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Akaoka, Kevin J. "Impact of coal-carrying trains on particulate matter concentrations in the Lower Mainland region of British Columbia, Canada." Thesis, University of British Columbia, 2015. http://hdl.handle.net/2429/55018.
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The transport of coal by train through residential neighbourhoods in Metro Vancouver, British Columbia, Canada is a growing concern for many residents living near the railway. This study aimed to identify and quantify any potential particulate matter (PM) increase caused by the presence of rail traffic adjacent to John Oliver Park in Delta, BC. Field work was carried out during August and September 2014, using a GRIMM optical particle counter that measured PM concentration at various size ranges. A select number of passing trains were confirmed visually, while the majority of passages were identified with audio data recorded by a microphone. A horizontally operating mini-micropulse lidar system was also set up at the park on three individual days to make intensive backscatter measurements. Wind data were recorded by collocated instruments maintained by Metro Vancouver. Finally, the Corporation of Delta had a dustfall measurement campaign during the same time period. Trains carrying coal are associated with a 5.28, 4.11, and 2.55 µg/m³ average increase in concentration over a 15 minute period, compared to control conditions for PM₃, PM₁₀, and PM₂₀, respectively. These increases are all statistically significant at α=0.01. PM concentrations during train passages of all types were not found to be significantly different from PM concentrations during control conditions. The presence of coal dust particles at the site was confirmed by the dustfall measurements carried out by the Corporation of Delta. Lidar backscatter imagery provided individual snapshots of train passages. However, it is clear that not every train passage causes an increase in PM concentration, and the effect appears to be highly dependent on wind direction and local meteorology.Science, Faculty of
Earth, Ocean and Atmospheric Sciences, Department of
Graduate
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Robert, William E. (William Edward). "Unit coal train networks : development and application of a computer simulation model." Thesis, Massachusetts Institute of Technology, 1997. http://hdl.handle.net/1721.1/10393.
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Humphreys, Michael Peter. "A study of track stability for locomotive transportation in British coal mines." Thesis, University of Nottingham, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.254385.
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Chaves-Fonnegra, Andia. "Increase of Excavating Sponges on Caribbean Coral Reefs: Reproduction, Dispersal, and Coral Deterioration." NSUWorks, 2014. http://nsuworks.nova.edu/occ_stuetd/5.
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Coral reefs ecosystems are deteriorating and facing dramatic changes. These changes suggest a shift in dominance from corals to other benthic organisms. Particularly in the Caribbean Sea, with corals dying, sponges have become the leading habitat-forming benthic animals. However, little is known about what life-history traits allow organisms to proliferate in a marine system that is undergoing change. Thus, the objective of this dissertation was to try to understand the current increase of encrusting excavating sponges on deteriorating Caribbean coral reefs through the study of reproduction, recruitment and dispersal potential of the widely distributed and currently expanding species, Cliona delitrix. Different methodological approaches were used, such as histology, electron microscopy, quantification of sponges in the field, genetics, and mathematical modeling. Results are presented in four different chapters. It was found that Cliona delitrix has an extended reproductive cycle in Florida, USA, from April - May to around November - December depending on a >25°C sea-water temperature threshold. C. delitrix gametogenesis is asynchronous and it has multiple spawning events. C. delitrix is recruiting abundantly on Caribbean coral reefs, preferentially on recent coral mortality than on old coral mortality. The increase in C. delitrix and other excavating sponges can be explained by the repeated spawning and by the coincidence in time and space of larval production with the availability of new dead coral, which tend to overlap during the warmest months of the year. Eggs or larvae of C. delitrix appear to survive enough to be transported by currents over larger distances. It was found that dispersal ranges for Cliona delitrix may reach as far as ~315 km in the Florida reef track, and over ~971 km in the South Caribbean Sea, between Belize and Panama. Thus, reproduction, dispersal, and recruitment patterns of C. delitrix along with oceanographic currents, and eddies that form at different periods of time, are sustaining the spread of this sponge on coral reefs. According to mathematical models carried out, C. delitrix increase on reefs fluctuates depending of coral mortality events and available space on old dead coral (colonized by algae and other invertebrates). However, under temperature anomalies, these sponges will 2 tend to increase and take over the reef system only if heat stress and coral mortality is moderate. Under massive mortality events both corals and sponges will tend to decline, although sponges at a slower rate than corals. In general, coral excavating sponges have been favored by coral mortality, especially during past few decades. However as bioeroders, their success is also limited by the success of calcifying corals. In a reef management context and based on this dissertation’s findings, it is suggested that excavating sponges, and especially Cliona delitrix, should be more formally included in reef monitoring programs. Their increase can be used to track coral mortality events on reefs (past and future), and also can be used as another major bioindicator of health on coral reefs.
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Kovalenko, I. D., A. Doressoundiram, E. Lellouch, E. Vilenius, T. Müller, and J. Stansberry. "“TNOs are Cool”: A survey of the trans-Neptunian region." EDP SCIENCES S A, 2017. http://hdl.handle.net/10150/626412.
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Context. Gravitationally bound multiple systems provide an opportunity to estimate the mean bulk density of the objects, whereas this characteristic is not available for single objects. Being a primitive population of the outer solar system, binary and multiple trans-Neptunian objects (TNOs) provide unique information about bulk density and internal structure, improving our understanding of their formation and evolution. Aims. The goal of this work is to analyse parameters of multiple trans-Neptunian systems, observed with Herschel and Spitzer space telescopes. Particularly, statistical analysis is done for radiometric size and geometric albedo, obtained from photometric observations, and for estimated bulk density. Methods. We use Monte Carlo simulation to estimate the real size distribution of TNOs. For this purpose, we expand the dataset of diameters by adopting the Minor Planet Center database list with available values of the absolute magnitude therein, and the albedo distribution derived from Herschel radiometric measurements. We use the 2-sample Anderson-Darling non-parametric statistical method for testing whether two samples of diameters, for binary and single TNOs, come from the same distribution. Additionally, we use the Spearman's coefficient as a measure of rank correlations between parameters. Uncertainties of estimated parameters together with lack of data are taken into account. Conclusions about correlations between parameters are based on statistical hypothesis testing. Results. We have found that the difference in size distributions of multiple and single TNOs is biased by small objects. The test on correlations between parameters shows that the effective diameter of binary TNOs strongly correlates with heliocentric orbital inclination and with magnitude difference between components of binary system. The correlation between diameter and magnitude difference implies that small and large binaries are formed by different mechanisms. Furthermore, the statistical test indicates, although not significant with the sample size, that a moderately strong correlation exists between diameter and bulk density.
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Turnbull, Jane. "A trans-disciplinary analysis of international environmental policy: The coral reef crisis." Thesis, University of Canterbury. Geography, 2005. http://hdl.handle.net/10092/4384.
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Focusing on coral reef policy, this thesis challenges orthodox understanding of international environmental policy, studying environmental crises as political assemblies, and policy endeavours as power-filled networks. This requires first rendering the subject accessible for critical research by constructing a 'multiperspectival' base from which to view it, thus elucidating how a Foucauldian discourse of modernisation hides the politics of orthodox understandings of international environmental policy. The thesis then investigates the efforts of a suite of science/policy/conservation agencies to save coral reefs from a perceived global crisis. It analyses how coral reef policy arises as an instrument of international governance, articulating with the Fiji Islands, a South Pacific archipelago. This reveals how global truths are created and translated into policies and action plans, enrolling places and people into a global network largely outside the formal interstate treaty system. Understanding these networks and the various modes of power operating within them-from seduction to coercion and hegemony-necessitates understanding how actors in both developed and developing counties exhibit similar agency, co-opting discourses to suit their interests.
The final section argues that this political assembly around ecological crisis represents a deepening integration of humankind in which ecology has become a model for the practice of development under the control of ecological technocrats. The West continues to dominate the Third World, however. Both environmental policy discourse and the universals through which policy travels the globe-the moral imperative to look after the planet plus science-based universals positioning coral reefs as a problem of common concern to humanity-contribute to this relationship of domination. Indeed, hegemony is predicated upon the universal of international cooperation as much as those of science and neoliberalism. Technical practices and expert technologies accepted as commonsense help sustain an asymmetrical relationship; practices used in creating global reports of coral health, capacity-building projects, ecoregion planning technologies and the rhetorical style used in scientific papers all contribute.
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Lange, Ian. "Investigating the effects of the 1990 Clean Air Act Amendments on inputs to coal-fired power plants /." Thesis, Connect to this title online; UW restricted, 2005. http://hdl.handle.net/1773/7421.
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Tusing, Donald S. "Modular track panels for improved safety in the mining transportation industry." Morgantown, W. Va. : [West Virginia University Libraries], 2003. http://etd.wvu.edu/templates/showETD.cfm?recnum=2853.
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Thesis (M.S.)--West Virginia University, 2003.Title from document title page. Document formatted into pages; contains xiv, 158 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 141).
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Romero, Natasha Elizabeth. "Evaluation of traits associated with bucking bull performance and behavior." [College Station, Tex. : Texas A&M University, 2008. http://hdl.handle.net/1969.1/ETD-TAMU-3097.
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Rankin, Tauna Leigh. "The Effects of Early Life History on Recruitment and Early Juvenile Survival of a Coral Reef Fish in the Florida Keys." Scholarly Repository, 2010. http://scholarlyrepository.miami.edu/oa_dissertations/405.
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Processes that influence the early life stages of fishes can significantly impact population dynamics, yet they continue to be poorly understood. This dissertation examined relationships between the environment, early life history traits (ELHTs), behavior, and post-settlement survival for a coral reef fish, Stegastes partitus, in the upper Florida Keys, to elucidate how they influence juvenile demography. Otolith analysis of settlers and recruits coupled with environmental data revealed that S. partitus surviving the early juvenile period settled at larger sizes and grew slower post-settlement. Water temperature also influenced the ranges of these and other ELHTs as well as the intensity and direction of selective mortality processes acting on some of these traits (i.e., pelagic larval duration, mean larval growth). Otolith analysis was paired with behavioral observations of newly settled juvenile S. partitus in the field to reveal that the relationship between size-at-settlement, early juvenile growth and survival is behaviorally-mediated. Individuals that were larger at settlement were more active (i.e., spent less time sheltered, swam farther from shelters) and grew more slowly post-settlement. Likewise, slower juvenile growth was associated with greater activity, more conspecific aggression, and faster escape swimming speeds. A six-year time series of recruitment densities revealed substantial temporal (interannual, seasonal, lunar) and spatial (by microhabitat, conspecific density) variability in recruitment which influenced the composition of recruits. For instance, larvae settling during the darkest phases of the moon were larger at settlement, but selective mortality processes during brighter periods removed more of the smallest settlers, resulting in juveniles with similar sizes-at-settlement regardless of when they arrived to the reef. Because recruitment strength and composition varied temporally, genetic markers (6 microsatellite and 1 mitochondrial loci) were used to determine if the genetic composition of monthly cohorts of settling larvae and juveniles also varies interannually, monthly, or across life stages. A lack of genetic structure suggested that S. partitus has a large effective population size and variation in ELHTs is not likely the result of successful spawning of a disproportionately small group of adults. As a whole, these results reveal processes associated with larval supply and post-settlement life that collectively shape juvenile demography.
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Patterson, Carl John. "In vitro properties and in vivo responses of CoaR, ZiaR & Zur (trans-family metal-sensing)." Thesis, University of Newcastle Upon Tyne, 2011. http://hdl.handle.net/10443/1077.
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In prokaryotic organisms metal-sensing transcriptional regulators must respond selectively to metal ions. The factors which govern selectivity across different sensor families from Synechocystis sp. PCC 6803 have been investigated using three sensor proteins; ZiaR, an ArsR-SmtB Zn2+-de-repressor; Zur, a Fur-like Zn2+ co-repressor and CoaR, a MerR-like Co2+-dependent activator. Zn2+ bound and allosterically regulated recombinant ZiaR and Zur in vitro. Cu+ failed to allosterically regulate recombinant Zur and inhibited Zn2+-mediated allostery in vitro. In Δatx1ΔgshB Synechocystis cells, proposed to be defective in normal cytosolic Cu+ trafficking, copper toxicity and inhibition of Zn2+-mediated repression of Zur-regulated gene expression was detected, consistent with inhibition of Zn2+-sensing in vivo by Cu+ normally bound to Atx1. Cu+ bound in preference to Zn2+ at the α3N sites of recombinant ZiaR and was allosterically ineffective; however, divalent metal binding and allostery were retained at the α5 sites in vitro. In Δatx1 Synechocystis cells, enhanced ZiaR-dependent expression was observed with no copper-dependency suggesting Atx1 also sequestered Zn2+. Hence, Atx1 is proposed to restrict access to Zn2+ and Cu+ ions in vivo. Co2+ bound to recombinant Zur and ZiaR, impaired ZiaR binding to DNA in vitro but ZiaR does not respond to Co2+ in vivo. Unexpectedly, the Co2+ affinity of recombinant CoaR was weaker than ZiaR and Zur, and Zur acquired Co2+ in preference to CoaR following direct competition. ZiaR and Zur are soluble however CoaR is membrane associated with predicted hydrophobic regions and requires a non-ionic detergent for preparation in vitro. Membrane-localised CoaR is proposed to exist in an intracellular niche in which [Co2+] >> CoaR KCo and is thus sufficient to activate the protein. Zn2+ binds to CoaR more tightly than Co2+ but ZiaR and Zur out-compete CoaR for Zn2+ Thus, in vivo responses to Zn2+ correlate with relative affinities for this group of sensors.
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Nordemar, Ingrid. "Human Abuses of Coral Reefs- Adaptive Responses and Regime Transitions." Doctoral thesis, Stockholm : Institutionen för systemekologi, Univ, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-250.
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Escamilla, Sanchez Diana Marcela. "Improving Breeding Selection of Seed Quality Traits for Food-Grade Soybeans." Thesis, Virginia Tech, 2018. http://hdl.handle.net/10919/81963.
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Natto and sprout soybeans are produced using small-seeded soybeans and their production is a high value alternative to grow grain soybeans for food in U.S. The development of soybean cultivars with improved natto and sprout quality is crucial for maintaining and increasing the soyfood market. However, there is insufficient information on sprout soybean characteristics. Therefore, the first objective of this study was to evaluate seed and sprout traits as potential selection criteria and study the storage effect on sprout quality. Seeds can be a vehicle for transmission of pathogens capable of causing human illness. That is why, the second objective was to identify seed-borne pathogens on a commercial soybean cultivar and to evaluate different seed decontamination treatments. Finally, seed coat deficiency is an undesirable trait for natto soybean seeds because it causes inferior appearance of the product. Thus, the third objective was to identify quantitative trait loci (QTL) underlying seed coat deficiency (SCD) and associated markers. Results showed that seed size, high-, average- and low-quality sprout percentage, hypocotyl thickness and length and sprout yield are the most important variables for breeding sprout cultivars; and one-year seed storage at room temperature reduced sprout quality. Fusarium, Alternaria and Diaphorte were the most frequent genera isolated from soybean seeds, and 2% calcium hypochlorite and 5% acetic acid were promising seed disinfection treatments. A stable QTL, qSCD20_1, was identified across two years explaining up to 25% of the variation of SCD; and eight molecular markers tightly linked and nearby qSCD20_1 were identified. Information presented will be helpful for sprout and natto soybean cultivar development.Master of Science
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Guan, Dailu. "Genomic analysis of dairy and pigmentation traits in Murciano-Granadina goats." Doctoral thesis, Universitat Autònoma de Barcelona, 2020. http://hdl.handle.net/10803/671155.
