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Contexts and patterns of sexuality and sexual risk-taking among young people : implication for Aids prevention in ThailandSoonthorndhada, Amara January 2000 (has links)
No description available.
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PROSTITUTION AND SEXUAL PROMISCUITY AMONG ADOLESCENT FEMALE OFFENDERSKagan, Herman, 1931- January 1969 (has links)
No description available.
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Catalytic promiscuity of two plant P450 enzymes: CYP725A4 from Taxus cuspidata and CYP71B102 from Isatis TinctoriaSagwan-Barkdoll, Laxmi 01 May 2018 (has links) (PDF)
Plants are abundant in cytochrome P450s constituting about 1% of their protein coding genes. Some of these P450s catalyze oxidation reactions in metabolic pathways that lead to valuable compounds, like the anticancer drug paclitaxel, the blue pigment indigo and the promising antileukemic agent indirubin. The promiscuous nature of P450 catalysis enables simultaneous production of indirubin and indigo from a common substrate, but it also decreases the yield of paclitaxel in both plants and heterologous hosts, respectively. In this thesis, the catalytic promiscuity of CYP725A4 from Taxus cuspidata and CYP71B102 from Isatis tinctoria were investigated. CYP725A4 and CYP71B102 are involved in the biosynthesis of paclitaxel and indigo/indirubin pathways, respectively. CYP725A4 is known to catalyze the hydroxylation of endotaxadiene to taxadiene-5α-ol (T5α-ol), a precursor to paclitaxel, while CYP71B102 catalyzes the production of indigo and indirubin via hydroxylation of indole. CYP725A4 exhibited catalytic promiscuity upon heterologous expression in Escherchia coli producing 5(12)-oxa-3(11)-cyclotaxane (OCT) and 5(11)-oxa-3(11)-cyclotaxane (iso-OCT) as major products, and T5α-ol as a minor product with trace amounts of unidentified monooxygenated taxanes. The presence of T5α-ol was confirmed by comparing its gas chromatography and mass spectroscopy (GC-MS) retention time and spectrum with a standard T5α-ol, while those of others were verified by matching mass spectra from previous studies. Coexpression of CYP725A4 with cytochrome P450 reductase, CPR (as either fused or separate proteins) and cytochrome b5 (Cb5) did not affect the ratios of OCT, iso-OCT, and T5α-ol, although Cb5 had an apparently negative impact on CYP725A4 activity. Attempts to modify the catalytic promiscuity of CYP725A4 were conducted by mutating key residues at the active site of the enzyme. A mutant V3741 increased the production of T5α-ol by ~10 fold, although it still supported the formation of OCT and iso-OCT as major products. The levels of these compounds in V374I were almost 45% less than in native CYP725A4. Site-directed mutagenesis was also performed on taxadiene synthase (TS) to find a mutant that only produced exotaxadiene, which could be provided to CYP725A4 as an alternative substrate. Among the TS mutants generated, none were capable of producing only exotaxadiene, but two of the TS mutants, Y684C and Q609E, produced a reasonable amount of exotaxadiene. However, coexpression of these mutants with CYP725A4 and TCPR continued to produce OCT and iso-OCT. When CYP71B102 was expressed in E. coli, indigo was the main product, while indirubin and 2-oxindole were minor products, as verified by high-performance liquid chromatography (HPLC). Half-strength terrific broth (TB) medium in combination with 5-aminolevulinic acid supplementation and isatin hydrolase coexpression altogether increased indigo formation, while supplementation with isatin and 2-oxindole increased indirubin formation. The results of this study showed that the catalytic promiscuity of CYP725A4 and CYP71B102 could be modulated by metabolic and enzyme engineering to increase the yield of commercially important compounds, like paclitaxel, indigo and indirubin.
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States of Honor: Sexual Ethics and the Politics of Promiscuity in AfghanistanAhsan, Sonia January 2015 (has links)
This dissertation is based on field-work conducted at a khane-aman (home of peace) in Kabul in 2011-2012. In this dissertation, I have argued that the Afghan state vacillates between a rational-honorable mode and an unintelligible promiscuous mode. In its rational-honorable mode, the state institutes norms and regulations and develops institutional infrastructures for their implementation. The state also manifests another mode, which I am calling a promiscuous mode. To engage in promiscuity is to cater to the basest and most abject fantasies, to indulge in the regions of precariousness and vulnerability. This vacillation produces the Afghan state as both feared and desired, as transparent and opaque. Carnal punishments like flogging or stoning render present the distant force of the law into the context of everyday lives. Here the state takes on a different presence, a promiscuous one, in which the spectacular threat of violence is brought into the midst of the communal formations. Once the state institutes these punishments, it opens up the possibility of misplaced blames and wrongful retribution. It is in these realms of indecorum and solecism that the state reinvents and reveals itself.
