Academic literature on the topic 'Nox inhibition'
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Journal articles on the topic "Nox inhibition"
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Han, Jin, Donghwi Park, Ji Young Park, and Seungwoo Han. "Inhibition of NADPH Oxidases Prevents the Development of Osteoarthritis." Antioxidants 11, no. 12 (November 27, 2022): 2346. http://dx.doi.org/10.3390/antiox11122346.
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Increased oxidative stress in osteoarthritis (OA) cartilage mediates catabolic signal transduction leading to extracellular matrix degradation and chondrocyte apoptosis. This study aimed to explore the contribution of NADPH oxidase (NOX), a major source of cellular reactive oxygen species (ROS), to the catabolic process of chondrocytes and to OA. The inhibition of NOX isoforms with a pan-NOX inhibitor, APX-115, significantly decreased IL-1β-induced ROS production in primary chondrocytes and, most potently, suppressed the expression of oxidative stress marker genes and catabolic proteases compared with the inhibition of other ROS sources. Catabolic stimuli by IL-1β treatment and in post-traumatic OA conditions upregulated the expression of NOX2 and NOX4 in chondrocytes. In the post-traumatic OA model, the pharmacologic inhibition of NOX protected mice against OA by modulating the oxidative stress and the expression of MMP-13 and Adamts5 in chondrocytes. Mechanistically, NOX inhibition suppresses Rac1, p38, and JNK MAPK signaling consistently and restores oxidative phosphorylation in IL-1β-treated chondrocytes. In conclusion, NOX inhibition prevented the development of OA by attenuating the catabolic signaling and restoring the mitochondrial metabolism and can thus be a promising class of drug for OA.
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Coby, Aaron J., and Flynn W. Picardal. "Inhibition of NO3− and NO2− Reduction by Microbial Fe(III) Reduction: Evidence of a Reaction between NO2− and Cell Surface-Bound Fe2+." Applied and Environmental Microbiology 71, no. 9 (September 2005): 5267–74. http://dx.doi.org/10.1128/aem.71.9.5267-5274.2005.
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ABSTRACT A recent study (D. C. Cooper, F. W. Picardal, A. Schimmelmann, and A. J. Coby, Appl. Environ. Microbiol. 69:3517-3525, 2003) has shown that NO3 − and NO2 − (NOx −) reduction by Shewanella putrefaciens 200 is inhibited in the presence of goethite. The hypothetical mechanism offered to explain this finding involved the formation of a Fe(III) (hydr)oxide coating on the cell via the surface-catalyzed, abiotic reaction between Fe2+ and NO2 −. This coating could then inhibit reduction of NOx − by physically blocking transport into the cell. Although the data in the previous study were consistent with such an explanation, the hypothesis was largely speculative. In the current work, this hypothesis was tested and its environmental significance explored through a number of experiments. The inhibition of ∼3 mM NO3 − reduction was observed during reduction of a variety of Fe(III) (hydr)oxides, including goethite, hematite, and an iron-bearing, natural sediment. Inhibition of oxygen and fumarate reduction was observed following treatment of cells with Fe2+ and NO2 −, demonstrating that utilization of other soluble electron acceptors could also be inhibited. Previous adsorption of Fe2+ onto Paracoccus denitrificans inhibited NOx − reduction, showing that Fe(II) can reduce rates of soluble electron acceptor utilization by non-iron-reducing bacteria. NO2 − was chemically reduced to N2O by goethite or cell-sorbed Fe2+, but not at appreciable rates by aqueous Fe2+. Transmission and scanning electron microscopy showed an electron-dense, Fe-enriched coating on cells treated with Fe2+ and NO2 −. The formation and effects of such coatings underscore the complexity of the biogeochemical reactions that occur in the subsurface.
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Kampschreur, M. J., N. C. G. Tan, C. Picioreanu, M. S. M. Jetten, I. Schmidt, and M. C. M. van Loosdrecht. "Role of nitrogen oxides in the metabolism of ammonia-oxidizing bacteria." Biochemical Society Transactions 34, no. 1 (January 20, 2006): 179–81. http://dx.doi.org/10.1042/bst0340179.
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Ammonia-oxidizing bacteria (AOB) can use oxygen and nitrite as electron acceptors. Nitrite reduction by Nitrosomonas is observed under three conditions: (i) hydrogen-dependent denitrification, (ii) anoxic ammonia oxidation with nitrogen dioxide (NO2) and (iii) NOx-induced aerobic ammonia oxidation. NOx molecules play an important role in the conversion of ammonia and nitrite by AOB. Absence of nitric oxide (NO), which is generally detectable during ammonia oxidation, severely impairs ammonia oxidation by AOB. The lag phase of recovery of aerobic ammonia oxidation was significantly reduced by NO2 addition. Acetylene inhibition tests showed that NO2-dependent and oxygen-dependent ammonia oxidation can be distinguished. Addition of NOx increased specific activity of ammonia oxidation, growth rate and denitrification capacity. Together, these findings resulted in a hypothetical model on the role of NOx in ammonia oxidation: the NOx cycle.
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Gaspar, Renato Simões, Tanya Sage, Gemma Little, Neline Kriek, Giordano Pula, and Jonathan M. Gibbins. "Protein Disulphide Isomerase and NADPH Oxidase 1 Cooperate to Control Platelet Function and Are Associated with Cardiometabolic Disease Risk Factors." Antioxidants 10, no. 3 (March 23, 2021): 497. http://dx.doi.org/10.3390/antiox10030497.
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Background: Protein disulphide isomerase (PDI) and NADPH oxidase 1 (Nox-1) regulate platelet function and reactive oxygen species (ROS) generation, suggesting potentially interdependent roles. Increased platelet reactivity and ROS production have been correlated with cardiometabolic disease risk factors. Objectives: To establish whether PDI and Nox-1 cooperate to control platelet function. Methods: Immunofluorescence microscopy was utilised to determine expression and localisation of PDI and Nox-1. Platelet aggregation, fibrinogen binding, P-selectin exposure, spreading and calcium mobilization were measured as markers of platelet function. A cross-sectional population study (n = 136) was conducted to assess the relationship between platelet PDI and Nox-1 levels and cardiometabolic risk factors. Results: PDI and Nox-1 co-localized upon activation induced by the collagen receptor GPVI. Co-inhibition of PDI and Nox-1 led to additive inhibition of GPVI-mediated platelet aggregation, activation and calcium flux. This was confirmed in murine Nox-1−/− platelets treated with PDI inhibitor bepristat, without affecting bleeding. PDI and Nox-1 together contributed to GPVI signalling that involved the phosphorylation of p38 MAPK, p47phox, PKC and Akt. Platelet PDI and Nox-1 levels were upregulated in obesity, with platelet Nox-1 also elevated in hypertensive individuals. Conclusions: We show that PDI and Nox-1 cooperate to control platelet function and are associated with cardiometabolic risk factors.
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Chen, Hai, Yun Seon Song, and Pak H. Chan. "Inhibition of NADPH Oxidase is Neuroprotective after Ischemia—Reperfusion." Journal of Cerebral Blood Flow & Metabolism 29, no. 7 (May 6, 2009): 1262–72. http://dx.doi.org/10.1038/jcbfm.2009.47.
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Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) is well known as a major source for superoxide radical generation in leukocytes. Superoxide radicals play a significant role in brain ischemia–reperfusion (I/R) injury. Recent data have also shown expression of NOX in the brain. However, the manner by which NOX is involved in pathologic processes after cerebral ischemia remains unknown. Therefore, we subjected mice deficient in the NOX subunit, gp91phox (gp91phox-/-), those treated with the NOX inhibitor, apocynin, and wild-type (WT) mice to 75 mins of focal ischemia followed by reperfusion. At 24 h of reperfusion, the gp91phox-/- and apocynin-treated mice showed 50% less brain infarction and 70% less cleaved spectrin compared with WT mice. The levels of 4-hydroxy-2-nonenal, malondialdehyde, and 8-hydroxy-2‘-deoxyguanosine increased significantly after I/R, indicating oxidative brain injury. NADPH oxidase inhibition reduced biomarker generation. Furthermore, NOX was involved in postischemic inflammation in the brains, as less intercellular adhesion molecule-1 upregulation and less neutrophil infiltration were found in the NOX-inhibited mice after I/R. Moreover, gp91phox expression increased after ischemia, and was further aggravated by genetic copper/zinc-superoxide dismutase (SOD1) ablation, but ameliorated in SOD1-overexpressing mice. This study suggests that NOX plays a role in oxidative stress and inflammation, thus contributing to ischemic brain injury.
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Wu, Tian Hua, and Ren Zhang Qian. "Study of NOx Inhibition Technology Based on Water-Gas Reaction." Applied Mechanics and Materials 737 (March 2015): 584–87. http://dx.doi.org/10.4028/www.scientific.net/amm.737.584.
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Pulverized coal combustion is one of the main NOx emission sources. The existing low NOx combustion technology can not meet the requirements of environment conservation. In this paper, a new low NOx combustion technology, the NOx inhibition method based on water-gas reaction, is presented, in which steam is injected into the anoxic flame of pulverized coal to bring water-gas reaction and produce CO and H2 which will inhibit the production of NOx. The produced H2 is especially very active. Water-gas reaction is endothermic, which has an effect of reducing the peak temperature of the flame and is very propitious to the inhibition of thermal type NOx. As the water-gas reaction is also an interim process, the heat absorbed in it will be released when burning with oxygen so that the whole amount of heat inside the furnace is not affected. The principle of the method is proved correct by experiments and industrial scale of 420 t/h boiler tests in which the effect of NOx reduction is obvious. The technology is consistent with that of air-staged combustion.
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Djerdjev, Alex M., Pramith Priyananda, Jeff Gore, James K. Beattie, Chiara Neto, and Brian S. Hawkett. "Safer emulsion explosives resulting from NOx inhibition." Chemical Engineering Journal 403 (January 2021): 125713. http://dx.doi.org/10.1016/j.cej.2020.125713.
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Wen, Yi, Ruohong Liu, Ning Lin, Hao Luo, Jiajia Tang, Qilin Huang, Hongyu Sun, and Lijun Tang. "NADPH Oxidase Hyperactivity Contributes to Cardiac Dysfunction and Apoptosis in Rats with Severe Experimental Pancreatitis through ROS-Mediated MAPK Signaling Pathway." Oxidative Medicine and Cellular Longevity 2019 (May 9, 2019): 1–18. http://dx.doi.org/10.1155/2019/4578175.