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Amb l'objectiu d'obtenir nous coneixements sobre la base molecular de la lactació en cabres de la raça Murciano-Granadina (MUG), hem dut a terme una anàlisi RNA-Seq de mostres de la glàndula mamària (N=7) obtingudes en tres punts temporals diferents: 78 dies (T1, lactació primerenca), 216 dies (T2, lactació tardana) i 285 dies (T3, període sec) després del part. Aquest experiment ens va permetre identificar 1654 gens expressats diferencialment (DE), les funcions dels quals estaven relacionades principalment amb el metabolisme de les proteïnes, lípids i carbohidrats, homeòstasi del calci, mort cel·lular programada, remodelació tissular i immunitat. A més, vam realitzar un estudi d'associació del genoma complet (GWAS) que va incloure 822 cabres amb registres per set fenotipus lleters mesurats durant la primera lactació amb la finalitat de contribuir a dilucidar l'arquitectura genòmica de la producció i la composició de la llet. Aquest estudi ens va permetre detectar 24 quantitative trait loci (QTL). No obstant això, només tres QTL van mostrar significació estadística a nivell genòmic, és a dir, QTL1 (cromosoma 2, 130,72-131,01 Mb) per al percentatge de lactosa de la llet, QTL6 (cromosoma 6, 78,90-93, 48) Mb) per al percentatge de proteïna i QTL17 (cromosoma 17, 11.20 Mb) per als percentatges de proteïna i matèria seca.
Mitjançant l'anàlisi del patró de segregació de polimorfismes d'un sol nucleòtid (SNP) dels genes de les caseïnes en bezoars (ancestre de la cabra domèstica) i cabres domèstiques d'Europa, Àfrica, Pròxim Orient i Extrem Orient, es va determinar que del 36,1% (CSN2) al 55,1% (CSN1S2) dels SNPs són compartits entre bezoar i cabra domèstica. Així mateix, més del 50% dels SNP dels gens de les caseïnes van ser compartits per 2 o més poblacions de cabra doméstica situades en diferents continents, i del 18 al 44% dels SNP van ser compartits per les quatre poblacions domèstiques esmentades anteriorment. Aquests resultats ens permeten concloure que una part important de la diversitat existent en els gens de les caseïnes caprines va emergir abans de la domesticació de les cabres.
Un altre objectiu de la Tesi va ser caracteritzar la variació del nombre de còpies (CNV) en una població de 1036 cabres MUG. Mitjançant l'ús del programari PennCNV i QuantiSNP, vam identificar 4617 i 7750 CNV autosòmics, respectivament, que posteriorment van ser acoblats en 486 regions CNV o CNVR. Els gens que mapegen dins de CNV mostren un enriquiment de funcions relacionades amb la transducció olfactiva, els transportadors ABC i el desenvolupament embrionari. Un dels CNVR identificats en el nostre estudi coincideix amb la posició del gen de la proteïna de senyalització agouti (ASIP), que afavoreix la síntesi de feomelanina groga/vermella. En diversos estudis, l'augment del nombre de còpies del gen ASIP va ser associat amb un patró de pigmentació blanc en cabres. No obstant això, al realitzar un experiment de qPCR amb l'objectiu de quantificar el nombre de còpies del gen ASIP en poblacions de cabres amb diferents patrons de pigmentació, vam esbrinar que el CNV de ASIP no solsament segrega en cabres Saanen (blanques), sinó també en cabres MUG (negres/marrons) i cabres Malaguenyes (vermelles/rosses). Aquest resultat indica l'absència d'una relació simple i lineal entre el nombre de còpies del gen ASIP i la diŀlució del patró de pigmentació en cabres. Finalment, hem investigat l'arquitectura genòmica de la coloració de la capa en cabres MUG mitjançant la combinació de diferents tècniques experimentals. Aquesta anàlisi ha revelat l'existència d'una estreta associació entre una mutació aminoacídica (c.801C> G, p.Cys267Trp) al gen de receptor de la melanocortina 1 (MC1R) i el color negre/marró de les cabres MUG, la qual cosa implica que l'herència de la pigmentació en aquesta raça és monogènica.Con el objetivo de obtener nuevos conocimientos sobre la base molecular de la lactación en cabras de la raza Murciano-Granadina (MUG), se llevó a cabo un análisis RNA-Seq de muestras de la glándula mamaria (N=7) obtenidas en tres puntos temporales distintos, es decir, 78 días (T1, lactación temprana), 216 días (T2, lactación tardía) y 285 días (T3, período seco) después del parto. Este experimento permitió identificar 1654 genes expresados diferencialmente (DE), cuyas funciones estaban relacionadas principalmente con el metabolismo de las proteínas, lípidos y carbohidratos, homeostasis del calcio, muerte celular programada, remodelación tisular e inmunidad. Con la finalidad de contribuir a dilucidar la arquitectura genómica de la producción y la composición de la leche, realizamos un estudio de asociación del genoma completo (GWAS) que incluyó 822 cabras con registros para siete fenotipos lecheros medidos durante la 1ª lactación. Este estudio permitió detectar 24 quantitative trait loci (QTL). No obstante, sólo tres QTL mostraron significación estadística a nivel genómico, es decir, QTL1 (cromosoma 2, 130,72-131,01 Mb) para el porcentaje de lactosa de la leche, QTL6 (cromosoma 6, 78,90-93,48) Mb) para el porcentaje de proteína y QTL17 (cromosoma 17, 11.20 Mb) para los porcentajes de proteína y materia seca. Mediante el análisis del patrón de segregación de polimorfismos nucleotídicos sencillos (SNP) de los genes de las caseínas en bezoares (ancestro de la cabra doméstica) y cabras domésticas de Europa, África, Cercano Oriente y Lejano Oriente, se determinó que del 36,1% (CSN2) al 55,1% (CSN1S2) de los SNPs son compartidos por el bezoar y la cabra doméstica. Asimismo, más del 50% de los SNP de los genes de las caseínas fueron compartidos por 2 o más poblaciones de cabra doméstica ubicadas en diferentes continentes, y del 18 al 44% de los SNP fueron compartidos por las cuatro poblaciones domésticas mencionadas anteriormente. Estos resultados nos permiten concluir que una parte importante de la diversidad existente en los genes de las caseínas caprinas emergió antes de la domesticación de las cabras. Otro objetivo de la Tesis consistió en caracterizar la variación del número de copias (CNV) en una población de 1036 cabras MUG. Mediante el uso del software PennCNV y QuantiSNP, identificamos 4617 y 7750 CNV autosómicos, respectivamente, que posteriormente fueron ensamblados en 486 regiones CNV o CNVR. Los genes que mapean dentro de CNVR muestran un enriquecimiento de funciones relacionadas con la transducción olfativa, los transportadores ABC y el desarrollo embrionario. Uno de los CNVR identificados en nuestro estudio coincide con la posición del gen de la proteína de señalización agouti (ASIP), que favorece la síntesis de feomelanina amarilla/roja. En diversos estudios, el aumento del número de copias del gen ASIP fue asociado con un patrón de pigmentación blanco en cabras. Sin embargo, al realizar un experimento de qPCR con el objetivo de cuantificar el número de copias del gen ASIP en poblaciones de cabras con diferentes patrones de pigmentación, averiguamos que el CNV del gen ASIP no sólo segrega en cabras Saanen (blancas), sino también en cabras MUG (negras/marrones) y cabras Malagueñas (rojas/rubias). Este resultado indica la ausencia de una relación simple y lineal entre el número de copias del gen ASIP caprino y la dilución del patrón de pigmentación. Finalmente, hemos investigado la arquitectura genómica de la coloración de la capa en cabras MUG mediante la combinación de distintas técnicas experimentales. Este análisis reveló la existencia de una estrecha asociación entre una mutación aminoacídica (c.801C> G, p.Cys267Trp) en el gen del receptor de la melanocortina 1 (MC1R) y el color negro/marrón de las cabras MUG, lo que implica que la herencia de la pigmentación en dicha raza es monogénico.
In order to obtain new insights into the molecular basis of lactation in Murciano-Granadina (MUG) goats, we carried out a RNA-Seq analysis of mammary gland samples (N = 7) obtained in three different time points, that is, 78 days (T1, early lactation), 216 days (T2, late lactation) and 285 days (T3, dry period) after parturition. This experiment allowed the identification of 1654 differentially expressed (DE) genes, the functions of which were mainly related to protein, lipid and carbohydrate metabolism, calcium homeostasis, programmed cell death, tissue remodeling and immunity. In order to help elucidate the genomic architecture of milk production and composition, we also carried out a genome-wide association study (GWAS) including 822 goats with records for seven dairy phenotypes measured during the first lactation. This study allowed the detection of 24 quantitative trait loci (QTL). However, only three QTL showed statistical significance at the genome-wide level, that is, QTL1 (chromosome 2, 130.72-131.01 Mb) for the percentage of lactose in milk, QTL6 (chromosome 6, 78.90-93, 48) Mb) for the percentage of protein and QTL17 (chromosome 17, 11.20 Mb) for the percentages of protein and dry matter. By analyzing the segregation patterns of single nucleotide polymorphisms (SNPs) mapping to the casein genes in bezoars (ancestor of the domestic goat) and domestic goats of Europe, Africa, the Near East and the Far East, it was determined that about 36.1% (CSN2) to 55.1% (CSN1S2) of casein SNPs are shared between bezoars and domestic goats. Besides, more than 50% of the SNPs of the casein genes were shared by 2 or more domestic goat populations located on different continents, and 18 to 44% of the SNPs were shared by the four previously mentioned domestic populations. These results allow us to conclude that an important part of the diversity existing in the caprine casein genes emerged before the domestication of goats. Another objective of the Thesis consisted of characterizing copy number variation (CNV) in a population of 1036 MUG goats. Using the PennCNV and QuantiSNP software, we identified 4617 and 7750 autosomal CNVs, respectively, which were subsequently assembled into 486 CNV regions (CNVR). Genes located within CNV show an enrichment of functions related to olfactory transduction, ABC transporters and embryonic development. Interestingly, one of the CNVR identified in our study coincides with the position of the agouti signaling protein (ASIP) gene, which favors the synthesis of yellow/red pheomelanin. In several studies, increased copy number of the ASIP gene was associated with a white pigmentation in goats. However, when conducting a qPCR experiment with the objective of quantifying the number of copies of the ASIP gene in goat populations with different coat colors, we found that the ASIP CNV not only segregates in Saanen (white) goats, but also in MUG (black/brown) and Malagueñas goats (brown/blond). This result indicates the absence of a simple and linear relationship between the number of copies of the goat ASIP gene and the dilution of pigmentation. Finally, we have investigated the genomic architecture of coat color in MUG goats by combining different experimental techniques. This analysis revealed the existence of a close association between a missense mutation (c.801C>G, p.Cys267Trp) in the melanocortin receptor 1 (MC1R) gene and the black/brown color of MUG goats, which implies that the inheritance of pigmentation in this breed is monogenic.
Universitat Autònoma de Barcelona. Programa de Doctorat en Producció Animal
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Jayan, Geetha C. Jr. "Activity and mRNA abundance of enzymes for fatty acid synthesis and desaturation in mammary cell cultures." Diss., Virginia Tech, 1998. http://hdl.handle.net/10919/40519.
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The effect of exogenous unsaturated fatty acids on cellular fatty acid biosynthesis in mammary cells was examined. Under normal situations, even though the diet of a dairy cow contains considerable amounts of unsaturated fatty acids, viz. oleic acid (18:1) and linoleic acid (18:2), the major 18-carbon fatty acid that enters the circulation post-ruminally for delivery to the mammary gland is saturated fatty acid, viz. stearic acid (18:0). This is due to extensive ruminal biohydrogenation of unsaturated fatty acids. Studies have indicated that saturated fatty acids such as 18:0 are enhancers and that certain unsaturated fatty acids are inhibitors of de novo fatty acid synthesis in tissues such as the liver and adipose tissue. The present study investigated the effect of cis and trans isomers of 18:1 and 18:2 on de novo fatty acid synthesis and desaturation in mouse and bovine mammary epithelial cell cultures, and compared it with the effect caused by 18:0. In the first experiment 12.5, 25, 50 or 100 micromoles stearic acid (SA), oleic acid (OA), elaidic acid (EA), trans-vaccenic acid (TVA), linoleic acid (LA) or conjugated linoleic acid (CLA) were supplemented in the media of mouse mammary epithelial (MME) cells that were grown to confluence in Dulbecco's modified Eagle's medium (DMEM). As indicated by cellular palmitic acid (16:0) content and fatty acid synthetase (FAS) activity, when compared with SA all unsaturated fatty acid treatments inhibited de novo fatty acid synthesis in MME cells. In addition, OA at all concentrations and LA and CLA at 50 and 100 micromoles inhibited cellular stearoyl-CoA desaturase (SCD) activity and mRNA abundance. However, EA and TVA, when compared with SA, enhanced SCD activity and mRNA abundance at 12.5 and 25 micromoles. In the second experiment 25, 50 or 100 micromoles SA, OA, TVA, LA or CLA were supplemented in the media of bovine mammary epithelial cells that were grown to confluence in DMEM. As indicated by cellular 16:0 content, acetyl-CoA carboxylase (ACC) activity and FAS activity, treatment with the unsaturated fatty acids inhibited de novo fatty acid synthesis at all concentrations, when compared with SA. Unsaturated fatty acid treatments also reduced the abundance of ACC and FAS mRNA in the cells. When compared with SA at all treatment-concentrations, OA and LA inhibited whereas TVA and CLA enhanced cellular SCD activity and mRNA abundance in the bovine cells. In both cell types, CLA and TVA appeared to be the most potent inhibitors of saturated fatty acid biosynthesis.Ph. D.
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Rotta, Mariane. "Efeitos do crowding macromolecular na atividade enzim?tica da 2-trans-ENOIL-ACP (COA) redutaze de Mycobacterium tuberculosis." Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2016. http://tede2.pucrs.br/tede2/handle/tede/7307.
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Conselho Nacional de Pesquisa e Desenvolvimento Cient?fico e Tecnol?gico - CNPq
The cellular milieu is a complex and crowded aqueous solution. It is thus expected that this large concentration of macromolecules causes deviations from solution ideality. To mimic the intracellular environment, crowding effects are commonly studied in vitro using crowding agents. The aim of the present study was to evaluate the effects of macromolecular synthetic crowding agents on the apparent steady-state kinetic parameters (Km, kcat, and kcat/Km) for the chemical reaction catalyzed by 2-trans-enoyl-ACP (CoA) from Mycobacterium tuberculosis (InhA). The results showed that ficoll 70, ficoll 400, and dextran 70 had negligible effects on InhA activity in the range of concentrations used. On the other hand, a complex effect was observed for PEG 6000. Sucrose, which was employed in control experiments, decreased both the kcat/Km values for NADH and kcat for 2-trans-dodecenoyl-CoA (DD-CoA) substrate in a concentration-dependent manner. Molecular dynamics results suggest that InhA adopts a more compact conformer in sucrose solution, which likely accounts for the steady-state kinetic results. The presence of crowding agents appears to alter the relative abundance of different conformers of InhA in solution. The effects of the crowding agents on the energy (Ea and E?), enthalpy (?H#), entropy (?S#), and Gibbs free energy (?G#) of activation were determined. The ?G# values for all crowding agents tested were similar to dilute buffer, suggesting that excluded volume effects did not facilitate stable activated ES# complex formation. Nonlinear Arrhenius plot for PEG 6000 suggests that "soft" interactions may play a role in macromolecular crowding effects.
O meio intracelular ? uma solu??o aquosa complexa, pois ? preenchida por diversos tipos de macromol?culas. Espera-se que essa grande concentra??o de macromol?culas resulte em um comportamento n?o ideal para a solu??o. Para mimetizar o ambiente intracelular, os efeitos do da ocupa??o macromolecular s?o comumente estudados in vitro utilizando agentes de crowding. O objetivo central do presente estudo ? avaliar os poss?veis efeitos de agentes de crowding macromolecular sint?ticos nos par?metros cin?ticos aparentes de estado-estacion?rio (Km, kcat e kcat/Km) para a rea??o qu?mica catalisada pela 2-trans-enoil-ACP(CoA) redutase de Mycobacterium tuberculosis (InhA). Os resultados mostraram que ficoll 70, ficoll 400 e dextran 70 t?m efeitos negligenci?veis na atividade da InhA na faixa de concentra??o utilizada. Por outro lado, um complexo efeito foi observado na presen?a do PEG 6000. A sacarose, que foi utilizada como controle nos experimentos, reduziu os valores de kcat/Km para o NADH e kcat para o 2-trans-dodecenoil-CoA de uma maneira concentra??o-dependente. Os resultados de din?mica molecular sugerem que a InhA adota uma forma mais compacta na presen?a de sacarose, o que provavelmente tem efeitos nos resultados de cin?tica de estado-estacion?rio. A presen?a dos agentes de crowding parece alterar a abund?ncia relativa dos diferentes conf?rmeros da InhA em solu??o. Os efeitos do crowding macromolecular na energia (Ea e E?), entalpia (?H#), entropia (?S#) e energia livre de Gibbs de ativa??o (?G#) foram determinados. Os valores de ?G# para todos os agentes de crowding testados foram similares ao tamp?o Pipes 100 mM, sugerindo que os efeitos do volume exclu?do n?o facilitam a forma??o do complexo ativado est?vel ES#. A n?o linearidade do gr?fico de Arrhenius para o PEG 6000 sugere que intera??es ?brandas? possam atuar nos efeitos do crowding macromolecular.
