bluuebunny/crossref_metadata_2025 huggingface dataset:
Ischemic preconditioning preserves proton leakage from mitochondrial membranes but not oxidative phosphorylation during heart reperfusion
Authors: Muscari Claudio , Bonafè Francesca , Gamberini Chiara , Giordano Emanuele , Lenaz Giorgio , Caldarera Claudio Marcello
Published: October 2005

The aim of this study was to evaluate the role of mitochondria in the recovery of cardiac energetics induced by ischaemic preconditioning at reperfusion. Isolated rat hearts were aerobically perfused (control), subjected to global ischaemia and reperfusion (reperfusion), or subjected to 3 brief cycles of ischaemia/reperfusion and then to the protocol of reperfusion (preconditioning). At the end of the perfusion, antimycin A was delivered to the heart for 25 min, to inhibit mitochondrial respiration and stimulate glycolysis. The increased amount of lactate released in the coronary effluent was correlated with the number of viable cells producing this end‐product of glycolysis. Preconditioned hearts released 18% more lactate than reperfused hearts (p < 0.05). This result indicates that preconditioning partially preserved cell viability, as was also evidenced by the MTT assay performed on cardiac biopsies. The difference between antimycin A‐stimulated and basal lactate concentration, representing the contribution of mitochondria to the overall energetics of cardiac tissue, was also 18% more elevated in the preconditioned hearts than in the reperfused hearts (p < 0.01). The study of the respiratory function of mitochondria isolated at the end of perfusion, showed that preconditioning did not improve the oxygen‐dependent production of ATP (state 3 respiration, ADP/O). On the contrary, state 4 respiration, which is related to proton leakage, was 35.0% lower in the preconditioned group than reperfusion group (p < 0.05). Thus, preconditioning ameliorates cardiac energetics by preserving cell death, but without affecting mitochondrial oxidative phosphorylation. Mitochondria can contribute to cell survival by the attenuation of proton leak from inner membrane. Copyright © 2005 John Wiley & Sons, Ltd.
Effects of intraperitoneally administered ubiquinone on the level of total lipid and fatty acids in rat liver
Authors: Çelik Sait , Akarçay Hatice , Yılmaz Ökkeş , Özkaya Ahmet
Published: October 2005

The purpose of the present study was to evaluate the effect of ubiquinone (coenzyme Q‐10) on total lipid and fatty acid composition of liver tissues in rats. Twenty male wistar rats were randomly divided into two groups. The first group was used as a control. The second group received ubiquinone (8 mg/every other day) intraperitoneally. This administration was done for a period of 38 days. Body weight increases in animals fed diets for 38 days were on average 35 g in control group (C), and only 11 g in the ubiquinone group. Total lipid content of liver tissues in the ubiquinone group (UB) decreased significantly (p < 0.0001) compared to the control group (C). The ratio of 22:6 and total ω3 fatty acid in the UB increased (p < 0.01) compared to C. While the level of oleic acid (18:1), palmitoleic acid (16:1) and total monounsaturated fatty acid (MUFA) in UB significantly decreased (p < 0.01, p < 0.001, p < 0.001, respectively), the level of stearic acid (18:0) in liver tissue increased (p < 0.05) in the same group when compared to C. Stearoyl‐CoA desaturase (SCD) is the rate‐limiting enzyme catalyzing the synthesis of monounsaturated fatty acid mainly oleate (18:1). We speculate that ubiquinone inhibits SCD activity. SCD is an important metabolic control point in body weight regulation. Our results indicate that ubiquinone supplementation may have an inhibitory effect on obesity and it seems that the level of 22:6 in liver increased due to ubiquinone. Copyright © 2005 John Wiley & Sons, Ltd.
Binding of Helix‐Threading Peptides to E. coli 16S Ribosomal RNA and Inhibition of the S15–16S Complex
Authors: Gooch Barry D. , Krishnamurthy Malathy , Shadid Mohammad , Beal Peter A.
Published: October 2005

Helix‐threading peptides (HTPs) constitute a new class of small molecules that bind selectively to duplex RNA structures adjacent to helix defects and project peptide functionality into the dissimilar duplex grooves. To further explore and develop the capabilities of the HTP design for binding RNA selectively, we identified helix 22 of the prokaryotic ribosomal RNA 16S as a target. This helix is a component of the binding site for the ribosomal protein S15. In addition, the S15–16S RNA interaction is important for the ordered assembly of the bacterial ribosome. Here we present the synthesis and characterization of helix‐threading peptides that bind selectively to helix 22 of E. coli 16S RNA. These compounds bind helix 22 by threading intercalation placing the N termini in the minor groove and the C termini in the major groove. Binding is dependent on the presence of a highly conserved purine‐rich internal loop in the RNA, whereas removal of the loop minimally affects binding of the classical intercalators ethidium bromide and methidiumpropyl–EDTA⋅Fe (MPE⋅Fe). Moreover, binding selectivity translates into selective inhibition of formation of the S15–16S complex.
Unidirectional Threading Synthesis of Isomer‐Free [2]Rotaxanes
Authors: Wang Qiao‐Chun , Ma Xiang , Qu Da‐Hui , Tian He
Published: October 2005