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NADPH oxidase (Nox) is considered a major source of reactive oxygen species (ROS) in the heart in normal and pathological conditions. However, the role of Nox in severe acute pancreatitis- (SAP-) associated cardiac injury remains unclear. Therefore, we aim to investigate the contribution of Nox to SAP-associated cardiac injury and to explore the underlying molecular mechanisms. Apocynin, a Nox inhibitor, was given at 20 mg/kg for 30 min before SAP induction by a retrograde pancreatic duct injection of 5% sodium taurocholate. Histopathological staining, Nox activity and protein expression, oxidative stress markers, apoptosis and associated proteins, cardiac-related enzyme indexes, and cardiac function were assessed in the myocardium in SAP rats. The redox-sensitive MAPK signaling molecules were also examined by western blotting. SAP rats exhibited significant cardiac impairment along with increased Nox activity and protein expression, ROS production, cell apoptosis, and proapoptotic Bax and cleaved caspase-3 protein levels. Notably, Nox inhibition with apocynin prevented SAP-associated cardiac injury evidenced by a decreased histopathologic score, cardiac-related enzymes, and cardiac function through the reduction of ROS production and cell apoptosis. This protective role was further confirmed by a simulation experiment in vitro. Moreover, we found that SAP-induced activation in MAPK signaling molecules in cardiomyocytes was significantly attenuated by Nox inhibition. Our data provide the first evidence that Nox hyperactivation acts as the main source of ROS production in the myocardium, increases oxidative stress, and promotes cell apoptosis via activating the MAPK pathway, which ultimately results in cardiac injury in SAP.
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Shin, Kyong-Oh, Sungeun Kim, Bokyung Kim, Hye-Yoon Park, Eunhee Jung, Garyun Kim, Donghee Kim, Hwang Eui Cho, Yoshikazu Uchida, and Kyungho Park. "Euphorbia supina Extracts Block NADPH Oxidase-Mediated, Ceramide-Induced Apoptosis Initiated by Diesel Particulate Matter." Pharmaceuticals 15, no. 4 (March 31, 2022): 431. http://dx.doi.org/10.3390/ph15040431.
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Air pollutants contribute to the development of diseases such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary cancer, cardiovascular problems, and some skin diseases. We recently found that a major air pollutant, diesel particulate matter (DPM), induces apoptosis in human keratinocytes by increasing a proapoptotic lipid mediator, ceramide. DPM activates nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), which stimulates sphingomyelinase, leading to an increased conversion of sphingomyelin to ceramide. Interestingly, we characterized that although NOX is a reactive oxygen species (ROS) generator, the activation of sphingomyelinases by NOX is an ROS-independent mechanism. A Korean weed, prostrate spurge Euphorbia supina Rafin (ESR), has been used for centuries as a folk medicine to treat bronchitis, hepatitis, hemorrhage, and skin inflammation. Flavonoids, terpenes and tannins are enriched in ESR, and although ESR has proven antioxidative activity, its biological activities are largely unknown. Here, we investigate whether and how ESR protects keratinocytes against DPM-mediated apoptosis. We found that ESR-extracts (ESR-Ex) protect keratinocytes from DPM-induced apoptosis by inhibiting NOX activation in keratinocytes in response to DPM. We also demonstrated that ESR-Ex suppresses NOX activation via a blockage of the aryl hydrocarbon receptor (AhR) activation-mediated transcription of neutrophil cytosolic factor 1 (NCF1)/p47phox, a subunit of NOX. Our study reveals previously uncharacterized biological activity of ESR-Ex; i.e., its inhibition of Ahr and NOX activation. Thus, because the inhibition of NOX has already been developed to treat NOX-mediated diseases, including various types of cardiovascular diseases and cancers, initiated by air pollutants and because AhR activation contributes to the development of chronic inflammatory diseases, our study provides further advantages for the medical use of ESR.
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Teng, Ru-Jeng, Jianhai Du, Scott Welak, Tongju Guan, Annie Eis, Yang Shi, and Girija G. Konduri. "Cross talk between NADPH oxidase and autophagy in pulmonary artery endothelial cells with intrauterine persistent pulmonary hypertension." American Journal of Physiology-Lung Cellular and Molecular Physiology 302, no. 7 (April 1, 2012): L651—L663. http://dx.doi.org/10.1152/ajplung.00177.2011.
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Autophagy is a process for cells to degrade proteins or entire organelles to maintain a balance in the synthesis, degradation, and subsequent recycling of cellular products. Increased reactive oxygen species formation is known to induce autophagy. We previously reported that increased NADPH oxidase (NOX) activity in pulmonary artery endothelial cells (PAEC) from fetal lambs with persistent pulmonary hypertension (PPHN) contributes to impaired angiogenesis in PPHN-PAEC compared with normal PAEC. We hypothesized that increased NOX activity in PPHN-PAEC is associated with increased autophagy, which, in turn, contributes to impaired angiogenesis in PPHN-PAEC. In the present study, we detected increased autophagy in PPHN-PAEC as shown by increased ratio of the microtubule-associated protein 1 light chain (LC3)-II to LC3-I and increased percentage of green fluorescent protein-LC3 punctate positive cells. Inhibiting autophagy by 3-methyladenine, chloroquine, and beclin-1 knockdown in PPHN-PAEC has led to decreased autophagy and increased in vitro angiogenesis. Inhibition of autophagy also decreased the association between gp91phox and p47phox, NOX activity, and superoxide generation. A nonspecific antioxidant N-acetylcysteine and a NOX inhibitor apocynin decreased autophagy in PPHN-PAEC. In conclusion, autophagy may contribute to impaired angiogenesis in PPHN-PAEC through increasing NOX activity. Our results suggest that, in PPHN-PAEC, a positive feedback relationship between autophagy and NOX activity may regulate angiogenesis.
Dissertations / Theses on the topic "Nox inhibition"
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Dakik, Hassan. "Caractérisation des NADPH oxydases et effet de leur inhibition dans les leucémies aigues myéloïdes." Thesis, Tours, 2017. http://www.theses.fr/2017TOUR3309.
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Dans le monde, 350 000 leucémies sont diagnostiquées chaque année. La rechute reste un problème majeur des leucémies aiguës myéloïdes (LAM) et le métabolisme oxydatif pourrait jouer un rôle essentiel dans la réponse au traitement. Un faible niveau des espèces réactives de l’oxygène (ROS) est associé à des propriétés des cellules souches leucémiques et la quiescence alors qu’un niveau plus élevé caractérise les leucoblastes proliférants. L’homéostasie des ROS repose sur un équilibre entre les systèmes oxydants et antioxydants. Les antioxydants sont bien documentés dans les LAM alors que les connaissances sur l’activité oxydante sont encore limitées. Dans ce travail nous avons choisi d’étudier les sept complexes NADPH oxydases (NOX) dans 25 lignées issues de LAM humaines et des LAM primaires. L’analyse des ARNm et des protéines montre des profils d’expression variables entre les lignées avec une expression plus forte des sous-unités du complexe NOX2 dans les lignées correspondant à des stades de différenciation myéloïde plus avancés. L’activité enzymatique des NOX est cependant équivalente entre les lignées. Deux inhibiteurs, DPI et VAS3947, ont été utilisés pour connaître la contribution des NOX à la production des ROS cellulaires. Alors qu’ils ont inhibé l’activité, ils ont aussi généré un stress oxydatif majeur conduisant à une diminution de la prolifération cellulaire et une forte apoptose, le DPI en augmentant les ROS mitochondriaux et VAS3047 les ROS cytoplasmiques. Afin de connaitre les sous-unités impliquées et de mieux comprendre les mécanismes, les sous-unités NOX2 et p22phox ont été inhibée par ARN interférence. Celle-ci n’ont pas affecté la prolifération mais ont montré des effets compensatoires. Nos data montrent qu’inhiber les NOX pourrait s’avérer une stratégie thérapeutique en augmentant le stress oxydatif dans les cellules leucémiques350,000 leukaemia are diagnosed each year worldwide. In acute myeloid leukaemia (AML), relapse remains a major problem and the oxidative metabolism might play a crucial role in the therapeutic response. Low level of reactive oxygen species (ROS) is associated with properties of leukemic stem cells and quiescence whereas higher level promotes leukoblasts proliferation. ROS homeostasis relies on a tightly regulated balance between the oxidant and antioxidant systems. Although the antioxidant system is extensively studied in AML, the oxidant system remains poorly documented. In this work we aimed to study the seven NADPH oxidases (NOX) complexes in 25 AML human cell lines and primary samples. NOX transcriptional and protein profiles are variable with a higher expression of NOX2 in cell lines belonging to mature differentiation stages. An equivalent level of enzymatic activity was observed across all the cell lines. To reveal the contribution of NOX to global ROS production in the cells, two NOX inhibitors, DPI and VAS3947, were then used. Although both inhibitors efficiently blocked NOX activity they unexpectedly triggered strong oxidative stress leading to reduced cell proliferation and strong apoptosis, DPI by increasing mitochondrial ROS while VAS3947 by increasing cytoplasmic ROS production. To highlight which of the subunits were involved and to understand the mechanisms, NOX2 and p22phox subunits were inhibited using shRNA strategy. These did not affect cell proliferation but revealed a compensation effect. Our data suggest that NOX inhibition might be potential therapeutic strategy by increasing oxidative stress in leukemic cells
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Ahmed, Mohamed. "Inhibition of mild steel corrosion in cooling systems by low- and non-toxic corrosion inhibitors." Thesis, University of Manchester, 2017. https://www.research.manchester.ac.uk/portal/en/theses/inhibition-of-mild-steel-corrosion-in-cooling-systems-by-low-and-nontoxic-corrosion-inhibitors(7dc2367d-7352-4ab2-85b1-39b09d6487d8).html.
