bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional properties of ryanodine receptors carrying three amino acid substitutions identified in patients affected by multi-minicore disease and central core disease, expressed in immortalized lymphocytes
Authors: Ducreux Sylvie , Zorzato Francesco , Ferreiro Ana , Jungbluth Heinz , Muntoni Francesco , Monnier Nicole , Müller Clemens R. , Treves Susan
Published: March 2006

More than 80 mutations in the skeletal muscle ryanodine receptor gene have been found to be associated with autosomal dominant forms of malignant hyperthermia and central core disease, and with recessive forms of multi-minicore disease. Studies on the functional effects of pathogenic dominant mutations have shown that they mostly affect intracellular Ca2+ homoeostasis, either by rendering the channel hypersensitive to activation (malignant hyperthermia) or by altering the amount of Ca2+ released subsequent to physiological or pharmacological activation (central core disease). In the present paper, we show, for the first time, data on the functional effect of two recently identified recessive ryanodine receptor 1 amino acid substitutions, P3527S and V4849I, as well as that of R999H, another substitution that was identified in two siblings that were affected by multi-minicore disease. We studied the intracellular Ca2+ homoeostasis of EBV (Epstein–Barr virus)-transformed lymphoblastoid cells from the affected patients, their healthy relatives and control individuals. Our results show that the P3527S substitution in the homozygous state affected the amount of Ca2+ released after pharmacological activation with 4-chloro-m-cresol and caffeine, but did not affect the size of the thapsigargin-sensitive Ca2+ stores. The other substitutions had no effect on either the size of the intracellular Ca2+ stores, or on the amount of Ca2+ released after ryanodine receptor activation; however, both the P3527S and V4849I substitutions had a small but significant effect on the resting Ca2+ concentration.
The CD38-independent ADP-ribosyl cyclase from mouse brain synaptosomes: a comparative study of neonate and adult brain
Authors: Ceni Claire , Pochon Nathalie , Villaz Michel , Muller-Steffner Hélène , Schuber Francis , Baratier Julie , De Waard Michel , Ronjat Michel , Moutin Marie-Jo
Published: March 2006

cADPR (cADP-ribose), a metabolite of NAD+, is known to modulate intracellular calcium levels and to be involved in calcium-dependent processes, including synaptic transmission, plasticity and neuronal excitability. However, the enzyme that is responsible for producing cADPR in the cytoplasm of neural cells, and particularly at the synaptic terminals of neurons, remains unknown. In the present study, we show that endogenous concentrations of cADPR are much higher in embryonic and neonate mouse brain compared with the adult tissue. We also demonstrate, by comparing wild-type and Cd38−/− tissues, that brain cADPR content is independent of the presence of CD38 (the best characterized mammalian ADP-ribosyl cyclase) not only in adult but also in developing tissues. We show that Cd38−/− synaptosome preparations contain high ADP-ribosyl cyclase activities, which are more important in neonates than in adults, in line with the levels of endogenous cyclic nucleotide. By using an HPLC method and adapting the cycling assay developed initially to study endogenous cADPR, we accurately examined the properties of the synaptosomal ADP-ribosyl cyclase. This intracellular enzyme has an estimated Km for NAD+ of 21 μM, a broad optimal pH at 6.0–7.0, and the concentration of free calcium has no major effect on its cADPR production. It binds NGD+ (nicotinamide–guanine dinucleotide), which inhibits its NAD+-metabolizing activities (Ki=24 μM), despite its incapacity to cyclize this analogue. Interestingly, it is fully inhibited by low (micromolar) concentrations of zinc. We propose that this novel mammalian ADP-ribosyl cyclase regulates the production of cADPR and therefore calcium levels within brain synaptic terminals. In addition, this enzyme might be a potential target of neurotoxic Zn2+.
Adaptation of enterocytic Caco-2 cells to glucose modulates triacylglycerol-rich lipoprotein secretion through triacylglycerol targeting into the endoplasmic reticulum lumen
Authors: Pauquai Thomas , Bouchoux Julien , Chateau Danielle , Vidal Romain , Rousset Monique , Chambaz Jean , Demignot Sylvie
Published: March 2006

Enterocytes are responsible for the absorption of dietary lipids, which involves TRL [TG (triacylglycerol)-rich lipoprotein] assembly and secretion. In the present study, we analysed the effect on TRL secretion of Caco-2 enterocyte adaptation to a differential glucose supply. We showed that TG secretion in cells adapted to a low glucose supply for 2 weeks after confluence was double that of control cells maintained in high-glucose-containing medium, whereas the level of TG synthesis remained similar in both conditions. This increased secretion resulted mainly from an enlargement of the mean size of the secreted TRL. The increased TG availability for TRL assembly and secretion was not due to an increase in the MTP (microsomal TG transfer protein) activity that is required for lipid droplet biogenesis in the ER (endoplasmic reticulum) lumen, or to the channelling of absorbed fatty acids towards the monoacylglycerol pathway for TG synthesis. Interestingly, by electron microscopy and subcellular fractionation studies, we observed, in the low glucose condition, an increase in the TG content available for lipoprotein assembly in the ER lumen, with the cytosolic/microsomal TG levels being verapamil-sensitive. Overall, we demonstrate that Caco-2 enterocytes modulate TRL secretion through TG partitioning between the cytosol and the ER lumen according to the glucose supply. Our model will help in identifying the proteins involved in the control of the balance between TRL assembly and cytosolic lipid storage. This mechanism may be a way for enterocytes to regulate TRL secretion after a meal, and thus impact on our understanding of post-prandial hypertriglyceridaemia.
Tumour necrosis factor α-converting enzyme mediates ectodomain shedding of Vps10p-domain receptor family members
Authors: Hermey Guido , Sjøgaard Susanne S. , Petersen Claus Munck , Nykjær Anders , Gliemann Jørgen
Published: March 2006