The threading of an α‐cyclodextrin (α‐CyD) by an unsymmetrical dumbbell generally results in two isomeric [2]rotaxanes differing in the orientation of the α‐CyD. In this work, two methods have been developed for the unidirectionally threading an α‐CyD to obtain isomer‐free [2]rotaxanes. These methods use the Suzuki coupling of a boronic acid derivative and a halide in aqueous alkaline solution. The conformations of the two unidirectional [2]rotaxanes‐R3 and R4 were determined by 2D 1H ROESY NMR spectra. The optical spectral studies revealed that each of the two [2]rotaxanes can proceed with E/Z photoisomerization and shuttling motions of the α‐CyD ring on the thread under alternating irradiation at 330 and 275 nm, accompanied by fluorescence intensity changes at 530 nm. The induced circular dichroism (ICD) spectra of another two analogous [2]rotaxanes R1 and R2 were also studied. Distinctive ICD signal changes resulting from the photoisomerization with respect to the movements of α‐CyD were detected. This demonstrates that, besides the fluorescence, ICD signal is another way to identify the shuttling motions of α‐CyD in these [2]rotaxanes.
Synthesis of Heterobimetallic RuMn Complexes and the Coupling Reactions of Epoxides with Carbon Dioxide Catalyzed by these Complexes
Authors: Man Man Lok , Lam King Chung , Sit Wing Nga , Ng Siu Man , Zhou Zhongyuan , Lin Zhenyang , Lau Chak Po
Published: October 2005

The heterobimetallic complexes [(η5‐C5H5)Ru(CO)(μ‐dppm)Mn(CO)4] and [(η5‐C5Me5)Ru(μ‐dppm)(μ‐CO)2Mn(CO)3] (dppm= bis‐diphenylphosphinomethane) have been prepared by reacting the hydridic complexes [(η5‐C5H5)Ru(dppm)H] and [(η5‐C5Me5)Ru(dppm)H], respectively, with the protonic [HMn(CO)5] complex. The bimetallic complexes can also be synthesized through metathetical reactions between [(η5‐C5R5)Ru(dppm)Cl] (R=H or Me) and Li+[Mn(CO)5]−. Although the complexes fail to catalyze the hydrogenation of CO2 to formic acid, they catalyze the coupling reactions of epoxides with carbon dioxide to yield cyclic carbonates. Two possible reaction pathways for the coupling reactions have been proposed. Both routes begin with heterolytic cleavage of the RuMn bond and coordination of an epoxide molecule to the Lewis acidic ruthenium center. In Route I, the Lewis basic manganese center activates the CO2 by forming the metallocarboxylate anion which then ring‐opens the epoxide; subsequent ring‐closure gives the cyclic carbonate. In Route II, the nucleophilic manganese center ring‐opens the ruthenium‐attached epoxide to afford an alkoxide intermediate; CO2 insertion into the RuO bond followed by ring‐closure yields the product. Density functional calculations at the B3LYP level of theory were carried out to understand the structural and energetic aspects of the two possible reaction pathways. The results of the calculations indicate that Route II is favored over Route I.
Medication safety in the ambulatory chemotherapy setting
Authors: Gandhi Tejal K. , Bartel Sylvia B. , Shulman Lawrence N. , Verrier Deborah , Burdick Elisabeth , Cleary Angela , Rothschild Jeffrey M. , Leape Lucian L. , Bates David W.
Published: October 2005

BACKGROUND

Little is known concerning the safety of the outpatient chemotherapy process. In the current study, the authors sought to identify medication error and potential adverse drug event (ADE) rates in the outpatient chemotherapy setting.

METHODS

A prospective cohort study of two adult and one pediatric outpatient chemotherapy infusion units at one cancer institute was performed, involving the review of orders for patients receiving medication and/or chemotherapy and chart reviews. The adult infusion units used a computerized order entry writing system, whereas the pediatric infusion unit used handwritten orders. Data were collected between March and December 2000.

RESULTS

The authors reviewed 10,112 medication orders (8008 adult unit orders and 2104 pediatric unit orders) from 1606 patients (1380 adults and 226 pediatric patients). The medication error rate was 3% (306 of 10,112 orders). Of these errors, 82% occurring in adults (203 of 249 orders) had the potential for harm and were potential ADEs, compared with 60% of orders occurring in pediatric patients (34 of 57 orders). Among these, approximately one‐third were potentially serious. Pharmacists and nurses intercepted 45% of potential ADEs before they reached the patient. Several changes were implemented in the adult and pediatric settings as a result of these findings.

CONCLUSIONS

In the current study, the authors found an ambulatory medication error rate of 3%, including 2% of orders with the potential to cause harm. Although these rates are relatively low, there is clearly the potential for serious patient harm. The current study identified strategies for prevention. Cancer 2005. © 2005 American Cancer Society.
Reducing adverse drug events in the outpatient chemotherapy setting
Authors: Nebeker Jonathan R. , Bennett Charles L.
Published: October 2005

Cancer agents have the potential for severe, and occasionally fatal, adverse drug events. Many receive accelerated approval for use after small clinical trials, with adverse drug events being identified after additional experience in the postmarketing clinical setting. Moreover, chemotherapy risks may be especially high in tertiary care settings where patients are frequently subject to complex treatment protocols with high dosages, novel agents, or novel combinations of agents. Recommendations from the study on medication errors by Gandhi et al. contribute to international efforts to prevent adverse drug reactions and improve their early recognition and treatment.

See also pages 2477–83.
Reciprocal expression of lin‐41 and the microRNAs let‐7 and mir‐125 during mouse embryogenesis
Authors: Schulman Betsy R. Maller , Esquela‐Kerscher Aurora , Slack Frank J.
Published: October 2005

In C. elegans, heterochronic genes control the timing of cell fate determination during development. Two heterochronic genes, let‐7 and lin‐4, encode microRNAs (miRNAs) that down‐regulate a third heterochronic gene lin‐41 by binding to complementary sites in its 3′UTR. let‐7 and lin‐4 are conserved in mammals. Here we report the cloning and sequencing of mammalian lin‐41 orthologs. We find that mouse and human lin‐41 genes contain predicted conserved complementary sites for let‐7 and the lin‐4 ortholog, mir‐125, in their 3′UTRs. Mouse lin‐41 (Mlin‐41) is temporally expressed in developing mouse embryos, most dramatically in the limb buds. Mlin‐41 is down‐regulated during mid‐embryogenesis at the time when mouse let‐7c and mir‐125 RNA levels are up‐regulated. Our results suggest that mammalian lin‐41 is temporally regulated by miRNAs in order to direct key developmental events such as limb formation. Developmental Dynamics 234:1046–1054, 2005. © 2005 Wiley‐Liss, Inc.
Altered primary CD8+ T cell response to a modified virus Ankara(MVA)‐vectored vaccine in the absence of CD4+ T cell help
Authors: Estcourt Marie J. , McMichael Andrew J. , Hanke Tomáš
Published: October 2005

