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Статті в журналах з теми "NOS inhibition"
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Bigal, Marcelo E. "NOS Inhibition." Headache Currents 1, no. 1 (July 2004): 23. http://dx.doi.org/10.1111/j.1743-5013.2004.10102d.x.
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Song, Michael Y., Charles F. Zwemer, Steven E. Whitesall, and Louis G. D'Alecy. "Acute and conditioned hypoxic tolerance augmented by endothelial nitric oxide synthase inhibition in mice." Journal of Applied Physiology 102, no. 2 (February 2007): 610–15. http://dx.doi.org/10.1152/japplphysiol.00894.2006.
Повний текст джерелаАнотація:
To identify a possible role for nitric oxide (NO) in acute hypoxic tolerance (HT) we measured hypoxic survival time (HST), effect of hypoxic conditioning (HC), and survival following hypoxic conditioning while blocking or mimicking the action of nitric oxide synthase (NOS). To inhibit NOS, CD-1 mice were given supplemental endogenous NOS inhibitor asymmetrical dimethylarginine (ADMA) or a synthetic NOS inhibitor Nω-nitro-l-arginine (l-NNA), both of which nonselectively inhibit three of the isoforms of NOS [inducible (iNOS), neuronal (nNOS), and endothelial NOS (eNOS)]. ADMA (10 mg/kg ip) or saline vehicle was given 5 min before HST testing. l-NNA was given orally at 1 g/l in drinking water with tap water as the control for 48 h before testing. Both ADMA and l-NNA significantly increased HST and augmented the HC effect on HST. Neither the nNOS selective inhibitor 7-nitroindazole (7-NI) nor the iNOS selective inhibitor N-{[3-(aminomethyl)phenyl]methyl}-enthanimidamide (1400W) had a statistically significant effect on HST or HT. The NO donor, 3-morpholinosydnoeimine, when given alone did not significantly decrease HT, but it did mitigate the increased HT effect of l-NNA. These data confirm that acute hypoxic conditioning increases HT and that NOS inhibition by endogenous (ADMA) and a synthetic NOS inhibitor (l-NNA) further increases HT, whereas iNOS and nNOS inhibition does not, suggesting that it is the inhibition of eNOS that mediates enhancement of HT.
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Wang, Xuemei, and William A. Cupples. "Brown Norway rats show impaired nNOS-mediated information transfer in renal autoregulationThis article is part of a Special Issue on Information Transfer in the Microcirculation." Canadian Journal of Physiology and Pharmacology 87, no. 1 (January 2009): 29–36. http://dx.doi.org/10.1139/y08-102.
Повний текст джерелаАнотація:
Nonselective inhibition of NO synthase (NOS) augments myogenic autoregulation of renal blood flow (RBF) and profoundly reduces RBF. Previously in Wistar rats, we showed that augmented autoregulation, but not vasoconstriction, is duplicated by intrarenal inhibition of neuronal NOS (nNOS), whereas intrarenal inhibition of inducible NOS (iNOS) has no effect on RBF or on RBF dynamics. Thus macula densa nNOS transfers information from tubuloglomerular feedback to the afferent arteriole. This information flow requires that macula densa nNOS can sufficiently alter ambient NO concentration, that is, that endothelial NOS (eNOS) and iNOS do not alter local NO concentration. Because the Brown Norway rat often shows exaggerated responses to NOS inhibition and has peculiarities of renal autoregulation that are related to NO, we used this strain to study systemic and renal vascular responses to NOS inhibition. The first experiment showed transient blood pressure reduction by bolus i.v. acetylcholine that was dose-dependent in both strains and substantially prolonged in Brown Norway rats. The depressor response decayed more rapidly after nonselective NOS inhibition and the difference between strains was lost, indicating a greater activity of eNOS in Brown Norway rats. In Brown Norway rats, selective inhibition of iNOS reduced RBF (–16% ± 7%) and augmented myogenic autoregulation, whereas nNOS inhibition reduced RBF (–25% ± 4%) and did not augment myogenic autoregulation. The significant responses to intrarenal iNOS inhibition, the reduced modulation of autoregulation by nNOS inhibition, and the enhanced endothelial depressor response suggest that physiological signalling by NO within the kidney is impaired in Brown Norway rats because of irrelevant or inappropriate input of NO by eNOS and iNOS.
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Niebauer, Josef, Andrew J. Maxwell, Patrick S. Lin, David Wang, Philip S. Tsao, and John P. Cooke. "NOS inhibition accelerates atherogenesis: reversal by exercise." American Journal of Physiology-Heart and Circulatory Physiology 285, no. 2 (August 2003): H535—H540. http://dx.doi.org/10.1152/ajpheart.00360.2001.
Повний текст джерелаАнотація:
In this study, we assessed the effects of chronic exercise training (12 wk) on atherosclerotic lesion formation in hypercholesterolemic apolipoprotein E-deficient mice ( n = 31). At the age of 9 wk, mice were assigned to the following groups: sedentary (Sed; n = 9); exercise (Ex; n = 12); sedentary and oral NG-nitro-l-arginine (l-NNA, Sed-NA; n = 4), or exercise and oral l-NNA (Ex-NA; n = 6). Chronic exercise training was performed on a treadmill for 12 wk (6 times/wk and twice for 1 h/day) at a final speed of 22 m/min, and an 8° grade. l-NNA was discontinued 5 days before final treadmill testing. The farthest distance run to exhaustion was observed in Ex-NA mice (Sed: 306 ± 32 m; Ex: 640 ± 87; Sed-NA: 451 ± 109 m; Ex-NA: 820 ± 49 m; all P < 0.05). Lesion formation was assessed in the proximal ascending aorta by dissection microscopy after oil red O staining. The aortas of Sed-NA mice manifested a threefold increase in lesion formation compared with the other groups. This l-NNA-induced lesion formation was reduced by chronic exercise training (Sed, 786 ± 144; Ex, 780 ± 206; Sed-NA, 2,147 ± 522; Ex-NA, 851 ± 253; Sed-NA vs. all other groups: P < 0.001). In conclusion, treatment with oral l-NNA (an nitric oxide synthase antagonist) leads to accelerated atherogenesis in genetically determined hypercholesterolemic mice. This adverse effect can be overcome by chronic exercise training.
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O’Riordan, Edmond, Natalia Mendelev, Susann Patschan, Daniel Patschan, Jonathan Eskander, Leona Cohen-Gould, Praveen Chander, and Michael S. Goligorsky. "Chronic NOS inhibition actuates endothelial-mesenchymal transformation." American Journal of Physiology-Heart and Circulatory Physiology 292, no. 1 (January 2007): H285—H294. http://dx.doi.org/10.1152/ajpheart.00560.2006.
