ability to detect continuous current electric fields (EFs) and respond to them with a directed migratory movement. Dictyostelium discoideum (D.d.) cells, a key model organism for the study of eukaryotic chemotaxis, orient and migrate toward the cathode under the influence of an EF. The underlying sensing mechanism and whether it is shared by the chemotactic response pathway remains unknown. Whereas genes and proteins that mediate the electric sensing as well as that define the migration direction have been previously investigated in D.d. cells, a deeper knowledge about the cellular kinematic effects caused by the EF is still lacking. Here we show that besides triggering a directional bias the electric field influences the cellular kinematics by accelerating the movement of cells along their path. We found that the migratory velocity of the cells in an EF increases linearly with the exposure time. Through the analysis of the PI3K and Phg2 distribution in the cytosol and of the cellular adherence to the substrate we aim at elucidating whereas this speed up effect in the electric field is due to either a molecular signalling or the interaction with the substrate. This work is part of the MaxSynBio Consortium which is jointly funded by the Federal Ministry of Education and Research of Germany and the Max Planck Society.

  20. Literature Review on Dynamic Cellular Manufacturing System

    Science.gov (United States)

    Nouri Houshyar, A.; Leman, Z.; Pakzad Moghadam, H.; Ariffin, M. K. A. M.; Ismail, N.; Iranmanesh, H.

    2014-06-01

    In previous decades, manufacturers faced a lot of challenges because of globalization and high competition in markets. These problems arise from shortening product life cycle, rapid variation in demand of products, and also rapid changes in manufcaturing technologies. Nowadays most manufacturing companies expend considerable attention for improving flexibility and responsiveness in order to overcome these kinds of problems and also meet customer's needs. By considering the trend toward the shorter product life cycle, the manufacturing environment is towards manufacturing a wide variety of parts in small batches [1]. One of the major techniques which are applied for improving manufacturing competitiveness is Cellular Manufacturing System (CMS). CMS is type of manufacturing system which tries to combine flexibility of job shop and also productivity of flow shop. In addition, Dynamic cellular manufacturing system which considers different time periods for the manufacturing system becomes an important topic and attracts a lot of attention to itself. Therefore, this paper made attempt to have a brief review on this issue and focused on all published paper on this subject. Although, this topic gains a lot of attention to itself during these years, none of previous researchers focused on reviewing the literature of that which can be helpful and useful for other researchers who intend to do the research on this topic. Therefore, this paper is the first study which has focused and reviewed the literature of dynamic cellular manufacturing system.

  1. Cellular vs. organ approaches to dose estimates

    International Nuclear Information System (INIS)

    The cellular distribution of tissue-incorporated radionuclides has generally been neglected in the dosimetry of internal emitters. Traditional dosimetry assumes homogeneous distribution of radionuclides in organs of interest, while presuming that the ranges of particulate radiations are large relative to typical cell diameters. The macroscopic distribution of dose thus calculated has generally served as a sufficient approximation for the energy deposited within radiosensitive sites. However, with the increasing utilization of intracellular agents, such as thallium-201, it has become necessary to examine the microscopic distribution of energy at the cellular level. This is particularly important in the instance of radionuclides that decay by electron capture or by internal conversion with the release of Auger and Coster-Kronig electrons. In many instances, these electrons are released as a dense shower of low-energy particles with ranges of subcellular dimensions. The high electron density in the immediate vicinity of the decaying atom produces a focal deposition of energy that far exceeds the average dose taken over several cell diameters. These studies point out the increasing need to take into account the microscopic distribution of dose on the cellular level as radionuclides distributed in cells become more commonplace, especially if the decay involves electron capture or internal conversion. As radiotracers are developed for the measurement of intracellular functions these factors should be given greater consideration. 16 references, 5 figures, 5 tables

  2. Coordination of autophagy with other cellular activities

    Institute of Scientific and Technical Information of China (English)

    Yan WANG; Zheng-hong QIN

    2013-01-01

    The cell biological phenomenon of autophagy has attracted increasing attention in recent years,partly as a consequence of the discovery of key components of its cellular machinery.Autophagy plays a crucial role in a myriad of cellular functions.Autophagy has its own regulatory mechanisms,but this process is not isolated.Autophagy is coordinated with other cellular activities to maintain cell homeostasis.Autophagy is critical for a range of human physiological processes.The multifunctional roles of autophagy are explained by its ability to interact with several key components of various cell pathways.In this review,we focus on the coordination between autophagy and other physiological processes,including the ubiquitin-proteasome system (UPS),energy homeostasis,aging,programmed cell death,the immune responses,microbial invasion and inflammation.The insights gained from investigating autophagic networks should increase our understanding of their roles in human diseases and their potential as targets for therapeutic intervention.

  3. Pirin inhibits cellular senescence in melanocytic cells.

    Science.gov (United States)

    Licciulli, Silvia; Luise, Chiara; Scafetta, Gaia; Capra, Maria; Giardina, Giuseppina; Nuciforo, Paolo; Bosari, Silvano; Viale, Giuseppe; Mazzarol, Giovanni; Tonelli, Chiara; Lanfrancone, Luisa; Alcalay, Myriam

    2011-05-01

    Cellular senescence has been widely recognized as a tumor suppressing mechanism that acts as a barrier to cancer development after oncogenic stimuli. A prominent in vivo model of the senescence barrier is represented by nevi, which are composed of melanocytes that, after an initial phase of proliferation induced by activated oncogenes (most commonly BRAF), are blocked in a state of cellular senescence. Transformation to melanoma occurs when genes involved in controlling senescence are mutated or silenced and cells reacquire the capacity to proliferate. Pirin (PIR) is a highly conserved nuclear protein that likely functions as a transcriptional regulator whose expression levels are altered in different types of tumors. We analyzed the expression pattern of PIR in adult human tissues and found that it is expressed in melanocytes and has a complex pattern of regulation in nevi and melanoma: it is rarely detected in mature nevi, but is expressed at high levels in a subset of melanomas. Loss of function and overexpression experiments in normal and transformed melanocytic cells revealed that PIR is involved in the negative control of cellular senescence and that its expression is necessary to overcome the senescence barrier. Our results suggest that PIR may have a relevant role in melanoma progression. PMID:21514450

  4. Cellular membrane trafficking of mesoporous silica nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Fang, I-Ju [Iowa State Univ., Ames, IA (United States)

    2012-01-01

    This dissertation mainly focuses on the investigation of the cellular membrane trafficking of mesoporous silica nanoparticles. We are interested in the study of endocytosis and exocytosis behaviors of mesoporous silica nanoparticles with desired surface functionality. The relationship between mesoporous silica nanoparticles and membrane trafficking of cells, either cancerous cells or normal cells was examined. Since mesoporous silica nanoparticles were applied in many drug delivery cases, the endocytotic efficiency of mesoporous silica nanoparticles needs to be investigated in more details in order to design the cellular drug delivery system in the controlled way. It is well known that cells can engulf some molecules outside of the cells through a receptor-ligand associated endocytosis. We are interested to determine if those biomolecules binding to cell surface receptors can be utilized on mesoporous silica nanoparticle materials to improve the uptake efficiency or govern the mechanism of endocytosis of mesoporous silica nanoparticles. Arginine-glycine-aspartate (RGD) is a small peptide recognized by cell integrin receptors and it was reported that avidin internalization was highly promoted by tumor lectin. Both RGD and avidin were linked to the surface of mesoporous silica nanoparticle materials to investigate the effect of receptor-associated biomolecule on cellular endocytosis efficiency. The effect of ligand types, ligand conformation and ligand density were discussed in Chapter 2 and 3. Furthermore, the exocytosis of mesoporous silica nanoparticles is very attractive for biological applications. The cellular protein sequestration study of mesoporous silica nanoparticles was examined for further information of the intracellular pathway of endocytosed mesoporous silica nanoparticle materials. The surface functionality of mesoporous silica nanoparticle materials demonstrated selectivity among the materials and cancer and normal cell lines. We aimed to determine

  5. Progress of Studies on Effects of Acupuncture on Cellular Signal Transduction%针刺调节细胞信号转导的研究及思考

    Institute of Scientific and Technical Information of China (English)

    徐甜; 李忠仁

    2011-01-01

    为了进一步阐明针刺作用机制,对于细胞信号转导的研究日趋深入.本文从针刺的物理信号传入,起效的效应分子G蛋白,第二信使环磷酸腺苷、Ca2+、三磷酸肌醇、二酰基甘油,信号转导通路有丝分裂原激活的蛋白激酶、Janus激酶-信号转导转录激活因子、一氧化氮-环磷酸鸟苷等及细胞信号转导网络方面出发,系统分析了针刺刺激引发的细胞信号转导机制.认为应关注结缔组织信号网的研究,并应重视研究各条转导通路相互之间的关系,提出对于整体信号转导网络的探索应是未来的研究方向.%In order to elucidate the underlying mechanism of acupuncture in regulating different physiological functional activities at cellular level, abundant researches have been conducted on cellular signal transduction activities. The present article preliminarily analyzes acupuncture stimulation induced various cellular signaling pathways from the afferent physical signals of the regional mechanical stimulation at the acupoint, activation of receptors of the cellular membrane such as Guanine nucleotide binding protein coupled receptors, etc., intracellular second messenger molecules including cAMP, Ca2+ , inositol triphosphate, diacyl glycerol, etc., signal transduction pathways as mitogen-activated protein kinase, Janus kinase-signal transduction and transcription activator, nitrogen oxide-cyclic guanylic acid, etc., to the extremely complicated cellular signal transduction networks.In addition, the present paper also makes a discussion on the present developing situation of acupuncture research. It is possible that the connective tissue of the body surface will become a key point in the future research on acupuncture remedy. More attention should be paid to the interrelation among various intracellular signaling pathways and the network of cellular signal transduction in the research on acupuncture therapy for regulating a variety of

  6. Strong Correlation Between Concentrations of Tenofovir (TFV) Emtricitabine (FTC) in Hair and TFV Diphosphate and FTC Triphosphate in Dried Blood Spots in the iPrEx Open Label Extension: Implications for Pre-exposure Prophylaxis Adherence Monitoring.

    Science.gov (United States)

    Gandhi, Monica; Glidden, David V; Liu, Albert; Anderson, Peter L; Horng, Howard; Defechereux, Patricia; Guanira, Juan V; Grinsztejn, Beatriz; Chariyalertsak, Suwat; Bekker, Linda-Gail; Grant, Robert M

    2015-11-01

    Self-reported adherence to pre-exposure prophylaxis (PrEP) has limitations, raising interest in pharmacologic monitoring. Drug concentrations in hair and dried blood spots (DBS) are used to assess long-term-exposure; hair shipment/storage occurs at room temperature. The iPrEx Open Label Extension collected DBS routinely, with opt-in hair collection; concentrations were measured with liquid chromatography/tandem mass spectrometry. In 806 hair-DBS pairs, tenofovir (TFV) hair levels and TFV diphosphate (DP) in DBS were strongly correlated (Spearman coefficient r = 0.734; P hair TFV/DBS emtricitabine (FTC) triphosphate (TP) (r = 0.781; P hair FTC/DBS TFV-DP (r = 0.74; P hair FTC/DBS FTC-TP (r = 0.587; P Hair TFV/FTC concentrations correlate strongly with DBS levels, which are predictive of PrEP outcomes.

  7. Cellular Dynamic Simulator: An Event Driven Molecular Simulation Environment for Cellular Physiology

    Science.gov (United States)

    Byrne, Michael J.; Waxham, M. Neal; Kubota, Yoshihisa

    2010-01-01

    In this paper, we present the Cellular Dynamic Simulator (CDS) for simulating diffusion and chemical reactions within crowded molecular environments. CDS is based on a novel event driven algorithm specifically designed for precise calculation of the timing of collisions, reactions and other events for each individual molecule in the environment. Generic mesh based compartments allow the creation / importation of very simple or detailed cellular structures that exist in a 3D environment. Multiple levels of compartments and static obstacles can be used to create a dense environment to mimic cellular boundaries and the intracellular space. The CDS algorithm takes into account volume exclusion and molecular crowding that may impact signaling cascades in small sub-cellular compartments such as dendritic spines. With the CDS, we can simulate simple enzyme reactions; aggregation, channel transport, as well as highly complicated chemical reaction networks of both freely diffusing and membrane bound multi-protein complexes. Components of the CDS are generally defined such that the simulator can be applied to a wide range of environments in terms of scale and level of detail. Through an initialization GUI, a simple simulation environment can be created and populated within minutes yet is powerful enough to design complex 3D cellular architecture. The initialization tool allows visual confirmation of the environment construction prior to execution by the simulator. This paper describes the CDS algorithm, design implementation, and provides an overview of the types of features available and the utility of those features are highlighted in demonstrations. PMID:20361275

  8. Mapping of cellular iron using hyperspectral fluorescence imaging in a cellular model of Parkinson's disease

    Science.gov (United States)

    Oh, Eung Seok; Heo, Chaejeong; Kim, Ji Seon; Lee, Young Hee; Kim, Jong Min

    2013-05-01

    Parkinson's disease (PD) is characterized by progressive dopaminergic cell loss in the substantianigra (SN) and elevated iron levels demonstrated by autopsy and with 7-Tesla magnetic resonance imaging. Direct visualization of iron with live imaging techniques has not yet been successful. The aim of this study is to visualize and quantify the distribution of cellular iron using an intrinsic iron hyperspectral fluorescence signal. The 1-methyl-4-phenylpyridinium (MPP+)-induced cellular model of PD was established in SHSY5Y cells. The cells were exposed to iron by treatment with ferric ammonium citrate (FAC, 100 μM) for up to 6 hours. The hyperspectral fluorescence imaging signal of iron was examined usinga high- resolution dark-field optical microscope system with signal absorption for the visible/ near infrared (VNIR) spectral range. The 6-hour group showed heavy cellular iron deposition compared with the small amount of iron accumulation in the 1-hour group. The cellular iron was dispersed in a small, particulate form, whereas extracellular iron was detected in an aggregated form. In addition, iron particles were found to be concentrated on the cell membrane/edge of shrunken cells. The cellular iron accumulation readily occurred in MPP+-induced cells, which is consistent with previous studies demonstrating elevated iron levels in the SN in PD. This direct iron imaging methodology could be applied to analyze the physiological role of iron in PD, and its application might be expanded to various neurological disorders involving other metals, such as copper, manganese or zinc.

  9. Shape Memory Alloy-Based Periodic Cellular Structures Project

    Data.gov (United States)

    National Aeronautics and Space Administration — This SBIR Phase II effort will continue to develop and demonstrate an innovative shape memory alloy (SMA) periodic cellular structural technology. Periodic cellular...

  10. Matrix-induced fragmentation of P3′-N5′ phosphoramidate-containing DNA: high-throughput MALDI-TOF analysis of genomic sequence polymorphisms

    OpenAIRE

    Shchepinov, Mikhail S.; Denissenko, Mikhail F.; Smylie, Kevin J.; Wörl, Ralf J.; Leppin, A. Lorieta; Cantor, Charles R.; Rodi, Charles P.

    2001-01-01

    Chemical and enzymatic approaches were used to produce polynucleotide fragments containing acid-labile internucleotide P3′-N5′ phosphoramidate bonds, either in a surface-bound form or in solution. The primer extension reaction utilizing 5′-amino-5′-deoxynucleoside 5′-triphosphates generates polynucleotides that can be fragmented into short, easy-to-analyze pieces simply by being premixed with the acidic matrices typically used for MALDI-TOF mass spectrometry of nuc...

  11. Cellular proteins in influenza virus particles.

    Directory of Open Access Journals (Sweden)

    Megan L Shaw

    2008-06-01

    Full Text Available Virions are thought to contain all the essential proteins that govern virus egress from the host cell and initiation of replication in the target cell. It has been known for some time that influenza virions contain nine viral proteins; however, analyses of other enveloped viruses have revealed that proteins from the host cell can also be detected in virions. To address whether the same is true for influenza virus, we used two complementary mass spectrometry approaches to perform a comprehensive proteomic analysis of purified influenza virus particles. In addition to the aforementioned nine virus-encoded proteins, we detected the presence of 36 host-encoded proteins. These include both cytoplasmic and membrane-bound proteins that can be grouped into several functional categories, such as cytoskeletal proteins, annexins, glycolytic enzymes, and tetraspanins. Interestingly, a significant number of these have also been reported to be present in virions of other virus families. Protease treatment of virions combined with immunoblot analysis was used to verify the presence of the cellular protein and also to determine whether it is located in the core of the influenza virus particle. Immunogold labeling confirmed the presence of membrane-bound host proteins on the influenza virus envelope. The identification of cellular constituents of influenza virions has important implications for understanding the interactions of influenza virus with its host and brings us a step closer to defining the cellular requirements for influenza virus replication. While not all of the host proteins are necessarily incorporated specifically, those that are and are found to have an essential role represent novel targets for antiviral drugs and for attenuation of viruses for vaccine purposes.

  12. From Cellular Mechanotransduction to Biologically Inspired Engineering

    Science.gov (United States)

    Ingber, Donald E.