T cell receptor‐transgenic F5 mice were used to assess primary CD8+ T cell responses to a modified virus Ankara (MVA)‐vectored vaccine in the absence of CD4+ T cell help. Naive, CD8‐enriched, CFSE‐labelled F5 cells were transferred into normal or CD4+ cell‐depleted mice and the mice were vaccinated with MVA.HIVA‐NP. At different time points during the primary response, F5 cells were re‐isolated and analysed on divisional basis for a number of parameters. We demonstrated that the primary CD8+ T cell response in the absence of CD4+ T cell help differed from that in normal CD4+ cell‐undepleted mice. While in the absence of CD4+ T cell help, the initial migratory progress from the local response to a systemic one was not grossly affected, the proportion of dying F5 cells during the expansion phase was markedly increased and resulted in an overall smaller expansion and significantly decreased frequency of CD8+ T cell memory after contraction. T cells primed without help displayed accelerated proliferation and activation, while expression of interferon‐γ remained similar. These phenomena were observed in the lymph nodes draining the MVA.HIVA‐NP immunization site and were similar, but delayed by 2–3 days in spleen and non‐draining lymph nodes.
Neural correlates of anosognosia for cognitive impairment in Alzheimer's disease
Authors: Salmon Eric , Perani Daniela , Herholz Karl , Marique Patricia , Kalbe Elke , Holthoff Vjera , Delbeuck Xavier , Beuthien‐Baumann Bettina , Pelati Oriana , Lespagnard Solange , Collette Fabienne , Garraux Gaëtan
Published: October 2005

We explored the neural substrate of anosognosia for cognitive impairment in Alzheimer's disease (AD). Two hundred nine patients with mild to moderate dementia and their caregivers assessed patients' cognitive impairment by answering a structured questionnaire. Subjects rated 13 cognitive domains as not impaired or associated with mild, moderate, severe, or very severe difficulties, and a sum score was calculated. Two measures of anosognosia were derived. A patient's self assessment, unconfounded by objective measurements of cognitive deficits such as dementia severity and episodic memory impairment, provided an estimate of impaired self‐evaluative judgment about cognition in AD. Impaired self‐evaluation was related to a decrease in brain metabolism measured with 18F‐2‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography (FDG‐PET) in orbital prefrontal cortex and in medial temporal structures. In a cognitive model of anosognosia, medial temporal dysfunction might impair a comparison mechanism between current information on cognition and personal knowledge. Hypoactivity in orbitofrontal cortex may not allow AD patients to update the qualitative judgment associated with their impaired cognitive abilities. Caregivers perceived greater cognitive impairments than patients did. The discrepancy score between caregiver's and patient's evaluations, an other measure of anosognosia, was negatively related to metabolic activity located in the temporoparietal junction, consistent with an impairment of self‐referential processes and perspective taking in AD. Hum Brain Mapp, 2005. © 2005 Wiley‐Liss, Inc.
Optimization of expression ofdhaT gene encoding 1,3‐propanediol oxidoreductase fromKlebsiella pneumoniaeinEscherichia coliusing the methods of uniform design and regression analysis
Authors: Cao Yang , Xia Qirong , Fang Baishan
Published: October 2005

This paper is concerned with the optimization of expression conditions of 1,3‐propanediol oxidoreductase (PDOR) using the uniform design (UD) method and regression analysis. The concentration of the inducer isopropyl‐β‐D‐thiogalactopyranoside (IPTG), the induction temperature and the induction time, which were identified as three crucial factors, were optimized in 50 mL cultivation tubes containing 5 mL LB culture. The optimal expression conditions for enhanced PDOR activity were found to be an IPTG concentration of 0.1 mmol l−1, an induction temperature of 21.2 °C and an induction time of 5 h. Subsequent experimental trials confirmed the validity of the model. These optimal expression conditions in the cultivation tube culture led to a PDOR activity of 9.25 U mL−1, which was considerably higher than those obtained in the optimizing experimental trials. Copyright © 2005 Society of Chemical Industry
Chemical characterization and liberation of pentose sugars from brewer's spent grain
Authors: Mussatto Solange I , Roberto Inês C
Published: October 2005

The chemical composition of brewer's spent grain (BSG), generated from a process using 100% malted barley, was investigated. BSG is mainly composed of (g kg−1) hemicellulose (284), lignin (278), cellulose (168) and protein (152.5), but it also contains extractives and ashes in smaller proportions. Minerals in BSG include calcium, sodium, potassium, magnesium, aluminum, iron, barium, strontium, manganese, copper, zinc, phosphorus, sulfur, chromium and silicon. In order to find alternative uses for BSG, this by‐product was subjected to acid hydrolysis process to recover the hemicellulosic sugars, which have a large number of industrial applications. The process was carried out under different conditions of liquid‐to‐solid ratio and acid concentration to evaluate the influence of these two variables on BSG hemicellulose hydrolysis. Under all the hydrolysis conditions evaluated, arabinose was recovered with higher efficiency than xylose. Under the best evaluated reaction conditions (liquid‐to‐solid ratio of 10 g g−1 and 120 mg H2SO4 g−1 dry matter) 76.2% of the hemicellulose was hydrolyzed and the xylose and arabinose sugars were recovered with 67 and 97.8% efficiency, respectively. Copyright © 2005 Society of Chemical Industry
A correlation for dispersed phase axial mixing coefficients in rotating disc contactors
Authors: Murugesan Thanapalan , Regupathi Iyyasami
Published: October 2005