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The aim of the research in this thesis was to study how environmentally friendly corrosion inhibitors for cooling water systems might be developed and used. Firstly, reduced toxicity inorganic corrosion inhibitors (i.e. nitrite/molybdate) were considered. Secondly, non-toxic inhibitors based on mono and di-basic salts of carboxylic acids were studied systematically as a function of carbon chain length. For nitrite inhibitor alone, a concentration of 7 mM NaNO2 was effective to inhibit carbon steel in chloride media of 10 mM NaCl, while 10 mM nitrite was needed in sulphate media of 3.66 mM Na2SO4. However, it was found possible to significantly reduce the concentration of nitrite by adding molybdate in synergy. This was attributed to the nitrite passivation combined with ferrous molybdate salt film pore plugging thus promoting a continuous and protective film on the material within these media. Thus, in pH 6-10 an inhibition efficiency of 97% was recorded with a mixture of 3 mM nitrite/2 mM molybdate in both chloride and sulphate media and at 25°C and 60°C. However as the solution pH decreased below pH 4 the inhibition efficiency decreased to about 47%.In the second part of the study, the use of sodium salts of carboxylic acids with different chain lengths has been investigated. In this part a summary of the performances and limitations of both mono- and di-sodium carboxylate inhibitors are presented. For mono-carboxylates, the inhibition efficiency reached a maximum value of 95% in stagnant aerated solutions at a chain length of C=4 with a critical inhibition concentration of 6 mM in 10 mM NaCl solution. However the inhibition efficiency gradually decreased as the number of carbon atoms in the chain length increased to more than 8, or less than 4, and this was in agreement with surface hydrophobicity and contact angle results. For lower chain lengths, the carboxylate anion becomes more acidic and complexing of the metal ion while for longer chain lengths, the carboxylate anion becomes less soluble and tends to micellise wherby the active groups are no longer available for surface adsorption. For di-carboxylates the inhibition efficiency improved in 10 mM NaCl at a given chain length compared with mono-carboxylates, and continued to increase to C=8 (sebacate), which achieved excellent inhibition efficiency. However, sebacate is costly so a blend with ethyl hexanoate was found to be economically favoured.
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Guan, Hua. "Investigation of wettability effects and non-aqueous scale inhibitor applications during the design of scale inhibition treatments." Thesis, Heriot-Watt University, 2004. http://hdl.handle.net/10399/335.
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Packham, Wayne. "Non-phage Inhibition Of Cheese Starter Lactococci." Connect to thesis, 2002. http://repository.unimelb.edu.au/10187/2879.
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Modern, large scale Cheddar cheese manufacture is dependent on reliable acid production by Lactococcus lactis subspecies cremoris and subspecies lactis starter cultures. Any inhibition of acid production may affect cheese quality, disrupt production schedules and reduce profitability. The presence of antibiotic residues in manufacturing milk resulting from the treatment of mastitis in lactating cattle is a potential source of starter culture inhibition. Therefore, a range of antibiotic concentrations was assessed for measurable inhibitory effects on acid production and compared to the minimum detectable concentrations by approved screening test procedures. Antibiotics were selected from formulations approved for use on lactating cattle for the treatment of mastitis. Novobiocin, lincomycin, oleandomycin and oxytetracyline HCl, all non-b-lactam antibiotics, inhibited acid production of one or more L. lactis strains at antibiotic concentrations below the detectable limit of standard screening procedures.Depending on the antibiotic, either or both the Bacillus stearothermophilus (var. calidolactis) disk assay and/or the Delvo SP assay were ineffective at detecting the antibiotics at concentrations required to inhibit the starter strains. Consequently, antibiotic residues below the detectable limits of these testing procedures could cause significant starter culture inhibition, disrupting cheese making schedules. Another potential source of starter culture inhibition is related to raw milk quality and the practice of refrigerated storage prior to processing. Previous studies differed as to whether the growth of psychrotrophic organisms would have a detrimental impact on subsequent acid production by starter bacteria employed in cheese manufacture. In this study, no inhibition of acid production by a commercial L. lactis subsp. cremoris strain was evident when grown in milk that had undergone short term temperature abuse. Antimicrobial systems native to bovine milk may also have an adverse impact on starter culture performance. The present study assessed the inhibitory effect of an activated lactoperoxidase system (LPS) on a range of L. lactis cultures. All of the strains were significantly inhibited when grown on reconstituted skim milk in the presence of an active LPS. Inhibition of acid production by strains grown on glucose was also observed, leading to further investigations to describe the inhibitory process. A non-phosphoenolpyruvate phosphotransferase (PEP/PTS) dependent glucose transport system, first observed in 1980 in one L. lactis subsp. lactis strain, was hypothesised as a link in strain variations in LPS sensitivity. However, the LPS sensitive L. lactis subsp. cremoris strains tested did not take up glucose in a PEP depleted state, most likely due to their inability to utilise arginine as an ATP generating energy source. The questions remain unanswered whether cremoris strains possess this glucose transport mechanism and whether it could contribute to strain variations in LPS sensitivity.
In a subsequent investigation, galactose phosphotransferase system (PTS) deficient L. lactis strain ATCC 7962 demonstrated log phase growth inhibition when grown on galactose in the presence of the model LPS. Previously reported LPS mediated effects on the glycolytic enzyme hexokinase do not appear to explain this result. The present study confirmed strain variability in sensitivity to the model LPS among both Lactococcus lactis subspecies lactis and subspecies cremoris strains. Further, the observation that dithiothreitol significantly alleviated the inhibition of a highly sensitive cremoris strain, implicated the involvement of sulphydryl groups as the target of the transient inhibitory factors. Data collected excluded the possibility that portions of the metabolic pathways involved in fructose and galactose metabolism are sensitive to the LPS in cells possessing PEP/PTS capability. This study also identified potential directions of further work to elucidate the mechanism(s) of LPS inhibition.
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Johansson, Hampus. "Nox2/4 inhibition in NB69 during ischemia/reperfusion : Inhibition of ROS-production using M4, M107, and M114." Thesis, Högskolan i Skövde, Institutionen för hälsa och lärande, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-17941.
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Cerebral stroke has become one of the leading causes of death and disability worldwide. During an ischemic stroke, oxygen and nutrient deprivation occurs, which combined lead to cell starvation, anoxia, and eventually cell death. However, when blood flow is restored, reperfusion damage occurs resulting in increased cell death through several mechanisms. One of the main reasons behind ischemia/reperfusion damage is oxidative stress due to elevated production of reactive oxygen species (ROS) during reperfusion. There are several proteins and processes that are thought to be involved in elevated oxidative stress and the formation of ROS during reperfusion, among which the NADPH oxidase (Nox) family is suggested to be the main contributor of ROS.To examine this hypothesis, in the present work, we inhibited activity of the Nox2 and Nox4 enzymes during ischemia/reperfusion with the Glucox Biotech AB (Sweden) inhibitors M4, M107, and M114 to evaluate whether reducing Nox activity could reduce the ischemia/reperfusion-induced cell death, hence be used as a potential stroke treatment, the cell viability was measured with MTS after ischemia/reperfusion induction and treatment with the Nox substances. We also examined the gene expression levels of the Nox enzymes Nox2 and Nox4 with qPCR after induced ischemia/reperfusion in the neuroblastoma cell line NB69.Our results showed a decrease in Nox4 gene expression after 1h ischemia/8h reperfusion and an increased expression after 1h ischemia/24h reperfusion in NB69 cells. Treatment with M114 resulted in increased cell viability after 2h ischemia/72h reperfusion. However, the toxic effect of ischemia/reperfusion-induced response was found to be inadequate, as indicated by extensive proliferation and lack of cell death. This unfavorable outcome is suggested to be excess of oxygen in medium, metabolization of L-glutamine, and effects of growth factors in the serum used in cell culture medium during the ischemic phase. Therefore, the cell culture protocol was modified to the use of PBS instead of glucose-free medium under serum-free condition during the ischemia. The altered ischemic conditions resulted in continuous reduction in cell viability at increasing ischemic time points with total cell death at 2h ischemia, suggesting applicable conditions for ischemia/reperfusion studies. Even though a conclusion could not be made about the inhibitors M4, M107, and M114 as the cell viability assay was performed under insufficient conditions; the Nox inhibitors shows high potential as future ischemic stroke treatments, which may help save lives and improve life quality for affected patients.
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Maizey, Leah. "Controlling for non-inhibitory processes in response inhibition research." Thesis, Cardiff University, 2016. http://orca.cf.ac.uk/95260/.
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Central to human adaptive behaviour is the ability to update one’s motor actions in the face of environmental changes, for which a key component is the ability to inhibit ongoing actions that are no longer appropriate. A substantial body of previous research has implicated the right inferior frontal gyrus (rIFG) and the pre-supplementary motor area (pre-SMA) as plausible sources of inhibitory control, but it remains unclear whether these regions host a specialised inhibitory control mechanism or instead support a more general system of action updating. This uncertainty stems from the limited number of studies that have controlled for non-inhibitory processes in response inhibition research. The overarching aim of this thesis was to resolve this ambiguity by studying behaviour, neurophysiology and neurochemistry during action updating in the presence and absence of inhibition. For the key experiments, detailed methods and hypotheses were pre-registered prior to data collection to minimise research bias and ensure transparent discrimination of confirmatory and exploratory inferences.
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Joubert, Jacques. "NOS inhibition of novel fluorescent polycyclic ligands / Jacques Joubert." Thesis, North-West University, 2007. http://hdl.handle.net/10394/1795.
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Baird, Agnes Anne. "Inhibition and excitation in non-propulsive mammalian smooth muscle." Thesis, University of Glasgow, 1990. http://theses.gla.ac.uk/1995/.