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Lin, Xiaobo. "Stearoyl-COA Desaturase Gene Transcription, mRNA, And Activity In Response To Trans-Vaccenic Acid And Conjugated Linoleic Acid Isomers." Diss., Virginia Tech, 2000. http://hdl.handle.net/10919/39192.
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Studies were conducted to investigate: 1) desaturation of dietary trans-vaccenic acid (TVA, trans11-18:1) to the cis9,trans11-18:2 isomer of conjugated linoleic acid (9/11CLA), 2) effects of two conjugated linoleic acid isomers [9/11CLA or trans10,cis12-18:2 (10/12CLA)] and TVA on enzyme activities and mRNA abundance for lipogenic enzymes, and 3) regulation of stearoyl-CoA desaturase (SCD) gene transcription. In the first study, lactating mice were fed 3% linoleic acid (LA), or 2% LA plus 1% stearic acid (SA), 1% TVA, or 1% CLA mixture. Dietary TVA enriched the 9/11CLA content of carcass, liver, and mammary tissue of lactating mice. A similar enhancement of 9/11CLA also was observed in liver, but not carcass, of suckling pups nursing TVA-fed dams. The CLA mixture decreased mammary acetyl-CoA carboxylase (ACC) activity compared with other treatments. However, total fatty acid content of mammary tissue was reduced only when compared with TVA. In the second experiment, lactating mice were fed 3% canola oil (OA), or 2% OA plus 1% SA, 1% TVA, 1% 9/11CLA, or 1% 10/12CLA. Dietary TVA, 9/11CLA, and 10/12CLA decreased mRNA abundance for ACC and fatty acid synthase (FAS) in mammary tissue, suggesting each had the potential to reduce de novo fatty acid synthesis. However, only the CLA isomers decreased ACC activity in mammary tissue and concentration of medium-chain fatty acids (MCFA = 12:0+14:0+16:0) in milk fat. The 10/12CLA isomer caused greater reductions in MCFA and milk fat percentage than the 9/11CLA, indicating that 10/12CLA is the primary CLA isomer affecting lipid metabolism in the mammary gland. Dietary TVA, 9/11CLA, or 10/12CLA decreased SCD enzyme activity and mRNA abundance in mammary tissue. In study 3, mouse (COMMA-D/MME) and bovine (Mac-T) mammary epithelial cells were transfected with the putative promoter (600 bp) of SCD gene. The 9/11CLA reduced SCD gene transcription in mouse cells, but not bovine cells. Transcription, however, was reduced in both cell lines by 10/12CLA, linoleic acid, and linolenic acid. Thus, reduced SCD transcription in response to the CLA isomers in mouse mammary cells in vitro may provide an explanation for reduced SCD enzyme activity and mRNA abundance in mammary tissue when lactating mice were fed either of the CLA isomers. In contrast, stearic acid, oleic acid, and TVA did not affect SCD transcription. Although TVA did not reduce SCD transcription in mouse mammary cells in vitro, it did reduce SCD enzyme activity and mRNA abundance in mammary tissue when fed to lactating mice. The results suggested TVA may influence SCD mRNA processing or stability in the nucleus after transcription. Despite the reduction in SCD mRNA and enzyme activity, however, substantial quantities of TVA were desaturated to the 9/11CLA isomer when TVA was fed to lactating mice in the first two studies. Thus, dietary TVA provides an alternate supply of the anticarcinogenic 9/11CLA isomer in tissues.Ph. D.
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Henchiri, Chérifa. "Contribution à l'étude des delta-6 et -5 désaturations par les microsomes hépatiques de rat : effets de l'obésité et des acides gras trans (présents dans les huiles chauffées)." Dijon, 1987. http://www.theses.fr/1987DIJOS034.
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Fernandes, José Fortunato. "Educação musical de adolescentes em cumprimento de medida socioeducativa através do canto coral." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/284367.
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Orientadores: Aci Taveira Meyer, José Roberto ZanTese (doutorado) - Universidade Estadual de Campinas, Instituto de Artes
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Resumo: Este trabalho procura abordar os problemas relacionados à educação musical de adolescentes em cumprimento de medida socioeducativa. Ele se propõe a ser um estudo de caso que analisa o processo de ensino e aprendizagem em aulas de canto coral ministradas dentro de uma instituição correcional. Ele tem como objetivo relatar essa experiência e auxiliar a formação do educador musical que pretende trabalhar com esse público. Como metodologia se utilizou a pesquisa bibliográfica nas áreas de conhecimento da educação musical - que já compreende as áreas de educação e música -, da sociologia e da psicologia. Após a pesquisa bibliográfica, se fez um trabalho de campo por meio de aulas de canto coral dentro de uma Unidade da Fundação CASA no interior do Estado de São Paulo durante o período de agosto a dezembro de 2010. Como resultado deste trabalho, se pode perceber os elementos que diferenciam a educação musical aplicada aos adolescentes em cumprimento de medida socioeducativa da aplicada aos que não estão em conflito com a lei. Identificou-se fatores socioculturais inerentes aos adolescentes que devem ser do conhecimento do educador musical para que o processo de ensino e aprendizagem seja eficaz. Percebeu-se que credibilidade com os adolescentes somente seria conseguida por meio de uma relação dialógica e com o estabelecimento de um vínculo afetivo, que nesse caso não se conseguiu devido ao pouco tempo de convívio entre educador e educandos. Tentou-se a abordagem de um repertório musical eclético que favorecesse o crescimento musical concomitantemente com letras que levariam à formação de um bom caráter, como também o desenvolvimento de conteúdos musicais, mas a não solidificação do vínculo afetivo não permitiu que tais objetivos fossem alcançados. Durante o processo pedagógico utilizou-se estratégias de ensino para minimizar os problemas comportamentais que se apresentaram durante as aulas como também para a resolução de problemas da execução musical, especialmente aos relacionados à técnica vocal. Conclui-se que os conhecimentos extramusicais relacionados às áreas de conhecimento da sociologia e da psicologia são imprescindíveis para o sucesso do desenvolvimento da educação musical de adolescentes em cumprimento de medida socioeducativa através do canto coral
Abstract: This work seeks to approach problems related to musical education of adolescents who are serving a socio-educational sentence. It intends to be a case study that analyses the teaching process and learning choir singing in classes given in a correctional institution. It aims to tell this experience and to assist the formation of the music teacher who intends to work with this population. The methodology used carried out bibliographic research in the areas of knowledge of music education - which already includes the areas of education and music -, sociology and psychology. Following the bibliographic research, some fieldwork was carried out through choir singing lessons in one of the units of Fundação CASA in the interior of the State of São Paulo from August to December 2010. As a result of this work, we can see the elements that differentiate musical education applied to adolescents who are serving a socio-educational sentence from that given to adolescents who do not have conflicts with the law. We identified sociocultural factors inherent in adolescents that should be known by the music educator so that the process of teaching and learning is effective. It was felt that credibility with the adolescents would only be obtained through a relationship of dialogue and the establishment of an emotional bond, which in this case was not achieved due to the short time of interaction between teacher and students. The approach of an eclectic musical repertoire was attempted as this favored not only musical development but, at the same time, it was hoped that the message of the lyrics would help build character, and develop musical content; however, as a firm affective bonding was not established it was not possible to achieve these goals. During the teaching process, teaching strategies were used to minimize behavioral problems that were manifested during the classes and also for solving problems of musical performance, especially those related to vocal techniques. The conclusion reached is that extramusical knowledge related to fields of sociology and psychology are essential to the successful development of musical education through choir singing of adolescents serving sentences in correctional institutions
Doutorado
Fundamentos Teoricos
Doutor em Música
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Hanák, Ondřej. "Implementace BI ve velkoobchodu se surovinami." Master's thesis, Vysoká škola ekonomická v Praze, 2012. http://www.nusl.cz/ntk/nusl-114070.
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This diploma thesis is focused on an implementation of a Business Intelligence (BI) in a raw materials trading company, which trades brown coal. At first, a Balanced Scorecard analysis is made in this trading company. Then results of this analysis are used for the implementation of the BI. The first chapter of this thesis describes goals, methods and structure of the thesis. The second chapter contains information about those theses, which have similar topics as my thesis. Next chapters are theoretical part of the thesis. The third chapter describes the Business Intelligence and the fourth chapter describes the Balanced Scorecard. The fifth chapter is a theoretical-practical chapter and describes the company and the brown coal market. Practical part starts on the chapter six, which describes the use of the Balanced Scorecard in the given company. Next chapter uses the outputs of the chapter six and in a chapter seven there is an implementation of the BI. The eighth chapter describes reports of the BI and the ninth chapter contains conclusion and an evaluation of achieving the goals set by this thesis. Main contribution of this thesis is in the demonstration of design and implementation of the BI in a raw materials trading company.
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Heimburger, Robert. "Determination d'elements traces dans les poudres par fluorescence x a dispersion d'energie." Université Louis Pasteur (Strasbourg) (1971-2008), 1987. http://www.theses.fr/1987STR13052.
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Leite, Jacinara Hody Gurgel Morais. "Aspectos morfofisiológicos associados ao equilíbrio térmico de ovelhas da raça Morada Nova." Universidade Federal Rural do Semi-Árido, 2016. http://bdtd.ufersa.edu.br:80/tede/handle/tede/645.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
The Morada Nova sheep is an important locally adapted genetic resource from the Brazilian Semiarid. However, the genetic variability of these animals has been reduced due to the selection criteria adopted by breeders who only select to breed traits. One of these criteria is related to coat color, where the animals of red variety with dark and light tonality are discarded, as well as all animals of the white variety, with the justification that they are less adapted to the semiarid environment. Thus, in the present thesis was built in order to evaluate all characteristics related to the adaptation of Morada Nova sheep with different hair and coat color. Four groups were used according to coat color: (1) dark red animals, (2) intermediate red, (3) light red, and (4) white-coated animals. Forty Morada Nova ewes were observed in each of three herds for 7 consecutive months. In the first study we evaluated the thermal exchanges of sensible and latent heat loss in the different groups. All groups maintained homeothermy even when exposed to high solar radiation. The red coat animals increased respiratory rate in conditions of greater thermal stress. This fact was not observed in the white variety, which showed higher skin evaporation. In the second study, were evaluated hair coat characteristics and their association in the heat transfer from animals to the environment as well as physiological responses of animals. The largest differences found in the coat characteristics were recorded between the extremes of coat color: dark red and white. The white variety exhibited characteristics that promoted the protection of the skin, while red variety had characteristics which favored heat dissipation. It was concluded that Morada Nova sheep have good adaptability to the Semiarid environment, regardless of the coat color, and should be used in farming systems, preserved and multiplied
A raça Morada Nova é um importante recurso genético localmente adaptado do semiárido brasileiro, e apresentam características adaptativas exclusivas dessa região do Brasil no qual foi formada ao longo de anos de seleção natural. Porém, a variabilidade genética desses animais vem reduzindo devido aos critérios de seleção adotado pelos criadores que visam somente o padrão racial. Um desses critérios está relacionado com a cor do pelame, no qual são descartados os animais de pelagem vermelha escura e clara, assim como a variedade branca com a justificativa que são menos adaptados ao ambiente semiárido. Com isso, a presente tese foi construída com o objetivo de avaliar todas as características ligadas à adaptação dos animais da raça Morada Nova com diferentes cores de pelame. Foram avaliados, por um período de sete meses consecutivos, três rebanhos comerciais sendo que cada rebanho foram acompanhadas 40 matrizes. Os animais foram divididos em grupos de forma que os com pelame vermelho foram classificados em: (1) tonalidade escura, (2) tonalidade intermediária e (3) tonalidade clara. Os animais de pelame branco foram classificados como grupo 4. A tese foi dividida em dois artigos, sendo que no primeiro foram avaliadas as trocas térmicas de calor sensível e latente nos diferentes grupos. Foi observado que todos os grupos conseguiram manter a homeotermia, mesmo expostos à elevada radiação solar. Os mecanismos sensíveis foram pouco expressivos para a perda de calor, enquanto que os mecanismos latentes foram mais eficientes na termólise em todos os grupos. Os animais de pelagem vermelha elevaram muito a frequência respiratória nas condições de maior estresse térmico, fato que não foi verificado nos animais com pelagem branca, que apresentaram maior evaporação cutânea. No segundo artigo foram avaliadas as características morfológicas de pelame e sua associação com a transferência térmica de calor, assim como as respostas fisiológicas dos animais. As maiores diferenças encontradas para essas características foram em relação aos extremos de cor de pelagem: vermelho escuro e branco. Os resultados mostraram que a variedade branca apresentou características que promovem a proteção da epiderme, enquanto que os animais da variedade vermelha apresentaram características que favorecem a dissipação de calor. Contudo, pode-se afirmar que todos os animais da raça Morada Nova representam importante material genético bem adaptados a região equatorial semiárida, e devem ser utilizados nos sistemas de criação, conservados e multiplicados
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Vasconcelos, Igor Bordin. "A enzima 2-trans-enoil-ACP (CoA) redutase de mycobacterium tuberculosis : estudos de liga??o e inibi??o por um complexo inorg?nico." Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2008. http://tede2.pucrs.br/tede2/handle/tede/5310.
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Previous issue date: 2008-02-28A tuberculose (TB) continua sendo a principal causa de mortalidade devido a um ?nico pat?geno bacteriano, Mycobacterium tuberculosis. A reemerg?ncia da tuberculose como uma amea?a potencial ? sa?de p?blica, a alta suscetibilidade de pessoas infectadas com o v?rus da imunodefici?ncia humana ? doen?a, a prolifera??o de cepas resistentes a m?ltiplas drogas (MDR-TB) e, mais recentemente, de cepas extensivamente resistentes ?s drogas (XDR-TB) criaram a necessidade do desenvolvimento de novos agentes antimicobacterianos. Existe uma necessidade cont?nua de inova??o em propor novas estruturas para o desenvolvimento de agentes quimioter?picos para o controle da TB. Os ?cidos mic?licos, caracter?sticos de micobact?rias, s?o ?cidos graxos ?-alquil, ?-hidr?xi de alto peso molecular que aparecem, principalmente, como ?steres ligados ao envelope micobacteriano. A isoniazida (INH) ? o agente quimioter?pico mais prescrito para a TB ativa e para a profilaxia e necessita de ativa??o pela atividade de catalase-peroxidase da KatG. O produto do gene estrutural M.tuberculosis inhA (InhA) demonstrou ser o alvo prim?rio da INH. A InhA foi identificada como uma enoil-ACP redutase dependente de NADH, possuindo especificidade por enoil tio?steres de cadeia longa. InhA ? um membro do sistema de bioss?ntese de ?cidos graxos micobacterianos do tipo II que elonga ?cidos graxos acilados, precursores dos ?cidos mic?licos. O foco principal de nossa contribui??o s?o dados descrevendo o modo de a??o de um complexo inorg?nico, pentaciano (isoniazida) ferrato II que n?o necessita de ativa??o pela KatG. Ademais ? um inibidor do tipo liga??o lenta da enoil redutase WT e resistente ? INH de M.tuberculosis. Este complexo inorg?nico representa uma nova classe de compostos l?deres para o desenvolvimento de agentes antituberculose objetivando a inibi??o de um alvo validado.
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Vasconcelos, Igor Bordin. "A enzima 2-trans-enoil-ACP (CoA) redutase de mycobacterium tuberculosis: estudos de ligação e inibição por um complexo inorgânico derivado da isoniazida." Pontifícia Universidade Católica do Rio Grande do Sul, 2007. http://hdl.handle.net/10923/1307.