Повний текст джерелаАнотація:
Chronic kidney diseases are accompanied by the accumulation of substances like asymmetric dimethylarginine, phenylacetic acid, homocysteine, and advanced glycation end products, known to either inhibit endothelial nitric oxide synthase (eNOS) or uncouple it, consequently limiting the amount of available nitric oxide (NO). Reduced bioavailability of NO induces endothelial dysfunction. An early loss of peritubular capillaries in tubulointerstitial fibrotic areas and injury to endothelial cells have been linked to progressive renal disease. Screening endothelial genes in cells treated with NOS inhibitors showed upregulation of collagen XVIII, a precursor of a potent antiangiogenic substance, endostatin. This finding was confirmed at the level of mRNA and protein expression. Tie-2 promoter-driven green fluorescent protein mice treated with nonhypertensinogenic doses of a NOS inhibitor exhibited upregulation of collagen XVIII/endostatin and rarefaction of capillary profiles. This was accompanied by the increased expression of transforming growth factor-β and connective tissue growth factor in the kidney. Occasional endothelial cells expressed both the marker of endothelial lineage (green fluorescent protein) and mesenchymal marker (α-smooth muscle actin or calponin). In vitro studies of endothelial cells treated with asymmetric dimethylarginine showed decreased expression of eNOS and Flk-1 and enhanced expression of calponin and fibronectin, additional markers of smooth muscle and mesenchymal cells. These cells overexpressed transforming growth factor-β and connective tissue growth factor, as well as endostatin. In conclusion, data presented here 1) ascribe to NO deficiency in endothelial cells the function of a profibrotic stimulus associated with the expression of an antiangiogenic fragment of collagen XVIII (endostatin) and 2) provide evidence of endothelial-mesenchymal transdifferentiation in the course of inhibition of NOS by a pathophysiologically important antagonist, asymmetric dimethylarginine. Both mechanisms may account for microvascular rarefaction.
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Cholet, Nathalie, Jacques Seylaz, Pierre Lacombe, and Gilles Bonvento. "Local Uncoupling of the Cerebrovascular and Metabolic Responses to Somatosensory Stimulation after Neuronal Nitric Oxide Synthase Inhibition." Journal of Cerebral Blood Flow & Metabolism 17, no. 11 (November 1997): 1191–201. http://dx.doi.org/10.1097/00004647-199711000-00008.
Повний текст джерелаАнотація:
It has recently been shown, using either genetically engineered mutant mice (nitric oxide synthase [NOS] knockout) or specific pharmacological tools, that type I NOS (neuronal isoform of NOS, [nNOS]) participates in coupling cerebral blood flow to functional activation. However, it has not been clearly established whether the associated metabolic response was preserved under nNOS inhibition and whether this action was exerted homogeneously within the brain. To address these issues, we analyzed the combined circulatory and metabolic consequences of inhibiting the nNOS both at rest and during functional activation in the rat anesthetized with α-chloralose. Cerebral blood flow and cerebral glucose use (CGU) were measured autoradiographically using [14C]iodoantipyrine and [14C]2-deoxyglucose during trigeminal activation induced by unilateral whiskers stimulation in vehicle- and 7-nitroindazole-treated rats. Our data show that inhibition of nNOS globally decreased CBF without altering CGU, indicating that NO-releasing neurons play a significant role in maintaining a resting cerebrovascular tone in the whole brain. During whisker stimulation, nNOS inhibition totally abolished the cerebrovascular response only in the second order relay stations (thalamus and somatosensory cortex) of the trigeminal relay without altering the metabolic response. These findings provide evidence that the involvement of neurally-derived NO in coupling flow to somatosensory activation is region-dependent, and that under nNOS inhibition, CBF and CGU may vary independently during neuronal activation.
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Fujii, Naoto, Robert D. Meade, Lacy M. Alexander, Pegah Akbari, Imane Foudil-bey, Jeffrey C. Louie, Pierre Boulay, and Glen P. Kenny. "iNOS-dependent sweating and eNOS-dependent cutaneous vasodilation are evident in younger adults, but are diminished in older adults exercising in the heat." Journal of Applied Physiology 120, no. 3 (February 1, 2016): 318–27. http://dx.doi.org/10.1152/japplphysiol.00714.2015.
Повний текст джерелаАнотація:
Nitric oxide synthase (NOS) contributes to sweating and cutaneous vasodilation during exercise in younger adults. We hypothesized that endothelial NOS (eNOS) and neuronal NOS (nNOS) mediate NOS-dependent sweating, whereas eNOS induces NOS-dependent cutaneous vasodilation in younger adults exercising in the heat. Further, aging may upregulate inducible NOS (iNOS), which may attenuate sweating and cutaneous vasodilator responses. We hypothesized that iNOS inhibition would augment sweating and cutaneous vasodilation in exercising older adults. Physically active younger ( n = 12, 23 ± 4 yr) and older ( n = 12, 60 ± 6 yr) adults performed two 30-min bouts of cycling at a fixed rate of metabolic heat production (400 W) in the heat (35°C). Sweat rate and cutaneous vascular conductance (CVC) were evaluated at four intradermal microdialysis sites with: 1) lactated Ringer (control), 2) nNOS inhibitor (nNOS-I, NPLA), 3) iNOS inhibitor (iNOS-I, 1400W), or 4) eNOS inhibitor (eNOS-I, LNAA). In younger adults during both exercise bouts, all inhibitors decreased sweating relative to control, albeit a lower sweat rate was observed at iNOS-I compared with eNOS-I and nNOS-I sites (all P < 0.05). CVC at the eNOS-I site was lower than control in younger adults throughout the intermittent exercise protocol (all P < 0.05). In older adults, there were no differences between control and iNOS-I sites for sweating and CVC during both exercise bouts (all P > 0.05). We show that iNOS and eNOS are the main contributors to NOS-dependent sweating and cutaneous vasodilation, respectively, in physically active younger adults exercising in the heat, and that iNOS inhibition does not alter sweating or cutaneous vasodilation in exercising physically active older adults.
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Rudd, M. Audrey, George Toolan, Maria R. Trolliet, Timothy Cloutier, Karlene Maitland, and Joseph Loscalzo. "Short-Term NOS II Inhibition Leads to Long-Term Salt-Sensitivity in Dahl Salt-Resistant Rats." Hypertension 36, suppl_1 (October 2000): 713. http://dx.doi.org/10.1161/hyp.36.suppl_1.713-b.
Повний текст джерелаАнотація:
P111 We have previously shown that inhibition of inducible nitric oxide synthase (NOS II) evokes a salt-sensitive increase in blood pressure in Dahl salt-resistant rats when given a high salt (8% NaCl) diet for 7 days. To determine whether or not the effect of NOS II inhibition is short-lived, we continued the high salt diet for an additional 3 weeks following the discontinuation of the NOS II inhibitor. DR rats were given one of two NOS II selective inhibitors, AMT (300 nmoles/hr) and 1400W (35 nmoles/hr) for 2 weeks. A high salt diet was initiated after the first week of NOS II inhibition and continued for an additional 3 weeks for a total of 4 weeks of high salt treatment. Control DR rats received high salt alone for 4 weeks. Systolic blood pressure was taken at baseline and once weekly for the treatment period. Blood pressure significantly increased in DR rats after 1 week of high salt following NOS II inhibition. The blood pressure remained elevated throughout the 4-week period of high salt treatment despite the discontinuation of NOS II inhibitors 1 week following the initiation of the high salt diet. There was no significant change in blood pressure in DR rats on high salt diet alone. These data suggest that salt-sensitive hypertension can be evoked by transient NOS II inhibitor exposure. We conclude that tranisent NOS II inhibition may initiate events or processes that high salt maintains leading to sustained elevation in systolic blood pressure.
