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1
Hay, Marshall Mark. "Control of Palmer amaranth (Amaranthus palmeri) and common waterhemp (Amaranthus rudis) in double crop soybean and with very long chain fatty acid inhibitor herbicides." Thesis, Kansas State University, 2017. http://hdl.handle.net/2097/35489.
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Master of ScienceDepartment of Agronomy
Dallas E. Peterson
During 2015 and 2016, five site years of research were implemented in double crop soybean after winter wheat at experiment fields in Kansas near Manhattan, Hutchinson, and Ottawa to assess various non-glyphosate herbicide treatments at three different application timings for control of Palmer amaranth (Amaranthus palmeri S. Wats.) and common waterhemp (Amaranthus rudis Sauer). Spring-post (SP) treatments with residual control of Palmer amaranth and waterhemp were applied in the winter wheat at Feekes 4 and resulted in less than 50% control of Palmer amaranth and waterhemp at the time of double crop soybean planting. Pre-harvest treatments were applied two weeks before winter wheat harvest. 2,4-D resulted in highly variable Palmer amaranth and waterhemp control whereas flumioxazin resulted in comparable control to PRE treatments that contained paraquat plus a residual herbicide. Excellent Palmer amaranth and waterhemp control was observed at 1 week after planting (WAP) double crop soybean with a preemergence (PRE) paraquat application; however, reduced control of Palmer amaranth and waterhemp was noted at 8WAP due to extended emergence. Palmer amaranth and waterhemp control was 85% or greater at 8WAP for most PRE treatments that included a combination of paraquat plus residual herbicides. PRE treatments that did not include the combination of paraquat and residual herbicides did not provide acceptable control. A second set of field experiments were established in 2015 and 2016 near Manhattan, Hutchinson, and Ottawa to assess residual Palmer amaranth and waterhemp control with very-long-chain-fatty acid (VLFCA) inhibiting herbicides. Acetochlor (non-encapsulated and encapsulated), alachlor, dimethenamid-P, metolachlor, S-metolachlor, and pyroxasulfone as well as the microtubule inhibiting herbicide pendimethalin were applied at three different field use rates (high, middle, and low) based on labeled rate ranges for soybean as PRE treatments in a non-crop scenario after the plot was clean tilled with a field cultivator. The experiment was conducted one time in 2015 and four times in 2016 at two different locations for a total of five site years of data. PRE applications were made June 1, 2015, near Manhattan. PRE applications in 2016 were made in April at locations near Hutchinson and Ottawa; the second run of the experiment was applied in June at the same locations on a different set of plot areas. At Manhattan pyroxasulfone, S-metolachlor, and dimethenamid-P resulted in the highest Palmer amaranth control at 4WAT. At Hutchinson, pyroxasulfone resulted in superior Palmer amaranth control compared to dimethenamid-P and pendimethalin at 4WAT and 8WAT. At Ottawa, acetochlor, S-metolachlor, and pyroxasulfone resulted in higher waterhemp control than alachlor and pendimethalin at 4WAT and 8WAT.
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Rothmayr, Christoph. "Common and distinct neural networks for theory of mind reasoning and inhibitory control." Diss., lmu, 2009. http://nbn-resolving.de/urn:nbn:de:bvb:19-124976.
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Pei, Fen, Susanne DiSalvo, Suzanne S. Sindi, and Tricia R. Serio. "A dominant-negative mutant inhibits multiple prion variants through a common mechanism." PUBLIC LIBRARY SCIENCE, 2017. http://hdl.handle.net/10150/626074.
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Prions adopt alternative, self-replicating protein conformations and thereby determine novel phenotypes that are often irreversible. Nevertheless, dominant-negative prion mutants can revert phenotypes associated with some conformations. These observations suggest that, while intervention is possible, distinct inhibitors must be developed to overcome the conformational plasticity of prions. To understand the basis of this specificity, we determined the impact of the G58D mutant of the Sup35 prion on three of its conformational variants, which form amyloids in S. cerevisiae. G58D had been previously proposed to have unique effects on these variants, but our studies suggest a common mechanism. All variants, including those reported to be resistant, are inhibited by G58D but at distinct doses. G58D lowers the kinetic stability of the associated amyloid, enhancing its fragmentation by molecular chaperones, promoting Sup35 resolubilization, and leading to amyloid clearance particularly in daughter cells. Reducing the availability or activity of the chaperone Hsp104, even transiently, reverses curing. Thus, the specificity of inhibition is determined by the sensitivity of variants to the mutant dosage rather than mode of action, challenging the view that a unique inhibitor must be developed to combat each variant.
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Maire, Marie-Aline Vasseur Paule. "Inhibition de l'apoptose comme facteur de la transformation morphologique des cellules embryonnaires de hamster Syrien." Metz : Université Metz, 2008. ftp://ftp.scd.univ-metz.fr/pub/Theses/2004/Maire.Marie_Aline.SMZ0434.pdf.
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Isaacs, Mark Allen. "Investigations on the Interations of Acetolactate Synthase (ALS)-Inhibiting Herbicides with Growth Regulator and non ALS-Inhibiting Herbicides in Corn (Zea mays) and Selected Weeds." Diss., Virginia Tech, 2000. http://hdl.handle.net/10919/77970.