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Mechanisms underlying relaxation in response to inhibitory NANC nerve stimulation and putative neurotransmitters of these nerves have been examined in the guinea-pig internal anal sphincter (IAS) and compared with those in the bovine retractor penis muscle (ERP) and guinea-pig taenia caeci. Two types of techniques were employed. One which measured the effects of nerve stimulation and drugs on electrical membrane properties where intracellular microelectrode and simultaneous mechanical recording techniques were used. Drugs, for example ATP or cromakalim were applied by perfusion in the Krebs' solution, microinjection into the bath, or by hydrostatic pressure ejection. A second method assessed the underlying biochemical changes accompanying relaxation by measuring alterations in second messenger systems, for example cyclic AMP and cyclic GMP using radiomimmunoassay techniques. Electrical events were clearly an important accompaniment to mechanical inhibition in the IAS. Field stimulation (single pulse and 5 pulses at 5, 10 and 20 Hz; 0.5ms; supramaximal voltage) produced large inhibitory junction potentials of up to 15mV in amplitude which accompanied relaxation of 80% of muscle tone. Indeed, hyperpolarising electrotonic current passed into the IAS produced relaxation. The neurotransmitter which is released by field stimulation of the inhibitory nerves is probably ATP since exogenous application of purine by hydrostatic pressure ejection (5.8x10-4M; 10-55ms) produced a dose-dependent hyperpolarisation. The membrane potential change was similar in size, rate of decline and duration to the ijp. Neither hyperpolarisation nor relaxation could be achieved with the P2x-purinergic agonist, betaMeATP (10-5-10-3M) or the P2-purinergic agonist adenosine (10-3M) thus ATP was acting on the P2y-purinergic receptor. Inhibitory NANC neurotransmission was not peptidergic since VIP (10-7-10-5M), bradykinin (10-3M), neuropeptide Y (10-5M), bombesin (10-5M), leu-enkephalin (1.8x10-4M), met-enkephalin (1.8x10-5M), somatostatin (10-6-10-3M) and substance P (7.6x10-6 - 7.6x10-4M) each had no effect on the membrane potential of the IAS. There is also evidence that stimulation of -adrenoceptors by isoprenaline (10^-9 - 10^-5M) produced relaxation which was accompanied hyperpolarisation of the IAS. In all cases where hyperpolarisation and relaxation are associated in the IAS, the mechanism underlying the electrical change appeared to be an increase in K^+ conductance. Apamin (4.5 x 10^-6M) which blocks certain Ca^2+-mediated K^+ channels, antagonised the electrical and mechanical responses produced by field stimulation and ATP. Similarly, TEA (8x10^-2M), which blocks most K^+ channels, antagonised the hyperpolarisations and relaxations produced by field stimulation, ATP and isoprenaline. Indeed, the K^+ channel activator cromakalim (10^-9-10^-5M) produced hyperpolarisation and relaxation of the IAS suggesting that an increase in K^+ conductance is important in the mediation of mechanical inhibition of the IAS. Relaxation of the IAS was also produced without a significant change in membrane potential by altering the levels of cyclic nucleotides within the smooth muscle cells of the IAS. Forskolin (10^-9-10^-5M), which activates adenylate cyclase with a subsequent increase in cyclic AMP, relaxed the IAS. Similarly, sodium nitroprusside (10^-9-10^-4M) - a cyclic GMP phosphodiesterase inhibitor, and 8-bromo-cyclic GMP (10^-4M) each increased cyclic GMP and produced relaxation of the IAS. Direct measurement of cyclic nucleotide levels of the IAS showed that field stimulation (80 pulses at 8H_Z; 0.5ms; supramaximal voltage) and ATP (10^-4) elevated the cyclic AMP and cyclic GMP contents of the IAS. All other stimuli which produced slow, prolonged electrical and mechanical changes increased the level of only one cyclic nucleotide. Isoprenaline (10^-4M), cromakalim (10^-5M) and forskolin (10^-5) increased cyclic AMP content while sodium nitroprusside (10^-5M) increased the cyclic GMP content. Further investigation of other second messenger systems involved in relaxation of the IAS showed that increase in inositol phosphate turnover was not associated with stimulation of inhibitory P_2y-purinoceptors by ATP (10^-2M) in the IAS. However, an increase in inositol phosphate accumulation was produced by noradrenaline (10^-4M) and associated with contraction. A method was devised to measure the intraluminal pressure changes of the internal anal spincter in the anaesthetised guinea-pig using a Millar pressure transducer. Using this method the in vitro results were largely confirmed by this in vivo study. Basal intraluminal sphincter pressure was increased by noradrenaline acting on -adrenoceptors and decreased by isoprenaline acting on -adrenoceptors, ATP on P_2y-purinoceptors and 2-chloroadenosine on P_1-purinoceptors.
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Ibrahime, Stéphane. "Traitement cognitif d'une tâche prioritaire. Déterminants et influences de l'inhibition d'un processus concurrent non prioritaire." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS516/document.
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Alors que le traitement de nombreuses tâches ordinaires (e.g., parler à son passager, répondre à un e-mail) est en cours, l'apparition d'un stimulus important (e.g., le klaxon d'un voiture) peut nécessiter un traitement prioritaire. Paradoxalement, l'investigation de ce constat dans le champs de la psychologie expérimentale ne rend compte que très rarement compte de la possibilité d'interrompre une action en cours en vue de donner la priorité à une autre réponse motrice. Il apparait donc heuristique d'approfondir les limites et les effets de cette possibilité relativement répandue d'un point de vue écologique. Pour ce faire, nous avons articulé les problématiques inhérentes à l'interférence en double tâche et à l'inhibition motrice afin de mettre au point une série de quatre volets expérimentaux lors desquels la possibilité d'interrompre une réponse non prioritaire en vue de donner la priorité à une autre réponse motrice fut systématiquement donnée aux participants. L'ensemble des résultats convergent vers une diminution de la probabilité d'interruption de la réponse motrice non prioritaire lorsque le stimulus prioritaire apparaît tardivement et peu fréquemment. De plus, le caractère prioritaire d'une tâche motrice ne semble pas constituer un paramètre suffisant permettant d'isoler les processus correspondants de ralentissement. Corollairement, l'interruption de la réponse motrice non prioritaire ne semble pas non plus totalement prémunir le traitement de la tâche prioritaire de ralentissement notamment lorsqu'il n'est pas possible de prédire avec certitude l'apparition du stimulus correspondantWhile many ordinary task processes are ongoing (e.g., to talk with a passenger, answer an e-mail), the apparition of an important stimulus (e.g., a car honking at us) can urge a prioritized process. Paradoxically, investigations about this observation in experimental psychology's field give very few account of the possibility to interrupt a processing action in order to give all priority to another one. Thus, it seems heuristic to deepen the limits and the effects of this widespread possibility from an ecological perspective. To do so, we articulated dual task and motor inibition problematics in order to set up a serie four experimental parts where the possibility to interrupt a low priority response in order to prioritize another response was systematically given to the participants. The whole results converge toward a diminution of the capability to interrupt a low prioritized motor response when the prioritized stimulus appears belatedly and rarely. Moreover, the prioritized nature of a motor task seems to not represent a sufficient parameter alowing isolation of its processes from slowing. As a corollary, interruption of the low prioritized response seems to not prevent the prioritized process from slowing especially when corresponding stimulus apparition is not predictable
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Kornacka, Monika. "Don't stop me now… I'm ruminating ! : the distinctive impact of processing modes on emotional regulation, inhibition and attentional disengagement." Thesis, Lille 3, 2015. http://www.theses.fr/2015LIL30032.
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Les pensées répétitives négatives (PRN) sont considérées comme un des processus transdiagnostiques impliqués dans le développement, le maintien et la récurrence de plusieurs troubles psychologiques tels que les troubles de l'humeur, les troubles anxieux ou les addictions. Une des priorités dans les recherches actuelles sur les PRN est de déterminer quel processus contribue au développement et au maintien des PRN inadaptés. La littérature suggère que les déficits d’inhibition et de désengagement attentionnel sont deux facteurs potentiellement impliqués dans la récurrence des PRN. L’objectif de la présente thèse de doctorat était, premièrement de systématiser les recherches antérieures sur le lien entre les PRN et l’inhibition. Deuxièmement nous avons testé dans des études expérimentales comment l’induction des PRN affectait l’inhibition et le désengagement attentionnel.Le premier article expérimental présente une série d’études testant l’impact des PRN sur l’efficacité de l’inhibition. Le second article expérimental montre comment l’induction des PRN affecte le désengagement attentionnel. Une plus-value des études présentées dans cette thèse est la différenciation faite entre les PRN constructives (concrètes expérientielles) et non constructives (abstraites analytiques) dans la procédure d’induction.Les résultats suggèrent que les pensées analytiques abstraites interfèrent avec la régulation émotionnelle dans une situation de problème non résolu. Contrairement aux prédictions, il semble que les pensées abstraites favorisent les processus inhibiteurs et attentionnels dans le traitement des stimuli verbaux.Les résultats sont discutés selon la perspective de la théorie du mode de traitement et de la théorie de dérégulation du niveau objectif/action. Une nouvelle approche des fonctions exécutives dans les PRN est également proposée : l’hypothèse de l’allocation des ressources cognitives dirigée par le mode de traitementRepetitive negative thinking (RNT) is one of the transdiagnostic processes involved in development, recurrence and relapse of various psychological disorders, i.e. mood disorders, or anxiety disorders. One of the priorities in the current RNT research is to identify the mechanisms responsible for RNT development and maintain. RNT theory and previous research identified inhibition and attentional disengagement impairment as two potential factors of RNT recurrence.The first aim of the dissertation was to systematize previous research exploring the relation between RNT and inhibition. The second aim was to experimentally test how RNT induction affects both, inhibition and attentional disengagement. The first two chapters present RNT concept itself and a systematic literature review on the links between RNT and inhibition. The following chapters are composed of two empirical articles. The first article presents three experimental studies exploring the impact of RNT induction on inhibition efficiency. The second article tests experimentally how RNT affects attentional disengagement. An important contribution of these experimental studies lays also in testing separately constructive (concrete experiential) and unconstructive (abstract analytic) RNT processing mode.The results suggest that abstract analytic thinking impairs emotional regulation in a non-resolved problem situation – a situation predicted to activate RNT. Contrarily to the predictions, it seems that abstract analytic processing enhances inhibition and attentional performance for verbal stimuli comparing to concrete processing.These results are discussed at the theoretical level in the processing mode theory and deregulation of goal/action level perspective. We provide also methodological recommendation for the further research on the link between RNT and executive functions. Finally, we propose a new framework for the hypothesis of processing mode driven resource allocation in RNT
Books on the topic "Nox inhibition"
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McCarty, Megan, and Steven Karau. Social Inhibition. Edited by Stephen G. Harkins, Kipling D. Williams, and Jerry Burger. Oxford University Press, 2016. http://dx.doi.org/10.1093/oxfordhb/9780199859870.013.9.
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Social inhibition is the tendency for behaviors that are exhibited when one is alone to be minimized in the presence of others. Despite the long tradition of research investigating the effects of social presence on behavior, research on social inhibition does not constitute a cohesive literature. This chapter integrates social inhibition research from different traditions, focusing on helping behaviors, emotional expression, and behaviors that elicit social disapproval. We discuss moderators and processes that explain when and why social inhibition occurs: arousal, ambiguity, pluralistic ignorance, diffusion of responsibility, feelings of capability, evaluation apprehension, and confusion of responsibility. Key distinctions between social inhibition and related concepts are presented, helping to establish social inhibition as a central social influence concept. We conclude with an analysis of why social inhibition research has not formed a cohesive literature, and we hope that our review of social inhibition facilitates the integration of future research on the topic.
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M, Dowsett, ed. Aromatase inhibition: Then, now, and tomorrow. London: Parthenon Pub. Group, 1994.