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Previous issue date: 2007Tuberculosis (TB) remains the leading cause of mortality due to a single bacterial pathogen, Mycobacterium tuberculosis. The reemergence of tuberculosis as a potential public health threat, the high susceptibility of human immunodeficiency virus-infected persons to the disease, the proliferation of multi-drug-resistant strains (MDR-TB) and, more recently, of extensively drug resistant isolates (XDR-TB) have created a need for the development of new antimycobacterial agents. There is an ongoing need for innovation in proposing new structural scaffolds for chemotherapeutic agent development to control TB. Mycolic acids, the hallmark of mycobacteria, are high-molecular-weight α-alkyl, β-hidroxy fatty acids, which appear mostly as bound esters in the mycobacterial envelope. Isoniazid (INH) is the most prescribed chemotherapeutic agent for active TB and prophylaxis and requires activation by the catalase-peroxidase activity of KatG. The product of the M. tuberculosis inhA structural gene (InhA) has been shown to be the primary target for INH. InhA was identified as an NADH-dependent enoyl-ACP reductase specific for long chain enoyl thioesters. InhA is a member of the mycobacterial Type II fatty acid biosynthesis system, which elongates acyl fatty acid precursors of mycolic acids. The main focus of our contribution is on data describing the mode of action of an inorganic complex, pentacyano (isoniazid) ferrateII that requires no KatG-activation and is an in vitro slow-onset inhibitor of WT and INH-resistant M. tuberculosis enoyl reductases. This inorganic complex represents a new class of lead compounds to the development of anti-tubercular agents aiming the inhibition of a validated target. We also describe the recent developments in the search for inorganic complexes with anti-tubercular activity.
A tuberculose (TB) continua sendo a principal causa de mortalidade devido a um único patógeno bacteriano, Mycobacterium tuberculosis. A reemergência da tuberculose como uma ameaça potencial à saúde pública, a alta suscetibilidade de pessoas infectadas com o vírus da imunodeficiência humana à doença, a proliferação de cepas resistentes a múltiplas drogas (MDR-TB) e, mais recentemente, de cepas extensivamente resistentes às drogas (XDR-TB) criaram a necessidade do desenvolvimento de novos agentes antimicobacterianos. Existe uma necessidade contínua de inovação em propor novas estruturas para o desenvolvimento de agentes quimioterápicos para o controle da TB. Os ácidos micólicos, característicos de micobactérias, são ácidos graxos α-alquil, β-hidróxi de alto peso molecular que aparecem, principalmente, como ésteres ligados ao envelope micobacteriano. A isoniazida (INH) é o agente quimioterápico mais prescrito para a TB ativa e para a profilaxia e necessita de ativação pela atividade de catalase-peroxidase da KatG. O produto do gene estrutural M. tuberculosis inhA (InhA) demonstrou ser o alvo primário da INH. A InhA foi identificada como uma enoil-ACP redutase dependente de NADH, possuindo especificidade por enoil tioésteres de cadeia longa. InhA é um membro do sistema de biossíntese de ácidos graxos micobacterianos do tipo II que elonga ácidos graxos acilados, precursores dos ácidos micólicos. O foco principal de nossa contribuição são dados descrevendo o modo de ação de um complexo inorgânico, pentaciano (isoniazida) ferrato II que não necessita de ativação pela KatG. Ademais é um inibidor do tipo ligação lenta da enoil redutase WT e resistente à INH de M. tuberculosis. Este complexo inorgânico representa uma nova classe de compostos líderes para o desenvolvimento de agentes antituberculose objetivando a inibição de um alvo validado.Nós também descrevemos os avanços recentes na busca por complexos inorgânicos com atividade antituberculose.
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Costa, André Luciano Pasinato da. "Estudo da interação da 2-trans-Enoil-ACP (CoA) Redutase de Mycobacterium tuberculosis com o complexo inorgânico Isoniazida-pentacianoferrato por simulação pela dinâmica molecular." Pontifícia Universidade Católica do Rio Grande do Sul, 2008. http://hdl.handle.net/10923/1325.
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Previous issue date: 2008The reemergence of tuberculosis is a current public health problem. The World Health Organization (WHO) reported in 2006 that 2 billion people, or one-third of the world’s total population, are infected with the bacilli Mycobacterium tuberculosis (MTB), and in 2007 reported that 1. 6 million people died from TB in 2005. Multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) are forms of TB that does not respond to the standard drug treatment. Isoniazid (INH, isonicotinic acid hydrazide) is one of oldest synthetic antitubercular drugs. The mechanism of action of INH is complex, as mutations in at least five different genes (katG, inhA, ahpC, kasA, and ndh) have been found to correlate with INH resistance. Pentacyano(isoniazid)ferrate II (PIF) is a rational drug design effort to find alternative drugs capable of inhibiting InhA. It was found that PIF inhibit both wild type and isoniazid-resistant I21V mutants of InhA and this inactivation does not require activation by KatG. In this work we report the results of two molecular dynamics simulations of PIF-InhA interaction considering all atoms of this complex in aqueous solution. The results demonstrated that PIF strongly interacts with InhA and these interactions cause macromolecular instabilities due to substrate binding site perturbation. These instabilities are reflected in the long time necessary for trajectory convergence. Besides this, we observed that the residues Gly14, Ile15, Ile16, Ser20, Gly40, Phe41, Ile47, Ser94 and Thr196 of InhA are responsible for the PIF-InhA association. So, we conclude that PIF competes directly for the NADH binding site and indirectly with the substrate binding site.
A re-emergência da tuberculose é um problema de saúde pública mundial. A Organização Mundial da Saúde (OMS) estima que, em 2006, cerca de 2 bilhões de pessoas, ou um terço da população mundial, foram infectadas com o bacilo Mycobacterium tuberculosis (MTB), e em 2007 relata que 1,6 milhões de pessoas morreram de tuberculose (TB) no ano de 2005. O surgimento das formas de TB resistente a múltiplas drogas (MDR-TB) e extensivamente resistente a drogas (XDR-TB), as quais não respondem ao tratamento convencional, colaboram para este crescimento. A Isoniazida (INH, hidrazida do ácido isonicotínico) é uma das drogas sintéticas mais antigas, e seu mecanismo de ação é complexo. Mutações em pelo menos cinco genes diferentes (katG, inhA, ahpC, kasA, e ndh) foram correlacionadas com a resistência a INH. O complexo inorgânico Isoniazida-pentacianoferrato (IPF) é o resultado do desenho racional de drogas na tentativa de achar uma alternativa capaz de inibir a InhA. O IPF é capaz de inibir os tipos selvagem e o mutante I21V da InhA, resistente à INH, e esta inativação não requer ativação por KatG. Neste trabalho, realizamos duas simulações por dinâmica molecular do complexo IPF-InhA, utilizando todos os átomos em solução aquosa, com o objetivo de investigar os eventos moleculares relacionados ao modo de interação droga-alvo e suas afinidades. Observamos que o IPF interage fortemente com a InhA e estas interações causam instabilidades na macromolécula devido a perturbação no sítio de ligação do substrato. Estas instabilidades se refletem no longo tempo necessário para a convergência da trajetória. Observamos também que os resíduos Gly14, Ile15, Ile16, Ser20, Gly40, Phe41, Ile47, Ser94 e Thr196 são os responsáveis por intermediar a associação IPF-InhA. Concluímos então que o IPF compete diretamente com o NADH pelo seu sítio de ligação e indiretamente com o substrato através da desestabilização do seu sítio de ligação.
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Rotta, Mariane. "9H-fluoren-9-IL(difenilmetil)-piperazinas: síntese, inibição da enzima 2-trans-enoil-ACP (CoA) redutase de mycobacterium tuberculosis e estudos de relação estrutura-atividade." Pontifícia Universidade Católica do Rio Grande do Sul, 2014. http://hdl.handle.net/10923/6787.
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Previous issue date: 2014The Mycobacterium tuberculosis NADH-dependent enoyl-acyl carrier protein reductase (MtInhA) catalyzes hydride transfer to long-chain enoyl thioester substrates. MtInhA is a member of the mycobacterial type II dissociated fatty acid biosynthesis system, and is the bona fide target for isoniazid, the most prescribed drug for tuberculosis treatment. Here, a series of piperazine derivatives was synthesized and screened as MtInhA inhibitors, which resulted in the identification of compounds with IC50 values in the submicromolar range. A structure-activity relationship (SAR) evaluation indicated the importance of the chemical environment surrounding the carbonyl group for inhibition. In addition, the structure of one selected compound was supported by crystallographic studies, and experimental geometrical values were compared with semi-empirical quantum chemical calculations. Furthermore, the mode of inhibition and inhibitory dissociation constants were determined for the nine most active compounds. These findings suggest that these compounds interact with MtInhA at the enoyl thioester (2-trans-dodecenoyl-CoA) substrate binding site. Finally, two 9H-fluoren-9-yl-piperazine-containing compounds exhibited moderate antimycobacterial activity against the M. tuberculosis H37Rv strain.
A enzima 2-trans-enoil-ACP redutase de Mycobacterium tuberculosis (MtInhA) catalisa a etapa enzimática final no ciclo de alongamento da via de biossíntese de ácidos graxos, convertendo 2-trans-enoil-ACP à acil-ACP em um mecanismo dependente de NADH. Essa enzima vem sendo descrita como alvo validado para a descoberta de fármacos. Nesse trabalho uma série de piperazinas foi sintetizada e avaliada quanto ao potencial inibitório da atividade enzimática da MtInhA, resultando em compostos com valores de IC50 na faixa de inibição de nanomolar. Avaliações de relação estrutura-atividade (SAR) indicam a importância do ambiente químico adjacente à carbonila para a inibição. Além disso, a estrutura de um composto foi confirmada por estudos cristalográficos e os valores geométricos experimentais foram comparados com valores obtidos através de cálculos semi-empíricos de obitais moleculares. Experimentos para determinação do modo de inibição e obtenção dos valores das constantes de dissociação foram realizados para os nove compostos mais ativos. Os resultados sugerem que esses compostos interagem com MtInhA no sítio de ligação dos substratos acil-graxos. Finalmente, dois compostos, contendo na sua estrutura 9H-fluoren-9-il-piperazina exibiram moderada atividade antimicrobiana contra a cepa Mycobacterium tuberculosis H37Rv.
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Costa, Andr? Luciano Pasinato da. "Estudo da intera??o da 2-trans-Enoil-ACP (CoA) Redutase de Mycobacterium tuberculosis com o complexo inorg?nico Isoniazida-pentacianoferrato por simula??o pela din?mica molecular." Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2008. http://tede2.pucrs.br/tede2/handle/tede/5314.
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Previous issue date: 2008-03-28A re-emerg?ncia da tuberculose ? um problema de sa?de p?blica mundial. A Organiza??o Mundial da Sa?de (OMS) estima que, em 2006, cerca de 2 bilh?es de pessoas, ou um ter?o da popula??o mundial, foram infectadas com o bacilo Mycobacterium tuberculosis (MTB), e em 2007 relata que 1,6 milh?es de pessoas morreram de tuberculose (TB) no ano de 2005. O surgimento das formas de TB resistente a m?ltiplas drogas (MDR-TB) e extensivamente resistente a drogas (XDR-TB), as quais n?o respondem ao tratamento convencional, colaboram para este crescimento. A Isoniazida (INH, hidrazida do ?cido isonicot?nico) ? uma das drogas sint?ticas mais antigas, e seu mecanismo de a??o ? complexo. Muta??es em pelo menos cinco genes diferentes (katG, inhA, ahpC, kasA, e ndh) foram correlacionadas com a resist?ncia a INH. O complexo inorg?nico Isoniazida-pentacianoferrato (IPF) ? o resultado do desenho racional de drogas na tentativa de achar uma alternativa capaz de inibir a InhA. O IPF ? capaz de inibir os tipos selvagem e o mutante I21V da InhA, resistente ? INH, e esta inativa??o n?o requer ativa??o por KatG. Neste trabalho, realizamos duas simula??es por din?mica molecular do complexo IPF-InhA, utilizando todos os ?tomos em solu??o aquosa, com o objetivo de investigar os eventos moleculares relacionados ao modo de intera??o droga-alvo e suas afinidades. Observamos que o IPF interage fortemente com a InhA e estas intera??es causam instabilidades na macromol?cula devido a perturba??o no s?tio de liga??o do substrato. Estas instabilidades se refletem no longo tempo necess?rio para a converg?ncia da trajet?ria. Observamos tamb?m que os res?duos Gly14, Ile15, Ile16, Ser20, Gly40, Phe41, Ile47, Ser94 e Thr196 s?o os respons?veis por intermediar a associa??o IPF-InhA. Conclu?mos ent?o que o IPF compete diretamente com o NADH pelo seu s?tio de liga??o e indiretamente com o substrato atrav?s da desestabiliza??o do seu s?tio de liga??o
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Rotta, Mariane. "9H-fluoren-9-IL(difenilmetil)-piperazinas : s?ntese, inibi??o da enzima 2-trans-enoil-ACP (CoA) redutase de mycobacterium tuberculosis e estudos de rela??o estrutura-atividade." Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2014. http://tede2.pucrs.br/tede2/handle/tede/5501.
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Previous issue date: 2014-07-16The Mycobacterium tuberculosis NADH-dependent enoyl-acyl carrier protein reductase (MtInhA) catalyzes hydride transfer to long-chain enoyl thioester substrates. MtInhA is a member of the mycobacterial type II dissociated fatty acid biosynthesis system, and is the bona fide target for isoniazid, the most prescribed drug for tuberculosis treatment. Here, a series of piperazine derivatives was synthesized and screened as MtInhA inhibitors, which resulted in the identification of compounds with IC50 values in the submicromolar range. A structure-activity relationship (SAR) evaluation indicated the importance of the chemical environment surrounding the carbonyl group for inhibition. In addition, the structure of one selected compound was supported by crystallographic studies, and experimental geometrical values were compared with semi-empirical quantum chemical calculations. Furthermore, the mode of inhibition and inhibitory dissociation constants were determined for the nine most active compounds. These findings suggest that these compounds interact with MtInhA at the enoyl thioester (2-trans-dodecenoyl-CoA) substrate binding site. Finally, two 9H-fluoren-9-yl-piperazine-containing compounds exhibited moderate antimycobacterial activity against the M. tuberculosis H37Rv strain.
A enzima 2-trans-enoil-ACP redutase de Mycobacterium tuberculosis (MtInhA) catalisa a etapa enzim?tica final no ciclo de alongamento da via de bioss?ntese de ?cidos graxos, convertendo 2-trans-enoil-ACP ? acil-ACP em um mecanismo dependente de NADH. Essa enzima vem sendo descrita como alvo validado para a descoberta de f?rmacos. Nesse trabalho uma s?rie de piperazinas foi sintetizada e avaliada quanto ao potencial inibit?rio da atividade enzim?tica da MtInhA, resultando em compostos com valores de IC50 na faixa de inibi??o de nanomolar. Avalia??es de rela??o estrutura-atividade (SAR) indicam a import?ncia do ambiente qu?mico adjacente ? carbonila para a inibi??o. Al?m disso, a estrutura de um composto foi confirmada por estudos cristalogr?ficos e os valores geom?tricos experimentais foram comparados com valores obtidos atrav?s de c?lculos semi-emp?ricos de obitais moleculares. Experimentos para determina??o do modo de inibi??o e obten??o dos valores das constantes de dissocia??o foram realizados para os nove compostos mais ativos. Os resultados sugerem que esses compostos interagem com MtInhA no s?tio de liga??o dos substratos acil-graxos. Finalmente, dois compostos, contendo na sua estrutura 9H-fluoren-9-il-piperazina exibiram moderada atividade antimicrobiana contra a cepa Mycobacterium tuberculosis H37Rv.
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Gargano, Furia. "Efeito da temperatura na enzima 2-trans-enoil-ACP (CoA) redutase (EC 1.3.1.9) de Mycobacterium tuberculosis em complexo com o NADH: um estudo por simulação pela dinâmica molecular." Pontifícia Universidade Católica do Rio Grande do Sul, 2009. http://hdl.handle.net/10923/1336.
