bluuebunny/crossref_metadata_2025 huggingface dataset:
13C MAS NMR and 1H-29Si and 1H-13C heteronuclear correlation study of model xylooligosaccharides
Authors: Schraml Jan , Petráková Eva , Hirsch Ján , Čermák Jan , Chvalovský Václav , Teeaar Raivo , Lippmaa Endel
Published: June 2010

Anomer structures of crystalline D-xylopyranose, all positional isomers of β-D-xylopyranosyl-D-xylopyranose and 2,4-di-β-D-xylopyranosyl-D-xylopyranose were determined by 13C MAS NMR spectroscopy. The saccharides were pertrimethylsilylated by different methods yielding different ratios of pertrimethylsilylated anomers. The NMR spectra (1H, 13C, and 29Si) were assigned by two-dimensional chemical shift correlations. In the anomeric mixtures complete overlap in parts of proton spectra is frequent. In such a case, samples with different anomer ratios considerably facilitate assignment of both 13C and 29Si NMR lines. In analytical applications, however, that method of trimethylsilylation must be chosen which does not allow anomerization prior to silylation. 29Si NMR spectra furnish correct number of OH groups present in the parent compound prior to silylation. Assigned silicon chemical shifts can be used for determination of the sites of glycosidation in oligosaccharides. Glycosidic carbon atoms are considerably shielded after pertrimethylsilylation.
15N, 13C, and 1H NMR spectra of acylated ureas and thioureas
Authors: Jirman Josef , Lyčka Antonín
Published: June 2010

A series of 1-acylated and 1,3-diacylated (acyl = acetyl or benzoyl) ureas and thioureas have been prepared and their proton-coupled and proton-decoupled 15N, 13C, and 1H NMR spectra have been measured. All the signals have been assigned. The 15N NMR chemical shifts in 1-acylated ureas and thioureas are shifted downfield as compared with δ(15N) of urea and thiourea, resp. This shift is greater for N-1 than for N-3 nitrogen atoms in both the series. When comparing acylureas and acylthioureas it is obvious from the Δδ(15N) differences that the CS group is better than CO group in transferring the electron-acceptor effect of acyl group. The proton-coupled 15N NMR spectra of the acylureas dissolved in hexadeuteriodimethyl sulphoxide exhibit a doublet of NH group and a triplet of NH2 group at 25 °C. At the same conditions the acylthioureas exhibit a doublet of NH group, the NH2 group signal being split into a doublet of doublets with different coupling constants 1J(15N, H). The greater one of these coupling constants is due to the s-trans proton with respect to the sulfur atom of the thiourea.
A mathematical modelling of acid catalyzed decomposition of 3-methyl-1,3-diphenyltriazene
Authors: Pytela Oldřich , Svoboda Petr , Večeřa Miroslav
Published: June 2010

The effect of acids on the decomposition of 3-methyl-1,3-diphenyltriazene has been studied in aqueous ethanol (40% (v/v) ethanol). The dependences found between the rate constant and acid concentration have been analyzed by means of non-linear regression using models including the specific and general catalysis and formation of associates between the substrate and the buffer components. The substrate has been found to form electrostatic associates with the conjugated base of acid. The complex formed is decomposed with the assistance of the proton or a general acid in the rate-limiting step to form the product. The Bronsted coefficient α = 0.81 has been found. Investigation of the activation parameters supports the earlier conclusions, indicating a dependence between the reaction mechanism and composition of the aqueous organic solvent.
A convenient synthesis of crown and azacrown ethers with pendant oxirane group
Authors: Bělohradský Martin , Stibor Ivan , Holý Petr , Závada Jiří
Published: June 2010

Synthesis of 4,5-epoxy-2-oxa-1-pentylcrown (I) and N-(2,3-epoxy-1-propyl)azacrown ethers (II) from accessible materials is described.
β-Glucosides of steroidal unsaturated nitriles
Authors: Černý Ivan , Pouzar Vladimír , Drašar Pavel , Havel Miroslav
Published: June 2010

Reaction of 3β-methoxymethoxy-5-pregnen-20-one (Ia) with diethyl cyanomethylphosphonate and subsequent removal of the protecting group afforded (20E)-3β-hydroxy-24-norchola-5,20(22)-diene-23-nitrile (IIIa). Besides the analogous derivative IIIb with another double bond in position 14, the fully saturated compounds IIIc and IIId with configuration 5α and 5β, respectively, were prepared similarly. Silver silicate-catalyzed glycosylation of IIIa-IIId with tetra-O-acetyl-α-D-glucopyranosyl bromide gave β-D-glucopyranosides IVa-IVd in 77-89% yield. A parallel series of hemisuccinates VIa-VId was prepared in 64-81% yields by reaction of IIIa-IIId with 2-(trimethylsilyl)ethyl hydrogen butanedioate followed by deblocking with tetrabutylammonium fluoride. The glucoside IVa was prepared also by an alternative reaction pathway starting from 3β-hydroxy-5-pregnen-20-one (VIII). Compound VIII was converted in 80% yield into the glucoside IX which, after protection as the tetra-O-(trimethylsilyl)derivative XII, was treated with diethyl cyanomethylphosphonate.
Potential antidepressants: 3-Methyl-6-dimethylamino-1,2-diphenylhexan-3-ol and related compounds
Authors: Červená Irena , Holubek Jiří , Svátek Emil , Valchář Martin , Protiva Miroslav
Published: June 2010

