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Selected AbstractsLC-MS: a powerful tool in workplace drug testingDRUG TESTING AND ANALYSIS, Issue 3 2009E. Gallardo Abstract Workplace drug testing is a well-established application of forensic toxicology and it aims to reduce workplace accidents caused by affected workers. Several classes of abused substances may be involved, such as alcohol, amphetamines, cannabis, cocaine, opiates and also prescription drugs, such as benzodiazepines. The use of alternative biological specimens such as hair, oral fluid or sweat in workplace drug testing presents several advantages over urinalysis,mainly the fact that sample collection can be performed easily without infringing on the examinee's privacy, so the subject is more likely to perform the test. However, drugs are usually present in these alternative specimens at low concentrations and the amount of sample available for analysis is small. The use of highly sensitive techniques is therefore necessary. In fact, the successful interface of liquid chromatography with mass spectrometry (LC-MS) has brought a new light into bioanalytical and forensic sciences as it allows the detection of drugs and metabolites at concentrations that are difficult to analyse using the more commonly adopted GC-MS based techniques. This paper will discuss the importance of LC-MS in supporting workplace drug-testing programmes. The combination of LC-MS with innovative instrumentation such as triple quadrupoles, ion traps and time-of-flight mass spectrometers will also be focused. Copyright © 2009 John Wiley & Sons, Ltd. [source] Protein aggregation in motor neurone disordersNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 6 2003J. D. Wood Toxicity associated with abnormal protein folding and protein aggregation are major hypotheses for neurodegeneration. This article comparatively reviews the experimental and human tissue-based evidence for the involvement of such mechanisms in neuronal death associated with the motor system disorders of X-linked spinobulbar muscular atrophy (SBMA; Kennedy's disease) and amyotrophic lateral sclerosis (ALS), especially disease related to mutations in the superoxide dismutase (SOD1) gene. Evidence from transgenic mouse, Drosophila and cell culture models of SBMA, in common with other trinucleotide repeat expansion disorders, show protein aggregation of the mutated androgen receptor, and intraneuronal accumulation of aggregated protein, to be obligate mechanisms. Strong experimental data link these phenomena with downstream biochemical events involving gene transcription pathways (CREB-binding protein) and interactions with protein chaperone systems. Manipulations of these pathways are already established in experimental systems of trinucleotide repeat disorders as potential beneficial targets for therapeutic activity. In contrast, the evidence for the role of protein aggregation in models of SOD1-linked familial ALS is less clear-cut. Several classes of intraneuronal inclusion body have been described, some of which are invariably present. However, the lack of understanding of the biochemical basis of the most frequent inclusion in sporadic ALS, the ubiquitinated inclusion, has hampered research. The toxicity associated with expression of mutant SOD1 has been intensively studied however. Abnormal protein aggregation and folding is the only one of the four major hypotheses for the mechanism of neuronal degeneration in this disorder currently under investigation (the others comprise oxidative stress, axonal transport and cytoskeletal dysfunctions, and glutamatergic excitotoxicity). Whilst hyaline inclusions, which are strongly immunoreactive to SOD1, are linked to degeneration in SOD1 mutant mouse models, the evidence from human tissue is less consistent and convincing. A role for mutant SOD1 aggregation in the mitochondrial dysfunction associated with ALS, and in potentially toxic interactions with heat shock proteins, both leading to apoptosis, are supported by some experimental data. Direct in vitro data on mutant SOD1 show evidence for spontaneous oligomerization, but the role of such oligomers remains to be elucidated, and therapeutic strategies are less well developed for this familial variant of ALS. [source] REVIEW: ,-Secretase Inhibitors for the Treatment of Alzheimer's Disease: The Current StateCNS: NEUROSCIENCE AND THERAPEUTICS, Issue 5 2010Francesco Panza SUMMARY Aims: Drugs currently used for the treatment of Alzheimer's disease (AD) partially stabilize patients' symptoms without modifying disease progression. Brain accumulation of oligomeric species of ,-amyloid (A,) peptides, the principal components of senile plaques, is believed to play a crucial role in the development of AD. Based on this hypothesis, huge efforts are being spent to identify drugs able to interfere with proteases regulating A, formation from amyloid precursor protein (APP). This article briefly reviews the profile of ,-secretase inhibitors, compounds that inhibit ,-secretase, the pivotal enzyme that generates A,, and that have reached the clinic. Discussion: Several classes of potent ,-secretase inhibitors have been designed and synthesized. Preclinical studies have indicated that these compounds are able to lower brain A, concentrations and, in some cases, reduce A, plaque deposition in transgenic mouse models of AD. The most developmentally advanced of these compounds is semagacestat, presently in Phase III clinical trials. In animals, semagacestat reduced A, levels in the plasma, cerebrospinal fluid (CSF), and the brain. However, studies have not reported on its cognitive effects. Studies in both healthy volunteers and patients with AD have demonstrated a dose-dependent inhibition of plasma A, levels, and a recent study in healthy subjects demonstrated a robust, dose-dependent inhibition of newly generated A, in the CSF after single oral doses. Conclusions: Unfortunately, ,-secretase inhibitors may cause intestinal goblet cell hyperplasia, thymus atrophy, decrease in lymphocytes, and alterations in hair color, effects associated with the inhibition