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Otterson, Mary F., Shawn C. Leming, Xiaoqi Liu, and John E. Moulder. "NOS inhibition reduces the contractile response to irradiation." Gastroenterology 118, no. 4 (April 2000): A411. http://dx.doi.org/10.1016/s0016-5085(00)83755-5.
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Nevoral, J., T. Krejčová, J. Petr, P. Melicharová, A. Vyskočilová, M. Dvořáková, I. Weingartová, et al. "The role of nitric oxide synthase isoforms in aged porcine oocytes." Czech Journal of Animal Science 58, No. 10 (September 27, 2013): 453–59. http://dx.doi.org/10.17221/6994-cjas.
Повний текст джерелаАнотація:
In the sphere of reproductive biotechnologies, the demand for sufficient numbers of high-quality oocytes is still increasing. In some cases, this obstacle is overcome by in vitro prolonged cultivation. However, a prolonged oocyte culture is accompanied by changes called ageing. Ageing is manifested by spontaneous parthenogenetic activation, programmed cell death or lysis. Various substances, such as caffeine or dithiothreitol, have been tested for ageing suppression. In this respect, research into gasotransmitters (hydrogen sulphide, carbon monoxide, and nitric oxide) has currently been intensified. The objectives of the present study were to localize nitric oxide synthases (NOS) and to evaluate NOS inhibition of aged porcine oocytes. We demonstrated the presence of NOS isoforms in oocyte cultivation prolonged by 24, 48, and 72 h. After 72 h of prolonged cultivation, NOS inhibition by the non-specific inhibitor L-NAME or the specific inhibitor aminoguanidine caused suppression both of programmed cell death and lysis. Although NOS amount rapidly decreased after the 72-h cultivation, changes induced by NOS inhibition were statistically significant. We can presume that NOS play an important physiological role in porcine oocyte ageing.
Дисертації з теми "NOS inhibition"
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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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Moura, Wlamir Corrêa de. "Aplicação do conceito dos três Rs nos ensaios de controle da qualidade de imunobiológicos para raiva." reponame:Repositório Institucional da FIOCRUZ, 2009. https://www.arca.fiocruz.br/handle/icict/8238.
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Previous issue date: 2009Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde
O presente estudo é uma aplicação prática do conceito dos Três Rs (3Rs) de Russell e Burch (1959) nos ensaios de controle da qualidade de imunobiológicos para Raiva preconizados pela Farmacopéia Brasileira através de: uma análise retrospectiva de dados para a Redução do nº de animais no Ensaio de Potencia NIH para vacina contra raiva de uso humano (vaccinum rabiei ad usum humanum); mudanças no método de avaliação da inativação viral destas vacinas utilizando animais e células e validação de um ensaio in vitro para substituir o ensaio in vivo no teste de potência de imunoglobulinas anti-rábicas (Immunosera rabicum ex animali ad usum humanum e immunoglobulinum humanum rabicum). Todos os três protocolos de ensaio testados no estudo demonstraram viabilidade de utilização.
The present study is a practical application of the Russell and Burch 3Rs concept (1959) in the in vivo tests described in the Farmacopéia Brasileira for quality control of rabies biologicals by testing: A reduction in the number of mice in the NIH potency test for rabies vaccine for human use (vaccinum rabiei ad usum humanum); changes in the evaluation of virus inactivation method using suckling mice and cells as an alternative to the current Brazilian Pharmacopoeia official test (Reduction, Refinement and Replacement) and the validation of an in vitro assay to replace the in vivo assay for the potency test of Rabies Immunoglobulins (Immunosera rabicum ex animali ad usum humanum e immunoglobulinum humanum rabicum) (Replacement). All the three assay protocols have shown viability of use.
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Lewis, Sophronia. "The effect of ablation and acute inhibition of plasma membrane calcium ATPase 4 (PMCA4) with a novel inhibitor on isolated mouse mesenteric resistance arterial contractility." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/the-effect-of-ablation-and-acute-inhibition-of-plasma-membrane-calcium-atpase-4-pmca4-with-a-novel-inhibitor-on-isolated-mouse-mesenteric-resistance-arterial-contractility(676a26ea-867e-4947-9544-76b356fce23a).html.
Повний текст джерелаАнотація:
Plasma membrane calcium ATPase 4 (PMCA4) is a calcium extrusion pump which may also modulate Ca2+-triggered signal transduction pathways. Previous studies postulate that PMCA4 modulates signalling via an interaction with neuronal nitric oxide synthase (nNOS) in localised plasmalemmal microdomains. The effect of PMCA4 on vascular contractility is unclear. This project has utilised PMCA4 ablated mice (PMCA4 KO (-/-)) and a novel specific PMCA4 inhibitor (termed AP2) to study the role of PMCA4 in mouse resistance artery contractility.Immunohistochemistry, Western blotting and polymerase chain reaction (PCR) confirmed the absence of PMCA4 in the brain, vasculature and ear snips obtained from PMCA4 KO (-/-) mice whereas it was present in those from wild type (WT (+/+)) mice. Pressure myography was employed to assesss contractile function of isolated, pressurised (to 60 mmHg) mesenteric resistance arteries from 3 months old male PMCA4 KO (-/-) and WT (+/+) mice, in response to high K+ physiological salt solution (KPSS) (40mM & 100mM) and noradrenaline (NA) (Log[NA] -9.0 to -5.0M). Passive lumen diameter and left and right wall thicknesses of arteries from PMAC4 KO (-/-) and WT (+/+) mice were taken at transmural pressures of 5-140 mmHg. Effects of acute PMCA4 inhibition with AP2 (10µM and 1µM), nitric oxide synthase (NOS) inhibition with LNNA (100µM) and specific nNOS inhibition with Vinyl-L-Nio (10µM) were also investigated. Effects of PMCA4 ablation and AP2 (10µM) on global intracellular Ca2+ changes ([Ca2+]i) in pressurised mesenteric arteries were assessed after loading arteries with the Ca2+-sensitive indicator indo-1. PMCA4 ablation had no effect on the magnitude of arterial constrictions or on the changes of [Ca2+]i in response to KPSS (40mM & 100mM) or to noradrenaline. The passive intra-lumen diameter, wall thickness, wall to lumen diameter and cross sectional area of mesenteric arteries across the intravascular pressure range studied were also not modulated by PMCA4 ablation. A leftwards shift in the stress to strain relationship and significant increase in beta elastic modulus (β) were revealed in arteries from PMCA4 KO (-/-) mice compared to those from WT (+/+) mice, suggesting that PMCA4 ablation reduces mesenteric arterial distensibility. Acute PMCA4 inhibition with AP2, significantly reduced arterial constrictions and the increase in [Ca2+]i in response to noradrenaline in arteries from WT (+/+) mice, but had no effect on arterial constrictions elicited by arteries from PMCA4 KO (-/-) mice. Inhibitory effects of AP2 were not present in arteries after NOS inhibition by LNNA and also after nNOS inhibition with Vinly-L-Nio. Hence, PMCA4 inhibition with AP2 reduces vascular constriction by a nNOS-dependent mechanism.In conclusion, the main findings of the study were that ablation and acute inhibition of PMCA4 with AP2 have different effects on mouse mesenteric resistance arterial contractility. This study provides more insight into PMCA4 as a significant modulator of signalling within the vasculature via effects on nNOS.