    2010-01-01

    This article is based on a lecture I presented as the recipient of the 2009 Pritzker Distinguished Lecturer Award at the Biomedical Engineering Society annual meeting in October 2009. Here, I review more than thirty years of research from my laboratory, beginning with studies designed to test the theory that cells use tensegrity (tensional integrity) architecture to stabilize their shape and sense mechanical signals, which I believed to be critical for control of cell function and tissue development. Although I was trained as a cell biologist, I found that the tools I had at my disposal were insufficient to experimentally test these theories, and thus I ventured into engineering to find critical solutions. This path has been extremely fruitful as it has led to confirmation of the critical role that physical forces play in developmental control, as well as how cells sense and respond to mechanical signals at the molecular level through a process known as cellular mechanotransduction. Many of the predictions of the cellular tensegrity model relating to cell mechanical behaviors have been shown to be valid, and this vision of cell structure led to discovery of the central role that transmembrane adhesion receptors, such as integrins, and the cytoskeleton play in mechanosensing and mechanochemical conversion. In addition, these fundamental studies have led to significant unexpected technology fallout, including development of micromagnetic actuators for non-invasive control of cellular signaling, microfluidic systems as therapeutic extracorporeal devices for sepsis therapy, and new DNA-based nanobiotechnology approaches that permit construction of artificial tensegrities that mimic properties of living materials for applications in tissue engineering and regenerative medicine. PMID:20140519

  13. Cellular heterogeneity and live cell arrays.

    Science.gov (United States)

    Walling, Maureen A; Shepard, Jason R E

    2011-07-01

    In the past decade, the tendency to move from a global, one-size-fits-all treatment philosophy to personalized medicine is based, in part, on the nuanced differences and sub-classifications of disease states. Our knowledge of these varied states stems from not only the ability to diagnose, classify, and perform experiments on cell populations as a whole, but also from new technologies that allow interrogation of cell populations at the individual cell level. Such departures from conventional thinking are driven by the recognition that clonal cell populations have numerous activities that manifest as significant levels of non-genetic heterogeneity. Clonal populations by definition originate from a single genetic origin so are regarded as having a high level of homogeneity as compared to genetically distinct cell populations. However, analysis at the single cell level has revealed a different phenomenon; cells and organisms require an inherent level of non-genetic heterogeneity to function properly, and in some cases, to survive. The growing understanding of this occurrence has lead to the development of methods to monitor, analyze, and better characterize the heterogeneity in cell populations. Following the trend of DNA- and protein microarrays, platforms capable of simultaneously monitoring each cell in a population have been developed. These cellular microarray platforms and other related formats allow for continuous monitoring of single live cells and simultaneously generate individual cell and average population data that are more descriptive and information-rich than traditional bulk methods. These technological advances have helped develop a better understanding of the intricacies associated with biological processes and afforded greater insight into complex biological systems. The associated instruments, techniques, and reagents now allow for highly multiplexed analyses, which enable multiple cellular activities, processes, or pathways to be monitored

  14. Probing cellular behaviors through nanopatterned chitosan membranes

    International Nuclear Information System (INIS)

    This paper describes a high-throughput method for developing physically modified chitosan membranes to probe the cellular behavior of MDCK epithelial cells and HIG-82 fibroblasts adhered onto these modified membranes. To prepare chitosan membranes with micro/nanoscaled features, we have demonstrated an easy-to-handle, facile approach that could be easily integrated with IC-based manufacturing processes with mass production potential. These physically modified chitosan membranes were observed by scanning electron microscopy to gain a better understanding of chitosan membrane surface morphology. After MDCK cells and HIG-82 fibroblasts were cultured on these modified chitosan membranes for various culture durations (i.e. 1, 2, 4, 12 and 24 h), they were investigated to decipher cellular behavior. We found that both cells preferred to adhere onto a flat surface rather than on a nanopatterned surface. However, most (> 80%) of the MDCK cells showed rounded morphology and would suspend in the cultured medium instead of adhering onto the planar surface of negatively nanopatterned chitosan membranes. This means different cell types (e.g. fibroblasts versus epithelia) showed distinct capabilities/preferences of adherence for materials of varying surface roughness. We also showed that chitosan membranes could be re-used at least nine times without significant contamination and would provide us consistency for probing cell–material interactions by permitting reuse of the same substrate. We believe these results would provide us better insight into cellular behavior, specifically, microscopic properties and characteristics of cells grown under unique, nanopatterned cell-interface conditions. (paper)

  15. Microwave components for cellular portable radiotelephone

    Science.gov (United States)

    Muraguchi, Masahiro; Aikawa, Masayoshi

    1995-09-01

    Mobile and personal communication systems are expected to represent a huge market for microwave components in the coming years. A number of components in silicon bipolar, silicon Bi-CMOS, GaAs MESFET, HBT and HEMT are now becoming available for system application. There are tradeoffs among the competing technologies with regard to performance, cost, reliability and time-to-market. This paper describes process selection and requirements of cost and r.f. performances to microwave semiconductor components for digital cellular and cordless telephones. Furthermore, new circuit techniques which were developed by NTT are presented.

  16. Imaging Cellular Architecture with X-rays

    OpenAIRE

    Larabell, Carolyn A.; Nugent, Keith A.

    2010-01-01

    X-ray imaging of biological samples is progressing rapidly. In this paper we review the progress to date in high resolution imaging of cellular architecture. In particular we survey the progress in soft X-ray tomography and argue that the field is coming of age and that important biological insights are starting to emerge. We then review the new ideas based on coherent diffraction. These methods are at a much earlier stage of development but, as they eliminate the need for X-ray optics, have ...

  17. Cellular and physical mechanisms of branching morphogenesis

    Science.gov (United States)

    Varner, Victor D.; Nelson, Celeste M.

    2014-01-01

    Branching morphogenesis is the developmental program that builds the ramified epithelial trees of various organs, including the airways of the lung, the collecting ducts of the kidney, and the ducts of the mammary and salivary glands. Even though the final geometries of epithelial trees are distinct, the molecular signaling pathways that control branching morphogenesis appear to be conserved across organs and species. However, despite this molecular homology, recent advances in cell lineage analysis and real-time imaging have uncovered surprising differences in the mechanisms that build these diverse tissues. Here, we review these studies and discuss the cellular and physical mechanisms that can contribute to branching morphogenesis. PMID:25005470

  18. Effect of cellular mobility on immune response

    Science.gov (United States)

    Pandey, R. B.; Mannion, R.; Ruskin, H. J.

    2000-08-01

    Mobility of cell types in our HIV immune response model is subject to an intrinsic mobility and an explicit directed mobility, which is governed by Pmob. We investigate how restricting the explicit mobility, while maintaining the innate mobility of a viral-infected cell, affects the model's results. We find that increasing the explicit mobility of the immune system cells leads to viral dominance for certain levels of viral mutation. We conclude that increasing immune system cellular mobility indirectly increases the virus’ inherent mobility.

  19. Cellular spaces, null spaces and homotopy localization

    CERN Document Server

    Farjoun, Emmanuel Dror

    1996-01-01

    In this monograph we give an exposition of some recent development in homotopy theory. It relates to advances in periodicity in homotopy localization and in cellular spaces. The notion of homotopy localization is treated quite generally and encompasses all the known idempotent homotopy functors. It is applied to K-theory localizations, to Morava-theories, to Hopkins-Smith theory of types. The method of homotopy colimits is used heavily. It is written with an advanced graduate student in topology and research homotopy theorist in mind.

  20. Wireless communications, cellular phones and relay antennas

    International Nuclear Information System (INIS)

    Wireless communications using radiofrequency fields (RF) have seen an increasing use with the massive deployment of cellular systems GSM, UMTS and now LTE. In parallel, public concerns have been raised about possible health effects. During the last decade, about 10 million Euros per year have been dedicated to research. In vivo, in vitro, animal and human studies have been carried out. This paper gives an overview of the subject. The applicable limits and regulation as well as the typical human exposure are presented. The state of knowledge on biological and health effect is summarized. The recent classification of RF by the IARC and some sociological aspects are also discussed. (authors)

  1. Cellular automata modelling of hantarvirus infection

    Energy Technology Data Exchange (ETDEWEB)

    Abdul Karim, Mohamad Faisal [School of Distance Education, Universiti Sains Malaysia, Minden 11800, Penang (Malaysia)], E-mail: faisal@usm.my; Md Ismail, Ahmad Izani [School of Mathematical Sciences, Universiti Sains Malaysia, Minden 11800, Penang (Malaysia)], E-mail: izani@cs.usm.my; Ching, Hoe Bee [School of Mathematical Sciences, Universiti Sains Malaysia, Minden 11800, Penang (Malaysia)], E-mail: Bee_Ching_Janice_Hoe@dell.com

    2009-09-15

    Hantaviruses are a group of viruses which have been identified as being responsible for the outbreak of diseases such as the hantavirus pulmonary syndrome. In an effort to understand the characteristics and dynamics of hantavirus infection, mathematical models based on differential equations have been developed and widely studied. However, such models neglect the local characteristics of the spreading process and do not include variable susceptibility of individuals. In this paper, we develop an alternative approach based on cellular automata to analyze and study the spatiotemporal patterns of hantavirus infection.

  2. Single spin measurement using cellular automata techniques

    CERN Document Server

    Perez-Delgado, C A; Cory, D G; Mosca, M; Cappellaro, Paola; Cory, David G.; Mosca, Michele; Perez-Delgado, Carlos A.

    2006-01-01

    We propose an approach for single spin measurement. Our method uses techniques from the theory of quantum cellular automata to correlate a large amount of ancillary spins to the one to be measured. It has the distinct advantage of being efficient, and to a certain extent fault-tolerant. Under ideal conditions, it requires the application of only order of cube root of N steps (each requiring a constant number of rf pulses) to create a system of N correlated spins. It is also fairly robust against pulse errors, imperfect initial polarization of the ancilla spin system, and does not rely on entanglement. We study the scalability of our scheme through numerical simulation.

  3. Single spin measurement using cellular automata techniques

    OpenAIRE

    Perez-Delgado, Carlos A.; Mosca, Michele; Cappellaro, Paola; Cory, David G.

    2006-01-01

    We propose an approach for single spin measurement. Our method uses techniques from the theory of quantum cellular automata to correlate a large amount of ancillary spins to the one to be measured. It has the distinct advantage of being efficient, and to a certain extent fault-tolerant. Under ideal conditions, it requires the application of only order of cube root of N steps (each requiring a constant number of rf pulses) to create a system of N correlated spins. It is also fairly robust agai...

  4. Cellular automata modeling of pedestrian's crossing dynamics

    Institute of Scientific and Technical Information of China (English)

    张晋; 王慧; 李平

    2004-01-01

    Cellular automata modeling techniques and the characteristics of mixed traffic flow were used to derive the 2-dimensional model presented here for simulation of pedestrian's crossing dynamics.A conception of "stop point" is introduced to deal with traffic obstacles and resolve conflicts among pedestrians or between pedestrians and the other vehicles on the crosswalk.The model can be easily extended,is very efficient for simulation of pedestrian's crossing dynamics,can be integrated into traffic simulation software,and has been proved feasible by simulation experiments.

  5. Cellular trafficking of nicotinic acetylcholine receptors

    Institute of Scientific and Technical Information of China (English)

    Paul A ST JOHN

    2009-01-01

    Nicotinic acetylcholine receptors (nAChRs) play critical roles throughout the body. Precise regulation of the cellular location and availability of nAChRs on neurons and target cells is critical to their proper function. Dynamic, post-translational regulation of nAChRs, particularly control of their movements among the different compartments of cells, is an important aspect of that regulation. A combination of new information and new techniques has the study of nAChR trafficking poised for new breakthroughs.

  6. Propagation Mechanism of Cylindrical Cellular Detonation

    Science.gov (United States)

    Han, Wen-Hu; Wang, Cheng; Ning, Jian-Guo

    2012-10-01

    We investigate the evolution of cylindrical cellular detonation with different instabilities. The numerical results show that with decreasing initial temperature, detonation becomes more unstable and the cells of the cylindrical detonation tend to be irregular. For stable detonation, a divergence of cylindrical detonation cells is formed eventually due to detonation instability resulting from a curved detonation front. For mildly unstable detonation, local overdriven detonation occurs. The detonation cell diverges and its size decreases. For highly unstable detonation, locally driven detonation is more obvious and the front is highly wrinkled. As a result, the diverging cylindrical detonation cell becomes highly irregular.

  7. Immunometabolism: Cellular Metabolism Turns Immune Regulator.

    Science.gov (United States)

    Loftus, Róisín M; Finlay, David K

    2016-01-01

    Immune cells are highly dynamic in terms of their growth, proliferation, and effector functions as they respond to immunological challenges. Different immune cells can adopt distinct metabolic configurations that allow the cell to balance its requirements for energy, molecular biosynthesis, and longevity. However, in addition to facilitating immune cell responses, it is now becoming clear that cellular metabolism has direct roles in regulating immune cell function. This review article describes the distinct metabolic signatures of key immune cells, explains how these metabolic setups facilitate immune function, and discusses the emerging evidence that intracellular metabolism has an integral role in controlling immune responses. PMID:26534957

  8. Conference on radionuclide labelled cellular blood elements

    International Nuclear Information System (INIS)

    The South African Medical Research Council presented this conference on radionuclide labelled cellular blood elements with application in atherosclerosis and thrombosis. The conference was held in Bloemfontein from 3-6 February 1986. This work only consists of the abstracts of the seminars that were delivered on the conference. The radioisotopes that occur most of the time in the abstracts include Indium 111, Indium 114, Chromium 51, Iodine 125, Iodine 131 and Carbon 14. Especially Indium 111 seems to be the method of choice for all labelling

  9. Cellular Scaling Rules for Primate Spinal Cords

    OpenAIRE

    Burish, Mark J.; Peebles, J. Klint; Baldwin, Mary K.; Tavares, Luciano; Kaas, Jon H.; Herculano-Houzel, Suzana

    2010-01-01

    The spinal cord can be considered a major sensorimotor interface between the body and the brain. How does the spinal cord scale with body and brain mass, and how are its numbers of neurons related to the number of neurons in the brain across species of different body and brain sizes? Here we determine the cellular composition of the spinal cord in eight primate species and find that its number of neurons varies as a linear function of cord length, and accompanies body mass raised to an expone...

  10. A Computation in a Cellular Automaton Collider Rule 110

    CERN Document Server

    Martinez, Genaro J; McIntosh, Harold V

    2016-01-01

    A cellular automaton collider is a finite state machine build of rings of one-dimensional cellular automata. We show how a computation can be performed on the collider by exploiting interactions between gliders (particles, localisations). The constructions proposed are based on universality of elementary cellular automaton rule 110, cyclic tag systems, supercolliders, and computing on rings.

  11. 47 CFR 32.5003 - Cellular mobile revenue.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular mobile revenue. 32.5003 Section 32... SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES Instructions For Revenue Accounts § 32.5003 Cellular mobile revenue. This account shall include message revenue derived from cellular...

  12. Feasibility investigation of a cellularly organized data processor

    Science.gov (United States)

    Minnick, R. C.; Jump, J. R.; Arnold, R. G.; Beirne, J. M.

    1972-01-01

    The application of cellular arrays to NASA missions was studied. Cellular arrays are iterative logical and memory structures which can be programmed to accomplish a wide variety of logical tasks. Used in long-duration space missions, spare cellular arrays can be remotely programmed to replace faulty logical subsystems as the need arises.

  13. Dynamics of active cellular response under stress

    Science.gov (United States)

    de, Rumi; Zemel, Assaf; Safran, Samuel

    2008-03-01

    Forces exerted by and on adherent cells are important for many physiological processes such as wound healing and tissue formation. In addition, recent experiments have shown that stem cell differentiation is controlled, at least in part, by the elasticity of the surrounding matrix. Using a simple theoretical model that includes the forces due to both the mechanosensitive nature of cells and the elastic response of the matrix, we predict the dynamics of orientation of cells. The model predicts many features observed in measurements of cellular forces and orientation including the increase with time of the forces generated by cells in the absence of applied stress and the consequent decrease of the force in the presence of quasi-static stresses. We also explain the puzzling observation of parallel alignment of cells for static and quasi-static stresses and of nearly perpendicular alignment for dynamically varying stresses. In addition, we predict the response of the cellular orientation to a sinusoidally varying applied stress as a function of frequency. The dependence of the cell orientation angle on the Poisson ratio of the surrounding material can be used to distinguish systems in which cell activity is controlled by stress from those where cell activity is controlled by strain. Reference: Nature Physics, vol. 3, pp 655 (2007).

  14. Huntington's disease: implications of associated cellular radiosensitivity

    International Nuclear Information System (INIS)

    Ionizing radiation sensitivity was studied in a series of Huntington's Disease (HD) patients and controls by measurement of radiation-induced chromosome aberrations in lymphocytes and by clonogenic survival of lymphoblastoid cell lines. As a group, HD patients were found to be significantly more radioisensitive than controls (p<0.001), but there was an overlap between values for the two groups such that an absolute distinction is not possible. These data are consistent with an association between HD and radiosensitivity but not with identity between HD and a radiosensitive phenotype, so that cellular radiosensitivity cannot be used for individual diagnosis. Analysis of three families including 5 HD patients and 11 first-degree relatives confirmed this conclusion and demonstrated that even within a given family presymptomatic diagnosis cannot be based on measurement of radiosensitivity. However, the common association of cellular radiosensitivity with HD probands and their families provides a potential lead to the identification of HD gene(s) and so to an eventual understanding of the aetiopathogenesis of this disease at the molecular level. (author)

  15. Cellular Prion Protein: From Physiology to Pathology

    Directory of Open Access Journals (Sweden)

    Yutaka Kikuchi

    2012-11-01

    Full Text Available The human cellular prion protein (PrPC is a glycosylphosphatidylinositol (GPI anchored membrane glycoprotein with two N-glycosylation sites at residues 181 and 197. This protein migrates in several bands by Western blot analysis (WB. Interestingly, PNGase F treatment of human brain homogenates prior to the WB, which is known to remove the N-glycosylations, unexpectedly gives rise to two dominant bands, which are now known as C-terminal (C1 and N-terminal (N1 fragments. This resembles the β-amyloid precursor protein (APP in Alzheimer disease (AD, which can be physiologically processed by α-, β-, and γ-secretases. The processing of APP has been extensively studied, while the identity of the cellular proteases involved in the proteolysis of PrPC and their possible role in prion biology has remained limited and controversial. Nevertheless, there is a strong correlation between the neurotoxicity caused by prion proteins and the blockade of their normal proteolysis. For example, expression of non-cleavable PrPC mutants in transgenic mice generates neurotoxicity, even in the absence of infectious prions, suggesting that PrPC proteolysis is physiologically and pathologically important. As many mouse models of prion diseases have recently been developed and the knowledge about the proteases responsible for the PrPC proteolysis is accumulating, we examine the historical experimental evidence and highlight recent studies that shed new light on this issue.

  16. A Mathematical Model for Cisplatin Cellular Pharmacodynamics

    Directory of Open Access Journals (Sweden)

    Ardith W. El-Kareh

    2003-03-01

    Full Text Available A simple theoretical model for the cellular pharmacodynamics of cisplatin is presented. The model, which takes into account the kinetics of cisplatin uptake by cells and the intracellular binding of the drug, can be used to predict the dependence of survival (relative to controls on the time course of extracellular exposure. Cellular pharmacokinetic parameters are derived from uptake data for human ovarian and head and neck cancer cell lines. Survival relative to controls is assumed to depend on the peak concentration of DNA-bound intracellular platinum. Model predictions agree well with published data on cisplatin cytotoxicity for three different cancer cell lines, over a wide range of exposure times. In comparison with previously published mathematical models for anticancer drug pharmacodynamics, the present model provides a better fit to experimental data sets including long exposure times (∼100 hours. The model provides a possible explanation for the fact that cell kill correlates well with area under the extracellular concentration-time curve in some data sets, but not in others. The model may be useful for optimizing delivery schedules and for the dosing of cisplatin for cancer therapy.

