bluuebunny/crossref_metadata_2025 huggingface dataset:
Biotechnology: the language of multiple views in Māori communities
Authors: Te Momo O. H. Fiona
Published: August 2007

In Aotearoa (New Zealand), the government funded studies on communicating biotechnology to different sectors in the community from 2003 to 2006. Subsequently, a researcher covering the Māori sector performed a content analysis of data gathered in the community. Qualitative analysis methods included examining text from participant interviews, focus groups, government documents, newspapers, Internet sites, and current literature. Content was coded by identifying common themes in the English and the Māori language. Words like genetic modification (GM), genetic engineering (GE), and biotechnology were explained to provide a basic understanding between the communities and researcher. The terminology applied in the research was essential to achieve communication between the researcher and the community. The resultant themes represented seven views to interpret the communities association with biotechnology: purist Māori, religious Māori, anti Māori, pro Māori, no Māori, uncertain Māori, and middle Māori views. The themes are taken from the analysis of data compiled after 3 years of completing different stages of a research project. The views indicate that a common understanding can be achieved in the diverse range of Māori tribal communities providing those communicating biotechnology can identify the view and interpretations communities associate with biotechnology. This knowledge is essential for government agencies, researchers, community practitioners, scientist, and businesses that desire to dialogue with Māori communities in the language of biotechnology.
Transparent communication strategy on GMOs: Will it change public opinion?
Authors: Sinemus Kristina , Egelhofer Marc
Published: August 2007

Innovations are central for the economic growth; however, the use of new technologies needs to be widely accepted in the general public and the society as a whole. Biotechnology in general, and the use of genetic engineering in food production in particular are seen critically by the European public and perceived as “risky”, and a transatlantic divide between European and US citizens has been observed. This review investigates the reasons for those differing perceptions and proposes new strategies to communicate the benefits of biotechnology in agriculture to a broader public. When analyzing the dialogue process that has taken place between public, scientists, governmental organizations and industry, questions arise on what has been done differently in Europe, in order to propose new, more successful and efficient communication strategies for the future.
Enhancement of PCB degradation by Burkholderia xenovorans LB400 in biphasic systems by manipulating culture conditions
Authors: Rehmann Lars , Daugulis Andrew J.
Published: August 2007

Two‐phase partitioning bioreactors (TPPBs) can be used to biodegrade environmental contaminants after their extraction from soil. TPPBs are typically stirred tank bioreactors containing an aqueous phase hosting the degrading microorganism and an immiscible, non‐toxic and non‐bioavailable organic phase functioning as a reservoir for hydrophobic compounds. Biodegradation of these compounds in the aqueous phase results in thermodynamic disequilibrium and partitioning of additional compounds from the organic phase into the aqueous phase. This self‐regulated process can allow the delivery of large amounts of hydrophobic substances to degrading microorganisms. This paper explores the reactor conditions under which the polychlorinated biphenyl (PCB) degrader Burkholderia xenovorans LB400 can degrade significant amounts of the PCB mixture Aroclor® 1242. Aroclor® degradation was found to stall after approximately 40 h if no carbon source other than PCBs was available in the reactor. Sodium pyruvate was found to be a suitable carbon source to maintain microbial activity against PCBs and to function as a substrate for additional cell growth. Both biphenyl (while required during the inoculum preparation) and glucose had a negative effect during the Aroclor® degradation phase. Initial Aroclor® 1242 degradation rates in the presence of pyruvate were high (6.2 mg L−1 h−1) and 85% of an equivalent concentration of 100 mg Aroclor® 1242 per L aqueous phase could be degraded in 48 h, which suggest that solvent extraction of PCBs from soil followed by their biodegradation in TPPBs might be a feasible remediation option. Biotechnol. Bioeng. 2008;99: 521–528. © 2007 Wiley Periodicals, Inc.
Purification of equine IgG using membrane based enhanced hybrid bioseparation technique: A potential method for manufacturing hyperimmune antibody
Authors: Wang Lu , Sun Xinghua , Ghosh Raja
Published: August 2007

Hyperimmune equine IgG is widely used as antivenom and anti‐rabies agents. This article discusses a membrane based enhanced hybrid bioseparation technique for efficient and scalable purification of equine immunoglobulin G (IgG) from horse serum. This technique is an improved version of a standard hybrid bioseparation technique developed within our group earlier for fractionation of human plasma proteins (Ghosh. 2004. J Membr Sci 237: 109–117). In the presence of a high antichaotropic salt concentration, equine IgG is selectively and reversibly captured within a stirred cell membrane module from horse serum, partly due to precipitation and microfiltration, and partly due to hydrophobic interaction based membrane adsorption, while the impurities are washed out from the device. The reversibly sequestered IgG is then released by lowering the salt concentration which favor both dissolution of the precipitated IgG and desorption of the membrane bound IgG. The enhanced hybrid bioseparation technique improves the IgG recovery from the membrane module by switching from a stirring to non‐stirring mode during the IgG release phase. It also reduces membrane fouling by an appropriate pH switch. The effects of operating conditions on equine IgG capture were first systematically studied. The enhanced hybrid bioseparation technique was followed by an ultrafiltration step to remove ammonium sulfate and low molecular weight impurities. The equine IgG purity obtained under optimized conditions was 88% and its recovery was over 90%, both being significantly higher than corresponding values obtained using currently used purification techniques. Biotechnol. Bioeng. 2008;99: 625–633. © 2007 Wiley Periodicals, Inc.
Monitoring of fluoroquinolone residual levels in chicken eggs by microbiological assay and confirmation by liquid chromatography
Authors: Cho Hee‐Jung , Abd El‐Aty A. M. , Goudah Ayman , Sung Gi‐Min , Yi Hee , Seo Dong‐Cheol , Kim Jin‐Suk , Shim Jae‐Han , Jeong Ji‐Yoon , Lee Soon‐Ho , Shin Ho‐Chul
Published: August 2007

