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Breakdown Products (breakdown + products)
Selected AbstractsGenotoxicity of nitrosulfonic acids, nitrobenzoic acids, and nitrobenzylalcohols, pollutants commonly found in ground water near ammunition facilitiesENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2006Tamara Grummt Abstract 2-Amino-4,6-dinitrobenzoic acid (2-A-4,6-DNBA), 4-amino-2,6-dinitrobenzoic acid (4-A-2,6-DNBA), 2,4,6-trinitrobenzoic acid (2,4,6-TNBA), 2-amino-4, 6-dinitrobenzylalcohol (2-A-4,6-DNBAlc), 4-amino-2,6-dinitrobenzylalcohol (4-A-2,6-DNBAlc), 2,4-dinitrotoluol-5-sulfonic acid (2,4-DNT-5-SA), 2,4-dinitrotoluol-3-sulfonic acid (2,4-DNT-3-SA), and 2, 4-dinitrobenzoic acid (2,4-DNBA) are derivatives of nitro-explosives that have been detected in groundwater close to munitions facilities. In the present study, the genotoxicity of these compounds was evaluated in Salmonella/microsome assays (in strains TA100 and TA98, with and without S9 and in TA98NR without S9), in chromosomal aberration (CA) tests with Chinese hamster fibroblasts (V79), and in micronucleus (MN) assays with human hepatoma (HepG2) cells. All compounds except the sulfonic acids were positive in the bacterial mutagenicity tests, with 2,4,6-TNBA producing the strongest response (8023 revertants/,mol in TA98 without S9 activation). 2-A-4,6-DNBA was a direct acting mutagen in TA98, but negative in TA100. The other positive compounds were ,1,3 orders of magnitude less mutagenic than 2,4,6-TNBA in TA98 and in TA100; relatively strong effects (,50,400 revertants/,mol) were produced by the benzylacohols in the two indicator strains. With the exception of 2,4-DNBA, the mutagenic responses were lower in the nitroreductase-deficient strain TA98NR than in the parental strain. 2,4-DNBA produced a marginally positive response in the V79-cell CA assay; the other substances were devoid of activity. Only the benzoic acids were tested for MN induction in HepG2 cells, and all produced positive responses. As in the bacterial assays, the strongest effect was seen with 2,4,6-TNBA (significant induction at ,1.9 ,M). 4-A-2,6-DNBA was positive at 432 ,M; the weakest effect was observed with 2,4,-DNBA (positive at ,920 ,M). The differences in the sensitivity of the indicator cells to these agents can be explained by differences in the activities of enzymes involved in the activation of the compounds. The strong responses produced by some of the compounds in the human-derived cells suggest that environmental exposure to these breakdown products of nitro-explosives may pose a cancer risk in man. Environ. Mol. Mutagen., 2006. © 2005 Wiley-Liss, Inc. [source] Glucosinolate Chemistry: Synthesis of O -Glycosylated Derivatives of GlucosinalbinEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 19 2010David Gueyrard Abstract The synthesis of the major glucosinolate of Moringa oleifera and of other non-natural O -glycosylated derivatives of glucosinalbin is reported. The synthetic sequence applied, which involves the conversion of carbohydrate-based nitrostyrenes into the key thiohydroximates, appears to be sufficiently versatile to synthesize a range of glucosinolatesbearing a glycosylated phenolic function. We synthesizedanalogues of the naturally occurring L -rhamnoside 1 with a view to estimating the importance of this phenol-protecting sugar moiety in modulating the biological activity of the parent glucosinolate and related breakdown products. [source] Optimization of Full-Scale Permanganate ISCO System Operation: Laboratory and Numerical StudiesGROUND WATER MONITORING & REMEDIATION, Issue 4 2008Jeffrey L. Heiderscheidt Laboratory characterization studies, one-dimensional flow-through studies, and numerical model simulations were conducted to examine site conditions and system features that may have adversely affected in situ chemical oxidation (ISCO) performance at the Naval Training Center's (NTC) Operable Unit 4 located in Orlando, Florida, and to identify potential ISCO system modifications to achieve the desired remediation performance. At the NTC site, ISCO was implemented using vertical injection wells to deliver potassium permanganate into a ground water zone for treatment of tetrachloroethylene and its breakdown products. However, oxidant distribution was much more