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Previous issue date: 2009Temperature can interfere with protein structure and function, affecting its ability to bind to other molecules, its conformational microstates distribution, as well as the rate of its enzymatic reactions. Since the mid-20th the in silico or computer experiments have increasingly been used in different areas of science to help better understand and prove theoretical hypotheses. In this context, molecular dynamic (MD) simulations, a computational molecular biophysics technique was used in the study of structural variations in the native state of proteins as well as in the design and development of new drugs. The focus of the present study is on the effect of temperature in the enzyme 2-trans-enoil-ACP (CoA) reductase (InhA) from Mycobacterium tuberculosis by means of MD simulations. The InhA enzyme is the bonafide target of isoniazid (INH), the most important medicine used in the treatment of tuberculosis. The InhA-NADH enzymatic complex was submitted to MD simulations at 25 oC (298 K) and at 37 oC (310 K) for a total simulation time of 20 ns each. The temperature of 37 oC was chosen because it is the human body temperature, whilst 25 oC is used in in vitro experiments under normal conditions of temperature and pressure (NTP). Structural parameters such as root-mean square deviation or RMSD, radius of gyration, B-factors, and solvent accessible surface area were calculated from the MD trajectories. There are statistically significant conformational differences between the 3D structures resulting from 25 ºC and 37 ºC MSD. We also investigated the effect of temperature in the molecular flexibility. While observing a significant increase in flexibility in the substrate binding region (A- and Bloops and in the substrate biding loop), at 37 ºC the helices α6, α7 and α2 presented low B-factors at human body temperature. In the NADH coenzyme binding site, only three residues (Ser20, Ile21 e Phe41) presented lower flexibility with temperature increase. Small increases in temperature significantly affect the protein conformation in important regions that are relevant to its function. The increase in temperature changes the protein flexibility but in a heterogeneous way, preserving regions that need more stability in the functional aspect. The clear changes in the InhA enzyme and its coenzyme NADH during the temperature increase process from 25 ºC to 37 ºC must be considered in planning new drugs against this target. Therefore, we should take into account the environmental conditions (air pressure, temperature and pH) which they will be submitted on in vivo. We suggest, for the future, that research of targets to be done in temperature equal or very close to body temperature and to the one used at the dynamic spectrum of these target structures in molecular docking experiments, an important step in rational drug design.
Esta pesquisa refere-se a um estudo computacional via simulação por dinâmica molecular (DM) que investiga os efeitos da temperatura na InhA, enzima 2-trans-enoil-ACP (CoA) redutase do Mycobacterium tuberculosis (MTB). A temperatura pode interferir na estrutura e função protéicas, na habilidade de ligação de uma proteína, na distribuição dos microestados, na conformação molecular média e nas reações enzimáticas. A partir do início do século XX, os experimentos in silico tem sido cada vez mais utilizados para auxiliar na compreensão e comprovação das hipóteses teóricas elaboradas em diversas áreas da ciência. Neste contexto, a simulação por dinâmica molecular (DM) tem sido uma das técnicas da biofísica molecular computacional utilizadas no estudo da variação das propriedades estruturais do estado nativo das proteínas e no planejamento e design de fármacos. Esta pesquisa investigou o efeito da temperatura sobre a enzima 2-trans-enoil-ACP (CoA) redutase (InhA) através de um estudo por simulação pela DM (SDM). A enzima InhA é um importante alvo para a isoniazida (INH), um dos fármacos utilizados no tratamento da tuberculose (TBC). O complexo enzimático InhA-NADH foi submetido a uma SMD a 25 ºC (298 K) e outra a 37 ºC (310 K) durante um período de 20 ns. A temperatura de 37 ºC foi escolhida por corresponder à temperatura corporal humana. Por outro lado, 25 ºC representa a temperatura ambiente utilizada nos experimentos realizados em condições normais de temperatura e pressão (NTP). Alguns parâmetros iniciais (desvio médio quadrático, raio de giro, superfície acessível ao solvente) foram obtidos a partir da análise dos dados das duas trajetórias. Existem diferenças conformacionais estatisticamente significativas entre as estruturas 3D resultantes das SDM a 25 ºC e 37 ºC. Também pesquisou-se o efeito da temperatura sobre a flexibilidade molecular. Enquanto observamos um importante aumento da flexibilidade na região de ligação do vi substrato (alça A, alça B e alça de ligação do substrato) aos 37 ºC, as hélices α6, α7 e α2 apresentaram Fatores-B menores na temperatura corporal humana. Na região do sítio de ligação da coenzima, apenas três resíduos (Ser20, Ile21 e Phe41) apresentaram uma menor flexibilidade com o aumento da temperatura. Pequenos aumentos de temperatura afetam significativamente a conformação de uma proteína em regiões importantes para o desempenho de suas funções. A elevação da temperatura aumenta a flexibilidade da estrutura protéica, porém de forma heterogênea, preservando regiões que necessitam de maior estabilidade no aspecto funcional. As nítidas modificações da enzima InhA e sua coenzima NADH durante um processo de alteração de temperatura de 25 ºC para 37 ºC devem ser consideradas no decorrer do planejamento e design de qualquer fármaco. O conhecimento detalhado das estruturas alvo, portanto, deve levar em conta as condições ambientais (pressão, temperatura, pH) às quais serão submetidas em in vivo. Sugerem-se, para o futuro, pesquisas com temperaturas maiores e trabalhos com docking.
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Oliveira, Jaim Simoes de. "A enzima 2-trans-enoil-ACP (COA) redutase de Mycobacterium tuberculosis : inibição por um novo composto e estudos espectroscópicos do seu mecanismo de resistência à hidrazida do ácido isonicotínico." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2009. http://hdl.handle.net/10183/18799.
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Tuberculosis (TB) is a neglected disease, which continue to be major cause of morbidity and mortality worldwide, killing together around 5 million people each year. Mycolic acids, the hallmark of mycobacteria, are high-molecular-weight α-alkyl, β-hydroxy fatty acids. Biochemical and genetic experimental data have shown that the product of the M. tuberculosis inhA structural gene (InhA) is the primary target of isoniazid mode of action, the most prescribed anti-tubercular agent. InhA was identified as an NADH-dependent enoyl-ACP(CoA) reductase specific for long-chain enoyl thioesters and is a member of the Type II fatty acid biosynthesis system, which elongates acyl fatty acid precursors of mycolic acids. M. tuberculosis is a target for the development of anti-tubercular agents. Here we present a brief description of the mechanism of action of, and resistance to, isoniazid. In addition, data on inhibition of mycobacterial enoyl reductase by triclosan are presented. We also describe recent efforts to develop inhibitors of M. tuberculosis enoyl reductase enzyme activity.
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Gargano, Furia. "Efeito da temperatura na enzima 2-trans-enoil-ACP (CoA) redutase (EC 1.3.1.9) de Mycobacterium tuberculosis em complexo com o NADH : um estudo por simula??o pela din?mica molecular." Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2009. http://tede2.pucrs.br/tede2/handle/tede/5352.
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Previous issue date: 2009-07-21Esta pesquisa refere-se a um estudo computacional via simula??o por din?mica molecular (DM) que investiga os efeitos da temperatura na InhA, enzima 2-trans-enoil-ACP (CoA) redutase do Mycobacterium tuberculosis (MTB). A temperatura pode interferir na estrutura e fun??o prot?icas, na habilidade de liga??o de uma prote?na, na distribui??o dos microestados, na conforma??o molecular m?dia e nas rea??es enzim?ticas. A partir do in?cio do s?culo XX, os experimentos in silico tem sido cada vez mais utilizados para auxiliar na compreens?o e comprova??o das hip?teses te?ricas elaboradas em diversas ?reas da ci?ncia. Neste contexto, a simula??o por din?mica molecular (DM) tem sido uma das t?cnicas da biof?sica molecular computacional utilizadas no estudo da varia??o das propriedades estruturais do estado nativo das prote?nas e no planejamento e design de f?rmacos. Esta pesquisa investigou o efeito da temperatura sobre a enzima 2-trans-enoil-ACP (CoA) redutase (InhA) atrav?s de um estudo por simula??o pela DM (SDM). A enzima InhA ? um importante alvo para a isoniazida (INH), um dos f?rmacos utilizados no tratamento da tuberculose (TBC). O complexo enzim?tico InhA-NADH foi submetido a uma SMD a 25 ?C (298 K) e outra a 37 ?C (310 K) durante um per?odo de 20 ns. A temperatura de 37 ?C foi escolhida por corresponder ? temperatura corporal humana. Por outro lado, 25 ?C representa a temperatura ambiente utilizada nos experimentos realizados em condi??es normais de temperatura e press?o (NTP). Alguns par?metros iniciais (desvio m?dio quadr?tico, raio de giro, superf?cie acess?vel ao solvente) foram obtidos a partir da an?lise dos dados das duas trajet?rias. Existem diferen?as conformacionais estatisticamente significativas entre as estruturas 3D resultantes das SDM a 25 ?C e 37 ?C. Tamb?m pesquisou-se o efeito da temperatura sobre a flexibilidade molecular. Enquanto observamos um importante aumento da flexibilidade na regi?o de liga??o do vi substrato (al?a A, al?a B e al?a de liga??o do substrato) aos 37 ?C, as h?lices α6, α7 e α2 apresentaram Fatores-B menores na temperatura corporal humana. Na regi?o do s?tio de liga??o da coenzima, apenas tr?s res?duos (Ser20, Ile21 e Phe41) apresentaram uma menor flexibilidade com o aumento da temperatura. Pequenos aumentos de temperatura afetam significativamente a conforma??o de uma prote?na em regi?es importantes para o desempenho de suas fun??es. A eleva??o da temperatura aumenta a flexibilidade da estrutura prot?ica, por?m de forma heterog?nea, preservando regi?es que necessitam de maior estabilidade no aspecto funcional. As n?tidas modifica??es da enzima InhA e sua coenzima NADH durante um processo de altera??o de temperatura de 25 ?C para 37 ?C devem ser consideradas no decorrer do planejamento e design de qualquer f?rmaco. O conhecimento detalhado das estruturas alvo, portanto, deve levar em conta as condi??es ambientais (press?o, temperatura, pH) ?s quais ser?o submetidas em in vivo. Sugerem-se, para o futuro, pesquisas com temperaturas maiores e trabalhos com docking.
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Schroeder, Evelyn Koeche. "Efeito das mutações I16T, I21V, I47T e S94A na afinidade da enzima 2-trans-Enoil-ACP (CoA) redutase de Mycobacterium tuberculosis pelo cofator NADH : estudos por simulação pela dinâmica molecular e docking molecular." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2004. http://hdl.handle.net/10183/12025.
Full textAbstract:
aumento do número de casos de tuberculose e o surgimento de cepas de Mycobacterium tuberculosis (MTB) resistentes a múltiplas drogas, entre elas a isoniazida (INH) representa um sério problema de saúde pública. A enzima InhA, ou 2-trans-Enoil-ACP (CoA) redutase de MTB, catalisa a redução NADHdependente de ácidos graxos α,β-insaturados, precursores dos ácidos micólicos (importantes componentes do envelope celular do MTB). Mutações no gene estrutural da InhA estão associadas à resistência in vivo à INH devido a uma menor afinidade pela molécula de NADH, sugerindo que o mecanismo de resistência deva estar relacionado com interações específicas entre a enzima e o cofator. Para verificar os eventos moleculares associados à afinidade da enzima pelo ligante e identificar os aspectos moleculares relacionados com a resistência, foram realizados estudos de simulação por dinâmica molecular (DM) dos sistemas InhA-NADH (espécie selvagem wt e mutantes) completamente solvatados.Todos os sistemas enzimáticos apresentaram grande flexibilidade durante as trajetórias por DM. Apesar da flexibilidade, no complexo wt InhA-NADH, a molécula de NADH permanece firmemente ligada ao sítio da enzima numa conformação estendida. Nos complexos mutantes I21V e I16T, onde as mutações ocorrem na alça rica em glicina, as interações entre enzima e cofator são menos efetivas, permitindo que a porção pirofosfato do NADH experimente importantes mudanças conformacionais e se afaste de sua região de ligação, indicando, provavelmente, um estágio inicial da dissociação do ligante. No mutante I47T, a substituição da Ile por Thr causa uma contração no sítio de ligação do NADH, que é refletida no rearranjo conformacional do NADH e na expulsão de moléculas de água importantes para a associação do cofator O mutante S94A apresentacomportamento muito semelhante à enzima selvagem, como esperado a partir dos experimentos cristalográficos. As afinidades das enzimas pelo NADH foram avaliadas por experimentos de docking molecular, onde as estruturas instantâneas geradas durante as trajetórias da DM foram utilizadas como forma de considerar explicitamente a flexibilidade da macromolécula. Os resultados do docking molecular mostraram que todos os mutantes apresentam menor afinidade pelo NADH, exceto o mutante S94A, cuja energia livre de ligação do NADH foi estatisticamente igual à observada para a enzima selvagem. Os resultados apresentados neste trabalho devem contribuir para o entendimento do mecanismo molecular específico de resistência à INH, que é crucial para o desenvolvimento de novos fármacos para o controle da tuberculose.The increasing prevalence of tuberculosis in many areas of the world, coupled with the rise in drug-resistant Mycobacterium tuberculosis (MTB) strains presents a major threat to global health. InhA, the enoyl-ACP reductase from MTB, catalyzes the NADH-dependent reduction of long chain trans-2-enoyl-ACP fatty acids, an intermediate in mycolic acids biosynthesis. Mutations in the structural gene for InhA are associated with isoniazid resistance in vivo due to a reduced affinity for NADH, suggesting that the mechanism of drug resistance may be related to specific interactions between enzyme and cofactor within the NADH binding site. In order to compare the molecular events underlying this ligand affinity in the wild type and S94A, I21V, I16T and I47T clinical mutant enzymes, and to identify the molecular aspects related to resistance, molecular dynamics (MD) simulations of fully solvated NADH-InhA (wt and mutants) systems were performed.All InhA-NADH systems showed a large flexibility during the MD trajectories. Although very flexible, in the wt InhA-NADH complex, the NADH molecule keeps its extended conformation firmly bounded to the enzyme’s binding site. In the I21V and I16T mutant complexes, where mutated residues were located in the glycine rich loop, interactions between enzyme and cofactor became more labile, and the NADH pyrophosphate moiety undergoes to considerable conformational changes, becoming more hydrated and moving apart from its binding site, probably indicating the initial phase of ligand expulsion. In the I47T mutant, the substitution of an Ile residue for Thr causes a binding site contraction with conformational changes of the NADH molecule and expulsion of water molecules important for cofactor binding to the enzyme. The S94A mutant showed to be very similar to the wt enzyme, in agreement to crystallographic experiments observations. The enzyme-ligand affinities were evaluated by molecular docking experiments which were performed in the trajectory ensembles of MD snapshots asa way to explicit consider the macromolecular flexibility. All mutant enzymes had lower affinities for the NADH molecule, except the S94A mutant, whose free energy of NADH binding was statistically similar to that of the wild type enzyme. This results presented here should contribute to our understanding of specific molecular mechanisms of drug resistance, which is crucial for designing more potent antimycobacterial agents for controlling tuberculosis.
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Minville, Mélaine. "Altérations métaboliques cellulaires : la voie de biosynthèse des acides gras monoinsaturés comme cible thérapeutique." Thesis, Dijon, 2010. http://www.theses.fr/2010DIJOS079/document.