The primary objective of this study was to develop a simple, rapid, and efficient method for the simultaneous determination of four fluoroquinolone residues, ciprofloxacin (CFX), danofloxacin (DFX), enrofloxacin (EFX) and norfloxacin (NFX), in chicken eggs. The samples were first monitored by microbiological assay using Escherichia coli as the reference organism, and were then quantified using HPLC with a fluorescence detector. Egg samples were extracted by the liquid‐phase extraction process, and the analytes were analyzed via an ODS column using a mixture of acetonitrile and 0.4% phosphoric acid–0.4% triethylamine (15: 85, v/v) as a mobile phase (pH = 2) without purification. The calibration curves were linear (r2 ≥ 0.999) over a concentration range of 0.1–1.0 µg/mL. The majority of the mean recoveries at four different fortification levels, 0.1, 0.2, 0.5 and 1.0 ppm, ranged from 73.7 ± 7.2% to 87.1 ± 12.7%, and the repeatability (as the relative standard deviation) from three repetitive determinations of recovery was between 1.03 and 18.83%. The calculated limit of quantitation (LOQ) was 9 ppb for CFX, EFX and NFX and 0.6 ppb for DFX. Both the bioassay and HPLC methods were applied to 120 total egg samples collected from the six major cities in the Republic of Korea. The bioassay, showed that two samples were positive (i.e contained inhibiting substances). On the other hand, the results of HPLC only identified and quantified the residues of enrofloxacin (from 0.43 to 1.02 ppm) in three samples out of 120. We concluded that the bioassay can be used as a routine screening method for the presence of fluoroquinolones in chicken eggs, which can be confirmed and quantified using LC. Copyright © 2007 John Wiley & Sons, Ltd.
Up to Seven‐Component Adducts by Unprecedented Multiple Alkyne and Carbonyl Insertions in the Metal–Carbon Bond of Chromium Alkoxy Alkynyl Carbene Complexes
Authors: Barluenga José , García‐García Patricia , Fernández‐Rodríguez Manuel A. , Rocaboy Christian , Aguilar Enrique , Andina Facundo , Merino Isabel
Published: August 2007

Chromium alkoxy alkynyl Fischer carbene complexes react with symmetrical internal alkynes to form new and different organometallic species, which result from consecutive insertions of several alkyne units and carbonyl groups into the metal–carbon bond. The insertion sequence can be controlled and, by slight modification of the reaction conditions, it can be directed to the preparation of either seven‐ or five‐component adducts. Three molecules of alkyne, two carbonyl groups, the carbene ligand and the chromium metal moiety partake in the creation of seven new carbon–carbon bonds and two five‐membered carbocycles in the first case while four new carbon–carbon bonds, a σ CrC(sp2) bond and a cyclopentadienyl moiety are built in the second case. Evidence that five‐component chromium complexes are intermediates in the formation of seven‐component adducts is provided; they are also able to insert a unit of a different internal alkyne which confers more diversity to the seven‐component adducts. The presence of the σ CrC(sp2) bond has also been exploited to develop the synthesis of both cyclopentene‐fused and novel spiro‐cyclopentenones as well as symmetrical biscyclopentenones. Finally, the isolation of six‐component adducts, when tolane was employed as the initial alkyne, provides further support to the proposed mechanism.
Numerische und experimentelle Untersuchung der Partikelbewegung beim Plasmaschweißen
Authors: Tchikango Siagam A. , Giese P. , Brenner G. , Wesling V.
Published: August 2007

Plasma‐Pulver‐Verfahren werden heute bei einer Vielzahl schweißtechnischer Aufgaben eingesetzt. Besonders weit verbreitet ist hierbei die Herstellung von Beschichtungen zum Verschleiß‐ oder Korrosionsschutz durch das Plasma‐Pulver‐Auftragsschweißen (PPA). Zur Optimierung des Verfahrens wird zunächst eine Aufklärung der Vorgänge angestrebt, die zu einer maximalen Auftragsleistung (also maximal umgesetzte Pulvermenge pro Zeiteinheit) führen. Von Interesse sind hierbei insbesondere die Gas‐ und Partikelströmung im Bereich zwischen Schweißdüse und Werkstück.

Zur Untersuchung der komplexen Einflussgrößen bei der Auslegung des Schweißprozesses wurden Strömungssimulationen (CFD) durchgeführt. Die Validierung der Berechnungen dienten Geschwindigkeitsmessungen mit der Particle Image Velocimetrie (PIV). Dieses Messverfahren ermöglicht einerseits die Erfassung der Geschwindigkeit der Gasphase, andererseits kann die Geschwindigkeit der dispersen Partikelströmung untersucht werden. Aufgrund der hohen Intensität des Plasmalichts wurde in den vorliegenden Untersuchungen ein modifizierter PIV‐Aufbau verwendet. Vergleiche zwischen Numerik und Messungen zeigen eine gute Übereinstimmung der Geschwindigkeitsfelder für größere Partikel. Für eine für die Praxis relevante simultane Untersuchung von Partikeln verschiedener Größen ist eine modifizierte Datennachbearbeitung in Erwägung zu ziehen, die auf der Einteilung des von den Partikeln gestreuten Lichts in verschiedene Intensitätsbereiche beruhen würde.
Ectopic expression and dynamics of TPM1α and TPM1κ in myofibrils of avian myotubes
Authors: Wang Jushuo , Sanger Jean M. , Kang Songman , Thurston Harold , Abbott Lynn Z. , Dube Dipak K. , Sanger Joseph W.
Published: August 2007