of the cleavage of Notch, a protein involved in cell development and differentiation. Nevertheless, at least other two promising ,-secretase inhibitors are being tested clinically. This class of drugs represents a major hope to slow the rate of decline of AD. [source] Translational medicine perspective in development of disease modifying therapies for Alzheimer's disease: biomarkers to buy down the riskDRUG DEVELOPMENT RESEARCH, Issue 2 2009Hong I. Wan Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of age-related dementia. Currently available pharmacologic therapies, including acetylcholinesterase (AChE) inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists, only treat symptoms and do not address the underlying neurodegeneration. In addition to potentially improve the accuracy of diagnosis, biomarkers serve important roles for the development of putative disease-modifying drugs for AD. In this article, we review the existing and emerging areas of biomarker research and development for AD. Biochemical biomarkers in cerebrospinal fluid have been used to provide a link to disease pathology and may provide important proof of concept data for several classes of emerging therapeutics. Imaging biomarkers including volumetric magnetic resonance imaging and positron emission tomography assessing either glucose utilization or radioligands binding to amyloid plaque are discussed. Appropriate uses of these biomarkers in the context of the development of disease-modifying therapies are discussed. Drug Dev Res 70, 2009. © 2009 Wiley-Liss, Inc. [source] A rapid screening LC-MS/MS method based on conventional HPLC pumps for the analysis of low molecular weight xenobiotics: application to doping control analysisDRUG TESTING AND ANALYSIS, Issue 7 2010Monica Mazzarino Abstract This study presents a fast multi-analyte screening method specifically developed for the detection of xenobiotics in urine. The proposed method allows the screening of several classes of substance in a single chromatographic method with a run-time of 11 min, inclusive of post-run and reconditioning times. Chromatographic separation is achieved in 7.2 min using a reversed-phase 2.7 µm fused-core particle column, generating a back-pressure not exceeding 400 bar and therefore enabling the use of traditional high performance liquid chromatography (HPLC) instruments. The effectiveness of this approach was evaluated, by liquid-chromatography tandem mass spectrometry (LC-MS/MS) in positive electrospray ionization, using 20 blank urine samples spiked with 45 compounds prohibited in sport: 11 diuretics, 16 glucocorticoids, 9 stimulants, 5 anti-oestrogens, as well as formoterol, carboxy-finasteride (previously prohibited by the World Anti-Doping Agency (WADA) in 2008), gestrinone and tetrahydrogestrinone. Qualitative validation shows the proposed method to be specific with no significant interference. All of the analytes considered in this study were clearly distinguishable in urine, with limits of detection ranging from 5 ng/mL to 350 ng/mL, significantly below the Minimum Required Performance Levels (MRPL) set by WADA for the accredited sports anti-doping laboratories. All compounds of interest were separated, including synthetic and endogenous glucocorticoids with similar retention times and fragmentation patterns. Copyright © 2010 John Wiley & Sons, Ltd. [source] Plasma angiopoietin-1, angiopoietin-2 and Tie-2 in breast and prostate cancer: a comparison with VEGF and Flt-1EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2003G. J. Caine Abstract Background, Angiogenesis is essential for tumour growth and metastasis, and is coordinated by several classes of growth factors mediating their effect through receptors linked, in turn, to tyrosine kinase. These growth factors include angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF), which act through receptors Flt-1 and Tie-2. Materials and methods, In order to further determine abnormalities in levels of Ang-1, Ang-2, Tie-2, sFlt-1 and VEGF in human cancer (and their interrelationships), these molecules were measured in plasma from 30 patients with breast cancer, 30 patients with prostate cancer and 12 healthy controls per cancer group. Results, In breast cancer, levels of Ang-1 (P = 0·0005), Ang-2 (P = 0·0173), Tie-2 (P = 0·0001), and VEGF (P = 0·0001) were all significantly raised, and plasma levels of sFlt-1 (P = 0·045) were significantly reduced compared with controls. However, in prostate cancer, only levels of VEGF and Tie-2 were significantly higher (both P= 0·001). There were no significant differences between levels of any molecule between the two groups of cancer. The only difference between the healthy control groups was lower Ang-1 in the women compared with men. Significant correlations were found between levels of Ang-1 and Tie-2 both in breast (r = 0·498, P= 0·005) and prostate cancer (r = 0·643, P= < 0·001). Angiopoietin-1 was also positively correlated with Ang-2 in both breast (r = 0·422, P= 0·02) and prostate cancer (r = 0·543, P= 0·002). Conclusions, Abnormal levels of Ang-1, Ang-2 and their receptor, Tie-2, are present in breast and prostate cancer, and their interrelationships may be important in the pathophysiology of these conditions. [source] Subventricular zone-derived neuroblast migration to the olfactory bulb is modulated by matrix remodellingEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2007Serena Bovetti Abstract In the rodent brain neural progenitor cells are born in the subventricular zone and migrate along a pathway called the rostral migratory stream (RMS) into the olfactory bulb where they differentiate into several classes of interneurones. In the adult, tangential migration in the RMS takes place in ,chains' of cells contained within glial tubes. In contrast, neonatal neuroblasts along the RMS lack these defined glial tubes and chains, migrating instead as individual cells. Time-lapse confocal microscopy of neuroblasts at each of these ages shows that individual cells migrate in a saltatory manner with bursts of high speed followed by periods of slower speed. Tangential migration