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Kim, Sehyun. "Nde1-mediated inhibition of ciliogenesis controls cell cycle re-entry." Oklahoma City : [s.n.], 2009.
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Flanigan, Matt. "Modulation of the sodium/iodide symporter (NIS) by MEK inhibition in MCF7 breast cancer cells." Connect to resource, 2009. http://hdl.handle.net/1811/36943.
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Lalande, Stéphanie. "Biogenèse et fonctions de petits ARN non-codants dérivant d'ARN de transfert, les tRF, chez les plantes." Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAJ109.
Повний текст джерелаАнотація:
Des petits ARN non codants dérivant d'ARN de transfert (tRF) ont été identifiés dans tous les domaines de la vie, et de plus en plus de fonctions importantes leur sont attribuées chez de nombreux organismes. Dans ce travail mené sur la plante modèle Arabidopsis, nous avons d’abord montré que la population en tRF varie en fonction des tissus et des conditions de stress. Concernant leur biogenèse, les endoribonucléases responsables du clivage des ARNt ont été identifiées, il s'agit des RNases T2, RNS1, 2 et 3. Afin de réaliser une étude structure/fonction, une approche d’expression en système de levure a été initiée pour permettre l’obtention de quantité suffisante de RNS1 purifiée. L’étude des fonctions des tRF montre que certains d’entre eux sont associés à AGO1, qu'ils semblent cibler entre-autres des éléments transposables et qu’ils pourraient avoir une localisation nucléaire. Enfin, deux tRF, le tRF-5D (Ala) et le tRF-5D (Asn) inhibent efficacement la traduction in vitro. Une association de tRF-5D (Ala) aux polyribosomes de plantules d'Arabidopsis a pu être visualisée, suggérant que certains tRF puissent agir en tant que régulateur global de la traductionSmall non-coding RNAs derived from transfer RNAs (tRFs) have been identified in all domains of life, and more and more important functions are attributed to them in many organisms. In this work on the model plant Arabidopsis, we first showed that the tRF population varies according to tissues and stress conditions. With regard to their biogenesis, the endoribonucleases responsible for tRNA cleavage were identified, it is the RNases T2, RNS1, 2 and 3. In order to carry out a structure / function analysis, heterologous expression in yeast has been developed with the hope to get sufficient amount of purified RNS1. The question of tRF functions has also been studied. It has been shown that some tRFs are associated with AGO1, that they often seem to target transposable elements and could have a nuclear localization. Finally, the study of the involvement of the tRFs in the regulation of translation was tackled. Two tRFs, tRF-5D (Ala) and tRF-5D (Asn) efficiently inhibit translation in vitro. An association of tRF-5D (Ala) with polyribosomes of Arabidopsis seedlings could be visualized suggesting that some plant tRFs could as global regulator of the translation process
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Kent, Timothy Robert. "Mechanistic Understanding of the NOB Suppression by Free Ammonia Inhibition in Continuous Flow Aerobic Granulation Bioreactors." Thesis, Virginia Tech, 2019. http://hdl.handle.net/10919/87706.
Повний текст джерелаАнотація:
A partial nitritation-anammox continuous flow reactor (CFR) was operated for eight months demonstrating that a mixture of large anammox-supported aerobic granules (ASAGs) and small conventional aerobic granules (CAGs) can be maintained stably for extended periods of time. The influent NH4+ was kept at 50 - 60 mg N L-1 to verify that the upper range of total ammonia nitrogen (TAN) for domestic wastewater can supply an inhibitory level of free ammonia (FA) for nitrite oxidizing bacteria (NOB) suppression in CFRs at pH around 7.8. The ammonia oxidizing bacteria (AOB):NOB activity ratio was determined for a series of granule sizes to understand the impact of mass diffusion limitation on the FA inhibition of NOB. When dissolved oxygen (DO) limitation is the only mechanism for NOB suppression, the AOB:NOB ratio was usually found in previous studies to increase with the granule size. However, the trend is reversed when FA has an inhibitory effect on NOB, as was observed in this study. The decrease in AOB:NOB ratio indicates that the resistance to the diffusion of FA along the granule radius limited its ability to inhibit NOB. This means smaller granules, e.g. diameter < 150 microns, are preferred for nitrite accumulation when high FA is present, e.g. in the partial nitritation-anammox process. The trend was further verified by observing the increase in the apparent inhibition coefficient, KI,FAapp, as granule size increased. This study for the first time quantified the effect of diffusion limitation on the KI,FAapp of NOB in granules and biofilms. A mathematical model was then utilized to interpret the observed suppression of NOB. The model predicted that NOB suppression was only complete at the granule surface. The NOB that did survive in larger granules was forced to dwell within the granule interior, where the FA concentration was lower than that in the bulk solution. This means FA inhibition can be taken advantage of as an effective means for NOB suppression in small granules and thin biofilms. Further, FA and DO were found to be both required for the stratification of AOB and NOB in partial nitritation-anammox CFRs. The structural stratification commonly observed in granules is then concluded to be a consequence but not a cause of the NOB suppression.MS
A partial nitritation-anammox continuous flow reactor (CFR) was operated for eight months demonstrating that granular sludge can be maintained stably for extended periods of time. In this approach, NH3 is only partially converted to NO2 - (partial nitritation), and the conversion to NO3 - is prevented by the suppression of nitrite oxidizing bacteria (NOB). NH3 and NO2 - are then utilized by anammox bacteria to create N2 gas. The influent NH4 + fed to the reactor was kept at 50 to 60 mg N L-1 to verify that the upper range of total ammonia nitrogen (TAN) for domestic wastewater can supply a sufficiently high level of free ammonia (FA) to inhibit NOB growth in CFRs at a pH around 7.8. It is expected that the penetration of a substrate into granule sludge will experience diffusional resistance as it moves from water to denser solid material and is consumed by bacteria. The ammonia oxidizing bacteria (AOB):NOB activity ratio was determined for a series of granule sizes to understand the impact of mass diffusion limitation on the FA inhibition of NOB. When dissolved oxygen (DO) limitation is the only mechanism for NOB suppression, the AOB:NOB ratio was usually found in previous studies to increase with the granule size. However, the trend is reversed when FA has an inhibitory effect on NOB, as was observed in this study. The decrease in AOB:NOB ratio indicates that the resistance to the diffusion of FA, which increases with increasing granule size, along the granule radius limited its ability to inhibit NOB. This means smaller granules, e.g. diameter < 150 µm, are preferred for NO2 - accumulation when high FA is present. The trend was further verified by observing the increase in the apparent inhibition coefficient, KI,FAapp, as granule size increased. This coefficient quantifies the effectiveness of an inhibitor, with larger values indicating weaker inhibition. This study for the first time quantified the effect of diffusion limitation on the KI,FAapp of NOB in granules and biofilms. A mathematical model was then utilized to interpret the observed suppression of NOB. The model predicted that NOB suppression was only complete at the granule surface. The NOB that did survive in larger granules was forced to dwell within the granule interior, where the FA concentration was lower than that in the bulk solution. This means FA inhibition can be taken advantage of as an effective means for NOB suppression in small granules and thin biofilms. Further, FA and DO were found to be both required for the stratification of a layer of AOB at the surface over a layer of NOB in partial nitritation-anammox CFRs. The structural stratification commonly observed in granules is then concluded to be a consequence but not a cause of the NOB suppression.