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Howardell, Maynard J. Cox-2 Inhibitor Research. Nova Science Publishers, Incorporated, 2006.
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Howardell, Maynard J. Trends in Cox-2 Inhibitor Research. Nova Science Publishers, 2006.
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Mease, Philip. Biologic treatments for psoriatic arthritis apart from TNF inhibition. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198737582.003.0030.
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Psoriatic arthritis (PsA) is an immunologically mediated inflammatory disease characterized by arthritis, enthesitis, dactylitis, spondylitis, and psoriasis. Prior to the introduction of targeted biologic medications, such as TNF inhibitors, the ability to control disease activity was limited, with only modest effects noted with traditional oral medications such as methotrexate and sulfasalazine. The introduction of TNF inhibitors substantially changed the outlook of PsA patients, yielding significant response in all relevant clinical domains and demonstrating the ability to inhibit progressive structural damage of joints. However, not all patients responded to these agents and many patients displayed initial response which waned over time, partly due to immunogenicity (development of antibodies which blocked full therapeutic effect of the biologic protein), or because of tolerability and side effect issues. Thus, it has been important to develop new medicines which target other key cytokines and immunologic pathways. Several medicines with a different mechanism of action have been approved or are in development for the treatment of PsA. Ustekinumab inhibits both IL12 and IL23 and thus is felt to work in both the TH1 and TH7 pathways of inflammation. The oral medicine apremilast inhibits phosphodiesterase 4, thus modulating the cyclic AMP pathway in immunologic cells, yielding an anti-inflammatory effect. Both of these medicines have been approved for the treatment of PsA as well as psoriasis. An emerging group of therapies, the IL17 inhibitors, has demonstrated significant effectiveness in psoriasis and PsA and one of these, Secukinumab, has been approved for psoriasis, PsA, and AS. Other medicines in development include the co-stimulatory blockade agent, abatacept, oral Janus Kinase (JAK) inhibitors, and an emerging group of therapies which inhibit IL23. As modulators of immune cell function, these agents have the potential to increase risk for infection, as well as other side effects. These must be discussed with the patient and considered when determining overall risk benefit analysis regarding their use. The emergence of medicines with a different mechanism of action than TNF inhibition has broadened and strengthened our ability to effectively treat PsA.
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Levi, Marcel, and Marcus J. Schultz. Disseminated intravascular coagulation in the critically ill. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0270.
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Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic intravascular activation of coagulation, leading to widespread deposition of fibrin in the circulation. In patients with DIC, a variety of altered coagulation parameters may be detectable, such as thrombocytopenia, prolonged global coagulation times, reduced levels of coagulation inhibitors, or high levels of fibrin split products. There is not a single test, however, that is sufficiently accurate to establish or reject a diagnosis of DIC. Nevertheless, a combination of widely available tests may be helpful in making the diagnosis of DIC and can also be helpful in guiding the selection of DIC patients that require specific, often expensive, interventions in the coagulation system. Recent knowledge on important pathogenetic mechanisms that may lead to DIC has resulted in novel preventive and therapeutic approaches to patients with DIC. Strategies aimed at the inhibition of coagulation activation may theoretically be justified and have been found beneficial in experimental and clinical studies. These strategies comprise inhibition of tissue factor-mediated activation of coagulation or restoration of physiological anticoagulant pathways.
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Bueno, Héctor, and José A. Barrabés. Non-ST-segment elevation acute coronary syndromes. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199687039.003.0046.
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Non-ST-segment elevation acute coronary syndromes are life-threatening disorders, usually caused by acute coronary thrombosis and subsequent myocardial ischaemia, presenting without persistent ST-segment elevation in the initial electrocardiogram. According to the occurrence of myocardial necrosis, non-ST-segment elevation acute coronary syndromes are divided into non-ST-segment myocardial infarction or unstable angina. The management of non-ST-segment elevation acute coronary syndromes requires an early diagnosis and risk stratification, urgent hospitalization, monitoring, and medical treatment, including antithrombotic therapy with dual antiplatelet therapy (aspirin plus one P2Y12 inhibitor) and parenteral anticoagulation, anti-ischaemic treatment, and preventative therapies. After the initial medical therapy is established, an invasive strategy, consisting of coronary angiography with coronary revascularization (either percutaneous coronary intervention or coronary bypass graft surgery), as appropriate, should be decided. The timing of the invasive strategy should be adjusted, according to the patient’s risk. Given the high event rate of patients with non-ST-segment elevation acute coronary syndromes after hospital discharge, an aggressive long-term preventative therapy should be put in place to improve prognosis.
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Bueno, Héctor, and José A. Barrabés. Non-ST-segment elevation acute coronary syndromes. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199687039.003.0046_update_001.
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Non-ST-segment elevation acute coronary syndromes are life-threatening disorders, usually caused by acute coronary thrombosis and subsequent myocardial ischaemia, presenting without persistent ST-segment elevation in the initial electrocardiogram. According to the occurrence of myocardial necrosis, non-ST-segment elevation acute coronary syndromes are divided into non-ST-segment myocardial infarction or unstable angina. The management of non-ST-segment elevation acute coronary syndromes requires an early diagnosis and risk stratification, urgent hospitalization, monitoring, and medical treatment, including antithrombotic therapy with dual antiplatelet therapy (aspirin plus one P2Y12 inhibitor) and parenteral anticoagulation, anti-ischaemic treatment, and preventative therapies. After the initial medical therapy is established, an invasive strategy, consisting of coronary angiography with coronary revascularization (either percutaneous coronary intervention or coronary bypass graft surgery), as appropriate, should be decided. The timing of the invasive strategy should be adjusted, according to the patient’s risk. Given the high event rate of patients with non-ST-segment elevation acute coronary syndromes after hospital discharge, an aggressive long-term preventative therapy should be put in place to improve prognosis.
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Bueno, Héctor, and José A. Barrabés. Non-ST-segment elevation acute coronary syndromes. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199687039.003.0046_update_002.
Full textAbstract:
Non-ST-segment elevation acute coronary syndromes are life-threatening disorders, usually caused by acute coronary thrombosis and subsequent myocardial ischaemia, presenting without persistent ST-segment elevation in the initial electrocardiogram. According to the occurrence of myocardial necrosis, non-ST-segment elevation acute coronary syndromes are divided into non-ST-segment myocardial infarction or unstable angina. The management of non-ST-segment elevation acute coronary syndromes requires an early diagnosis and risk stratification, urgent hospitalization, monitoring, and medical treatment, including antithrombotic therapy with dual antiplatelet therapy (aspirin plus one P2Y12 inhibitor) and parenteral anticoagulation, anti-ischaemic treatment, and preventative therapies. After the initial medical therapy is established, an invasive strategy, consisting of coronary angiography with coronary revascularization (either percutaneous coronary intervention or coronary bypass graft surgery), as appropriate, should be decided. The timing of the invasive strategy should be adjusted, according to the patient’s risk. Given the high event rate of patients with non-ST-segment elevation acute coronary syndromes after hospital discharge, an aggressive long-term preventative therapy should be put in place to improve prognosis.
Book chapters on the topic "Nox inhibition"
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Daly, Hesham El, and Uwe M. Martens. "Telomerase Inhibition and Telomere Targeting in Hematopoietic Cancer Cell Lines with Small Non-Nucleosidic Synthetic Compounds (BIBR1532)." In Telomerase Inhibition, 47–60. Totowa, NJ: Humana Press, 2007. http://dx.doi.org/10.1007/978-1-60327-070-0_6.
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Perez, L. A., and D. F. Zidovec. "Scale Control by Using a New Non-Phosphorus, Environmentally Friendly Scale Inhibitor." In Mineral Scale Formation and Inhibition, 47–61. Boston, MA: Springer US, 1995. http://dx.doi.org/10.1007/978-1-4899-1400-2_5.
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Gaede, Andrea H., and Paul M. Pilowsky. "Excitatory Responses to Microinjection of Glutamate Depend on Dose Not Volume: A Meta-Analysis of Studies in Rat RVLM." In Stimulation and Inhibition of Neurons, 37–46. Totowa, NJ: Humana Press, 2012. http://dx.doi.org/10.1007/978-1-62703-233-9_3.
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Cooney, R. V., A. A. Franke, L. J. Mordan, P. J. Harwood, V. Hatch-Pigott, and L. J. Custer. "Tocopherol Inhibition of NO2-Mediated Nitrosation." In Nitrosamines and RelatedN-Nitroso Compounds, 317–19. Washington, DC: American Chemical Society, 1994. http://dx.doi.org/10.1021/bk-1994-0553.ch028.
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Patrono, C., P. Patrignani, M. R. Panara, F. Cipollone, G. Santini, M. G. Sciulli, M. T. Rotondo, R. Padovano, and M. Di Giamberardino. "COX-2 expression and inhibition in human monocytes." In Improved Non-Steroid Anti-Inflammatory Drugs: COX-2 Enzyme Inhibitors, 121–31. Dordrecht: Springer Netherlands, 1996. http://dx.doi.org/10.1007/978-94-010-9029-2_7.
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Grigorescu, Cosmin, Nicolai Petkov, and Michel A. Westenberg. "Improved Contour Detection by Non-classical Receptive Field Inhibition." In Biologically Motivated Computer Vision, 50–59. Berlin, Heidelberg: Springer Berlin Heidelberg, 2002. http://dx.doi.org/10.1007/3-540-36181-2_5.
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Kogej, Tina, Michael H. Wheeler, Tea Lanišnik Rižner, and Nina Gunde-Cimerman. "Inhibition of DHN-Melanin Biosynthesis by Tricyclazole in Hortaea Werneckii." In Non-Conventional Yeasts in Genetics, Biochemistry and Biotechnology, 143–48. Berlin, Heidelberg: Springer Berlin Heidelberg, 2003. http://dx.doi.org/10.1007/978-3-642-55758-3_22.
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Keppler, Bernhard K., and Ellen A. Vogel. "Overview of Tumor-Inhibiting Non-Platinum Compounds." In Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy 2, 253–68. Boston, MA: Springer US, 1996. http://dx.doi.org/10.1007/978-1-4899-0218-4_24.
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Boggio, Lisa N., and Mindy L. Simpson. "Non-Genetic Risk Factors for Inhibitor Development." In Current and Future Issues in Hemophilia Care, 84–88. Oxford, UK: Wiley-Blackwell, 2011. http://dx.doi.org/10.1002/9781119979401.ch17.