Several transmembrane molecules are cleaved at juxtamembrane extracellular sites leading to shedding of ectodomains. We analysed shedding of members of the Vps10p-D (Vps10p domain; where Vps is vacuolar protein sorting) family of neuronal type-I receptors with partially overlapping functions, and additional proteolytic events initiated by the shedding. When transfected into CHO (Chinese-hamster ovary) cells (CHO-K1), sorCS1a–sorCS1c isoforms were shed at high rates (∼0.61%·min−1) that were increased approx. 3-fold upon stimulation with phorbol ester. sorCS1c identified in the cultured neuroblastoma cell line SH-SY5Y was shed similarly. In CHO-K1 transfectants, constitutive and stimulated shedding of sorCS3 also occurred at high rates (0.29% and 1.03%·min−1). By comparison, constitutive and stimulated shedding of sorLA occurred at somewhat lower rates (0.07% and 0.48%·min−1), whereas sorCS2 and sortilin were shed at very low rates even when stimulated (∼0.01%·min−1). Except for sorCS2, shedding of the receptors was dramatically reduced in mutant CHO cells (CHO-M2) devoid of active TACE (tumour necrosis factor α-converting enzyme), demonstrating that this enzyme accounts for most sheddase activity. The release of sorCS1 and sorLA ectodomains initiated rapid cleavage of the membrane-tethered C-terminal stubs that accumulated only in the presence of γ-secretase inhibitors. Purified shed sorLA bound several ligands similarly to the entire luminal domain of the receptor, including PDGF-BB (platelet-derived growth factor-BB) and amyloid-β precursor protein. In addition, PDGF-BB also bound to the luminal domains of sorCS1 and sorCS3. The results suggest that ectodomains shed from a subset of Vps10p-D receptors can function as carrier proteins.
rhEPO (recombinant human eosinophil peroxidase): expression inPichia pastorisand biochemical characterization
Authors: Ciaccio Chiara , Gambacurta Alessandra , Sanctis Giampiero DE , Spagnolo Domenico , Sakarikou Christina , Petrella Giovanni , Coletta Massimo
Published: March 2006

A Pichia pastoris expression system has for the first time been successfully developed to produce rhEPO (recombinant human eosinophil peroxidase). The full-length rhEPO coding sequence was cloned into the pPIC9 vector in frame with the yeast α-Factor secretion signal under the transcriptional control of the AOX (acyl-CoA oxidase) promoter, and transformed into P. pastoris strain GS115. Evidence for the production of rhEPO by P. pastoris as a glycosylated dimer precursor of approx. 80 kDa was determined by SDS/PAGE and gel filtration chromatography. Recombinant hEPO undergoes proteolytic processing, similar to that in the native host, to generate two chains of approx. 50 and 20 kDa. A preliminary biochemical characterization of purified rhEPO demonstrated that the spectral and kinetic properties of the recombinant wild-type EPO are comparable with those of the native enzyme and are accompanied by oxidizing activity towards several physiological anionic substrates such as SCN−, Br− and Cl−. On the basis of the estimated Km and kcat values it is evident that the pseudohalide SCN− is the most specific substrate for rhEPO, consistent with the catalytic properties of other mammalian EPOs purified from blood.
The TLX2 homeobox gene is a transcriptional target of PHOX2B in neural-crest-derived cells
Authors: Borghini Silvia , Bachetti Tiziana , Fava Monica , Di Duca Marco , Cargnin Francesca , Fornasari Diego , Ravazzolo Roberto , Ceccherini Isabella
Published: March 2006

The TLX2 (HOX11L1, Ncx, Enx) and PHOX2B genes encode transcription factors crucial in the development of neural-crest-derived cells, leading to ANS (autonomic nervous system) specific neuronal lineages. Moreover, they share a similar expression pattern and are both involved in downstream steps of BMP (bone morphogenetic protein) signalling. In an attempt to reconstruct the gene network sustaining the correct development of the ANS, we have undertaken an in vitro experimental strategy to identify direct upstream regulators of the TLX2 gene. After characterizing a sequence displaying enhancer property in its 5′ flanking region, we confirmed the functional link between the human PHOX2B and TLX2 genes. Transient transfections and electrophoretic-mobility-shift assays suggested that PHOX2B is able to bind the cell-specific element in the 5′ regulatory region of the TLX2 gene, determining its transactivation in neuroblastoma cells. Such interaction was also confirmed in vivo by means of chromatin immunoprecipitation assay and, in addition, up-regulation of endogenous TLX2 mRNA level was demonstrated following PHOX2B over-expression, by quantitative real-time PCR. Finally, PHOX2B proteins carrying mutations responsible for CCHS (congenital central hypoventilation syndrome) development showed a severe impairment in activating TLX2 expression, both in vitro and in vivo. Taken together, these results support the PHOX2B–TLX2 promoter interaction, suggesting a physiological role in the transcription-factor cascade underlying the differentiation of neuronal lineages of the ANS during human embryogenesis.
Ca2+-ATPases in non-failing and failing heart: evidence for a novel cardiac sarco/endoplasmic reticulum Ca2+-ATPase 2 isoform (SERCA2c)
Authors: Dally Saoussen , Bredoux Raymonde , Corvazier Elisabeth , Andersen Jens P. , Clausen Johannes D. , Dode Leonard , Fanchaouy Mohammed , Gelebart Pascal , Monceau Virginie , Del Monte Frederica , Gwathmey Judith K. , Hajjar Roger , Chaabane Chiraz , Bobe Régis , Raies Aly , Enouf Jocelyne
Published: March 2006