A correlation for the estimation of dispersed phase axial mixing coefficients in terms of all the operating and fundamental variables was established. The proposed correlations are found to be a good representation of the present data (260 data points) obtained using four liquid‐liquid systems from two different sources. Copyright © 2005 Society of Chemical Industry
The effect of substrate concentrations on the production of biodiesel by lipase‐catalysed transesterification of vegetable oils
Authors: Al‐Zuhair Sulaiman
Published: October 2005

All the kinetic studies, found in the literature, on the production of biodiesel (fatty acids methyl esters) considered the esterifications of free fatty acids rather than the transesterification of the vegetable oil itself. The main industrial interest, however, is for the production of biodiesel with the triglyceride (oil) being the substrate. A mathematical model taking into account the mechanism of the methanolysis reaction starting from the vegetable oil as substrate, rather than the free fatty acids, has been developed. From the proposed model equation, the regions where the effect of alcohol inhibition fades, at different substrate concentrations, were identified. The proposed model equation can be used to predict the rate of methanolysis of vegetable oils in a batch or a continuous reactor and to determine the optimal conditions for biodiesel production. Copyright © 2005 Society of Chemical Industry
Metal chelate absorption coupled with microbial reduction for the removal of NOx from flue gas
Authors: Li Wei , Wu Cheng‐Zhi , Shi Yao
Published: October 2005

A novel process for the removal of NOx from flue gas by a combined Fe(II)EDTA absorption and microbial reduction has been demonstrated. Fe(II)EDTA–NO and Fe(III)EDTA (EDTA: ethylenediaminetetraacetate) can be effectively reduced to the active Fe(II)EDTA in the reactor containing microorganisms. In a steady‐state absorption and regeneration process, the final removal efficiency of NO is up to 88%. The effects of four main parameters (i.e. NO, O2 and SO2 concentrations, and the amount of cyclic solution) on NOx removal efficiency were experimentally investigated at 50 °C. The results provide some insight into conditions required for the successful removal of NOx from flue gas using the approach of Fe(II)EDTA absorption combined with microbial reduction. Copyright © 2005 Society of Chemical Industry
Specific recognition of non‐denatured nitrite‐oxidizing system of Nitrospira moscoviensis by monoclonal antibody Hyb 153‐3
Authors: Litman Matthew R , Chiu Norman HL , Wang James
Published: October 2005

The objective of this research project is to develop a rapid molecular method for monitoring nitrification in a wastewater reactor. In the developed method, a monoclonal antibody (Hyb 153‐3) was used because it can specifically recognize non‐denatured enzymes responsible for nitrite oxidation in Nitrobacter and Nitrospira. The recognition of these enzymes under non‐denatured conditions can significantly simplify the procedures of future immunoassays for environmental samples collected from various natural and engineered systems. This paper presents the ability of the selected Hyb 153‐3 antibody to recognize the non‐denatured form of the nitrite‐oxidizing enzyme of Nitrospira in an aqueous phase as well as when the enzyme has been immobilized on a solid surface. Copyright © 2005 Society of Chemical Industry
Surface properties and catalytic behavior of MoO3/SiO2 in esterification of acetic acid with ethanol
Authors: A Said Abd El‐Aziz , Abd El‐Wahab Mohamed MM
Published: October 2005

A series of MoO3/SiO2 catalysts was prepared by an impregnation method with Mo loadings ranging from 1 to 50 wt%. The original and calcined samples at 400 °C were characterized by thermogravimetry (TG), differential thermogravimetry (DTG), differential scanning calorimetry (DSC), X‐ray diffraction (XRD), Fourier transform infra‐red (FTIR) spectroscopy, and nitrogen adsorption measurements. The surface acidity and basicity of the catalysts were investigated by the dehydration–dehydrogenation of isopropanol and the chemisorption of pyridine. The catalytic esterification of acetic acid with ethanol was carried out at 220 °C in a conventional fixed‐bed reactor at 1 atm using air as a carrier gas. The results clearly revealed that silica–molybdena catalysts were active and selective towards the formation of ethyl acetate. Moreover, the catalyst containing 20 wt% MoO3 was the most active and selective one. The results emphasize the importance of the surface acid sites together with the specific surface area of the prepared catalyst, towards ester formation. Copyright © 2005 Society of Chemical Industry
Photocatalytic degradation of 3‐nitrobenzenesulfonic acid in aqueous TiO2 suspensions
Authors: Gautam Satyen , Kamble Sanjay P , Sawant Sudhir B , Pangarkar Vishwas G
Published: October 2005

The photocatalytic degradation of 3‐nitrobenzenesulfonic acid in the presence of solar radiation and artificial UV radiation with suspended TiO2 was studied in a batch and continuous annular reactor, respectively. The effects of catalyst loading, pH, presence of anions and cations and initial concentration on the rate of photocatalytic degradation were investigated. Concentration–time data were correlated with the rate equation d[Ct=0]/dt = krK[Ct=0]/(1 + K[Ct=0]). Studies were carried out to compare the photolytic, photochemical and photocatalytic methods of degradation. Copyright © 2005 Society of Chemical Industry
Photocatalytic degradation of m‐dinitrobenzene by illuminated TiO2 in a slurry photoreactor
Authors: Kamble Sanjay P , Sawant Sudhir B , Pangarkar Vishwas G
Published: October 2005