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A Mechanistic study of Catalytic Promiscuity in Protein Phosphase 1Chu, Yuan 01 August 2012 (has links)
"Catalytic promiscuous" enzymes, which possess additional activities besides their "native" activity, albeit with a lower efficiency than the main reaction, have become a new frontier for biochemistry and have received considerable attention. Catalytic promiscuity has been suggested to contribute to enzyme evolution through the mechanism of gene duplication followed by specialization of one of the two copies for the new function. Mimicking this evolutionary shortcut could also provide a more efficient route to changing the function of proteins by directed evolution. The promiscuous phosphatase PP1 is a member of the phosphoprotein phosphatase (PPP) gene family, which is critical for the control of many cellular pathways by antagonizing the effects of protein phosphorylation mediated by kinases. The catalytic promiscuity of PP1&gamma WT and two mutants has been investigated with a set of monoanionic and dianioic phosphester substrates. PP1&gamma is an effective catalyst for the hydrolysis of both monoanionic and dianionic phosphate-ester based substrates 1-5, with second-order rate accelerations that fall within the narrow range of 1011 to 1013. While the transition states of the uncatalyzed hydrolysis reactions of these substrates differ, those for the PP1&gamma-catalyzed reactions are similar. Thus, the enzyme catalyzes the hydrolysis of these substrates by transition states that are controlled by the active site environment more than by the intrinsic nature of the substrates. The reason for the inability of PP1&gamma to catalyze the hydrolysis of a sulfate ester is unclear, and unexpected, since the charge and transition state of this substrate are well within the range of those of the phosphorus-based substrates that are effectively catalyzed. Inhibition experiments suggest that the PP1&gamma active site is tolerant of variations in the geometry of bound ligands. This characteristic may permit the effective catalysis even of substrates whose steric requirements may result in perturbations to the positioning of the transferring group, both in the initial enzyme-substrate complex and in the transition state. The conservative mutation of arginine 221 to lysine results in a mutant that more effectively catalyzes monoanionic substrates than the native enzyme. The surprising result in substrate preference from a single, conservative mutation lends support to the notion that mutations following gene duplication can result in an altered enzyme with different catalytic capabilities and preferences, and may, following subsequent mutations, provide a pathway for the evolution of new enzymes.
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Deciphering Substrate Promiscuity by Aminoglycoside Resistance Enzymes via a Biophysical Characterization and Dynamics of the Aminoglycoside Acetyltransferase-(3)-IIIb and the Aminoglycoside Phosphotransferase-(3′)-IIIaNorris, Adrianne Lee 01 May 2011 (has links)
Aminoglycoside antibiotics are losing their bactericidal efficacy due to the spread of enzymes that catalyze a covalent modification to them. A common property of many of these aminoglycoside modifying enzymes (AGMEs) is the capacity to modify multiple diverse aminoglycosides thus conferring resistance to these drugs among several pathogenic bacterial species. To gain a better understanding of the protein-antibiotic interactions responsible for resistance and the promiscuous nature of AGMEs, a variety of biophysical techniques including nuclear magnetic resonance (NMR), isothermal titration calorimetry (ITC), steady state kinetics, intrinsic tryptophan fluorescence, and computational modeling are employed in this work. Results and discussion presented herein are divided into two parts.
In Part I, a detailed thermodynamic and kinetic characterization of the association between the aminoglycoside acetyltransferase-(3)-IIIb (AAC) and several antibiotics and/or coenzyme(s) provides insight into the global properties of the protein. AAC is shown to have a broad substrate range where antibiotic interaction occurs with a favorable enthalpy and unfavorable entropy. When coenzyme A (the non-catalytic form of the acetyl donor, acetyl coenzyme A) is present, enthalpy becomes more favored, entropy more disfavored, and antibiotic affinity significantly increases. AAC shows preference for antibiotics with amine groups at the 2′ and 6′ positions and to those possessing four or more pseudo-saccharide rings. These and other data lay the foundation for understanding AAC and lead into the next discussion wherein the source of promiscuity of AGMEs is explored in Part II.