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Herbicide combinations are common in corn production in the United States to control broadleaf and grass weed species. Studies were conducted in 1995 and 1996 to: (1) investigate the interactions of 2,4-D and dicamba with halosulfuron-methyl on common lambsquarters and common ragweed control in corn, (2) determine the effect of 2,4-D on the foliar absorption, translocation, and metabolism of 14C halosulfuron-methyl in common lambsquarters, (3) examine the interactions of 2,4-D, dicamba, and ALS-inhibitor herbicides with rimsulfuron plus thifensulfuron-methyl (RT) and with sethoxydim on giant foxtail, common ragweed, and common lambsquarters control in corn. Combinations of halosulfuron-methyl with 2,4-D or dicamba were generally additive in their effects on common lambsquarters and common ragweed control, and were occasionally synergistic on common lambsquarters. Synergistic herbicide interactions in the greenhouse were observed with 2,4-D (17 g/ha ) and halosulfuron-methyl (18 g/ha) and 2,4-D (70 g/ha ) in combination with halosulfuron-methyl at 4.5 and 36 g/ha, respectively. Absorption and translocation of 14C-halosulfuron-methyl were not influenced by the addition of 2,4-D, with absorption increasing with time. Three unknown halosulfuron-methyl metabolites (M1, M2, and M3) with Rf values of 0.0, 0.97, and 0.94, respectively, were isolated. The addition of 2,4-D increased the level of M3 at the 18 g/ha halosulfuron-methyl rate, which may contribute to common lambsquarters phytotoxicity. Antagonism on giant foxtail control was observed with all combinations of RT and 2,4-D. Tank mixtures of RT with flumetsulam plus clopyralid plus 2,4-D, atrazine, 2,4-D, and dicamba plus atrazine controlled giant foxtail £ 78% 65 (DAT). RT mixed with flumetsulam plus clopyralid plus 2,4-D injured corn 26%, and yields were reduced 34% when compared to RT alone. Giant foxtail control from sethoxydim tank-mixed with bentazon plus atrazine with urea ammonium nitrate (UAN), or with ALS-inhibiting herbicides except halosulfuron-methyl in combination with 2,4-D was 24% lower when averaged over treatments. Yields of sethoxydim-resistant (SR) corn treated with sethoxydim mixed with combinations of sulfonylurea herbicides plus 2,4-D were low, with the exception of the combination halosulfuron-methyl with sethoxydim and 2,4-D. These studies indicate that thoroughly understanding postemergence (POST) corn herbicide tank mixtures is crucial for effective weed management.Ph. D.
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Lang, Jean. "Calcium et actions pharmacologiques sur les tissus spécialisé et commun auriculaires." Lyon 1, 1987. http://www.theses.fr/1987LYO1H069.
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Zaffarano, Jennifer I. "MINIMUM INHIBITORY CONCENTRATIONS OF TWO COMMON FOOD PHENOLIC COMPOUNDS AND THEIR EFFECT ON THE MICROBIAL ECOLOGY OF SWINE FECES IN VITRO." UKnowledge, 2003. http://uknowledge.uky.edu/gradschool_theses/182.
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Feeding sub-therapeutic levels of antibiotics to livestock has been associated withdevelopment and spread of antibiotic resistant bacteria. The present experiment was conductedto investigate the effect of antibiotic alternatives (caffeic acid, chlorogenic acid, and carbadox)on the microbial ecology of swine feces in vitro.Minimum inhibitory concentrations of caffeic and chlorogenic acids were determined forseveral pathogens using macrobroth and agar dilution techniques. Gram-negative bacteria werenot inhibited. Caffeic acid inhibited four Staphylococcus aureus strains at 200 ppm or less, andtwo Clostridium perfringens strains at 300 ppm. Chlorogenic acid inhibited all S. aureus strainsat 500 ppm, and one C. perfringens strain at 400 ppm.Effects of antibiotic alternatives on fecal microbial ecology were determined using an invitro incubation. Caffeic acid lowered total anaerobes, Bifidobacteria, Escherichia coli, andpercent E. coli (pandlt;0.01). Chlorogenic acid lowered total anaerobes, Bifidobacteria, andlactobacilli (pandlt;0.01), and increased acetate concentration (pandlt;0.0001). Carbadox lowered totalanaerobes, Bifidobacteria, E. coli, and coliforms (pandlt;0.01), and lowered acetate, propionate,butyrate, valerate, and total volatile fatty acid concentrations (pandlt;0.01). It can be concluded thataddition of caffeic acid, chlorogenic acid, or carbadox effected bacterial and chemicalcomponents of the microbial ecology of swine feces.
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Zaffarano, Jennifer I. "Minimum inhibitory concentration of two common food phenolic compounds and their effects on the microbial ecology of swine feces in vitro." Lexington, Ky. : [University of Kentucky Libraries], 2003. http://lib.uky.edu/ETD/ukyansc2003t00099/JZThesis.pdf.
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Thesis--University of Kentucky (M.S.), 2003.Title from document title page. Document formatted into pages; contains ix, 127 p. : ill. Includes abstract and vita. Includes bibliographical references (p. 110-126).
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Sekhon, Jaspreet. "Antisense inhibition of methylenetetrahydrofolate reductase as a cancer treatment and a pharmacogenetic study to examine the effects of a common polymorphism." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=33029.
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Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme in the metabolism of folate and methionine. MTHFR catalyzes the conversion of 5,10 methylenetetrahydrofolate (5,10-methyleneTHF) to 5-methyltetrahydrofolate (5-methylTHF). 5-MethylTHF is a co-substrate for homocysteine remethylation to methionine catalyzed by the vitamin B12-dependent enzyme methionine synthase. A common MTHFR variant, 677C → T substitution resulting in the conversion of an alanine to a valine residue, has been shown to be a thermolabile form of MTHFR and to have reduced activity (Frosst et al., 1995). Since many diverse cancer cells have been documented to be methionine-dependent in culture, the effects of MTHFR downregulation on cell survival of transformed cells was examined. In addition, the influence of the MTHFR 677C → T polymorphism on the sensitivity of transformed lines to antifolate drug treatment was studied.To test the effect of decreased MTHFR expression on cell viability, we transfected antisense oligonucleotides (ASOs) complementary to the MTHFR mRNA into the colon carcinoma cell line SW620. (Abstract shortened by UMI.)