  17. Impaired nonspecific cellular immunity in experimental cholestasis.

    Science.gov (United States)

    Roughneen, P T; Drath, D B; Kulkarni, A D; Rowlands, B J

    1987-11-01

    The abilities of polymorphonuclear leukocytes (PMN) and pulmonary alveolar macrophages (PAM), to demonstrate chemotaxis, phagocytosis, and superoxide release after bile duct ligation in the rat were investigated to determine the effect of cholestasis on nonspecific cellular immune mechanisms. Chemotactic response to C5a and FMLP, phagocytosis of 14C labeled Staphylococcus aureus, and zymosan-induced superoxide release were evaluated 21 days after bile duct ligation (BDL), sham operation, or in normal controls. Serum total bilirubin level was elevated after BDL (p less than 0.01). Chemotactic ability was similar to each group. PMN phagocytic uptake of 14C labeled Staphylococcus aureus was depressed in BDL (p less than 0.05). BDL rats exhibited impaired PAM phagocytic indices and improved PMN superoxide release (p less than 0.03). PAM superoxide release was similar in each study group. Alterations in phagocytic function with cholestasis are important deficits in nonspecific cellular immunity that may contribute to the high incidence of infective complications associated with obstructive jaundice. PMID:2823730

  18. EFFECTIVENESS OF CELLULAR INJECTION MOLDING PROCESS

    Directory of Open Access Journals (Sweden)

    Tomasz Garbacz

    2013-06-01

    Full Text Available In a study of cellular injection, molding process uses polyvinylchloride PVC. Polymers modified with introducing blowing agents into them in the Laboratory of the Department of Technologies and Materiase of Technical University of Kosice. For technological reasons, blowing agents have a form of granules. In the experiment, the content of the blowing agent (0–2,0 % by mass fed into the processed polymer was adopted as a variable factor. In the studies presented in the article, the chemical blowing agents occurring in the granulated form with a diameter of 1.2 to 1.4 mm were used. The view of the technological line for cellular injection molding and injection mold cavity with injection moldings are shown in Figure 1. The results of the determination of selected properties of injection molded parts for various polymeric materials, obtained with different content of blowing agents, are shown in Figures 4-7. Microscopic examination of cross-sectional structure of the moldings were obtained using the author's position image analysis of porous structure. Based on analysis of photographs taken (Figures 7, 8, 9 it was found that the coating containing 1.0% of blowing agents is a clearly visible solid outer layer and uniform distribution of pores and their sizes are similar.

  19. Single-Molecule Imaging of Cellular Signaling

    Science.gov (United States)

    De Keijzer, Sandra; Snaar-Jagalska, B. Ewa; Spaink, Herman P.; Schmidt, Thomas

    Single-molecule microscopy is an emerging technique to understand the function of a protein in the context of its natural environment. In our laboratory this technique has been used to study the dynamics of signal transduction in vivo. A multitude of signal transduction cascades are initiated by interactions between proteins in the plasma membrane. These cascades start by binding a ligand to its receptor, thereby activating downstream signaling pathways which finally result in complex cellular responses. To fully understand these processes it is important to study the initial steps of the signaling cascades. Standard biological assays mostly call for overexpression of the proteins and high concentrations of ligand. This sets severe limits to the interpretation of, for instance, the time-course of the observations, given the large temporal spread caused by the diffusion-limited binding processes. Methods and limitations of single-molecule microscopy for the study of cell signaling are discussed on the example of the chemotactic signaling of the slime-mold Dictyostelium discoideum. Single-molecule studies, as reviewed in this chapter, appear to be one of the essential methodologies for the full spatiotemporal clarification of cellular signaling, one of the ultimate goals in cell biology.

  20. CUSTOMER SATISFACTION MEASUREMENT TOWARDS IDEA CELLULAR

    Directory of Open Access Journals (Sweden)

    Yousef Mehdipour

    2013-05-01

    Full Text Available Measuring customer satisfaction provides an indication of how successful the organization is at providing products and/or services to the marketplace. Customer satisfaction is a collective outcome of perception, evaluation, and psychological reactions to the consumption experience with a product or service. This researcharticle investigated the attitude of Idea cellular customers to Idea services. All the customers of Idea cellular in Hyderabad city (Andhra Pradesh constituted the population. The sample of the study is 2000 customers that randomly selected. A questionnaire was developed and validated through pilot testing and administered to thesample for the collection of data. The researcher personally visited respondents, thus 100% data were collected.The collected data were tabulated and analyzed by SPSS. Results showed that majority of the respondents of Idea prefer post-paid service than to pre paid and largest segment of respondents are of idea then comes Cell one, Airtel and Vodafone. this study showed that most of the respondents need improvement in service. Majority of respondents gave an excellent rate for “Idea Cellular” services.

  1. Cellular contractility requires ubiquitin mediated proteolysis.

    Directory of Open Access Journals (Sweden)

    Yuval Cinnamon

    Full Text Available BACKGROUND: Cellular contractility, essential for cell movement and proliferation, is regulated by microtubules, RhoA and actomyosin. The RhoA dependent kinase ROCK ensures the phosphorylation of the regulatory Myosin II Light Chain (MLC Ser19, thereby activating actomyosin contractions. Microtubules are upstream inhibitors of contractility and their depolymerization or depletion cause cells to contract by activating RhoA. How microtubule dynamics regulates RhoA remains, a major missing link in understanding contractility. PRINCIPAL FINDINGS: We observed that contractility is inhibited by microtubules not only, as previously reported, in adherent cells, but also in non-adhering interphase and mitotic cells. Strikingly we observed that contractility requires ubiquitin mediated proteolysis by a Cullin-RING ubiquitin ligase. Inhibition of proteolysis, ubiquitination and neddylation all led to complete cessation of contractility and considerably reduced MLC Ser19 phosphorylation. CONCLUSIONS: Our results imply that cells express a contractility inhibitor that is degraded by ubiquitin mediated proteolysis, either constitutively or in response to microtubule depolymerization. This degradation seems to depend on a Cullin-RING ubiquitin ligase and is required for cellular contractions.

  2. A new description of cellular quiescence.

    Directory of Open Access Journals (Sweden)

    Hilary A Coller

    2006-03-01

    Full Text Available Cellular quiescence, defined as reversible growth/proliferation arrest, is thought to represent a homogenous state induced by diverse anti-mitogenic signals. We used transcriptional profiling to characterize human diploid fibroblasts that exited the cell cycle after exposure to three independent signals--mitogen withdrawal, contact inhibition, and loss of adhesion. We show here that each signal caused regulation of a unique set of genes known to be important for cessation of growth and division. Therefore, contrary to expectation, cells enter different quiescent states that are determined by the initiating signal. However, underlying this diversity we discovered a set of genes whose specific expression in non-dividing cells was signal-independent, and therefore representative of quiescence per se, rather than the signal that induced it. This fibroblast "quiescence program" contained genes that enforced the non-dividing state, and ensured the reversibility of the cell cycle arrest. We further demonstrate that one mechanism by which the reversibility of quiescence is insured is the suppression of terminal differentiation. Expression of the quiescence program was not simply a downstream consequence of exit from the cell cycle, because key parts, including those involved in suppressing differentiation, were not recapitulated during the cell cycle arrest caused by direct inhibition of cyclin-dependent kinases. These studies form a basis for understanding the normal biology of cellular quiescence.

  3. Engineering Cellular Photocomposite Materials Using Convective Assembly

    Directory of Open Access Journals (Sweden)

    Orlin D. Velev

    2013-05-01

    Full Text Available Fabricating industrial-scale photoreactive composite materials containing living cells, requires a deposition strategy that unifies colloid science and cell biology. Convective assembly can rapidly deposit suspended particles, including whole cells and waterborne latex polymer particles into thin (<10 µm thick, organized films with engineered adhesion, composition, thickness, and particle packing. These highly ordered composites can stabilize the diverse functions of photosynthetic cells for use as biophotoabsorbers, as artificial leaves for hydrogen or oxygen evolution, carbon dioxide assimilation, and add self-cleaning capabilities for releasing or digesting surface contaminants. This paper reviews the non-biological convective assembly literature, with an emphasis on how the method can be modified to deposit living cells starting from a batch process to its current state as a continuous process capable of fabricating larger multi-layer biocomposite coatings from diverse particle suspensions. Further development of this method will help solve the challenges of engineering multi-layered cellular photocomposite materials with high reactivity, stability, and robustness by clarifying how process, substrate, and particle parameters affect coating microstructure. We also describe how these methods can be used to selectively immobilize photosynthetic cells to create biomimetic leaves and compare these biocomposite coatings to other cellular encapsulation systems.

  4. Cellular Auxin Homeostasis:Gatekeeping Is Housekeeping

    Institute of Scientific and Technical Information of China (English)

    Michel Ruiz Rosquete; Elke Barbez; Jürgen Kleine-Vehn

    2012-01-01

    The phytohormone auxin is essential for plant development and contributes to nearly every aspect of the plant life cycle.The spatio-temporal distribution of auxin depends on a complex interplay between auxin metabolism and cell-to-cell auxin transport.Auxin metabolism and transport are both crucial for plant development;however,it largely remains to be seen how these processes are integrated to ensure defined cellular auxin levels or even gradients within tissues or organs.In this review,we provide a glance at very diverse topics of auxin biology,such as biosynthesis,conjugation,oxidation,and transport of auxin.This broad,but certainly superficial,overview highlights the mutual importance of auxin metabolism and transport.Moreover,it allows pinpointing how auxin metabolism and transport get integrated to jointly regulate cellular auxin homeostasis.Even though these processes have been so far only separately studied,we assume that the phytohormonal crosstalk integrates and coordinates auxin metabolism and transport.Besides the integrative power of the global hormone signaling,we additionally introduce the hypothetical concept considering auxin transport components as gatekeepers for auxin responses.

  5. Piezoelectric nanoribbons for monitoring cellular deformations

    Science.gov (United States)

    Nguyen, Thanh D.; Deshmukh, Nikhil; Nagarah, John M.; Kramer, Tal; Purohit, Prashant K.; Berry, Michael J.; McAlpine, Michael C.

    2012-09-01

    Methods for probing mechanical responses of mammalian cells to electrical excitations can improve our understanding of cellular physiology and function. The electrical response of neuronal cells to applied voltages has been studied in detail, but less is known about their mechanical response to electrical excitations. Studies using atomic force microscopes (AFMs) have shown that mammalian cells exhibit voltage-induced mechanical deflections at nanometre scales, but AFM measurements can be invasive and difficult to multiplex. Here we show that mechanical deformations of neuronal cells in response to electrical excitations can be measured using piezoelectric PbZrxTi1-xO3 (PZT) nanoribbons, and we find that cells deflect by 1 nm when 120 mV is applied to the cell membrane. The measured cellular forces agree with a theoretical model in which depolarization caused by an applied voltage induces a change in membrane tension, which results in the cell altering its radius so that the pressure remains constant across the membrane. We also transfer arrays of PZT nanoribbons onto a silicone elastomer and measure mechanical deformations on a cow lung that mimics respiration. The PZT nanoribbons offer a minimally invasive and scalable platform for electromechanical biosensing.

  6. Astrobiological complexity with probabilistic cellular automata.

    Science.gov (United States)

    Vukotić, Branislav; Ćirković, Milan M

    2012-08-01

    The search for extraterrestrial life and intelligence constitutes one of the major endeavors in science, but has yet been quantitatively modeled only rarely and in a cursory and superficial fashion. We argue that probabilistic cellular automata (PCA) represent the best quantitative framework for modeling the astrobiological history of the Milky Way and its Galactic Habitable Zone. The relevant astrobiological parameters are to be modeled as the elements of the input probability matrix for the PCA kernel. With the underlying simplicity of the cellular automata constructs, this approach enables a quick analysis of large and ambiguous space of the input parameters. We perform a simple clustering analysis of typical astrobiological histories with "Copernican" choice of input parameters and discuss the relevant boundary conditions of practical importance for planning and guiding empirical astrobiological and SETI projects. In addition to showing how the present framework is adaptable to more complex situations and updated observational databases from current and near-future space missions, we demonstrate how numerical results could offer a cautious rationale for continuation of practical SETI searches. PMID:22832998

  7. Tension and robustness in multitasking cellular networks.

    Directory of Open Access Journals (Sweden)

    Jeffrey V Wong

    Full Text Available Cellular networks multitask by exhibiting distinct, context-dependent dynamics. However, network states (parameters that generate a particular dynamic are often sub-optimal for others, defining a source of "tension" between them. Though multitasking is pervasive, it is not clear where tension arises, what consequences it has, and how it is resolved. We developed a generic computational framework to examine the source and consequences of tension between pairs of dynamics exhibited by the well-studied RB-E2F switch regulating cell cycle entry. We found that tension arose from task-dependent shifts in parameters associated with network modules. Although parameter sets common to distinct dynamics did exist, tension reduced both their accessibility and resilience to perturbation, indicating a trade-off between "one-size-fits-all" solutions and robustness. With high tension, robustness can be preserved by dynamic shifting of modules, enabling the network to toggle between tasks, and by increasing network complexity, in this case by gene duplication. We propose that tension is a general constraint on the architecture and operation of multitasking biological networks. To this end, our work provides a framework to quantify the extent of tension between any network dynamics and how it affects network robustness. Such analysis would suggest new ways to interfere with network elements to elucidate the design principles of cellular networks.

  8. Cellular distributions of monocarboxylate transporters: a review.

    Science.gov (United States)

    Iwanaga, Toshihiko; Kishimoto, Ayuko

    2015-01-01

    Lactate and ketone bodies play important roles as alternative energy substrates, especially in conditions with a decreased utility of glucose. Short-chain fatty acids (acetate, propionate, and butyrate), produced by bacterial fermentation, supply most of the energy substrates in ruminants such as the cow and sheep. These monocarboxylates are transfered through the plasma membrane by proton-coupled monocarboxylate transporters (MCTs) and sodium-coupled MCTs (SMCTs). To reveal the metabolism and functional significance of monocarboxylates, the cellular localization of MCTs and SMCTs together with the expressed intensities holds great importance. This paper reviews the immunohistochemical localization of SMCTs and major MCT subtypes throughout the mammalian body. MCTs and SMCTs display a selective membrane-bound localization with porality. In contrast to the limited expression of SMCTs in the intestine and kidney, MCTs display a broader distribution pattern than GLUTs. The brain, kidney, placenta, and male genital tract express multiple subtypes of the MCT family. Determination of the cellular localization of MCTs is most controversial in the brain, possibly due to regional differences and the transcriptional modification of MCT proteins. Information on the localization of MCTs and SMCTs aids in understanding the nutrient absorption and metabolism throughout the mammalian body. In some cases, the body may use monocarboxylates as signal molecules, like hormones. PMID:26522146

  9. Mechanisms of cellular invasion by intracellular parasites.

    Science.gov (United States)

    Walker, Dawn M; Oghumu, Steve; Gupta, Gaurav; McGwire, Bradford S; Drew, Mark E; Satoskar, Abhay R

    2014-04-01

    Numerous disease-causing parasites must invade host cells in order to prosper. Collectively, such pathogens are responsible for a staggering amount of human sickness and death throughout the world. Leishmaniasis, Chagas disease, toxoplasmosis, and malaria are neglected diseases and therefore are linked to socio-economical and geographical factors, affecting well-over half the world's population. Such obligate intracellular parasites have co-evolved with humans to establish a complexity of specific molecular parasite-host cell interactions, forming the basis of the parasite's cellular tropism. They make use of such interactions to invade host cells as a means to migrate through various tissues, to evade the host immune system, and to undergo intracellular replication. These cellular migration and invasion events are absolutely essential for the completion of the lifecycles of these parasites and lead to their for disease pathogenesis. This review is an overview of the molecular mechanisms of protozoan parasite invasion of host cells and discussion of therapeutic strategies, which could be developed by targeting these invasion pathways. Specifically, we focus on four species of protozoan parasites Leishmania, Trypanosoma cruzi, Plasmodium, and Toxoplasma, which are responsible for significant morbidity and mortality.

  10. Rhabdomyosarcoma: Advances in Molecular and Cellular Biology

    Directory of Open Access Journals (Sweden)

    Xin Sun

    2015-01-01

    Full Text Available Rhabdomyosarcoma (RMS is the most common soft tissue malignancy in childhood and adolescence. The two major histological subtypes of RMS are alveolar RMS, driven by the fusion protein PAX3-FKHR or PAX7-FKHR, and embryonic RMS, which is usually genetically heterogeneous. The prognosis of RMS has improved in the past several decades due to multidisciplinary care. However, in recent years, the treatment of patients with metastatic or refractory RMS has reached a plateau. Thus, to improve the survival rate of RMS patients and their overall well-being, further understanding of the molecular and cellular biology of RMS and identification of novel therapeutic targets are imperative. In this review, we describe the most recent discoveries in the molecular and cellular biology of RMS, including alterations in oncogenic pathways, miRNA (miR, in vivo models, stem cells, and important signal transduction cascades implicated in the development and progression of RMS. Furthermore, we discuss novel potential targeted therapies that may improve the current treatment of RMS.

  11. Cellular factors implicated in filovirus entry.

    Science.gov (United States)

    Bhattacharyya, Suchita; Hope, Thomas J

    2013-01-01

    Although filoviral infections are still occurring in different parts of the world, there are no effective preventive or treatment strategies currently available against them. Not only do filoviruses cause a deadly infection, but they also have the potential of being used as biological weapons. This makes it imperative to comprehensively study these viruses in order to devise effective strategies to prevent the occurrence of these infections. Entry is the foremost step in the filoviral replication cycle and different studies have reported the involvement of a myriad of cellular factors including plasma membrane components, cytoskeletal proteins, endosomal components, and cytosolic factors in this process. Signaling molecules such as the TAM family of receptor tyrosine kinases comprising of Tyro3, Axl, and Mer have also been implicated as putative entry factors. Additionally, filoviruses are suggested to bind to a common receptor and recent studies have proposed T-cell immunoglobulin and mucin domain 1 (TIM-1) and Niemann-Pick C1 (NPC1) as potential receptor candidates. This paper summarizes the existing literature on filoviral entry with a special focus on cellular factors involved in this process and also highlights some fundamental questions. Future research aimed at answering these questions could be very useful in designing novel antiviral therapeutics. PMID:23365575

  12. Cellular Factors Implicated in Filovirus Entry

    Directory of Open Access Journals (Sweden)

    Suchita Bhattacharyya

    2013-01-01

    Full Text Available Although filoviral infections are still occurring in different parts of the world, there are no effective preventive or treatment strategies currently available against them. Not only do filoviruses cause a deadly infection, but they also have the potential of being used as biological weapons. This makes it imperative to comprehensively study these viruses in order to devise effective strategies to prevent the occurrence of these infections. Entry is the foremost step in the filoviral replication cycle and different studies have reported the involvement of a myriad of cellular factors including plasma membrane components, cytoskeletal proteins, endosomal components, and cytosolic factors in this process. Signaling molecules such as the TAM family of receptor tyrosine kinases comprising of Tyro3, Axl, and Mer have also been implicated as putative entry factors. Additionally, filoviruses are suggested to bind to a common receptor and recent studies have proposed T-cell immunoglobulin and mucin domain 1 (TIM-1 and Niemann-Pick C1 (NPC1 as potential receptor candidates. This paper summarizes the existing literature on filoviral entry with a special focus on cellular factors involved in this process and also highlights some fundamental questions. Future research aimed at answering these questions could be very useful in designing novel antiviral therapeutics.