limited than anticipated. Characterization studies revealed that the ground water zone being treated by ISCO was very fine sand with a small effective particle size and low uniformity coefficient, along with a high organic carbon content, high natural oxidant demand (NOD), and a high ground water dissolved solids concentration, all of which contributed to full-scale ISCO application difficulties. These site conditions contributed to injection well permeability loss and an inability to achieve the design oxidant injection flow rate, limiting the actual oxidant distribution at the site. Flow-through experiments demonstrated that more favorable oxidant delivery and distribution conditions are enabled by applying a lower oxidant concentration at a faster delivery rate for a greater number of pore volumes. Numerical simulations, run for a variety of conditions (injection/extraction well flow rates, injected oxidant concentration, amount of NOD present, and NOD oxidation rate), also revealed that low,oxidant concentration injection at a high flow rate is a more effective method to deliver the required mass of oxidant to the target treatment zone. [source] Calpain-mediated breakdown of cytoskeletal proteins contributes to cholecystokinin-induced damage of rat pancreatic aciniINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2009Heike Weber Summary The cytosolic cysteine protease calpain is implicated in a multitude of cellular functions but also plays a role in cell damage. Our previous results suggest that an activation of calpain accompanied by a decrease in its endogenous inhibitor calpastatin may contribute to pancreatic damage during cerulein-induced acute pancreatitis. The present study aimed at the time course of secretagogue-induced calpain activation and cellular substrates of the protease. Isolated rat pancreatic acini were incubated with a supramaximal concentration of cholecystokinin (0.1 ,M CCK) for 30 min in the presence or absence of the calpain inhibitor Z-Val-Phe methyl ester (100 ,M ZVP). The activation of calpain and the expression of calpastatin and the actin cytoskeleton-associated proteins ,II-spectrin, E-cadherin and vinculin were studied by immunoblotting. The cell damage was assessed by lactate dehydrogenase release and ultrastructural analysis including fluorescence-labelled actin filaments. Immediately after administration, CCK led to activation of both calpain isoforms, ,- and m-calpain. The protease activation was accompanied by a decrease in the E-cadherin level and formation of calpain-specific breakdown products of ,II-spectrin. A calpain-specific cleavage product of vinculin appeared concomitantly with changes in the actin filament organization. No effect of CCK on calpastatin was found. Inhibition of calpain by ZVP reduced CCK-induced damage of the actin-associated proteins and the cellular ultrastructure including the actin cytoskeleton. The results suggest that CCK-induced acinar cell damage requires activation of calpain and that the actin cytoskeleton belongs to the cellular targets of the protease. [source] Chronic expanding hematoma in the psoas muscleINTERNATIONAL JOURNAL OF UROLOGY, Issue 12 2005TOSHINARI YAMASAKI Abstract, We report an unusual case of chronic expanding hematoma in the psoas muscle. A 53-year-old man was admitted for evaluation of a mass shadow in the left lower lung field on chest X-rays. He had also been suffering from dull left back pain. A computed tomography scan showed a cystic lesion with a rim enhancement in the left retroperitoneal space. Mixed signal intensity in a mosaic pattern was seen on a T2-weighted magnetic resonance image. We could not rule out a suspicion of a neoplastic intratumoral hemorrhage. Due to increased pain and the definite diagnosis, surgery was performed. Histopathological examination confirmed the diagnosis of chronic expanding hematoma. The expansion process is thought to be due to the irritant effects of blood and its breakdown products, which cause repeated exudation and bleeding from capillaries in the granulation tissues. [source] Hepatic Kupffer cell phagocytotic function in rats with erythrocytic-stage malariaJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2002MICHAEL S NOBES AbstractBackground: In the erythrocytic phase of malaria, Kupffer cells show