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Dembinska-Kiec, A., M. Burchert, J. Hartwich, R. Gryglewski, and B. A. Peskar. "A Neutrophil-Derived No-Synthase (NOS) Inhibitor." In Mediators in the Cardiovascular System: Regional Ischemia, 163–68. Basel: Birkhäuser Basel, 1995. http://dx.doi.org/10.1007/978-3-0348-7346-8_23.
Full textConference papers on the topic "Nox inhibition"
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Devarakonda, Maruthi, Russell Tonkyn, Diana Tran, Jong Lee, and Darrell Herling. "Modeling Species Inhibition of NO Oxidation in Urea-SCR Catalysts for Diesel Engine NOx Control." In ASME 2010 Internal Combustion Engine Division Fall Technical Conference. ASMEDC, 2010. http://dx.doi.org/10.1115/icef2010-35054.
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Urea-selective catalytic reduction (SCR) catalysts are regarded as the leading NOx aftertreatment technology to meet the 2010 NOx emission standards for on-highway vehicles running on heavy-duty diesel engines. However, issues such as low NOx conversion at low temperature conditions still exist due to various factors, including incomplete urea thermolysis, inhibition of SCR reactions by hydrocarbons and H2O. We have observed a noticeable reduction in the standard SCR reaction efficiency at low temperature with increasing water content. We observed a similar effect when hydrocarbons are present in the stream. This effect is absent under fast SCR conditions where NO ∼ NO2 in the feed gas. As a first step in understanding the effects of such inhibition on SCR reaction steps, kinetic models that predict the inhibition behavior of H2O and hydrocarbons on NO oxidation are presented in the paper. A one-dimensional SCR model was developed based on conservation of species equations and was coded as a C-language S-function and implemented in Matlab/Simulink environment. NO oxidation and NO2 dissociation kinetics were defined as a function of the respective adsorbate’s storage in the SCR catalyst. The corresponding kinetic models were then validated on temperature ramp tests that showed good match with the test data.
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Jiang, Xu-Guang, Jian-Hua Yan, Xiang-Pai Li, Bing-Chi Liu, Sheng-Yong Lu, Yong Chi, and Ke-Fa Cen. "Experimental Study of HCl Emission and Removal on Incinerating of Typical MSW Components in Fluidized Bed." In 18th International Conference on Fluidized Bed Combustion. ASMEDC, 2005. http://dx.doi.org/10.1115/fbc2005-78045.
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As incineration is widely used in the disposal of municipal solid waste (MSW), the relation of harmful gas HCl, SOx, NOx, CO from incineration should not be neglected. In order to study the characteristics of HCl emission and removal during MSW incineration, several kinds of typical MSW components are selected for experiments in a Φ 150mm fluidized bed test rig. The effect of temperature on Cl → HCl conversion rate is discussed; the influence of HCl concentration on emission of NO, SO2 during incineration is analyzed. Finally the effect of Ca-based sorbents on dechlorination is also discussed. Results show that The Cl → HCl conversion rate varies obviously as temperature increases. With the increase of HCl concentration, the concentration of NO decreases, The inhibition of HCl to NOx is very obvious. At the temperature of 920 °C the capture of SO2 become more than at the temperature of 880°C. The type and amount of Ca-based sorbents can affect dechlorination rate.
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Liu, Shie-chau, Reem Alomran, Fang Quan, Milton Merchant, Steffan Zollner, Anna Kruschinski, Laurence Recht, and Martin Brown. "Abstract 4382: Inhibition of SDF-1 (CXCL12) using the Spiegelmer NOX-A12 markedly delays the recurrence of ENU-induced rat brain tumors following irradiation." In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-4382.
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Smith, Michael A., Christopher D. Depcik, John W. Hoard, Stanislav V. Bohac, and Dionissios N. Assanis. "Modeling of SCR NH3 Storage in the Presence of H2O." In ASME 2011 Internal Combustion Engine Division Fall Technical Conference. ASMEDC, 2011. http://dx.doi.org/10.1115/icef2011-60233.
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Diesel engines offer excellent fuel economy, but this comes at the expense of higher emissions of nitrogen oxides (NOx) and Particulate Matter (PM). To meet current emissions standards, diesel engines require aftertreatment devices. Concepts using combinations of catalysts are becoming more common in aftertreatment systems to reduce the cost and size of these aftertreatment systems. One combination is an LNT-SCR system where the LNT releases NH3 during a regeneration to be used by the SCR catalyst for further NOx reduction. This involves rich-lean cycling of the exhaust stream, which alters species concentrations in the exhaust. Most notably H2O and CO2 levels can vary from 4%–14% during lean-rich cycling. An investigation was performed using multiple Temperature Programmed Desorption (TPD) experiments to determine how H2O and CO2 affect NH3 storage capacity of an Fe-based zeolite SCR catalyst. It was determined that H2O and CO2 inhibit NH3 storage capacity of the SCR catalyst. This inhibition has shown a linear dependence on H2O and CO2 concentration at constant temperature. It was also determined that H2O is a much stronger inhibitor of NH3 storage capacity then CO2. Additional Temperature Programmed Desorption (TPD) experiments, were run where H2O and CO2 concentration (0%, 6%, and 10%) and the initial storage temperature (200°C, 250°C, 300°C, 350°C) were varied. Results suggest the addition of a reaction that creates competition for active sites on the catalyst between H2O and NH3. The additional reaction allows H2O and NH3 to be stored on open catalytic sites and has improved model accuracy by accounting for large changes in H2O, CO2, and temperature.
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Liu, Shie-Chau, Reem Alomran, Jason Stafford, Milton Merchant, Taichang Jang, Stefan Zollner, Anna Kruschinski, Laurence Recht, and J. Martin Brown. "Abstract 385: Inhibition of recurrences of experimental brain tumors after irradiation by blocking the activity of SDF-1 (CXCL12) using the Spiegelmer® NOX-A12." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-385.
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Zboralski, Dirk, Lisa Bauer, Dirk Eulberg, and Axel Vater. "Abstract 1473: CXCL12 inhibition with NOX-A12 (olaptesed pegol) increases T-cell infiltration in tumor-stroma spheroids and synergizes with PD-1 immune checkpoint blockade." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-1473.
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Fuhrer, G., M. J. Gallimore, W. Heller, and H. E. Hoffmeister. "REDUCED β-FXIIa-INHIBITION CAPACITY IN KEPARINIZED PLASMA SAMPLES." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643298.
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It has been shown by our group that B-FXIIa-inhibi-tion was reduced in platelet rich plasma. To investigate the effect of heparin on B-FXIIa-inhibition, kallikrein inhibition and C1-esterase inhibition high and low molecular weight heparin preparations were added to plasma samples. Using high molecular weight heparin from 0 to 5 anti Xa/ml a reduction in B-FXIIa-inhibition was seen from 103% to 59%.These effects were abolished by the addition of protamine chloride. No changes of kallikrein inhibition and C1-esterase-inhibition were observed in heparinized plasma samples After the addition of a low molecular heparin preparation to plasma samples, the reduction of B-FXIIa-inhibition was markedly decreased. The levels of the Hage-man fragment inhibitor capacity were lowered to 22% compared to initial values of 91%. The antagonization of heparin normalized these values. No reduction in kallikrein inhibition and C1-esterase inhibition were found in these samples because in all three assays C1-inhibitor activity is analysed, purified C1-inhibitor was added to buffer containing several heparin concentration ( see table )These results suggest that the inhibition of B-FXIIa is markedly affected by heparin whilst no changes were seen in the inhibition capacity for C1-esterase and kallikrein.
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Al-Arfaj, Mohammed K. "An Experimental Study on Shale-Fluid Interactions to Help Drill Stable Shale Formations." In International Petroleum Technology Conference. IPTC, 2022. http://dx.doi.org/10.2523/iptc-22113-ms.
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Abstrac Drilling stable boreholes in shale formations is a challenging task due to the potential interactions of clay-rich shales with aqueous phase of drilling fluids. The objective of this paper is to look into some testing techniques utilized to characterize shale rock samples and assess the reactivity, recommend a strategy and best practices to overcome the wellbore instability problems when drilling shale formations. Wellbore instability associated with drilling shale formations is a major source of non-productive time in drilling operations. Inhibiting shale-fluid interactions and minimizing the scope of time-dependent shale problems are essential to mitigate this challenge. The solution is of two-fold: mechanical and chemical. This paper addresses the chemical aspects of the problem and recommends a novel type and combination of shale inhibitors to use in drilling. Different testing techniques were employed to assess the shale reactivity with different types of drilling fluids. After characterizing the shale samples in terms of mineralogy, petrography and inhibition testing has been carried out to reveal the reactivity extent of the shales. Dispersion test predict the shale-fluid interactions to help in optimizing the drilling fluid formulations to drill those shale formations. Two shale inhibitor combinations were tested against shale samples with different characteristics and clay mineralogy to develop a semi-universal type of inhibitive drilling fluid formulation.
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Lian, Tiangan, Gregory E. Gdowski, Phillip D. Hailey, and Raul B. Rebak. "Crevice Repassivation Potential of Alloy 22 in High-Nitrate Dust Deliquescence Type Environments." In ASME 2007 Pressure Vessels and Piping Conference. ASMEDC, 2007. http://dx.doi.org/10.1115/pvp2007-26164.
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The nitrate ion (NO3−) is an inhibitor for crevice corrosion of Alloy 22 (N06022) in chloride (Cl−) aqueous solutions. Naturally formed electrolytes may contain both chloride and nitrate ions. The higher the ratio R = [NO3−]/[Cl−] in the solution the stronger the inhibition of crevice corrosion. Atmospheric desert dust contains both chloride and nitrate salts, generally based on sodium (Na+) and potassium (K+). Some of these salts may deliquescence at relatively low humidity at temperatures on the order of 150°C and higher. The resulting deliquescent brines are highly concentrated and especially rich in nitrate. Electrochemical tests have been performed to explore the anodic behavior of Alloy 22 in high chloride high nitrate electrolytes at temperatures as high as 150°C at ambient atmospheres. Naturally formed brines at temperatures higher than 120°C do not induce crevice corrosion in Alloy 22 because they contain high levels of nitrate. The inhibitive effect of nitrate on crevice corrosion is still active for temperatures higher than 100°C.
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Ng, Jun Hong Clarence, Tariq Almubarak, and Hisham A. Nasr-El-Din. "Stems as Natural, Green, Non-Toxic Corrosion Inhibitors." In SPE/IADC Middle East Drilling Technology Conference and Exhibition. SPE, 2021. http://dx.doi.org/10.2118/202113-ms.