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Correa, Cristia Rosineiri Gonçalves Lopes. "A dimensão do ideal nas dificuldades de aprendizagem." Universidade Federal de Juiz de Fora (UFJF), 2011. https://repositorio.ufjf.br/jspui/handle/ufjf/2677.
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CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
A presente dissertação tem como proposta investigar no campo de interlocução entre Psicanálise e Educação a problemática das dificuldades de aprendizagem. Partimos da pergunta: “nos quadros de dificuldades de aprendizagem trata-se de um Outro que não sabe, ou um Outro que sabe demais”? O nosso caminho para responder a essa questão partirá da verificação lógica da sugestão de Lacan (1967): a segregação do real pelo Ideal. Com esse percurso, pretendemos avançar nesse ponto da segregação que a dimensão do Ideal coloca em jogo. Subsequentemente, visaremos a uma interlocução entre a abordagem psicanalítica e a teoria piagetiana das aprendizagens, discutindo a noção do egocentrismo infantil reivindicado por Piaget. Também, visaremos posteriormente uma interlocução com uma abordagem crítica das políticas públicas educacionais que denuncia uma forte dimensão idealizante no fundamento dessas políticas. Tal interlocução se dará no sentido de verificar se essa visada é a mesma da visada psicanalítica, avançando um pouquinho mais nesse tema. O passo seguinte será a investigação detida das dificuldades de aprendizagem na psicanálise a partir da abordagem da inibição neurótica da qual a inibição na aprendizagem faz parte, à luz da tragédia “Hamlet”, de Shakespeare, onde podemos encontrar a inibição de Hamlet intimamente articulada com um Outro que sabe demais. Trabalharemos com a hipótese de uma dimensão excessivamente idealizante no cerne de quadros de séria inibição na aprendizagem. Dimensão de um saber idealizado demais que obstrui o ato de aprender. É justamente essa hipótese que será investigada.
This dissertation aims at investigating learning difficulties at the intersection of Psychoanalysis and Education. We begin with the following question: “Learning difficulties pictures: the Other does not knowledge or knowledge too much”? To deal with this question we will begin with the logical verification for Lacan’s suggestion (1967) about the segregation of the real order comprised by Ideal dimension. With this approach, we aim at advancing in this segregation notion introduced by the Ideal. Subsequently, we will be concerned with the conversation between psychoanalysis and Piaget’s theory about learning, discussing child’s egocentrism claimed by this researcher. After, we will also be concerned with the conversation with a critical approach of educational public policies denounces a strong Ideal dimension in the core of these policies. Such a conversation will take place in the sense of verifying whether this reading and psychoanalytical one are the same, advancing a bit more, in this theme. The following step will be the learning difficulties detailed investigation from the neurotic inhibition approach from which the learning inhibition takes part, on the lights from Shakespeare’s Hamlet, where we can find the Hamlet’s inhibition closely related to an Other that kowledges too much. We will be concerned with the excessively idealized dimension hypothesis in the core of the learning difficulties pictures. Dimension which comprises an idealized knowledge that prevents the act of learning. It is justly this hypothesis which will be investigated.
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Billinger, Erika. "An investigation of protective formulations containing enzyme inhibitors : Model experiments of trypsin." Thesis, Uppsala universitet, Institutionen för kemi - BMC, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-181173.
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This master thesis considers an investigation of protective formulations (ointment, cream) containing enzyme inhibitors. Model experiments have been made on the enzyme trypsin. It is well accepted that feces and urine are an important causing factor for skin irritation (dermatitis) while using diaper. A protective formulation is a physical barrier that separates the harmful substances from the skin. It can also be an active barrier containing active substances, which can be active both towards the skin, and the substances from feces and urine. By preventing contact from these substances the skin will not be harmed, at least for a period of time. A number of different inhibitors were tested towards trypsin and they all showed good inhibition, two of the inhibitors were selected to be immobilized with the help of NHS-activated Sepharose. Immobilization of these two inhibitors leads to a lesser extent of the risk of developing allergy and also that the possible toxic effect can be minimized.
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Chitnis, Meenali M. "Type 1 insulin-like growth factor receptor inhibition as treatment for urological cancer." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:21282ce9-ce6b-4d26-b262-a3fca6d9c9fc.
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The type 1 insulin-like growth factor receptor (IGF-1R) is a receptor tyrosine kinase that mediates diverse cellular functions including growth, differentiation, migration and apoptosis protection. IGF-1R signalling has been implicated in tumorigenesis in a variety of cancers, and IGF-1R inhibitory drugs are currently undergoing clinical evaluation. Previous work in our laboratory has shown IGF-1R over-expression in urological cancers at both the mRNA and protein level, thus making it a potential therapeutic target. The first aim of this project was to develop a protocol for IGF-1R immunohistochemistry, investigate the expression and cellular distribution of the IGF-1R receptor in clear cell renal cell carcinomas (ccRCC), and assess correlation with clinical parameters. In tissue microarray analysis, IGF-1R was detected in ~90% of 195 ccRCCs, with signal in the plasma membrane, cytoplasm and also in the nucleus. The presence of nuclear IGF-1R in up to 50% of ccRCCs and its association with adverse prognosis was a novel finding, and suggests that nuclear IGF-1R may influence ccRCC biology. Further investigations will clarify its role in the nucleus and its potential as a prognostic biomarker. The second aim was to investigate effects of IGF-1R inhibition on radiosensitivity and DNA repair, following previous work in our laboratory showing that IGF-1R depletion enhances chemo- and radio-sensitivity, delays double strand break (DSB) resolution, and may play a role in the homologous recombination (HR) pathway of DNA DSB repair. However, the repair defect seen in these early experiments was larger than could be entirely explained by a defect in HR. The current project used a small molecule IGF-1R tyrosine kinase inhibitor AZ12253801 (AstraZeneca), which blocked IGF-1 induced IGF-1R activation and inhibited cell survival. AZ12253801 enhanced the radiosensitivity of prostate cancer cells, which appeared to be independent of effects of IGF-1R inhibition on cell cycle distribution and apoptosis induction. IGF-1R inhibition delayed the resolution of γH2AX foci, supporting a potential role for the IGF-1R in DSB repair. This delay in focus resolution was apparent at early time-points (less than 4 hr), and was epistatic with DNA dependent protein kinase (DNAPK) inhibition in prostate cancer cells and DNAPK deficiency in glioblastoma cells. These results suggest a role for the IGF-1R in the non-homologous end-joining (NHEJ) pathway of DNA DSB repair. A cell-based reporter assay in HEK-293 cells confirmed that IGF-1R inhibition suppressed DSB repair by NHEJ, helping to explain the radiosensitization demonstrated upon IGF-1R inhibition. There was lack of support for a transcriptional effect, with no significant change observed in gene expression on microarray analysis. Although the mechanism of this effect remains unclear, the observed inhibition of NHEJ has implications for the use of IGF-1R inhibitors in combination with DNA damaging agents in cancer treatment.