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Sköld, Anna-Carin. "Teratogenicity as a consequence of drug-induced embryonic cardiac arrhythmia : Common mechanism for almokalant, sotalol, cisapride, and phenytoin via inhibition of IKr." Doctoral thesis, Uppsala University, Department of Pharmaceutical Biosciences, 2000. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-515.
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During the last years, drugs that prolong the repolarisation phase of the myocardial action potential, due to inhibition of the rapid component of the delayed-rectifying potassium channel (IKr) have been in focus. In addition to arrhythmogenic potential, selective Ikr-blockers have also been shown to be embryotoxic and teratogenic in animal studies. The aim of this thesis was to investigate a theory that these developmental toxic results from pharmacologically induced episodes of embryonic cardiac arrhythmias leading to hypoxia related damage in the embryo. Almokalant (ALM) was used as a model compound for selective Ikr-blockers. ALM induced embryonic cardiac arrhythmia, and in similarity with results obtained by maternal hypoxia, ALM induced embryonic death and growth retardation in both rats, and mice.
The theory of a hypoxia-related mechanism was strengthened by the results that ALM induce phase specific external and visceral defects (e.g. cleft lip/palate, distal digital, cardiovascular, and urogenital defects), and that the skeletal defects (not shown before) showed a clear trend; the later the treatment the more caudal was the site of the defect, which is in accordance with results from maternal hypoxia induced by e.g. lowering of the O2 content in the air. The spin trapping agent PBN decreased almokalant induced malformations, suggesting that the defects mainly are caused by reoxygenation damage after episodes of severe embryonic dysrhythmia, rather than "pure hypoxia".
Sotalol was tested in a third species, the rabbit who expresses functional IKr channels both in the embryo and in the adult, where it induced developmental toxicity, and indicating that the embryo is more sensitive than the adult towards arrhythmia caused by IKr-blockers.
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Djuv, Ane. "Co-Use of Drugs and Herbal Remedies in General Practice and In Vitro Inhibition of CYP3A4, CYP2D6 and P-Glycoprotein by the Common Herb Aloe Vera." Doctoral thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for kreftforskning og molekylær medisin, 2013. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-23578.
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There is a widespread use of complementary and alternative medicine (CAM) and herbal remedies in particular in different patients groups, but very few are published about co-use among patients in general practice (GP) and herb-drug combinations at risk. Co-use of herbal remedies and drugs can result in none or server adverse effects. Of this reason, knowledge about the GP patients co-use and research on mechanisms of such interactions is needed. The aims of this thesis were divided; 1) To register the co-use of drugs and herbs among GP patients in Norway and the patients communication of such use with health care professionals; 2) To evaluate the interaction potential of one of the commonly used herbs in GPs office, Aloe vera (Aloe barbadensis), on the P-glycoprotein (P-gp) and the cytochrome P-450 (CYP) enzymes, CYP3A4 and CYP2D6. Among the 381 patients answering the questionnaire in the GP office, 44% used herbs. The most common herbs were bilberry (41%), green tea (31%), garlic (27%), Aloe vera (26%) and purple coneflower (18%). Almost every third (29%) patient co-used drugs and herbs. They combined 255 different drug-groups and herbs whereas 18 of these were considered to have a clinically relevant interaction potential. Close to 40% of patients on anticoagulants co-used herbs, reporting garlic and bilberry most frequently. Co-users had significantly (p<0.05) increased odds to be female, elderly, use herbs to treat an illness, use two or more herbs and experienced adverse effects of herbal use compared to other GP patients. Co-use was also associated with use of analgesics or dermatological drugs. Only 23% of the GP patients discussed their herb use with a health care professional. Even though Aloe vera is a well-known, old medicine plant used both in cosmetics and as therapeutics, few or no earlier systematic research on its interaction potential has been investigated when co-used with drugs in vitro. Overall three enzymes accounts for the majority of the pharmacokinetics on the drugs in the market: the efflux-protein P-gp transporting the medicinal drug out of the cell and CYP3A4 and CYP2D6, metabolizing the medicinal drugs to less active components. These enzymes can be influenced by other substances (inhibited or induced) and is therefore important regarding herb-drug interactions. Aloe vera juice (AVJ) did not inhibit P-gp mediated digoxin efflux for the investigated AVJ concentrations in vitro. However, it was shown that both AVJ (10.0 mg/ml) and digoxin (≥3µM) was cytotoxic in large concentrations. Two different AVJs were used in the CYP3A4 and CYP2D6 assays. Both juices inhibited CYP3A4 and CYP2D6 irreversible in vitro, having significant different IC50 values. This can come from different concentrations of active components in the juices. Both IC50 values seems, however, to be too high to be clinical relevant alone. Precautions should although, be made with excessive consumption of AVJ, with poor CYP2D6 activity ("poor metabolisers") or with use of drugs having a narrow therapeutic window. It can be concluded that GP patients co-using drugs and herbs and that this use can give clinical relevant interactions (e.g. excessive haemorrhage when co-using garlic and warfarin). Elderly patients are most vulnerable for co-use. One of the common used herbs among GP patients, Aloe vera, was investigated for in vitro pharmacokinetic interactions on the enzymes P-gp, CYP3A4, CYP2D6. Although it was concluded with low possibility of clinical relevant pharmacokinetic interactions co-using Aloe vera and drugs, patients with poor CYP2D6 activity might risk interactions when co-using large quantities of Aloe vera with conventional drugs which is metabolized of CYP2D6 (e.g. codeine). Clinical in vivo studies are needed to reveal any interactions in humans for Aloe vera and other herbs at risk of herb-drug interactions. Until then, the GPs and other health care professionals are advised to ask all patients about herbal use.