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Abstract Corrosion during acid treatments causes severe damage to the tubulars and downhole equipment. Consequently, this leads to an increase in expenditure to maintain well production rates and well integrity. NACE estimates the cost of corrosion costs to be roughly 1.372 billion USD annually to the industry, making corrosion control extremely important. Therefore, corrosion inhibitors must be included in any acid treatment formulation. This work aims to develop environmentally friendly and non-toxic corrosion inhibitors that can work in the harsh oilfield conditions. Samples of 10 different stems were tested as sources of potential corrosion inhibitors. To determine the inhibition effectiveness of the different samples, N-80 coupons were exposed to 15 wt% HCl solutions at temperatures between 77-200 °F with 2 wt% of each sample for 6 hours. In addition, a control solution containing no corrosion inhibitor was used to establish a corrosion rate for a base case. At a concentration of 2 wt%, sample 1, 2, and 3 were found to perform the best, exhibiting 94.4% to 99.9% corrosion inhibition efficiency at 77°F. Sample 8 was observed to perform the worst with a corrosion inhibition efficiency of 57.3%. At 150°F, the corrosion rate of sample 1 was found to be 0.0275 lb/ft2, while that of sample 2 was 0.0171 lb/ft2. At this temperature, sample 3 did not perform well, exhibiting a corrosion rate of 0.155 lb/ft2 and thus was not tested at higher temperatures. At 200°F, the addition of a corrosion inhibitor intensifier resulted in a corrosion rate of 0.0136 lb/ft2 for sample 1 and 0.00878 lb/ft2 for sample 2. These results show that a naturally occurring, green, non-toxic corrosion inhibitor can be developed from these stems and can comfortably pass the industry requirement for low carbon steel. Currently used corrosion inhibitors are associated with environmental concerns and severe health risks. Recent developments in corrosion inhibition technology successfully tackled the environmental concerns, but still faces issues with toxicity and performance at high temperatures. The results in this work share two new naturally occurring, green, non-toxic, high-temperature stable corrosion inhibitors that can be developed from stems and can successfully protect the tubular during acid treatments.
Reports on the topic "Nox inhibition"
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Lance, Richard, and Xin Guan. Variation in inhibitor effects on qPCR assays and implications for eDNA surveys. Engineer Research and Development Center (U.S.), August 2021. http://dx.doi.org/10.21079/11681/41740.
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Aquatic environmental DNA (eDNA) surveys are sometimes impacted by polymerase chain reaction (PCR) inhibitors. We tested varying concentrations of different inhibitors (humic, phytic, and tannic acids; crude leaf extracts) for impacts on quantitative PCR (qPCR) assays designed for eDNA surveys of bighead and silver carp (Hypophthalmichthys nobilis and Hypophthalmichthys molitrix). We also tested for inhibition by high concentrations of exogenous DNA, hypothesizing that DNA from increasingly closely related species would be increasingly inhibitory. All tested inhibitors impacted qPCR, though only at very high concentrations — likely a function, in part, of having used an inhibitor-resistant qPCR solution. Closer phylogenetic relatedness resulted in inhibition at lower exogenous DNA concentrations, but not at relatively close phylogenetic scales. Inhibition was also influenced by the qPCR reporter dye used. Importantly, different qPCR assays responded differently to the same inhibitor concentrations. Implications of these results are that the inclusion of more than one assay for the same target taxa in an eDNA survey may be an important countermeasure against false negatives and that internal positive controls may not, in the absence of efforts to maximize inhibition compatibility, provide useful information about the inhibition of an eDNA assay.
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Friedman, Haya, Chris Watkins, Susan Lurie, and Susheng Gan. Dark-induced Reactive Oxygen Species Accumulation and Inhibition by Gibberellins: Towards Inhibition of Postharvest Senescence. United States Department of Agriculture, December 2009. http://dx.doi.org/10.32747/2009.7613883.bard.
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Dark-induced senescence could pose a major problem in export of various crops including cuttings. The assumption of this work was that ROS which is increased at a specific organelle can serve as a signal for activation of cell senescence program. Hormones which reduce senescence in several crops like gibberellic acid (GA) and possibly cytokinin (CK) may reduce senescence by inhibiting this signal. In this study we worked on Pelargonium cuttings as well as Arabidopsis rosette. In Pelargonium the increase in ROS occurred concomitantly with increase in two SAGs, and the increase persisted in isolated chloroplasts. In Arabidopsis we used two recentlydeveloped technologies to examine these hypotheses; one is a transcriptome approach which, on one hand, enabled to monitor expression of genes within the antioxidants network, and on the other hand, determine organelle-specific ROS-related transcriptome footprint. This last approach was further developed to an assay (so called ROSmeter) for determination of the ROS-footprint resulting from defined ROS stresses. The second approach involved the monitoring of changes in the redox poise in different organelles by measuring fluorescence ratio of redox-sensitive GFP (roGFP) directed to plastids, mitochondria, peroxisome and cytoplasm. By using the roGFP we determined that the mitochondria environment is oxidized as early as the first day under darkness, and this is followed by oxidation of the peroxisome on the second day and the cytoplast on the third day. The plastids became less oxidized at the first day of darkness and this was followed by a gradual increase in oxidation. The results with the ROS-related transcriptome footprint showed early changes in ROS-related transcriptome footprint emanating from mitochondria and peroxisomes. Taken together these results suggest that the first ROS-related change occurred in mitochondria and peroxisomes. The analysis of antioxidative gene’s network did not yield any clear results about the changes occurring in antioxidative status during extended darkness. Nevertheless, there is a reduction in expression of many of the plastids antioxidative related genes. This may explain a later increase in the oxidation poise of the plastids, occurring concomitantly with increase in cell death. Gibberellic acid (GA) prevented senescence in Pelargonium leaves; however, in Arabidopsis it did not prevent chlorophyll degradation, but prevented upregulation of SAGs (Apendix Fig. 1). Gibberellic acid prevented in Pelargonium the increase in ROS in chloroplast, and we suggested that this prevents the destruction of the chloroplasts and hence, the tissue remains green. In Arabidopsis, reduction in endogenous GA and BA are probably not causing dark-induced senescence, nevertheless, these materials have some effect at preventing senescence. Neither GA nor CK had any effect on transcriptome footprint related to ROS in the various organelles, however while GA reduced expression of few general ROS-related genes, BA mainly prevented the decrease in chloroplasts genes. Taken together, GA and BA act by different pathways to inhibit senescence and GA might act via ROS reduction. Therefore, application of both hormones may act synergistically to prevent darkinduced senescence of various crops.
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Shahak, Yosepha, and Donald R. Ort. Physiological Bases for Impaired Photosynthetic Performance of Chilling-Sensitive Fruit Trees. United States Department of Agriculture, May 2001. http://dx.doi.org/10.32747/2001.7575278.bard.
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Chilling-sensitivity is an important agricultural problem in both the U.S. and Israel. Most research attention has focused so far on herbaceous crop plants, even though the problem is also acute in the fruit tree industry. Under BARD funding we made substantial progress in identifying the mechanisms involved in the disruption of photosynthesis following a chill in mango. Our investigation with fruit trees has been substantially accelerated by drawing on our knowledge and experience with herbaceous crops. The four original research objectives, focused or discovering the underlying mechanisms of chill-induced inhibition of photosynthesis in fruit trees, and the main achievements are listed below. [1] Separating stomatal from non-stomatal components of chilling on photosynthesis in fruit trees. We found evidence that the dark chill-induced inhibition of photosynthesis in mango was E combination of both stomatal and mesophyll components. [2] Differentiating photo damage from light-induced photo protection of photosystem II (PSII). Dark chilling exacerbate high light photoinhibition, as a result of primary inhibition in the carbor reduction cycle. Nevertheless, in Israeli orchards we observed chronic photoinhibition of PSII photochemistry in the winter. This photo damage was reversible over a few days if sunlight was attenuated with filters or night temperature rose. Practical implications of this finding deserve further investment. Additional achievement was the development of a new biophysical tool to study macro-structural changes of LHCII particles in intact, attached leaves. [3] Determine the role of oxidative stress in the dark-chilling-induced inhibition, with emphasis on oxygen radical scavenging, lipid peroxidation and redox-controlled carbon-cycle enzymes. We found an increase in lipid peroxidation following a dark chill, and partial protective effects or an antioxidant. However, the photoinhibition observed in mango orchards in Israel during the winter did not appear to be a general oxidative stress. [4] Investigate whether chilling interferes with the diurnal and circadian rhythm of gene expression of key photosynthetic proteins as has been shown for chilling-sensitive crop plants. The results indicated that most of the circadian rhythm in photosynthesis was due to reduced lea: internal CO2 concentrations during the subjective night, as a result of rhythmic stomatal closure Chilling-induced interference with circadian timing in mango, does not play the central role in chilling inhibition of photosynthesis that has previously been demonstrated in certain chilling sensitive herbaceous plants. Practical implications of the research achievements are feasible, but require few more years of research.
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Horwitz, Benjamin A., and Barbara Gillian Turgeon. Fungal Iron Acquisition, Oxidative Stress and Virulence in the Cochliobolus-maize Interaction. United States Department of Agriculture, March 2012. http://dx.doi.org/10.32747/2012.7709885.bard.