From the four known vertebrate tropomyosin genes (designated TPM1, TPM2, TPM3, and TPM4) over 20 isoforms can be generated. The predominant TPM1 isoform, TPM1α, is specifically expressed in both skeletal and cardiac muscles. A newly discovered alternatively spliced isoform, TPM1κ, containing exon 2a instead of exon 2b contained in TPM1α, was found to be cardiac specific and developmentally regulated. In this work, we transfected quail skeletal muscle cells with green fluorescent proteins (GFP) coupled to chicken TPM1α and chicken TPM1κ and compared their localizations in premyofibrils and mature myofibrils. We used the technique of fluorescence recovery after photobleaching (FRAP) to compare the dynamics of TPM1α and TPM1κ in myotubes. TPM1α and TPM1κ incorporated into premyofibrils, nascent myofibrils, and mature myofibrils of quail myotubes in identical patterns. The two tropomyosin isoforms have a higher exchange rate in premyofibrils than in mature myofibrils. F‐actin and muscle tropomyosin are present in the same fibers at all three stages of myofibrillogenesis (premyofibrils, nascent myofibrils, mature myofibrils). In contrast, the tropomyosin‐binding molecule nebulin is not present in the initial premyofibrils. Nebulin is gradually added during myofibrillogenesis, becoming fully localized in striated patterns by the mature myofibril stage. A model of thin filament formation is proposed to explain the increased stability of tropomyosin in mature myofibrils. These experiments are supportive of a maturing thin filament and stepwise model of myofibrillogenesis (premyofibrils to nascent myofibrils to mature myofibrils), and are inconsistent with models that postulate the immediate appearance of fully formed thin filaments or myofibrils. Cell Motil. Cytoskeleton 2007. © 2007 Wiley‐Liss, Inc.
Clinical management and outcome of papillary and follicular (differentiated) thyroid cancer presenting with distant metastasis at diagnosis
Authors: Sampson Elliot , Brierley James D. , Le Lisa W. , Rotstein Lorne , Tsang Richard W.
Published: August 2007

BACKGROUND.

Differentiated thyroid cancer has a good prognosis and only rarely presents with distant metastasis at diagnosis. The clinical outcome of this presentation was assessed with respect to survival and factors that may determine prognosis.

METHODS.

A retrospective review was undertaken of patients with stage M1 differentiated thyroid cancer at presentation (n = 49), referred from 1980–2000 at a single institution.

RESULTS.

The median age was 68 (range, 17–90), with 69% females. The initial site(s) of metastasis were lung only, 45%, bone only, 39%, other single site, 4%, and multiple sites, 12%. Histology: papillary, 51%, follicular, 49%. Initial treatment(s) included: thyroidectomy, 82%, radioactive iodine (RAI), 88%, excision of metastasis, 29%, radiotherapy, 47%, and chemotherapy, 6%. With a median follow‐up time of 3.5 years, 25 patients are alive (51%) and 24 died (49%), with 3‐year and 5‐year actuarial survivals of 69% and 50%, respectively. Only a minority of patients (4/25, 16%) had no clinical evidence of disease at last follow‐up. Most deaths (17/24, 71%) were due to progressive cancer. Prognosis was associated with age, site of metastasis, histology, and iodine avidity of the metastasis. Patients aged ≤45 (n = 8) had a 3‐year survival of 100%, versus 62% for those age > 45 years (P = .001). The 3‐year survival for lung only versus bone only metastasis was 77% versus 56% (P = .02); for papillary versus follicular carcinoma, 75% versus 62% (P = .006); for iodine‐avid disease (n = 29) versus not avid (n = 14), 82% versus 57% (P = .02), respectively. In multivariate analysis after adjusting for age, only histology and iodine avidity remained significant for survival. The hazard ratio for follicular histology was 3.7 (95% confidence interval [CI], 1.1–12.1, P = .03), and for tumors not avid for iodine, 3.4 (95% CI, 1.2–9.2, P = .02).

CONCLUSIONS.

The data support the aggressive management of patients presenting with stage M1 thyroid cancer, with thyroidectomy and RAI. Complete clinical eradication of disease was rarely seen, and 50% of patients survived for more than 5 years. Young patients with papillary tumors and/or iodine‐avid disease have an even better prognosis. Cancer 2007. © 2007 American Cancer Society.
Increased host neuronal survival and motor function in BMT Parkinsonian mice: Involvement of immunosuppression
Authors: Keshet Gilmor I. , Tolwani Ravi J. , Trejo Angelica , Kraft Peggy , Doyonnas Regis , Clayberger Carol , Weimann James M. , Blau Helen M.
Published: August 2007

We examined the potential of bone marrow transplantation (BMT) to rescue dopaminergic neurons in a mouse model of Parkinson's disease (PD). A BMT from mice transgenic for green fluorescent protein (GFP+) given either before or after administration of the neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) led to the accumulation of transplanted adult GFP+bone‐marrow‐derived cells (BMDC) in the substantia nigra, where dopaminergic neurodegeneration occurs in PD. Post‐BMT, mice exposed to MPTP had substantially greater numbers of endogenous tyrosine hydroxylase‐positive neuronal cell bodies in the substantia nigra and increased dopamine transporter‐positive projections into the striatum compared to controls. Moreover, motor function was restored to normal within 1 month post‐MPTP in BMT‐treated mice assayed by a rotarod behavioral test. The effect of BMT on PD was indirect, as no evidence of BMDC fusion with or transdifferentiation into dopaminergic neurons was observed. BMDC activated by BMT or associated factors could play a trophic role in rescuing damaged cells. Alternatively, the beneficial effects of BMT are due to immunosuppression reflected by a reduction in the proportion of T‐cells and a reduction of T‐cell proliferation in BMT mice. These findings highlight that when immunosuppression is required for transplantation studies, the amelioration of symptoms may not be due to the transplant itself. Further, they suggest that the immune system plays a role in the development of characteristics typical of PD. J. Comp. Neurol. 504:690–701, 2007. © 2007 Wiley‐Liss, Inc.
Vaccination with plasmacytoid dendritic cells induces protection against infection with Leishmania major in mice
Authors: Remer Katharina A. , Apetrei Calin , Schwarz Tobias , Linden Christian , Moll Heidrun
Published: August 2007