marked hypertrophy and hyperplasia and are filled with malarial pigment. However, phagocytic function in this state has not been well characterized. The aim of the present study was to use mouse Plasmodium berghei to infect rats with malaria and study the phagocytic function and morphology of Kupffer cells. Methods: We used a recirculating isolated perfused rat liver (IPRL) to quantitate Kupffer cell phagocytic clearance of radiolabeled albumin,latex over 120 min in high parasitemia (53 ± 6%; n = 7) and low parasitemia (,1%; n = 4) malaria-infected rats and littermate controls (n = 7 and n = 4, respectively). In a further group of high-parasitemic rats, perfusion was ceased after 7 min and liver radioactivity also measured. Electron microscopy was performed after perfusions. Results: In high-parasitemia malaria rats, clearance of radiolabeled latex from IPRL perfusate over 120 min was significantly (P < 0.01) faster than in controls, with a lower area under the curve (0.19 ± 0.02 vs 0.43 ± 0.07 /mL per min, respectively) and shorter half-life (t1/2k; 2.4 ± 0.6 vs 10.0 ± 2.3 min, respectively). Low-parasitemia rats were identical to controls. After 7 min perfusion in high-parasitemic rats (n = 4), total radioactivity in liver homogenates was higher than in controls (n = 4; 33.1 ± 6.2 vs 18.4 ± 1.9% of injected radiolabel; P < 0.05). Electron microscopy showed latex in Kupffer cells, more abundantly seen in high-parasitemic animals. Conclusions: Total Kupffer cell phagocytic activity of the liver is markedly increased in rats with a high parasitemic load of malarial P. berghei infection. This is presumed to reflect an upregulation of scavenger activity phagocytosing erythrocytes and their breakdown products. © 2002 Blackwell Publishing Asia Pty Ltd [source] Imbalance of plasma membrane ion leak and pump relationship as a new aetiological basis of certain disease statesJOURNAL OF INTERNAL MEDICINE, Issue 6 2003G. Ronquist Abstract. The basis for life is the ability of the cell to maintain ion gradients across biological membranes. Such gradients are created by specific membrane-bound ion pumps [adenosine triphosphatases (ATPases)]. According to physicochemical rules passive forces equilibrate (dissipate) ion gradients. The cholesterol/phospholipid ratio of the membrane and the degree of saturation of phospholipid fatty acids are important factors for membrane molecular order and herewith a determinant of the degree of non-specific membrane leakiness. Other operative principles, i.e. specific ion channels can be opened and closed according to mechanisms that are specific to the cell. Certain compounds called ionophores can be integrated in the plasma membrane and permit specific inorganic ions to pass. Irrespective of which mechanism ions leak across the plasma membrane the homeostasis may be kept by increasing ion pumping (ATPase activity) in an attempt to restore the physiological ion gradient. The energy source for this work seems to be glycolytically derived ATP formation. Thus an increase in ion pumping is reflected by increased ATP hydrolysis and rate of glycolysis. This can be measured as an accumulation of breakdown products of ATP and end-products of anaerobic glycolysis (lactate). In certain disease entities, the balance between ATP formation and ion pumping may be disordered resulting in a decrease in inter alia (i.a.) cellular energy charge, and an increase in lactate formation and catabolites of adenylates. Cardiac syndrome X is proposed to be due to an excessive leakage of potassium ions, leading to electrocardiographic (ECG) changes, abnormal Tl-scintigraphy of the heart and anginal pain (induced by adenosine). Cocksackie B3 infections, a common agent in myocarditis might also induce an ionophore-like effect. Moreover, Alzheimer's disease is characterized by the formation of extracellular amyloid deposits in the brain of patients. Perturbation of cellular membranes by the amyloid peptide during the development of Alzheimer's disease is one of several mechanisms proposed to account for the toxicity of this peptide on neuronal membranes. We have studied the effects of the peptide and fragments thereof on 45Ca2+ -uptake in human erythrocytes and the energetic consequences. Treatment of erythrocytes with the ,1,40 peptide, results in