within a glial tube is 20% faster than migration as individual cells. Neuroblasts may also interact and modify the extracellular matrix during migration through expression of a family of proteins, the matrix metalloproteinases (MMPs). MMPs are present and active along the subventricular zone,olfactory bulb pathway. In the presence of inhibitors of MMPs, neuroblast migration rates were reduced only when cells migrate individually. Chain migration in the adult was unaffected by MMP inhibitors. Taken together, these data suggest that MMPs only influence migration as individual cells and not as chains. [source] ADAPTIVE POPULATION DIFFERENTIATION IN PHENOLOGY ACROSS A LATITUDINAL GRADIENT IN EUROPEAN ASPEN (POPULUS TREMULA, L.): A COMPARISON OF NEUTRAL MARKERS, CANDIDATE GENES AND PHENOTYPIC TRAITSEVOLUTION, Issue 12 2007David Hall A correct timing of growth cessation and dormancy induction represents a critical ecological and evolutionary trade-off between survival and growth in most forest trees (Rehfeldt et al. 1999; Horvath et al. 2003; Howe et al. 2003). We have studied the deciduous tree European Aspen (Populus tremula) across a latitudinal gradient and compared genetic differentiation in phenology traits with molecular markers. Trees from 12 different areas covering 10 latitudinal degrees were cloned and planted in two common gardens. Several phenology traits showed strong genetic differentiation and clinal variation across the latitudinal gradient, with QST values generally exceeding 0.5. This is in stark contrast to genetic differentiation at several classes of genetic markers (18 neutral SSRs, 7 SSRs located close to phenology candidate genes and 50 SNPs from five phenology candidate genes) that all showed FST values around 0.015. We thus find strong evidence for adaptive divergence in phenology traits across the latitudinal gradient. However, the strong population structure seen at the quantitative traits is not reflected in underlying candidate genes. This result fit theoretical expectations that suggest that genetic differentiation at candidate loci is better described by FST at neutral loci rather than by QST at the quantitative traits themselves. [source] FMRFamide gene and peptide expression during central nervous system development of the cephalopod mollusk, Idiosepius notoidesEVOLUTION AND DEVELOPMENT, Issue 2 2010Tim Wollesen SUMMARY Mollusks are a showcase of brain evolution represented by several classes with a varying degree of nervous system centralization. Cellular and molecular processes involved in the evolution of the highly complex cephalopod brain from a simple, monoplacophoran-like ancestor are still obscure and homologies on the cellular level are poorly established. FMRFamide (Phe-Ile-Arg-Phe-NH2)-related peptides (FaRPs) constitute an evolutionarily conserved and diverse group of neuropeptides in the central nervous system (CNS) of many metazoans. Herein, we provide a detailed description of the developing FMRFamide-like immunoreactive (Fa-lir) CNS of the pygmy squid Idiosepius notoides using gene expression analyses and immunocytochemistry. The open reading frame of the I. notoides FMRFamide gene InFMRF predicts one copy each of FIRFamide, FLRFamide (Phe-Leu-Arg-Phe-NH2), ALSGDAFLRFamide (Ala-Leu-Ser-Gly-Asp-Ala-Phe-Leu-Arg-Phe-NH2), and 11 copies of FMRFamide. Applying matrix-assisted laser desorption/ionization time-of-flight (ToF) mass spectrometry-based peptide profiling, we characterized all predicted FaRPs except ALSGDAFLRFamide. Two cell clusters express InFMRF and show FMRFamide-like-immunoreactivity within the palliovisceral ganglia, that is, the future posterior subesophageal mass, during the lobe differentiation phase. They project neurites via ventral axonal tracts, which form the scaffold of the future subesophageal mass. In the supraesophageal mass, InFMRF is first expressed during mid-embryogenesis in the superior and inferior buccal lobes. A neurite of the peduncle commissure represents the first Fa-lir element. Later, the sub- and supraesophageal mass interconnect via Fa-lir neurites and more brain lobes express InFMRF and FMRFamide-like peptides. InFMRF expression was observed in fewer brain lobes than Fa-lir elements. The early expression of InFMRF and FMRFamide-lir peptides in the visceral system and not the remaining CNS of the cephalopod I. notoides resembles the condition found in the majority of investigated gastropods. [source] Call admission control in cellular networks: A reinforcement learning solutionINTERNATIONAL JOURNAL OF NETWORK MANAGEMENT, Issue 2 2004Sidi-Mohammed Senouci In this paper, we address the call admission control (CAC) problem in a cellular network that handles several classes of traffic with different resource requirements. The problem is formulated as a semi-Markov decision process (SMDP) problem. We use a real-time reinforcement learning (RL) [neuro-dynamic programming (NDP)] algorithm to construct a dynamic call admission control policy. We show that the policies obtained using our TQ-CAC and NQ-CAC algorithms, which are two different implementations of the RL algorithm, provide a good solution and are able to earn significantly higher revenues than classical solutions such as guard channel. A large number of experiments illustrates the robustness of our policies and shows how they improve quality of service (QoS) and reduce call-blocking probabilities of handoff calls even with variable traffic conditions.,Copyright © 2004 John Wiley & Sons, Ltd. [source] Stabilization of complex cascade systems using boundedness information in finite timeINTERNATIONAL JOURNAL OF ROBUST AND NONLINEAR CONTROL, Issue 10 2009Huawen Ye Abstract In this paper, the stabilization problem of several classes of complex cascade systems is investigated from a new point of view. If the closed-loop system is proven to have no finite escape time, the boundedness information in finite time, which is obtained from robust stable subsystems or recursive analysis procedures, is then sufficiently employed to deal with crucial nonlinear terms. The proposed method does not rely on complicated Lyapunov