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Our project focused on genes for high affinity iron acquisition in Cochliobolus heterostrophus, a necrotrophic pathogen of maize, and their intertwined relationship to oxidative stress status and virulence of the fungus on the host. An intriguing question was why mutants lacking the nonribosomal peptide synthetase (NRPS) gene (NPS6) responsible for synthesis of the extracellular siderophore, coprogen, are sensitive to oxidative stress. Our overall objective was to understand the mechanistic connection between iron stress and oxidative stress as related to virulence of a plant pathogen to its host. The first objective was to examine the interface where small molecule peptide and reactive oxygen species (ROS) mechanisms overlap. The second objective was to determine if the molecular explanation for common function is common signal transduction pathways. These pathways, built around sensor kinases, response regulators, and transcription factors may link sequestering of iron, production of antioxidants, resistance to oxidative stress, and virulence. We tested these hypotheses by genetic manipulation of the pathogen, virulence assays on the host plant, and by following the expression of key fungal genes. An addition to the original program, made in the first year, was to develop, for fungi, a genetically encoded indicator of redox state based on the commercially available Gfp-based probe pHyper, designed for animal cell biology. We implemented several tools including a genetically encoded indicator of redox state, a procedure to grow iron-depleted plants, and constructed a number of new mutants in regulatory genes. Lack of the major Fe acquisition pathways results in an almost completely avirulent phenotype, showing how critical Fe acquisition is for the pathogen to cause disease. Mutants in conserved signaling pathways have normal ability to regulate NPS6 in response to Fe levels, as do mutants in Lae1 and Vel1, two master regulators of gene expression. Vel1 mutants are sensitive to oxidative stress, and the reason may be underexpression of a catalase gene. In nps6 mutants, CAT3 is also underexpressed, perhaps explaining the sensitivity to oxidative stress. We constructed a deletion mutant for the Fe sensor-regulator SreA and found that it is required for down regulation of NPS6 under Fe-replete conditions. Lack of SreA, though, did not make the fungus over-sensitive to ROS, though the mutant had a slow growth rate. This suggests that overproduction of siderophore under Fe-replete conditions is not very damaging. On the other hand, increasing Fe levels protected nps6 mutants from inhibition by ROS, implying that Fe-catalyzed Fenton reactions are not the main factor in its sensitivity to ROS. We have made some progress in understanding why siderophore mutants are sensitive to oxidative stress, and in doing so, defined some novel regulatory relationships. Catalase genes, which are not directly related to siderophore biosynthesis, are underexpressed in nps6 mutants, suggesting that the siderophore product (with or without bound Fe) may act as a signal. Siderophores, therefore, could be a target for intervention in the field, either by supplying an incorrect signal or blocking a signal normally provided during infection. We already know that nps6 mutants cause smaller lesions and have difficulty establishing invasive growth in the host. Lae1 and Vel1 are the first factors shown to regulate both super virulence conferred by T-toxin, and basic pathogenicity, due to unknown factors. The mutants are also altered in oxidative stress responses, key to success in the infection court, asexual and sexual development, essential for fungal dissemination in the field, aerial hyphal growth, and pigment biosynthesis, essential for survival in the field. Mutants in genes encoding NADPH oxidase (Nox) are compromised in development and virulence. Indeed the triple mutant, which should lack all Nox activity, was nearly avirulent. Again, gene expression experiments provided us with initial evidence that superoxide produced by the fungus may be most important as a signal. Blocking oxidant production by the pathogen may be a way to protect the plant host, in interactions with necrotrophs such as C. heterostrophus which seem to thrive in an oxidant environment.
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Sisler, Edward C., Raphael Goren, and Akiva Apelbaum. Controlling Ethylene Responses in Horticultural Crops at the Receptor Level. United States Department of Agriculture, October 2001. http://dx.doi.org/10.32747/2001.7580668.bard.
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Ethylene is a plant hormone that controls many plant responses, such as growth, senescence, ripening, abscission and seed germination. Recently, 1-methy- cyclopropene (1-MCP), was shown to bind to ethylene receptor for a certain period of time and prevent ethylene action. The objectives of this research were to synthesize analogues of 1-MCP and test their potency to block the ethylene receptor and inhibit ethylene action. During the course of this project, procedures for synthesis and shipment of the cyclopropene compounds were developed as well assay procedures for each compound were worked out. Thirteen new compounds were synthesized. All of them are structural analogues of 1-MCP, with substitution in the 1-position and a side chain containing 2 to 10 carbons. After preliminary studies, nine promising compounds were selected for in-depth study. The potency of the compounds to inhibit ethylene action was tested on a wide scope of systems like: climacteric fruits (banana, avocado and tomato), the triple response (etiolated peas), and leaf abscission (citrus). As the putative inhibitors are suspected to compete for the site of binding and a competitive type of inhibition could be considered, a high concentration of ethylene (300 m1.L-1) was used to induce ripening and other physiological processes. The tests were conducted under extreme conditions which hasten ripening like treatment and storage at 22 to 25oC. There were fluctuations in the responses as related to the concentrations of the inhibitors. Some required much higher concentration to exert the same effect, while some, when applied at the same concentration, blocked the receptor for a longer period of time than the others. Some fruits and other plant organs responded differently to the same inhibitor, indicating differences in characteristics and availability of the ethylene receptors in the various tissues. The potency of the putative inhibitors was found to be greatly affected by their molecular structural and size. In addition, it was found that treatment with the inhibitor should be given before the onset of ethylene action In the case of fruit, treatment should be carried out before the pre-climacteric stage. Simultaneous treatment with ethylene and the inhibitors reduced the inhibitors' effect. The relationship between ethylene and the inhibitors is of a non-competitive nature. All the fruits treated with the putative inhibitors resumed normal ripening after recovery from the inhibition. This fact is of great importance when considering the inhibitors for practical use. The advantage of using inhibitors of ethylene action over inhibitors of ethylene production lies in the ability of the inhibitors of ethylene action to protect the tissue against both endogenous and exogenous ethylene, thus providing better overall protection. Our findings indicate that 1-MCP and its structural analogues are potent inhibitors of ethylene action capable of providing good protection against endogenous and exogenous ethylene. The fact that the compounds are in a gas phase and are non-phytotoxic, odorless and effective at minute concentrations, renders them promising candidates for commercial use. However, the development of water-soluble inhibitors will expand the potential use of the inhibitors in agriculture.
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Young, Erin, Cem Kuscu, Christine Watkins, and Murat Dogan. Using CRISPR Gene Editing to Prevent Accumulation of Lipids in Hepatocytes. University of Tennessee Health Science Center, January 2022. http://dx.doi.org/10.21007/com.lsp.2022.0007.
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CRISPR gene editing is a molecular technology that can be used to silence gene expression. In this experiment, genes that are known to play a role in lipid accumulation in hepatocytes were targeted. Specifically, levels of fatty acid transport proteins 2 and 5 (FATP2 & 5) have been shown to be elevated in cases of non-alcoholic fatty liver disease. The goal of this experiment was to reduce expression of these genes by using a dead Cas9 (dCas9) protein with an attached inhibitory domain (KRAB) that acts on the promotor region. When measuring the mRNA expression, it was determined that the levels of the CRISPR-modified gene products were significantly reduced compared to the control. However, the same extent of inhibition was not consistently observed when conducting flow cytometry. Current work is aimed at discovering why lipid accumulation is not inhibited to the expected degree based on the results of mRNA expression.
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Naim, Michael, Andrew Spielman, Shlomo Nir, and Ann Noble. Bitter Taste Transduction: Cellular Pathways, Inhibition and Implications for Human Acceptance of Agricultural Food Products. United States Department of Agriculture, February 2000. http://dx.doi.org/10.32747/2000.7695839.bard.
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Historically, the aversive response of humans and other mammals to bitter-taste substances has been useful for survival, since many toxic constituents taste bitter. Today, the range of foods available is more diverse. Many bitter foods are not only safe for consumption but contain bitter constituents that provide nutritional benefits. Despite this, these foods are often eliminated from our current diets because of their unacceptable bitterness. Extensive technology has been developed to remove or mask bitterness in foods, but a lack of understanding of the mechanisms of bitterness perception at the taste receptor level has prevented the development of inhibitors or efficient methods for reducing bitterness. In our original application we proposed to: (a) investigate the time course and effect of selected bitter tastants relevant to agricultural products on the formation of intracellular signal molecules (cAMP, IP3, Ca2+) in intact taste cells, in model cells and in membranes derived therefrom; (b) study the effect of specific bitter taste inhibitors on messenger formation and identify G-proteins that may be involved in tastant-induced bitter sensation; (c) investigate interactions and self-aggregation of bitter tastants within membranes; (d) study human sensory responses over time to these bitter-taste stimuli and inhibitors in order to validate the biochemical data. Quench-flow module (QFM) and fast pipetting system (FPS) allowed us to monitor fast release of the aforementioned signal molecules (cGMP, as a putative initial signal was substituted for Ca2+ ions) - using taste membranes and intact taste cells in a time range below 500 ms (real time of taste sensation) - in response to bitter-taste stimulation. Limonin (citrus) and catechin (wine) were found to reduce cellular cAMP and increase IP3 contents. Naringin (citrus) stimulated an IP3 increase whereas the cheese-derived bitter peptide cyclo(leu-Trp) reduced IP3 but significantly increased cAMP levels. Thus, specific transduction pathways were identified, the results support the notion of multiple transduction pathways for bitter taste and cross-talk between a few of those transduction pathways. Furthermore, amphipathic tastants permeate rapidly (within seconds) into liposomes and taste cells suggesting their availability for direct activation of signal transduction components by means of receptor-independent mechanisms within the time course of taste sensation. The activation of pigment movement and transduction pathways in frog melanophores by these tastants supports such mechanisms. Some bitter tastants, due to their amphipathic properties, permeated (or interacted with) into a bitter tastant inhibitor (specific phospholipid mixture) which apparently forms micelles. Thus, a mechanism via which this bitter taste inhibitor acts is proposed. Human sensory evaluation experiments humans performed according to their 6-n-propyl thiouracil (PROP) status (non-tasters, tasters, super-tasters), indicated differential perception of bitterness threshold and intensity of these bitter compounds by different individuals independent of PROP status. This suggests that natural products containing bitter compounds (e.g., naringin and limonin in citrus), are perceived very differently, and are in line with multiple transduction pathways suggested in the biochemical experiments. This project provides the first comprehensive effort to explore the molecular basis of bitter taste at the taste-cell level induced by economically important and agriculturally relevant food products. The findings, proposing a mechanism for bitter-taste inhibition by a bitter taste inhibitor (made up of food components) pave the way for the development of new, and perhaps more potent bitter-taste inhibitors which may eventually become economically relevant.
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Reddy, E. P. A Non-ATP Competitive Inhibitor of BCR-ABL for the Therapy of Imatinib-Resistant Cmls. Fort Belvoir, VA: Defense Technical Information Center, May 2008. http://dx.doi.org/10.21236/ada487510.
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Reddy, E. P. ON012380: A Non-ATP Competitive Inhibitor of BCR-ABL for the Therapy of Imatinib-Resistant CMLs. Fort Belvoir, VA: Defense Technical Information Center, May 2010. http://dx.doi.org/10.21236/ada532978.
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Reddy, E. P. ON012380: A Non-ATP Competitive Inhibitor of BCR-ABL for the Therapy of Imatinib-Resistant CMLs. Fort Belvoir, VA: Defense Technical Information Center, May 2009. http://dx.doi.org/10.21236/ada510718.
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