DC‐based vaccination against Leishmania major induces a parasite‐specific Th1 response and long‐lasting protective immunity in susceptible mice. Since distinct DC subsets have been proposed to direct the predominant development of either Th1 or Th2 cells, we analyzed the capability of plasmacytoid DC (pDC) to induce protection and elicit a Th1 response against L. major. Pulsing with L. major lysate induced the activation and maturation of semi‐mature murine pDC that had been isolated from the spleen, as indicated by up‐regulation of the co‐stimulatory molecules CD86 and CD80, but did not enhance the level of IFN‐α secretion by pDC. Vaccination of susceptible mice with L. major lysate‐pulsed pDC induced highly effective T cell‐mediated immunity against subsequent infection with L. major parasites. Surprisingly, the protection was not accompanied by a polarized Th1 cytokine profile. Co‐activation of pDC with CpG‐containing oligodeoxynucleotides, which has been shown to be critical for activating the protective potential of myeloid DC, was not required for the protective effect of L. major antigen‐pulsed pDC. These findings demonstrate that antigen‐loaded pDC are able to induce T cell‐mediated protection against a parasite disease and that experimental leishmaniasis is a suitable model to elucidate the mechanisms underlying DC‐based vaccination against infections.
Nod1 and Nod2 induce CCL5/RANTES through the NF‐κB pathway
Authors: Werts Catherine , le Bourhis Lionel , Liu Jianguo , Magalhaes Joao G. , Carneiro Leticia A. , Fritz Jörg H. , Stockinger Silvia , Balloy Viviane , Chignard Michel , Decker Thomas , Philpott Dana J. , Ma Xiaojing , Girardin Stephen E.
Published: August 2007

The Nod‐like receptor proteins Nod1 and Nod2 participate in innate immune responses against bacteria through intracellular detection of peptidoglycan, a component of bacterial cell wall. Recent evidence has demonstrated that Nod1 stimulates the release of chemokines that attract neutrophils at the site of infection, such as CXCL8/IL‐8 in humans, and CXCL1/keratinocyte‐derived chemokine and CXCL2/MIP‐2 in mice. We aimed to determine whether Nod proteins could trigger the release of CCL5/RANTES, a chemokine known to attract a number of immune cells, but not neutrophils. Our results demonstrate that activation of both Nod1 and Nod2 results in substantial secretion of CCL5 by murine macrophages. Moreover, in vivo, the intraperitoneal injection of murine Nod1 or Nod2 agonists resulted in a rapid secretion of CCL5 into the bloodstream. We also observed that Nod‐dependent secretion of CCL5 did not correlate with the induction of the interferon‐β pathway, a major signaling cascade for the activation of CCL5 by viruses. In contrast, we identified a key role of the NF‐κB pathway in Nod‐dependent stimulation of the CCL5 promoter. Together, these results identify a novel target downstream of Nod1 and Nod2, which is likely to play a key role in orchestrating the global Nod‐dependent immune defense during bacterial infections.
NF‐κB p50 and p65 subunits control intestinal homeostasis
Authors: Gadjeva Mihaela , Wang Yanyan , Horwitz Bruce H.
Published: August 2007

Mice which lack the p50 subunit of NF‐κB and are heterozygous for the p65 subunit (3X mice), are exquisitely sensitive to LPS‐induced shock. Here, we demonstrate that prior to becoming moribund, 3X mice challenged with LPS develop a profound enteropathy. The enteropathy is characterized by defects in intestinal barrier function, increased epithelial apoptosis, and deregulated intestinal cytokine gene expression. The defect that sensitizes 3X mice to LPS‐induced enteropathy is located within the innate immune compartment, as LPS induced similar findings in 3X mice lacking lymphocytes (3X/RAG). TNF‐α depletion ameliorated the ability of LPS to induce pathology and TNF‐α was able to independently induce similar findings, suggesting that TNF‐α plays a critical role in the development of LPS‐induced pathology in these mice. These data highlight that NF‐κB subunits have essential functions in regulating intestinal homeostasis during acute inflammation.
Supramolecular Threaded Complexes from Fullerene–Crown Ether and π‐Extended TTF Derivatives
Authors: Illescas Beatriz M. , Santos José , Díaz Marta C. , Martín Nazario , Atienza Carmen M. , Guldi Dirk M.
Published: August 2007