  13. Two Phase Flow Simulation Using Cellular Automata

    International Nuclear Information System (INIS)

    The classical mathematical treatment of two-phase flows is based on the average of the conservation equations for each phase.In this work, a complementary approach to the modeling of these systems based on statistical population balances of aut omata sets is presented.Automata are entities defined by mathematical states that change following iterative rules representing interactions with the neighborhood.A model of automata for two-phase flow simulation is presented.This model consists of fie lds of virtual spheres that change their volumes and move around a certain environment.The model is more general than the classical cellular automata in two respects: the grid of cellular automata is dismissed in favor of a trajectory generator, and the rules of interaction involve parameters representing the actual physical interactions between phases.Automata simulation was used to study unsolved two-phase flow problems involving high heat flux rates. One system described in this work consists of a vertical channel with saturated water at normal pressure heated from the lower surface.The heater causes water to boil and starts the bubble production.We used cellular automata to describe two-phase flows and the interaction with the heater.General rule s for such cellular automata representing bubbles moving in stagnant liquid were used, with special attention to correct modeling of different mechanisms of heat transfer.The results of the model were compared to previous experiments and correlations finding good agreement.One of the most important findings is the confirmation of Kutateladze's idea about a close relation between the start of critical heat flux and a change in the flow's topology.This was analyzed using a control volume located in the upper surface of the heater.A strong decrease in the interfacial surface just before the CHF start was encountered.The automata describe quite well some characteristic parameters such as the shape of the local void fraction in the

  14. Benchmark study between FIDAP and a cellular automata code

    Science.gov (United States)

    Akau, R. L.; Stockman, H. W.

    A fluid flow benchmark exercise was conducted to compare results between a cellular automata code and FIDAP. Cellular automata codes are free from gridding constraints, and are generally used to model slow (Reynolds number approximately 1) flows around complex solid obstacles. However, the accuracy of cellular automata codes at higher Reynolds numbers, where inertial terms are significant, is not well-documented. In order to validate the cellular automata code, two fluids problems were investigated. For both problems, flow was assumed to be laminar, two-dimensional, isothermal, incompressible and periodic. Results showed that the cellular automata code simulated the overall behavior of the flow field.

  15. Recursive definition of global cellular-automata mappings

    DEFF Research Database (Denmark)

    Feldberg, Rasmus; Knudsen, Carsten; Rasmussen, Steen

    1994-01-01

    A method for a recursive definition of global cellular-automata mappings is presented. The method is based on a graphical representation of global cellular-automata mappings. For a given cellular-automaton rule the recursive algorithm defines the change of the global cellular-automaton mapping...... as the number of lattice sites is incremented. A proof of lattice size invariance of global cellular-automata mappings is derived from an approximation to the exact recursive definition. The recursive definitions are applied to calculate the fractal dimension of the set of reachable states and of the set...

  16. Oxidative stress action in cellular aging

    Directory of Open Access Journals (Sweden)

    Monique Cristine de Oliveira

    2010-12-01

    Full Text Available Various theories try to explain the biological aging by changing the functions and structure of organic systems and cells. During lifetime, free radicals in the oxidative stress lead to lipid peroxidation of cellular membranes, homeostasis imbalance, chemical residues formation, gene mutations in DNA, dysfunction of certain organelles, and the arise of diseases due to cell death and/or injury. This review describes the action of oxidative stress in the cells aging process, emphasizing the factors such as cellular oxidative damage, its consequences and the main protective measures taken to prevent or delay this process. Tests with antioxidants: vitamins A, E and C, flavonoids, carotenoids and minerals, the practice of caloric restriction and physical exercise, seeking the beneficial effects on human health, increasing longevity, reducing the level of oxidative stress, slowing the cellular senescence and origin of certain diseases, are discussed.Diferentes teorias tentam explicar o envelhecimento biológico através da alteração das funções e estrutura dos sistemas orgânicos e células. Ao longo da vida, os radicais livres presentes no estresse oxidativo conduzem à peroxidação dos lipídios das membranas celulares, desequilíbrio da homeostase, formação de resíduos químicos, mutações gênicas no DNA, disfunção de certas organelas, bem como ao surgimento de doenças devido à lesão e/ou morte celular. Nesta revisão descreve-se a ação do estresse oxidativo no processo de envelhecimento das células, enfatizando fatores como os danos oxidativos celulares, suas conseqüências e as principais medidas protetoras adotadas para se prevenir ou retardar este processo. Testes com antioxidantes: vitaminas A, E e C, flavonóides, carotenóides e minerais; a prática de restrição calórica e exercícios físicos, que buscam efeitos benéficos sobre a saúde humana, aumentando a longevidade, reduzindo o nível de estresse oxidativo

  17. Cellular Automata Models for Diffusion of Innovations

    CERN Document Server

    Fuks, H; Fuks, Henryk; Boccara, Nino

    1997-01-01

    We propose a probabilistic cellular automata model for the spread of innovations, rumors, news, etc. in a social system. The local rule used in the model is outertotalistic, and the range of interaction can vary. When the range R of the rule increases, the takeover time for innovation increases and converges toward its mean-field value, which is almost inversely proportional to R when R is large. Exact solutions for R=1 and $R=\\infty$ (mean-field) are presented, as well as simulation results for other values of R. The average local density is found to converge to a certain stationary value, which allows us to obtain a semi-phenomenological solution valid in the vicinity of the fixed point n=1 (for large t).

  18. Call Admission Control in Mobile Cellular Networks

    CERN Document Server

    Ghosh, Sanchita

    2013-01-01

    Call Admission Control (CAC) and Dynamic Channel Assignments (DCA) are important decision-making problems in mobile cellular communication systems. Current research in mobile communication considers them as two independent problems, although the former greatly depends on the resulting free channels obtained as the outcome of the latter. This book provides a solution to the CAC problem, considering DCA as an integral part of decision-making for call admission. Further, current technical resources ignore movement issues of mobile stations and fluctuation in network load (incoming calls) in the control strategy used for call admission. In addition, the present techniques on call admission offers solution globally for the entire network, instead of considering the cells independently.      CAC here has been formulated by two alternative approaches. The first approach aimed at handling the uncertainty in the CAC problem by employing fuzzy comparators.  The second approach is concerned with formulation of CAC ...

  19. Graviperception and graviresponse at the cellular level

    Science.gov (United States)

    Bräucker, Richard; Cogoli, Augusto; Hemmersbach, Ruth

    Studies under varied acceleration conditions demonstrated that free living cells such as protists are able to perceive changes of the acceleration conditions. Recent studies favorite the hypothesis that in these systems gravity is perceived either by intracellular receptors (statocyst-like organelles), heavy cell organelles (such as nucleus) and/or by sensing the cell mass by means of ion channels located in the cell membrane. Mammalian cells in microgravity were profoundly influenced. Alteration in the cellular mechanisms and structures in mammalian cells like signal transduction and the cytoskeleton were detected. It can be speculated that the depression of the immune system may become a serious health issue on flights to and from Mars.

  20. Wireless traffic steering for green cellular networks

    CERN Document Server

    Zhang, Shan; Zhou, Sheng; Niu, Zhisheng; Shen, Xuemin (Sherman)

    2016-01-01

    This book introduces wireless traffic steering as a paradigm to realize green communication in multi-tier heterogeneous cellular networks. By matching network resources and dynamic mobile traffic demand, traffic steering helps to reduce on-grid power consumption with on-demand services provided. This book reviews existing solutions from the perspectives of energy consumption reduction and renewable energy harvesting. Specifically, it explains how traffic steering can improve energy efficiency through intelligent traffic-resource matching. Several promising traffic steering approaches for dynamic network planning and renewable energy demand-supply balancing are discussed. This book presents an energy-aware traffic steering method for networks with energy harvesting, which optimizes the traffic allocated to each cell based on the renewable energy status. Renewable energy demand-supply balancing is a key factor in energy dynamics, aimed at enhancing renewable energy sustainability to reduce on-grid energy consum...

  1. Cellular antioxidant activity of common vegetables.

    Science.gov (United States)

    Song, Wei; Derito, Christopher M; Liu, M Keshu; He, Xiangjiu; Dong, Mei; Liu, Rui Hai

    2010-06-01

    The measurement of antioxidant activity using biologically relevant assays is important to screen fruits, vegetables, natural products, and dietary supplements for potential health benefits. The cellular antioxidant activity (CAA) assay quantifies antioxidant activity using a cell culture model and was developed to meet the need for a more biologically representative method than the popular chemistry antioxidant capacity measures. The objective of the study was to determine the CAA, total phenolic contents, and oxygen radical absorbance capacity (ORAC) values of 27 vegetables commonly consumed in the United States. Beets, broccoli, and red pepper had the highest CAA values, whereas cucumber had the lowest. CAA values were significantly correlated to total phenolic content. Potatoes were found to be the largest contributors of vegetable phenolics and CAA to the American diet. Increased fruit and vegetable consumption is an effective strategy to increase antioxidant intake and decrease oxidative stress and may lead to reduced risk of developing chronic diseases, such as cancer and cardiovascular disease.

  2. Commercialization of cellular immunotherapies for cancer.

    Science.gov (United States)

    Walker, Anthony; Johnson, Robert

    2016-04-15

    Successful commercialization of a cell therapy requires more than proving safety and efficacy to the regulators. The inherent complexity of cellular products delivers particular manufacturing, logistical and reimbursement hurdles that threaten commercial viability for any therapy with a less than spectacular clinical profile that truly changes the standard of care. This is particularly acute for autologous cell therapies where patients receive bespoke treatments manufactured from a sample of their own cells and where economies of scale, which play an important role in containing the production costs for small molecule and antibody therapeutics, are highly limited. Nevertheless, the promise of 'game-changing' efficacy, as exemplified by very high levels of complete responses in refractory haematological malignancies, has attracted capital investments on a vast scale, and the attendant pace of technology development provides promising indicators for future clinical and commercial success. PMID:27068936

  3. Traffic jam dynamics in stochastic cellular automata

    Energy Technology Data Exchange (ETDEWEB)

    Nagel, K. [Los Alamos National Lab., NM (United States)]|[Santa Fe Inst., NM (United States); Schreckenberg, M. [Univ. Duisburg (Germany)

    1995-09-01

    Simple models for particles hopping on a grid (cellular automata) are used to simulate (single lane) traffic flow. Despite their simplicity, these models are astonishingly realistic in reproducing start-stop-waves and realistic fundamental diagrams. One can use these models to investigate traffic phenomena near maximum flow. A so-called phase transition at average maximum flow is visible in the life-times of jams. The resulting dynamic picture is consistent with recent fluid-dynamical results by Kuehne/Kerner/Konhaeuser, and with Treiterer`s hysteresis description. This places CA models between car-following models and fluid-dynamical models for traffic flow. CA models are tested in projects in Los Alamos (USA) and in NRW (Germany) for large scale microsimulations of network traffic.

  4. A cellular automata model for ant trails

    Indian Academy of Sciences (India)

    Sibel Gokce; Ozhan Kayacan

    2013-05-01

    In this study, the unidirectional ant traffic flow with U-turn in an ant trail was investigated using one-dimensional cellular automata model. It is known that ants communicate with each other by dropping a chemical, called pheromone, on the substrate. Apart from the studies in the literature, it was considered in the model that (i) ant colony consists of two kinds of ants, goodand poor-smelling ants, (ii) ants might make U-turn for some special reasons. For some values of densities of good- and poor-smelling ants, the flux and mean velocity of the colony were studied as a function of density and evaporation rate of pheromone.

  5. Simulating Complex Systems by Cellular Automata

    CERN Document Server

    Kroc, Jiri; Hoekstra, Alfons G

    2010-01-01

    Deeply rooted in fundamental research in Mathematics and Computer Science, Cellular Automata (CA) are recognized as an intuitive modeling paradigm for Complex Systems. Already very basic CA, with extremely simple micro dynamics such as the Game of Life, show an almost endless display of complex emergent behavior. Conversely, CA can also be designed to produce a desired emergent behavior, using either theoretical methodologies or evolutionary techniques. Meanwhile, beyond the original realm of applications - Physics, Computer Science, and Mathematics – CA have also become work horses in very different disciplines such as epidemiology, immunology, sociology, and finance. In this context of fast and impressive progress, spurred further by the enormous attraction these topics have on students, this book emerges as a welcome overview of the field for its practitioners, as well as a good starting point for detailed study on the graduate and post-graduate level. The book contains three parts, two major parts on th...

  6. Particles and Patterns in Cellular Automata

    International Nuclear Information System (INIS)

    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). Our objective has been to develop tools for studying particle interactions in a class of dynamical systems characterized by discreteness, determinism, local interaction, and an inherently parallel form of evolution. These systems can be described by cellular automata (CA) and the behavior we studied has improved our understanding of the nature of patterns generated by CAs, their ability to perform global computations, and their relationship to continuous dynamical systems. We have also developed a rule-table mathematics that enables one to custom-design CA rule tables to generate patterns of specified types, or to perform specified computational tasks

  7. Knowledge discovery for geographical cellular automata

    Institute of Scientific and Technical Information of China (English)

    LI Xia; Anthony Gar-On Yeh

    2005-01-01

    This paper proposes a new method for geographical simulation by applying data mining techniques to cellular automata. CA has strong capabilities in simulating complex systems. The core of CA is how to define transition rules. There are no good methods for defining these transition rules. They are usually defined by using heuristic methods and thus subject to uncertainties. Mathematical equations are used to represent transition rules implicitly and have limitations in capturing complex relationships. This paper demonstrates that the explicit transition rules of CA can be automatically reconstructed through the rule induction procedure of data mining. The proposed method can reduce the influences of individual knowledge and preferences in defining transition rules and generate more reliable simulation results. It can efficiently discover knowledge from a vast volume of spatial data.

  8. Determining Lineage Pathways from Cellular Barcoding Experiments

    Directory of Open Access Journals (Sweden)

    Leïla Perié

    2014-02-01

    Full Text Available Cellular barcoding and other single-cell lineage-tracing strategies form experimental methodologies for analysis of in vivo cell fate that have been instrumental in several significant recent discoveries. Due to the highly nonlinear nature of proliferation and differentiation, interrogation of the resulting data for evaluation of potential lineage pathways requires a new quantitative framework complete with appropriate statistical tests. Here, we develop such a framework, illustrating its utility by analyzing data from barcoded multipotent cells of the blood system. This application demonstrates that the data require additional paths beyond those found in the classical model, which leads us to propose that hematopoietic differentiation follows a loss of potential mechanism and to suggest further experiments to test this deduction. Our quantitative framework can evaluate the compatibility of lineage trees with barcoded data from any proliferating and differentiating cell system.

  9. Biological (molecular and cellular) markers of toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Shugart, L.R.; D' Surney, S.J.; Gettys-Hull, C.; Greeley, M.S. Jr.

    1991-12-15

    Several molecular and cellular markers of genotoxicity were adapted for measurement in the Medaka (Oryzias latipes), and were used to describe the effects of treatment of the organism with diethylnitrosamine (DEN). NO{sup 6}-ethyl guanine adducts were detected, and a slight statistically significant, increase in DNA strand breaks was observed. These results are consistent with the hypothesis that prolonged exposure to high levels of DEN induced alkyltransferase activity which enzymatically removes any O{sup 6}-ethyl guanine adducts but does not result in strand breaks or hypomethylation of the DNA such as might be expected from excision repair of chemically modified DNA. Following a five week continuous DEN exposure with 100 percent renewal of DEN-water every third day, the F values (DNA double strandedness) increased considerably and to similar extent in fish exposed to 25, 50, and 100 ppM DEN. This has been observed also in medaka exposed to BaP.

  10. Threshold effects and cellular recognition. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Rando, R R

    1980-01-01

    In the first year we focused on developing the techniques required for the successful incorporation of synthetic glycolipids into cells. To these ends a new water-soluble spacer group (8-amino-3-6-dioxaoctanoic acid) was developed and incorporated into the cholesterol based synthetic glycolipids. These glycolipids could be incorporated into liposomes, rendering them susceptible to aggregation by the appropriate lectin. They also allowed us to define the minimal distance between the sugar moiety and membrane required for agglutination. Finally and most importantly, we were able to functionally incorporate these new glycolipids in cells and render them agglutinable with the appropriate lectins. Functional incorporation does not occur with glycolipids bearing hydropholic spacer groups. We are now in a position to begin using the new glycolipids to answer questions about the roles of cell surface sugars in cellular recognition, which is the subject of this renewal proposal.

  11. Mathematical analysis of complex cellular activity

    CERN Document Server

    Bertram, Richard; Teka, Wondimu; Vo, Theodore; Wechselberger, Martin; Kirk, Vivien; Sneyd, James

    2015-01-01

    This book contains two review articles on mathematical physiology that deal with closely related topics but were written and can be read independently. The first article reviews the basic theory of calcium oscillations (common to almost all cell types), including spatio-temporal behaviors such as waves. The second article uses, and expands on, much of this basic theory to show how the interaction of cytosolic calcium oscillators with membrane ion channels can result in highly complex patterns of electrical spiking. Through these examples one can see clearly how multiple oscillatory processes interact within a cell, and how mathematical methods can be used to understand such interactions better. The two reviews provide excellent examples of how mathematics and physiology can learn from each other, and work jointly towards a better understanding of complex cellular processes. Review 1: Richard Bertram, Joel Tabak, Wondimu Teka, Theodore Vo, Martin Wechselberger: Geometric Singular Perturbation Analysis of Burst...

  12. Cellular telephone-based radiation detection instrument

    Science.gov (United States)

    Craig, William W.; Labov, Simon E.

    2011-06-14

    A network of radiation detection instruments, each having a small solid state radiation sensor module integrated into a cellular phone for providing radiation detection data and analysis directly to a user. The sensor module includes a solid-state crystal bonded to an ASIC readout providing a low cost, low power, light weight compact instrument to detect and measure radiation energies in the local ambient radiation field. In particular, the photon energy, time of event, and location of the detection instrument at the time of detection is recorded for real time transmission to a central data collection/analysis system. The collected data from the entire network of radiation detection instruments are combined by intelligent correlation/analysis algorithms which map the background radiation and detect, identify and track radiation anomalies in the region.

  13. Simulation of earthquakes with cellular automata

    Directory of Open Access Journals (Sweden)

    P. G. Akishin

    1998-01-01

    Full Text Available The relation between cellular automata (CA models of earthquakes and the Burridge–Knopoff (BK model is studied. It is shown that the CA proposed by P. Bak and C. Tang,although they have rather realistic power spectra, do not correspond to the BK model. We present a modification of the CA which establishes the correspondence with the BK model.An analytical method of studying the evolution of the BK-like CA is proposed. By this method a functional quadratic in stress release, which can be regarded as an analog of the event energy, is constructed. The distribution of seismic events with respect to this “energy” shows rather realistic behavior, even in two dimensions. Special attention is paid to two-dimensional automata; the physical restrictions on compression and shear stiffnesses are imposed.