Full textAbstract:
La stéaroyl Co-A désaturase (SCD) est l’enzyme clé du métabolisme des acides gras mono-insaturés (AGMI). Son activité 9 désaturase introduit une double liaison cis en position 9 des acides gras saturés (AGS), formant des AGMI. Une altération de la voie de biosynthèse des AGMI est impliquée dans de nombreuses pathologies, telles que le cancer et les maladies cardiovasculaires. Les cellules cancéreuses présentent une synthèse de novo en acide gras accrue avec une accumulation d'AGMI. Ce changement dans le métabolisme des acides gras est associé à la surexpression de la SCD1. Plusieurs études ont démontré que l'inhibition de SCD1 conduit au blocage de la prolifération et l'induction de l'apoptose dans les cellules cancéreuses. Néanmoins, les mécanismes d'activation mort cellulaire restent à être mieux compris. Dans cette étude, nous avons démontré que l’extinction de SCD1 par siRNA, inhibiteur synthétique ou naturel induit l’abolition de la synthèse de novo AGMI dans les cellules cancéreuses ou non. L’activation de la mort cellulaire par apoptose lors de l’inhibition de SCD1 n’est observée que dans les cellules cancéreuses. En outre, la déplétion en SCD1 induite un stress du réticulum endoplasmique, ces caractéristiques étant l’épissage de l'ARNm XBP1, la phosphorylation de eIF2α et augmentation de l'expression CHOP. Toutefois, l'activation du stress du RE lors de l’abolition de SCD1 est particuliers puisque nous ne mettons pas en évidence de modification de l’expression de la protéine chaperonne GRP78, une autre caractéristique du stress du RE. Enfin, nous avons montré que l'induction de CHOP participe à l’activation de la mort cellulaire lors de l’extinction de SCD1. En effet, la surexpression de constructions dominants négatifs et anti-CHOP restaure partiellement la viabilité des cellules cancéreuses déplétées en SCD1. Pour conclure, ces résultats suggèrent que l’inhibition de la synthèse de novo en AGMI via l’extinction de SCD1 pourrait être une cible thérapeutique prometteuse contre le cancer en induisant la mort cellulaire par l’activation de la voie du stress du réticulum endoplasmique et du facteur de transcription CHOP. Nous nous sommes également intéressés à la régulation de SCD par différents AGMI dans un modèle cellulaire en lien avec la pathologie athéromateuse. De nombreux facteurs de risque participent au développement de cette pathologie, parmi lesquels les acides gras trans (AGT). En effet, des études épidémiologiques ont mis en corrélation la consommation d’AGT d’origine industrielle et le risque de maladie cardiovasculaire. Les AGT pourraient jouer leurs effets athérogènes par l’altération du métabolisme lipidiques des cellules vasculaires. L'accumulation de lipides dans les cellules musculaires lisses vasculaires (CML) est une caractéristique de l'athérosclérose et une conséquence de la lipogenèse accrue. L’expression de la SCD est associée à l'induction de la lipogenèse et développement de l'athérosclérose. Nous nous sommes intéressés à la régulation de l'activité SCD1 dans les CML exposés à des isomères d’AGMI en C18 [l’acide cis-9oléique(OL), l'acide trans-11 vaccénique (TVA) ou l’acide trans-9 élaïdique (ELA)]. Nous avons montré que la SCD, présente dans les CML était régulée différemment selon l’isomère en C18 :1. En effet, nous observons une augmentation de l’expression et de l’activité de SCD1 sous l’effet d’un traitement par ELA et une diminution importante pour le traitement par OL. L’effet du TVA sur l’expression et l’activité dans les CML reste modeste mais une diminution est néanmoins trouvée. Nous avons corrélé l'activité de SCD avec son niveau d'expression protéique. En effet, celle-ci est augmentée par l’ELA et diminuée par l'OL. Cette régulation n’est pas post-traductionnelle et l’expression de SCD1 lors des traitements par l’OL et l’ELA est moduler au niveau transcriptionnel.Pour conclure, nous avons démontré une modulation de l'activité SCD par des AGMI (C18: 1) de configuration cis et [...]Stearoyl Co-A desaturase (SCD) is the key enzyme of the metabolism of mono-unsaturated fatty acids (MUFA). Its activity 9 desaturase introduces a double bond cis in position 9 of saturated fatty acids (SFA), induced formation of MUFA. Impaired biosynthesis of MUFA is involved in many diseases such as cancer and cardiovascular disease. Cancer cells have a de novo synthesis of fatty acids increased with an accumulation MUFA. This change in the metabolism of fatty acids is associated with overexpression SCD1 which catalyzes the conversion of saturated fatty acids, monounsaturated fat. Several reports have shown that inhibition of SCD1 leads to blockage of proliferation and induction of apoptosis in cancer cells. However, the mechanism of cell death activation remains to be understood. In this study, we demonstrated that the extinction of SCD1 by siRNA, synthetic or natural inhibitor induces the abolition of de novo MUFA synthesis in cancer cells or not. SCD1 inhibition activates cell death by apoptosis only in cancer cells. In addition, depletion of SCD1 induced endoplasmic reticulum stress, these features being XBP1 mRNA splicing, phosphorylation of eIF2α and increased expression of CHOP. However, activation of ER stress in the abolition of SCD1 is special because we do not show changes in expression of the chaperone protein GRP78, another characteristic of ER stress. Finally, we showed that induction of CHOP is involved in activation of cell death during shutdown of SCD1. Indeed, overexpression of dominant negative constructs and anti-CHOP partially restores the viability of cancer cells depleted of SCD1. In conclusion, these results suggest that inhibition of de novo synthesis of MUFA through the extinction of SCD1 could be a promising therapeutic target against cancer by inducing cell death through the activation of the stress and endoplasmic reticulum transcription factor CHOP. We are also interested in the regulation of SCD by different MUFA in a cellular model linked with atherosclerotic disease. Many risk factors contribute to the development of this disease, including trans fatty acid (TFA). Indeed, epidemiological studies have correlated the consumption of TFA from industrial sources and the risk of cardiovascular disease. TFA could play their atherogenic effects by altering the lipid metabolism of vascular cells. The accumulation of lipids in vascular smooth muscle cells (SMC) is a feature of atherosclerosis and a consequence of increased lipogenesis. The expression of SCD is associated with the induction of lipogenesis and development of atherosclerosis. We are interested in the regulation of SCD1 activity in SMCs exposed to isomers of MUFA C18 [cis-9 oleic (OL), trans-11 vaccenic acid (TVA) and acid trans -9 elaidic (ELA)]. We showed that SCD which is present in SMC was regulated differently depending on the isomer C18: 1. Indeed, we observed an increase in the expression and activity of SCD1 as a result of treatment with ELA and a significant decrease for treatment with OL. The effect of the TVA on the expression and activity in SMCs remains modest decrease is nevertheless found. We correlated the activity of SCD with its level of protein expression. Indeed, it is increased by the ELA and decreased by OL. This regulation is posttranslational and expression of SCD1 during treatment with the OL and the ELA is modulated at the transcriptional level. To conclude, we demonstrated a modulation of SCD activity by MUFA (C18: 1) cis and trans-mediated regulation of SCD1 gene transcription
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Gabrieli, Jacopo. "Les éléments présents à l'état de traces et les hydrocarbures aromatiques polycycliques dans la neige et la glace prélevées au col Gnifetti, massif du Mont Rose (4450 m) : implications environnementales et climatiques." Université Joseph Fourier (Grenoble), 2008. http://www.theses.fr/2008GRE10218.
Full textAbstract:
Nous avons conçu, construit et testé un nouveau système pour la décontamination en ligne et l'analyse en continu de carottes de neige ou de glace des Alpes. L'eau de fusion obtenue à partir de la partie centrale des carottes est directement introduite dans un spectromètre de masse à quadrupole (ICP-QMS) et un conductimètre, pour la détermination en continu de différents éléments présents à l'état de traces et de la conductivité. Des échantillons sont également prélevés en discontinu pour la détermination de divers éléments présents à l'état de traces, des isotopes du Plomb et du Plutonium par spectrométrie de masse à secteur magnétique (ICP-SFMS) et par ICP-OES. L'eau de fusion obtenue à partir de la partie externe des carottes est quant à elle utilisée pour la détermination en semi-continu des Hydrocarbures Aromatiques Polycycliques (HAPs), avec extraction en ligne à l'aide de cartouches en phase solide. D'importantes variations saisonnières des concentrations sont observées pour tous les éléments, aussi bien les éléments qui proviennent de manière prédominante de la croûte terrestre (Mg, Al) que les éléments enrichis par suite d'apports anthropiques (Pb). Pour comprendre ces variations à court terme, il est important de se référer aux rétro-trajectoires des masses d'air. D'autres paramètres importants sont la dynamique des inversions de températures et les caractéristiques de la couche limite. Ils jouent en effet un rôle majeur dans le transport et la dispersion des aérosols et des gaz à partir des sources d'émissions situées à basse altitude. Les émissions les plus importantes de Plomb au cours de l'histoire ont eu lieu pendant les 19e et 20e siècles, et plus particulièrement des années 1950 aux années 1970. Pour déterminer si les variations observées dans la carotte du Colle Gnifetti reflètent fidèlement les variations des émissions dans les pays européens voisins, nous avons comparé les données obtenues pour la neige et la glace avec les données d'émission disponibles. De 1800 jusqu'à la première décennie du 20e siècle, les concentrations de Plomb ont augmenté de manière très marquée, atteignant un maximum dans les années 1920. Pendant les années 1920, les concentrations de Plomb décroissent rapidement d'un facteur deux, et restent à ce niveau pendant les deux décennies suivantes. Après la fin de la 2e guerre mondiale, les flux de retombées de Plomb augmentent de manière très importante par suite de l'utilisation des additifs au Plomb dans l'essence, et atteignent un maximum au milieu des années 1970. A partir de 1975, les concentrations de Plomb mesurées dans la neige et la glace du Colle Gnifetti commencent à décroître par suite des règlementations adoptées en Europe pour limiter les émissions de polluants. Avant 1875, les concentrations de HAP étaient très basses: les concentrations observées dans la glace datant d'avant les années 1750 représentent très probablement le niveau de bruit de fond de ces composés. Les concentrations cumulées des HAP au cours de la décennie 1945-1955 sont supérieures d'un facteur dix aux valeurs de bruit de fond, alors que les concentrations cumulées de HAP* sont environ 40 à 50 fois plus élevées. A partir des années 1900, les concentrations de HAP augmentent de façon très importante, atteignant un maximum vers 1920. Pendant les années 1920, après la première guerre mondiale, la récession économique en Europe conduit à une chute des activités industrielles. A partir du milieu des années 1930, les concentrations de HAP doublent rapidement, atteignant un maximum pendant les années 1940. La concentration cumulée des HAP* les plus lourds décroit ensuite d'un facteur cinq de 1950 à 1975 alors que la concentration cumulée des HAP décroit d'un facteur deux. De 1975 à 2003, la concentration totale des HAP augmente à nouveau, approchant les valeurs des années 1910. De manière globale, les variations temporelles observées pour les HAP sont fortement corrélées aux variations des émissions anthropiques. Cependant, les variations détaillées sont difficiles à interpréter et pourraient être influencées par divers paramètres. Le Plutonium est présent dans l'environnement par suite des essais nucléaires atmosphériques des années 1960, de la production des armes nucléaires et des rejets par l'industrie nucléaire au cours des 50 dernières années. Le profil de variations du Plutonium dans la neige et la glace du Colle Gnifetti met en évidence les trois périodes principales d'essais nucléaires atmosphériques. Le rapport isotopique 206Pb/207Pb est compris entre 1. 18 et 1. 20 pour la glace datant d'avant 1700, en accord avec la composition des roches locale. Bien que les retombées de Plomb au Colle Gnifetti après les années 1900 soient presque entièrement dues à des apports anthropiques, on n'observe pas de variations importantes du rapport isotopique jusqu'en 1975. Ceci est lié au fait que la composition isotopique moyenne du Plomb dans l'essence et le pétrole utilisés était très semblable à la composition isotopique des roches et des sols locaux. Après 1975, on observe une décroissance brutale et forte du rapport isotopique 206Pb/207Pb, jusqu'à des valeurs proches de 1. 11 en 1979-1980. Cette décroissance brutale est liée à une expérience réalisée entre 1975 et 1980 dans la région du Piémont au Nord-Ouest de l'Italie (Isotopic Lead Experiment)A new melting device for on-line decontamination and continuous analysis of alpine firn/ice cores has been designed, built and tested. Melt water from the inner part of each ice core section was pumped to an ICP-QMS and a conductivity micro-cell for continuous measurements of trace elements concentrations and conductivity, respectively. Discrete samples were also collected for trace elements, Pb isotopes and 239Pu determinations by ICP-SFMS and ICP-OES. Melt water from the outer section was extracted on-line by solid-phase cartridges for semi-continuous Polycyclic Aromatic Hydrocarbons (PAHs) analysis. Pronounced seasonal variations were observed for all elements, both crustal (Mg, Al) and anthropogenically enriched (Pb). To understand short-time variations, air mass back trajectories are an important parameter which must be considered. Also the knowledge of the temperature inversion dynamics and the boundary layer features is extremely important because they play a key role in the transport and dispersion of aerosol and gases from low-altitude emission sources. The largest emissions of Pb through history occurred during the 19th and 20th centuries and especially between the 1950s and 1970s. To determine if changes observed in Colle Gnifetti core faithfully reflect changes in emissions from nearby European countries, we have compared snow/ice data with emissions data present in the literature. For example, from 1800 AD to the first decade of 20th century Pb concentrations progressively increased, reaching a maximum in the 1920s. During the 1920s Pb concentrations suddenly halved and remained low for the next two decades. After the Second World War, Pb depositions increased dramatically with the introduction of Pb additives in gasoline, peaking in the mid-1970s. From 1975, Pb concentrations in Colle Gnifetti ice began to decrease in accordance with the first environmental policies in Europe which started to limit pollutant emissions. Before 1875 PAHs levels were very low: the pre-1750's PAHs concentrations were assumed to be the background level. ΣPAHs in the 1945-1955 ten-year period were 10 times greater than background values with ΣPAHs* greater by about 40-50 times. From 1900, PAHs concentrations increased exponentially, reaching a maximum in 1920. In the 1920s, after the First World War economic stagnation in Europe depressed industrial activities which were converting to civilan production. From the mid-1930s PAHs rapidly doubled reaching their maximum concentrations from 1940 to 1950. The heaviest ΣPAHs* concentrations decreased by a factor 5 from 1950 to 1975 while for total ΣPAHs the concentrations halved. From 1975 to 2003 ΣPAHs rose again and nearly returned to 1910s values. Although the general PAHs trends are strongly correlated with anthropogenic emission variation, the fine shape of the profile is less clear and could be influenced by several parameters. Plutonium is present in the environment as a consequence of the atmospheric nuclear testing carried out in the 1960s, the production of nuclear weapons and nuclear industry releases over the past 50 years. The shape of 239Pu profile reflects three main periods of atmospheric nuclear weapons testing. The 206Pb/207Pb ratio for the pre-1700 background period ranged between 1. 18 and 1. 20, in agreement with the composition of local rocks. Although Pb deposition on Colle Gnifetti after 1900 was almost totally due to anthropogenic emissions, the 206Pb/207Pb ratio does not decline intensely until 1975. This is due to the average Pb isotopic composition of industrial emissions and gasoline additives used which was very similar to the crustal composition in local rocks and soil. After 1975, a sudden and intense 206Pb/207Pb ratio depletion is recorded. This value reached a minimum of 1. 11 in 1979-1980. This behaviour is characteristic of the ILE experiment (Isotopic Lead Experiment) - a large scale isotopic tracer experiment using Pb isotopes that was carried out between 1975 and 1980 in the Piedmont region of northwest Italy centred on Turin
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Hawari, Haitham M. "Minimising track degradation through managing vehicle/track interaction." Thesis, Queensland University of Technology, 2007. https://eprints.qut.edu.au/16366/1/Haitham_Hawari_Thesis.pdf.
Full textAbstract:
The rate at which a railway track deteriorates depends on the response of the track
under different static and repeated dynamic forces. These wheel/rail forces lead to
imperfections in the rail surface and deviation in track geometry alignment. The
wheel/rail forces are dependent upon the quality of maintenance of the
characteristics of both train and track. If train components such as wheelsets and
suspensions are maintained to a high standard, less dynamic forces are generated
at the wheel/rail interface and less damage is caused over time. Therefore, the
amount and cost of maintenance of track are reduced. However, there is little
known about how the characteristics of train components affect time-dependent
track degradation.
Track degradation through deviation of track from its ideal position has the most
effect on maintenance costs. Therefore, the present research aims to investigate
this track degradation and improve understanding of the effects of train
characteristics (such as train mass and speed, suspension stiffness and damping)
on railway tracks. The research is conducted by looking into the relationship
between wheel/rail forces and track degradation on one hand and between
wheel/rail forces and train characteristics on the other hand, with the objective of
assisting in managing vehicle/track interaction in order to minimise track
degradation. This aim is achieved by investigating the above two relationships to
attain the desired relationship between track degradation and train characteristics.