A series of π‐extended TTFs (exTTFs) bearing one (8, 16,19) or two (14) dibenzylammonium units have been threaded through a dibenzo‐24‐crown‐8 (DB24C8) ring covalently linked to a C60 sphere. Whereas 8 and 14 were prepared in a multistep synthetic procedure involving Sonogashira cross‐coupling reactions affording rigid donors, exTTFs 16 and 19 were prepared by direct esterification reactions leading to more flexible systems. Complexation experiments carried out by 1H NMR titration and fluorescence studies show the formation of stable supramolecular dyads with binding constants ranging from 103 to 104 M–1. Although the UV/Vis and CV studies reveal the lack of interaction between the electroactive species (C60 and exTTF) in the ground state, fluorescence data indicate the presence of an electronic interaction in the excited state. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Synthesis, Structure, and Theoretical Study of Lower Trifluoromethyl Derivatives of [60]Fullerene
Authors: Dorozhkin Evgenii I. , Goryunkov Alexey A. , Ioffe Ilya N. , Avdoshenko Stanislav M. , Markov Vitaliy Yu. , Tamm Nadezhda B. , Ignat'eva Daria V. , Sidorov Lev N. , Troyanov Sergey I.
Published: August 2007

A number of C60(CF3)n compounds with n = 2–10 have been synthesized by the reaction of C60 with silver trifluoroacetate and successfully isolated by means of HPLC. This resulted in the first crystal structure determination of six lower trifluoromethyl derivatives with n = 2 (single isomer), 4 (two isomers), and 6 (three isomers). A kinetic model of sequential trifluoromethylation based on the Bell–Evans–Polanyi principle has been used to explain the experimentally observed isomeric distribution in the mixtures of C60(CF3)n compounds up ton = 6. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
A detailed analysis of hotspots and insulation breakdown phenomena in power inductor windings at high frequency regimes: overcurrents and overvoltages
Authors: Faria J. A. Brandão
Published: August 2007

This research paper is the last of a group of three papers dedicated to the analysis and computation of the high‐frequency electromagnetic behaviour of inductor windings where a multiconductor transmission line approach is used. The present work is essentially concerned with application aspects linked up with the important engineering problem of windings insulation damage, which can occur either because of excessive temperature (winding hotspots) or because of excessive electric field strength (dielectric breakdown). For single and multilayer windings we present here a wealth of information in graphical and tabular form concerning the distribution of voltages, currents, electric charges, charge densities, electric field components and power losses along the inductor winding turns, operating at the critical resonance frequencies characteristic of the structure (which is the worst possible scenario). This information is analysed and processed in order to allow for a detection of the winding zones where breakdown phenomena and hotspots could most probably occur. Copyright © 2007 John Wiley & Sons, Ltd.
MGF for gamma‐shadowed ricean fading channel
Authors: Kostić I. M.
Published: August 2007

The moment‐generating function (MGF) of the received signal‐to‐noise ratio (SNR) is a convenient tool in the performance analysis of modulation schemes in fading channels. In this letter, we derive the MGF for gamma‐shadowed Ricean fading channels under the assumption that the average power of the Ricean fading is characterised by a gamma distribution. The MGF is expressed in a series form. An application of the derived MGF for evaluating the average bit error probability (ABEP) for binary differential phase‐shift keying (DPSK) is given. The exact expression for ABEP and the corresponding asymptotic expression (assuming large SNR) are derived and mutually compared. The computational efficiency is elaborated on. Special cases of the exact expression for ABEP agree with corresponding known results. Copyright © 2007 John Wiley & Sons, Ltd.
Mechanisms of protection by the betaine-homocysteine methyltransferase/betaine system in HepG2 cells and primary mouse hepatocytes
Authors: Ji Cheng , Shinohara Masao , Kuhlenkamp John , Chan Christine , Kaplowitz Neil
Published: August 2007

Betaine-homocysteine methyltransferase (BHMT) regulates homocysteine levels in the liver. We previously reported that the alteration of BHMT is associated with alcoholic liver steatosis and injury. In this study, we tested whether BHMT protects hepatocytes from homocysteine-induced injury and lipid accumulation. Both BHMT transfectants of HepG2 cells and primary mouse hepatocytes with suppressed BHMT were generated. Comparisons were made between the cell models with respect to their response to homocysteine treatments. Homocysteine metabolism was impaired in HepG2 cells, and the expression of BHMT in HepG2 cells ameliorated the impairment and stabilized the levels of intracellular homocysteine after the addition of exogenous homocysteine. BHMT expression inhibited homocysteine-induced glucose-regulated protein 78 (GRP78) and C/EBP-homologous protein (CHOP) and homocysteine-induced cell death. A betaine treatment protected primary mouse hepatocytes from a homocysteine-induced increase in GRP78 and cell death but not a tunicamycin-induced increase. Homocysteine induced greater CHOP expression (2.7-fold) in BHMT small interfering RNA (siRNA)–transfected cells than in a control (1.9-fold). Homocysteine-induced cell death was increased by 40% in the siRNA-treated cells in comparison with the control. Apolipoprotein B (apoB) expression was higher and triglycerides and cholesterol were lower in HepG2 expressing BHMT. In primary mouse hepatocytes, homocysteine induced the accumulation of triglycerides and cholesterol, which was reduced in the presence of betaine. Betaine partially reduced homocysteine-induced sterol regulatory element binding protein 1 expression in HepG2 cells and increased S-adenosylmethionine in primary mouse hepatocytes.