qualitatively similar nucleotide pattern and decrease of energy charge as the treatment with Ca2+ -ionophore A23187. Finally, in recent studies we have revealed and published in this journal that a rare condition, Tarui's disease or glycogenosis type VII, primarily associated with a defect M-subunit of phosphofructokinase, demonstrates as a cophenomenon an increased leak of Ca2+ into erythrocytes. [source] Petrology of coesite-bearing eclogite from Habutengsu Valley, western Tianshan, NW China and its tectonometamorphic implicationJOURNAL OF METAMORPHIC GEOLOGY, Issue 9 2009Z. LÜ Abstract Coesite inclusions in garnet have been found in eclogite boudins enclosed in coesite-bearing garnet micaschist in the Habutengsu Valley, Chinese western Tianshan, which are distinguished from their retrograde quartz by means of optical characteristics, CL imaging and Raman spectrum. The coesite-bearing eclogite is mainly composed of porphyroblastic garnet, omphacite, paragonite, glaucophane and barroisite, minor amounts of rutile and dotted (or banded) graphite. In addition to coesite and quartz, the zoned porphyroblastic garnet contains inclusions of omphacite, Na-Ca amphibole, calcite, albite, chlorite, rutile, ilmenite and graphite. Multi-phase inclusions (e.g. Czo + Pg ± Qtz, Grt II + Qtz and Chl + Pg) can be interpreted as breakdown products of former lawsonite and possibly chloritoid. Coesite occurs scattered within a compositionally homogenous but narrow domain of garnet (outer core), indicative of equilibrium at the UHP stage. The estimate by garnet-clinopyroxene thermometry yields peak temperatures of 420,520 °C at 2.7 GPa. Phase equilibrium calculations further constrain the P,T conditions for the UHP mineral assemblage Grt + Omp + Lws + Gln + Coe to 2.4,2.7 GPa and 470,510 °C. Modelled modal abundances of major minerals along a 5 °C km,1 geothermal gradient suggests two critical dehydration processes at ,430 and ,510 °C respectively. Computed garnet composition patterns are in good agreement with measured core-rim profiles. The petrological study of coesite-bearing eclogite in this paper provides insight into the metamorphic evolution in a cold subduction zone. Together with other reported localities of UHP rocks from the entire orogen of Chinese western Tianshan, it is concluded that the regional extent of UHP-LT metamorphism in Chinese western Tianshan is extensive and considerably larger than previously thought, although intensive retrogression has erased UHP-LT assemblages at most localities. [source] Prograde P,T path of medium-pressure granulite facies calc-silicate rocks, Higo metamorphic terrane, central Kyushu, JapanJOURNAL OF METAMORPHIC GEOLOGY, Issue 2 2009K. MAKI Abstract This paper reports an occurrence of medium-pressure granulite facies calc-silicate rocks intercalated with pelitic gneisses in the Higo metamorphic terrane, central Kyushu, Japan, which is classified as a low- P/high- T (andalusite-sillimanite type) metamorphic belt. Three equilibrium stages are recognized in the calc-silicate rock based on reaction textures: M1 stage characterized by an assemblage of porphyroblastic garnet + coarse-grained clinopyroxene + plagioclase included in the clinopyroxene; M2 stage by two kinds of breakdown products of garnet, one is plagioclase + coronitic clinopyroxene within garnet and the other is plagioclase + vermicular clinopyroxene surrounding garnet; and M3 stage by amphibole replacing clinopyroxene. The key assemblage in the calc-silicate rock common to M1 and M2 stages is Grt + Cpx + Pl ± Qtz, which constrains the pressure and temperature (P,T) conditions for these stages by Fe,Mg exchange reaction and the two univariant net-transfer reactions: 2Grs + Alm + 3Qtz = 3Hd + 3An or 2Grs + Prp + 3Qtz = 3Di + 3An. The P,T conditions for M1 and M2 stages were estimated to be about 8.4 ± 1.9 kbar and 680 ± 122 °C, and 6.7 ± 1.9 to 8.9 ± 2.2 kbar and 700 ± 130 to 820 ± 160 °C, respectively. Estimates are consistent with an isobaric heating P,T path. The high peak temperature conditions at normal crustal depths and the prograde isobaric heating path probably require heat advection due to melt migration during the high- T metamorphism. [source] Cyclosporin A prevents calpain activation despite increased intracellular calcium concentrations, as well as