3,4-Diphenylbutan-2-one (III) and 3-methyl-3-phenylbutan-2-one were transformed by treatment with 3-dimethylaminopropylmagnesium chloride and 1-methyl-4-piperidylmagnesium chloride to the amino alcohols VI, VII, and X. Compound VI was dehydrated to the olefinic amine VIII, and reduced to the saturated amine IX. 2-(3-Fluoro-4-hydroxyphenyl)ethylamine (XI) was prepared by a modified route via the methoxy precursor XV. Only the amino alcohol VI showed antireserpine activity in one test. The fluoro analogue of dopamine XI did show neither the dopaminomimetic nor the antidopaminergic character.
Synthesis of phosphonylmethyl analogues of diribonucleoside monophosphates containing modified internucleotide bond
Authors: Rosenberg Ivan , Holý Antonín
Published: June 2010

Two types of (2'-5')- and (3'-5')-isomers of analogues of diribonucleoside monophosphates derived from O-phosphonylmethyl derivatives of ribonucleosides, differing in the position of the methylene group in the internucleotide bond (type A, B, C, and D) have been synthesized. The compounds were prepared from methyl esters of O-phosphonylmethylribonucleosides I and XVII by a procedure analogous to the phosphotriester method of oligonucleotide synthesis. The phosphonate moiety was protected with the methyl group. After protection of the hydroxyl or amino groups, the compounds I or XVII were condensed with protected ribonucleosides VIII, XI, XIV, XXIII to afford the neutral diesters IX, XII, XV, XXIV, XXVI, and XXVIII which were isolated by short column chromatography on silica gel. Deprotection, ion-exchange chromatography, and semipreparative HPLC gave (2'-5')- and (3'-5')-isomers of both types of O-phosphonylmethyl analogues of diribonucleoside monophosphates (X, XIII and XXV, XXVII). All these compounds are resistant towards cleavage with ribonucleases A and T2 and with snake venom exonuclease. Under conditions of alkaline hydrolysis of RNA, the analogues of the type A and B are completely stable whereas compounds of the type C and D are degraded to form 2'- or 3'-O-phosphonylmethylribonucleosides and 3'-terminal ribonucleosides.
Topological aspects of chemical reactivity. Valency changes in the course of chemical reactions
Authors: Ponec Robert
Published: June 2010

The Jug and Gopinathan approach to the use of valency changes for the characterization of chemical reactions is generalized by incorporating it into the framework of the recently proposed topological description of chemical reactivity in terms of the overlap determinant method. The conclusions of the simple topological analysis agree with the results of the direct quantum chemical treatment, indicating thus that the overlap determinant method depicts correctly the principal features of the electron density reorganization occuring during the chemical reactions.
A contribution to the nephelometry and turbidimetry of coarse dispersions
Authors: Tockstein Antonín , Skopal František
Published: June 2010

It was found that the flow of light Φr scattered by a dispersion at the angle of 900, integrated along the optical path of the incoming beam, exhibits an extremum in dependence on the dispersion concentration; its concentration coordinate is a linear function on the dimension of the dispersed particles. This linear dependence is also valid for the concentration corresponding to the selected transparence level on the dependence of the flow Φt of light transmitted by the dispersion. A physical model was constructed and the derived equations of the Φr(C) and Φt(C) dependences are in very good agreement with experiments in a concentration range of roughly three orders. The method can be practically applied in determinations of dispersed particle size.
The formation of single crystals of the salts of heteropolyacids in the fused salt
Authors: Drátovský Milan , Mosinger Jiří
Published: June 2010

The Bridgman method was employed to prepare single crystals of Na24As2Mo22O83 and Na24As2W22O83, the conditions for their formation were characterized and X-ray analysis carried out.
Hydrogen bonds in N-(3-chloro-2-benzo[b]thienocarbonyl)- and N-(2-benzo[b]thienocarbonyl)-N'-monosubstituted thioureas
Authors: Hritzová Oľga , Kutschy Peter , Imrich Ján , Schöffmann Thomas
Published: June 2010

N-(3-Chloro-2-benzo[b]thienocarbonyl)-N'-monosubstituted thiourea derivatives undergo photocyclizations with lower yields than those obtained from analogous N',N'-disubstituted derivatives. This decreased reactivity is caused by the existence of a six-membered cyclic form with the very strong hydrogen bond NH···O=C. The possibility of formation of various conformers has been found with N-(2-benzo[b]thienocarbonyl)-N'-monosubstituted thiourea derivatives as a consequence of the rotation around the C(2)-C(O) connecting line.
Reaction of arylmethylenemalonaldehydes with some nucleophiles
Authors: Dvořák Dalimil , Arnold Zdeněk
Published: June 2010

Reaction of arylmethylenemalonaldehydes with tributylphosphine and tertiary amines affords compounds of dipolar structure whereas reaction with primary and secondary amines leads to 1,4-addition products. Salts of nucleophilic inorganic anions add to arylmethylenemalonaldehydes under formation of salts of substituted malonaldehydes.
7-Alkyltheophyllin-8-carbaldehyde
Authors: Rybár Alfonz , Pfleiderer Wolfgang
Published: June 2010

Es wird die Synthese von 7-Alkyltheophyllin-8-carbaldehyd-diethylacetalen VIII-XI und 7-Alkyltheophyllin-8-carbaldehyden XIV-XVII durch Alkylierungsreaktion des Natrium-Salzes des Theophyllin-8-carbaldehyd-diethylacetals (V) oder des Natrium-Salzes des Theophyllin-8-carbaldehyds (XIII) beschrieben. Das benötigte Theophyllin-8-carbaldehyd-diethylacetal wurde entweder mittels der Traube-Synthese aus 4,5-Diamino-1,3-dimethyluracil (VI) oder durch Dehydratationscyclisierung von 4-(2-Diethoxyethylamino)-1,3-dimethyl-5-nitrosouracil (III) erhalten. Das Theophyllin-8-carbaldehyd (XII) wurde durch Hydrolyse des Diethylacetales IV hergestellt.
Studies on 4-(8-hydroxy-5-quinolylazo)benzenesulfonamides and their metal chelates as potential drugs
Authors: Abdel Hafez Ali A. A. , Awad Ibrahim M. A. , Hassan Khairy M.
Published: June 2010