  14. Inhibitors of the Cellular Trafficking of Ricin

    Directory of Open Access Journals (Sweden)

    Daniel Gillet

    2012-01-01

    Full Text Available Throughout the last decade, efforts to identify and develop effective inhibitors of the ricin toxin have focused on targeting its N-glycosidase activity. Alternatively, molecules disrupting intracellular trafficking have been shown to block ricin toxicity. Several research teams have recently developed high-throughput phenotypic screens for small molecules acting on the intracellular targets required for entry of ricin into cells. These screens have identified inhibitory compounds that can protect cells, and sometimes even animals against ricin. We review these newly discovered cellular inhibitors of ricin intoxication, discuss the advantages and drawbacks of chemical-genetics approaches, and address the issues to be resolved so that the therapeutic development of these small-molecule compounds can progress.

  15. Total Cellular RNA Modulates Protein Activity.

    Science.gov (United States)

    Majumder, Subhabrata; DeMott, Christopher M; Reverdatto, Sergey; Burz, David S; Shekhtman, Alexander

    2016-08-16

    RNA constitutes up to 20% of a cell's dry weight, corresponding to ∼20 mg/mL. This high concentration of RNA facilitates low-affinity protein-RNA quinary interactions, which may play an important role in facilitating and regulating biological processes. In the yeast Pichia pastoris, the level of ubiquitin-RNA colocalization increases when cells are grown in the presence of dextrose and methanol instead of methanol as the sole carbon source. Total RNA isolated from cells grown in methanol increases β-galactosidase activity relative to that seen with RNA isolated from cells grown in the presence of dextrose and methanol. Because the total cellular RNA content changes with growth medium, protein-RNA quinary interactions can alter in-cell protein biochemistry and may play an important role in cell adaptation, critical to many physiological and pathological states. PMID:27456029

  16. Environment Aware Location Estimation in Cellular Networks

    Directory of Open Access Journals (Sweden)

    Tuna Tugcu

    2008-03-01

    Full Text Available We propose a novel mobile positioning algorithm for cellular networks based on the estimation of the radio propagation environment. Since radio propagation characteristics vary in different environments, knowing the environment of the mobile user is essential for accurate Received Signal Strength- (RSS- based location estimation. The key feature of our method is its capability to estimate the environment of the mobile user using machine learning techniques and to utilize this information for enhancing RSS-based distance calculations. The proposed algorithm, namely, EARBALE, has been evaluated using field measurements collected from a GSM network in diverse geographic locations. Our approach turns out to be significantly beneficial, enhancing estimation accuracy, and thereby enabling high-performance mobile positioning in a practical and cost-effective manner. Additionally, it is computationally light-wei

  17. Cellular regulation of the dopamine transporter

    DEFF Research Database (Denmark)

    Eriksen, Jacob

    2010-01-01

    -membrane spanning protein Tac, thereby creating an extracellular antibody epitope. Upon expression in HEK293 cells this TacDAT fusion protein displayed functional properties similar to the wild type transporter. In an ELISA based internalization assay, TacDAT intracellular accumulation was increased by inhibitors......The dopamine transporter (DAT) mediates reuptake of dopamine from the synaptic cleft and is a target for widely abused psychostimulants such as cocaine and amphetamine. Nonetheless, little is known about the cellular distribution and trafficking of natively expressed DAT. DAT and its trafficking...... to natively expressed transporter, DAT was visualized directly in cultured DA neurons using the fluorescent cocaine analog JHC 1-64. These data showed pronounced colocalization upon constitutive internalization with Lysotracker, a late endosomal/lysosomal marker; however only little cololization was observed...

  18. Microfluidic electroporation for cellular analysis and delivery.

    Science.gov (United States)

    Geng, Tao; Lu, Chang

    2013-10-01

    Electroporation is a simple yet powerful technique for breaching the cell membrane barrier. The applications of electroporation can be generally divided into two categories: the release of intracellular proteins, nucleic acids and other metabolites for analysis and the delivery of exogenous reagents such as genes, drugs and nanoparticles with therapeutic purposes or for cellular manipulation. In this review, we go over the basic physics associated with cell electroporation and highlight recent technological advances on microfluidic platforms for conducting electroporation. Within the context of its working mechanism, we summarize the accumulated knowledge on how the parameters of electroporation affect its performance for various tasks. We discuss various strategies and designs for conducting electroporation at the microscale and then focus on analysis of intracellular contents and delivery of exogenous agents as two major applications of the technique. Finally, an outlook for future applications of microfluidic electroporation in increasingly diverse utilities is presented.

  19. Biological (molecular and cellular) markers of toxicity

    International Nuclear Information System (INIS)

    Several molecular and cellular markers of genotoxicity were adapted for measurement in the Medaka (Oryzias latipes), and were used to describe the effects of treatment of the organism with diethylnitrosamine (DEN). NO6-ethyl guanine adducts were detected, and a slight statistically significant, increase in DNA strand breaks was observed. These results are consistent with the hypothesis that prolonged exposure to high levels of DEN induced alkyltransferase activity which enzymatically removes any O6-ethyl guanine adducts but does not result in strand breaks or hypomethylation of the DNA such as might be expected from excision repair of chemically modified DNA. Following a five week continuous DEN exposure with 100 percent renewal of DEN-water every third day, the F values (DNA double strandedness) increased considerably and to similar extent in fish exposed to 25, 50, and 100 ppM DEN. This has been observed also in medaka exposed to BaP

  20. Cellular cardiomyoplasty A preliminary clinical report

    International Nuclear Information System (INIS)

    Background: Cellular cardiomyoplasty is the method of transplanting myogenic cells into injured myocardium to restore the lost heart muscle cells and to improve ventricular function. Method: Three patients, all with a history of coronary heart disease, underwent coronary artery bypass grafting and implantation of autologous satellite cells. A muscle biopsy of 2-4 g from the right vastus lateralis muscle was obtained for satellite cell (myogenic stem cell from skeletal muscle) isolation and proliferation before implanted into the donor's heart. The cells were suspended in serum-free medium and injected into 30-40 sites at and around the ischemic areas just before reversing the hypothermic cardioplegia to eliminate arrhythmia and to improve retention. After recovery, each patient was maintained at the intensive care unit for 3-4 days with ECG monitoring before transferring to the patient floor. Results: All patients survived the procedure with an uneventful recovery and were discharged from the hospital. At 3-4 months follow-up examination, increased left ventricular ejection fraction of 11% (35-46%), 5.4% (40-45.4%) and 1% (40-41%) and decreased left ventricular diastolic diameter of 4, 2 and 9 mm were observed for the patients, respectively. Arrhythmia was not detected during the follow-up evaluation by ECG. Improved perfusion (99mTC-MIBI) and increased metabolic activity (18F-deoxyglucose) were found at the sites of satellite cell implantation. Significant increase of wall thickness and movement at the areas of cell injection was also observed using 2D-echo. Conclusion: Cellular cardiomyoplasty using autologous satellite cells is a safe procedure with encouraging beneficial outcomes in patients

  1. Cellular scaling rules of insectivore brains

    Directory of Open Access Journals (Sweden)

    Diana K Sarko

    2009-06-01

    Full Text Available Insectivores represent extremes in mammalian body size and brain size, retaining various “primitive” morphological characteristics, and some species of Insectivora are thought to share similarities with small-bodied ancestral eutherians. This raises the possibility that insectivore brains differ from other taxa, including rodents and primates, in cellular scaling properties. Here we examine the cellular scaling rules for insectivore brains and demonstrate that insectivore scaling rules overlap somewhat with those for rodents and primates such that the insectivore cortex shares scaling rules with rodents (increasing faster in size than in numbers of neurons, but the insectivore cerebellum shares scaling rules with primates (increasing isometrically. Brain structures pooled as “remaining areas” appear to scale similarly across all three mammalian orders with respect to numbers of neurons, and the numbers of non-neurons appear to scale similarly across all brain structures for all three orders. Therefore, common scaling rules exist, to different extents, between insectivore, rodent and primate brain regions, and it is hypothesized that insectivores represent the common aspects of each order. The olfactory bulbs of insectivores, however, offer a noteworthy exception in that neuronal density increases linearly with increasing structure mass. This implies that the average neuronal cell size decreases with increasing olfactory bulb mass in order to accommodate greater neuronal density, and represents the first documentation of a brain structure gaining neurons at a greater rate than mass. This might allow insectivore brains to concentrate more neurons within the olfactory bulbs without a prohibitively large and metabolically costly increase in structure mass.

  2. 基于共面薄膜金电极的三磷酸腺苷适体传感器%An Aptamer-based Amperometric Biosensor for Adenosine Triphosphate Detection Based on Coplanar Thin-film Gold Electrode

    Institute of Scientific and Technical Information of China (English)

    姜利英; 王芬芬; 胡杰; 岳保磊; 闫艳霞; 陈青华

    2014-01-01

    Thin-film gold electrodes were fabricated based on MEMS technology. Adenosine triphosphate with mercapto-group was immobilized on a surface of gold electrode via self-assembly. An aptamer-based amperometric biosensor was constructed to measure the concentration of the ATP that using aptamer as the recognition element based on coplanar thin-film gold electrode. Adenosine triphosphate was detected by the characteristic impedance changes based on phosphate backbone of nucleic with negatively charge that electrostatic reject [ Fe( CN) 6 ] 3-/4-. Firstly, under the conditions of bare gold electrode and before and after ATP was added and whether 6-mercapto-1-hexanol was closed on electrode and the different self-assembly time (3, 8, 15, 24 and 30 h),the electrode of impedance changes in electrochemical impedance solution was researched with electrochemical Impedance Spectroscopy. The experiments show that the measurable linearity range of adenosine triphosphate is 1-500 nmol/L, the detection limit is 1 nmol/L and the correlation coefficient was 0 . 9842 when the time of the self-assembly was 24 h and closed gold electrode with 6-mercapto-hexanol. This electrochemical aptasensor was simplicity and has low detection limit and good repeatability.%为了检测三磷酸腺苷( ATP)的浓度,利用微系统( MEMS)技术小批量加工薄膜金电极,采用自组装法将巯基修饰的三磷酸腺苷适体固定到金电极表面,以三磷酸腺苷适体作为识别元件,构建了一种基于共面薄膜金电极的三磷酸腺苷适体传感器。依据核酸磷酸骨架荷负电特性静电排斥[Fe(CN)6]3-/4-所引起的阻抗变化实现对ATP浓度的检测。首先采用电化学阻抗谱法研究了裸金电极及ATP加入前后、6-巯基己醇封闭电极前后以及不同自组装时间(3,8,15,24和30 h)条件下,电极在电化学阻抗溶液中阻抗值变化。然后研究了不同浓度ATP适体传感器的电化学阻抗谱以及适体传感器的线性度和

  3. Restrictions to HIV-1 replication in resting CD4+T lymphocytes

    Institute of Scientific and Technical Information of China (English)

    Xiaoyu Pan; Hanna-Mari Baldauf; Oliver T Keppler; Oliver T Fackler

    2013-01-01

    CD4+ T lymphocytes represent the main target cell population of human immunodeficiency virus (HIV).In an activated state,CD4+ T cells residing in lymphoid organs are a major reservoir of ongoing HIV-1 replication in infected individuals.In contrast,resting CD4+ T cells are highly resistant to productive HIV-1 infection,yet are massively depleted during disease progression and represent a substantial latent reservoir for the virus in vivo.Barriers preventing replication of HIV-1 in resting CD4+ T cells include a rigid layer of cortical actin and,early after HIV-1entry,a block that limits reverse transcription of incoming viral RNA genomes.Defining the molecular bases of these restrictions has remained one of the central open questions in HIV research.Recent advances unraveled mechanisms by which HIV-1 bypasses the entry block and established the host cell restriction factor SAMHD1,a deoxynucleoside triphosphate triphosphohydrolase,as a central determinant of the cellular restriction to HIV-1 reverse transcription in resting CD4+ T cells.This review summarizes our current molecular and pathophysiological understanding of the multi-faceted interactions of HIV-1 with resting CD4+ T lymphocytes.

  4. 1,4-Naphthoquinones: From Oxidative Damage to Cellular and Inter-Cellular Signaling

    Directory of Open Access Journals (Sweden)

    Lars-Oliver Klotz

    2014-09-01

    Full Text Available Naphthoquinones may cause oxidative stress in exposed cells and, therefore, affect redox signaling. Here, contributions of redox cycling and alkylating properties of quinones (both natural and synthetic, such as plumbagin, juglone, lawsone, menadione, methoxy-naphthoquinones, and others to cellular and inter-cellular signaling processes are discussed: (i naphthoquinone-induced Nrf2-dependent modulation of gene expression and its potentially beneficial outcome; (ii the modulation of receptor tyrosine kinases, such as the epidermal growth factor receptor by naphthoquinones, resulting in altered gap junctional intercellular communication. Generation of reactive oxygen species and modulation of redox signaling are properties of naphthoquinones that render them interesting leads for the development of novel compounds of potential use in various therapeutic settings.

  5. Controlling Cellular Endocytosis at the Nanoscale

    Science.gov (United States)

    Battaglia, Giuseppe

    2011-03-01

    One of the most challenging aspects of drug delivery is the intra-cellular delivery of active agents. Several drugs and especially nucleic acids all need to be delivered within the cell interior to exert their therapeutic action. Small hydrophobic molecules can permeate cell membranes with relative ease, but hydrophilic molecules and especially large macromolecules such as proteins and nucleic acids require a vector to assist their transport across the cell membrane. This must be designed so as to ensure intracellular delivery without compromising cell viability. We have recently achieved this by using pH-sensitive poly(2-(methacryloyloxy)ethyl-phosphorylcholine)- co -poly(2-(diisopropylamino)ethyl methacrylate) (PMPC-PDPA) and poly(ethylene oxide)-co- poly(2-(diisopropylamino)ethyl methacrylate) (PEO-PDPA) diblock copolymers that self-assemble to form vesicles in aqueous solution. These vesicles combine a non-fouling PMPC or PEO block with a pH-sensitive PDPA block and have the ability to encapsulate both hydrophobic molecules within the vesicular membrane and hydrophilic molecules within their aqueous cores. The pH sensitive nature of the PDPA blocks make the diblock copolymers forming stable vesicles at physiological pH but that rapid dissociation of these vesicles occurs between pH 5 and pH 6 to form molecularly dissolved copolymer chains (unimers). We used these vesicles to encapsulate small and large macromolecules and these were successfully delivered intracellularly including nucleic acid, drugs, quantum dots, and antibodies. Dynamic light scattering, zeta potential measurements, and transmission electron microscopy were used to study and optimise the encapsulation processes. Confocal laser scanning microscopy, fluorescence flow cytometry and lysates analysis were used to quantify cellular uptake and to study the kinetics of this process in vitro and in vivo. We show the effective cytosolic delivery of nucleic acids, proteins, hydrophobic molecules

  6. Cellular membrane collapse by atmospheric-pressure plasma jet

    Science.gov (United States)

    Kim, Kangil; Jun Ahn, Hak; Lee, Jae-Hyeok; Kim, Jae-Ho; Sik Yang, Sang; Lee, Jong-Soo

    2014-01-01

    Cellular membrane dysfunction caused by air plasma in cancer cells has been studied to exploit atmospheric-pressure plasma jets for cancer therapy. Here, we report that plasma jet treatment of cervical cancer HeLa cells increased electrical conductivity across the cellular lipid membrane and caused simultaneous lipid oxidation and cellular membrane collapse. We made this finding by employing a self-manufactured microelectrode chip. Furthermore, increased roughness of the cellular lipid membrane and sequential collapse of the membrane were observed by atomic force microscopy following plasma jet treatment. These results suggest that the cellular membrane catastrophe occurs via coincident altered electrical conductivity, lipid oxidation, and membrane roughening caused by an atmospheric-pressure plasma jet, possibly resulting in cellular vulnerability to reactive species generated from the plasma as well as cytotoxicity to cancer cells.

  7. Cellular membrane collapse by atmospheric-pressure plasma jet

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kangil; Sik Yang, Sang, E-mail: jsjlee@ajou.ac.kr, E-mail: ssyang@ajou.ac.kr [Department of Electrical and Computer Engineering, Ajou University, Suwon 443-749 (Korea, Republic of); Jun Ahn, Hak; Lee, Jong-Soo, E-mail: jsjlee@ajou.ac.kr, E-mail: ssyang@ajou.ac.kr [Department of Biological Sciences, Ajou University, Suwon 443-749 (Korea, Republic of); Lee, Jae-Hyeok; Kim, Jae-Ho [Department of Molecular Science and Technology, Ajou University, Suwon 443-749 (Korea, Republic of)

    2014-01-06

    Cellular membrane dysfunction caused by air plasma in cancer cells has been studied to exploit atmospheric-pressure plasma jets for cancer therapy. Here, we report that plasma jet treatment of cervical cancer HeLa cells increased electrical conductivity across the cellular lipid membrane and caused simultaneous lipid oxidation and cellular membrane collapse. We made this finding by employing a self-manufactured microelectrode chip. Furthermore, increased roughness of the cellular lipid membrane and sequential collapse of the membrane were observed by atomic force microscopy following plasma jet treatment. These results suggest that the cellular membrane catastrophe occurs via coincident altered electrical conductivity, lipid oxidation, and membrane roughening caused by an atmospheric-pressure plasma jet, possibly resulting in cellular vulnerability to reactive species generated from the plasma as well as cytotoxicity to cancer cells.

  8. Numerical investigation on evolution of cylindrical cellular detonation

    Institute of Scientific and Technical Information of China (English)

    WANG Chun; JIANG Zong-lin; HU Zong-min; HAN Gui-lai

    2008-01-01

    Cylindrical cellular detonation is numerically investigated by solving twodimensional reactive Euler equations with a finite volume method on a two-dimensional self-adaptive unstructured mesh.The one-step reversible chemical reaction model is applied to simplify the control parameters of chemical reaction.Numerical results demonstrate the evolution of cellular cell splitting of cylindrical cellular detonation explored in experimentas.Split of cellular structures shows different features in the near-field and far-field from the initiation zone.Variation of the local curvature is a key factor in the behavior of cell split of cylindrical cellular detonation in propagation.Numerical results show that split of cellular structures comes from the self-organization of transverse waves corresponding to the development of small disturbances along the detonation front related to detonation instability.