translocation of apoptosis-inducing factor, cytochrome c and caspase-3 activation in neurons exposed to transient hypoglycemiaJOURNAL OF NEUROCHEMISTRY, Issue 6 2003Michel Ferrand-Drake Abstract Blockade of mitochondrial permeability transition protects against hypoglycemic brain damage. To study the mechanisms downstream from mitochondria that may cause neuronal death, we investigated the effects of cyclosporin A on subcellular localization of apoptosis-inducing factor and cytochrome c, activation of the cysteine proteases calpain and caspase-3, as well as its effect on brain extracellular calcium concentrations. Redistribution of cytochrome c occurred at 30 min of iso-electricity, whereas translocation of apoptosis-inducing factor to nuclei occurred at 30 min of recovery following 30 min of iso-electricity. Active caspase-3 and calpain-induced fodrin breakdown products were barely detectable in the dentate gyrus and CA1 region of the hippocampus of rat brain exposed to 30 or 60 min of insulin-induced hypoglycemia. However, 30 min or 3 h after recovery of blood glucose levels, fodrin breakdown products and active caspase-3 markedly increased, concomitant with a twofold increase in caspase-3-like enzymatic activity. When rats were treated with neuroprotective doses of cyclosporin A, but not with FK 506, the redistribution of apoptosis-inducing factor and cytochrome c was reduced and fodrin breakdown products and active caspase-3 immuno-reactivity was diminished whereas the extracellular calcium concentration was unaffected. We conclude that hypoglycemia leads to mitochondrial permeability transition which, upon recovery of energy metabolism, mediates the activation of caspase-3 and calpains, promoting cell death. [source] Heat-induced denaturation impairs digestibility of legume (Phaseolus vulgaris L and Vicia faba L) 7S and 11S globulins in the small intestine of ratJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 1 2005M Carbonaro Abstract 7S globulin from common bean (Phaseolus vulgaris L) and 11S globulin from faba bean (Vicia faba L) were isolated to over 90% purity and the digestibility of the proteins, either in native or denatured (120 °C, 20 min, 1 atm) state, was tested in the small intestine of growing rats in acute (1 h) experiments. Native globulins were well digested (92 and 95% for 7S and 11S proteins, respectively). However, after thermal denaturation, protein digestibility of 7S globulin was reduced to 88%, while that of 11S globulin to only 79%. SDS-PAGE revealed that high amounts of the intermediate proteolytic products of phaseolin (MW 22 000,27 000 Da) were present in the small intestine of rats after 1 h digestion of the denatured 7S globulin, while protein material in the high MW range (>55 000 Da) were recovered from the 11S globulin. The overall negative charge of unavailable proteins from the 7S globulin was found by anion exchange,FPLC separation to be higher than that of products from the 11S globulin. MALDI-MS analysis of proteins in the small intestine confirmed the presence of half-size phaseolin subunits (MW 23 700 Da) as breakdown products from the denatured 7S globulin, and of highly hydrophobic basic subunits (MW 20 000 Da) from the 11S globulin. Copyright © 2004 Society of Chemical Industry [source] An overview of the antifungal properties of allicin and its breakdown products , the possibility of a safe and effective antifungal prophylacticMYCOSES, Issue 2 2005Stephen R Davis Summary Reports about the safe and successful intravenous (i.v.) use of garlic derivatives in China against invasive fungal infections have been made, but little has been done to seriously investigate the in vivo use of these derivatives in the West. Laboratories have demonstrated impressive in vitro MICs using allitridium, one of these derivatives, against a range of medically important fungi. In addition, it has been demonstrated that allitridium shows in vitro synergy with amphotericin B, one of the main i.v. antifungal agents. Some of the breakdown products of allicin, the main parent antifungal compound in garlic, have been investigated for their general antimicrobial, anticancer and anticholesterol properties, and it appears that there is a common mode of action that underlies these activities. It appears that these small molecules