The aminoglycoside phosphotransferase-(3′)-IIIa (APH), a representative from the phosphotransferase family of AGMEs, has been well characterized previously. However, none of the data presented to date provides rationale for its promiscuity. In this work, NMR derived hydrogen-deuterium exchange experiments reveal that APH maneuvers its entire structure to accommodate diverse antibiotics. Furthermore, presence of an antibiotic creates a more stable APH conformation while coenzyme induces an antibiotic dependent increase in the flexibility of APH. For comparison, a computationally derived homology model of AAC predicts that its promiscuous nature may be due to a large flexible loop. Taken together, APH and AAC, two structurally and functionally diverse proteins, utilize different aspects of structural flexibility to facilitate a broad substrate repertoire that is key to bacterial survival.
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A life history assessment of early childhood sexual abuse in females /Vigil, Jacob Miguel, January 2004 (has links)
Thesis (M.A.)--University of Missouri-Columbia, 2004. / Typescript. Includes bibliographical references (leaves 51-67). Also available on the Internet.
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A life history assessment of early childhood sexual abuse in femalesVigil, Jacob Miguel, January 2004 (has links)
Thesis (M.A.)--University of Missouri-Columbia, 2004. / Typescript. Includes bibliographical references (leaves 51-67). Also available on the Internet.
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Promiscuity and Selectivity in Phosphoryl TransferasesBarrozo, Alexandre January 2016 (has links)
Phosphoryl transfers are essential chemical reactions in key life processes, including energy production, signal transduction and protein synthesis. They are known for having extremely low reaction rates in aqueous solution, reaching the scale of millions of years. In order to make life possible, enzymes that catalyse phosphoryl transfer, phosphoryl transferases, have evolved to be tremendously proficient catalysts, increasing reaction rates to the millisecond timescale. Due to the nature of the electronic structure of phosphorus atoms, understanding how hydrolysis of phosphate esters occurs is a complex task. Experimental studies on the hydrolysis of phosphate monoesters with acidic leaving groups suggest a concerted mechanism with a loose, metaphosphate-like transition state. Theoretical studies have suggested two possible concerted pathways, either with loose or tight transition state geometries, plus the possibility of a stepwise mechanism with the formation of a phosphorane intermediate. Different pathways were shown to be energetically preferable depending on the acidity of the leaving group. Here we performed computational studies to revisit how this mechanistic shift occurs along a series of aryl phosphate monoesters, suggesting possible factors leading to such change. The fact that distinct pathways can occur in solution could mean that the same is possible for an enzyme active site. We performed simulations on the catalytic activity of β-phosphoglucomutase, suggesting that it is possible for two mechanisms to occur at the same time for the phosphoryl transfer. Curiously, several phosphoryl transferases were shown to be able to catalyse not only phosphate ester hydrolysis, but also the cleavage of other compounds. We modeled the catalytic mechanism of two highly promiscuous members of the alkaline phosphatase superfamily. Our model reproduces key experimental observables and shows that these enzymes are electrostatically flexible, employing the same set of residues to enhance the rates of different reactions, with different electrostatic contributions per residue.
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Exploring Conjugate Addition Activity in <em>Pseudozyma antarctica</em> Lipase BSvedendahl, Maria January 2009 (has links)
<p>Multifunctional enzymes have alternative functions or activities, known as “moonlighting” or “promiscuous”, which are often hidden behind a native enzyme activity and therefore only visible under special environmental conditions. In this thesis, the active-site of Pseudozyma (formerly Candida) antarctica lipase B was explored for a promiscuous conjugate addition activity. Pseudozyma antarctica lipase B is a lipase industrially used for hydrolysis or transacylation reactions. This enzyme contains a catalytic triad, Ser105-His224-Asp187, where a nucleophilic attack from Ser105 on carboxylic acid/ester substrates cause the formation of an acyl enzyme. For conjugate addition activity in Pseudozyma antarctica lipase B, replacement of Ser105 was assumed necessary to prevent competing hemiacetal formation. However, experiments revealed conjugate addition activity in both wild-type enzyme and the Ser105Ala variant. Enzyme-catalyzed conjugate additions were performed by adding sec-amine, thiols or 1,3-dicarbonyl compounds to various α,β-unsaturated carbonyl compounds in both water or organic solvent. The reactions followed Michaelis-Menten kinetics and the native ping pong bi bi reaction mechanism of Pseudozyma antarctica lipase B for hydrolysis/transacylation was rerouted to a novel ordered bi uni reaction mechanism for conjugate addition (Paper I, II, III). The lipase hydrolysis activity was suppressed more than 1000 times by the replacement of the nucleophilic Ser105 to Ala (Paper III).</p>
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