Conclusion:

The BHMT/betaine system directly protects hepatocytes from homocysteine-induced injury but not tunicamycin-induced injury, including an endoplasmic reticulum stress response, lipid accumulation, and cell death. This system also exhibits a more generalized effect on liver lipids by inducing ApoB expression and increasing S-adenosylmethionine/S-adenosylhomocysteine.
Association of reduced extracellular brain ammonia, lactate, and intracranial pressure in pigs with acute liver failure
Authors: Rose Christopher , Ytrebφ Lars M. , Davies Nathan A. , Sen Sambit , Nedredal Geir I. , Belanger Mireille , Revhaug Arthur , Jalan Rajiv
Published: August 2007

We previously demonstrated in pigs with acute liver failure (ALF) that albumin dialysis using the molecular adsorbents recirculating system (MARS) attenuated a rise in intracranial pressure (ICP). This was independent of changes in arterial ammonia, cerebral blood flow and inflammation, allowing alternative hypotheses to be tested. The aims of the present study were to determine whether changes in cerebral extracellular ammonia, lactate, glutamine, glutamate, and energy metabolites were associated with the beneficial effects of MARS on ICP. Three randomized groups [sham, ALF (induced by portacaval anastomosis and hepatic artery ligation), and ALF+MARS] were studied over a 6-hour period with a 4-hour MARS treatment given beginning 2 hours after devascularization. Using cerebral microdialysis, the ALF-induced increase in extracellular brain ammonia, lactate, and glutamate was significantly attenuated in the ALF+MARS group as well as the increases in extracellular lactate/pyruvate and lactate/glucose ratios. The percent change in extracellular brain ammonia correlated with the percent change in ICP (

r

2 = 0.511). Increases in brain lactate dehydrogenase activity and mitochondrial complex activity for complex IV were found in ALF compared with those in the sham, which was unaffected by MARS treatment. Brain oxygen consumption did not differ among the study groups.

Conclusion

: The observation that brain oxygen consumption and mitochondrial complex enzyme activity changed in parallel in both ALF- and MARS-treated animals indicates that the attenuation of increased extracellular brain ammonia (and extracellular brain glutamate) in the MARS-treated animals reduces energy demand and increases supply, resulting in attenuation of increased extracellular brain lactate. The mechanism of how MARS reduces extracellular brain ammonia requires further investigation. (Hepatology 2007.)
Mechanisms of cytochrome P450 substrate oxidation: MiniReview
Authors: Guengerich F. Peter
Published: August 2007

Cytochrome P450 (P450) enzymes catalyze a variety of oxidation and some reduction reactions, collectively involving thousands of substrates. A general chemical mechanism can be used to rationalize most of the oxidations and involves a perfenyl intermediate (FeO3+) and odd‐electron chemistry, i.e. abstraction of a hydrogen atom or electron followed by oxygen rebound and sometimes rearrangement. This general mechanism can explain carbon hydroxylation, heteroatom oxygenation and dealkylation, epoxidation, desaturation, heme destruction, and other reactions. Another approach to understanding catalysis involves analysis of the more general catalytic cycle, including substrate specificity, because complex patterns of cooperativity are observed with several P450s. Some of the complexity is due to slow conformational changes in the proteins that occur on the same timescale as other steps. © 2007 Wiley Periodicals, Inc. J Biochem Mol Toxicol 21:163–168, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20174
Ontogeny of human hepatic cytochromes P450
Authors: Hines Ronald N.
Published: August 2007

Significant changes in drug‐metabolizing enzyme (DME) expression occur during ontogeny. Such changes can have a profound effect on therapeutic efficacy in the fetus and child, as well as the risk for adverse drug reactions. To gain a better understanding of DME ontogeny, enzyme contents for six key cytochromes P450 were measured in 240 human liver samples representing ages from 8 weeks gestation to 18 years. Where possible, both quantitative western blotting and activity assays with probe substrates were performed. Although oversimplified, the DME can be grouped into one of three categories. As typified by CYP3A7, some enzymes are expressed at their highest level during the first trimester and either remain at high concentrations or decrease during gestation and are silenced or expressed at low levels within 1–2 years after birth. These data cause one to query whether these enzymes have an important endogenous function. Representatives of a second group, CYP3A5 and CYP2C19, are expressed at relatively constant levels throughout gestation. Postnatal increases in CYP2C19 are observed within the first year, but not for CYP3A5. CYP2C9, 2E1, and 3A4 are more typical of a third group of enzymes that are not expressed or are expressed at low levels in the fetus with the onset of expression generally in either the second or third trimester. Substantial increases in expression are observed within the first 1–2 years after birth; however, considerable interindividual variability is observed in the immediate postnatal (1–6 months) onset or increase in expression of these enzymes, often resulting in a window of hypervariability. © 2007 Wiley Periodicals, Inc. J Biochem Mol Toxicol 21:169–175, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20179
Mechanisms of cytochrome P450 induction
Authors: Tompkins Leslie M. , Wallace Andrew D.
Published: August 2007

Cytochrome P450s (CYPs) are important heme‐containing proteins that play important roles in the metabolism of xenobiotics and endogenous compounds. The oxidative metabolisms of drugs, environmental chemicals, hormones, and fatty acids by CYP enzymes are critical pathways aiding in their excretion from the body, but in some cases metabolism may lead to bioactivation and enhanced toxicity. The expression and activity levels of CYPs can be elevated by a process of induction involving the activation of key transcription factors. The mechanisms by which CYP3A4, 2B6, and 1A1 are induced involving the activation of the transcription factors pregnane X receptor (PXR), constitutive androstane receptor (CAR), and aryl hydrocarbon receptor (AhR) will be discussed. © 2007 Wiley Periodicals, Inc. J Biochem Mol Toxicol 21:176–181, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20180
Theoretical study of the reactions CF3CH2OCHF2 + OH/Cl and its product radicals and parent ether(CH3CH2OCH3) with OH
Authors: Yang Lei , Liu Jing‐Yao , Wang Li , He Hong‐Qing , Wang Ying , Li Ze‐Sheng
Published: August 2007