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Maire, Marie-Aline. "Inhibition de l'apoptose comme facteur de la transformation morphologique des cellules embryonnaires de hamster Syrien." Metz, 2004. http://docnum.univ-lorraine.fr/public/UPV-M/Theses/2004/Maire.Marie_Aline.SMZ0434.pdf.
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Le but de ce travail consistait d'une part, à étudier l'hypothèse qu'une défaillance des processus apoptotiques favoriserait la transformation cellulaire, et d'autre part, à élucider certains des mécanismes moléculaires de substances inhibitrices de l'apoptose. Ce travail a été réalisé sur les cellules embryonnaires de hamster Syrien, des cellules normales, diploïdes et capables de métaboliser un grand nombre de substances chimiques. Cette étude a été appliquée à trois substances, le zinc, inhibiteur de l'apoptose, le DEHP (di-2-ethylhexyl phtalate), transformant in vitro, le 2,4-D (acide 2,4-dichlorodiphénoxyacétique), apparenté au DEHP au plan mécanistique, en tant que proliférateur de peroxysomes hépatiques. Dans une 1ère partie, nous avons montré que les substances anti-apoptotiques testées (zinc et DEHP) induisaient la transformation morphologique des cellules SHE. Quant au 2,4-D, il augmentait la transformation morphologique des cellules SHE mais sans inhiber l'apoptose. Dans une 2nde partie, nous avons montré que le zinc et le DEHP exerçaient leurs propriétés anti-apoptotiques en augmentant le ratio des protéines Bcl-2/Bax. Les résultats concernant l'implication du proto-oncogène c-myc dans l'apoptose et dans la transformation cellulaire, sont plus complexes. Le 2,4-D augmente l'expression de c-myc ce qui pourrait être relié à l'augmentation de la transformation morphologique. Quant au DEHP, il diminue l'expression de c-myc parallèlement à l'augmentation de Bcl-2, suggérant que c-myc pourrait interagir avec certains gènes de la voie apoptotique mitochondrialeApoptosis, a cell suicide pathway, is implicated in various physiological events, in particular the elimination of damaged cells. The defective regulation of apoptosis may contribute to the etiology of cancer and the impairment of normal cell death process has been implicated in neoplastic transformation. In order to test the hypothesis of a relationship between apoptosis and neoplastic transformation, we studied three chemicals, zinc as inhibitor of apoptosis, DEHP (di-2-ethylhexyl phtalate) which induced cell transformation and 2,4-D (2,4-dichlorodiphénoxyacetic acid), a peroxysome proliferators such DEHP. First, we demonstrated that anti-apoptotic chemicals (zinc and DEHP) induced SHE cell transformation. These results were in agreement with the theory of a relationship between the inhibition of apoptosis and the induction of cell transformation. However, 2,4-D induced SHE cell transformation while it has no effect on apoptosis. Second, we showed that zinc and DEHP inhibited apoptosis through an increase of the bcl-2/bax ratio. Results concerning the involvement of the proto-oncogene c-myc in apoptosis and in cell transformation are more complex. We showed that 2,4-D induced c-myc expression at concentrations which induced cell transformation. On the opposite, DEHP decreased c-myc expression which could be related to the increase of the Bcl-2 expression
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Pagé-Veillette, Hélène. "Caractérisation moléculaire d'un mutant d'arabidopsis thaliana résistant à la thaxtomine A." Mémoire, Université de Sherbrooke, 2012. http://hdl.handle.net/11143/5747.
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La thaxtomine A (TA) est la principale toxine produite par l'agent pathogène causant la gale commune Streptomyces scabies.La TA est nécessaire et suffisante à l'induction des symptômes de la maladie.La TA a un rôle d'inhibiteur de la synthèse de la cellulose et cause une inhibition importante de la croissance racinaire chez Arabidopsis thaliana. Ce projet avait pour objectif de caractériser un mutant d'Arabidopsis plus résistant à la TA, 9F32, dans le but de mieux comprendre le mécanisme d'action de la TA. 9F32 a démontré une résistance trois fois plus importante à la TA que Col 0, autant au niveau du phénotype global qu'au niveau de la croissance racinaire. Le taux d'entrée de la TA mesuré chez 9F32 est significativement inférieur à celui du type sauvage et comparable à celui d'un mutant présumé du transport de la toxine, txr1. Une analyse de micro-puces à ADN a montré la variation d'expression de 195 gènes chez 9F32, 174 gènes ont une expression augmentée et 21 sont réprimés (FC [supérieur ou égal] 2). Cette analyse a montré que le mutant présente une expression augmentée des réponses de stress, et plus particulièrement de la voie de réponse de défense de l'acide salicylique. 9F32 présente un phénotype et une expression transcriptionnelle partageant les caractéristiques d'une privation de phosphore, soit une petite taille et une production accrue d'anthocyanines. Finalement, l'infection du mutant 9F32 avec la bactérie S. scabies a montré une diminution des symptômes par rapport au type sauvage Col 0. Ces résultats suggèrent que la résistance à la TA procure un avantage important lors de l'infection. 9F32 est donc un outil adéquat pour l'étude du mécanisme de la TA et ses phénotypes laissent présager un nouveau mécanisme de résistance à la toxine.