The research focuses on wheel/rail vertical forces (both amplitudes and
frequencies), vertical track alignment (longitudinal vertical profile), and rail head
defects.
The study started by collecting wheel/rail vertical forces data in addition to data
on vertical track degradation under sustained traffic loads on a heavy haul railway section of track in Central Queensland. Also, five years of degradation and
maintenance history data were collected on three other test sections of railway
track under variety of traffic conditions and loads in Central Queensland. There
were four main analyses of this data employed to probe the study. The first
analysis was performed by examining the track degradation history data. The
standard deviation method was used in this first analysis to acquire the rate of
deterioration in terms of its relationship to track profile (roughness). The second
analysis was accomplished by correlating the vertical wheel/rail forces to both
vertical track profile and rail roughness using signal processing principles and a
function know as coherence. The third analysis was carried out by using the
computer simulation software NUCARS to obtain the link between wheel/rail
forces and the deterioration of the vertical track profile. The fourth analysis was
achieved by combining the results obtained from the above three analyses to
acquire the rate of track deterioration in terms of its relationship to varying train
characteristics.
The first analysis mentioned above quantified the relationship between the level of
roughness of the track and rate at which that roughness deteriorated. An important
outcome of this relationship is that there is a threshold of roughness below which
track deterioration is minimal. The track maintenance planners can now use that
threshold for cost effective targeting of tamping activities. The correlation study
between track roughness and wheel/rail forces using the coherence function
found, surprisingly, that the overall deterioration of the track roughness, in the
absence of frequencies of forces above 30 Hz, is due to the so-called quasi-static
lower frequency oscillations of dynamic forces. This conclusion together with the
relationship between vehicle characteristics and track forces, established in the
analyses above, has significant implications for the design of wagon bogies and
for charges track owners might levy on trains using their tracks.
This research is part of a larger Rail CRC project 11/4 called 'Enhancing the
Optimisation of Maintenance/Renewal' being carried out in the School of Urban
Development in Queensland University of Technology.
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Hawari, Haitham M. "Minimising track degradation through managing vehicle/track interaction." Queensland University of Technology, 2007. http://eprints.qut.edu.au/16366/.
Full textAbstract:
The rate at which a railway track deteriorates depends on the response of the track under different static and repeated dynamic forces. These wheel/rail forces lead to imperfections in the rail surface and deviation in track geometry alignment. The wheel/rail forces are dependent upon the quality of maintenance of the characteristics of both train and track. If train components such as wheelsets and suspensions are maintained to a high standard, less dynamic forces are generated at the wheel/rail interface and less damage is caused over time. Therefore, the amount and cost of maintenance of track are reduced. However, there is little known about how the characteristics of train components affect time-dependent track degradation. Track degradation through deviation of track from its ideal position has the most effect on maintenance costs. Therefore, the present research aims to investigate this track degradation and improve understanding of the effects of train characteristics (such as train mass and speed, suspension stiffness and damping) on railway tracks. The research is conducted by looking into the relationship between wheel/rail forces and track degradation on one hand and between wheel/rail forces and train characteristics on the other hand, with the objective of assisting in managing vehicle/track interaction in order to minimise track degradation. This aim is achieved by investigating the above two relationships to attain the desired relationship between track degradation and train characteristics. The research focuses on wheel/rail vertical forces (both amplitudes and frequencies), vertical track alignment (longitudinal vertical profile), and rail head defects. The study started by collecting wheel/rail vertical forces data in addition to data on vertical track degradation under sustained traffic loads on a heavy haul railway section of track in Central Queensland. Also, five years of degradation and maintenance history data were collected on three other test sections of railway track under variety of traffic conditions and loads in Central Queensland. There were four main analyses of this data employed to probe the study. The first analysis was performed by examining the track degradation history data. The standard deviation method was used in this first analysis to acquire the rate of deterioration in terms of its relationship to track profile (roughness). The second analysis was accomplished by correlating the vertical wheel/rail forces to both vertical track profile and rail roughness using signal processing principles and a function know as coherence. The third analysis was carried out by using the computer simulation software NUCARS to obtain the link between wheel/rail forces and the deterioration of the vertical track profile. The fourth analysis was achieved by combining the results obtained from the above three analyses to acquire the rate of track deterioration in terms of its relationship to varying train characteristics. The first analysis mentioned above quantified the relationship between the level of roughness of the track and rate at which that roughness deteriorated. An important outcome of this relationship is that there is a threshold of roughness below which track deterioration is minimal. The track maintenance planners can now use that threshold for cost effective targeting of tamping activities. The correlation study between track roughness and wheel/rail forces using the coherence function found, surprisingly, that the overall deterioration of the track roughness, in the absence of frequencies of forces above 30 Hz, is due to the so-called quasi-static lower frequency oscillations of dynamic forces. This conclusion together with the relationship between vehicle characteristics and track forces, established in the analyses above, has significant implications for the design of wagon bogies and for charges track owners might levy on trains using their tracks. This research is part of a larger Rail CRC project 11/4 called 'Enhancing the Optimisation of Maintenance/Renewal' being carried out in the School of Urban Development in Queensland University of Technology.
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Briand, Marine. "Place des poissons anguilliformes dans le fonctionnement des écosystèmes récifo- lagonaires de la Nouvelle-Calédonie : rôle trophique et impacts des contaminations." Thesis, Nouvelle Calédonie, 2014. http://www.theses.fr/2014NCAL0055/document.
Full textAbstract:
Les récifs coralliens de Nouvelle-Calédonie constituent un « hot-spot » de biodiversité marine et sont classés au patrimoine mondial de l’Unesco depuis 2008. Ces récifs sont dans un bon état général, mais ils sont soumis à des pressions anthropiques de plus en plus intenses, engendrées par un développement industriel (mines de nickel) et urbain croissant.Mieux comprendre le fonctionnement des écosystèmes lagonaires calédoniens est donc devenu un enjeu majeur. Ce travail s’inscrit dans cette démarche, avec pour objectifs principaux : (1) de reconstruire l’architecture des réseaux trophiques de ces écosystèmes (méthode des isotopes stables), (2) de déterminer leurs niveaux de contamination en éléments traces métalliques et en polluants organiques, et (3) de décrire l’intégration et le cheminement de certains de ces contaminants en leur sein. L’étude des écosystèmes récifo-lagonaires et de leurs réseaux trophiques a été réalisée au travers du prisme de prédateurs méconnus de hauts rangs trophiques : les poissons anguilliformes (murènes, congres et poissons-serpents). Pour ce faire, différentes sources de matière organique (MO) et divers consommateurs, parmi lesquels les poissons anguilliformes, ont été prélevés dans plusieurs sites répartis sur un gradient côte-large et provenant de deux zones du lagon sud.Quatre réseaux trophiques ont été identifiés au cours de ce travail. La voie benthique basée sur la MO du turf algal est la voie trophique majeure, commune à tous les poissons anguilliformes. L’utilisation complémentaire de la voie benthique sédimentaire et de la voie « pélagique lagonaire », est également mise en évidence avec une importance variable selon les espèces. En revanche, la MO provenant des phanérogames marines n’est intégrée qu’indirectement, par le biais de la voie détritique. Les différentes espèces d’anguilliformes appartiennent donc à des réseaux trophiques en partie divergents selon leur habitat (substrat dur ou meuble) et leur régime alimentaire (micro-, macrocarnivore ou piscivore). Ces prédateurs de hauts niveaux trophiques, consommant principalement des crustacés et des poissons mais également occasionnellement des annélides polychètes et des céphalopodes, se révèlent pour la plupart opportunistes. Une compétition entre certaines espèces est soulignée par le recouvrement de leurs niches trophiques. Les sources de MO et les consommateurs récifaux du lagon calédonien accumulent des concentrations modérées à fortes en éléments traces d’origine agricole, urbaine et minière. La bioaccumulation dépend des propriétés physico-chimiques du contaminant lui-même et des caractéristiques propres à l’organisme (taille, habitat, régime alimentaire, etc.). Ainsi, les contaminants sont répartis différemment entre les compartiments, et seuls Hg et As sont bioamplifiés le long des réseaux trophiques. Une contamination du lagon par les polluants organiques est également soulignée. Bien que les concentrations mesurées chez les poissons anguilliformes restent relativement faibles, l’étendue spatiale de cette contamination, ainsi que la détection de pesticides très toxiques dont l’utilisation est interdite (DDT), attestent de la nécessité à considérer cette pollution avec attention. Toutes ces considérations renforcent l’importance de mener un suivi à long terme des contaminations d’origines diverses en relation avec le fonctionnement trophique des systèmes récifo-lagonairesNew Caledonian coral reefs constitute a « hot spot » of marine biodiversity and were registered World Heritage by UNESCO in 2008. These reefs are in good health, but they are subject to intense anthropic threats, induced by the increase of industrial (nickel mining) and urban development. A better understanding of the functioning of the Caledonian coral reefs has become a major issue. This work is part of this approach, with as main goals to: (1) reconstruct the architecture of food webs of these ecosystems (stable isotope method), (2) determine their contamination levels in metallic and organic contaminants and (3) describe integration and pathways of some of these contaminants through the food webs. The description of ecosystems and their food webs was carried out by the study of unknown predators: the anguilliform fish (moray, conger and snake eels). Different sources of organic matter (OM) and consumers, including anguilliform fish, were sampled in several sites distributed over a coast to barrier reef gradient within two areas of the south lagoon. Four food webs were identified. The benthic pathway based on the algal turf OM is the main food web, common to all anguilliform fish. The complementary use of benthic sedimentary (SOM) and “lagoon pelagic” (POM) food webs, is also highlighted with variable importance according to species. In addition, OM from seagrasses is included indirectly by the detrital pathway. The numerous anguilliform fish species belong to diverse food webs in part, depending on their habitat (hard and/or soft bottom) and their diet (micro/macro carnivores or piscivores). These predators of high trophic level, consuming mainly crustaceans and fish but also more occasionally annelids and cephalopods, are mostly opportunistic. A competition between some species is underlined by the overlap of their trophic niches. Sources of OM and consumers of the Caledonian coral reefs accumulate moderate to strong concentrations of trace elements issued from agricultural, urban and mining origins. Bioaccumulation depends on both physical and chemical properties of the contaminant and the organism’s own characteristics (size, habitat, diet, etc.). So, contaminants are distributed differently between compartments and only Hg and As are biomagnified along food webs. Contamination of the lagoon by organic pollutants is also pointed out. Even if concentrations measured in anguilliform fish are rather low, widespread contamination, plus the detection of toxic and forbidden pesticides (DDT), confirm the necessity to include this pollution in further studies. All these considerations reinforce the importance of setting up a long-term tracking system of contamination from diverse origins, linked with the trophic functioning of food webs
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Schaefer-Koesterke, Heike Verfasser], Stefan [Akademischer Betreuer] Vidal, Heiko [Akademischer Betreuer] [Becker, and Bernd [Akademischer Betreuer] Ulber. "Effect of plant traits on host selection and performance of rape stem weevil (Ceutorhynchus napi Gyll.) (Col.: Curculionidae) on resynthesized lines and cultivars of oilseed rape (Brassica napus L.) / Heike Schaefer-Koesterke. Gutachter: Stefan Vidal ; Heiko C. Becker ; Bernd Ulber. Betreuer: Stefan Vidal." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2015. http://d-nb.info/1072820447/34.
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Biscéré, Tom. "Effets des métaux et des changements climatiques sur les coraux." Electronic Thesis or Diss., Sorbonne université, 2018. http://www.theses.fr/2018SORUS382.
Full textAbstract:
Les récifs coralliens se sont largement dégradés au cours de ces dernières décennies sous l’influence des activités anthropiques. Parmi ces perturbations, l’augmentation des concentrations métalliques concerne de nombreux récifs à travers le monde (e.g. grande barrière australienne, Costa Rica, Mer Rouge, Nouvelle-Calédonie). A ces stress locaux vient s’ajouter le changement climatique, et plus particulièrement l’élévation des températures et l’acidification des océans, auxquelles les coraux doivent désormais faire face. Dans ce contexte particulier, les objectifs de cette thèse ont donc été (1) de déterminer l’effet sur la physiologie corallienne, des principaux métaux présents dans les sédiments latéritiques (fer, manganèse, nickel et cobalt), à des concentrations représentatives de celles mesurées sur le littoral calédonien, et (2) de définir leurs rôles potentiels dans ce contexte de changement climatique. Les résultats obtenus ont montré que les métaux ont des effets très différents sur le métabolisme corallien. Alors qu’à température ambiante un apport en nickel ou en manganèse stimule le métabolisme de l’hôte et la photosynthèse des symbiotes, à l’inverse, un enrichissement en cobalt inhibe la calcification et devient même toxique dès 1.0 μg L-1 pour les symbiotes et l’hôte. De même, malgré son importance dans les processus photosynthétiques, un apport en fer diminue la densité en Symbiodinium des tissus et inhibe la calcification. En période de stress thermique, le manganèse augmente la tolérance des coraux à cette hausse de température, probablement en stimulant leurs défenses antioxydantes, tandis que le nickel aggrave ces effets en diminuant encore davantage leur croissance. Ces travaux constituent une étape importante vers une meilleure compréhension de la réaction des coraux aux enrichissements métalliques et permettraient d’expliquer, dans une certaine mesure, la sensibilité des espèces coralliennes aux changements climatiquesCoral reefs have largely degraded in recent decades under the influence of human activities. Among those disturbances, the increase in metal concentrations affects many reefs worldwide (e.g. Australian Great Barrier Reef, Costa Rica, Red Sea, New Caledonia). Furthermore, reefs have now to face climate change, and more particularly temperature increase and ocean acidification. In this context, the aims of my thesis were to (1) determine the effects of the main metals present in lateritic sediments (iron, manganese, nickel and cobalt) on coral physiology using concentrations representative of those measured along the New Caledonian coastline, and to (2) define their potential roles in this context of climate change. My results showed that metals affect coral metabolism in different ways. While at ambient temperature, a nickel or manganese enrichment stimulates host metabolism and symbiont photosynthesis, conversely a cobalt enrichment inhibits calcification and becomes even toxic for the host and symbionts, from 1 μg L-1. Despite its importance in photosynthetic processes, an iron enrichment induces a decrease in Symbiodinium densities and an inhibition of calcification rates. Under thermal stress, manganese enhances coral tolerance to temperature increase, likely by stimulating their antioxidant defenses, while nickel worsens its effects by decreasing even more their growth. These works represent an important step towards a better understanding of coral responses to metal enrichment and would explain, to some extent, species susceptibility to climate change
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Minville-Walz, Mélaine. "Altérations métaboliques cellulaires : la voie de biosynthèse des acides gras monoinsaturés comme cible thérapeutique." Phd thesis, Université de Bourgogne, 2010. http://tel.archives-ouvertes.fr/tel-00682619.