Some new drugs containing both azo sulfonamide and 8-hydroxyquinoline moieties have been prepared. Some metal chelates with Fe3+, Co2+, Cu2+, Ni2+, and Hg2+ ions have been synthesized and screened in vitro for their antibacterial activity.
Potential antihistamine agents: 4-(6,11-Dihydrodibenzo[b,e]thiepin-11-ylidene)-1-methyltetrahydrothiopyranium iodide and similar sulfonium salts derived from related tricyclic systems
Authors: Polívka Zdeněk , Holubek Jiří , Buděšínský Miloš , Matoušová Oluše , Svátek Emil , Metyš Jan , Protiva Miroslav
Published: June 2010

Thioxanthone, 10,11-dihydrodibenzo[a,d]cyclohepten-5-one, dibenzo[b,e]thiepin-11(6H)-one, its 2-methyl derivative, and thieno[2,3-c]-2-benzothiepin-4(9H)-one were reacted with 4-tetrahydrothiopyranylmagnesium bromide and the obtained tertiary alcohols IVabc, VIc, and XIX were dehydrated to the olefinic sulfides IXabc, Xc, and XXI. Addition of methyl iodide afforded the title compounds XIabc, XIIc, and XXII. The Grignard reactions were accompanied by the 1,6-addition giving the ketones XVI-XVIII as by-products. The reductive properties of tetrahydrothiopyranylmagnesium bromide were most striking in the case of reaction with 2-chlorothioxanthone; the isolation of thioxanthene and thioxanthone showed that nuclear dehalogenation took also place. Reactions of 11-chloro-6,11-dihydrodibenzo[b,e]thiepin and benzhydryl chloride with tetrahydrothiopyran-4-ol gave the sulfides XXV and XXVIII; whereas the latter reacted with methyl iodide under the formation of sulfonium salt XXIX, the former was cleaved and gave 4-hydroxyl-1-methyltetrahydrothiopyranium iodide (XXVI). The sulfonium salts are free of the central effects but their antihistamine activity is rather low.
Excess volumes and refractive indices in the benzene-tert-amyl methyl ether and cyclohexane-tert-amyl methyl ether systems at 298.15 K
Authors: Linek Jan
Published: June 2010

Excess molar volumes in the benzene-tert-amyl methyl ether and cyclohexane-tert-amyl methyl ether systems were measured by a vibrating-tube densimeter at 298.15 K and compared with the data for the methanol-tert-amyl methyl ether system determined previously. Besides, the refractive indices in both the systems were measured at the same temperature.
Absorption of oxygen into Ellis liquid
Authors: Potůček František , Stejskal Jiří
Published: June 2010

The authors studied absorption of oxygen by aqueous solutions of poly(acrylamide) which showed a pseudoplastic behaviour. The results were described by equations involving dimensionless criteria modified for the Ellis flow model. The equations were compared with those published for the power flow model.
Venturi tube and single pipe inlet as gas distributors in hydrogenation of rape seed oil
Authors: Rylek Milan , Svoboda Petr , Souček Jiří
Published: June 2010

The effect of hydrogenation conditions on rate of hydrogenation of rape seed oil was studied in a laboratory stirred tank reactor of 250 ml volume, with nickel on kieselguhr catalyst within the range of conditions (150 ⪬ t(°C) ⪬ 190), (0.1 ⪬ P(MPa) ⪬ 1.0), and (0.01 ⪬ cNi(%) ⪬ 0.37). On the basis of these results a comparison of the effect of a Venturi tube and single pipe gas inlet as gas distributors on hydrogenation rate was made in a bench scale unit of 5 l volume.
Infrared spectra of the NO3- anion in NaClO4, Na2SO4, NaClO3, and NaIO3 host structures
Authors: Hájek Bohumil , Muck Alexander , Smrčková Olga
Published: June 2010

The planar NO3- ion (own symmetry D3h) was embedded in NaClO4, Na2SO4, NaClO3 and NaIO3 host structures containing tetrahedral (Td) or pyramidal (C3v) anions, and its infrared spectra were interpreted in terms of group analysis of the crystal symmetry. Where the correlation is satisfied, viz. in NaClO4, NaClO3 and NaIO3, the NO3- anion possesses the site symmetry of the host structure (C2v, C3 and Cs, respectively), whereas in Na2SO4 an additional symmetry lowering takes place (D2 → C2).
Clathrates of tetracyanonickelates containing 1,4-dioxane
Authors: Reháková Mária , Sopková Anna
Published: June 2010

It was found after study of modifications of tetracyano complexes with 1,4-dioxane that a similar product is formed also by direct addition of 1,4-dioxane to a solution of [Ni(NH3)m][Ni(CN)4] or to solid NiNi(CN)4.nH2O; and 1,4-dioxane is initially bonded as a guest molecule and then as a ligand. The amount of guest component or ligand in the compounds Ni(NH3)m(C4H8O2)aNi(CN)4.(y-a)C4H8O2.nH2O and Ni(C4H8O2)aNi(CN)4.(n-a)C4H8O2 depends on the preparation conditions and on the conditions of storage of the solid product after isolation. The results of TA, IR, and GC analysis confirmed the presence of 1,4-dioxane bonded as a guest component and also 1,4-dioxane entering the host structure as a ligand.
Mechanism of action of NaCl on maize alcohol dehydrogenase and phosphoenolpyruvate carboxylase
Authors: Stiborová Marie , Kšinská Světlana , Leblová Sylva
Published: June 2010