functions, and in some cases it can avoid strong growth conditions and complicated small gain analysis. In addition, simple saturated control laws are explicitly constructed in an almost unified way. Copyright © 2008 John Wiley & Sons, Ltd. [source] Nanofilled polyethersulfone as matrix for continuous glass fibers composites: Mechanical properties and solvent resistance,ADVANCES IN POLYMER TECHNOLOGY, Issue 3 2010M. Aurilia Abstract Polyethersulfone (PES) is high performance thermoplastic polymer; however, its applications are limited by the poor resistance to several classes of solvents. Fumed silica and expanded graphite nanoparticles were used to prepare nanofilled PES by a melt-compounding technique with the view to improve the barrier properties. Solvent uptake at equilibrium and solvents resistance of nanofilled PES compounds were investigated by three different methodologies: (1) weight increase by methylene chloride absorption in a vapor-saturated atmosphere, (2) solvent uptake of acetone at equilibrium, and (3) decay of storage modulus induced by acetone diffusion. The storage modulus decay was measured by means of dynamic mechanical analysis on samples immersed in an acetone bath. The collected data were fitted to an ad hoc model to calculate the diffusion coefficient. The produced nanofilled PES showed a significant improvement in barrier properties and considerable reduction in acetone uptake at equilibrium, in comparison with the neat PES. Nanofilled PES compounds were also used to produce continuous glass fiber composites by the film-stacking manufacturing technique. The composites exhibited, by and large, improvements in flexural and shear strength. Their solvent resistance was evaluated by measuring the variation of mechanical properties after exposure to acetone for 1 and 5 days. These tests showed that the composites produced with the nanocomposite matrix did not exhibit higher solvent resistance than those prepared with neat PES, probably because of the deterioration of the fiber/nanocomposite-matrix interfacial bond in the wet state. © 2010 Wiley Periodicals, Inc. Adv Polym Techn 29:146,160, 2010; View this article online at wileyonlinelibrary. DOI 10.1002/adv.20187 [source] Methodology Optimization for Quantification of Total Phenolics and Individual Phenolic Acids in Sweetpotato (Ipomoea batatas L.) RootsJOURNAL OF FOOD SCIENCE, Issue 7 2007M.S. Padda ABSTRACT:, Phenolic acids are one of the several classes of naturally occurring antioxidant compounds found in sweetpotatoes. Simplified, robust, and rapid methodologies were optimized to quantify total and individual phenolic acids in sweetpotato roots. Total phenolic acid content was quantified spectrophotometrically using both Folin,Denis and Folin,Ciocalteu reagents. The Folin,Ciocalteu reagent gave an overestimation of total phenolic acids due to the absorbance of interfering compounds (that is, reducing sugars and ascorbic acid). Individual phenolic acids were quantified by high-performance liquid chromatography (HPLC) using the latest in column technology. Four reversed-phase C18 analytical columns with different properties (dimensions, particle size, particle shape, pore size, and carbon load) were compared. Three different mobile phases using isocratic conditions were also evaluated. A column (4.6 × 150 mm) packed with 5-,m spherical silica particles of pore size 110 Å combined with 14% carbon load provided the best and fast separation of individual phenolic acids (that is, chlorogenic acid, caffeic acid, and 3 isomers of dicaffeoylquinic acid) with a total analysis time of less than 7 min. Among the 3 mobile phases tested, a mobile phase consisting of 1% (v/v) formic acid aqueous solution: acetonitrile: 2-propanol, pH 2.5 (70:22:8, v/v/v) gave adequate separation. Among the solvents tested, aqueous mixtures (80:20, solvent:water) of methanol and ethanol provided higher phenolic acid extraction efficiency than the aqueous mixture of acetone. [source] Weight choosability of graphsJOURNAL OF GRAPH THEORY, Issue 3 2009Tomasz Bartnicki Abstract Suppose the edges of a graph G are assigned 3-element lists of real weights. Is it possible to choose a weight for each edge from its list so that the sums of weights around adjacent vertices were different? We prove that the answer is positive for several classes of graphs, including complete graphs, complete bipartite graphs, and trees (except K2). The argument is algebraic and uses permanents of matrices and Combinatorial Nullstellensatz. We also consider a directed version of the problem. We prove by an elementary argument that for digraphs the answer to the above question is positive even with lists of size two. © 2008 Wiley Periodicals, Inc. J Graph Theory 60: 242,256, 2009 [source] Evaluation of glycosylation and malonylation patterns in flavonoid glycosides during LC/MS/MS metabolite profilingJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 5 2008P. Kachlicki Abstract Flavonoid conjugates constitute several classes of plant phenolic secondary metabolites including many isomeric compounds differing in the hydroxylation pattern and substitution of their rings with different groups such as alkyls, acyls or sugars. These compounds occur in plant tissues mainly as glycosides and in many cases it is necessary to have reliable and detailed information concerning the structure of these natural products. Our results were obtained using leaf extracts of Arabidopsis thaliana and Lupinus angustifolius in which different glycosides of flavones, flavonols and isoflavones are present. Analysis of collision-induced dissociation (CID)/MS/MS spectra of protonated [M + H]+, sodiated [M + Na]+ or deprotonated [M , H], molecules recorded during HPLC runs may bring needed information in this respect. However, registration of mass spectra of [M + Na]+ ions with a good efficiency is possible only after post-column addition of a sodium acetate solution to the LC column eluate. The retention of sodium cation on the saccharidic parts of the molecule is observed after the CID fragmentation. In many cases, the location of this cation on