  9. Molecular and cellular neurocardiology: development, and cellular and molecular adaptations to heart disease.

    Science.gov (United States)

    Habecker, Beth A; Anderson, Mark E; Birren, Susan J; Fukuda, Keiichi; Herring, Neil; Hoover, Donald B; Kanazawa, Hideaki; Paterson, David J; Ripplinger, Crystal M

    2016-07-15

    The nervous system and cardiovascular system develop in concert and are functionally interconnected in both health and disease. This white paper focuses on the cellular and molecular mechanisms that underlie neural-cardiac interactions during development, during normal physiological function in the mature system, and during pathological remodelling in cardiovascular disease. The content on each subject was contributed by experts, and we hope that this will provide a useful resource for newcomers to neurocardiology as well as aficionados. PMID:27060296

  10. Molecular and cellular neurocardiology: development, and cellular and molecular adaptations to heart disease.

    Science.gov (United States)

    Habecker, Beth A; Anderson, Mark E; Birren, Susan J; Fukuda, Keiichi; Herring, Neil; Hoover, Donald B; Kanazawa, Hideaki; Paterson, David J; Ripplinger, Crystal M

    2016-07-15

    The nervous system and cardiovascular system develop in concert and are functionally interconnected in both health and disease. This white paper focuses on the cellular and molecular mechanisms that underlie neural-cardiac interactions during development, during normal physiological function in the mature system, and during pathological remodelling in cardiovascular disease. The content on each subject was contributed by experts, and we hope that this will provide a useful resource for newcomers to neurocardiology as well as aficionados.

  11. Cellular basis of gravity resistance in plants

    Science.gov (United States)

    Hoson, Takayuki; Matsumoto, Shouhei; Inui, Kenichi; Zhang, Yan; Soga, Kouichi; Wakabayashi, Kazuyuki; Hashimoto, Takashi

    Mechanical resistance to the gravitational force is a principal gravity response in plants distinct from gravitropism. In the final step of gravity resistance, plants increase the rigidity of their cell walls via modifications to the cell wall metabolism and apoplastic environment. We studied cellular events that are related to the cell wall changes under hypergravity conditions produced by centrifugation. Hypergravity induced reorientation of cortical microtubules from transverse to longitudinal directions in epidermal cells of stem organs. In Arabidopsis tubulin mutants, the percentage of cells with longitudinal microtubules was high even at 1 g, and it was further increased by hypergravity. Hypocotyls of tubulin mutants also showed either left-handed or right-handed helical growth at 1 g, and the degree of twisting phenotype was intensified under hypergravity conditions. The left-handed helical growth mutants had right-handed microtubule arrays, whereas the right-handed mutant had left-handed arrays. There was a close correlation between the alignment angle of epidermal cell files and the alignment of cortical microtubules. Gadolinium ions suppressed both the twisting phenotype and reorientation of microtubules in tubulin mutants. These results support the hypothesis that cortical microtubules play an es-sential role in maintenance of normal growth phenotype against the gravitational force, and suggest that mechanoreceptors are involved in modifications to morphology and orientation of microtubule arrays by hypergravity. Actin microfilaments, in addition to microtubules, may be involved in gravity resistance. The nucleus of epidermal cells of azuki bean epicotyls, which is present almost in the center of the cell at 1 g, was displaced to the cell bottom by increasing the magnitude of gravity. Cytochalasin D stimulated the sedimentation by hypergravity of the nu-cleus, suggesting that the positioning of the nucleus is regulated by actin microfilaments, which is

  12. Some Properties of Fractals Generated by Linear Cellular Automata

    Institute of Scientific and Technical Information of China (English)

    倪天佳

    2003-01-01

    Fractals and cellular automata are both significant areas of research in nonlinear analysis. This paper studies a class of fractals generated by cellular automata. The patterns produced by cellular automata give a special sequence of sets in Euclidean space. The corresponding limit set is shown to be a fractal and the dimension is independent of the choice of the finite initial seed. As opposed to previous works, the fractals here do not depend on the time parameter.

  13. Incorporation of cellular proteins into enveloped virus particles

    OpenAIRE

    Hammarstedt, Maria

    2006-01-01

    This thesis work aimed to investigate the assembly and budding of enveloped virus particles with focus on the fate of cellular proteins, present in or near the plasma membrane (PM) where the budding occurs. It was previously shown that compact viruses, like alphaviruses, with a covering outer protein coat, did not contain any cellular proteins in the envelope. However, cellular proteins were found in purified retroviral preparations and these proteins were thought to be spec...

  14. Are cellular phone blocking applications effective for novice teen drivers?

    OpenAIRE

    Creaser, J.

    2014-01-01

    Distracted driving is a significant concern for novice teen drivers. Although cellular phone bans are applied in many jurisdictions to restrict cellular phone use, teen drivers often report making calls and texts while driving. Method The Minnesota Teen Driver Study incorporated cellular phone blocking functions via a software application for 182 novice teen drivers in two treatment conditions. The first condition included 92 teens who ran a driver support application on a smartphone that als...

  15. Cell biology of the future: Nanometer-scale cellular cartography.

    Science.gov (United States)

    Taraska, Justin W

    2015-10-26

    Understanding cellular structure is key to understanding cellular regulation. New developments in super-resolution fluorescence imaging, electron microscopy, and quantitative image analysis methods are now providing some of the first three-dimensional dynamic maps of biomolecules at the nanometer scale. These new maps--comprehensive nanometer-scale cellular cartographies--will reveal how the molecular organization of cells influences their diverse and changeable activities.

  16. Multidimensional traveling waves in the Allen–Cahn cellular automaton

    International Nuclear Information System (INIS)

    Ultradiscretization is a limiting procedure transforming a given difference equation into a cellular automaton. The cellular automaton constructed by this procedure preserves the essential properties of the original equation, such as the structure of exact solutions for integrable equations. In this article, a cellular automaton analog of the multidimensional Allen–Cahn equation which is not an integrable system is constructed by the ultradiscretization. Moreover, the traveling wave solutions for the resulting cellular automaton are given. The shape, behavior and stability of the solutions in ultradiscrete systems are similar to those in continuous systems. (paper)

  17. Validation of self-reported cellular phone use

    DEFF Research Database (Denmark)

    Samkange-Zeeb, Florence; Berg, Gabriele; Blettner, Maria

    2004-01-01

    BACKGROUND: In recent years, concern has been raised over possible adverse health effects of cellular telephone use. In epidemiological studies of cancer risk associated with the use of cellular telephones, the validity of self-reported cellular phone use has been problematic. Up to now...... was compared with information derived from the network providers over a period of 3 months (taken as the gold standard). RESULTS: Using Spearman's rank correlation, the correlation between self-reported phone use and information from the network providers for cellular phone use in terms of the number of calls...

  18. Molecular and cellular mechanisms of adipogenesis

    Directory of Open Access Journals (Sweden)

    Aleksander Dmitrievich Egorov

    2015-03-01

    Full Text Available The main components of metabolic syndrome include insulin resistance, hypertriglyceridemia and arterial hypertension. Obesity is the cause of metabolic syndrome, mainly as a consequence of the endocrine function of adipose tissue. The volume of adipose tissue depends on the size of individual adipocytes and on their number. The number of adipocytes increases as a result of enhanced adipocyte differentiation. The transcriptional cascade that regulates this differentiation has been well studied. The major adipogenic transcription factor peroxisome proliferator-activated receptor gamma is a ligand-activated nuclear receptor with essential roles in adipogenesis. Its ligands are used to treat metabolic syndrome and type 2 diabetes mellitus. The present article describes the basic molecular and cellular mechanisms of adipogenesis and discusses the impact of insulin, glucocorticoids, cyclic adenosine monophosphate-activating agents, nuclear receptors and transcription factors on the process of adipogenesis. New regulatory regions of the genome that are capable of binding multiple transcription factors are described, and the most promising drug targets for the treatment of metabolic syndrome and obesity, including the homeodomain proteins Pbx1 and Prep1, are discussed.

  19. Modeling cellular effects of coal pollutants

    International Nuclear Information System (INIS)

    The goal of this project is to develop and test models for the dose and dose-rate dependence of biological effects of coal pollutants on mammalian cells in tissue culture. Particular attention is given to the interaction of pollutants with the genetic material (deoxyribonucleic acid, or NDA) in the cell. Unlike radiation, which can interact directly with chromatin, chemical pollutants undergo numerous changes before the ultimate carcinogen becomes covalently bound to the DNA. Synthetic vesicles formed from a phospholipid bilayer are being used to investigate chemical transformations that may occur during the transport of pollutants across cellular membranes. The initial damage to DNA is rapidly modified by enzymatic repair systems in most living organisms. A model has been developed for predicting the effects of excision repair on the survival of human cells exposed to chemical carcinogens. In addition to the excision system, normal human cells also have tolerance mechanisms that permit continued growth and division of cells without removal of the damage. We are investigating the biological effect of damage passed to daughter cells by these tolerance mechanisms

  20. Cellular automata modelling of biomolecular networks dynamics.

    Science.gov (United States)

    Bonchev, D; Thomas, S; Apte, A; Kier, L B

    2010-01-01

    The modelling of biological systems dynamics is traditionally performed by ordinary differential equations (ODEs). When dealing with intracellular networks of genes, proteins and metabolites, however, this approach is hindered by network complexity and the lack of experimental kinetic parameters. This opened the field for other modelling techniques, such as cellular automata (CA) and agent-based modelling (ABM). This article reviews this emerging field of studies on network dynamics in molecular biology. The basics of the CA technique are discussed along with an extensive list of related software and websites. The application of CA to networks of biochemical reactions is exemplified in detail by the case studies of the mitogen-activated protein kinase (MAPK) signalling pathway, the FAS-ligand (FASL)-induced and Bcl-2-related apoptosis. The potential of the CA method to model basic pathways patterns, to identify ways to control pathway dynamics and to help in generating strategies to fight with cancer is demonstrated. The different line of CA applications presented includes the search for the best-performing network motifs, an analysis of importance for effective intracellular signalling and pathway cross-talk. PMID:20373215

  1. Cellular Automata Model for Elastic Solid Material

    Institute of Scientific and Technical Information of China (English)

    DONG Yin-Feng; ZHANG Guang-Cai; XU Ai-Guo; GAN Yan-Biao

    2013-01-01

    The Cellular Automaton (CA) modeling and simulation of solid dynamics is a long-standing difficult problem.In this paper we present a new two-dimensional CA model for solid dynamics.In this model the solid body is represented by a set of white and black particles alternatively positioned in the x-and y-directions.The force acting on each particle is represented by the linear summation of relative displacements of the nearest-neighboring particles.The key technique in this new model is the construction of eight coefficient matrices.Theoretical and numerical analyses show that the present model can be mathematically described by a conservative system.So,it works for elastic material.In the continuum limit the CA model recovers the well-known Navier equation.The coefficient matrices are related to the shear module and Poisson ratio of the material body.Compared with previous CA model for solid body,this model realizes the natural coupling of deformations in the x-and y-directions.Consequently,the wave phenomena related to the Poisson ratio effects are successfully recovered.This work advances significantly the CA modeling and simulation in the field of computational solid dynamics.

  2. [Cellular structure of propionibacteria during their multiplication].

    Science.gov (United States)

    Sobczak, E; Kocoń, J

    1983-01-01

    The aim of the present study was to determine the structure of bacterial cells from Propionibacterium genus as well as their structure during the cellular division. On the basis of the observations made in the electron transmission microscope, in uranyl-acetates-tained preparations of ultra-thin specimens of bacteria, it was stated that propionic bacteria appeared in a shape of short rods, possessing regular profiles of cell walls as opposed to Gram-negative bacteria with a very creased edge line. Besides, it was observed that division of cells had place by formation of septum, most probably preceded by the division of mezosome, which is a signal for creating the divisional wall. In the conducted studies, the following phenomena were started: presence of membraneous structure of mezosomes, which is linked with the chain of circular DNA in bacterial cell, appearance of numerous ribosomes in the regions of tangled threads of nucleic acids, and existence of other undefinite elements. Mezosome present in the cell of propionic bacteria is probably linked with the cell wall at least in two places and on the surface of external cell wall at the site of its linking; it causes the change in electronic density, demonstrated by the undefined holes or scars in cell wall. This finding gives the possibility of distinguishing this genus of Propionibacterium, in the respect of morphology, from other bacteria what, in the opinion of the authors, is a new achievement in the studies on the structure of propionic bacteria.

  3. Cellular pathways controlling integron cassette site folding.

    Science.gov (United States)

    Loot, Céline; Bikard, David; Rachlin, Anna; Mazel, Didier

    2010-08-01

    By mobilizing small DNA units, integrons have a major function in the dissemination of antibiotic resistance among bacteria. The acquisition of gene cassettes occurs by recombination between the attI and attC sites catalysed by the IntI1 integron integrase. These recombination reactions use an unconventional mechanism involving a folded single-stranded attC site. We show that cellular bacterial processes delivering ssDNA, such as conjugation and replication, favour proper folding of the attC site. By developing a very sensitive in vivo assay, we also provide evidence that attC sites can recombine as cruciform structures by extrusion from double-stranded DNA. Moreover, we show an influence of DNA superhelicity on attC site extrusion in vitro and in vivo. We show that the proper folding of the attC site depends on both the propensity to form non-recombinogenic structures and the length of their variable terminal structures. These results draw the network of cell processes that regulate integron recombination. PMID:20628355

  4. [Cellular structure of propionibacteria during their multiplication].

    Science.gov (United States)

    Sobczak, E; Kocoń, J

    1983-01-01

    The aim of the present study was to determine the structure of bacterial cells from Propionibacterium genus as well as their structure during the cellular division. On the basis of the observations made in the electron transmission microscope, in uranyl-acetates-tained preparations of ultra-thin specimens of bacteria, it was stated that propionic bacteria appeared in a shape of short rods, possessing regular profiles of cell walls as opposed to Gram-negative bacteria with a very creased edge line. Besides, it was observed that division of cells had place by formation of septum, most probably preceded by the division of mezosome, which is a signal for creating the divisional wall. In the conducted studies, the following phenomena were started: presence of membraneous structure of mezosomes, which is linked with the chain of circular DNA in bacterial cell, appearance of numerous ribosomes in the regions of tangled threads of nucleic acids, and existence of other undefinite elements. Mezosome present in the cell of propionic bacteria is probably linked with the cell wall at least in two places and on the surface of external cell wall at the site of its linking; it causes the change in electronic density, demonstrated by the undefined holes or scars in cell wall. This finding gives the possibility of distinguishing this genus of Propionibacterium, in the respect of morphology, from other bacteria what, in the opinion of the authors, is a new achievement in the studies on the structure of propionic bacteria. PMID:6845903

  5. Multistructural biomimetic substrates for controlled cellular differentiation

    International Nuclear Information System (INIS)

    Multidimensional scaffolds are considered to be ideal candidates for regenerative medicine and tissue engineering based on their potential to provide an excellent microenvironment and direct the fate of the cultured cells. More recently, the use of stem cells in medicine has opened a new technological opportunity for controlled tissue formation. However, the mechanism through which the substrate directs the differentiation of stem cells is still rather unclear. Data concerning its specific surface chemistry, topology, and its signaling ability need to be further understood and analyzed. In our study, atomic force microscopy was used to study the stiffness, roughness, and topology of the collagen (Coll) and metallized collagen (MC) substrates, proposed as an excellent substrate for regenerative medicine. The importance of signaling molecules was studied by constructing a new hybrid signaling substrate that contains both collagen and laminin extracellular matrix (ECM) proteins. The cellular response—such as attachment capability, proliferation and cardiac and neuronal phenotype expression on the metallized and non-metallized hybrid substrates (collagen + laminin)—was studied using MTT viability assay and immunohistochemistry studies. Our findings indicate that such hybrid materials could play an important role in the regeneration of complex tissues. (paper)

  6. Optimal flux patterns in cellular metabolic networks

    Energy Technology Data Exchange (ETDEWEB)

    Almaas, E

    2007-01-20

    The availability of whole-cell level metabolic networks of high quality has made it possible to develop a predictive understanding of bacterial metabolism. Using the optimization framework of flux balance analysis, I investigate metabolic response and activity patterns to variations in the availability of nutrient and chemical factors such as oxygen and ammonia by simulating 30,000 random cellular environments. The distribution of reaction fluxes is heavy-tailed for the bacteria H. pylori and E. coli, and the eukaryote S. cerevisiae. While the majority of flux balance investigations have relied on implementations of the simplex method, it is necessary to use interior-point optimization algorithms to adequately characterize the full range of activity patterns on metabolic networks. The interior-point activity pattern is bimodal for E. coli and S. cerevisiae, suggesting that most metabolic reaction are either in frequent use or are rarely active. The trimodal activity pattern of H. pylori indicates that a group of its metabolic reactions (20%) are active in approximately half of the simulated environments. Constructing the high-flux backbone of the network for every environment, there is a clear trend that the more frequently a reaction is active, the more likely it is a part of the backbone. Finally, I briefly discuss the predicted activity patterns of the central-carbon metabolic pathways for the sample of random environments.

  7. Cellular and molecular aspects of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Malcolm G Smith; Georgina L Hold; Eiichi Tahara; Emad M El-Omar

    2006-01-01

    Gastric cancer remains a global killer with a shifting burden from the developed to the developing world.The cancer develops along a multistage process that is defined by distinct histological and pathophysiological phases. Several genetic and epigenetic alterations mediate the transition from one stage to another and these include mutations in oncogenes, tumour suppressor genes and cell cycle and mismatch repair genes. The most significant advance in the fight against gastric caner came with the recognition of the role of Helicobacter pylori (H pylori) as the most important acquired aetiological agent for this cancer. Recent work has focussed on elucidating the complex host/microbial interactions that underlie the neoplastic process. There is now considerable insight into the pathogenesis of this cancer and the prospect of preventing and eradicating the disease has become a reality. Perhaps more importantly, the study of H pylori-induced gastric carcinogenesis offers a paradigm for understanding more complex human cancers. In this review, we examine the molecular and cellular events that underlie H pyloriinduced gastric cancer.

  8. On the topological sensitivity of cellular automata

    Science.gov (United States)

    Baetens, Jan M.; De Baets, Bernard

    2011-06-01

    Ever since the conceptualization of cellular automata (CA), much attention has been paid to the dynamical properties of these discrete dynamical systems, and, more in particular, to their sensitivity to the initial condition from which they are evolved. Yet, the sensitivity of CA to the topology upon which they are based has received only minor attention, such that a clear insight in this dependence is still lacking and, furthermore, a quantification of this so-called topological sensitivity has not yet been proposed. The lack of attention for this issue is rather surprising since CA are spatially explicit, which means that their dynamics is directly affected by their topology. To overcome these shortcomings, we propose topological Lyapunov exponents that measure the divergence of two close trajectories in phase space originating from a topological perturbation, and we relate them to a measure grasping the sensitivity of CA to their topology that relies on the concept of topological derivatives, which is introduced in this paper. The validity of the proposed methodology is illustrated for the 256 elementary CA and for a family of two-state irregular totalistic CA.