Alcohol dehydrogenase (ADH) and phosphoenolpyruvate carboxylase (PEPC) are inhibited by NaCl. PEPC is more sensitive to NaCl than ADH. Chloride ions act toward maize ADH as an inhibitor which is competitive with respect to the substrate, i.e. ethanol; the inhibition with respect to acetaldehyde is of the mixed, competitive-uncompetitive type. The inhibition constants for Cl- ions and ADH are of the order of 10-1 mol l-1. The binding site for Cl- ions constitutes most likely the central Zn atom present in the active center of ADH. NaCl also inhibits two PEPC isozymes (PEPC I and PEPC II) isolated from corn leaves. Isozyme PEPC I is inhibited more strongly than isozyme PEPC II. Sodium chloride acts on both PEPC isozymes as a competitive inhibitor with respect to the substrate, i.e. phosphoenolpyruvate, the inhibition constants being of the order of 10-2 mol l-1. NaCl also acts as an allosteric effector of PEPC I, binding not only to the active center of the enzyme but also to the allosteric site of the protein molecule of PEPC I. The reversible inhibition of PEPC isozymes is converted into irreversible inactivation of the isozymes. The irreversible inhibition is probably a result of a change in the quaternary structure in the protein molecule of PEPC.
Inhibitors of pancreatic and leukocyte elastase
Authors: Kasafírek Evžen , Frič Přemysl , Slabý Jan , Kocna Petr
Published: June 2010

The following alkylamides of ω-carboxyalkanoyldi- and tripeptides of the Ala-Pro or Ala-Ala-Pro sequence have been prepared: ethylamide-, propylamide-, and isobutylamide of 3-carboxypropionylalanyl-proline, ethylamide of 3-carboxypropionylalanyl-alanyl-proline and ethylamide-, propylamide, and isobutylamide of 4-carboxybutyrylalanyl-alanyl-proline. The inhibitors were synthesized by fragment condensation in solution or by gradual construction. The inhibition constants Ki were determined by means of pancreatic elastase (substrates - p-nitroanilides of 4-carboxybutyrylalanyl-alanyl-alanyl-alanine and 3-carboxypropionylalanyl-alanyl-alanyl-alanine) and leukocyte elastase (substrate - p-nitroanilide of 4-carboxybutyrylalanyl-alanyl-alanyl-valine). The strongest inhibitions (Ki) were recorded in ethylamide of 4-carboxybutyrylalanyl-alanyl-proline, 2.0 and 1.6 μmol l-1 for pancreatic elastase, and in propylamide of 4-carboxybutyrylalanyl-alanyl-proline, 0.4 mmol l-1 for leukocyte elastase.
GLOBAL ANALYSIS OF A VIRAL INFECTION MODEL WITH APPLICATION TO HBV INFECTION
Authors: JI YU , MIN LEQUAN , YE YONGAN
Published: June 2010

The basic models of within-host viral infection, proposed by Nowak and May2and Perelson and Nelson,5have been widely used in the studies of HBV and HIV infections. The basic reproduction numbers of the two models are proportional to the number of total cells of the host's organ prior to the infection. In this paper, we formulate an amended Perelson and Nelson's model with standard incidence. The basic reproduction number of the amended model is independent of total cells of the host's organ. If the basic reproduction number R0< 1, then the infection-free equilibrium is globally asymptotically stable and the virus is cleared; if R0> 1, then the virus persists in the host, and solutions approach either an endemic equilibrium or a periodic orbit. Numerical simulations of this model agree well with the clinical HBV infection data. This can provide a possible interpretation for the viral oscillation behaviors, which were observed in chronic HBV infection patients.
MICROBIAL PEST CONTROL: A MATHEMATICAL MODEL
Authors: PATHAK SWETA , MAITI ALAKES
Published: June 2010

The traditional method for controlling pests is the application of chemical pesticides. Growing concern on the negative effects of chemicals has encouraged the development of alternatives. Inundatively and inoculatively applied microbial control agents (virus, bacteria, fungi, and entomopathogenic nematodes) have been developed as alternative control methods of a wide variety of pests. A mathematical model for microbial control of pests is formulated in this paper. The dynamical characteristics of the system are studied. The role of time-delay has been discussed. Numerical simulations are carried out to illustrate the analytical findings. Biological implications have been discussed.
OCCURRENCE OF CHAOS AND ITS POSSIBLE CONTROL IN A PREDATOR-PREY MODEL WITH DENSITY DEPENDENT DISEASE-INDUCED MORTALITY ON PREDATOR POPULATION
Authors: DAS KRISHNA PADA , CHATTERJEE SAMRAT , CHATTOPADHYAY J.
Published: June 2010

Eco-epidemiological models are now receiving much attention to the researchers. In the present article we re-visit the model of Holling-Tanner which is recently modified by Haque and Venturino1with the introduction of disease in prey population. Density dependent disease-induced predator mortality function is an important consideration of such systems. We extend the model of Haque and Venturino1with density dependent disease-induced predator mortality function. The existence and local stability of the equilibrium points and the conditions for the permanence and impermanence of the system are worked out. The system shows different dynamical behaviour including chaos for different values of the rate of infection. The model considered by Haque and Venturino1also exhibits chaotic nature but they did not shed any light in this direction. Our analysis reveals that by controlling disease-induced mortality of predator due to ingested infected prey may prevent the occurrence of chaos.
INTEROPERABLE SUPPLY-CHAIN APPLICATIONS: MESSAGE METAMODEL-BASED SEMANTIC RECONCILIATION OF B2B MESSAGES
Authors: VUJASINOVIC MARKO , BARKMEYER EDWARD , IVEZIC NENAD , MARJANOVIC ZORAN
Published: June 2010