A dual‐level direct dynamic method is employed to study the reaction mechanisms of CF3CH2OCHF2 (HFE‐245fa2; HFE‐245mf) with the OH radicals and Cl atoms. Two hydrogen abstraction channels and two displacement processes are found for each reaction. For further study, the reaction mechanisms of its products (CF3CH2OCF2 and CF3CHOCHF2) and parent ether CH3CH2OCH3 with OH radical are investigated theoretically. The geometries and frequencies of all the stationary points and the minimum energy paths (MEPs) are calculated at the B3LYP/6‐311G(d,p) level. The energetic information along the MEPs is further refined at the G3(MP2) level of theory. For reactions CF3CH2OCHF2 + OH/Cl, the calculation indicates that the hydrogen abstraction from CH2 group is the dominant reaction channel, and the displacement processes may be negligible because of the high barriers. The standard enthalpies of formation for the reactant CF3CH2OCHF2, and two products CF3CH2OCF2 and CF3CHOCHF2 are evaluated via group‐balanced isodesmic reactions. The rate constants of reactions CF3CH2OCHF2 + OH/Cl and CH3CH2OCH3 + OH are estimated by using the variational transition state theory over a wide range of temperature (200–2000 K). The agreement between the theoretical and experimental rate constants is good in the measured temperature range. From the comparison between the rate constants of the reactions CF3CH2OCHF2 and CH3CH2OCH3 with OH, it is shown that the fluorine substitution decreases the reactivity of the CH bond. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
Extension of the MST continuum solvation model to the RM1 semiempirical hamiltonian
Authors: Forti Flavio , Barril Xavier , Luque F. Javier , Orozco Modesto
Published: August 2007

The need to simulate large‐sized molecules or to deal with large series of compounds is a challenging topic in computational chemistry, which has stimulated the development of accurate semiempirical methods, such as the recently reported Recife Model 1 (RM1; J Comput Chem 2006, 27, 1101). Even though RM1 may prove to be of value simply due to the enhanced quantitative accuracy in gas phase, it is unclear how the new parameters optimized for RM1 affect the suitability of this semiempirical Hamiltonian to study chemical processes in condensed phases. To address this question, we report the parametrization of the MST/RM1 continuum model for neutral solutes in water, octanol, chloroform and carbon tetrachloride, and for ions in water. The results are used to discuss the transferability of the solvation parameters implemented in previous MST/AM1 and MST/PM3 models. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
Finite symmetric graphs with two‐arc transitive quotients II
Authors: Lu Zaiping , Zhou Sanming
Published: August 2007

Let $\Gamma$ be a finite G‐symmetric graph whose vertex set admits a nontrivial G‐invariant partition $\cal B$. It was observed that the quotient graph $\Gamma_{\cal B}$ of $\Gamma$ relative to $\cal B$ can be (G, 2)‐arc transitive even if $\Gamma$ itself is not necessarily (G, 2)‐arc transitive. In a previous article of Iranmanesh et al., this observation motivated a study of G‐symmetric graphs ($\Gamma, \cal B$) such that $\Gamma_{\cal B}$ is (G, 2)‐arc transitive and, for blocks B, C ∈ $\cal B$ adjacent in $\Gamma_{\cal B}$, there are exactly |B| − 2(≥1) vertices in B which have neighbors in C. In the present article we investigate the general case where $\Gamma_{\cal B}$ is (G, 2)‐arc transitive and is not multicovered by $\Gamma$ (i.e., at least one vertex in B has no neighbor in C for adjacent B, C ∈ $\cal B$) by analyzing the dual $\cal D^\ast$(B) of the 1‐design $\cal D$(B) ≔ (B, $\Gamma_{\cal B}$(B), I), where $\Gamma_{\cal B}$(B) is the neighborhood of B in $\Gamma_{\cal B}$ and αIC 〈α ∈ B, C ∈  $\Gamma_{\cal B}$(B)〉 in $\cal D$(B) if and only if α has at least one neighbor in C. In this case, a crucial feature is that $\cal D^\ast$(B) admits G as a group of automorphisms acting 2‐transitively on points and transitively on blocks and flags. It is proved that the case when no point of $\cal D$(B) is incident with two blocks can be reduced to multicovers, and the case when no point of $\bar {\cal D}(B)$ is incident with two blocks can be partially reduced to the 3‐arc graph construction, where $\bar {\cal D}(B)$ is the complement of $\cal D$(B). In the general situation, both $\cal D^\ast$(B) and its complement $\bar {{\cal D}^\ast}(B)$ are (G, 2)‐point‐transitive and G‐block‐transitive 2‐designs, and exploring relationships between them and $\Gamma$ is an attractive research direction. In the article we investigate the degenerate case where $\cal D^\ast$(B) or $\bar {{\cal D}^\ast}(B)$ is a trivial Steiner system with block size 2, that is, a complete graph. In each of these cases, we give a construction which produces symmetric graphs with the corresponding properties, and we prove further that every such graph $\Gamma$ can be constructed from $\Gamma_{\cal B}$ by using the construction. © 2007 Wiley Periodicals, Inc. J Graph Theory 56: 167–193, 2007
Fluorine‐18 labelling of small interfering RNAs (siRNAs) for PET imaging
Authors: Viel Thomas , Kuhnast Bertrand , Hinnen Françoise , Boisgard Raphaël , Tavitian Bertrand , Dollé Frédéric
Published: August 2007

Small interfering RNAs (siRNAs), a class of macromolecules constituted by the association of two single‐stranded ribonucleic acids of short sequences, have been labelled with the positron‐emitter fluorine‐18 (T1/2: 109.8 min). The strategy involves (1) prosthetic conjugation of a single‐stranded oligonucleotide with [18F]FPyBrA (N‐[3‐(2‐[18F]fluoropyridin‐3‐yloxy)‐propyl]‐2‐bromoacetamide) followed by (2) formation of the target duplex by annealing with the complementary sequence, therefore, permitting parallel and combinatorial preparation of [18F]siRNAs. Pure fluorine‐18‐labelled siRNAs (0.55–1.11 GBq, specific activity: 74–148 GBq/µmol at EOB) could be obtained within 165 min starting from 37.0 GBq of starting [18F]fluoride (1.5–3.0%, non‐decay‐corrected isolated yields). Copyright © 2007 John Wiley & Sons, Ltd.
From ICI to AstraZeneca: the development of synthetic isotope chemistry at Alderley Park, UK
Authors: Harding John R.
Published: August 2007