1,3‐dinitrobenzene (m‐DNB) is one of the compounds released to water in discharges during the manufacture of explosives. Its widespread distribution as an environmental contaminant is a potential threat to wildlife and other ecological receptors. Therefore, removal of m‐DNB from aqueous solution is very important. In this work, which is a continuation of our ongoing investigation of the effect of various functional groups in aromatic derivatives, a study of the destruction of m‐DNB in aqueous solution, was carried out using both concentrated solar radiation and artificial UV radiation. It was found that a variety of phenolic intermediates are formed via hydroxyl radicals attacking the parent compound. The effects of the various parameters such as adsorption, initial concentration, catalyst loading, pH and anions on the photocatalytic degradation of m‐DNB was studied. The kinetics of the photocatalytic reaction were also studied. The effect of the second nitro group in m‐DNB was elucidated by comparison with our earlier work on PCD of nitrobenzene. Copyright © 2005 Society of Chemical Industry
Molecular basis for regulation of Src by the docking protein p130Cas
Authors: Nasertorabi Fariborz , Tars Kaspars , Becherer Kathleen , Kodandapani Ramadurgam , Liljas Lars , Vuori Kristiina , Ely Kathryn R.
Published: October 2005

The docking protein p130Cas (Cas) becomes tyrosine‐phosphorylated in its central substrate domain in response to extracellular stimuli such as integrin‐mediated cell adhesion, and transmits signals through interactions with various intracellular signaling molecules such as the adaptor protein Crk. Src‐family kinases (SFKs) bind a specific site in the carboxyl‐terminal region of Cas and subsequently SFKs phosphorylate progressively the substrate domain in Cas. In this study crystallography, mutagenesis and binding assays were used to understand the molecular basis for Cas interactions with SFKs. Tyrosine phosphorylation regulates binding of Cas to SFKs, and the primary site for this phosphorylation, Y762, has been proposed. A phosphorylated peptide corresponding to Cas residues 759MEDpYDYVHL767 containing the key phosphotyrosine was crystallized in complex with the SH3–SH2 domain of the SFK Lck. The results provide the first structural data for this protein–protein interaction. The motif in Cas 762pYDYV binds to the SH2 domain in a mode that mimics high‐affinity ligands, involving dual contacts of Y762 and V765 with conserved residues in SFK SH2 domains. In addition, Y764 is in position to make an electrostatic contact after phosphorylation with a conserved SFK arginine that mediates interactions with other high‐affinity SH2 binders. These new molecular data suggest that Cas may regulate activity of Src as a competing ligand to displace intramolecular interactions that occur in SFKs (between the C‐terminal tail and the SH2 domain) and restrain and down‐regulate the kinase in an inactive form. Copyright © 2005 John Wiley & Sons, Ltd.
Tobacco cembranoids protect the function of acute hippocampal slices against NMDA by a mechanism mediated by α4β2 nicotinic receptors
Authors: Ferchmin P.A. , Hao Jiukuan , Perez Dinely , Penzo Mario , Maldonado Hector M. , Gonzalez Maria T. , Rodriguez Abimael D. , de Vellis Jean
Published: October 2005

Nicotine has been reported to be neuroprotective in experimental and epidemiological studies. In addition to nicotine, tobacco and cigarette smoke contain cembranoids, which are antagonists of neuronal nicotinic receptors (nAChR). Exposure of hippocampal slices toN‐methyl‐D‐aspartate (NMDA) decreases the population spikes (PS). This parameter has been used as a measure of excitotoxicity. Surprisingly, both nicotine and tobacco cembranoids protected against NMDA and this neuroprotection was not blocked by methyllycaconitine (MLA), an antagonist of α7 nAChR. On the contrary, MLA had a neuroprotective effect of its own. We examined the effect of the tobacco cembranoid (1S,2E,4R,6R,7E,11E)‐cembra‐2,7,11‐triene‐4,6‐diol (4R) on the neuroprotection against NMDA. DHβE, a selective antagonist of α4β2 nAChR, inhibited the neuroprotection by nicotine, 4R, and MLA, suggesting the involvement of α4β2 nAChRs in the neuroprotection. The cell‐signaling pathways underlying the neuroprotection by 4R and by nicotine are different. The activity of phosphatidylinositol‐3 kinase (PI3K) was required in both cases; however, 4R required the activity of L‐type calcium channels and CAM kinase, whereas nicotine required the extracellular signal regulated kinase‐1,2 (ERK) and protein kinase C (PKC). In addition, 4R did not enhance total phospho‐ERK‐1/2 but increased the amount of total Akt/PKB phosphorylated on the activation site and of glycogen synthase kinase 3‐β phosphorylated on the inhibitory site. Total levels of phosphoenzymes are presented instead of the ratio of phospho‐ over total enzyme because in preliminary experiments total ERK‐1/2 levels were slightly increased by 4R. In conclusion, these findings demonstrate that there are two different nicotinic neuroprotective mechanisms mediated by α4β2. © 2005 Wiley‐Liss, Inc.
Postsynaptic excitation of prefrontal cortical pyramidal neurons by hypocretin‐1/orexin a through the inhibition of potassium currents
Authors: Xia Jianxia , Chen Xiaowei , Song Chenghui , Ye Jianning , Yu Zhengping , Hu Zhian
Published: October 2005