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Messaadia, Hocine. "Les facteurs d'inhibition de la régénération naturelle du hêtre (fagus sylvatica L. ) dans la forêt domaniale de Lyons (Haute-Normandie), influence de l'allélopathie et du mode de recyclage des litières forestières." Rouen, 1987. http://www.theses.fr/1987ROUES041.
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Cette étude consacrée aux facteurs d'inhibition de la régénération du hêtre (fagus sylvica L) dans les stations à moder mulleux met en évidence l'action allélopathique de composés phénoliques (acides benzoïque, salicylique, cinnamique) qui proviennent des litières fraîches et des feuilles de hêtre et de ronce (Rubus sp)
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Wang, Hsi-Hua, and 王晞華. "Purification and activity of α-amylase inhibitor 1 from NaN3-induced common bean mutants." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/87146006711412832532.
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碩士國立中興大學
農藝學系所
98
Common bean (Phaseolus vulgaris L.) contain α-amylase inhibitor 1 (α-AI1), which would bind α-amylase and subsequently reduce starch digestion. Thus, α-AI1 can be used to control the deterioration of type II diabetes and obesity. In this study, a three-phase partitioning (TPP) technique was used to extract and purify α-AI1 from common bean. The crud extracts were adjusted to pH 5.25, and 30% ammonium sulfate was added. Then the tert-butanol was added to the mixing solution for obtaining three phases. The results indicated that the α-AI1 proteins were mainly recovered in the aqueous phase. The purified α-AI1 for varieties PI-40 and Hwachia were 7.6 fold and 18 fold, respectively. The recovery of total activity was 81 % and 66 %, respectively, for PI-40 and Hwachia. AFLP (amplified fragment length polymorphism) was subsequently used to assess genetic diversity among Hwachia and it 34 NaN3-induced mutants. Nine NaN3-induced mutants and Hwachia and 2 introduced varieties used for α-AI1 purification by using TPP and then the α-AI1 inhibitor activity was determined. The results showed that the mutant SA-05 had higher inhibitor activity than other NaN3-induced mutants and Hwachia. Thus, mutant SA-05 may be useful in commercial preparation of α-AI1.
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PATEL, KUNAL. "PARALLEL VIRTUAL SCREENING TO DISCOVER PHYTOCOMPOUNDS TO COUNTER THE RESISTANCE INDUCING EFFECT OF DOUBLE MUTATIONS IN MDR TUBERCULOSIS." Thesis, 2014. http://dspace.dtu.ac.in:8080/jspui/handle/repository/15469.
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Drug resistant tuberculosis has threaten all the advances made in tuberculosis control at the
global stage in the last few decades. Resistance to quinolone class of drug like Ofloxacin
which are being used as a main drug for multiple drug resistant tuberculosis treatment have
given rise to cases of extensive drug resistant tuberculosis. DNA gyrase enzyme, essential for
DNA replication, translation, and transcription are targeted by quinolones for their
bactericidal effect and can be an excellent target for antibacterial drug discovery. Mutations
in quinolone resistance determining region of gyrase enzyme, especially in gyrA subunit have
conferred resistance to quinolones based drugs. Here we report, a successful application of
High Throughput Virtual Screening (HTVS) in identification of a common inhibitor for both
wild type and mutant type Mycobacterium DNA gyrase. The most prevalent double mutant
strain of tuberculosis that were targeted here is 90V94G, 74S94G and 90V91P DNA gyrase.
Chebulinic Acid (CA), a phytocompound obtained from Terminalia chebula was the outcome
of present HTVS study as a most potent inhibitor. Also, four more compounds were
identified along with CA from a virtual library of 1, 79,299 compounds, but they were less
potent compared to CA. CA scored high Extra Precision docking score i.e. -14.63, -16.46,
15.94 and -15.11 against wild type and 90V94G, 74S94G and 90V91P double mutants
respectively. The complex was stabilized by multiple H bonding and numerous hydrophobic
interaction. This was shown by molecular dynamics simulation studies for a period of 16ns,
lower root mean square deviation (RMSD) value and lower root mean square fluctuation
(RMSF) value of residues interacting with ligand indicated a formation of stable complexes
in all the four cases. The dual inhibition mechanism seems to be pretty effective as CA is
causing displacement of catalytic tyr129 residue from 1.6A ْ to 7.3 A ْ from its target
phosphate molecule. Also, the CA is causing stearic hindrance to DNA strand at the DNA
gate site resulting in loss of cleavage and religation activity of the enzyme. This
phytocompound displays desirable quality for carrying forward as a lead compound for drug
development.
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Van, der Walt Lydia. "Reproductive inhibition in female common and highveld mole-rats: neuroanatomical and neuroendocrine perspectives." Thesis, 2004. http://hdl.handle.net/2263/24996.