We recently documented the expression of a novel human mRNA variant encoding a yet uncharacterized SERCA [SR (sarcoplasmic reticulum)/ER (endoplasmic reticulum) Ca2+-ATPase] protein, SERCA2c [Gélébart, Martin, Enouf and Papp (2003) Biochem. Biophys. Res. Commun. 303, 676–684]. In the present study, we have analysed the expression and functional characteristics of SERCA2c relative to SERCA2a and SERCA2b isoforms upon their stable heterologous expression in HEK-293 cells (human embryonic kidney 293 cells). All SERCA2 proteins induced an increased Ca2+ content in the ER of intact transfected cells. In microsomes prepared from transfected cells, SERCA2c showed a lower apparent affinity for cytosolic Ca2+ than SERCA2a and a catalytic turnover rate similar to SERCA2b. We further demonstrated the expression of the endogenous SERCA2c protein in protein lysates isolated from heart left ventricles using a newly generated SERCA2c-specific antibody. Relative to the known uniform distribution of SERCA2a and SERCA2b in cardiomyocytes of the left ventricle tissue, SERCA2c was only detected in a confined area of cardiomyocytes, in close proximity to the sarcolemma. This finding led us to explore the expression of the presently known cardiac Ca2+-ATPase isoforms in heart failure. Comparative expression of SERCAs and PMCAs (plasma-membrane Ca2+-ATPases) was performed in four nonfailing hearts and five failing hearts displaying mixed cardiomyopathy and idiopathic dilated cardiomyopathies. Relative to normal subjects, cardiomyopathic patients express more PMCAs than SERCA2 proteins. Interestingly, SERCA2c expression was significantly increased (166±26%) in one patient. Taken together, these results demonstrate the expression of the novel SERCA2c isoform in the heart and may point to a still unrecognized role of PMCAs in cardiomyopathies.
The secreted Salmonella dublin phosphoinositide phosphatase, SopB, localizes to PtdIns(3)P-containing endosomes and perturbs normal endosome to lysosome trafficking
Authors: Dukes Joseph D. , Lee Huailo , Hagen Rachel , Reaves Barbara J. , Layton Abigail N. , Galyov Edouard E. , Whitley Paul
Published: March 2006

Invasion and survival in mammalian cells by Salmonella enterica is mediated by bacterial proteins that are delivered to the host cell cytoplasm by type III secretion systems. One of these proteins, SopB/SigD, is a phosphoinositide phosphatase that can hydrolyse a number of substrates in vitro including PtdIns(3,5)P2. These substrates are, however, likely to be restricted in vivo by the localization of SopB, as different phosphoinositides have distinct spatial distributions in mammalian cells. In the present study, we show that heterologously expressed SopB localizes almost exclusively to endosomes containing the lipid PtdIns(3)P, and on which ESCRT (endosomal sorting complexes required for transport) proteins assemble. Furthermore, we present evidence that SopB can inhibit trafficking of activated epidermal growth factor receptor to the lysosome. These results provide further evidence that PtdIns(3,5)P2, a lipid involved in endosomal maturation, may be a relevant in vivo substrate of SopB. We hypothesize that reduction of PtdIns(3,5)P2 levels in cells by the action of SopB may perturb the function of a subset of ESCRT proteins that have previously been shown to bind to this lipid.
Radical scavenger can scavenge lipid allyl radicals complexed with lipoxygenase at lower oxygen content
Authors: Koshiishi Ichiro , Tsuchida Kazunori , Takajo Tokuko , Komatsu Makiko
Published: March 2006

Lipoxygenases have been proposed to be a possible factor that is responsible for the pathology of certain diseases, including ischaemic injury. In the peroxidation process of linoleic acid by lipoxygenase, the E,Z-linoleate allyl radical–lipoxygenase complex seems to be generated as an intermediate. In the present study, we evaluated whether E,Z-linoleate allyl radicals on the enzyme are scavenged by radical scavengers. Linoleic acid, the content of which was greater than the dissolved oxygen content, was treated with soya bean lipoxygenase-1 (ferric form) in the presence of radical scavenger, CmP (3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl). The reaction rate between oxygen and lipid allyl radical is comparatively faster than that between CmP and lipid allyl radical. Therefore a reaction between linoleate allyl radical and CmP was not observed while the dioxygenation of linoleic acid was ongoing. After the dissolved oxygen was depleted, CmP stoichiometrically trapped linoleate-allyl radicals. Accompanied by this one-electron redox reaction, the resulting ferrous lipoxygenase was re-oxidized to the ferric form by hydroperoxylinoleate. Through the adduct assay via LC (liquid chromatography)–MS/MS (tandem MS), four E,Z-linoleate allyl radical–CmP adducts corresponding to regio- and diastereo-isomers were detected in the linoleate/lipoxygenase system, whereas E,E-linoleate allyl radical–CmP adducts were not detected at all. If E,Z-linoleate allyl radical is liberated from the enzyme, the E/Z-isomer has to reach equilibrium with the thermodynamically favoured E/E-isomer. These data suggested that the E,Z-linoleate allyl radicals were not liberated from the active site of lipoxygenase before being trapped by CmP. Consequently, we concluded that the lipid allyl radicals complexed with lipoxygenase could be scavenged by radical scavengers at lower oxygen content.
Characterization of Schistosoma mansoni Sds homologue, a leucine-rich repeat protein that interacts with protein phosphatase type 1 and interrupts a G2/M cell-cycle checkpoint
Authors: Daher Wassim , Cailliau Katia , Takeda Kojiro , Pierrot Christine , Khayath Naji , Dissous Colette , Capron Monique , Yanagida Mitsuhiro , Browaeys Edith , Khalife Jamal
Published: March 2006