Hypocretins are crucial for the regulation of wakefulness by the excitatory actions on multiple subcortical arousal systems. To date, there is little information about the direct postsynaptic excitatory effects of hypocretins on the neurons in prefrontal cortex (PFC), which is important for higher cognitive functions and is correlated with level of wakefulness. In this study, we tested the excitatory effects of hypocretin‐1 on acutely isolated PFC pyramidal neurons of rats and studied the possible ionic mechanisms by using whole‐cell patch‐clamp techniques. Puff application of hypocretin‐1 caused a dose‐dependent excitation. Further observations that perfusion of Ca2+‐free artificial cerebrospinal fluid did not influence the depolarizing effects of hypocretin‐1, in conjunction with the findings that hypocretin‐1 could decrease net whole‐cell K+ currents, demonstrate that the excitatory effects of hypocretin‐1 on PFC neurons are mediated by the inhibition of K+ currents but not Ca2+ influx. Finally, the decrease in K+ currents induced by hypocretin‐1 was abolished by a protein kinase C (PKC) inhibitor (BIS II) or a phospholipase C (PLC) inhibitor (D609), suggesting that PKC and PLC appear to be involved in mediating the inhibitory effects of hypocretin‐1 on K+ currents. These results indicate that hypocretin‐1 exerts a postsynaptic excitatory action on PFC neurons through the inhibition of K+ currents, which probably results from activation of PKC and PLC signaling pathways. © 2005 Wiley‐Liss, Inc.
Hormonal and sensory inputs regulate distinct neuroblast cell cycle properties in adult cricket brain
Authors: Cayre Myriam , Malaterre Jordane , Scotto‐Lomassese Sophie , Aouane Aïcha , Strambi Colette , Strambi Alain
Published: October 2005

From invertebrates to humans, it has been demonstrated that new neurons are added to specific brain structures throughout adult life. In the house cricket, adult neurogenesis occurs in the mushroom bodies, the main sensory integrative center of the brain, often considered an analogue of vertebrate hippocampus. We have previously shown that this neurogenesis can be modulated by hormones through the polyamine pathway and by environmental conditions through sensory inputs and the nitric oxide pathway. Environment‐induced neurogenesis is independent of juvenile hormone levels, so we addressed the roles of sensory inputs and hormones in the control of neuroblast proliferation. Here, by using double labelling of cells specifically in S phase (5‐bromo‐2′‐deoxyuridine) together with labelling of mitotically active cells in any phase (proliferating cell nuclear antigen), we show that juvenile hormone acts on progenitor cell proliferation by inducing quiescent neuroblasts to enter the cell cycle, whereas sensory inputs act by shortening the cell cycle. Thus, in the adult house cricket, regulation of neuroblast proliferation by hormonal and environmental cues occurs through two independent modes of action. © 2005 Wiley‐Liss, Inc.
Transplanted human embryonic germ cell‐derived neural stem cells replace neurons and oligodendrocytes in the forebrain of neonatal mice with excitotoxic brain damage
Authors: Mueller Dawn , Shamblott Michael J. , Fox Harold E. , Gearhart John D. , Martin Lee J.
Published: October 2005

Stem cell therapy is a hope for the treatment of some childhood neurological disorders. We examined whether human neural stem cells (hNSCs) replace lost cells in a newborn mouse model of brain damage. Excitotoxic lesions were made in neonatal mouse forebrain with the N‐methyl‐D‐aspartate (NMDA) receptor agonist quinolinic acid (QA). QA induced apoptosis in neocortex, hippocampus, striatum, white matter, and subventricular zone. This degeneration was associated with production of cleaved caspase‐3. Cells immunopositive for inducible nitric oxide synthase were present in damaged white matter and subventricular zone. Three days after injury, mice received brain parenchymal or intraventricular injections of hNSCs derived from embryonic germ (EG) cells. Human cells were prelabeled in vitro with DiD for in vivo tracking. The locations of hNSCs within the mouse brain were determined through DiD fluorescence and immunodetection of human‐specific nestin and nuclear antigen 7 days after transplantation. hNSCs survived transplantation into the lesioned mouse brain, as evidenced by human cell markers and DiD fluorescence. The cells migrated away from the injection site and were found at sites of injury within the striatum, hippocampus, thalamus, and white matter tracts and at remote locations in the brain. Subsets of grafted cells expressed neuronal and glial cell markers. hNSCs restored partially the complement of striatal neurons in brain‐damaged mice. We conclude that human EG cell‐derived NSCs can engraft successfully into injured newborn brain, where they can survive and disseminate into the lesioned areas, differentiate into neuronal and glial cells, and replace lost neurons. © 2005 Wiley‐Liss, Inc.
A cyanopropyl reversed phase chromatography enables resolution of huperzine A and B on analytical and preparative scales
Authors: Li Xiu‐Nan , Sun Hai‐Hong , Zhang Gui‐Feng , Bi Jing‐Xiu , Ma Guang‐Hui , Ma Run‐Yu , Su Zhi‐Guo
Published: October 2005

Huperzine A (HupA) and huperzine B (HupB) are two medically important components of Huperzia serrata. It is difficult to obtain high yields of the separation from the plant using conventional liquid extraction and chromatography. However, this study has found that RP chromatography with cyanopropyl (CN) medium was able to separate these two analogs simultaneously from the plant extract with higher resolution. Comparison between a CN medium and a popular C18 medium demonstrated the superiority of the CN over the C18 in resolution for both analytical and preparative separation of HupA and HupB. A preparative process was developed for simultaneous purification of HupA and HupB from H. serrata. The yields on the basis of the mass of the herbal powder for HupA and HupB were 0.019 and 0.008% respectively, which were about 1.9 and 10 times of those reported in the literature.
Application of multiwalled carbon nanotubes as solid phase extraction sorbent for preconcentration of trace copper in water samples
Authors: Liang Pei , Ding Qiong , Song Feng
Published: October 2005