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The social reproductive inhibition evident in female common (Cryptomys hottentotus hottentotus) and highveld (Cryptomys hottentotus pretoriae) mole-rats was investigated, focussing on intra- and inter-subspecies differences in gonadotropin¬releasing hormone (GnRH) neuroanatomy and neuroendocrinology and potential mechanisms mediating social infertility through the suppression of luteinizing hormone (LH) and/or GnRH synthesis or release. The molecular structure of the GnRH peptide present in highveld mole-rat tissue was determined. Messenger ribonucleic acid (mRNA) coding for GnRH was isolated from hypothalamic tissue of a female highveld mole-rat. The nucleotide sequence of the transcribed complimentary deoxyribonucleic acid (cDNA) predicts amino acid sequences that indicate a potential polymorphism in the mature peptide. These sequences differ from classic 'mammalian' GnRH by either one or two amino acid positions. One form of mole-rat GnRH is identical to the unique GnRH expressed by guinea pigs, while the second form differs from guinea pig GnRH in one amino acid position. These results indicate that classic 'mammalian' GnRH is not the chief structural form of GnRH in the mole-rat. In both the common and highveld mole-rat, GnRH structures were loosely distributed along the septo-preoptico-infundibular pathway. Highveld mole-rats consistently had more GnRH cell bodies and higher levels of the peptide than common mole-rats. The subspecies also differed with regards to the relative distribution of GnRH cell bodies in the preoptic area and the medio-basal hypothalamus. Reproductive status and season did not influence GnRH neuroanatomy (numbers and morphology of cell bodies, distribution of GnRH structures and density of GnRH staining in the median eminence) or endogenous brain GnRH content in male or female common mole-rats. Likewise reproductive and non-reproductive male highveld mole-rats did not differ with regards to the GnRH neuroanatomical and neuroendocrinological parameters investigated. Dominant and subordinate female highveld mole-rats had similar numbers of GnRH cell bodies, and did not differ with regards to the distribution of GnRH structures. Brain GnRH levels was however significantly lower in reproductive females compared to non-reproductive females. Similarly, GnRH staining in the median eminence was significantly less intense in reproductive compared to non-reproductive females, indicating reduced release in the latter. Excess peptide most likely accumulates in the nerve terminals and the cell bodies. Endogenous opioid peptides (EOPs) are tentatively considered to playa role in the socially-induced infertility in non-reproductive female highveld mole-rats. Intact reproductive females and intact and ovariectmized non-reproductive females were treated with the opioid antagonist naloxone, alone and in different combinations with exogenous GnRH, to establish the role of EOPs and gonadal hormones in the reduced GnRH release evident in subordinate female highveld mole-rats. Naloxone treatment failed to alter plasma LH levels in any of the intact groups, while ovariectomized non-reproductive females showed a significant response. The pituitary response to a GnRH challenge was not influenced by either a single naloxone administration or longer term naloxone-priming regimens. In the absence of the negative feedback effects of gonadal steroids following ovariectomy, non¬reproductive females showed GnRH-chalienged plasma LH levels similar to that seen in intact reproductive females, both being significantly higher compared to intact non-reproductive females. Steroid-dependent mechanisms altering GnRH secretion and/or pituitary sensitivity to the endogenous peptide may therefore playa role in the social reproductive regulation displayed by the highveld mole-rat. EOPs may be indirectly involved in steroid negative feedback suppression of GnRH. In conclusion, the GnRH neuroanatomy and neuroendocrinology of female common mole-rats provide no evidence for a physiological component to the behavioural reproductive restraint in subordinate females due to incest avoidance. Non¬reproductive female highveld mole-rats are, however, temporarily infertile due to pituitary insensitivity to GnRH coupled with suppressed hypothalamic GnRH release potentially mediated by steroid-dependent mechanisms.Thesis (PhD)--University of Pretoria, 2005.
Zoology and Entomology
unrestricted
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Rothmayr, Christoph [Verfasser]. "Common and distinct neural networks for theory of mind reasoning and inhibitory control / vorgelegt von Christoph Rothmayr." 2009. http://d-nb.info/1009712195/34.
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Biegler, Kelly Ann. "Competition and inhibition in lexical retrieval: Are common mechanisms used in language and memory tasks?" Thesis, 2007. http://hdl.handle.net/1911/20578.
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The following series of experiments examined whether common mechanisms are involved in word retrieval within language and memory domains. Four patients with short-term memory (STM) deficits were examined; however, two of the patients showed a consistent impairment in inhibiting irrelevant verbal information as well. To the extent that repeatedly retrieving verbal items from the same category would require the capacity to suppress competing items to select the target, we investigated whether patients with a verbal inhibitory deficit, in addition to a reduced STM capacity, would be impaired in retrieving items in a semantic context relative to STM patients who do not display a similar verbal inhibition deficit and normal control subjects. Experiments 1- 4 consisted of language tasks which required the repeated naming or matching of items in a semantic or unrelated context. The findings revealed that verbal inhibition patients showed the greatest degree of difficulty during picture naming relative to the matching tasks in a semantic context, suggesting that they are susceptible to interference from semantic competitors to a greater extent at a lexical level. Experiments 5 - 7 consisted of recall and recognition memory tasks with items in a semantically related or unrelated context. Experiments 5 and 6 showed that while STM patients and controls displayed a similar degree of interference for items in a semantic context, STM patients can recall and recognize items near or within the range of controls when demands on STM capacity are minimal during encoding. However, Experiment 7 showed that recall can decline for patients with STM deficits when items are processed more rapidly during encoding. The results from Experiments 5 - 7 suggest that interference among items from the same category can occur in memory tasks (at a conceptual level), but verbal inhibition patients are not affected to a greater degree than control subjects. The overall findings are interpreted within the framework of spreading activation models, and provide implications for potential differences in competition and selection demands at lexical and conceptual levels of representation.
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Chiang, Yi-Chen, and 江怡晨. "Characteristics of common bean seed extracts and their inhibitory activities against aldose reductase, α-amylase, and α-glucosidase in vitro." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/umvjeh.