Книги з теми "NOS 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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Depa, Larisse, Larissa Depa, Crhisllane Vasconcelos, Vagner Fonseca, and Diego Frias. Estudo do uso de códons nos vírus da Dengue, Zika e Chikungunya com foco em terapia por inibição seletiva de tRNAs contra arboviroses. Edited by Diego Mariano. Alfahelix, 2021. http://dx.doi.org/10.51780/978-6-5992753-3-3.
Повний текст джерелаАнотація:
O vírus da dengue (DENV), o vírus da Zika (ZIKV) e o vírus da chikungunya (CHIKV) são espécies que apresentam relevância clínica para a saúde pública. Porém, ainda não existe um tratamento específico ou vacina disponível para esses arbovírus. Nesse contexto, é fundamental encontrar novos alvos terapêuticos que possam auxiliar estratégias e tratamentos mais eficientes. A metodologia de codon usage tem demonstrado bons resultados para encontrar alvos para terapias que visam inibidores de tradução. Este estudo buscou analisar o uso de códons e o equilíbrio entre a abundância relativa dos RNAs transportadores (tRNAs) para encontrar alvos terapêuticos que irão estimular novas alternativas de tratamento para infecções causadas pelos DENV, ZIKV e CHIKV. Para tanto, foi replicada uma estratégia computacional, assumindo uma terapia hipotética de inibição seletiva de tRNA (Selective Transport RNA Inhibition Therapy - STRIT), onde foi estabelecido um índice de potencial terapêutico (T-score) para encontrar potenciais espécies de tRNA que poderiam ser inibidas seletivamente para atenuar a replicação viral na célula hospedeira. Foram identificados os cinco códons com maior frequência relativa vírus/hospedeiro (mais relevantes para o vírus) nas seis espécies de arbovírus, notando que todos terminam com purinas A ou G. Os códons GGA (Glicina), AGA (Arginina) e ATA (Isoleucina) são relevantes em todos os flavivirus (ZIKV, DENV-1, DENV-2, DENV-3, DENV-4), mas não no alphavirus CHIKV, onde os códons ACG (Treonina) e CCG (Prolina) são os mais relevantes. Posteriormente, selecionando os cinco códons com maiores T-score nas seis espécies virais (30 códons em total) encontramos apenas 11 códons diferentes, todos terminados com A ou G. Agrupados segundo o nucleotídeo na primeira posição do códon estes 11 códons são: (AGA, ACA, ATA, ACG), (GGA, GCA, GTA, GCG), (CTA, CCG) e (TGG). No agrupamento, notamos outro fato intrigante: que 10 dos 11 códons mais bem ranqueados por T-score, terminam com GA, CA, TA ou CG. Nosso método identificou as espécies de tRNA (através da identificação do códon cognato com maior T-score), cuja inibição funcional por qualquer método específico a anticódon, poderia ter potenciais efeitos terapêuticos em células infectadas pelo vírus da Dengue, Zika e Chikungunya causando a inibição da tradução das proteínas do vírus sem ter um efeito deletério na sobrevivência das células hospedeiras durante o período da infeção. A predominância absoluta dos nucleotídeos A e G na terceira posição dos 11 códons com maior T-score, que por sua vez indica uma preferência dos arbovírus por 11 espécies de tRNA com C ou T na primeira posição do anticódon, abre um novo espaço de pesquisa na interação vírus-hospedeiro.
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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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Hodges, John R. Testing Cognitive Function at the Bedside. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780198749189.003.0005.
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This chapter explores the second component of assessment in patients with suspected cognitive dysfunction: testing cognitive function at the bedside. The first part of the examination should assess distributed cognitive functions, notably orientation and attention, episodic and semantic memory, and frontal executive function (initiation in the form of verbal fluency, abstraction, response inhibition, and set shifting); deficits in these indicate damage to particular brain systems, but not to focal areas of one hemisphere. The second part of the assessment deals with localized functions, divided into those associated with the dominant (i.e. the left side, in right-handers) and non-dominant hemispheres. The former relates largely to tests of spoken language with supplementary tests of reading, writing, calculation, and praxis when applicable. Testing right hemisphere function focuses on neglect (personal and extrapersonal), visuospatial and constructional abilities, and the agnosias including object and face agnosia.
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Purdon, Christine, and C. Psych. Pathological Responsibility, Thought-Action Fusion, and Thought Control in OCD. Edited by Christopher Pittenger. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190228163.003.0018.
Повний текст джерелаАнотація:
Leading models of obsessive-compulsive disorder (OCD) implicate overvalued beliefs about responsibility, beliefs about the relationship of thoughts to external events and morality (thought-action fusion), and thought control as key factors in the development and the persistence of the disorder. This chapter provides an overview of these three factors and presents case examples, empirical support, and clinical implications. Considerable empirical research indicates that people with OCD tend to endorse beliefs reflecting an overvalued responsibility and thought-action fusion (TAF). However, it is also clear that these beliefs, particularly TAF beliefs, are not unique to OCD. It has been proposed that attempts at thought suppression ironically lead to an increase in thought frequency; research has generally not yielded support for such an effect, nor for response inhibition deficits. However, there is converging evidence that suppression may have insidious effects on the appraisal of thought recurrences and mood state. Clinical implications are discussed.
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Hogan, Patrick Colm. Gender and Regulatory Regimes. Oxford University Press, 2017. http://dx.doi.org/10.1093/oso/9780190857790.003.0006.
Повний текст джерелаАнотація:
The fifth chapter continues the focus on regulatory regimes, now turning to gender and taking up ideology and socialization rather than coercion. This chapter first considers some short stories by Tagore. Specifically, it examines the role of humiliation in the inhibition of boys’ empathic response, especially sensitivity about attachment needs. From here, the chapter turns to Woolf’s Orlando. In this novel, Woolf presents a situationist account of gender regulation. Orlando’s apparently masculine or feminine behaviors are provoked by such seemingly trivial situations as the nature of his/her clothing. Woolf nuances the situationist account by showing that some forms of situated behavior, as well as thought and feeling, are likely to become habitual through repetition. In short, it is not differences in minds that produce differences in behaviors, which in turn create social situations. Rather, differences in social situations produce differences in behaviors, leading to differences in thoughts and feelings.
Частини книг з теми "NOS inhibition"
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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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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.
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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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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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Billard, Christian, Claire Quiney, and Jean-Pierre Kolb. "Inhibition of Apoptosis by Endogenous Nitric Oxide in Chronic Lymphocytic Leukaemia." In Nitric Oxide (NO) and Cancer, 169–85. New York, NY: Springer New York, 2010. http://dx.doi.org/10.1007/978-1-4419-1432-3_9.
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Romero, Manuel, Celia Mayer, Andrea Muras, and Ana Otero. "Silencing Bacterial Communication Through Enzymatic Quorum-Sensing Inhibition." In Quorum Sensing vs Quorum Quenching: A Battle with No End in Sight, 219–36. New Delhi: Springer India, 2014. http://dx.doi.org/10.1007/978-81-322-1982-8_19.
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Lanning, Jennifer D., and Stephen C. Meredith. "Strategies for Inhibiting Protein Aggregation: Therapeutic Approaches to Protein-Aggregation Diseases." In Non-fibrillar Amyloidogenic Protein Assemblies - Common Cytotoxins Underlying Degenerative Diseases, 433–560. Dordrecht: Springer Netherlands, 2011. http://dx.doi.org/10.1007/978-94-007-2774-8_14.