The suppressor of the dis2 mutant (sds22+) has been shown to be an essential regulator in cell division of fission and budding yeast where its deletion causes mitotic arrest. Its role seems to take place through the activation of PP1 (protein phosphatase type 1) in Schizosaccharomyces pombe. In the trematode Schistosoma mansoni, we have identified the Sds22 homologue (SmSds), and the PP1 (SmPP1). We showed by using a GST (glutathione S-transferase) pull-down assay that the SmSds gene product interacts with SmPP1 and that the SmSds–SmPP1 complex is present in parasite extracts. Furthermore, we observed that SmSds inhibited PP1 activity. Functional studies showed that the microinjection of SmSds into Xenopus oocytes interacted with the Xenopus PP1 and disrupted the G2/M cell-cycle checkpoint by promoting progression to GVBD (germinal vesicle breakdown). Similar results showing the appearance of GVBD were observed when oocytes were treated with anti-PP1 antibodies. Taken together, these observations suggest that SmSds can regulate the cell cycle by binding to PP1.
Removal of the glycosylphosphatidylinositol anchor from PrPSc by cathepsin D does not reduce prion infectivity
Authors: Lewis Patrick A. , Properzi Francesca , Prodromidou Kanella , Clarke Anthony R. , Collinge John , Jackson Graham S.
Published: March 2006

According to the protein-only hypothesis of prion propagation, prions are composed principally of PrPSc, an abnormal conformational isoform of the prion protein, which, like its normal cellular precursor (PrPC), has a GPI (glycosylphosphatidylinositol) anchor at the C-terminus. To date, elucidating the role of this anchor on the infectivity of prion preparations has not been possible because of the resistance of PrPSc to the activity of PI-PLC (phosphoinositide-specific phospholipase C), an enzyme which removes the GPI moiety from PrPC. Removal of the GPI anchor from PrPSc requires denaturation before treatment with PI-PLC, a process that also abolishes infectivity. To circumvent this problem, we have removed the GPI anchor from PrPSc in RML (Rocky Mountain Laboratory)-prion-infected murine brain homogenate using the aspartic endoprotease cathepsin D. This enzyme eliminates a short sequence at the C-terminal end of PrP to which the GPI anchor is attached. We found that this modification has no effect (i) on an in vitro amplification model of PrPSc, (ii) on the prion titre as determined by a highly sensitive N2a-cell based bioassay, or (iii) in a mouse bioassay. These results show that the GPI anchor has little or no role in either the propagation of PrPSc or on prion infectivity.
Molecular cloning of disintegrins from Cerastes vipera and Macrovipera lebetina transmediterranea venom gland cDNA libraries: insight into the evolution of the snake venom integrin-inhibition system
Authors: Sanz Libia , Bazaa Amine , Marrakchi Naziha , Pérez Alicia , Chenik Mehdi , Bel Lasfer Zakaria , El Ayeb Mohamed , Calvete Juan J.
Published: March 2006

We report the cloning and sequence analysis of Cerastes vipera and Macrovipera lebetina transmediterranea cDNAs coding for short non-RGD (Arg-Gly-Asp) disintegrins and for dimeric disintegrin subunits. The mRNAs belong to the short-coding class, suggesting that these disintegrin mRNAs may be more widely distributed than previously thought. Our data also argue for a common ancestry of the mRNAs of short disintegrins and those coding for precursors of dimeric disintegrin chains. The Macrovipera lebetina transmediterranea dimeric disintegrin reported to inhibit the laminin-binding integrins α3β1, α6β1 and α7β1 was analysed using a proteomic approach and was shown to bear MLD (Met-Leu-Asp) and VGD (Val-Gly-Asp) motifs. The results highlight the fact that disintegrins have evolved a restricted panel of integrin-blocking sequences that segregate with defined branches of the phylogenetic tree of the integrin α-chains, providing novel insights into the evolutionary adaptation of the snake venom antagonists to the ligand-binding sites of their target integrin receptors.
The ABC transporter BmrA from Bacillus subtilis is a functional dimer when in a detergent-solubilized state
Authors: Ravaud Stéphanie , Do Cao Marie-Ange , Jidenko Marie , Ebel Christine , Le Maire Marc , Jault Jean-Michel , Di Pietro Attilio , Haser Richard , Aghajari Nushin
Published: March 2006

BmrA from Bacillus subtilis is a half-size ABC (ATP-binding cassette) transporter involved in multidrug resistance. Although its supramolecular organization has been investigated after reconstitution in a lipid bilayer environment, and shows a dimeric and possibly a tetrameric form, the precise quaternary structure in a detergent-solubilized state has never been addressed. In the present study, BmrA was purified from Escherichia coli membranes using an optimized purification protocol and different detergents. Furthermore, the ATPase activity of BmrA and the quantity of bound lipids and detergent were determined, and the oligomeric state was analysed using SEC (size-exclusion chromatography) and analytical ultracentrifugation. The activity and the quaternary structure of BmrA appeared to be strongly influenced by the type and concentration of the detergent used. SEC data showed that BmrA could be purified in a functional form in 0.05 and 0.01% DDM (n-dodecyl-β-D-maltoside) and was homogeneous and monodisperse with an Rs (Stokes radius) of 5.6 nm that is compatible with a dimer structure. Sedimentation-velocity and equilibrium experiments unequivocally supported that BmrA purified in DDM is a dimer and excluded the presence of other oligomeric states. These observations, which are discussed in relation to results obtained in proteoliposomes, also constitute an important first step towards crystallographic studies of BmrA structure.
Mutations in the regulatory subunit of yeast acetohydroxyacid synthase affect its activation by MgATP
Authors: Lee Yu-Ting , Duggleby Ronald G.
Published: March 2006