Full textAbstract:
碩士國立中興大學
農藝學系所
101
Common bean (Phaseolus vulgaris L.) contain many polyphenolics compounds and and α-amylase inhibitor 1 (α-AI1). These bioactive compounds can be used to regulate the carbohydrate metabolism, slow down the intake of sugars and thus reduce the risks of diabetes mellitus and related diabetic complications. In this study, the polyphenolics andα-AI1s were extracted from the seeds of NaN3-induced mutant SA-05 and its wild type Hwachia by using various solvents. The chemical contents and the inhibitory activities of prepared extracts against α-amylase, α-glucosidase and aldose reductase, which were involved in carbohydrate metabolism, were examined. The result indicated that the mutant SA-05 produced higher extraction yield and extracted more bioactive compounds that Hwachia. Both the 50%- ethanol and 80%-methanol polyphenolics rich extracts prepared from mutant SA-05 and Hwachia had potent inhibitory abilities against aldose reductase and α-glucosidase with estimated IC50 values ranged between 1.32 ~ 1.94 and 0.36 ~ 0.46 mg dry mass weight ml-1, respectively. The 50%-ethanol polyphenolics rich extract also demonstrated inhibitory activity against α-amylase activity. The α-AI1 rich extracts prepared from the seeds of mutant SA-05 exhibited higher inhibitor activity against α-amylase than the extract prepared form the seeds of Hwachia. The estimated IC50 values for SA-05 ranged between s 17.68 ~ 31.11 μg dry mass weight ml-1. Thus, an initial 50%-ethanol extraction followed with a subsequent H2O extraction appears to be an appropriate choice for producing polyphenolics-rich extracts and α-amylase inhibitor-rich extracts because this way increased production of polyphenol and reduced costs. However, mutant SA-05 produced more proteinaceous α-amylase inhibitor with higher level of inhibitory activity than variety Hwachia. Therefore, mutant SA-05 is a desirable choice for producing anti-hyperglycemic compounds.
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Liu, Yueh-Sung, and 劉岳松. "Study on the inhibitory effects of immobilized antibacterial substrata coated with quaternary ammonium salt or silver ion against common waterborne pathogens." Thesis, 1999. http://ndltd.ncl.edu.tw/handle/52146364516901914484.
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碩士國立海洋大學
食品科學系
87
Immobilized antibacterial substrata are carrying the antibacterial component via binding or coating to the surface of solid material, and make the solid material have antibacterial activities. The inhibitory effect of this coating substratum is mainly progressing by contacting or releasing gradually the antibacterial compound. This study takes honeycombs ceramic and carborundum coating with quaternary ammonium salt or silver ions were produced by Cargico Engineering Corp. to study the influence of antimicrobes substratum to the usual seen pathogens in water. The antibacterial substrata coated with quaternary ammonium salt (QAS) showed no inhibitory effect on Escherichia coli O157 and Pseudomonas aeruginosa, but showed evidently inhibitory effect on Listeria monocytogenes, Staphylococcus aureus, Streptococcus faecalis, and Shigella dysenteriae. The sensitive bacteria had their aerobic plate count (APC) decreased from 7.0 to below 2.3 log CFU/mL in 24 hours. The most sensitive bacteria in this study is Staph. aureus, because that its APC could be lowered down 5.0 log CFU/mL in 1 hour. The inhibitory effect of carborundum coated with 1.0 wt% quaternary ammonium salt is more efficiently than honeycombs ceramic had same coating treatment. The different range of APC between these two QAS coated substrata is about 1.0-4.0 log CFU/mL depending on test bacterial strains. The result of this study showed the inhibitory effect of carborundum coated with 1.0 wt% QAS is more efficiently than the 0.2 wt% QAS coated carborundum had (about 1.0-2.0 log CFU/mL). The streaming reacting mode could show more efficiently inhibitory effect. As every 20 g carborundum is added to the reacting solution, the survivors would decrease about 1.0-2.0 log CFU/mL in each time. The immobilized QAS antibacterial substrata would show higher inhibitory effect as pH value of the reacting mixture rise to pH 8.0. The antibacterial substrata used in this study coated with silver ions (1.0 wt%) would showed different inhibitory effect while coating with different carriers, under different operational conditions, the amount of carborundum added for testing were varied, and the value of pH in testing medium was changed. It showed the APC of survivors of L. monocytogenes, P. aeruginosa, Staph. aureus, and Strept. faecalis were lowered from 7.0 to below 2.3 log CFU/mL in 8 hours, but the APC of survivors of E. coli O157 and S. dysenteriae were only degraded to 5.0 log CFU/mL. The inhibitory effect of carborundum coated with 1.0 wt% silver ions is stronger than honeycombs ceramic with same coating treatment did. The different range on the APC of these two experiments is about 1.0-3.0 log CFU/mL. The streaming reacting mode showed higher inhibitory effect than the other two reacting modes, unmoved and shaking. The former has decreasing the APC of the testing bacteria to the amount lower than the two less efficient reacting modes approximately 0.5-1.5 log CFU/mL. As the amount of carborundum used in the testing would increase 20 g every time, the survivors of testing bacteria would decrease on the APC about 0.5-2.0 log CFU/mL. The immobilized silver ion antibacterial substrata would show higher inhibitory effect as pH value of the reacting solution rise to pH 8.0. While the dissociation degrees of QAS and silver ions from the antibacterial substrata in aqueous solution were examined, the amount of QAS and silver ions released was below 0.2 and 1.0 ppm. These results indicated that the amount of dissociation of the QAS and silver ions from antibacterial substrata in water are trace. The results observed under SEM showed cellular morphologies of tested bacteria with few change when adsorbed to carborundum coated with 1.0 wt% QAS (QA-S-2). Although the cellular morphologies of tested bacteria changed significantly while adsorbed to carborundum coated with 1.0 wt% silver ions (Ag-S).
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Hsueh, Shu-Ping, and 薛淑萍. "SV40 T/t-common polypeptide inhibits angiogenesis and enhances the cytotoxic activity of chemotherapeutic agents in human HER2-overexpressing tumors." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/57959984650785599184.