Synthetic isotope chemistry has played a key role in the discovery and development of candidate drugs for over 40 years at Alderley Park, UK. This review highlights the range of isotopically labelled compounds that have been synthesized and the applications for which they were used. The continually increasing demand for isotopically labelled compounds demonstrates their valuable contribution to the pharmaceutical industry. Copyright © 2007 John Wiley & Sons, Ltd.
Neutral desorption sampling coupled to extractive electrospray ionization mass spectrometry for rapid differentiation of biosamples by metabolomic fingerprinting
Authors: Chen Huanwen , Wortmann Arno , Zenobi Renato
Published: August 2007

It is of increasing interest and practical importance to develop convenient methods based on mass spectrometry for high‐throughput analyses of biological samples. This is usually difficult because of the complex matrix and ion suppression effects. Generation of ions at ambient conditions is a promising solution to these problems because the sample is easily accessible and the ion suppression effect is reduced significantly. A new method for rapid on‐line detection of metabolic markers in complex biological samples is described here. It combines atmospheric pressure desorption sampling by a gentle stream of air or nitrogen with extractive electrospray ionization (EESI) and mass spectrometric analysis. The resulting mass spectral fingerprints are shown to be able to detect spoilage of meat even in the frozen (−20 °C) state and the contamination of spinach by E. coli, and to identify metabolites and contaminants on human skin within seconds, in an on‐line and high‐throughput fashion. Typical molecular markers are identified using MS/MS data and by comparison with reference compounds. Differences between closely related samples are easily visualized by using principal component analysis (PCA) of the mass spectra data. The detection limit achieved is 10 fg/cm2 (S/N = 3) for histamine on the surface of frozen meat. The technique reported here shows potential for more advanced applications in multiple disciplines, including food regulation, homeland security, in vivo metabolomics, and clinical diagnosis. Copyright © 2007 John Wiley & Sons, Ltd.
Frequent detection of cell‐associated HIV‐1 RNA in patients with plasma viral load <50 copies/ml
Authors: Kupfer Bernd , Matz Bertfried , Däumer Martin P. , Roden Fabienne , Rockstroh Jürgen K. , Qurishi Nazifa , Spengler Ulrich , Kaiser Rolf
Published: August 2007

Despite prolonged undetectable plasma viral load some HIV‐1 infected patients have been reported to develop resistance‐associated mutations leading to treatment failure. The mechanisms for this phenomenon and the point of origin for residual viral evolution are still not elucidated. In order to quantify cell‐associated HIV‐1 RNA in patients with different levels of plasma viremia paired cell‐associated HIV‐1 RNA loads and plasma viral loads were determined. Weak inverse correlation between these parameters and the amounts of CD4+ T cells was observed, whereas there was no correlation between viral loads and CD8+ T cells or CD14+ monocytes, respectively. In a subset of patients, cell‐associated and plasma HIV‐1 env V3 sequences were analyzed. Plasma viral load and the amount of cell‐associated HIV‐RNA correlated strongly. However, in 62.3% of patients with undetectable plasma viral load cell‐associated HIV‐RNA could be detected. Analyses of HIV‐RNA in plasma and blood cells showed identical sequences in 4/19 patients, whereas the majority of patients had differing HIV‐1 RNA sequences in plasma and cells, respectively. In summary, this study shows that residual viral replication in peripheral blood still occurs in the majority of patients with undetectable plasma viral load. Since these replication events could lead to ongoing viral evolution it should be considered to optimize antiretroviral therapy in order to minimize the development of drug resistance. J. Med. Virol. 79:1440–1445, 2007. © Wiley‐Liss, Inc.
Development and evaluation of a real‐time PCR assay for rapid identification and semi‐quantitation of measles virus
Authors: Thomas Brenda , Beard Stuart , Jin Li , Brown Kevin E. , Brown David W.G.
Published: August 2007

A real‐time PCR assay for measles virus was designed and validated using clinical samples including oral fluids, sera, urines, throat swabs, blood samples, and nasopharyngeal aspirates. The test was specific for measles virus, with a slightly higher sensitivity compared to the conventional nested PCR. Calculation of viral genome number in these samples, by comparison with a standard curve prepared from dilutions of cloned measles virus H gene, indicated that, overall, serum samples tended to have a lower viral load than oral fluid samples, and that the viral load decreased with increasing time after onset of symptoms. The real‐time PCR is considered to be a sensitive and specific alternative to the conventional measles PCR, especially in situations where early and rapid diagnosis are important. J. Med. Virol. 79:1587–1592, 2007. © Wiley‐Liss, Inc.
Alpha‐synuclein and its role in metal binding: Relevance to Parkinson's disease
Authors: Wright Josephine A. , Brown David R.
Published: August 2007

Parkinson's disease and some other neurodegenerative disorders are associated with a protein that can aggregate and form fibrils called alpha‐synuclein. Like many other proteins associated with neurodegenerative disorders, this protein has no known function, and the mechanism by which it could cause diseases is poorly defined. It was recently suggested that it binds copper. This review assesses what is known about alpha‐synuclein and its interaction with metals. © 2007 Wiley‐Liss, Inc.