Isoleucine, leucine and valine are synthesized via a common pathway in which the first reaction is catalysed by AHAS (acetohydroxyacid synthase; EC 2.2.1.6). This heterotetrameric enzyme is composed of a larger subunit that contains the catalytic machinery and a smaller subunit that plays a regulatory role. The RSU (regulatory subunit) enhances the activity of the CSU (catalytic subunit) and mediates end-product inhibition by one or more of the branched-chain amino acids, usually valine. Fungal AHAS differs from that in other organisms in that the inhibition by valine is reversed by MgATP. The fungal AHAS RSU also differs from that in other organisms in that it contains a sequence insert. We suggest that this insert may form the MgATP-binding site and we have tested this hypothesis by mutating ten highly conserved amino acid residues of the yeast AHAS RSU. The modified subunits were tested for their ability to activate the yeast AHAS CSU, to confer sensitivity to valine inhibition and to mediate reversal of the inhibition by MgATP. All but one of the mutations resulted in substantial changes in the properties of the RSU. Unexpectedly, four of them gave a protein that required MgATP in order for strong stimulation of the CSU and valine inhibition to be observed. A model to explain this result is proposed. Five of the mutations abolished MgATP activation and are suggested to constitute the binding site for this modulator.
Misincorporation of free m-tyrosine into cellular proteins: a potential cytotoxic mechanism for oxidized amino acids
Authors: Gurer-Orhan Hande , Ercal Nuran , Mare Suneetha , Pennathur Subramaniam , Orhan Hilmi , Heinecke Jay W.
Published: March 2006

In vitro studies demonstrate that the hydroxyl radical converts L-phenylalanine into m-tyrosine, an unnatural isomer of L-tyrosine. Quantification of m-tyrosine has been widely used as an index of oxidative damage in tissue proteins. However, the possibility that m-tyrosine might be generated oxidatively from free L-phenylalanine that could subsequently be incorporated into proteins as an L-tyrosine analogue has received little attention. In the present study, we demonstrate that free m-tyrosine is toxic to cultured CHO (Chinese-hamster ovary) cells. We readily detected radiolabelled material in proteins isolated from CHO cells that had been incubated with m-[14C]tyrosine, suggesting that the oxygenated amino acid was taken up and incorporated into cellular proteins. m-Tyrosine was detected by co-elution with authentic material on HPLC and by tandem mass spectrometric analysis in acid hydrolysates of proteins isolated from CHO cells exposed to m-tyrosine, indicating that free m-tyrosine was incorporated intact rather than being metabolized to other products that were subsequently incorporated into proteins. Incorporation of m-tyrosine into cellular proteins was sensitive to inhibition by cycloheximide, suggesting that protein synthesis was involved. Protein synthesis using a cell-free transcription/translation system showed that m-tyrosine was incorporated into proteins in vitro by a mechanism that may involve L-phenylalanine-tRNA synthetase. Collectively, these observations indicate that m-tyrosine is toxic to cells by a pathway that may involve incorporation of the oxidized amino acid into proteins. Thus misincorporation of free oxidized amino acids during protein synthesis may represent an alternative mechanism for oxidative stress and tissue injury during aging and disease.
Hepatic very-low-density lipoprotein and apolipoprotein B production are increased following in vivo induction of betaine–homocysteine S-methyltransferase
Authors: Sparks Janet D. , Collins Heidi L. , Chirieac Doru V. , Cianci Joanne , Jokinen Jenny , Sowden Mark P. , Galloway Chad A. , Sparks Charles E.
Published: March 2006

We have previously reported a positive correlation between the expression of BHMT (betaine–homocysteine S-methyltransferase) and ApoB (apolipoprotein B) in rat hepatoma McA (McArdle RH-7777) cells [Sowden, Collins, Smith, Garrow, Sparks and Sparks (1999) Biochem. J. 341, 639–645]. To examine whether a similar relationship occurs in vivo, hepatic BHMT expression was induced by feeding rats a Met (L-methionine)-restricted betaine-containing diet, and parameters of ApoB metabolism were evaluated. There were no generalized metabolic abnormalities associated with Met restriction for 7 days, as evidenced by control levels of serum glucose, ketones, alanine aminotransferase and L-homocysteine levels. Betaine plus the Met restriction resulted in lower serum insulin and non-esterified fatty acid levels. Betaine plus Met restriction induced hepatic BHMT 4-fold and ApoB mRNA 3-fold compared with Met restriction alone. No changes in percentage of edited ApoB mRNA were observed on the test diets. An increase in liver ApoB mRNA correlated with an 82% and 46% increase in ApoB and triacylglycerol production respectively using in vivo Triton WR 1339. Increased secretion of VLDL (very-low-density lipoprotein) with Met restriction plus betaine was associated with a 45% reduction in liver triacylglycerol compared with control. Nuclear run-off assays established that transcription of both bhmt and apob genes was also increased in Met-restricted plus betaine diets. No change in ApoB mRNA stability was detected in BHMT-transfected McA cells. Hepatic ApoB and BHMT mRNA levels were also increased by 1.8- and 3-fold respectively by betaine supplementation of Met-replete diets. Since dietary betaine increased ApoB mRNA, VLDL ApoB and triacylglycerol production and decreased hepatic triacylglycerol, results suggest that induction of apob transcription may provide a potential mechanism for mobilizing hepatic triacylglycerol by increasing ApoB available for VLDL assembly and secretion.
Measures of chaos and equipartition in integrable and nonintegrable lattices
Authors: Zabusky Norman J. , Sun Zhanyu , Peng Gaozhu
Published: March 2006