  9. Noise Reduction Potential of Cellular Metals

    Directory of Open Access Journals (Sweden)

    Björn Hinze

    2012-06-01

    Full Text Available Rising numbers of flights and aircrafts cause increasing aircraft noise, resulting in the development of various approaches to change this trend. One approach is the application of metallic liners in the hot gas path of aero-engines. At temperatures of up to 600 °C only metallic or ceramic structures can be used. Due to fatigue loading and the notch effect of the pores, mechanical properties of porous metals are superior to the ones of ceramic structures. Consequently, cellular metals like metallic foams, sintered metals, or sintered metal felts are most promising materials. However, acoustic absorption depends highly on pore morphology and porosity. Therefore, both parameters must be characterized precisely to analyze the correlation between morphology and noise reduction performance. The objective of this study is to analyze the relationship between pore morphology and acoustic absorption performance. The absorber materials are characterized using image processing based on two dimensional microscopy images. The sound absorption properties are measured using an impedance tube. Finally, the correlation of acoustic behavior, pore morphology, and porosity is outlined.

  10. Biological (molecular and cellular) markers of toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Shugart, L.R.

    1990-10-01

    The overall objective of this study is to evaluate the use of the small aquarium fish, Japanese Medaka (Oryzias latipes), as a predictor of potential genotoxicity following exposure to carcinogens. This will be accomplished by quantitatively investigating the early molecular events associated with genotoxicity of various tissues of Medaka subsequent to exposure of the organism to several known carcinogens, such as diethylnitrosamine (DEN) and benzo(a)pyrene (BaP). Because of the often long latent period between initial contact with certain chemical and physical agents in our environment and subsequent expression of deleterious health or ecological impact, the development of sensitive methods for detecting and estimating early exposure is needed so that necessary interventions can ensue. A promising biological endpoint for detecting early exposure to damaging chemicals is the interaction of these compounds with cellular macromolecules such as Deoxyribonucleic acids (DNA). This biological endpoint assumes significance because it can be one of the critical early events leading eventually to adverse effects (neoplasia) in the exposed organism.

  11. Analytical Modeling of Uplink Cellular Networks

    CERN Document Server

    Novlan, Thomas D; Andrews, Jeffrey G

    2012-01-01

    Cellular uplink analysis has typically been undertaken by either a simple approach that lumps all interference into a single deterministic or random parameter in a Wyner-type model, or via complex system level simulations that often do not provide insight into why various trends are observed. This paper proposes a novel middle way that is both accurate and also results in easy-to-evaluate integral expressions based on the Laplace transform of the interference. We assume mobiles and base stations are randomly placed in the network with each mobile pairing up to its closest base station. The model requires two important changes compared to related recent work on the downlink. First, dependence is introduced between the user and base station point processes to make sure each base station serves a single mobile in the given resource block. Second, per-mobile power control is included, which further couples the locations of the mobiles and their receiving base stations. Nevertheless, we succeed in deriving the cov...

  12. Mobile telephony (cellular) and public health

    International Nuclear Information System (INIS)

    One third of the world population uses mobile phones or cellular (TM), as possible repercussions on health has resulted in numerous studies. TM and their bases (antennae) exchange information through microwaves, which are non-ionizing electromagnetic radiations. Microwaves have thermal effects, which are avoided by current safety standards. However, there are lingering doubts about possible adverse health consequences of non-thermal effects of microwaves. As a whole, basic and epidemiological research on TM and cancer indicates a very low or nonexistent risk, although longer prospective studies are needed. In the nervous system, TM microwaves cause electrophysiological changes and modifications of blood flow, with little effect on performance. Possible effects on the thyroid gland, the reproductive system, and oxidative stress demand additional research. Some TM users complain of unspecific symptoms, but no causal relationship has been proved either in normal subjects or those self-characterized as hypersensitive to electromagnetic fields. Epidemiological research on populations living close to base stations suggests adverse effects from exposition, but experimental work has yielded contradictory results. The effects on children have just begun to be explored. TM may interfere with medical equipment when the phones are operated very close to the devices. Ironically, the clearest adverse effect of TM has no direct relationship with microwaves. The use of TM while driving causes a decrease in performance comparable to moderate consumption of alcohol and quadruples the risk of accidents. (author)

  13. Cellular recurrent deep network for image registration

    Science.gov (United States)

    Alam, M.; Vidyaratne, L.; Iftekharuddin, Khan M.

    2015-09-01

    Image registration using Artificial Neural Network (ANN) remains a challenging learning task. Registration can be posed as a two-step problem: parameter estimation and actual alignment/transformation using the estimated parameters. To date ANN based image registration techniques only perform the parameter estimation, while affine equations are used to perform the actual transformation. In this paper, we propose a novel deep ANN based image rigid registration that combines parameter estimation and transformation as a simultaneous learning task. Our previous work shows that a complex universal approximator known as Cellular Simultaneous Recurrent Network (CSRN) can successfully approximate affine transformations with known transformation parameters. This study introduces a deep ANN that combines a feed forward network with a CSRN to perform full rigid registration. Layer wise training is used to pre-train feed forward network for parameter estimation and followed by a CSRN for image transformation respectively. The deep network is then fine-tuned to perform the final registration task. Our result shows that the proposed deep ANN architecture achieves comparable registration accuracy to that of image affine transformation using CSRN with known parameters. We also demonstrate the efficacy of our novel deep architecture by a performance comparison with a deep clustered MLP.

  14. Thermal effects of radiation from cellular telephones

    Science.gov (United States)

    Wainwright, Peter

    2000-08-01

    A finite element thermal model of the head has been developed to calculate temperature rises generated in the brain by radiation from cellular telephones and similar electromagnetic devices. A 1 mm resolution MRI dataset was segmented semiautomatically, assigning each volume element to one of ten tissue types. A finite element mesh was then generated using a fully automatic tetrahedral mesh generator developed at NRPB. There are two sources of heat in the model: firstly the natural metabolic heat production; and secondly the power absorbed from the electromagnetic field. The SAR was derived from a finite difference time domain model of the head, coupled to a model `mobile phone', namely a quarter-wavelength antenna mounted on a metal box. The steady-state temperature distribution was calculated using the standard Pennes `bioheat equation'. In the normal cerebral cortex the high blood perfusion rate serves to provide an efficient cooling mechanism. In the case of equipment generally available to the public, the maximum temperature rise found in the brain was about 0.1 °C. These results will help in the further development of criteria for exposure guidelines, and the technique developed may be used to assess temperature rises associated with SARs for different types of RF exposure.

  15. Cellular automata modeling of cooperative eutectic growth

    Directory of Open Access Journals (Sweden)

    E. Olejnik

    2010-01-01

    Full Text Available The model and results of the 2D simulation of the cooperative growth of two phases in the lamellar eutectic are presented. The pro-posed model takes into account heat transfer, components diffusion and nonstationary concentration distribution in the liquid and solid phases, non-equlibrium nature of the phase transformation and kinetics of the growth, influence of the surface energy and interface curva-ture on the conditions of the thermodynamic equilibrium. For the determination of the phase interface shape the Cellular Automata tech-nique (CA was used. For the calculation of temperature and concentration distribution the numerical solution of the Fourier equation was used. The partial differential equations were solved by Finite Differences Method (FDM. The spatial position and cell sizes of CA lattice and FDM mesh are equal.Proposed model can predict the steady state growth with a constant interlamellar spacing in the regular plate eutectic, as well as some transient processes that bring to the changes of that parameters. Obtained simulation data show the solid-liquid interface changes result in the termination of lamella and enlargement of interlamellar spacing. Another simulation results illustrate a pocket formation in the center of one phase that forestalls nucleation (or intergrowth of the new lamellae of another phase. The data of the solidification study of the transparent material (CBr4 – 8,4% C2Cl6 obtained in the thin layer demonstrate the qualita-tive agreement of the simulation.

  16. Bacterial Cellular Materials as Precursors of Chloroform

    Science.gov (United States)

    Wang, J.; Ng, T.; Zhang, Q.; Chow, A. T.; Wong, P.

    2011-12-01

    The environmental sources of chloroform and other halocarbons have been intensively investigated because their effects of stratospheric ozone destruction and environmental toxicity. It has been demonstrated that microorganisms could facilitate the biotic generation of chloroform from natural organic matters in soil, but whether the cellular materials itself also serves as an important precursor due to photo-disinfection is poorly known. Herein, seven common pure bacterial cultures (Acinetobacter junii, Aeromonas hydrophila, Bacillus cereus, Bacillus substilis, Escherichia coli, Shigella sonnei, Staphylococcus sciuri) were chlorinated to evaluate the yields of chloroform, dibromochloromethane, dichlorobromomethane, and bromoform. The effects of bromide on these chemical productions and speciations were also investigated. Results showed that, on average, 5.64-36.42 μg-chloroform /mg-C were generated during the bacterial chlorination, in similar order of magnitude to that generated by humic acid (previously reported as 78 μg-chloroform/mg-C). However, unlike humic acid in water chlorination, chloroform concentration did not simply increase with the total organic carbon in water mixture. In the presence of bromide, the yield of brominated species responded linearly to the bromide concentration. This study provides useful information to understand the contributions of chloroform from photodisinfection processes in coastal environments.

  17. Unstable vicinal crystal growth from cellular automata

    Science.gov (United States)

    Krasteva, A.; Popova, H.; KrzyŻewski, F.; Załuska-Kotur, M.; Tonchev, V.

    2016-03-01

    In order to study the unstable step motion on vicinal crystal surfaces we devise vicinal Cellular Automata. Each cell from the colony has value equal to its height in the vicinal, initially the steps are regularly distributed. Another array keeps the adatoms, initially distributed randomly over the surface. The growth rule defines that each adatom at right nearest neighbor position to a (multi-) step attaches to it. The update of whole colony is performed at once and then time increases. This execution of the growth rule is followed by compensation of the consumed particles and by diffusional update(s) of the adatom population. Two principal sources of instability are employed - biased diffusion and infinite inverse Ehrlich-Schwoebel barrier (iiSE). Since these factors are not opposed by step-step repulsion the formation of multi-steps is observed but in general the step bunches preserve a finite width. We monitor the developing surface patterns and quantify the observations by scaling laws with focus on the eventual transition from diffusion-limited to kinetics-limited phenomenon. The time-scaling exponent of the bunch size N is 1/2 for the case of biased diffusion and 1/3 for the case of iiSE. Additional distinction is possible based on the time-scaling exponents of the sizes of multi-step Nmulti, these are 0.36÷0.4 (for biased diffusion) and 1/4 (iiSE).

  18. Modeling the topological organization of cellular processes.

    Science.gov (United States)

    Giavitto, Jean-Louis; Michel, Olivier

    2003-07-01

    The cell as a dynamical system presents the characteristics of having a dynamical structure. That is, the exact phase space of the system cannot be fixed before the evolution and integrative cell models must state the evolution of the structure jointly with the evolution of the cell state. This kind of dynamical systems is very challenging to model and simulate. New programming concepts must be developed to ease their modeling and simulation. In this context, the goal of the MGS project is to develop an experimental programming language dedicated to the simulation of this kind of systems. MGS proposes a unified view on several computational mechanisms (CHAM, Lindenmayer systems, Paun systems, cellular automata) enabling the specification of spatially localized computations on heterogeneous entities. The evolution of a dynamical structure is handled through the concept of transformation which relies on the topological organization of the system components. An example based on the modeling of spatially distributed biochemical networks is used to illustrate how these notions can be used to model the spatial and temporal organization of intracellular processes. PMID:12915272

  19. Movies of cellular and sub-cellular motion by digital holographic microscopy

    Directory of Open Access Journals (Sweden)

    Yu Lingfeng

    2006-03-01

    Full Text Available Abstract Background Many biological specimens, such as living cells and their intracellular components, often exhibit very little amplitude contrast, making it difficult for conventional bright field microscopes to distinguish them from their surroundings. To overcome this problem phase contrast techniques such as Zernike, Normarsky and dark-field microscopies have been developed to improve specimen visibility without chemically or physically altering them by the process of staining. These techniques have proven to be invaluable tools for studying living cells and furthering scientific understanding of fundamental cellular processes such as mitosis. However a drawback of these techniques is that direct quantitative phase imaging is not possible. Quantitative phase imaging is important because it enables determination of either the refractive index or optical thickness variations from the measured optical path length with sub-wavelength accuracy. Digital holography is an emergent phase contrast technique that offers an excellent approach in obtaining both qualitative and quantitative phase information from the hologram. A CCD camera is used to record a hologram onto a computer and numerical methods are subsequently applied to reconstruct the hologram to enable direct access to both phase and amplitude information. Another attractive feature of digital holography is the ability to focus on multiple focal planes from a single hologram, emulating the focusing control of a conventional microscope. Methods A modified Mach-Zender off-axis setup in transmission is used to record and reconstruct a number of holographic amplitude and phase images of cellular and sub-cellular features. Results Both cellular and sub-cellular features are imaged with sub-micron, diffraction-limited resolution. Movies of holographic amplitude and phase images of living microbes and cells are created from a series of holograms and reconstructed with numerically adjustable

  20. Klenow Fragment Discriminates against the Incorporation of the Hyperoxidized dGTP Lesion Spiroiminodihydantoin into DNA.

    Science.gov (United States)

    Huang, Ji; Yennie, Craig J; Delaney, Sarah

    2015-12-21

    Defining the biological consequences of oxidative DNA damage remains an important and ongoing area of investigation. At the foundation of understanding the repercussions of such damage is a molecular-level description of the action of DNA-processing enzymes, such as polymerases. In this work, we focus on a secondary, or hyperoxidized, oxidative lesion of dG that is formed by oxidation of the primary oxidative lesion, 2'-deoxy-8-oxo-7,8-dihydroguanosine (8-oxodG). In particular, we examine incorporation into DNA of the diastereomers of the hyperoxidized guanosine triphosphate lesion spiroiminodihydantoin-2'-deoxynucleoside-5'-triphosphate (dSpTP). Using kinetic parameters, we describe the ability of the Klenow fragment of Escherichia coli DNA polymerase I lacking 3' → 5' exonuclease activity (KF(-)) to utilize (S)-dSpTP and (R)-dSpTP as building blocks during replication. We find that both diastereomers act as covert lesions, similar to a Trojan horse: KF(-) incorporates the lesion dNTP opposite dC, which is a nonmutagenic event; however, during the subsequent replication, it is known that dSp is nearly 100% mutagenic. Nevertheless, using kpol/Kd to define the nucleotide incorporation specificity, we find that the extent of oxidation of the dGTP-derived lesion correlates with its ability to be incorporated into DNA. KF(-) has the highest specificity for incorporation of dGTP opposite dC. The selection factors for incorporating 8-oxodGTP, (S)-dSpTP, and (R)-dSpTP are 1700-, 64000-, and 850000-fold lower, respectively. Thus, KF(-) is rigorous in its discrimination against incorporation of the hyperoxidized lesion, and these results suggest that the specificity of cellular polymerases provides an effective mechanism to avoid incorporating dSpTP lesions into DNA from the nucleotide pool. PMID:26572218

  1. Oral administration of amino acidic supplements improves protein and energy profiles in skeletal muscle of aged rats: elongation of functional performance and acceleration of mitochondrial recovery in adenosine triphosphate after exhaustive exertion.

    Science.gov (United States)

    Chen Scarabelli, Carol; McCauley, Roy B; Yuan, Zhaokan; Di Rezze, Justin; Patel, David; Putt, Jeff; Raddino, Riccardo; Allebban, Zuhair; Abboud, John; Scarabelli, Gabriele M; Chilukuri, Karuna; Gardin, Julius; Saravolatz, Louis; Faggian, Giuseppe; Mazzucco, Alessandro; Scarabelli, Tiziano M

    2008-06-01

    Sarcopenia is an inevitable age-related degenerative process chiefly characterized by decreased synthesis of muscle proteins and impaired mitochondrial function, leading to progressive loss of muscle mass. Here, we sought to probe whether long-term administration of oral amino acids (AAs) can increase protein and adenosine triphosphate (ATP) content in the gastrocnemius muscle of aged rats, enhancing functional performance. To this end, 6- and 24-month-old male Fisher 344 rats were divided into 3 groups: group A (6-month-old rats) and group B (24-month-old rats) were used as adult and senescent control group, respectively, while group C (24-month-old rats) was used as senescent treated group and underwent 1-month oral treatment with a mixture of mainly essential AAs. Untreated senescent animals exhibited a 30% reduction in total and fractional protein content, as well as a 50% reduction in ATP content and production, compared with adult control rats (p supplementation with mixed AAs significantly improved protein and high-energy phosphate content, as well as the rate of mitochondrial ATP production, conforming their values to those of adult control animals (p energy substrates in the gastrocnemius muscle of treated aged rats paralleled a significant enhancement in functional performance assessed by swim test, with dramatic elongation of maximal exertion times compared with untreated senescent rats (p supplementation with oral AAs improved protein and energy profiles in the gastrocnemius of treated rats, enhancing functional performance and accelerating high-energy phosphate recovery after exhaustive exertion.

  2. Simultaneous determination of 2',3'-dideoxyinosine and the active metabolite, 2',3'-dideoxyadenosine-5'-triphosphate in human peripheral-blood mononuclear cell by HPLC-MS/MS and the application to cell pharmacokinetics.

    Science.gov (United States)

    Lan, Xu; Mingdao, Lei; Huilin, Guo; Wei, Gan; Lvjiang, Hu; Yan, Zhou; Gang, Li

    2015-10-01

    A specific and reliable HPLC-MS/MS method was developed and validated for the simultaneous determination of 2',3'-dideoxyinosine (ddI) and the active metabolites, 2',3'-dideoxyadenosine-5'-triphosphate (ddA-TP) in human peripheral-blood mononuclear cell for the first time. The analytes were separated on a HILIC column (100mm×2.1mm, 1.7μm) and a triple-quadrupole mass spectrometry equipped with an electrospray ionization (ESI) source was used for detection. The cell homogenates sample was prepared by the solid phase extraction. The calibration curves were linear over a concentration range of 0.5-200.0ng/mL for ddI and 0.25-100.0ng/mL for ddA-TP. The intra-day and inter-day precision was less than 15% and the relative error (RE) were all within ±15%. The validated method was successfully applied to assess the disposition characteristics of ddI and support cell pharmacokinetics after the patients with AIDS were orally administrated with ddI and tenofovir disoproxyl fumarate (TDF).