the glycan attached to C-3 hydroxyl group of flavonol led to assignment of its structure. Additionally, the determination of the structure of the aglycone and of the sequence of the glycan part was made possible through the CID data obtained from the [M + H]+ and [M , H], ions. CID spectra show a different order of sugar elimination from hydroxyl groups at C-3 and C-7 in flavonol glycosides isolated from A. thaliana leaves and give sufficient information to discriminate flavonoid O-diglycosides from flavonoid di-O-glycosides. Copyright © 2007 John Wiley & Sons, Ltd. [source] Maximum likelihood estimation in semiparametric regression models with censored dataJOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES B (STATISTICAL METHODOLOGY), Issue 4 2007D. Zeng Summary., Semiparametric regression models play a central role in formulating the effects of covariates on potentially censored failure times and in the joint modelling of incomplete repeated measures and failure times in longitudinal studies. The presence of infinite dimensional parameters poses considerable theoretical and computational challenges in the statistical analysis of such models. We present several classes of semiparametric regression models, which extend the existing models in important directions. We construct appropriate likelihood functions involving both finite dimensional and infinite dimensional parameters. The maximum likelihood estimators are consistent and asymptotically normal with efficient variances. We develop simple and stable numerical techniques to implement the corresponding inference procedures. Extensive simulation experiments demonstrate that the inferential and computational methods proposed perform well in practical settings. Applications to three medical studies yield important new insights. We conclude that there is no reason, theoretical or numerical, not to use maximum likelihood estimation for semiparametric regression models. We discuss several areas that need further research. [source] Information Structure and Syntactic StructureLINGUISTICS & LANGUAGE COMPASS (ELECTRONIC), Issue 4 2009Betty J. Birner This article explores the interface between syntactic structure and information structure , in particular, the broad generalizations that can be made between certain noncanonical word orders and information-structural constraints on their use. Various ways of implementing the distinction between ,given' and ,new' information are described, and several classes of word orders (such as preposings, postposings, argument reversals, and clefts) are discussed in terms of the information-status constraints to which they are sensitive. It is argued that classes of related word orders share related constraints but that , both cross-linguistically and within a single language , there are also construction-specific constraints on the correlation between word order and information status. [source] NO message from muscleMICROSCOPY RESEARCH AND TECHNIQUE, Issue 3 2001Zarko Grozdanovic Abstract The synthesis of the free radical gas nitric oxide (NO) is catalyzed by the enzyme NO synthase (NOS). NOS converts arginine and molecular oxygen to NO and citrulline in a reaction that requires NADPH, FAD, FMN, and tetrahydrobiopterin as cofactors. Three types of NOS have been identified by molecular cloning. The activity of the constitutively expressed neuronal NOS (nNOS) and endothelial NOS (eNOS) is Ca2+/calmodulin-dependent, whereas that the inducible NOS (iNOS) is Ca2+ -insensitive. The predominant NOS isoform in skeletal muscle is nNOS. It is present at the sarcolemma of both extra- and intrafusal muscle fibers. An accentuated accumulation of nNOS is found in the endplate area. This strict sarcolemmal localization of nNOS is due its association with the dystrophin-glycoprotein complex, which is mediated by the syntrophins. The activity of nNOS in skeletal muscle is regulated by developmental, myogenic, and neurogenic influences. NO exerts several distinct effects on various aspects of skeletal muscle function, such as excitation-contraction coupling, mitochondrial energy production, glucose metabolism, and autoregulation of blood flow. Inside the striated muscle fibers, NO interacts directly with several classes of proteins, such as soluble guanylate cyclase, ryanodine receptor, sarcoplasmic reticulum Ca2+ -ATPase, glyceraldehyde-3-phosphate dehydrogenase, and mitochondrial respiratory chain complexes, as well as radical oxygen species. In addition, NO produced and released by contracting muscle fibers diffuses to nearby arterioles where it acts to inhibit reflex sympathetic vasoconstriction. Microsc. Res. Tech. 55:148,153, 2001. © 2001 Wiley-Liss, Inc. [source] Genetic analysis of functions involved in the late stages of biofilm development in Burkholderia cepacia H111MOLECULAR MICROBIOLOGY, Issue 2 2002Birgit Huber Summary Burkholderia cepacia and Pseudomonas aeruginosa often co-exist as mixed biofilms in the lungs of patients suffering from cystic fibrosis (CF). Here, we report the isolation of 13 random mini-Tn 5 insertion mutants of B. cepacia H111 that are defective in biofilm formation on a polystyrene surface. We show that the screening procedure used in this study is biased towards mutants defective in the late stages of biofilm development. A detailed quantitative analysis of the biofilm structures formed by wild-type and mutant strains revealed that the isolated mutants are impaired in their abilities to develop a typical three-dimensional biofilm structure. Molecular investigations showed that the genes required for biofilm maturation fall into several classes: (i) genes encoding for surface proteins; (ii) genes involved in the biogenesis and maintenance of an integral outer membrane; and (iii) genes encoding regulatory factors. It is shown that three of the regulatory mutants produce greatly reduced amounts of N -octanoylhomoserine lactone (C8-HSL). This compound serves as the major signal molecule of the cep quorum-sensing system. As this density-dependent regulatory system is involved in the regulation of biofilm maturation, we investigated the interplay between the three regulatory genes and the quorum-sensing cascade. The results of these investigations show that the identified genes encode for regulatory elements that are positioned upstream of the cep system, indicating that the quorum-sensing system of B. cepacia is a major checkpoint for biofilm formation. [source] Porphyromonas gingivalis lipids and diseased dental tissuesMOLECULAR ORAL MICROBIOLOGY, Issue 2 2006F. C. Nichols Background/aim:,Porphyromonas gingivalis synthesizes several classes of dihydroceramides and at least one of these lipid classes promotes proinflammatory secretory reactions in gingival fibroblasts as well as alters fibroblast morphology in culture. The purpose of this investigation was to determine whether the dihydroceramide lipids of P. gingivalis are recovered in lipid extracts of subgingival plaque, diseased teeth, and diseased gingival tissue samples. Methods:, Lipids were extracted from P. gingivalis, subgingival plaque, subgingival calculus, teeth laden with gross accumulations of subgingival calculus, and gingival tissue samples obtained from chronic severe periodontitis sites. Lipid samples were analyzed by gas chromatography-mass spectrometry as trimethylsilyl derivatives or by electrospray-mass spectrometry as underivatized products. High-performance liquid chromatography fractions of P. gingivalis lipids and gingival tissue lipids were also analyzed by electrospray-mass spectrometry analysis. Results:,P. gingivalis phosphorylated dihydroceramides were recovered in lipid extracts of subgingival plaque, subgingival calculus, calculus contaminated teeth, and diseased gingival tissue samples. However, the distribution of phosphorylated dihydroceramides varied between these samples. Conclusion:, Subgingival plaque, subgingival calculus, diseased teeth, and gingival tissue are contaminated with phosphorylated dihydroceramides produced by P. gingivalis. The previously reported biological activity of these substances together with the recovery of these lipids at periodontal disease sites argues strongly for their classification as virulence factors in promoting chronic inflammatory periodontal disease. [source] Pathogen-induced resistance and alarm signals in the phloemMOLECULAR PLANT PATHOLOGY, Issue 5 2004AART J. E. VAN BEL SUMMARY Despite a long-standing notion of long-distance signals triggering systemic acquired resistance (SAR), the translocation pathway and the identity of the signals involved have not been determined with any degree of certainty. A critical assessment indicates that, in parallel to signalling via the phloem, alternative modes for SAR induction such as signalling via the xylem or air-borne signalling by volatile substances may occur. This review further evaluates several classes of compounds as being functional in systemic resistance signalling. Evidence in favour of SAR involvement of phloem-mobile substances such as salicylic acid, lipid-derived molecules, reactive oxygen species and components of the antioxidant machinery is contradictory, circumstantial or inconclusive, at best. Nitric oxide bound to proteins or thiols seems a good candidate for signalling, but has not been found in phloem sap thus far. No convincing support of the involvement in SAR of phloem-mobile substances such as calcium, oligosaccharides, peptides or RNA species, which function in other systemic signalling cascades, has yet been produced. Nevertheless, phloem-mobile macromolecules are considered as potential tools for SAR given their pivotal role in remote gene expression under stress conditions. In this framework, the existence of several cascades for signal generation along the phloem pathway is envisaged. Finally, recent methods for detection of molecular signals in phloem sap and their expression in companion cells are presented. [source] Cost minimization in wireless networks with a bounded and unbounded number of interfacesNETWORKS: AN INTERNATIONAL JOURNAL, Issue 3 2009Ralf Klasing Given a graph G = (V,E) with |V| = n and |E| = m, which models a set of wireless devices (nodes V) connected by multiple radio interfaces (edges E), the aim is to switch on the minimum cost set of interfaces at the nodes to satisfy all the connections. A connection is satisfied when the endpoints of the corresponding edge share at least one active interface. Every node holds a subset of all the possible k interfaces. Depending on whether k is a priori bounded or not, the problem is called Cost Minimization in Multi-Interface Networks or Cost Minimization in Unbounded Multi-Interface Networks, respectively. We distinguish two main variations for both problems by treating the cost of maintaining an active interface as uniform (i.e., the same for all interfaces), or nonuniform. For bounded k, we show that the problem is APX-hard while we obtain an approximation factor of min for the uniform caseand a (k , 1)-approximation for the nonuniform case. For unbounded k, i.e., k is not set a priori but depends on the given instance, we prove that the problem is not approximable within O(log k) while the same approximation factor of the k -bounded case holds in the uniform case, and a min -approximation factor holds for the nonuniform case. Next, we also provide hardness and approximation results for several classes of networks: with bounded degree, trees, planar, and complete graphs. © 2008 Wiley Periodicals, Inc. NETWORKS, 2009 [source] Plasticity and ambiguity of the electrophysiological phenotypes of enteric neuronsNEUROGASTROENTEROLOGY & MOTILITY, Issue 9 2009K. Nurgali Abstract, Advances in knowledge of enteric neurons electrophysiological characteristics have led to the realisation that the properties of the neurons are dependent on the state of the intestine, the region, the method of recording and the species. Thus, under different experimental conditions, electrophysiological studies cannot provide a reliable signature that identifies the functional type of neuron. In the normal guinea-pig small intestine, taken as a model tissue, neurons can be separated into two electrophysiological groups, S and AH neurons. Combined morphological and physiological studies place several classes of motor and interneurons in the S group, and intrinsic primary afferent neurons in the AH group. There is some evidence for subgroups of S neurons, in which electrophysiological differences are correlated with functional subtypes, but these subgroups have been incompletely investigated. Morphologically characterized Dogiel type II (DII) neurons are recognisable in many species, from mouse to human, but their electrophysiological characteristics are only partly conserved across species or cannot be satisfactorily defined due to technical difficulties. There is a strong need for a comprehensive analysis of channels and currents of S/Dogiel type I neuron subtypes, similar to the comprehensive analysis of AH/DII neurons in the guinea-pig, and similar studies need to be conducted in human and other species. The purpose of this review is to highlight that criteria used for electrophysiological definition of enteric neurons might not be sufficient to distinguish between functional classes of neurons, due to intrinsic properties of neuronal subpopulations, plasticity in pathological conditions and differences in recording techniques. [source] Nursery pollination by a moth in Silene latifolia: the role of odours in eliciting antennal and behavioural responsesNEW PHYTOLOGIST, Issue 4 2006S. Dötterl Summary ,,Since the 1970s it has been known that the nursery pollinator Hadena bicruris is attracted to the flowers of its most important host plant, Silene latifolia, by their scent. Here we identified important compounds for attraction of this noctuid moth. ,,Gas chromatographic and electroantennographic methods were used to detect compounds eliciting signals in the antennae of the moth. Electrophysiologically active compounds were tested in wind-tunnel bioassays to foraging naļve moths, and the attractivity of these compounds was compared with that to the natural scent of whole S. latifolia flowers. ,,The antennae of moths detected substances of several classes. Phenylacetaldehyde elicited the strongest signals in the antennae, but lilac aldehydes were the most attractive compounds in wind-tunnel bioassays and attracted 90% of the moths tested, as did the scent of single flowers. ,,Our results show that the most common and abundant floral scent compounds in S. latifolia, lilac aldehydes, attracted most of the moths tested, indicating a specific adaptation of H. bicruris to its host plant. [source] Composition of volatiles of banana cultivars from Madeira IslandPHYTOCHEMICAL ANALYSIS, Issue 2 2003J. M. F. Nogueira Abstract The composition of the volatiles of banana fruit from various cultivars grown on Madeira Island has been determined. Using GC-MS, the volatiles were shown to be complex mixtures of several classes of components, mainly esters, alcohols, aldehydes, ketones and acids. The average contents of the total volatiles from cultivars "Dwarf Cavendish", "Giant Cavendish", "Robusta" and "Williams" were 93.0, 116.5, 157.3 and 157.0,mg/kg, respectively. The ester and alcoholic fractions appear to play a decisive role in the organoleptic characteristics of banana fruit, presenting a substantial content ranging from 57.2 to 89.8,mg/kg and 19.0 to 47.7,mg/kg, respectively, in all cultivars from Madeira Island studied. 3-Methyl butyl butanoate ester was the major constituent. Copyright © 2003 John Wiley & Sons, Ltd. [source] Calystegines in Calystegia sepium do not Inhibit Fungal Growth and Invertase Activity but Interact with Plant InvertasePLANT BIOLOGY, Issue 2 2004D. Höke Abstract: Calystegines are alkaloidal glycosidase inhibitors. They accumulate predominantly in young and meristemic parts of Calystegia sepium (Convolvulaceae). C. sepium, bindweed, infests meadows and cereal fields and is difficult to control chemically. Fungal pathogens against C. sepium are established as mycoherbicides. Stagonospora convolvuli LA39 attacks C. sepium and does not affect crop plants, but young plants of C. sepium are less susceptible to the fungus. The interaction of Stagonospora convolvuli with calystegines was investigated. Further, endophytic fungi of several classes were isolated from wild-grown Calystegia sepium leaves, and selected strains were tested for interaction with calystegines. Fungal growth on agar containing calystegines was not affected considerably. Plants in climate chambers were infected with an endophyte, Phomopsis, and with the fungal pathogen, Stagonospora convolvuli. Calystegine levels were measured in infected and non-infected plant tissues. Accumulation depended on developmental stage of the plant tissue and was not influenced by infection. Acid invertase was measured from fungal mycelia and from infected and non-infected plant tissues. Fungal acid invertase activity was not inhibited by 10 mM calystegine B2, while invertase from C. sepium leaves was inhibited. It is concluded that calystegines do not inhibit fungal development and sucrose consumption under the conditions of the present investigation, but may act by redirection of plant carbohydrate metabolism. [source] Comparative proteomic and transcriptional profiling of a bread wheat cultivar and its derived transgenic line overexpressing a low molecular weight glutenin subunit gene in the endospermPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 14 2008Federico Scossa Abstract We carried out a parallel transcriptional and proteomic comparison of seeds from a transformed bread wheat line that overexpresses a transgenic low molecular weight glutenin subunit gene relative to the corresponding nontransformed genotype. Proteomic analyses showed that, during seed development, several classes of endosperm proteins were differentially accumulated in the transformed endosperm. As a result of the strong increase in the amount of the transgenic protein, the endogenous glutenin subunit, all subclasses of gliadins, and metabolic as well as chloroform/methanol soluble proteins were diminished in the transgenic genotype. The differential accumulation detected by proteomic analyses, both in mature and developing seeds, was paralleled by the corresponding changes in transcript levels detected by microarray experiments. Our results suggest that the most evident effect of the strong overexpression of the transgenic glutenin gene consists in a global compensatory response involving a significant decrease in the amounts of polypeptides belonging to the prolamin superfamily. It is likely that such compensation is a consequence of the diversion of amino acid reserves and translation machinery to the synthesis of the transgenic glutenin subunit. [source] Association between neuropeptide Y gene and its receptor Y1 gene and methamphetamine dependencePSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 3 2009Yuko Okahisa md Aims:, Neuropeptide Y (NPY) is a 36-amino acid peptide that is widely distributed in the brain, adrenal medulla, and sympathetic nervous system. Several lines of evidence suggest a possible involvement of the NPY system in the physiological effects of several classes of abused substances including alcohol, phencyclidine, cocaine, and marijuana and in endogenous psychosis. Accordingly, it was hypothesized that the NPY system may also be involved in methamphetamine dependence or psychosis. Methods:, The single nucleotide polymorphisms rs16147 of the NPY gene (,485C>T) and rs7687423 of the NPY receptor Y1 (NPY1R) gene were analyzed in 222 patients with methamphetamine dependence and psychosis and 288 age- and gender-matched controls. Results:, Genotypic distribution of the NPY1R gene showed a significant association with methamphetamine dependence and psychosis (P = 0.04), whereas the NPY gene had no significant association with them. Conclusion:, It is possible that genetic variants of the NPY1R gene affect the NPY-NPY receptor type Y1 signaling system in the brain, which may result in susceptibility to methamphetamine dependence or the development of methamphetamine psychosis, but the present findings need to be confirmed on replication. [source] Determination of patterns of biologically relevant aldehydes in exhaled breath condensate of healthy subjects by liquid chromatography/atmospheric chemical ionization tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 7 2003Roberta Andreoli A method for the simultaneous determination of several classes of aldehydes in exhaled breath condensate (EBC) was developed using liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry (LC/APCI-MS/MS). EBC is a biological matrix obtained by a relatively new, simple and noninvasive technique and provides an indirect assessment of pulmonary status. The measurement of aldehydes in EBC represents a biomarker of the effect of oxidative stress caused by smoke, disease, or strong oxidants like ozone. Malondialdehyde (MDA), acrolein, ,,, -unsaturated hydroxylated aldehydes [namely 4-hydroxyhexenal (4-HHE) and 4-hydroxynonenal (4-HNE)], and saturated aldehydes (n -hexanal, n -heptanal and n -nonanal) were measured in EBC after derivatization with 2,4-dinitrophenylhydrazine (DNPH). Atmospheric pressure chemical ionization of the analytes was obtained in positive-ion mode for MDA, and in negative-ion mode for acrolein, 4-HHE, 4-HNE, and saturated aldehydes. DNPH derivatives were separated on a C18 column using variable proportions of 20,mM aqueous acetic acid and methanol. Linearity was established over 4,5 orders of magnitude and limits of detection were in the 0.3,1.0 nM range. Intra-day and inter-day precision were in the 1.3,9.9% range for all the compounds. MDA, acrolein and n -alkanals were detectable in all EBC samples, whereas the highly reactive 4-HHE and 4-HNE were found in only a few samples. Statistically significant higher concentrations of MDA, acrolein and n -hexanal were found in EBC from smokers. Copyright © 2003 John Wiley & Sons, Ltd. [source] The Facial Integument of Centrosaurine Ceratopsids: Morphological and Histological Correlates of Novel Skin StructuresTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 9 2009Tobin L. Hieronymus Abstract The horned dinosaur Pachyhinosaurus possesses rugose bony bosses across the skull roof in lieu of the projecting bony horn cores seen in most ceratopsians. This elaboration of typical ceratopsian ornaments provides an opportunity to test hypotheses of ceratopsian facial skin morphology and function. We analyze bone morphology and histology associated with several classes of skin features in extant amniotes using a classification tree analysis. We isolate key osteological and histological correlates for unpreserved skin structures, including both a pattern of pitting and resorption characteristic of muskox (Ovibos) frontal horn boss, and a pattern of metaplastic ossification characteristic of rhinoceros nasal horn boss. We also describe correlates for other skin features, such as epidermal scales and horn sheaths. Dermatocranial elements from centrosaurine ceratopsians are then examined for the same osteological and histological correlates. From this comparison we propose that the rugose bosses that replace horn cores in many centrosaurine dinosaurs, most notably Achelousaurus and Pachyrhinosaurus, were covered by a thick pad of cornified skin derived from the caudodorsal side of the primitive horn sheath comparable to the horny boss of extant muskoxen (Ovibos). We examine extant taxa with skin morphologies similar to Pachyrhinosaurus for consistent adaptive relationships between structure and behavior. We determine that high-energy headbutting is consistently associated with the acquisition of thick cornified pads, seen in muskoxen as well as helmeted hornbills [Buceros (=Rhinoplax) vigil] and African buffalo (Syncerus). The association of the bony ornaments of Pachyrhinosaurus with risky agonistic behaviors casts doubt on the role of species recognition as a primary selection pressure driving the diversity of all ceratopsian horns. We conclude that social selection (a broad form of intraspecific competition) is a more appropriate explanation for the diversity of centrosaurine ceratopsian ornaments in the Late Cretaceous. Anat Rec, 292:1370,1396, 2009. © 2009 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||