We have simulated numerically the behavior of the one-dimensional, periodic FPU-alpha and Toda lattices to optical and acoustic initial excitations of small-but finite and large amplitudes. For the small-through-intermediate amplitudes (small initial energy per particle) we find nearly recurrent solutions, where the acoustic result is due to the appearance of solitons and where the optical result is due to the appearance of localized breather-like packets. For large amplitudes, we find complex-but-regular behavior for the Toda lattice and “stochastic” or chaotic behaviors for the alpha lattice. We have used the well-known diagnostics: Localization parameter; Lyapounov exponent, and slope of a linear fit to linear normal mode energy spectra. Space-time diagrams of local particle energy and a wave-related quantity, a discretized Riemann invariant are also shown. The discretized Riemann invariants of the alpha lattice reveal soliton and near-soliton properties for acoustic excitations. Except for the localization parameter, there is a clear separation in behaviors at long-time between integrable and nonintegrable systems.
Dispersion relation of the nonlinear Klein-Gordon equation through a variational method
Authors: Amore Paolo , Raya Alfredo
Published: March 2006

We derive approximate expressions for the dispersion relation of the nonlinear Klein-Gordon equation in the case of strong nonlinearities using a method based on the linear delta expansion. All the results obtained in this article are fully analytical, never involve the use of special functions, and can be used to obtain systematic approximations to the exact results to any desired degree of accuracy. We compare our findings with similar results in the literature and show that our approach leads to better and simpler results.
Molecular-dynamics evaluation of fluid-phase equilibrium properties by a novel free-energy perturbation approach: Application to gas solubility and vapor pressure of liquid hexane
Authors: Kuwajima Satoru , Kikuchi Hiroaki , Fukuda Mitsuhiro
Published: March 2006

A novel free-energy perturbation method is developed for the computation of the free energy of transferring a molecule between fluid phases. The methodology consists in drawing a free-energy profile of the target molecule moving across a binary-phase structure built in the computer. The novelty of the method lies in the difference of the definition of the free-energy profile from the common definition. As an important element of the method, the process of making a correction to the transfer free energy with respect to the cutoff of intermolecular forces is elucidated. In order to examine the performance of the method in the application to fluid-phase equilibrium properties, molecular-dynamics computations are carried out for the evaluation of gas solubility and vapor pressure of liquid n-hexane at 298.15K. The gas species treated are methane, ethane, propane, and n-butane, with the gas solubility expressed as Henry’s constant. It is shown that the method works fine and calculated results are generally in good agreement with experiments. It is found that the cutoff correction is strikingly large, constituting a dominant part of the calculated transfer free energy at the cutoff of 8Å.
Adaptive synchronization of neural networks with or without time-varying delay
Authors: Cao Jinde , Lu Jianquan
Published: March 2006

In this paper, based on the invariant principle of functional differential equations, a simple, analytical, and rigorous adaptive feedback scheme is proposed for the synchronization of almost all kinds of coupled identical neural networks with time-varying delay, which can be chaotic, periodic, etc. We do not assume that the concrete values of the connection weight matrix and the delayed connection weight matrix are known. We show that two coupled identical neural networks with or without time-varying delay can achieve synchronization by enhancing the coupling strength dynamically. The update gain of coupling strength can be properly chosen to adjust the speed of achieving synchronization. Also, it is quite robust against the effect of noise and simple to implement in practice. In addition, numerical simulations are given to show the effectiveness of the proposed synchronization method.
Phase transitions of methane using molecular dynamics simulations
Authors: El-Sheikh S. M. , Barakat K. , Salem N. M.
Published: March 2006

Using a short ranged Lennard-Jones interaction and a long ranged electrostatic potential, CH4under high pressure was modeled. Molecular dynamics simulations on small clusters (108 and 256molecules) were used to explore the phase diagram. Regarding phase transitions at different temperatures, our numerical findings are consistent with experimental results to a great degree. In addition, the hysteresis effect is displayed in our results.
Enol-keto tautomerism of aromatic photochromic Schiff base N,N′-bis(salicylidene)-p-phenylenediamine: Ground state equilibrium and excited state deactivation studied by solvatochromic measurements on ultrafast time scale
Authors: Ziółek Marcin , Kubicki Jacek , Maciejewski Andrzej , Naskrȩcki Ryszard , Grabowska Anna
Published: March 2006

A photochromic symmetric Schiff base, N,N′-bis(salicylidene)-p-phenylenediamine, is proposed as a probe for the study of solvent dependent enol-keto tautomerism in the ground and excited states. The ground state equilibrium between the enol-keto tautomers is found to depend mainly not on polarity but on the proton donating ability of the solvent. Upon selective excitation of each of these tautomers, the same excited state of a keto tautomer is created: in enol, after the ultrafast excited state intramolecular proton transfer (ESIPT), reaction, and in keto tautomer, directly. Then some part (<30%) of excited molecules are transferred to the photochromic form in its ground state. The evidence of another ultrafast deactivation channel in the excited enol tautomer competing with ESIPT has been found. The solvent does not influence the ESIPT dynamics nor the efficiency of the creation of the photochrome.
Phenomenological theory of the kink instability in a slender plasma column
Authors: Ryutov D. D. , Furno I. , Intrator T. P. , Abbate S. , Madziwa-Nussinov T.
Published: March 2006