have the ability to cross cell membranes and combine with sulfur-containing molecular groups in amino acids and proteins, thus interfering with cell metabolism. It has been suggested that the reason human cells are not poisoned by allicin derivatives is that they contain glutathione, a sulfur-containing amino acid that combines with the allicin derivative, thus preventing cell damage. In addition to their biochemical mechanism, these derivatives appear to stimulate cellular immunity, an important ability lacking in conventional antifungal chemotherapy. These derivatives appear to be safe, cheap, wide-spectrum and immunostimulatory, as well as possibly synergistic with conventional antifungal therapy, making them ideal candidates for investigation into their use as prophylactic antifungal agents. [source] Quantitative trait loci for glucosinolate accumulation in Brassica rapa leavesNEW PHYTOLOGIST, Issue 4 2008Ping Lou Summary ,,Glucosinolates and their breakdown products have been recognized for their effects on plant defense, human health, flavor and taste of cruciferous vegetables. Despite this importance, little is known about the regulation of the biosynthesis and degradation in Brassica rapa. ,,Here, the identification of quantitative trait loci (QTL) for glucosinolate accumulation in B. rapa leaves in two novel segregating double haploid (DH) populations is reported: DH38, derived from a cross between yellow sarson R500 and pak choi variety HK Naibaicai; and DH30, from a cross between yellow sarson R500 and Kairyou Hakata, a Japanese vegetable turnip variety. ,,An integrated map of 1068 cM with 10 linkage groups, assigned to the international agreed nomenclature, is developed based on the two individual DH maps with the common parent using amplified fragment length polymorphism (AFLP) and single sequence repeat (SSR) markers. Eight different glucosinolate compounds were detected in parents and F1s of the DH populations and found to segregate quantitatively in the DH populations. QTL analysis identified 16 loci controlling aliphatic glucosinolate accumulation, three loci controlling total indolic glucosinolate concentration and three loci regulating aromatic glucosinolate concentrations. ,,Both comparative genomic analyses based on Arabidopsis,Brassica rapa synteny and mapping of candidate orthologous genes in B. rapa allowed the selection of genes involved in the glucosinolate biosynthesis pathway that may account for the identified QTL. [source] Investigation of norflurazon pesticide photodegradation using plasma desorption time-of-flight mass spectrometry analysisRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 16 2008J.-P. Thomas We have previously demonstrated that PD-TOFMS (plasma desorption time-of-flight mass spectrometry) analysis is a powerful technique for the in situ analysis of pesticides deposited or adsorbed on solid materials. With the aim of producing reproducible data on the modification of a pesticide under controlled photodegradation conditions, we have now undertaken a study where both the substrate and the pesticide are well characterized. This is the case for norflurazon deposited onto an aluminium substrate, in particular regarding the reproducibility of preparation of the samples and the change with time of their chemical composition. Degradation parameters have been derived from the variation in yield of ions representative of the molecule and of its breakdown products and, particularly, from the time required for 50% dissipation of their initial concentration (DT50). DT50 values ranging between 1 and 10,h have been found. An interpretation of the degradation process is proposed from the decay of other ions. As expected, the degradation is faster when the UV sunlight is unfiltered (a factor of 3.8 for the molecule, and around 5 for the breakdown products). Copyright © 2008 John Wiley & Sons, Ltd. [source] Cuticular defects lead to full immunity to a major plant pathogenTHE PLANT JOURNAL, Issue 6 2007Céline Chassot Summary In addition to its role as a barrier, the cuticle is also a source of signals perceived by invading fungi. Cuticular breakdown products have been shown previously to be potent inducers of cutinase or developmental processes in fungal pathogens. Here the question was addressed as to whether