Supply-chain applications exchange numerous electronic business-to-business (B2B) messages of varied types. Traditionally, prior to a message exchange, partners adopt one particular message specification that constrains message structure and syntax to implement compatible application message interfaces. However, in open, dynamic supply-chains, the applications need to interact even though their message interfaces are based on different, yet incompatible message specifications. To achieve such interactions, we propose the Message Metamodel-based semantic reconciliation of B2B messages. The Message Metamodel is a novel, ontological form that provides for common representation of B2B message specifications and messages of various syntaxes, such as Extensible Markup Language (XML) or Electronic Data Interchange (EDI). The experimental investigation showed that proposed semantic reconciliation architecture built atop the Message Metamodel (1) insulates the reconciliation activities from the specific message syntaxes, (2) supports the reconciliation of messages irrespective of message standards used, and (3) enables seamless interoperable message exchange between heterogeneous supply-chain applications.
Actin reorganization contributes to loss of cell adhesion in pemphigus vulgaris
Authors: Gliem Martin , Heupel Wolfgang-Moritz , Spindler Volker , Harms Gregory S. , Waschke Jens
Published: June 2010

In the human autoimmune blistering skin disease pemphigus vulgaris autoantibodies (PV-IgG), which are mainly directed against keratinocyte cell adhesion molecules desmoglein (Dsg) 3 and Dsg1, cause keratinocyte cell dissociation (acantholysis). Recent studies reported that loss of keratinocyte cell adhesion was accompanied by profound alterations of the actin cytoskeleton. Nevertheless, the relevance of actin reorganization in this process is unclear at present. In this study, we provide evidence for an important role of actin reorganization in pemphigus pathogenesis. In parallel to loss of cell adhesion and fragmentation of Dsg3 staining along cell borders, PV-IgG treatment resulted in striking changes in actin cytoskeleton organization. Moreover, in experiments using fluorescence recovery after photobleaching (FRAP), PV-IgG were detected to interfere with actin dynamics. Therefore, we investigated whether pharmacological manipulation of actin polymerization modulates pathogenic effects of PV-IgG. Pharmacological stabilization of actin filaments via jasplakinolide significantly blocked cell dissociation and Dsg3 fragmentation, whereas cytochalasin D-induced actin depolymerization strongly enhanced pathogenic effects of PV-IgG. To substantiate these findings, we studied whether the protective effects of Rho GTPases, which are potent regulators of the actin cytoskeleton and were shown to be involved in pemphigus pathogenesis, were dependent on modulation of actin dynamics. Cytotoxic necrotizing factor-1 (CNF-1)-mediated activation of Rho-GTPases enhanced the cortical junction-associated actin belt and blunted PV-IgG-induced cell dissociation. However, when actin polymerization was blocked under these conditions via addition of latrunculin B, the protective effects of CNF-1 were abrogated. Taken together, these experiments indicate that reorganization of cortical actin filaments is a critical step in PV-IgG-induced keratinocyte dissociation.
Angiotensin II-induced upregulation of AT1 receptor expression: sequential activation of NF-κB and Elk-1 in neurons
Authors: Mitra Amit K. , Gao Lie , Zucker Irving H.
Published: June 2010

It has been clearly established that increased circulating angiotensin II (ANG II) with concurrent upregulation of brain and peripheral ANG II type 1 receptors (AT1R) are important mediators in the pathophysiology of several diseases characterized by sympatho-excitation. In an effort to further understand the regulation of AT1R expression in neurons, we determined the role of sequential activation of the transcription factors nuclear factor-κB (NF-κB) and Ets-like protein 1 (Elk-1) in AT1R upregulation. We used CATH.a neurons as our neuronal cell model. Cells were treated with ANG II (100 nM) over a preset time course. Following ANG II activation, there was a temporal increase in the p65 subunit of NF-κB that was observed at 30 min, peaked at 1 h, and was sustained up to 24 h. There was a concomitant decrease of IκB and increased IκK expression. We also observed an increase in AT1R expression which followed the temporal increase of NF-κB. The activation of NF-κB was blocked by using the inhibitors parthenolide or p65 small interfering RNA (siRNA) which both led to a decrease in AT1R expression. The expression of Elk-1 was upregulated over a time period following ANG II activation and was decreased following NF-κB inhibition. p65-DNA binding was assessed using electrophoretic mobility shift assay, and it was shown that there was a time-dependent increased binding that was inhibited by means of parthenolide pretreatment or siRNA-mediated p65 gene silencing. Therefore, our results suggest a combined role for the transcription factors NF-κB and Elk-1 in the upregulation of AT1R in the CATH.a cell neuronal model. These data imply a positive feedback mechanism that may impact neuronal discharge sensitivity in response to ANG II.
Oxytocin release in magnocellular nuclei: neurochemical mediators and functional significance during gestation
Authors: Bealer Steven L. , Armstrong William E. , Crowley William R.
Published: June 2010

When released from dendrites within the supraoptic (SON) and paraventricular (PVN) nuclei (intranuclear release) during suckling, oxytocin exerts autocrine and paracrine effects on oxytocin neurons that are necessary for the unique timing and episodic pattern of oxytocin release into the systemic circulation that is characteristic of lactation. Recent reports have shown that stimulation of central noradrenergic and histaminergic receptors are both necessary for intranuclear release of oxytocin in response to suckling. In addition, in vitro studies indicate that excitatory amino acids may also be critical for central oxytocin secretion, although in vivo experiments have not provided direct support for this hypothesis. In addition to a critical role in intranuclear oxytocin release during lactation, norepinephrine has also been shown to stimulate central oxytocin during gestation. Stimulation of central oxytocin receptors during gestation appears critical for normal systemic oxytocin secretion in responses to suckling during the subsequent period of lactation. Oxytocin receptor blockade during pregnancy alters normal timing of systemic oxytocin release during suckling and reduces milk delivery. Several adaptations occur in the central oxytocin system that are necessary for determining the unique response characteristic observed during parturition and gestation. Central oxytocin receptor stimulation during gestation has been implicated in pregnancy-related morphological changes in magnocellular oxytocin neurons, disinhibition of oxytocin neurons to GABA, and adaptations in membrane response characteristics of oxytocin neurons. In conclusion, intranuclear oxytocin release during gestation and lactation are critical for establishing, and then evoking the unique pattern of systemic oxytocin secretion in response to the suckling offspring necessary for adequate milk delivery. Furthermore, activation of central noradrenergic receptors appears to be critical for release of central oxytocin in both of these reproductive states.
Effects of gastric distension on blood pressure and superior mesenteric artery blood flow responses to intraduodenal glucose in healthy older subjects
Authors: Vanis Lora , Gentilcore Diana , Hausken Trygve , Pilichiewicz Amelia N. , Lange Kylie , Rayner Christopher K. , Feinle-Bisset Christine , Meyer James H. , Horowitz Michael , Jones Karen L.
Published: June 2010