  3. Strong Correlation Between Concentrations of Tenofovir (TFV) Emtricitabine (FTC) in Hair and TFV Diphosphate and FTC Triphosphate in Dried Blood Spots in the iPrEx Open Label Extension: Implications for Pre-exposure Prophylaxis Adherence Monitoring

    Science.gov (United States)

    Gandhi, Monica; Glidden, David V.; Liu, Albert; Anderson, Peter L.; Horng, Howard; Defechereux, Patricia; Guanira, Juan V.; Grinsztejn, Beatriz; Chariyalertsak, Suwat; Bekker, Linda-Gail; Grant, Robert M.

    2015-01-01

    Self-reported adherence to pre-exposure prophylaxis (PrEP) has limitations, raising interest in pharmacologic monitoring. Drug concentrations in hair and dried blood spots (DBS) are used to assess long-term-exposure; hair shipment/storage occurs at room temperature. The iPrEx Open Label Extension collected DBS routinely, with opt-in hair collection; concentrations were measured with liquid chromatography/tandem mass spectrometry. In 806 hair-DBS pairs, tenofovir (TFV) hair levels and TFV diphosphate (DP) in DBS were strongly correlated (Spearman coefficient r = 0.734; P < .001), as were hair TFV/DBS emtricitabine (FTC) triphosphate (TP) (r = 0.781; P < .001); hair FTC/DBS TFV-DP (r = 0.74; P < .001); hair FTC/DBS FTC-TP (r = 0.587; P < .001). Drug detectability was generally concordant by matrix. Hair TFV/FTC concentrations correlate strongly with DBS levels, which are predictive of PrEP outcomes. PMID:25895984

  4. Intracellular Secretory Leukoprotease Inhibitor Modulates Inositol 1,4,5-Triphosphate Generation and Exerts an Anti-Inflammatory Effect on Neutrophils of Individuals with Cystic Fibrosis and Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Emer P. Reeves

    2013-01-01

    Full Text Available Secretory leukoprotease inhibitor (SLPI is an anti-inflammatory protein present in respiratory secretions. Whilst epithelial cell SLPI is extensively studied, neutrophil associated SLPI is poorly characterised. Neutrophil function including chemotaxis and degranulation of proteolytic enzymes involves changes in cytosolic calcium (Ca2+ levels which is mediated by production of inositol 1,4,5-triphosphate (IP3 in response to G-protein-coupled receptor (GPCR stimuli. The aim of this study was to investigate the intracellular function of SLPI and the mechanism-based modulation of neutrophil function by this antiprotease. Neutrophils were isolated from healthy controls (n=10, individuals with cystic fibrosis (CF (n=5 or chronic obstructive pulmonary disease (COPD (n=5. Recombinant human SLPI significantly inhibited fMet-Leu-Phe (fMLP and interleukin(IL-8 induced neutrophil chemotaxis (P<0.05 and decreased degranulation of matrix metalloprotease-9 (MMP-9, hCAP-18, and myeloperoxidase (MPO (P<0.05. The mechanism of inhibition involved modulation of cytosolic IP3 production and downstream Ca2+ flux. The described attenuation of Ca2+ flux was overcome by inclusion of exogenous IP3 in electropermeabilized cells. Inhibition of IP3 generation and Ca2+ flux by SLPI may represent a novel anti-inflammatory mechanism, thus strengthening the attractiveness of SLPI as a potential therapeutic molecule in inflammatory airway disease associated with excessive neutrophil influx including CF, non-CF bronchiectasis, and COPD.

  5. Biodegradable Magnetic Particles for Cellular MRI

    Science.gov (United States)

    Nkansah, Michael Kwasi

    Cell transplantation has the potential to treat numerous diseases and injuries. While magnetic particle-enabled, MRI-based cell tracking has proven useful for visualizing the location of cell transplants in vivo, current formulations of particles are either too weak to enable single cell detection or have non-degradable polymer matrices that preclude clinical translation. Furthermore, the off-label use of commercial agents like Feridex®, Bangs beads and ferumoxytol for cell tracking significantly stunts progress in the field, rendering it needlessly susceptible to market externalities. The recent phasing out of Feridex from the market, for example, heightens the need for a dedicated agent specifically designed for MRI-based cell tracking. To this end, we engineered clinically viable, biodegradable particles of iron oxide made using poly(lactide-co-glycolide) (PLGA) and demonstrated their utility in two MRI-based cell tracking paradigms in vivo. Both micro- and nanoparticles (2.1±1.1 μm and 105±37 nm in size) were highly magnetic (56.7-83.7 wt% magnetite), and possessed excellent relaxometry (r2* relaxivities as high as 614.1 s-1mM-1 and 659.1 s -1mM-1 at 4.7 T respectively). Magnetic PLGA micropartides enabled the in vivo monitoring of neural progenitor cell migration to the olfactory bulb in rat brains over 2 weeks at 11.7 T with ˜2-fold greater contrast-to-noise ratio and ˜4-fold better sensitivity at detecting migrated cells in the olfactory bulb than Bangs beads. Highly magnetic PLGA nanoparticles enabled MRI detection (at 11.7 T) of up to 10 rat mesenchymal cells transplanted into rat brain at 100-μm resolution. Highly magnetic PLGA particles were also shown to degrade by 80% in mice liver over 12 weeks in vivo. Moreover, no adverse effects were observed on cellular viability and function in vitro after labeling a wide range of cells. Magnetically labeled rat mesenchymal and neural stem cells retained their ability to differentiate into multiple

  6. Amplitude metrics for cellular circadian bioluminescence reporters.

    Science.gov (United States)

    St John, Peter C; Taylor, Stephanie R; Abel, John H; Doyle, Francis J

    2014-12-01

    Bioluminescence rhythms from cellular reporters have become the most common method used to quantify oscillations in circadian gene expression. These experimental systems can reveal phase and amplitude change resulting from circadian disturbances, and can be used in conjunction with mathematical models to lend further insight into the mechanistic basis of clock amplitude regulation. However, bioluminescence experiments track the mean output from thousands of noisy, uncoupled oscillators, obscuring the direct effect of a given stimulus on the genetic regulatory network. In many cases, it is unclear whether changes in amplitude are due to individual changes in gene expression level or to a change in coherence of the population. Although such systems can be modeled using explicit stochastic simulations, these models are computationally cumbersome and limit analytical insight into the mechanisms of amplitude change. We therefore develop theoretical and computational tools to approximate the mean expression level in large populations of noninteracting oscillators, and further define computationally efficient amplitude response calculations to describe phase-dependent amplitude change. At the single-cell level, a mechanistic nonlinear ordinary differential equation model is used to calculate the transient response of each cell to a perturbation, whereas population-level dynamics are captured by coupling this detailed model to a phase density function. Our analysis reveals that amplitude changes mediated at either the individual-cell or the population level can be distinguished in tissue-level bioluminescence data without the need for single-cell measurements. We demonstrate the effectiveness of the method by modeling experimental bioluminescence profiles of light-sensitive fibroblasts, reconciling the conclusions of two seemingly contradictory studies. This modeling framework allows a direct comparison between in vitro bioluminescence experiments and in silico ordinary

  7. Celecoxib transiently inhibits cellular protein synthesis.

    Science.gov (United States)

    Pyrko, Peter; Kardosh, Adel; Schönthal, Axel H

    2008-01-15

    To uncover the full spectrum of its pharmacological activities, the selective COX-2 inhibitor celecoxib is routinely being used at concentrations of up to 100 microM in cell culture. At these elevated concentrations, several COX-2-independent effects were identified, although many details of these events have remained unclear. Here, we report a COX-2-independent effect of celecoxib that might have profound consequences for the interpretation of previous results obtained at elevated concentrations of this drug in vitro. We found that celecoxib rapidly inhibits general protein translation at concentrations as low as 30 microM. This appears to be a consequence of endoplasmic reticulum (ER) stress and entails the phosphorylation and inactivation of eukaryotic translation initiation factor 2 alpha (eIF2alpha). These effects were not achieved by other coxibs (rofecoxib, valdecoxib) or traditional NSAIDs (indomethacin, flurbiprofen), but were mimicked by the COX-2-inactive celecoxib analog, 2,5-dimethyl-celecoxib (DMC), indicating COX-2 independence. Considering the obvious impact of blocked translation on cellular function, we provide evidence that this severe inhibition of protein synthesis might suffice to explain some of the previously reported COX-2-independent effects of celecoxib, such as the down-regulation of the essential cell cycle regulatory protein cyclin D, which is a short-lived protein that rapidly disappears in response to the inhibition of protein synthesis. Taken together, our findings establish ER stress-induced inhibition of general translation as a critical outcome of celecoxib treatment in vitro, and suggest that this effect needs to be considered when interpreting observations from the use of this drug in cell culture. PMID:17920040

  8. Cysteinyl-Leukotriene Receptors and Cellular Signals

    Directory of Open Access Journals (Sweden)

    G. Enrico Rovati

    2007-01-01

    Full Text Available Cysteinyl-leukotrienes (cysteinyl-LTs exert a range of proinflammatory effects, such as constriction of airways and vascular smooth muscle, increase of endothelial cell permeability leading to plasma exudation and edema, and enhanced mucus secretion. They have proved to be important mediators in asthma, allergic rhinitis, and other inflammatory conditions, including cardiovascular diseases, cancer, atopic dermatitis, and urticaria. The classification into subtypes of the cysteinyl-LT receptors (CysLTRs was based initially on binding and functional data, obtained using the natural agonists and a wide range of antagonists. CysLTRs have proved remarkably resistant to cloning. However, in 1999 and 2000, the CysLT1R and CysLT2R were successfully cloned and both shown to be members of the G-protein coupled receptors (GPCRs superfamily. Molecular cloning has confirmed most of the previous pharmacological characterization and identified distinct expression patterns only partially overlapping. Recombinant CysLTRs couple to the Gq/11 pathway that modulates inositol phospholipids hydrolysis and calcium mobilization, whereas in native systems, they often activate a pertussis toxin-insensitive Gi/o-protein, or are coupled promiscuously to both G-proteins. Interestingly, recent data provide evidence for the existence of an additional receptor subtype that seems to respond to both cysteinyl-LTs and uracil nucleosides, and of an intracellular pool of CysLTRs that may have roles different from those of plasma membrane receptors. Finally, a cross-talk between the cysteinyl-LT and the purine systems is being delineated. This review will summarize recent data derived from studies on the molecular and cellular pharmacology of CysLTRs.

  9. Viscoelastic properties of cellular polypropylene ferroelectrets

    Science.gov (United States)

    Gaal, Mate; Bovtun, Viktor; Stark, Wolfgang; Erhard, Anton; Yakymenko, Yuriy; Kreutzbruck, Marc

    2016-03-01

    Viscoelastic properties of cellular polypropylene ferroelectrets (PP FEs) were studied at low frequencies (0.3-33 Hz) by dynamic mechanical analysis and at high frequencies (250 kHz) by laser Doppler vibrometry. Relaxation behavior of the in-plane Young's modulus ( Y11 ' ˜ 1500 MPa at room temperature) was observed and attributed to the viscoelastic response of polypropylene matrix. The out-of-plane Young's modulus is very small ( Y33 ' ≈ 0.1 MPa) at low frequencies, frequency- and stress-dependent, evidencing nonlinear viscoelastic response of PP FEs. The high-frequency mechanical response of PP FEs is shown to be linear viscoelastic with Y33 ' ≈ 0.8 MPa. It is described by thickness vibration mode and modeled as a damped harmonic oscillator with one degree of freedom. Frequency dependence of Y33 * in the large dynamic strain regime is described by the broad Cole-Cole relaxation with a mean frequency in kHz range attributed to the dynamics of the air flow between partially closed air-filled voids in PP FEs. Switching-off the relaxation contribution causes dynamic crossover from the nonlinear viscoelastic regime at low frequencies to the linear viscoelastic regime at high frequencies. In the small strain regime, contribution of the air flow seems to be insignificant and the power-law response, attributed to the mechanics of polypropylene cell walls and closed air voids, dominates in a broad frequency range. Mechanical relaxation caused by the air flow mechanism takes place in the sound and ultrasound frequency range (10 Hz-1 MHz) and, therefore, should be taken into account in ultrasonic applications of the PP FEs deal with strong exciting or receiving signals.

  10. Cellular events and biomarkers of wound healing

    Directory of Open Access Journals (Sweden)

    Shah Jumaat Mohd. Yussof

    2012-01-01

    Full Text Available Researchers have identified several of the cellular events associated with wound healing. Platelets, neutrophils, macrophages, and fibroblasts primarily contribute to the process. They release cytokines including interleukins (ILs and TNF-α, and growth factors, of which platelet-derived growth factor (PDGF is perhaps the most important. The cytokines and growth factors manipulate the inflammatory phase of healing. Cytokines are chemotactic for white cells and fibroblasts, while the growth factors initiate fibroblast and keratinocyte proliferation. Inflammation is followed by the proliferation of fibroblasts, which lay down the extracellular matrix. Simultaneously, various white cells and other connective tissue cells release both the matrix metalloproteinases (MMPs and the tissue inhibitors of these metalloproteinases (TIMPs. MMPs remove damaged structural proteins such as collagen, while the fibroblasts lay down fresh extracellular matrix proteins. Fluid collected from acute, healing wounds contains growth factors, and stimulates fibroblast proliferation, but fluid collected from chronic, nonhealing wounds does not. Fibroblasts from chronic wounds do not respond to chronic wound fluid, probably because the fibroblasts of these wounds have lost the receptors that respond to cytokines and growth factors. Nonhealing wounds contain high levels of IL1, IL6, and MMPs, and an abnormally high MMP/TIMP ratio. Clinical examination of wounds inconsistently predicts which wounds will heal when procedures like secondary closure are planned. Surgeons therefore hope that these chemicals can be used as biomarkers of wounds which have impaired ability to heal. There is also evidence that the application of growth factors like PDGF will help the healing of chronic, nonhealing wounds.

  11. Fluorescopic evaluation of protein-lipid relations in cellular signalling.

    NARCIS (Netherlands)

    Pap, E.H.W.

    1994-01-01

    IntroductionCellular communication is partly mediated through the modulation of protein activity, structure and dynamics by lipids. In contrast to the biochemical aspects of lipid signalling, relatively little is known about the physical properties of the "signal" lipids (lipids involved in cellular

  12. Simulated Annealing for Location Area Planning in Cellular networks

    OpenAIRE

    Prajapati, N. B.; R. R. Agravat; Hasan, M I

    2010-01-01

    LA planning in cellular network is useful for minimizing location management cost in GSM network. In fact, size of LA can be optimized to create a balance between the LA update rate and expected paging rate within LA. To get optimal result for LA planning in cellular network simulated annealing algorithm is used. Simulated annealing give optimal results in acceptable run-time.

  13. A Wireless Communications Laboratory on Cellular Network Planning

    Science.gov (United States)

    Dawy, Z.; Husseini, A.; Yaacoub, E.; Al-Kanj, L.

    2010-01-01

    The field of radio network planning and optimization (RNPO) is central for wireless cellular network design, deployment, and enhancement. Wireless cellular operators invest huge sums of capital on deploying, launching, and maintaining their networks in order to ensure competitive performance and high user satisfaction. This work presents a lab…

  14. Dynamic production scheduling in virtual cellular manufacturing systems

    OpenAIRE

    马俊; Ma, Jun

    2012-01-01

    Manufacturing companies must constantly improve productivity to respond to dynamic changes in customer demand in order to maintain their competitiveness and marketshares. This requires manufacturers to adopt more efficient methodologies to design and control their manufacturing systems. In recent decades, virtual cellular manufacturing (VCM), as an advanced manufacturing concept, has attracted increasing attention in the research community, because traditional cellular manufacturing is inadeq...

  15. Influence of income on tertiary students acquisition of cellular products

    Directory of Open Access Journals (Sweden)

    G. A.P Drotsky

    2007-12-01

    Full Text Available Purpose: The purpose of the article is to determine whether there are any differences between high and low-income group students in their selection of a cellular phone brand or network operator. Design/Methodology/Approach: Four hypotheses are set to determine if there are any significant differences between the two income groups in current decision-making. It is established that there exist no significant difference between high and low-income students in their selection of cellular phones and network operators. The levels of agreement or disagreement on various statements do, however, give an indication of the importance that students place on aspects that they view as important when acquiring a cellular phone or network operator.Findings: In the article, it is established that no significant differences exist between the two income groups. The levels of agreement or disagreement indicate the importance that subscription method, social value, service quality and branding has on student decision-making. Implications: The article provides a better understanding of the influence that income plays in student's decision-making in acquiring cellular products and services. Possible future research in student cellular usage can be guided through the information obtained in this article. Originality/Value: The article provides information to cellular network operators, service providers and cellular phone manufactures regarding the influence of income on students' acquisition of cellular products and services. Information from the article can assist in the establishment of marketing plans for the student market by these role players.

  16. Insights Into Quantitative Biology: analysis of cellular adaptation

    OpenAIRE

    Agoni, Valentina

    2013-01-01

    In the last years many powerful techniques have emerged to measure protein interactions as well as gene expression. Many progresses have been done since the introduction of these techniques but not toward quantitative analysis of data. In this paper we show how to study cellular adaptation and how to detect cellular subpopulations. Moreover we go deeper in analyzing signal transduction pathways dynamics.

  17. Cellular concentrations of glutamine synthetase in murine organs

    NARCIS (Netherlands)

    H.W.M. van Straaten; Y.J. He; M.M. van Duist; W.T. Labruyere; J.L.M. Vermeulen; P.J. van Dijk; J.M. Ruijter; W.H. Lamers; T.B.M. Hakvoort

    2006-01-01

    Glutamine synthetase (GS) is the only enzyme that can synthesize glutamine, but it also functions to detoxify glutamate and ammonia. Organs with high cellular concentrations of GS appear to function primarily to remove glutamate or ammonia. whereas those with a low cellular concentration appear to p

  18. Teen Perceptions of Cellular Phones as a Communication Tool

    Science.gov (United States)

    Jonas, Denise D.

    2011-01-01

    The excitement and interest in innovative technologies has spanned centuries. However, the invention of the cellular phone has surpassed previous technology interests, and changed the way we communicate today. Teens make up the fastest growing market of current cellular phone users. Consequently, the purpose of this study was to determine teen…

  19. Cellular phones: to talk or not to talk.

    Science.gov (United States)

    Munshi, Anusheel

    2011-01-01

    Cellular phone use has exponentially increased in recent years. There have been some reports of an association of use of these phones with brain tumours. This article gives a summary view of the possible effects related to cellular phone use. It further discusses if we need to observe precautions while using these devices.

  20. Simulated Annealing for Location Area Planning in Cellular networks

    Directory of Open Access Journals (Sweden)

    N. B. Prajapati

    2010-03-01

    Full Text Available LA planning in cellular network is useful for minimizing location management cost in GSM network. Infact, size of LA can be optimized to create a balance between the LA update rate and expected pagingrate within LA. To get optimal result for LA planning in cellular network simulated annealing algorithmis used. Simulated annealing give optimal results in acceptable run-time.