The adsorption behavior of multiwalled carbon nanotubes (MWNTs) toward copper has been investigated systemically, and a new method has been developed for the determination of trace copper in water samples based on preconcentration with a microcolumn packed with MWNTs prior to its determination by flame atomic absorption spectrometry. The optimum experimental parameters for preconcentration of copper, such as pH of the sample, sample flow rate and volume, elution solution and interfering ions, have been investigated. Copper can be quantitatively retained by MWNTs in the pH range 5–8, and then eluted completely with 0.5 M HNO3. The detection limit of this method for Cu was 0.42 ng/mL, and the RSD was 3.5% at the 10 ng/mL Cu level. The method was validated using a certified reference material, and has been successfully applied for the determination of trace copper in water samples.
Ionene‐dynamically coated capillary for analysis of urinary and recombinant human erythropoietin by capillary electrophoresis and online electrospray ionization mass spectrometry
Authors: Yu Bing , Cong Hailin , Liu Huwei , Li Yuanzong , Liu Feng
Published: October 2005

In this article, a series of ionene polymers were synthesized and used to coat fused‐silica capillaries for the separation of recombinant and urinary human erythropoietin (rhEPO and uEPO) standards by CE. The influence of the charge density of coatings on the separation of rhEPO and uEPO glycoforms was investigated. Then, we further studied the method for fast separation and detection of rhEPO and uEPO standards by CE‐ESI‐MS. The influence of several CE and MS operating parameters, such as the concentration of CE running buffer, applied external pressure, and the composition and flow rate of sheath liquid on CE‐ESI‐MS was studied. The results demonstrated that when the capillary was permanently coated with 6,6‐ionene and the pH value of acetic acid‐ammonium acetate running buffer was 4.80 and 5.50, respectively, a significantly reproducible separation was achieved for rhEPO and uEPO glycoforms. In the online CE‐ESI‐MS experiments, we not only achieved the online MS signal of uEPO, but also obtained baseline separation of three major rhEPO glycoforms successfully and reproducibly on the 6,6‐ionene‐coated capillaries. Furthermore, the standard mixture of rhEPO and uEPO was separated, and two incompletely resolved peaks that were identified to be rhEPO and uEPO by the unique MS “fingerprint” were obtained. Additionally, the molecular weight of rhEPO and uEPO were verified and compared to the results by MALDI‐TOF‐MS. It can be concluded that, in contrast to other indirect methods, the online CE‐ESI‐MS technique with the combination of the advantages of both CE and MS shows great potential for the separation and detection of rhEPO doping directly in competitive sports.
Development and validation of an HPLC confirma‐tory method for the determination of tetracycline antibiotics residues in bovine muscle according to the European Union regulation 2002/657/EC
Authors: Samanidou Victoria F. , Nikolaidou Konstantina I. , Papadoyannis Ioannis N.
Published: October 2005

A high‐performance liquid chromatographic method with diode‐array detection, at 351 nm, was developed and validated for the determination of five tetracyclines (TCs): minocycline, tetracycline, oxytetracycline, chlortetracycline, and doxycycline in bovine muscle. Samples were macerated with a buffer solution, centrifuged, and purified using Abselut Nexus SPE cartridges. The separation of the examined TCs was achieved on an Inertsil ODS‐3 5 μm, 250×4 mm analytical column, at ambient temperature. A multistep gradient elution was followed using 0.05 M oxalic acid and CH3CN, at a flow rate of 1.65 mL/min. The procedure was validated according to the European Union regulation 2002/657/EC determining selectivity, stability, decision limit, detection capability, accuracy, and precision. The results of the validation process demonstrate that the method can be readily applied to European Union statutory veterinary drug residue surveillance programmes. Mean recoveries of TCs from bovine muscle samples spiked at three concentrations (100, 250, and 400 ng/g) were in the range of 98.7–103.3%. Method's LOQ values achieved were 40 μg/kg for MNC, CTC, and DC and 25 μg/kg for OTC and TC. The decision limits (CCα) were in the range of 104.7–109.8 μg/kg, while the detection capability (CCβ) was in the range of 108.4–116.7 μg/kg for all compounds.
Gradual DNA demethylation of the Oct4 promoter in cloned mouse embryos
Authors: Yamazaki Yukiko , Fujita Toko C. , Low Eleanor W. , Alarcón Vernadeth B. , Yanagimachi Ryuzo , Marikawa Yusuke
Published: October 2005

During differentiation, somatic cell nuclei acquire unique patterns of epigenetic modifications, such as DNA methylation, which affect the transcriptional activity of specific genes. Upon transfer into oocytes, however, the somatic nucleus undergoes reprogramming of these epigenetic modifications to achieve pluripotency. Oct4 is one of the critical pluripotency regulators, and is expressed in the germ line, including the pluripotent early embryonic cells. Previous studies showed that the upstream regulatory sequences of the Oct4 gene are distinctly methylated in somatic cells, and the DNA methylation of the regulatory sequences suppresses the transcriptional activity. Thus, successful reprogramming of the somatic cell nucleus to gain pluripotency must be accompanied by the demethylation of the Oct4 regulatory sequences. Here, we investigated the methylation pattern of the Oct4 promoter during early development of cloned mouse embryos. We found that the Oct4 promoter was only gradually demethylated during the early cleavage stages and that the ineffective demethylation of the promoter was associated with developmental retardation. We also found that the upstream sequences of the other pluripotency regulators, namely Nanog, Sox2, and Foxd3, were considerably under‐methylated in cumulus cells. These results suggest that the Oct4 gene, as compared to the other pluripotency regulators, needs to undergo extensive demethylation during nuclear reprogramming, and that the failure of such demethylation is associated with inefficient development of cloned somatic cell embryos. Mol. Reprod. Dev. © 2005 Wiley‐Liss, Inc.
A unified magnetic resonance imaging pharmacokinetic theory: Intravascular and extracellular contrast reagents
Authors: Li Xin , Rooney William D. , Springer Charles S.
Published: October 2005