Postprandial hypotension occurs frequently and is associated with increased morbidity. Gastric distension may attenuate the postprandial fall in blood pressure (BP). Using a barostat, we sought to determine the effects of gastric distension on BP, heart rate (HR), and superior mesenteric artery (SMA) blood flow responses to intraduodenal glucose in eight (6 men, 2 women) healthy older (65–75 yr old) subjects. BP and HR were measured using an automated device and SMA blood flow was measured using Doppler ultrasound on 4 days in random order. SMA blood flow was calculated using the radius of the SMA and time-averaged mean velocity. Subjects were intubated with a nasoduodenal catheter incorporating a duodenal infusion port. On 2 of the 4 days, they were intubated orally with a second catheter, incorporating a barostat bag, positioned in the fundus and set at 8 mmHg above minimal distending pressure. Each subject received a 60-min (0–60 min) intraduodenal infusion of glucose (3 kcal/min) or saline (0.9%); therefore, the four study conditions were as follows: intraduodenal glucose + barostat (glucose + distension), intraduodenal saline + barostat (saline + distension), intraduodenal glucose (glucose), and intraduodenal saline (saline). Systolic and diastolic BP fell during glucose compared with saline ( P = 0.05 and P = 0.003, respectively) and glucose + distension ( P = 0.01 and P = 0.05, respectively) and increased during saline + distension compared with saline ( P = 0.04 and P = 0.006, respectively). The maximum changes in systolic BP were −14 ± 5, +11 ± 2, −3 ± 4, and +15 ± 3 mmHg for glucose, saline, glucose + distension, and saline + distension, respectively. There was an increase in HR during glucose and glucose + distension (maximum rise = 14 ± 2 and 14 ± 3 beats/min, respectively), but not during saline or saline + distension. SMA blood flow increased during glucose and glucose + distension (2,388 ± 365 and 1,673 ± 187 ml/min, respectively), but not during saline, and tended to decrease during saline + distension (821 ± 115 and 864 ± 116 ml/min, respectively). In conclusion, gastric distension has the capacity to abolish the fall in BP and attenuate the rise in SMA blood flow induced by intraduodenal glucose in healthy older subjects.
BCATm deficiency ameliorates endotoxin-induced decrease in muscle protein synthesis and improves survival in septic mice
Authors: Lang Charles H. , Lynch Christopher J. , Vary Thomas C.
Published: June 2010

Endotoxin (LPS) and sepsis decrease mammalian target of rapamycin (mTOR) activity in skeletal muscle, thereby reducing protein synthesis. Our study tests the hypothesis that inhibition of branched-chain amino acid (BCAA) catabolism, which elevates circulating BCAA and stimulates mTOR, will blunt the LPS-induced decrease in muscle protein synthesis. Wild-type (WT) and mitochondrial branched-chain aminotransferase (BCATm) knockout mice were studied 4 h after Escherichia coli LPS or saline. Basal skeletal muscle protein synthesis was increased in knockout mice compared with WT, and this change was associated with increased eukaryotic initiation factor (eIF)-4E binding protein-1 (4E-BP1) phosphorylation, eIF4E·eIF4G binding, 4E-BP1·raptor binding, and eIF3·raptor binding without a change in the mTOR·raptor complex in muscle. LPS decreased muscle protein synthesis in WT mice, a change associated with decreased 4E-BP1 phosphorylation as well as decreased formation of eIF4E·eIF4G, 4E-BP1·raptor, and eIF3·raptor complexes. In BCATm knockout mice given LPS, muscle protein synthesis only decreased to values found in vehicle-treated WT control mice, and this ameliorated LPS effect was associated with a coordinate increase in 4E-BP1·raptor, eIF3·raptor, and 4E-BP1 phosphorylation. Additionally, the LPS-induced increase in muscle cytokines was blunted in BCATm knockout mice, compared with WT animals. In a separate study, 7-day survival and muscle mass were increased in BCATm knockout vs. WT mice after polymicrobial peritonitis. These data suggest that elevating blood BCAA is sufficient to ameliorate the catabolic effect of LPS on skeletal muscle protein synthesis via alterations in protein-protein interactions within mTOR complex-1, and this may provide a survival advantage in response to bacterial infection.
Colorectal and rectocolonic reflexes in canines: involvement of tone, compliance, and anal sphincter relaxation
Authors: Chen Ji-Hong , Sallam Hanaa S. , Lin Lin , Chen Jiande D. Z.
Published: June 2010

Distention of the proximal colon may have inhibitory or excitatory effects on the rectum and vice versa. The reflexes between the proximal colon and the rectum have not been well studied due to difficulties in accessing the proximal colon. The aim of this study was to investigate the reflex responses and their mechanisms between the proximal colon and the rectum in consideration of distention-related changes in tone and compliance of these regions as well as anal sphincter relaxation in a canine model. Proximal colon/rectal tone, compliance, and anal sphincter relaxation were investigated in six dogs chronically implanted with a proximal colon cannula while in the fasting state and during proximal colon distention or rectal distention. It was found that: 1) both rectal distention and proximal colon distention significantly and substantially decreased the compliance of the opposite regions, and guanethidine abolished proximal colon distention-induced changes in rectal compliance; 2) rectal/proximal colon distension decreased proximal colonic/rectal tone, and guanethidine abolished both of these inhibitory effects; 3) the anal sphincter was more sensitive to rectal distention than proximal colon distention; and 4) the minimal distention pressure required to induce anal inhibitory reflex was lower for rectal distention than proximal colon distention. It was concluded that distention-related changes in tone and compliance suggest the long inhibitory reflexes between the proximal colon and the rectum with the sympathetic involvement in rectal responses. The anal sphincter is more sensitive to the distention of the rectum than that of the proximal colon.
Role of β-adrenergic receptors in the hyperphagic and hypermetabolic responses to dietary methionine restriction
Authors: Plaisance Eric P. , Henagan Tara M. , Echlin Haley , Boudreau Anik , Hill Kasey L. , Lenard Natalie R. , Hasek Barbara E. , Orentreich Norman , Gettys Thomas W.
Published: June 2010

Dietary methionine restriction (MR) limits fat deposition and decreases plasma leptin, while increasing food consumption, total energy expenditure (EE), plasma adiponectin, and expression of uncoupling protein 1 (UCP1) in brown and white adipose tissue (BAT and WAT). β-adrenergic receptors (β-AR) serve as conduits for sympathetic input to adipose tissue, but their role in mediating the effects of MR on energy homeostasis is unclear. Energy intake, weight, and adiposity were modestly higher in β3-AR−/−mice on the Control diet compared with wild-type (WT) mice, but the hyperphagic response to the MR diet and the reduction in fat deposition did not differ between the genotypes. The absence of β3-ARs also did not diminish the ability of MR to increase total EE and plasma adiponectin or decrease leptin mRNA, but it did block the MR-dependent increase in UCP1 mRNA in BAT but not WAT. In a further study, propranolol was used to antagonize remaining β-adrenergic input (β1- and β2-ARs) in β3-AR−/−mice, and this treatment blocked >50% of the MR-induced increase in total EE and UCP1 induction in both BAT and WAT. We conclude that signaling through β-adrenergic receptors is a component of the mechanism used by dietary MR to increase EE, and that β1- and β2-ARs are able to substitute for β3-ARs in mediating the effect of dietary MR on EE. These findings are consistent with the involvement of both UCP1-dependent and -independent mechanisms in the physiological responses affecting energy balance that are produced by dietary MR.
Toll-like receptor 2 mediates inhibition of HCO3−absorption by bacterial lipoprotein in medullary thick ascending limb
Authors: Good David W. , George Thampi , Watts Bruns A.
Published: June 2010

Bacterial infection and sepsis are associated with renal tubule dysfunction and dysregulation of systemic electrolyte balance but the underlying mechanisms are incompletely understood. Recently, we demonstrated that HCO3−absorption by the medullary thick ascending limb (MTAL) is inhibited by gram-negative bacterial LPS through activation of Toll-like receptor 4 (TLR4). Here, we examined whether MTAL transport is altered by activation of TLR2, the receptor predominantly responsible for recognizing gram-positive bacteria. Confocal immunofluorescence showed expression of TLR2 in the basolateral membrane domain of rat and mouse MTALs. The functional role of TLR2 was examined in perfused MTALs using Pam3CSK4, a bacterial lipoprotein analog that specifically activates TLR2. Adding Pam3CSK4to the bath decreased HCO3−absorption by 25%. The inhibition by Pam3CSK4was eliminated in MTALs from TLR2−/−mice. HCO3−absorption was also inhibited by the TLR2 agonists lipoteichoic acid and peptidoglycan, two cell wall components of gram-positive bacteria. The MEK/ERK inhibitor U0126 eliminated inhibition of HCO3−absorption by bath LPS but had no effect on inhibition by Pam3CSK4. The inhibition by Pam3CSK4was eliminated by the protein kinase C inhibitors chelerythrine Cl and bisindolylmaleimide. Moreover, the inhibition by Pam3CSK4, lipoteichoic acid, and peptidoglycan was additive to inhibition by LPS. Thus, agonists of basolateral TLR2 and TLR4 inhibit HCO3−absorption independently through distinct signaling pathways. We conclude that bacterial components act directly through TLRs to modify the transport function of renal tubules. During polymicrobial sepsis, gram-positive bacterial molecules acting through TLR2 and gram-negative LPS acting through TLR4 can function through parallel signaling pathways to impair MTAL transport. The inhibition of luminal acidification may impair the ability of the kidneys to correct systemic acidosis that contributes to sepsis pathogenesis.
Bidirectional Neuron–Glia Interactions Triggered by Deficiency of Glutamate Uptake at Spinal Sensory Synapses
Authors: Nie Hui , Zhang Haijun , Weng Han-Rong
Published: June 2010

Bidirectional interactions between neurons and glial cells are crucial to the genesis of pathological pain. The mechanisms regulating these interactions and the role of this process in relaying synaptic input in the spinal dorsal horn remain to be established. We studied the role of glutamate transporters in the regulation of such interactions. On pharmacological blockade of glutamate transporters, slow inward currents (SICs) appeared spontaneously and/or were evoked by peripheral synaptic input in the spinal superficial dorsal horn neurons, including the spinothalamic tract neurons. We showed that the SICs were induced by the release of glutamate from glial cells. On inhibition of glutamate uptake, the stimulation-induced, synaptically released glutamate activated glial cells and caused glial cells to release glutamate. Glial-derived glutamate acted on extrasynaptic N-methyl-d-aspartate (NMDA) receptors mainly composed of NR2B receptors and generated SICs, which led to depolarization and action potential generation in superficial spinal dorsal horn neurons. Thus glutamate transporters regulate glutamatergic neuron–glia interactions at spinal sensory synapses. When glutamate uptake is impaired, glial cells function like excitatory interneurons—they are activated by peripheral synaptic input and release glutamate to activate postsynaptic neurons in spinal pain pathways.
Impaired Transmission in the Corticospinal Tract and Gait Disability in Spinal Cord Injured Persons
Authors: Barthélemy Dorothy , Willerslev-Olsen Maria , Lundell Henrik , Conway Bernard A. , Knudsen Hanne , Biering-Sørensen Fin , Nielsen Jens Bo
Published: June 2010

Rehabilitation following spinal cord injury is likely to depend on recovery of corticospinal systems. Here we investigate whether transmission in the corticospinal tract may explain foot drop (inability to dorsiflex ankle) in persons with spinal cord lesion. The study was performed in 24 persons with incomplete spinal cord lesion (C1 to L1) and 15 healthy controls. Coherence in the 10- to 20-Hz frequency band between paired tibialis anterior muscle (TA) electromyographic recordings obtained in the swing phase of walking, which was taken as a measure of motor unit synchronization. It was significantly correlated with the degree of foot drop, as measured by toe elevation and ankle angle excursion in the first part of swing. Transcranial magnetic stimulation was used to elicit motor-evoked potentials (MEPs) in the TA. The amplitude of the MEPs at rest and their latency during contraction were correlated to the degree of foot drop. Spinal cord injured participants who exhibited a large foot drop had little or no MEP at rest in the TA muscle and had little or no coherence in the same muscle during walking. Gait speed was correlated to foot drop, and was the lowest in participants with no MEP at rest. The data confirm that transmission in the corticospinal tract is of importance for lifting the foot during the swing phase of human gait.
Sensitization of Rapid Dopamine Signaling in the Nucleus Accumbens Core and Shell After Repeated Cocaine in Rats
Authors: Addy Nii A. , Daberkow David P. , Ford Jeremy N. , Garris Paul A. , Wightman R. Mark
Published: June 2010

Repeated cocaine exposure and withdrawal leads to long-term changes, including behavioral and dopamine sensitization to an acute cocaine challenge, that are most pronounced after long withdrawal periods. However, the changes in dopamine neurotransmission after short withdrawal periods are less well defined. To study dopamine neurotransmission after 1-day withdrawal, we used fast-scan cyclic voltammetry (FSCV) to determine whether repeated cocaine alters rapid dopamine release and uptake in the nucleus accumbens (NAc) core and shell. FSCV was performed in urethane anesthetized male Sprague-Dawley rats that had previously received one or seven daily injections of saline or cocaine (15 mg/kg, ip). In response to acute cocaine, subjects showed increased dopamine overflow that resulted from both increased dopamine release and slowed dopamine uptake. One-day cocaine pre-exposure, however, did not alter dopaminergic responses to a subsequent cocaine challenge. In contrast, 7-day cocaine-treated subjects showed a potentiated rapid dopamine response in both the core and shell after an acute cocaine challenge. In addition, kinetic analysis during the cocaine challenge showed a greater increase in apparent Kmof 7-day cocaine exposed subjects. Together, the data provide the first in vivo demonstration of rapid dopamine sensitization in the NAc core and shell after a short withdrawal period. In addition, the data clearly delineate cocaine's release and uptake effects and suggest that the observed sensitization results from greater uptake inhibition in cocaine pre-exposed subjects.
Relationship Between Firing Rate and Recruitment Threshold of Motoneurons in Voluntary Isometric Contractions
Authors: De Luca Carlo J. , Hostage Emily C.
Published: June 2010

We used surface EMG signal decomposition technology to study the control properties of numerous simultaneously active motor units. Six healthy human subjects of comparable age (21 ± 0.63 yr) and physical fitness were recruited to perform isometric contractions of the vastus lateralis (VL), first dorsal interosseous (FDI), and tibialis anterior (TA) muscles at the 20, 50, 80, and 100% maximum voluntary contraction force levels. EMG signals were collected with a five-pin surface array sensor that provided four channels of data. They were decomposed into the constituent action potentials with a new decomposition algorithm. The firings of a total of 1,273 motor unit action potential trains, 20–30 per contraction, were obtained. The recruitment thresholds and mean firing rates of the motor units were calculated, and mathematical equations were derived. The results describe a hierarchical inverse relationship between the recruitment thresholds and the firing rates, including the first and second derivatives, i.e., the velocity and the acceleration of the firing rates. This relationship describes an “operating point” for the motoneuron pool that remains consistent at all force levels and is modulated by the excitation. This relationship differs only slightly between subjects and more distinctly across muscles. These results support the “onion skin” property that suggests a basic control scheme encoded in the physical properties of motoneurons that responds consistently to a “common drive” to the motoneuron pool.
Fast Nonnegative Deconvolution for Spike Train Inference From Population Calcium Imaging
Authors: Vogelstein Joshua T. , Packer Adam M. , Machado Timothy A. , Sippy Tanya , Babadi Baktash , Yuste Rafael , Paninski Liam
Published: June 2010

Fluorescent calcium indicators are becoming increasingly popular as a means for observing the spiking activity of large neuronal populations. Unfortunately, extracting the spike train of each neuron from a raw fluorescence movie is a nontrivial problem. This work presents a fast nonnegative deconvolution filter to infer the approximately most likely spike train of each neuron, given the fluorescence observations. This algorithm outperforms optimal linear deconvolution (Wiener filtering) on both simulated and biological data. The performance gains come from restricting the inferred spike trains to be positive (using an interior-point method), unlike the Wiener filter. The algorithm runs in linear time, and is fast enough that even when simultaneously imaging >100 neurons, inference can be performed on the set of all observed traces faster than real time. Performing optimal spatial filtering on the images further refines the inferred spike train estimates. Importantly, all the parameters required to perform the inference can be estimated using only the fluorescence data, obviating the need to perform joint electrophysiological and imaging calibration experiments.