plants themselves can perceive modifications of the cuticle. This was studied using Arabidopsis thaliana plants with altered cuticular structure. The expression of a cell wall-targeted fungal cutinase in A. thaliana was found to provide total immunity to Botrytis cinerea. The response observed in such cutinase-expressing plants is independent of signal transduction pathways involving salicylic acid, ethylene or jasmonic acid. It is accompanied by the release of a fungitoxic activity and increased expression of members of the lipid transfer protein, peroxidase and protein inhibitor gene families that provide resistance when overexpressed in wild-type plants. The same experiments were made in the bodyguard (bdg) mutant of A. thaliana. This mutant exhibits cuticular defects and remained free of symptoms after inoculation with B. cinerea. The expression of resistance was accompanied by the release of a fungitoxic activity and increased expression of the same genes as observed in cutinase-expressing plants. Structural defects of the cuticle can thus be converted into an effective multi-factorial defence, and reveal a hitherto hidden aspect of the innate immune response of plants. [source] Cellular efflux of auxin catalyzed by the Arabidopsis MDR/PGP transporter AtPGP1THE PLANT JOURNAL, Issue 2 2005Markus Geisler Summary Directional transport of the phytohormone auxin is required for the establishment and maintenance of plant polarity, but the underlying molecular mechanisms have not been fully elucidated. Plant homologs of human multiple drug resistance/P-glycoproteins (MDR/PGPs) have been implicated in auxin transport, as defects in MDR1 (AtPGP19) and AtPGP1 result in reductions of growth and auxin transport in Arabidopsis (atpgp1, atpgp19), maize (brachytic2) and sorghum (dwarf3). Here we examine the localization, activity, substrate specificity and inhibitor sensitivity of AtPGP1. AtPGP1 exhibits non-polar plasma membrane localization at the shoot and root apices, as well as polar localization above the root apex. Protoplasts from Arabidopsis pgp1 leaf mesophyll cells exhibit reduced efflux of natural and synthetic auxins with reduced sensitivity to auxin efflux inhibitors. Expression of AtPGP1 in yeast and in the standard mammalian expression system used to analyze human MDR-type proteins results in enhanced efflux of indole-3-acetic acid (IAA) and the synthetic auxin 1-naphthalene acetic acid (1-NAA), but not the inactive auxin 2-NAA. AtPGP1-mediated efflux is sensitive to auxin efflux and ABC transporter inhibitors. As is seen in planta, AtPGP1 also appears to mediate some efflux of IAA oxidative breakdown products associated with apical sites of high auxin accumulation. However, unlike what is seen in planta, some additional transport of the benzoic acid is observed in yeast and mammalian cells expressing AtPGP1, suggesting that other factors present in plant tissues confer enhanced auxin specificity to PGP-mediated transport. [source] Carbohydrate utilization by juvenile silver perch, Bidyanus bidyanus (Mitchell).AQUACULTURE RESEARCH, Issue 2 2003Abstract The ability of silver perch (Bidyanus bidyanus) to digest and utilize dietary starch or starch breakdown products was investigated. For experiment 1 the ability of silver perch (2.7 ± 0.01 g) to digest wheat starch at two dietary inclusion levels (30% or 60%), each at four levels of gelatinization (0%, 25%, 50% or 80%), was investigated over a 31-day period. For experiment 2, the ability of silver perch (15.9± 0.25 g) to digest wheat starch, dextrin (at three levels of dextrinization), maltose, glucose and pea starch, all at the 30% inclusion level, was investigated over a 41-day period. Water temperature for both experiments was 25 ± 1 °C. Apparent digestibility coefficients (ADCs) for starch, dry matter (DM) and energy were affected by both degree of gelatinization (80% > 50% > 25% = 0%) and inclusion level (30% > 60%). Specific growth rate (SGR) was unaffected by the inclusion of 30% starch; however, it was reduced at the 60% starch content level. Degree of gelatinization had no effect on SGR. For experiment 2, there were significant differences between carbohydrate and DM ADCs for the test ingredients. The carbohydrate, DM and energy ADCs were ranked as follows: dextrin (Fieldose 9) = dextrin (Fieldose 17) = dextrin (Fieldose 30) = gelatinized wheat starch = maltose = glucose > raw wheat starch > raw pea starch. The protein ADC of the diets, postprandial plasma glucose concentration and SGR were all unaffected by ingredient type. For both experiments, HSI tended to increase with carbohydrate inclusion. Liver glycogen concentrations were also elevated, but muscle glycogen and liver and muscle triacylglycerol concentrations were unaffected. Digestibility of starch by silver perch is clearly affected by inclusion content and processing. [source] Modified expression of the ADAMTS enzymes and tissue inhibitor of metalloproteinases 3 during human intervertebral disc degenerationARTHRITIS & RHEUMATISM, Issue 2 2009Aneta J. Pockert Objective Intervertebral disc degeneration is linked to loss of extracellular matrix (ECM), particularly the early loss of aggrecan. A group of metalloproteinases called aggrecanases are important mediators of aggrecan turnover. The present study was undertaken to investigate the expression of the recognized aggrecanases and their inhibitor, tissue inhibitor of metalloproteinases 3 (TIMP-3), in human intervertebral disc tissue. Methods Twenty-four nondegenerated and 30 degenerated disc samples were analyzed for absolute messenger RNA (mRNA) copy number of ADAMTS 1, 4, 5, 8, 9, and 15 and TIMP-3 by real-time reverse transcription,polymerase chain reaction. Thirty-six formalin-fixed embedded intervertebral disc samples of varying grades of degeneration were used for immunohistochemical analyses. In addition, samples from 8 subjects were analyzed for the presence of matrix metalloproteinase (MMP), and aggrecanase-generated aggrecan products. Results Messenger RNA for all the aggrecanases other than ADAMTS-8 was identified in intervertebral disc tissue, as was mRNA for TIMP-3. Levels of mRNA expression of ADAMTS 1, 4, 5, and 15 were significantly increased in degenerated tissue compared with nondegenerated tissue. All these aggrecanases and TIMP-3 were also detected immunohistochemically in disc tissue, and numbers of nucleus pulposus cells staining positive for ADAMTS 4, 5, 9, and 15 were significantly increased in degenerated tissue compared with nondegenerated tissue. Aggrecan breakdown products generated by MMP and aggrecanase activities were also detected in intervertebral disc tissue. Conclusion The aggrecanases ADAMTS 1, 4, 5, 9, and 15 may contribute to the changes occurring in the ECM during intervertebral disc degeneration. Targeting these enzymes may be a possible future therapeutic strategy for the prevention of intervertebral disc degeneration and its associated morbidity. [source] Electrolytic liver ablation is not associated with evidence of a systemic inflammatory response syndromeBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 2 2004B. D. Teague Background Local ablation has been proposed for treatment of liver tumours. Cryoshock, a variant of the systemic inflammatory response syndrome (SIRS), is a potentially fatal complication of cryoablation caused by systemic release of necrotic breakdown products from ablated liver. The proinflammatory cytokines tissue necrosis factor (TNF) , and interleukin (IL) 1 are important mediators of this response. This study assessed the risk of SIRS complicating electrolytic liver ablation by measuring circulating levels of inflammatory cytokines, other inflammatory markers and clinical markers of organ function. Methods Electrolytic liver ablation was performed in 16 pigs and four pigs served as controls. Platelet count, and serum levels of urea, creatinine, liver enzymes, C-reactive protein (CRP), TNF-, and IL-1, were measured before treatment and for 72 h after the procedure. Results There were significant dose-related increases in CRP and alanine aminotransferase levels with liver electrolysis. There was no significant derangement in renal function or platelet count following ablation. A rise in serum TNF-, and IL-1, levels was not associated with liver electrolysis. Conclusion There was no evidence of organ failure or significantly raised levels of proinflammatory cytokines as a result of liver electrolysis, suggesting that this is a safe procedure for liver ablation. Copyright © 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] | |||||||||||||||||||