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Harrington, Kevin J. "Is there a Role for Adjuvant Targeted and Immunotherapies in Patients with Locoregionally-Advanced Head and Neck Cancer?" In Critical Issues in Head and Neck Oncology, 205–19. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-63234-2_14.
Повний текст джерелаАнотація:
AbstractDespite significant technical improvements in the management of patients with locoregionally-advanced head and neck cancers, too many patients fail to achieve durable remissions that ultimately translate into cures. Loco-regional recurrence and/or metastatic relapse after intensive local therapies remain the scourge of those who suffer from this disease, and the surgeons and physicians who treat them. Regrettably, until now, we have failed to develop effective adjuvant therapies that can be delivered after the completion of definitive loco-regional treatment in order to reduce the risk of disease relapse. In this chapter, approaches based on cytotoxic chemotherapy, targeted therapies directed against c-erbB/HER receptors and immune checkpoint inhibition will be discussed. Neither cytotoxic chemotherapy nor anti-HER-family targeted therapies have proven to be successful as adjuvant therapies for locoregionally-advanced head and neck cancers, but there is significant hope that anti-PD1/anti-PD-L1-targeted antibody therapies may deliver progress in this area for the first time.
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Pairet, M., and G. Engelhardt. "Differential inhibition of COX-1 and COX-2 in vitro and pharmacological profile in vivo of NSAIDs." In Improved Non-Steroid Anti-Inflammatory Drugs: COX-2 Enzyme Inhibitors, 103–19. Dordrecht: Springer Netherlands, 1996. http://dx.doi.org/10.1007/978-94-010-9029-2_6.
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Bonavida, Benjamin, Stavroula Baritaki, Sara Huerta-Yepez, Mario I. Vega, Ali R. Jazirehi, and James Berenson. "Nitric Oxide Donors Are a New Class of Anti-cancer Therapeutics for the Reversal of Resistance and Inhibition of Metastasis." In Nitric Oxide (NO) and Cancer, 459–77. New York, NY: Springer New York, 2010. http://dx.doi.org/10.1007/978-1-4419-1432-3_24.
Повний текст джерелаТези доповідей конференцій з теми "NOS inhibition"
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Robert, Cardnell J. G., and Ross B. Mikkelsen. "Abstract 1321: ERK1/2 show different activity profilesin vitroandin vivosubsequent to NOS inhibition." In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-1321.
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Davila-Gonzalez, D., DS Choi, J. Kuhn, SM Granados, RR Rosato, B. Dave, and JC Chang. "Abstract P3-03-02: Inhibition of NOS promotes ER stress response and augments docetaxel-mediated apoptosis in TNBC." In Abstracts: 2016 San Antonio Breast Cancer Symposium; December 6-10, 2016; San Antonio, Texas. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.sabcs16-p3-03-02.
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Ebong, E. E., D. C. Spray, and J. M. Tarbell. "The Roles of HS and Its Glypican-1 Core Protein in Flow-Induced Endothelial NOS Activation and Cell Remodeling." In ASME 2011 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2011. http://dx.doi.org/10.1115/sbc2011-53294.
Повний текст джерелаАнотація:
Endothelial cell (EC) glycocalyx (GCX) is an endovascular protective coat that is degraded in disease. GCX heparan sulfate (HS) proteoglycan is essential for flow-induced nitric oxide (NO) release and cell remodeling, but the HS core proteins involved in these mechanotransduction events are unknown. We hypothesize that the glypican-1 (GPC1) HS core protein mediates flow-induced EC NO synthase (eNOS) activation and is less important for flow-induced cell remodeling, because GPC1 is located in the caveolae where eNOS resides but, to our knowledge, GPC1 has no direct association with the cytoskeleton. We tested our hypotheses by exposing monolayers of bovine aortic EC (BAEC) with intact GCX, heparinase III (HepIII) enzymatically degraded HS, and RNA-silenced GPC1 to 12–15 dyne/cm2 average shear stress for 3 and 24 hours. HS removal by HepIII and GPC1 inhibition by shRNA equally blocked shear-induced eNOS activation that occurs in shear-conditioned BAEC with fully intact GCX. EC remodeling in response to flow was attenuated by HS degradation, but preserved with GPC1 knockdown. These results suggest that while HS is involved in both centralized and decentralized GCX-mediated mechanotransduction mechanisms, GPC1 plays a role in only centralized GCX-mediated mechanotransduction.
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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.
Повний текст джерелаАнотація:
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.
Повний текст джерелаАнотація:
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.
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Zhang, Yixiang, Ewa Sicinska, Samuel Moss, Jeffrey T. Czaplinski, Yuchuan Wang, Christopher Brain, George D. Demetri, Sunkyu Kim, Andrew L. Kung, and Andrew J. Wagner. "Abstract A236: Human liposarcoma growth inhibition by novel CDK4/6 inhibitor LEE011." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Nov 12-16, 2011; San Francisco, CA. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1535-7163.targ-11-a236.
Повний текст джерела
8
Nordfang, O., M. Ezban, and J. B. Knudsen. "IMMUNOASSAY FOR FACTOR VIII-HEAVY CHAIN. AN INDICATOR FOR IMMUNE COMPLEXES DURING HIGH DOSE FVIII INHIBITOR TREATMENT." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644718.
Повний текст джерелаАнотація:
Specificity studies have shown that most hemophilia A inhibitor antibodies are directed towards the light chain of coagulation factor VIII (FVIII). Thus, conventional immunoassays for FVIII-antigen (FVIII:Ag) presumably have reactivity for FVIII-Light Chain (FVIII-LC) . Our sandwich FVIII :Ag assay has been shewn to be specific for only FVIII-LC. We have now developed a specific immunoassay for FVIII-Heavy Chain (FVIII-HC) . This has made it possible to investigate the FVIII-HC content in hemophilia A plasma, and to study the expression of FVIII-HC in culture medium frcm transfected cell lines.By adding purified FVIII-LC and FVIII-HC in coagulation inhibition assay, plasma frcm one of seven hemophilia A inhibitor patients was found to be reactive with both FVIII-LC and FVIII-HC. IgG frcm this plasma was used for a FVIII-HC specific inhibition radioimmunoassay. The polyspecific antibodies were coated to microplates with removable wells. The coated wells were incubated with test sample and with purified 125I-FVIII-HC. When normal human plasma pool contains 1 U/ml of FVIII-HC, the sensitivity of the assay was 0.004 U/ml.For normal plasma and plasma frcm non inhibitor hemophilia A patients, FVIII-HC measurements correlated with FVIII:C and FVIII-LC measurements. However, after FVIII injection hemophilia A inhibitor patients in high dose FVIII treatment showed a much higher FVIII-HC content (1-5 U/ml) than FVIII-LC and FVIII:C (< 0.05 U/ml). These patients have previously been shown to have antibodies towards FVIII-LC. Therefore the antigen measurements indicate that inhibitor patients in high dose FVIII treatment have FVIII/anti-FVIII-LC immune complexes. These circulating immune complexes may be the mediator of an antibody dependent immune tolerance, during the high dose FVIII treatment.