In this paper we are concerned with the kink instability of a current-carrying plasma column whose radius a is much smaller than its length L. In the limit a⪡L, one can consider the column as a thin filament whose kinking can be adequately described simply by a two dimensional 2D displacement vector, ξx=ξx(z,t); ξy=ξy(z,t). Details of the internal structure of the column such as the radial distribution of the current, density, and axial flow can be lumped into some phenomenological parameters. This approach is particularly efficient in the problems with nonideal (sheath) boundary conditions (BC) at the end electrodes, with the finite plasma resistivity, and with a substantial axial flow. With the sheath BC imposed at one of the endplates, we find instability in the domain well below the classical Kruskal-Shafranov limit. The presence of an axial flow causes the onset of rotation of the kink and strong axial “skewness” of the eigenfunction, with the perturbation amplitude increasing in the flow direction. The limitations of the phenomenological approach are analyzed and are related to the steepness with which the plasma resistivity increases at the plasma boundary with vacuum.
Quantum mechanical investigations of the N(S4)+O2(XΣg−3)→NO(XΠ2)+O(P3) reaction
Authors: Sultanov Renat A. , Balakrishnan N.
Published: March 2006

The reaction between energetic nitrogen atoms and oxygen molecules has received important attention in connection with nitric oxide chemistry in the lower thermosphere. We report time-independent quantum mechanical calculations of the N(S4)+O2→NO+O reaction employing the XA′2 and aA′4 electronic potential energy surfaces of Sayós et al. [J. Chem. Phys. 117, 670 (2002)]. We confirm the production of highly vibrationally excited NO molecules, consistent with previous semiclassical and more recent time-dependent quantum wave packet studies. Calculations are carried out for total angular momentum quantum number J=0 and cross sections and rate coefficients are extracted using the J-shifting approximation. The results are in good agreement with available experimental and theoretical data.
Microwave plasma torch abatement of NF3 and SF6
Authors: Hong Yong Cheol , Uhm Han Sup , Chun Byung Jun , Lee Sun Ku , Hwang Sang Kyu , Kim Dong Su
Published: March 2006

An atmospheric pressure microwave plasma torch as a tool for fluorinated compounds (FCs) abatement was presented. Detailed experiments were conducted on the abatement of NF3 and SF6 in terms of destruction and removal efficiency (DRE) using Fourier transform infrared (FTIR). Swirl gas, compressed air for stable plasma, was tangentially injected into the microwave plasma torch and a mixture of N2, NF3, or SF6, and C2H4 was axially injected. The DRE of 99.1% for NF3 was achieved without an additive gas at the total flow rate of 50.1 liters per minute (lpm) by applying a microwave power of 1.4kW. Also, a DRE of SF6 up to 90.1% was obtained at the total flow rate of 40.6lpm using an applied microwave power of 1.4kW. Experimental results indicate that the microwave plasma abatement device can successfully eliminate FCs in the semiconductor industry.
Study of proton acceleration at the target front surface in laser-solid interactions by neutron spectroscopy
Authors: Youssef A. , Kodama R. , Tampo M.
Published: March 2006

Proton acceleration inside solid LiF and CH–LiF targets irradiated by a 450-fs, 20-J, 1053-nm laser at an intensity of 3×1018W∕cm2 has been studied via neutron spectroscopy. Neutron spectra produced through the Li7(p,n)Be7 reaction that occurs between accelerated protons, at the front surface, and background Li7 ions inside the target. From measured and calculated spectra, by three–dimensional Monte Carlo code, the maximum energy, total number, and slope temperature of the accelerated protons are investigated. The study indicates that protons originate at the front surface and are accelerated to a maximum energy that is reasonably consistent with the calculated one due to the ponderomotive force.
Using white noise to enhance synchronization of coupled chaotic systems
Authors: Lin Wei , Chen Guanrong
Published: March 2006

In the paper, complete synchronization of two chaotic oscillators via unidirectional coupling determined by white noise distribution is investigated. It is analytically proved that chaos synchronization could be achieved with probability one merely via white-noise-based coupling. The established theoretical result supports the observation of an interesting phenomenon that a certain kind of white noise could enhance chaos synchronization between two chaotic oscillators. Furthermore, numerical examples are provided to illustrate some possible applications of the theoretical result.
Streaked extreme ultraviolet imaging of the motion of low-Z foam buffered indirectly driven intermediate and high-Z payloads
Authors: Pasley J. , Nilson P. , Willingale L. , Haines M. G. , Notley M. , Tolley M. , Neely D. , Nazarov W. , Willi O.
Published: March 2006