Full textAbstract:
博士國立臺灣大學
微生物學研究所
100
Overexpression of HER2 has been frequently detected in many types of human cancer, most notably breast and ovarian cancers. HER2 overexpression is associated with increased angiogenesis, increased metastasis, increased chemoresistance and reduced survival. Inhibition of HER2 in HER2-overexpressing cancers can lead to reduced angiogenesis, reduced chemoresistance and improved survival. Previously, we reported that Simian Virus 40 T/t-common polypeptide can inhibit HER2, suppress the tumorigenic potential of HER2-overexpressing cancer cells and specifically induce apoptosis in HER2-overexpressing human cancer cell lines. In the part I of this thesis, we further explored the effect of T/t-common on tumor angiogenesis. We found that T/t-common could inhibit the ability of HER2-overexpressing cancer cells, but not low HER2-expressing cancer cells, to induce the migration and tube formation of endothelial cells. Reexpression of HER2 could block T/t-common’s activity to inhibit the ability of HER2-overexpressing cancer cells to induce the migration and tube formation of endothelial cells. We further tested whether T/t-common could affect HER2-overexpressing cancer cells to express and secrete angiogenic and anti-angiogenic factors. We found that T/t-common could inhibit the expression of proangiogenic factor VEGF-A, IL-8, bFGF, uPA and MMP-2, and induce the expression of anti-angiogenic factor TSP-1and TIMP-1 in HER2-overexpressing human SK-OV-3 ovarian cancer cells. T/t-common was found to be able to repress the expression of HIF-1α, a transcription factor required for VEGF-A expression, through inhibiting HER2-mediated ERK1/2 activity. Moreover, T/t-common was found to be able to activate p38 pathway, leading to up-regulation of TSP-1. Through regulating HER2-ERK1/2-HIF-1α-VEGF-A and HER2-p38-TSP-1 signaling pathways in HER2-overexpressing cancer cells, T/t-common could inhibit these cancer cells to recruit endothelial cells, leading to inhibition of angiogenesis in HER2-overexpressing tumors. Two experiments described below demonstrated that T/t-common indeed can inhibit tumor angiogenesis. First, in Matrigel plug assays, we demonstrated that conditioned medium from T/t-common-transduced SK-OV-3 cancer cells had lower ability to induce blood vessel formation in Matrigel plugs than that from control SK-OV-3 cells. Second, infection of adenovirus carrying T/t-common gene could lead to inhibition of the growth and microvessel formation of SK-OV-3 tumors in NOD/SCID mice model. Taken together, the above suggest that T/t-common had the potential to be developed as a new antiangiogenic agent specific for treating HER2-overexpressing ovarian cancers. In the part II of this thesis, we investigated whether T/t-common could enhance the sensitivity of HER2-overexpressing human cancer cells to chemotherapeutic agents such as cisplatin (CDDP) and doxorubicin (DXR). We found that T/t-common could specifically enhance the sensitivity of HER2-overexpressing human cancer cells, but not that of HER2 low-expressing human cancer cells, to CDDP and DXR. T/t-common could specifically enhance CDDP- or DXR-induced apoptosis by activating caspase-3 activity in HER2-overexpressing cancer cells. T/t-common expression led to down-regulation of Bcl-2 and Bcl-XL, inhibition of ERK activity, and activation of JNK activity in CDDP- or DXR-treated HER2-overexpressing BT-474 cancer cells. This modulation of apoptosis regulatory molecules by T/t-common may contribute to its ability to enhance CDDP- or DXR-induced apoptosis in HER2-overexpressing cancer cells. Finally, we showed that T/t-common could enhance the antitumor activity of DXR on HER2-overexpressing SK-OV-3.ip1 tumor in NOD/SCID mice. Together, these data demonstrated that T/t-common could sensitize HER2-overexpressing cancer cells to chemotherapeutic agents CDDP or DXR, and suggest that combination therapy using T/t-common gene and chemotherapeutic agents (such as CDDP or DXR) may overcome tumor chemoresistance and thus provide a new approach for treatment of HER2-overexpressing cancers.
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Mera, Mario Felix. "Recurrent selection for nodule mass and identification of tolerance to nitrate-induced inhibition of dinitrogen fixaton in common bean (Phaseolus vulgaris L.)." 1993. http://catalog.hathitrust.org/api/volumes/oclc/31128198.html.
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Bayat, Mokhtari Reza. "Dietary Chemoprevention Agent Sulforaphane Inhibits Growth, Survival and Tumorigenic Activity in Human Neuroblastoma." Thesis, 2010. http://hdl.handle.net/1807/25424.
Full textAbstract:
Objective: To evaluate the anti-tumor and histone deacetylase (HDAC) inhibitory activity of the dietary isothiocyanate, sulforaphane (SFN) in the paediatric cancer,neuroblastoma (NB). Materials and Methods: NB cell line (NUB-7), fibroblasts (FLF; negative control) and
MCF-7 (positive control), were treated with SFN for up to 7 days and effects on growth, cytotoxicity, differentiation and tumorigenicity assessed. HDAC inhibition was determined by histone (H3/ H4) acetylation. Results: 10 μM SFN significantly decreased in vitro growth and survival of NUB-7 to 10.22 ± 0.71% (p < 0.001) with no significant effect on FLF. SFN induced G1, G2 and S phase cell cycle arrests and stimulated H3/H4 histone acetylation. SFN markedly decreased NUB-7 clonogenicity and tumorigenicity in vivo. Conclusion: Results suggest that low dose SFN reduces proliferation, survival and
tumorigenicity of NB NUB-7. As a dietary factor of negligible intrinsic toxicity SFN is a promising therapeutic agent for the treatment of NB.