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Ng, Jun Hong Clarence, Tariq Almubarak, and Hisham A. Nasr-El-Din. "Seed Extracts as Natural, Green, Non-Toxic Corrosion Inhibitors." In SPE Trinidad and Tobago Section Energy Resources Conference. SPE, 2021. http://dx.doi.org/10.2118/200935-ms.
Повний текст джерелаАнотація:
Abstract Acid treatments are commonly used in the oilfield to remove inorganic scale or to stimulate formatio ns. These treatments typically consist of using hydrochloric acid (HCl), acetic acid, formic acid, or chelating agents. At elevated temperatures, these acids are highly corrosive and can cause severe damage to tubulars as well as downhole equipment. To reduce damage from these acids, corrosion inhibitors are added to the treatment solution. Corrosion inhibitors used in the oil and gas industry are typically quaternary amines or sulfur-containing compounds. These compounds adsorb to the surface of the metal, thereby reducing contact between the metal surface and the corrosive substance. However, these corrosion inhibitors are damaging to the environment and harmful to human health. Alternative new environmentally-friendly corrosion inhibitors are also either toxic to the human body or face performance limitations at higher temperature field applications. To develop new environmentally friendly and non-toxic corrosion inhibitors for high-temperature applications, 15 edible seeds were tested as alternative sources of corrosion inhibitors. In order to determine the inhibition effect of 15 different seeds, N-80 and S13Cr coupons were exposed to 15 wt.% HCl solutions at temperatures between 77-250°F with 2 wt.% of grounded seed added for 6 hours. In addition, a control solution containing no corrosion inhibitor was used to establish a corrosion rate for a base case. This paper will show the results of such seeds and attempt to provide an awareness of natural seeds extract for use as corrosion inhibitors in conjunction with well acid treatments. It was noted that out of the 15 seeds, seeds 1 and 2 were found to perform the best at these conditions, exhibiting more than 90% corrosion inhibition efficiency. Seed 4 was observed to perform the worst, exhibiting only 16.8% inhibition efficiency. At 150°F, 2 wt.% of seeds 1 and 2 were tested with seed 1 achieving a corrosion rate of 0.00253 lb/ft2 while seed 2 was unable to provide sufficient inhibition with a corrosion rate of 0.153 lb/ft2. The control solution was found to have a corrosion rate of 0.371 lb/ft2 over the 6 hours at 150°F. Seed 1 was further tested at 200°F with the addition of corrosion inhibitor intensifiers and resulted in a corrosion rate of 0.00087 lb/ft2, while at 250°F, a corrosion rate of 0.00811 lb/ft2 was observed. The tests using S13Cr also showed that seed 1 worked well as a corrosion inhibitor for CRAs. The thermal degradation of seed 1 was also examined using NMR. These results show a new naturally occurring, green, non-toxic, high-temperature applicable corrosion inhibitor that can be developed from edible seeds.
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Giannessi, D., R. De Caterina, G. Lazzerini, R. Sicari, and P. Gazzetti. "RELATIVE SENSITIVITY OF CARDIAC PROSTACYCLIN AND THROMBOXANE TO INHIBITION BY NON-STEROIDAL ANTIINFLAMMATORY DRUGS IN THE RAT HEART." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643390.
Повний текст джерелаАнотація:
We have previously shown that the isolated perfused rat Langendorff heart is able to synthesize detectable amounts of thromboxane (TX) A2, as well as prostacyclin (PGI2). Eicosanoid production in this system is increased during post-ischemic reperfusion, reflecting greater availability of substrate and net increase of synthesis. We assessed relative sensitivity of cyclooxygenases synthesizing TX and prostacyclin (probably located in different cell types) to aspirin (0.1, 0.5, 1 g/1), ibuprofen (1, 10, 80, 160, 320 mg/1) and diclofenac (0.01, 0.1, 0.5, 2.5, 5, 10, 25 mg/1), by radioimmunoassays of TXB2 and 6-keto-PGFα in the perfusate. Sixty Wistar male rat hearts were perfused with buffer containing control vehicle or drugs for 30 min, followed by 5 min clamping of the perfusion line and subsequent post-ischemic reperfusion. Baseline production was (mean±SD, pg/min/g wet weight) 754±261 and 143±66 for PGI2 and TXA2, respectively. Peak post-ischemic production was 7628±2673 and 1036±135, respectively. At doses of aspirin, ibuprofen and diclofenac (100, 10 and 2.5 mg/1, respectively) which were equally effective on prostacyclin production (mean % inhibition: 68, 67 and 72 for basal production and 90, 86 and 85 for peak post-ischemic production, respectively), % inhibition of TX production was consistently less, but also similar for the three drugs: 55, 58 and 56 for basal production and 78, 81 and 76 for peak post-ischemic production, for aspirin, ibuprofen and diclofenac, respectively; difference between inhibition of prostacyclin and TX: P < .01, difference for subsets among different drugs: N.S.). TX production was, on the contrary, selectively inhibited by the TX-synthase inhibitor 0KY 046 (by 79 and 92% at 0.1 mg/1, versus a complete sparing of prostacyclin production). The lesser sensitivity of cardiac (vascular?) TX versus prostacyclin to non-steroidal antiinflammatory drugs (NSAIDs) inhibition and the similar degree of inhibition by various NSAIDs, differing in structure and diffusing capacity, suggest heterogeneity among cyclooxygenases present in the system and different intrinsic sensitivity of TX- from prostacyclin-producing cyclooxygenases.
Звіти організацій з теми "NOS inhibition"
1
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.
Повний текст джерелаАнотація:
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.
Повний текст джерелаАнотація:
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.
Повний текст джерелаАнотація:
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.
4
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.
Повний текст джерелаАнотація:
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.
5
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.
Повний текст джерела
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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.
Повний текст джерела
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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.
Повний текст джерела
8
Kang, Jing, Jun Zhang, Zongsheng Tian, Ye Xu, Jiangbi Li, and Mingxina Li. The efficacy and safety of immune-checkpoint inhibitor plus chemotherapy versus chemotherapy for non-small cell lung cancer: an updated systematic review and meta-analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, May 2022. http://dx.doi.org/10.37766/inplasy2022.5.0156.
Повний текст джерелаАнотація:
Review question / Objective: Population: histologically confirmed advanced NSCLC patients; Intervention: received immune-checkpoint inhibitor plus chemotherapy; Comparison:received chemotherapy; Outcome: reported OS, PFS, ORR and TRAEs; Study design: RCT. Condition being studied: Lung cancer is the primary cause of cancer-related deaths, with an estimated 2.20 million new cases and 1.79 million deaths every year, and 85% of all primary lung cancers are non-small cell lung cancer. Eligibility criteria: Studies were considered eligible if they met the following criteria: (1) being an randomized controlled trial published in English, (2) histologically confirmed advanced NSCLC patients, (3) reported OS, PFS, ORR and TRAEs, (4) the intervention group received immune-checkpoint inhibitor plus chemotherapy, while the control group received chemotherapy, (5) When numerous papers reporting the same trial were found, the most current or most complete publications were chosen. The following were the exclusion criteria: (1) duplicate articles, (2) reviews, meta-analyses, case reports, editorials and letters, (3) molecular biology or animal research, (4) retrospective or prospective observational cohort studies.
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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.
Повний текст джерелаАнотація:
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.
Повний текст джерелаАнотація:
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.