Results of experiments conducted at the Central Laser Facility (Rutherford Appleton Laboratory), illustrating the efficacy of utilizing a combination of transonic and subsonic ablation to increase the impulse delivered to an indirectly driven payload, are reported. Extreme ultraviolet imaging has been utilized to map the trajectory of the rear surface of an accelerating payload driven by a hohlraum with a peak energy-density-equivalent radiation temperature of around 130eV. Payloads comprising an approximately 30–μm–thick solid-density plastic foil doped with chlorine, both with and without a gold flashing on the driver-facing surface, were accelerated by a combination of subsonic x-ray ablation of the rear surface of the payload and either subsonic, transonic, or supersonic ablation in a hohlraum facing low-density foam layer in intimate contact with the payload. Two different thicknesses of foam layer were incorporated in the experiment — 150 and 200μm — in addition to a range of different foam densities from 30to100mg∕cc. It was observed that the maximum impulse was delivered in the case where the ablation wave propagation was approximately transonic in the foam layer. In such cases the impulse delivered to the payload was significantly greater than that achieved by direct (subsonic) ablation of the payload.
Velocity-space resolution, entropy production, and upwind dissipation in Eulerian gyrokinetic simulations
Authors: Candy J. , Waltz R. E.
Published: March 2006

Equations which describe the evolution of volume-averaged gyrokinetic entropy are derived and added to GYRO [J. Candy and R.E. Waltz, J. Comput. Phys. 186, 545 (2003)], a Eulerian gyrokinetic turbulence simulation code. In particular, the creation of entropy through spatial upwind dissipation (there is zero velocity-space dissipation in GYRO) and the reduction of entropy via the production of fluctuations are monitored in detail. This new diagnostic has yielded several key confirmations of the validity of the GYRO simulations. First, fluctuations balance dissipation in the ensemble-averaged sense, thus demonstrating that turbulent GYRO simulations achieve a true statistical steady state. Second, at the standard spatial grid size, neither entropy nor energy flux is significantly changed by a 16-fold increase (from 32 to 512 grid points per cell) in the number of grid points in the two-dimensional velocity space. Third, the measured flux is invariant to an eightfold increase in the upwind dissipation coefficients. A notable conclusion is that the lack of change in entropy with grid refinement refutes the familiar but incorrect notion that Eulerian gyrokinetic codes miss important velocity-space structure. The issues of density and energy conservation and their relation to negligible second-order effects such as the parallel nonlinearity are also discussed.
Alfvén multistability: Transient and intermittent dynamics induced by noise
Authors: Rempel Erico L. , Santana Wanderson M. , Chian Abraham C.-L.
Published: March 2006

The effects of noise in the dynamics of Alfvén waves described by the derivative nonlinear Schrödinger equation are investigated. In a complex region of the parameter space, where multistability is observed, an external stochastic source can effectively destroy attractors present in the noise-free system, as well as induce chaotic transients and extrinsic intermittency. In the intermittent regime, the Alfvén wave exhibits random qualitative changes in its behavior as a result of a competition between three attractors and a chaotic saddle embedded in the fractal basin boundary.
Synthesis and electronic properties of ZnO∕CoZnO core-shell nanowires
Authors: Han Song , Zhang Daihua , Zhou Chongwu
Published: March 2006

ZnO ∕ CoZnO core-shell nanowires have been synthesized by depositing an epitaxial layer of CoxZn1−xO (x=0.05−0.25) onto single-crystalline ZnO nanowires via pulsed-laser deposition. Detailed material analysis confirmed the core-shell structure and revealed a homogeneous distribution of Co atoms in the ZnO lattice. Field-effect transistors have been fabricated based on individual ZnO∕CoZnO nanowires. These devices exhibited n-type transistor characteristics and intriguing magnetoresistance below 30K.
Fluid simulation studies of the dynamical behavior of one-dimensional relativistic electromagnetic solitons
Authors: Saxena Vikrant , Das Amita , Sen Abhijit , Kaw Predhiman
Published: March 2006

A numerical fluid simulation investigation of the temporal evolution of a special class of traveling wave solutions of the one-dimensional relativistic cold plasma model is reported. The solutions consist of coupled electromagnetic and plasma waves in a solitary pulse shape [Sov. Phys. JETP 49, 75 (1979); Phys. Rev. Lett. 68, 3172 (1992); Phys. Plasmas 9, 1820 (2002)]. Issues pertaining to their stability, mutual collisional interactions, and propagation in an inhomogeneous plasma medium are addressed. It is found that solitary pulses that consist of a single light peak trapped in a modulated density structure are long-lived whereas structures with multiple peaks of trapped light develop an instability at the trailing edge. The interaction properties of two single peak structures show interesting dependencies on their relative amplitudes and propagation speeds and can be understood in terms of their propagation characteristics in an inhomogeneous plasma medium.
Mass transfer and chemical reactions in reactive deformable bubble swarms
Authors: Koynov Athanas , Tryggvason Grétar , Schlüter Michael , Khinast Johannes G.
Published: March 2006

A hybrid numerical/experimental technique was developed for the study of the impact of the multiphase hydrodynamics on mass transfer and chemical reactions at deformable interfaces. Different material properties and flow conditions can yield flows with qualitatively different mass transfer and transport characteristics. As many (bio-) reaction systems exhibit sensitivity to mass transport in general, and mixing specifically, it is possible to control their product distribution by tailoring the system parameters.
Pseudopotential band structures of rocksalt MgO, ZnO, and Mg1−xZnxO
Authors: Fritsch Daniel , Schmidt Heidemarie , Grundmann Marius
Published: March 2006

The electronic properties of the rocksalt group-II oxides MgO and ZnO are investigated by means of the empirical pseudopotential method. Using a simple empty core model potential and experimentally known low-temperature transition energies of rocksalt MgO and wurtzite ZnO, we obtained cationic model potential parameters for Mg and Zn atoms, respectively. Making use of the transferability of ionic model potential parameters, we obtained one single set of anionic model potential parameters for the O atom. The electronic properties of the Mg1−xZnxO alloy system are investigated by means of the virtual crystal approximation for x<0.5 in the rocksalt phase.