A fundamental reworking of pharmacokinetic theory for the use of contrast reagents (CRs) in T1‐weighted MRI studies is presented. Unlike the standard model in common use, this derivation starts with the quantities measured, the intravascular, interstitial, and intracellular 1H2O signals. The time dependences of CR concentrations are introduced as perturbations of the T1 values of these. Since there is an explicit accounting for the equilibrium exchange of water molecules between tissue compartments, the approach here is a new (second) generation of the shutter‐speed model (S2M). When the first‐order rate constant measuring CR extravasation (Ktrans) is of sufficient magnitude, simulations presented here confirm that neglect of plasma CR, a feature of the first generation of S2M, is a valid approximation. The second S2M generation (S2M2) also automatically accommodates excursions of either or both of the two major equilibrium water exchange systems (transendothelial and transcytolemmal) into any or all possible exchange conditions, from their fast‐exchange limits to their slow‐exchange limits. This can happen not because the exchange kinetics themselves vary during the isothermal CR passage, but because the MR shutter speeds for these processes can vary. When Ktrans is sufficiently small, the S2M2 also naturally accounts for the hyperfine blood agent level dependent (BALD) effect that is easily detectable at high magnetic field. This can be seen for virtually all CRs in normal brain tissue and for virtually all tissues with sufficiently intravascular CRs. Thus, S2M2 represents a unified pharmacokinetic theory for intravascular and extracellular T1 contrast reagents. Magn Reson Med, 2005. © 2005 Wiley‐Liss, Inc.
Nitric oxide modulates neuromuscular transmission during hypoxia in rat diaphragm
Authors: Zhu Xiaoping , Heunks Leo M. A. , Ennen Leo , Machiels Herwin A. , Van Der Heijden Henricus F. M. , Dekhuijzen P. N. Richard
Published: October 2005

Hypoxia impairs neuromuscular transmission in the rat diaphragm. In previous studies, we have shown that nitric oxide (NO) plays a role in force modulation of the diaphragm under hypoxic conditions. The role of NO, a neurotransmitter, on neurotransmission in skeletal muscle under hypoxic conditions is unknown. The effects of the NO synthase (NOS) inhibitor nomega‐nitro‐L‐arginine (L‐NNA, 1 mM) and the NO donor spermine NONOate (Sp‐NO, 1 mM) were evaluated on neurotransmission failure during nonfatiguing and fatiguing contractions of the rat diaphragm under hypoxic (PO2 ∼ 5.8 kPa) and hyperoxic conditions (PO2 ∼ 64.0 kPa). Hypoxia impaired force generated by both muscle stimulation at 40 HZ (P40M) and by nerve stimulation at 40 HZ (P40N). The effect of hypoxia in the latter was more pronounced. L‐NNA increased P40N whereas Sp‐NO decreased P40N during hypoxia. In contrast, neither L‐NNA nor Sp‐NO affected P40N during hyperoxia. L‐NNA only slightly reduced neurotransmission failure during fatiguing contractions under hyperoxic conditions. Consequently, neurotransmission failure assessed by comparing force loss during repetitive nerve simulation and superimposed direct muscle stimulation was more pronounced in hypoxia, which was alleviated by L‐NNA and aggravated by Sp‐NO. These data provide insight in the underlying mechanisms of hypoxia‐induced neurotransmission failure. This is important as respiratory muscle failure may result from hypoxia in vivo. Muscle Nerve, 2005
Mechanical and fire properties of styrenic polymer nanocomposites based on an oligomerically‐modified clay
Authors: Zhang Jinguo , Jiang David D. , Wang Dongyan , Wilkie Charles A.
Published: October 2005

Styrenic polymer clay nanocomposites were made through melt blending the polymer with an oligomerically‐modified clay. Polymers used in this study are polystyrene (PS), high‐impact polystyrene (HIPS), styrene‐acrylonitrile copolymer (SAN) and acrylonitrile‐butadiene‐styrene (ABS). X‐ray diffraction and transmission electron microscopy were used to evaluate the structure of the nanocomposites. Intercalated nanocomposites were formed for PS and HIPS by this method while delaminated nanocomposites were formed for SAN and ABS. The thermal stability and fire properties were evaluated using thermogravimetric analysis and cone calorimetry, respectively. Nanocomposite formation has a small effect on the thermal stability while the reduction in peak heat release rate is comparable with other nanocomposites. Tensile testing showed that the nanocomposites had enhanced Young's modulus, which means the plasticizing effect from the oligomer was suppressed. Copyright © 2005 John Wiley & Sons, Ltd.
Magnetic investigations of titanium‐doped gamma iron oxides dispersed in polymers
Authors: Chipara Mircea , Morjan Ioan , Alexandrescu Rodica , Zaleski Jeffrey M. , Remmes Nicholas , Baxter David V.
Published: October 2005

The preparation and characterization of titanium‐doped iron oxides–styrene isoprene styrene block copolymer composites is reported. The precursor, as‐synthesized nanoparticles, contains akaganeite, maghemite, and titanium‐doped maghemite. Hysteresis loops obtained by SQUID measurements revealed an exchange biased field assigned to the presence of akaganeite nanoparticles. It was found that the coercive field and the exchange bias field decreases as the temperature of the sample is increased. The temperature dependence of the magnetization revealed a blocking temperature of about 220 K. The ESR spectra in the temperature range 150 K to about 300 K are single broad resonance lines. It was observed that the resonance line position is strongly temperature dependent due to the combined action of the external and molecular magnetic fields. The decrease of the resonance line width as the temperature is increased is governed by the reorientation of the magnetization. Thermally activated movements of magnetic nanoparticles within the soft phase (polyisoprene) of the matrix may also contribute to resonance line narrowing. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 3432–3437, 2005
Abbreviations and symbols in peptide science: a revised guide and commentary
Authors: Jones John H
Published: October 2005

The abbreviations and symbols used in Peptide Science are surveyed, with comment and recommendations. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd.