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Selected AbstractsEffect of Piperine, a Major Component of Black Pepper, on the Intestinal Absorption of Fexofenadine and Its Implication on Food,Drug InteractionJOURNAL OF FOOD SCIENCE, Issue 3 2010Ming-Ji Jin ABSTRACT:, The present study aimed to investigate the effect of piperine, a major component of black pepper, on the oral exposure of fexofenadine in rats. Pharmacokinetic parameters of fexofenadine were determined in rats following an oral (10 mg/kg) or intravenous (5 mg/kg) administration of fexofenadine in the presence and absence of piperine (10 or 20 mg/kg, given orally). Compared to the control group given fexofenadine alone, the combined use of piperine increased the oral exposure (AUC) of fexofenadine by 180% to 190% while there was no significant change in,Cmax and,T1/2 of fexofenadine in rats. The bioavailability of fexofenadine was increased by approximately 2-folds via the concomitant use of piperine. Furthermore,,Tmax tends to be increased which might be attributed to the delayed gastric emptying in the presence of piperine. In contrast, piperine did not alter the intravenous pharmacokinetics of fexofenadine, implying that piperine may increase mainly the gastrointestinal absorption of fexofenadine rather than reducing hepatic extraction. In conclusion, piperine significantly enhanced the oral exposure of fexofenadine in rats likely by the inhibition of P-glycoprotein-mediated cellular efflux during the intestinal absorption, suggesting that the combined use of piperine or piperine-containing diet with fexofenadine may require close monitoring for potential drug,diet interactions. [source] Wallerian Degeneration: A Major Component of Early Axonal Pathology in Multiple SclerosisBRAIN PATHOLOGY, Issue 5 2010Tomasz Dziedzic Abstract Axonal loss is a major component of the pathology of multiple sclerosis (MS) and the morphological basis of permanent clinical disability. It occurs in demyelinating plaques but also in the so-called normal-appearing white matter (NAWM). However, the contribution of Wallerian degeneration to axonal pathology is not known. Here, we analyzed the extent of Wallerian degeneration and axonal pathology in periplaque white matter (PPWM) and lesions in early multiple sclerosis biopsy tissue from 63 MS patients. Wallerian degeneration was visualized using an antibody against the neuropeptide Y receptor Y1 (NPY-Y1R). The number of SMI-32-positive axons with non-phosphorylated neurofilaments was significantly higher in both PPWM and plaques compared to control white matter. APP-positive, acutely damaged axons were found in significantly higher numbers in plaques compared to PPWM. Strikingly, the number of NPY-Y1R-positive axons undergoing Wallerian degeneration was significantly higher in PPWM and plaques than in control WM. NPY-Y1R-positive axons in PPWM were strongly correlated to those in the lesions. Our results show that Wallerian degeneration is a major component of axonal pathology in the periplaque white matter in early MS. It may contribute to radiological changes observed in early MS and most likely plays a major role in the development of disability. [source] Bacterial synthesis of poly(hydroxybutyrate- co-hydroxyvalerate) using carbohydrate-rich mahua (Madhuca sp.) flowersJOURNAL OF APPLIED MICROBIOLOGY, Issue 1 2007P.K. Anil Kumar Abstract Aims:, The objective of the present work was to utilize an unrefined natural substrate namely mahua (Madhuca sp.) flowers, as a carbon source for the production of bacterial polyhydroxyalkanoate (PHA) copolymer by Bacillus sp-256. Methods and Results:, In the present work, three bacterial strains were tested for PHA production on mahua flower extract (to impart 20 g l,1 sugar) amongst which, Bacillus sp-256 produced higher concentration of PHA in its biomass (51%) compared with Rhizobium meliloti (31%) or Sphingomonas sp (22%). Biosynthesis of poly(hydroxybutyrate-co-hydroxyvalerate) , P(HB-co-HV) , of 90 : 10 mol% by Bacillus sp-256 was observed by gas chromatographic analysis of the polymer. Major component of the flower is sugars (57% on dry weight basis) and additionally it also contains proteins, vitamins, organic acids and essential oils. The bacterium utilized malic acid present in the substrate as a co-carbon source for the copolymer production. The flowers could be used in the form of aqueous extract or as whole flowers. PHA content of biomass (%) and yield (g l,1) in a 3·0-l stirred tank fermentor after 30 h of fermentation under constant pH (7) and dissolved oxygen content (40%) were 54% and 2·7 g l,1, respectively. Corresponding yields for control fermentation with sucrose as carbon source were 52% and 2·5 g l,1. The polymer was characterized by proton NMR. Conclusions:, Utilization of mahua flowers, a natural substrate for bacterial fermentation aimed at PHA production, had additional advantage, as the sugars and organic acids present in the flowers were metabolized by Bacillus sp-256 to synthesize P(HB-co-HV) copolymer. Significance and Impact of the Study:, Literature reports on utilization of suitable cheaper natural substrate for PHA copolymer production is scanty. Mahua flowers used in the present experiment is a cheaper carbon substrate compared with several commercial substrates and it is rich in main carbon as well as co-carbon sources that can be utilized by bacteria for PHA copolymer production. [source] Major components of a sea urchin block to polyspermy are structurally and functionally conservedEVOLUTION AND DEVELOPMENT, Issue 3 2004Julian L. Wong Summary One sperm fusing with one egg is requisite for successful fertilization; additional sperm fusions are lethal to the embryo. Because sperm usually outnumber eggs, evolution has selected for mechanisms that prevent this polyspermy by immediately modifying the egg extracellular matrix. We focus here on the contribution of cortical granule contents in the sea urchin block to polyspermy to begin to understand how well this process is conserved. We identified each of the major constituents of the fertilization envelope in two species of seaurchins, Strongylocentrotus purpuratus and Lytechinus variegatus, that diverged 30 to 50 million years ago. Our results show that the five major structural components of the fertilization envelope, derived from the egg cortical granules, are semiconserved. Most of these orthologs share sequence identity and encode multiple low-density lipoprotein receptor type A repeats or CUB domains but at least two contain radically different carboxy-terminal repeats. Using a new association assay, we also show that these major structural components are functionally conserved during fertilization envelope construction. Thus, it seems that this population of female reproductive proteins has retained functional motifs while gaining significant sequence diversity,two opposing paths that may reflect cooperativity among the proteins that compose the fertilization envelope. [source] Soil greenhouse gas fluxes and global warming potential in four high-yielding maize systemsGLOBAL CHANGE BIOLOGY, Issue 9 2007M. A. A. ADVIENTO-BORBE Abstract Crop intensification is often thought to increase greenhouse gas (GHG) emissions, but studies in which crop management is optimized to exploit crop yield potential are rare. We conducted a field study in eastern Nebraska, USA to quantify GHG emissions, changes in soil organic carbon (SOC) and the net global warming potential (GWP) in four irrigated systems: continuous maize with recommended best management practices (CC-rec) or intensive management (CC-int) and maize,soybean rotation with recommended (CS-rec) or intensive management (CS-int). Grain yields of maize and soybean were generally within 80,100% of the estimated site yield potential. Large soil surface carbon dioxide (CO2) fluxes were mostly associated with rapid crop growth, high temperature and high soil water content. Within each crop rotation, soil CO2 efflux under intensive management was not consistently higher than with recommended management. Owing to differences in residue inputs, SOC increased in the two continuous maize systems, but decreased in CS-rec or remained unchanged in CS-int. N2O emission peaks were mainly associated with high temperature and high soil water content resulting from rainfall or irrigation events, but less clearly related to soil NO3 -N levels. N2O fluxes in intensively managed systems were only occasionally greater than those measured in the CC-rec and CS-rec systems. Fertilizer-induced N2O emissions ranged from 1.9% to 3.5% in 2003, from 0.8% to 1.5% in 2004 and from 0.4% to 0.5% in 2005, with no consistent differences among the four systems. All four cropping systems where net sources of GHG. However, due to increased soil C sequestration continuous maize systems had lower GWP than maize,soybean systems and intensive management did not cause a significant increase in GWP. Converting maize grain to ethanol in the two continuous maize systems resulted in a net reduction in life cycle GHG emissions of maize ethanol relative to petrol-based gasoline by 33,38%. Our study provided evidence that net GHG emissions from agricultural systems can be kept low when management is optimized toward better exploitation of the yield potential. Major components for this included (i) choosing the right combination of adopted varieties, planting date and plant population to maximize crop biomass productivity, (ii) tactical water and nitrogen (N) management decisions that contributed to high N use efficiency and avoided extreme N2O emissions, and (iii) a deep tillage and residue management approach that favored the build-up of soil organic matter from large amounts of crop residues returned. [source] Procysteine Stimulates Expression of Key Anabolic Factors and Reduces Plantaris Atrophy in Alcohol-Fed RatsALCOHOLISM, Issue 8 2009Jeffrey S. Otis Background:, Long-term alcohol ingestion may produce severe oxidant stress and lead to skeletal muscle dysfunction. Emerging evidence has suggested that members of the interleukin-6 (IL-6) family of cytokines play diverse roles in the regulation of skeletal muscle mass. Thus, our goals were (i) to minimize the degree of oxidant stress and attenuate atrophy by supplementing the diets of alcohol-fed rats with the glutathione precursor, procysteine, and (ii) to identify the roles of IL-6 family members in alcoholic myopathy. Methods:, Age- and gender-matched Sprague-Dawley rats were fed the Lieber-DeCarli liquid diet containing either alcohol or an isocaloric substitution (control diet) for 35 weeks. Subgroups of alcohol-fed rats received procysteine (0.35%, w/v) for the final 12 weeks. Plantaris morphology was assessed by hematoxylin and eosin staining. Major components of glutathione metabolism were determined using assay kits. Real-time PCR was used to determine expression levels of several genes. Results:, Plantaris muscles from alcohol-fed rats displayed extensive atrophy, as well as decreased glutathione levels, decreased activities of glutathione reductase and glutathione peroxidase, decreased superoxide dismutase (SOD)-2 (Mn-SOD2), and increased NADPH oxidase-1 gene expression,each indicative of significant oxidant stress. Alcohol also induced gene expression of catabolic factors including IL-6, oncostatin M, atrogin-1, muscle ring finger protein-1, and IGFBP-1. Procysteine treatment attenuated plantaris atrophy, restored glutathione levels, and increased catalase, Cu/Zn-SOD1, and Mn-SOD2 mRNA expression, but did not reduce other markers of oxidant stress or levels of these catabolic factors. Instead, procysteine stimulated gene expression of anabolic factors such as insulin-like growth factor-1, ciliary neurotrophic factor, and cardiotrophin-1. Conclusions:, Procysteine significantly attenuated, but did not completely abrogate, alcohol-induced oxidant stress or catabolic factors. Rather, procysteine minimized the extent of plantaris atrophy by inducing components of several anabolic pathways. Therefore, anti-oxidant treatments such as procysteine supplementation may benefit individuals with alcoholic myopathy. [source] Coumarins and phenolic fingerprints of oak and Brazilian woods extracted by sugarcane spiritJOURNAL OF SEPARATION SCIENCE, JSS, Issue 21 2009Alexandre Ataide da Silva Abstract A total of 25 sugarcane spirit extracts of six different Brazilian woods and oak, commonly used by cooperage industries for aging cachaça, were analyzed for the presence of 14 phenolic compounds (ellagic acid, gallic acid, vanillin, syringaldehyde, synapaldehyde, coniferaldehyde, vanillic acid, syringic acid, quercetin, trans -resveratrol, catechin, epicatechin, eugenol, and myricetin) and two coumarins (scopoletin and coumarin) by HPLC-DAD-fluorescence and HPLC-ESI-MSn. Furthermore, an HPLC-DAD chromatographic fingerprint was build-up using chemometric analysis based on the chromatographic elution profiles of the extracts monitored at 280,nm. Major components identified and quantified in Brazilian wood extracts were coumarin, ellagic acid, and catechin, whereas oak extracts shown a major contribution of catechin, vanillic acid, and syringaldehyde. The main difference observed among oak and Brazilian woods remains in the concentration of coumarin, catechin, syringaldehyde, and coniferaldehyde. The chemometric analysis of the quantitative profile of the 14 phenolic compounds and two coumarins in the wood extracts provides a differentiation between the Brazilian wood and oak extracts. The chromatographic fingerprint treated by multivariate analysis revealed significant differences among Brazilian woods themselves and oak, clearly defining six groups of wood extracts: (i) oak extracts, (ii) jatobá extracts, (iii) cabreúva-parda extracts, (iv) amendoim extracts, (v) canela-sassafrás extracts and (vi) pequi extracts. [source] Volatiles Released by a Streptomyces Species Isolated from the North SeaCHEMISTRY & BIODIVERSITY, Issue 7 2005Jeroen The North Sea Streptomyces strain GWS-BW-H5 was investigated by analyzing headspace extracts of agar-plate cultures (HE) or liquid cultures (LCE), obtained with a closed-loop stripping apparatus (CLSA), by GC/MS (Table,1). The volatile profile of the HE is dominated by the known volatiles (,)-geosmin (4) and 2-methyisoborneol (1). Small amounts of sesquiterpenes occur, which are present in a more-diverse structural variety and in higher quantities in the LCE. The different structures can be rationalized by few cationic intermediates along their biosynthetic pathway. The most-prominent difference between the two culture methods were the presence of the Me-branched , - and , -lactones 31,38, not previously reported from nature, in the LCE. Major components were 10-methyldodecan-5-olide (34), 10-methyldodec-2-en-4-olide (36), and 10-methyldodec-3-en-4-olide (38). The structures of all new lactones were verified by synthesis. Furthermore, more volatiles in higher amounts were produced by the liquid culture than by to the agar plate culture. Since 36 showed inhibitory growth effects against strain GWS-BW-H5, growth inhibition against twelve other strains isolated from the same habitat was tested. Antagonistic activity against four of the strains was observed, with a slightly higher threshold level than found for penicillin G, which was used in control experiments (Table,2). [source] BetweenIT: An Interactive Tool for Tight InbetweeningCOMPUTER GRAPHICS FORUM, Issue 2 2010Brian Whited Abstract The generation of inbetween frames that interpolate a given set of key frames is a major component in the production of a 2D feature animation. Our objective is to considerably reduce the cost of the inbetweening phase by offering an intuitive and effective interactive environment that automates inbetweening when possible while allowing the artist to guide, complement, or override the results. Tight inbetweens, which interpolate similar key frames, are particularly time-consuming and tedious to draw. Therefore, we focus on automating these high-precision and expensive portions of the process. We have designed a set of user-guided semi-automatic techniques that fit well with current practice and minimize the number of required artist-gestures. We present a novel technique for stroke interpolation from only two keys which combines a stroke motion constructed from logarithmic spiral vertex trajectories with a stroke deformation based on curvature averaging and twisting warps. We discuss our system in the context of a feature animation production environment and evaluate our approach with real production data. [source] Tropomyosin expression and dynamics in developing avian embryonic musclesCYTOSKELETON, Issue 5 2008Jushuo Wang Abstract The expression of striated muscle proteins occurs early in the developing embryo in the somites and forming heart. A major component of the assembling myofibrils is the actin-binding protein tropomyosin. In vertebrates, there are four genes for tropomyosin (TM), each of which can be alternatively spliced. TPM1 can generate at least 10 different isoforms including the striated muscle-specific TPM1, and TPM1,. We have undertaken a detailed study of the expression of various TM isoforms in 2-day-old (stage HH 10,12; 33 h) heart and somites, the progenitor of future skeletal muscles. Both TPM1, and TPM1, are expressed transiently in embryonic heart while TPM1, is expressed in somites. Both RT-PCR and in situ hybridization data suggest that TPM1, is expressed in embryonic heart whereas TPM1, is expressed in embryonic heart, and also in the branchial arch region of somites, and in the somites. Photobleaching studies of Yellow Fluorescent Protein-TPM1, and -TPM1, expressed in cultured avian cardiomyocytes revealed that the dynamics of the two probes was the same in both premyofibrils and in mature myofibrils. This was in sharp contrast to skeletal muscle cells in which the fluorescent proteins were more dynamic in premyofibrils. We speculate that the differences in the two muscles is due to the appearance of nebulin in the skeletal myocytes premyofibrils transform into mature myofibrils. Cell Motil. Cytoskeleton 2008. © 2008 Wiley-Liss, Inc. [source] Two different unique cardiac isoforms of protein 4.1R in zebrafish, Danio rerio, and insights into their cardiac functions as related to their unique structuresDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 7 2010Kenji Murata Protein 4.1R (4.1R) has been identified as the major component of the human erythrocyte membrane skeleton. The members of the protein 4.1 gene family are expressed in a tissue-specific alternative splicing manner that increases their functions in each tissue; however, the exact roles of cardiac 4.1R in the developing myocardium are poorly understood. In zebrafish (ZF), we identified two heart-specific 4.1R isoforms, ZF4.1RH2 and ZF4.1RH3, encoding N-terminal 30 kDa (FERM) domain and spectrin-actin binding domain (SABD) and C-terminal domain (CTD), separately. Applying immunohistochemistry using specific antibodies for 30 kDa domain and CTD separately, the gene product of ZF4.1RH2 and ZF4.1RH3 appeared only in the ventricle and in the atrium, respectively, in mature hearts. During embryogenesis, both gene expressions are expressed starting 24 h post-fertilization (hpf). Following whole-mount in situ hybridization, ZF4.1RH3 gene expression was detected in the atrium of 37 hpf embryos. These results indicate that the gene product of ZF4.1RH3 is essential for normal morphological shape of the developing heart and to support the repetitive cycles of its muscle contraction and relaxation. [source] Periostin promotes a fibroblastic lineage pathway in atrioventricular valve progenitor cellsDEVELOPMENTAL DYNAMICS, Issue 5 2009Russell A. Norris Abstract Differentiation of prevalvular mesenchyme into valve fibroblasts is an integral step towards the development of functionally mature cardiac valves. Although clinically relevant, little is known regarding the molecular and cellular mechanisms by which this process proceeds. Genes that are regulated in a spatio-temporal pattern during valve remodeling are candidates for affecting this differentiation process. Based on its expression pattern, we have focused our studies on the role of the matricellular gene, periostin, in regulating the differentiation of cushion mesenchymal cells into valve fibroblasts. Herein, we demonstrate that periostin expression is coincident with and regulates type I collagen protein production, a major component of mature valve tissue. Adenoviral-mediated knock-down of periostin in atrioventricular mesenchyme resulted in a decrease in collagen I protein expression and aberrant induction of myocyte markers indicating an alteration in AV mesenchyme differentiation. In vitro analyses using a novel "cardiotube" assay further demonstrated that expression of periostin regulates lineage commitment of valve precursor cells. In these cells, expression of periostin and collagen I are regulated, in part, by TGF,-3. We further demonstrate that TGF,-3, through a periostin/collagen pathway, enhances the viscoelastic properties of AV cushion tissue surface tension and plays a crucial role in regulating valve remodeling. Thus, data presented here demonstrate that periostin, a TGF,-3 responsive gene, functions as a crucial mediator of chick AV valve maturation via promoting mesenchymal-to-fibroblast differentiation while blocking differentiation of alternative cell types (myocytes). Developmental Dynamics 238:1052,1063, 2009. © 2009 Wiley-Liss, Inc. [source] Pattern-reversal visual evoked potentials in infants: gender differences during early visual maturationDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 5 2002CA Malcolm BScN RN RGN This paper investigates gender differences in the peak latency and amplitude of the P1 component of the pattern-reversal visual evoked potential (pattern-reversal VEP) recorded in healthy term infants. Pattern-reversal VEPs in response to a series of high contrast black and white checks (check widths 120,, 60,, 30,, 24,, 12,, 6,) were recorded in 50 infants (20 males, 30 females) at 50 weeks post-conceptional age (PCA) and in 49 infants (22 males, 27 females) at 66 weeks PCA. Peak latency of the major component, P1, was considerably shorter in female compared with male infants. Differences in head circumference do not entirely account for the gender differences in peak latency reported here. A gender difference in P1 amplitude was not detected. These findings stress the importance of considering gender norms as well as age-matched norms when utilizing the pattern-reversal VEP in clinical investigations. Studies including a wider range of ages are clearly necessary in order to establish whether the earlier peak latencies in female infants represents a difference in the onset or rate of visual maturation. [source] A new look at viruses in type 1 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2003Hee-Sook Jun Abstract Type 1 diabetes (T1D) results from the destruction of pancreatic beta cells. Genetic factors are believed to be a major component for the development of T1D, but the concordance rate for the development of diabetes in identical twins is only about 40%, suggesting that nongenetic factors play an important role in the expression of the disease. Viruses are one environmental factor that is implicated in the pathogenesis of T1D. To date, 14 different viruses have been reported to be associated with the development of T1D in humans and animal models. Viruses may be involved in the pathogenesis of T1D in at least two distinct ways: by inducing beta cell-specific autoimmunity, with or without infection of the beta cells, [e.g. Kilham rat virus (KRV)] and by cytolytic infection and destruction of the beta cells (e.g. encephalomyocarditis virus in mice). With respect to virus-mediated autoimmunity, retrovirus, reovirus, KRV, bovine viral diarrhoea-mucosal disease virus, mumps virus, rubella virus, cytomegalovirus and Epstein-Barr virus (EBV) are discussed. With respect to the destruction of beta cells by cytolytic infection, encephalomyocarditis virus, mengovirus and Coxsackie B viruses are discussed. In addition, a review of transgenic animal models for virus-induced autoimmune diabetes is included, particularly with regard to lymphocytic choriomeningitis virus, influenza viral proteins and the Epstein-Barr viral receptor. Finally, the prevention of autoimmune diabetes by infection of viruses such as lymphocytic choriomeningitis virus is discussed. Copyright © 2002 John Wiley & Sons, Ltd. [source] Variation in the risk of being wounded: an overlooked factor in studies of invertebrate immune function?ECOLOGY LETTERS, Issue 6 2003S. J. Plaistow Abstract In invertebrates, wounding can trigger an immune response, and will often expose organisms to parasites and pathogens. Here we show that in the amphipod Gammarus pulex, wounding abundance is negatively correlated with PhenolOxidase activity (a major component of the invertebrate immune response), and that the occurrence and abundance of wounding is extremely high and varies significantly between five natural populations. In some populations the prevalence and abundance of wounds also varied between sexes. Given that, using and maintaining an efficient immune system is costly, we suggest that the frequency of wounding may be an important selective pressure influencing an organism's optimal investment in immune defences. [source] Natural killer cells in viral hepatitis: facts and controversiesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2010Mario U. Mondelli Eur J Clin Invest 2010; 40 (9): 851,863 Abstract Background, Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major human hepatotropic pathogens responsible for a large number of chronic infections worldwide. Their persistence is thought to result from inefficiencies of innate and adaptive immune responses; however, very little information is available on the former. Natural killer (NK) cells are a major component of innate immunity and their activity is tightly regulated by several inhibitory and activating receptors. Design, In this review, we examine controversial findings regarding the role of NK cells in the pathogenesis of acute and chronic liver disease caused by HCV and HBV. Results, Recent studies built up on technical advances to identify NK receptors and their functional correlates in this setting. While NK cells seem to behave correctly during acute hepatitis, it would appear that the NK cytotoxic potential is generally conserved in chronic hepatitis, if not increased in the case of HCV. In contrast, their ability to secrete antiviral cytokines such as interferon ex vivo or after cytokine stimulation is severely impaired. Conclusions, Current evidence suggests the existence of an NK cell functional dichotomy, which may contribute to virus persistence, while maintaining low-level chronic liver inflammation. The study of liver-infiltrating NK cells is still at the very beginning, but it is likely that it will shed more light on the role of this simple and at the same time complex innate immune cell in liver disease. [source] Cellular microparticles: new players in the field of vascular disease?EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2004M. Diamant Abstract Microparticles are small membrane vesicles that are released from cells upon activation or during apoptosis. Cellular microparticles in body fluids constitute a heterogeneous population, differing in cellular origin, numbers, size, antigenic composition and functional properties. Microparticles support coagulation by exposure of negatively charged phospholipids and sometimes tissue factor, the initiator of coagulation in vivo. Microparticles may transfer bioactive molecules to other cells or microparticles, thereby stimulating cells to produce cytokines, cell-adhesion molecules, growth factors and tissue factor, and modulate endothelial functions. Microparticles derived from various cells, most notably platelets but also leucocytes, lymphocytes, erythrocytes and endothelial cells, are present in the circulation of healthy subjects. Rare hereditary syndromes with disturbances in membrane vesiculation leading to a decreased numbers of microparticles clinically present with a bleeding tendency. In contrast, elevated numbers of microparticles are encountered in patients with a great variety of diseases with vascular involvement and hypercoagulability, including disseminated intravascular coagulation, acute coronary syndromes, peripheral arterial disease, diabetes mellitus and systemic inflammatory disease. Finally, microparticles are a major component of human atherosclerotic plaques. In view of their functional properties, cell-derived microparticles may be an important intermediate in the cascade of cellular and plasmatic dysfunctions underlying the process of atherogenesis. [source] Funding Allocation and Staff Management.EUROPEAN JOURNAL OF EDUCATION, Issue 1 2009A Portuguese Example For many years the Portuguese Ministry of Education used a funding formula to allocate the State budget to public higher education institutions. Some of its major objectives were higher enrolments and allocation equity. As the expenditure on salaries was a major component of the budget, the formula was supposed to force convergence to established standard staff/student ratios. This article analyses the evolution of staff numbers in Portuguese public universities to assess how successful the funding formula has been in forcing convergence to standard staff numbers. [source] Potential MRI Contrast Agents Based on Micellar Incorporation of Amphiphilic Bis(alkylamide) Derivatives of [(Gd,DTPA)(H2O)]2,EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 16 2003Kristof Kimpe Abstract DTPA-bisamide derivatives with alkyl chains containing 14, 16 and 18 carbon atoms were synthesized and complexes of various trivalent lanthanide ions (Ln = Gd, La, Pr, Eu) were formed. Variable temperature proton NMR spectroscopy of paramagnetic praseodymium(III) and europium(III) complexes revealed that long aliphatic substituents considerably increase the energy barrier for the intramolecular rearrangement around the lanthanide ion. The gadolinium(III) complexes were incorporated into mixed micelles, and photon correlation spectroscopy showed that the mean sizes of all the micelles were within the same range. The NMRD curves of all three DTPA-bisamide-gadolinium complexes incorporated in mixed micelles display higher relaxivity values than the commercially available Gd,DTPA contrast agent. The higher relaxivity obtained for the micellar DTPA-bisamide-gadolinium complexes with C14 and C16 chains relative to the micellar DTPA-bisamide-GdIII C18 chain complex could be attributable to the fact that the alkyl chain containing 18 carbon atoms is longer than the alkyl chain of the major component of the micelles, DPPC, in which it is inserted. This would allow increased mobility of the polar head and hence a lower relaxivity. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Chemical composition of Pinus sibirica nut oilsEUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 7 2009Ryszard Zadernowski Abstract The chemical composition of oil obtained from Pinus sibirica was investigated. The nonpolar lipids were the predominant lipid fraction while the triacylglycerols were the major component of this fraction. ,- and ,-tocopherols were the dominant tocopherols in pine oils. Eleven fatty acids (FA) were identified in pine nut oil. The unsaturated FA comprised over 90% of the total FA. Of these, polyunsaturated FA accounted for 66% of the total FA. 18:2 and 18:3 acids were the dominant unsaturated FA, while palmitic and stearic acids were the major saturated FA. Three unusual FA, namely 10,13-octadecadienoic, gorlic and 11,13-eicosadienoic acid, were tentatively identified in pine nut oil. [source] Comparative analysis of phytosterol components from rapeseed (Brassica napus,L.) and olive (Olea europaea,L.) varietiesEUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 9 2006Muhammet K. Gül Abstract Phytosterols occur in relatively high concentration in the seeds of rapeseed (Brassica napus,L.) and in lower concentration in olive (Olea europaea,L.) oil. The aim of this research was to investigate some new rapeseed varieties and olive genotypes that are grown in Northwest Turkey and to compare the phytosterol contents of both crops. For rapeseed, the data were collected in the growing seasons 2004,2005 from a field experiment with 19,new rapeseed varieties and three replications. For olives, 21,different varieties were used in the 2004,2005 and 2005,2006 growing seasons. The separation and identification of free phytosterols and the analysis of their contents were successfully achieved using the capillary column-gas chromatographic method. According to the obtained results, for rapeseed, sitosterol (1.54,2.36,g/kg) was the major component of total phytosterols, followed by campesterol (0.02,1.58,g/kg) and brassicasterol (0.26,0.58,g/kg). Regarding the olive varieties, the sitosterol content changed between 1.03 and 2.01,g/kg, followed by avenasterol ranging from 0.07 to 0.44,g/kg. The brassicasterol, campesterol and stigmasterol contents did not affect the total amount of sterols. The total phytosterol content ranged between 4.25 and 11.37,g/kg for rapeseed and 1.29 and 2.38,g/kg for olives. [source] A role for synGAP in regulating neuronal apoptosisEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2005Irene Knuesel Abstract The brain-specific Ras/Rap GTPase-activating protein synGAP is a major component of the postsynaptic density at glutamatergic synapses. It is a target for phosphorylation by Ca2+/calmodulin-dependent protein kinase II, which up-regulates its GTPase-activating activity. Thus, SynGAP may play an important role in coupling N -methyl- d -aspartate-type glutamate receptor activation to signaling pathways downstream of Ras or Rap. Homozygous deletion of synGAP is lethal within the first few days after birth. Therefore, to study the functions of synGAP, we used the cre/loxP recombination system to produce conditional mice mutants in which gradual loss of synGAP begins at ,,1 week, and usually becomes maximal by 3 weeks, after birth. The resulting phenotypes fall into two groups. In a small group, the level of synGAP protein is reduced to 20,25% of wild type, and they die at 2,3 weeks of age. In a larger group, the levels remain higher than ,,40% of wild type, and they survive and remain healthy. In all mutants, however, an abnormally high number of neurons in the hippocampus and cortex undergo apoptosis, as detected by caspase-3 activation. The effect is cell autonomous, occurring only in neuronal types in which the synGAP gene is eliminated. The level of caspase-3 activation in neurons correlates inversely with the level of synGAP protein measured at 2 and 8 weeks after birth, indicating that neuronal apoptosis is enhanced by reduction of synGAP. These data show that synGAP plays a role in regulation of the onset of apoptotic neuronal death. [source] Exogenous nitric oxide causes potentiation of hippocampal synaptic transmission during low-frequency stimulation via the endogenous nitric oxide,cGMP pathwayEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2001Christelle L. M. Bon Abstract Nitric oxide (NO) is a putative participant in synaptic plasticity and demonstrations that exogenous NO can elicit the same plastic changes have been taken to support such a role. The experiments, carried out on the CA1 region of rat hippocampal slices, were aimed at testing this interpretation. A major component of tetanus-induced long-term potentiation (LTP) was lost in response to l -nitroarginine, which inhibits NO synthase, and 1H -[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one (ODQ), which inhibits NO-sensitive soluble guanylyl cyclase (sGC). At 0.2 Hz afferent fibre stimulation, exogenous NO produced, concentration-dependently, a synaptic depression that reverted on washout to a persistent potentiation that occluded tetanus-induced LTP. The NO concentrations necessary (estimated in the 100-nm range), however, were mostly supramaximal for stimulating hippocampal slice sGC activity. Nevertheless the potentiation, but not the preceding depression, was blocked by ODQ. l -nitroarginine and an NMDA antagonist were similarly effective, indicating mediation by the endogenous NMDA receptor,NO synthase,sGC pathway. At a concentration normally too low to affect synaptic transmission but sufficient to stimulate sGC (estimated to be 50 nm), exogenous NO reversed the effect of l -nitroarginine and caused a potentiation which was blocked by ODQ. At a concentration inducing the depression/potentiation sequence, NO partially inhibited hippocampal slice oxygen consumption. It is concluded that, at physiological levels, exogenous NO can directly elicit a potentiation of synaptic transmission through sGC, provided that the synapses are suitably primed. At higher concentrations, NO inhibits mitochondrial respiration, which can result in an enduring synaptic potentiation due to secondary activation of the endogenous NO,cGMP pathway. [source] Increase in the fracture toughness and bond energy of clay by a root exudateEUROPEAN JOURNAL OF SOIL SCIENCE, Issue 5 2008B. Zhang Summary Root exudates help drive the formation of the rhizosphere by binding soil particles, but the underlying physical mechanisms have not been quantified. This was addressed by measuring the impact of a major component of root exudates, polygalacturonic acid (PGA), on the interparticle bond energy and fracture toughness of clay. Pure kaolinite was mixed with 0, 1.2, 2.4, 4.9 or 12.2 g PGA kg,1 to form test specimens. Half of the specimens were washed repeatedly to remove unbound PGA and evaluate the persistence of the effects, similar to weathering in natural soils. Fracture toughness, KIC, increased exponentially with added PGA, with washing increasing this trend. In unwashed specimens KIC ranged from 54.3 ± 2.5 kPa m,1/2 for 0 g PGA kg,1 to 86.9 ± 4.7 kPa m,1/2 for 12.2 g PGA kg,1. Washing increased KIC to 61.3 ± 1.2 kPa m,1/2 for 0 g PGA kg,1 and 132.1 ± 4.9 kPa m,1/2 for 12.2 g PGA kg,1. The apparent bond energy, ,, of the fracture surface increased from 5.9 ± 0.6 J m,2 for 0 g kg,1 to 12.0 ± 1.1 J m,2 for 12.2 g kg,1 PGA in the unwashed specimens. The washed specimens had , of 13.0 ± 1.9 J m,2 for 0 g kg,1 and 21.3 ± 2.6 J m,2 for 12.2 g PGA kg,1. Thus PGA, a major component of root exudates, has a large impact on the fracture toughness and bond energy of clay, and is likely to be a major determinant in the formation of the rhizosphere. This quantification of the thermodynamics of fracture will be useful for modelling rhizosphere formation and stability. [source] TOWARD THE EVOLUTIONARY GENOMICS OF GAMETOPHYTIC DIVERGENCE: PATTERNS OF TRANSMISSION RATIO DISTORTION IN MONKEYFLOWER (MIMULUS) HYBRIDS REVEAL A COMPLEX GENETIC BASIS FOR CONSPECIFIC POLLEN PRECEDENCEEVOLUTION, Issue 12 2008Lila Fishman Conspecific pollen precedence (CPP) is a major component of reproductive isolation between many flowering plant taxa and may reveal mechanisms of gametophytic evolution within species, but little is known about the genetic basis and evolutionary history of CPP. We systematically investigated the genetic architecture of CPP using patterns of transmission ratio distortion (TRD) in F2 and backcross hybrids between closely related species of Mimulus (Phrymaceae) with divergent mating systems. We found that CPP in Mimulus hybrids was polygenic and was the majority source of interspecific TRD genome-wide, with at least eight genomic regions contributing to the transmission advantage of M. guttatus pollen grains on M. guttatus styles. In aggregate, these male-specific transmission ratio distorting loci (TRDLs) were more than sufficient to account for the 100% precedence of pure M. guttatus pollen over M. nasutus pollen in mixed pollinations of M. guttatus. All but one of these pollen TRDLs were style-dependent; that is, we observed pollen TRD in F1 and/or M. guttatus styles, but not in M. nasutus styles. These findings suggest that species-specific differences in pollen tube performance accumulate gradually and may have been driven by coevolution between pollen and style in the predominantly outcrossing M. guttatus. [source] Evolution of a novel function: nutritive milk in the viviparous cockroach, Diploptera punctataEVOLUTION AND DEVELOPMENT, Issue 2 2004Anna Williford Summary Cockroach species show different degrees of maternal contribution to the developing offspring. In this study, we identify a multigene family that encodes water-soluble proteins that are a major component of nutritive "Milk" in the cockroach, Diploptera punctata. This gene family is associated with the evolution of a new trait, viviparity, in which the offspring receive nutrition during the gestation period. Twenty-five distinct Milk complementary DNAs were cloned and partially characterized. These complementary DNAs encode 22 distinct Milk peptides, each of length 171 amino acids, including a 16-amino acid signal peptide sequence. Southern blot analysis confirms the presence of multiple copies of Milk genes in D. punctata. Northern analysis indicates tissue- and stage-specific Milk gene expression. Examination of the deduced amino acid sequences identifies the presence of structurally conserved regions diagnostic of the lipocalin protein family. The shared exon/intron structure of one of the Milk loci with lipocalin genes further supports a close evolutionary relationship between these sequences. [source] Quantitative analysis of the synthesis and secretion of type VII collagen in cultured human dermal fibroblasts with a sensitive sandwich enzyme-linked immunoassayEXPERIMENTAL DERMATOLOGY, Issue 2 2007Satoshi Amano Abstract:, Type VII collagen is the major component of anchoring fibrils in the epidermal basement membrane. Its expression has been analyzed by immunostaining or Northern blotting, but rarely at the protein level. In this study, we have quantitatively examined the effects of ascorbic acid and various cytokines/growth factors on the protein synthesis and secretion of type VII collagen by human dermal fibroblasts in culture, using a developed, highly sensitive sandwich enzyme-linked immunoassay with two kinds of specific monoclonal antibodies against the non-collagenous domain-1. Ascorbic acid and its derivative induced a twofold increase in type VII collagen synthesis, and markedly increased the secretion of type VII collagen into the medium when compared with the control culture. This effect was not influenced by the presence of transforming growth factor- ,1 (TGF- ,1). The synthesis of type VII collagen was elevated by TGF- ,1, platelet-derived growth factor, tumor necrosis factor- ,, and interleukin-1,, but not by TGF- ,. Thus, our data indicate that the synthesis and secretion of type VII collagen in human dermal fibroblasts are regulated by ascorbate and the enhancement of type VII collagen gene expression by cytokines/growth factors is accompanied with elevated production of type VII collagen at the protein level. [source] Nuclear factor TDP-43 can affect selected microRNA levelsFEBS JOURNAL, Issue 10 2010Emanuele Buratti TDP-43 has recently been described as the major component of the inclusions found in the brain of patients with a variety of neurodegenerative diseases, such as frontotemporal lobar degeneration and amyotrophic lateral sclerosis. TDP-43 is a ubiquitous protein whose specific functions are probably crucial to establishing its pathogenic role. Apart from its involvement in transcription, splicing and mRNA stability, TDP-43 has also been described as a Drosha-associated protein. However, our knowledge of the role of TDP-43 in the microRNA (miRNA) synthesis pathway is limited to the association mentioned above. Here we report for the first time which changes occur in the total miRNA population following TDP-43 knockdown in culture cells. In particular, we have observed that let-7b and miR-663 expression levels are down- and upregulated, respectively. Interestingly, both miRNAs are capable of binding directly to TDP-43 in different positions: within the miRNA sequence itself (let-7b) or in the hairpin precursor (miR-663). Using microarray data and real-time PCR we have also identified several candidate transcripts whose expression levels are selectively affected by these TDP-43,miRNA interactions. [source] Insulin is a kinetic but not a thermodynamic inhibitor of amylin aggregationFEBS JOURNAL, Issue 12 2009Wei Cui One of the most important pathological features of type 2 diabetes is the formation of islet amyloid, of which the major component is amylin peptide. However, the presence of a natural inhibitor such as insulin may keep amylin stable and physiologically functional in healthy individuals. Some previous studies demonstrated that insulin was a potent inhibitor of amylin fibril formation in vitro, but others obtained contradictory results. Hence, it is necessary to elucidate the effects of insulin on amylin aggregation. Here we report that insulin is a kinetic inhibitor of amylin aggregation, only keeping its inhibitory effect for a limited time period. Actually, insulin promotes amylin aggregation after long-term incubation. Furthermore, we found that this promotional effect could be attributed to the copolymerization of insulin and amylin. We also found that insulin copolymerized with amylin monomer or oligomer rather than preformed amylin fibrils. These results suggest that the interaction between insulin and amylin may contribute not only to the inhibition of amylin aggregation but also to the coaggregation of both peptides in type 2 diabetes. [source] Mapping of the 45M1 epitope to the C-terminal cysteine-rich part of the human MUC5AC mucinFEBS JOURNAL, Issue 3 2008Martin E. Lidell Mucins are large glycoproteins protecting mucosal surfaces throughout the body. Their expressions are tissue-specific, but in disease states such as cystic fibrosis, inflammation and cancer, this specificity can be disturbed. MUC5AC is normally expressed in the mucous cells of the epithelia lining the stomach and the trachea, where it constitutes a major component of the gastric and respiratory mucus. A number of mAbs have been raised against the gastric M1 antigen, an early marker for colonic carcinogenesis. Several of these mAbs recognize epitopes present on MUC5AC, suggesting that MUC5AC is the antigen. However, some of the mAbs raised against the gastric M1 antigen are widely used as antibodies against MUC5AC, despite the fact that their specificity for MUC5AC has not been clearly shown. In this study, we have tested the reactivity of the latter antibodies against a recombinantly expressed C-terminal cysteine-rich part of human MUC5AC. We demonstrate for the first time that the widely used mAb 45M1, as well as 2-12M1 and 166M1, are true antibodies against MUC5AC, with epitopes located in the C-terminal cysteine-rich part of the mucin. [source] |