Full textAbstract:
La stéaroyl Co-A désaturase (SCD) est l'enzyme clé du métabolisme des acides gras mono-insaturés (AGMI). Son activité 9 désaturase introduit une double liaison cis en position 9 des acides gras saturés (AGS), formant des AGMI. Une altération de la voie de biosynthèse des AGMI est impliquée dans de nombreuses pathologies, telles que le cancer et les maladies cardiovasculaires. Les cellules cancéreuses présentent une synthèse de novo en acide gras accrue avec une accumulation d'AGMI. Ce changement dans le métabolisme des acides gras est associé à la surexpression de la SCD1. Plusieurs études ont démontré que l'inhibition de SCD1 conduit au blocage de la prolifération et l'induction de l'apoptose dans les cellules cancéreuses. Néanmoins, les mécanismes d'activation mort cellulaire restent à être mieux compris. Dans cette étude, nous avons démontré que l'extinction de SCD1 par siRNA, inhibiteur synthétique ou naturel induit l'abolition de la synthèse de novo AGMI dans les cellules cancéreuses ou non. L'activation de la mort cellulaire par apoptose lors de l'inhibition de SCD1 n'est observée que dans les cellules cancéreuses. En outre, la déplétion en SCD1 induite un stress du réticulum endoplasmique, ces caractéristiques étant l'épissage de l'ARNm XBP1, la phosphorylation de eIF2α et augmentation de l'expression CHOP. Toutefois, l'activation du stress du RE lors de l'abolition de SCD1 est particuliers puisque nous ne mettons pas en évidence de modification de l'expression de la protéine chaperonne GRP78, une autre caractéristique du stress du RE. Enfin, nous avons montré que l'induction de CHOP participe à l'activation de la mort cellulaire lors de l'extinction de SCD1. En effet, la surexpression de constructions dominants négatifs et anti-CHOP restaure partiellement la viabilité des cellules cancéreuses déplétées en SCD1. Pour conclure, ces résultats suggèrent que l'inhibition de la synthèse de novo en AGMI via l'extinction de SCD1 pourrait être une cible thérapeutique prometteuse contre le cancer en induisant la mort cellulaire par l'activation de la voie du stress du réticulum endoplasmique et du facteur de transcription CHOP. Nous nous sommes également intéressés à la régulation de SCD par différents AGMI dans un modèle cellulaire en lien avec la pathologie athéromateuse. De nombreux facteurs de risque participent au développement de cette pathologie, parmi lesquels les acides gras trans (AGT). En effet, des études épidémiologiques ont mis en corrélation la consommation d'AGT d'origine industrielle et le risque de maladie cardiovasculaire. Les AGT pourraient jouer leurs effets athérogènes par l'altération du métabolisme lipidiques des cellules vasculaires. L'accumulation de lipides dans les cellules musculaires lisses vasculaires (CML) est une caractéristique de l'athérosclérose et une conséquence de la lipogenèse accrue. L'expression de la SCD est associée à l'induction de la lipogenèse et développement de l'athérosclérose. Nous nous sommes intéressés à la régulation de l'activité SCD1 dans les CML exposés à des isomères d'AGMI en C18 [l'acide cis-9oléique(OL), l'acide trans-11 vaccénique (TVA) ou l'acide trans-9 élaïdique (ELA)]. Nous avons montré que la SCD, présente dans les CML était régulée différemment selon l'isomère en C18 :1. En effet, nous observons une augmentation de l'expression et de l'activité de SCD1 sous l'effet d'un traitement par ELA et une diminution importante pour le traitement par OL. L'effet du TVA sur l'expression et l'activité dans les CML reste modeste mais une diminution est néanmoins trouvée. Nous avons corrélé l'activité de SCD avec son niveau d'expression protéique. En effet, celle-ci est augmentée par l'ELA et diminuée par l'OL. Cette régulation n'est pas post-traductionnelle et l'expression de SCD1 lors des traitements par l'OL et l'ELA est moduler au niveau transcriptionnel.Pour conclure, nous avons démontré une modulation de l'activité SCD par des AGMI (C18: 1) de configuration cis et [...]
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Chu, Chunhua. "La planification française comme instrument de politique industrielle de la Libération au milieu de la présidence du Général De Gaulle (1945-1965)." Thesis, Sorbonne université, 2018. http://www.theses.fr/2018SORUL101.
Full textAbstract:
Immédiatement après la Seconde Guerre mondiale, sous l’impulsion du Général de Gaulle et de Jean Monnet, le Gouvernement provisoire de la République française décida d’engager dans le système capitaliste français une politique économique à moyen terme désignée par le terme de « planification ». Le Plan, en tant qu’outil d’élaboration et de mise en œuvre de politiques industrielles, dirigea l’industrie française pour qu’elle puisse se développer et s’adapter aux différentes circonstances. Quatre plans furent successivement mis en œuvre dès la Libération jusqu’en 1965 par le Commissariat Général du Plan (CGP) sous la direction successive de trois commissaires généraux du Plan, à savoir Jean Monnet, Etienne Hirsch, Pierre Massé. Dans ce laps de temps furent lancés les plans suivants : Plan Pinay-Rueff, Plan intérimaire, Plan d’adaptation des charbonnages, Plan de stabilisation. Imbriquée de multiples manières à une « expansion industrielle », la planification française réussit à transformer la France rurale en une société industrielle et à faire passer l’industrie française de la situation fermée et protégée à la confrontation de la concurrence internationale. Elle joua aussi un rôle important dans le mode de rapport entre le secteur public et privé et en particulier, le fonctionnement des entreprises nationales. À plus long terme, c’était encore au Plan que revenait le mérite de tracer les lignes d’un harmonieux développement des régions françaises, surtout de l’aménagement du territoireImmediately after the Second World War, the Provisional Government of the French Republic, under the leadership of General de Gaulle and Jean Monnet, decided to engage in the French capitalist system a medium-term economic policy designated by the term "planning". The Plan, as a tool for the elaboration and implementation of industrial policies, directed French industry so that it could develop and adapt to different circumstances. Four Plans were successively implemented from the Liberation until 1965 by the General Planning Agency under the successive direction of three commissioners, namely Jean Monnet, Etienne Hirsch, Pierre Massé. Meanwhile, the Rueff-Pinay Stabilization Plan, Interim Plan, Plan d’adaptation des charbonnages, Giscard d’Estaing’s Stabilization Plan were launched. Interwoven in many ways with an "industrial expansion", French planning succeeded in transforming rural France into an industrial society and to shift French industry from the closed and protected situation to the confrontation of international competition. It also played an important role in the relationship between the public and private sectors and, in particular, the functioning of national enterprises. In the longer term, it was again in the Plan that the merit of drawing the lines of a harmonious development of the French regions, especially of the Spatial planning
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(9788021), Colin Cole. "Longitudinal train dynamics: Characteristics, modelling, simulation and neural network prediction for Central Queensland coal trains." Thesis, 1999. https://figshare.com/articles/thesis/Longitudinal_train_dynamics_Characteristics_modelling_simulation_and_neural_network_prediction_for_Central_Queensland_coal_trains/13465427.
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(9817391), Mitchell Mcclanachan. "Investigation of extreme wagon dynamics in Central Queensland coal trains." Thesis, 1999. https://figshare.com/articles/thesis/Investigation_of_extreme_wagon_dynamics_in_Central_Queensland_coal_trains/13457270.
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Gagliano, Monica. "The role of early life history traits on the survival of a coral reef fish." Thesis, 2006. https://researchonline.jcu.edu.au/1606/1/01front.pdf.
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Selective mortality within a population, based on the phenotype of individuals, is
the foundation of the theory of natural selection. Even small phenotypic differences among
individuals early in ontogeny can strongly affect survival and performance later in life.
Consequently, variation in early life history traits can have important repercussions on
population structure and dynamics. Yet, the role of phenotypic variation throughout the
ontogeny of tropical marine fishes remains largely unexplored. This study examined the
extent to which environmental and parental effects generate variation in the early life
history of a tropical marine fish (Pomacentrus amboinensis) and the consequences of such variation for survival in the wild.
Variation in early life history traits and survivorship during embryonic and larval
development of the coral reef damselfish, P. amboinensis was examined in relation to
water temperature. High rearing temperature (31ºC) strongly defined the relative number of embryos that successfully hatched and their post-hatching longevity. Embryonic mortality
was significantly higher in hotter rearing environments (31ºC) than in cooler ones (25 and
29ºC) and accounted for over 54% of mortality prior to hatching across all three rearing
temperatures. Under high temperature conditions, the probability of embryonic survival
was largely determined by the initial size of the yolk-sac with larger energy stores
reflecting enhanced rates of survival. Following hatching however, the survival advantages
afforded by yolk-sac size switched to egg size, a commonly cited indicator of fitness. Yet,
the benefits associated with egg size were heavily dependent on temperature. Overall, early
environmental conditions and intrinsic developmental schedules had a significant influence
on the outcome of selective mortality by producing substantial shifts in selective pressure
through the early ontogeny of this species.
The extent to which maternal condition at the time of gametogenesis affected the
relationships among early life history traits and survivorship during early development of
P. amboinensis was examined in a field study. Maternal condition was manipulated by
altering food availability, a key factor influencing maternal energy allocation to offspring.
Surprisingly, maternal condition had no effect on the number of offspring that successfully
completed the embryonic phase, nor did it influence the relative number of individuals that survived to a given time after hatching. Nonetheless, maternal nutritional state did
significantly affect offspring quality by causing substantial changes in individual egg
composition (i.e. yolk-sac and oil globule size) and thus, the energetic value of embryos
and hatchlings. By acquiring additional nutritional resources, supplemented mothers gained
a fitness advantage over fish feeding on natural levels of plankton. Most importantly,
however, they passed this advantage on to their offspring by provisioning their eggs with
greater energy reserves (yolk-sac and oil globule size) than non-supplemented fish. Among
offspring originating from supplemented mothers, those with larger yolk-sacs were more
likely to hatch successfully and survive for longer periods on these reserves after hatching.
Among offspring from non-supplemented mothers, yolk-sac size was either
inconsequential to offspring survival or, peculiarly, individuals with smaller yolk-sac sizes
were favoured. Mothers appear to influence the physiological capacity of their progeny and
in turn, the efficiency of individual offspring to utilise endogenous reserves. Interestingly
and contrary to theoretical predictions, there were no significant differences in egg size in
relation to maternal nutritional state, suggesting that provision of energy reserves, rather
than egg size, more closely reflected the maternal condition. Overall, the maternal
environment greatly influenced the relationship between offspring life history
characteristics and survival through energy-driven selective mechanisms.
To determine the relevance of these findings to patterns of future survival on the
reef, the early life history traits of P. amboinensis surviving on the reef were compared
with those of individuals from that same cohort at earlier times. Growth information stored
in the otoliths of individual fish revealed that both maternally-determined condition at
hatching and environmental conditions encountered early in the larval life had strong carryover
effects. Consistent with the findings presented above, wild individuals with larger
energy stores were found to survive through to settlement and beyond in the new reef
environment. Interestingly, results revealed that not all selective advantages established
during embryonic and larval phases were maintained later in life. The direction of selective pressures acting on growth rates changed significantly and repeatedly during the first few weeks of post-settlement life. These changes in phenotypic selection may mediate growth-mortality
trade-offs between the risk of predation and that of starvation during early
juvenile life.
To explore the mechanisms underlying early juvenile survival, growth histories
exhibited by individuals that survived the first 4 weeks on the reef were compared with
conspecifics outgrown experimentally to produce fast- and slow-growing fish. Nutritional
conditions experienced by new recruits during the first few weeks contributed noticeably to
observed patterns of juvenile survival. Results revealed considerable flexibility in the
growth rates of young fish. Specifically, the occurrence of periods of rapid (presumably
compensatory) growth may enhance post-settlement survival by attenuating the high risk of
size-selective mortality.
By exploring the causes and consequences of phenotypic variation in the life of a
tropical reef fish, this study unveiled the significant contribution past and present events
make in sculpting patterns of survival in the wild. In addition, it suggests that changes in
selective pressures that shape an individual’s life are a critically important mechanism
maintaining phenotypic (and hence genetic) variation within a population and, ultimately
regulating the dynamics of natural populations.
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Gagliano, Monica. "The role of early life history traits on the survival of a coral reef fish /." 2006. http://eprints.jcu.edu.au/1606.
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Pombo-Ayora, Lucía. "Functional diversity of herbivorous fishes in coral reefs in central Red Sea." Thesis, 2019. http://hdl.handle.net/10754/652886.
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In this research, I explore the changes in the functional diversity of herbivorous fishes in zones of coral reefs with different benthic composition: a zone dominated by corals, a zone dominated by algae and a transition zone in between the previous two. I choose to use functional traits which explain the feeding mechanics of this group of fish, as well their feeding rates and their previously established functional groups to understand how different assemblages of this fishes could affect their environment in different ways. I found clear differences in the functional diversity by calculating five indexes, functional dispersion (FDis), functional richness (FRic), functional divergence (FDiv), functional evenness (FEve) and functional specialization (FSpe). Each zone showed different species composition with different abundances; both parameters contribute to obtaining different values of the indexes. The coral-dominated zone showed the biggest multidimensional functional trait space (MFTS) with a value of FRic equals to 1 which means that its assemblage occupies 100% of the MFTS, while the transition zone assemblage occupied 83% and the algae-dominated zone occupied 16% of it. Thanks to this index I identified three functionally redundant species in the coral-dominated and the transition zones. The algae-dominated zone showed the lower FDis explained by the high abundance of grazers individuals. FDiv did not vary significantly between the three zones. FEve was higher in the algae-dominated zone; the index value decreased in the transition and coral-dominated zones, a similar tendency was shown by FSpe. Finally, to explore the importance of including functional diversity I made a comparison between the taxonomic and functional β-diversity. This research showed close relations of herbivorous fishes with their environment, but I could not establish if the benthic composition shapes the herbivorous fish assemblage or the other way around. This research can be a baseline to start working in functional diversity in the Red Sea coral reefs, can help to understand what to expect in the evaluation of reefs in different health state and to identify which herbivorous fish species or groups are more vulnerable and more important according to their function for coral reefs.
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Machaka, Chiedza Lucia Amanda. "Sustainability, trans-boundary protection of resources and mining : the coal of Africa case / Chiedza Lucia Amanda Machaka." Thesis, 2013. http://hdl.handle.net/10394/11825.
Full textAbstract:
This paper investigates the sustainability, trans-boundary protection of resources and mining with particular emphasis on the Coal of Africa case example. It explores the issues pertaining to the sustainability and trans-boundary protection of resources that were taken into account as part of the decision- making process with regard to mining by Coal of Africa in the Greater Mapungubwe area in South Africa. At the centre of the dispute was the mining of coal by Coal of Africa without obtaining a water use licence and other related legal authorisations. This was in violation of sector specific legislation such as the National Environmental Management Act 107 of 1998 and the National Environmental Management Biodiversity Act 10 of 2004, to name just a few. The importance of the Mapungubwe area is that it has a world heritage site and the mining is taking place adjacent to the world heritage site. Therefore, the mining activities by Coal of Africa should be conducted in a sustainable manner and should take into cognisance the four pillars of sustainability, namely, the environment, economic, social and cultural aspects. Furthermore, the mining activities must also take into account principles of sustainable development. The role of the government in regulating mining activities in areas such as Mapungubwe to ensure trans-boundary protection of resources including mineral resources for the current benefit of the communities and future use. In addition, regional instruments such as the African Charter on Human and Peoples' Rights, the Convention on the Conservation of Nature and Natural Resources, the Cultural Charter for Africa, SADC Treaty, SADC Protocol on Mining, provide for sustainable development. Also, the Revised SADC Protocol on Shared Watercourses places an obligation to parties to a shared watercourse to consult before embarking on any activity that may have detrimental environmental consequences. This paper established that to a certain degree economic issues were considered, as mining has the benefits of job creation. However, the failure by Coal of Africa to obtain the water use licence in the beginning could have been avoided. It is recommended that for such future activities an Intergovernmental Mining and Sustainability Forum be established to deal with such issues. In order for such a Forum to effectively function, there is need to amend 2013
MPRDA Amendment Bill.LLM (Environmental Law and Governance), North-West University, Potchefstroom Campus, 2014
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Feng, Shenghao. "China’s climate mitigation challenges and tools: essays on rebalancing, coal-use efficiency and emissions trading." Phd thesis, 2016. http://hdl.handle.net/1885/107169.
Full textAbstract:
The contribution of this thesis lies in its original application
of Computable General Equilibrium (CGE) modelling to some of the
most important climate change mitigation challenges China faces,
and some of the tools it could use to overcome them. The original
findings of the thesis are summarized below. Overall, they
underline the need for China to implement new methods, carefully
designed, to reduce emissions.
Chapter 2 focuses on the challenge of China’s economic
structure, and the tool of restructuring. A two-stage estimation
process is implemented within CHINAGEM, a dynamic general
equilibrium model of the Chinese economy, to study the potential
contribution of successful economic rebalancing – from
investment to consumption, and from industry to services – to
reducing the country’s carbon dioxide emissions. The results
show that economic rebalancing alone may lead to 17 per cent
reduction in the emissions intensity of GDP between 2012 and
2030. This estimate is higher than existing partial equilibrium
estimates in the literature, and points to the importance of
economic rebalancing from an environmental perspective.
Chapter 3 focuses on the challenge of China’s heavy level of
coal dependency, and the tool of improving the efficiency of the
use of coal in power generation. The analysis, again based on
CHINAGEM, suggests that this will be a less important contributor
to mitigation in the future than in the past. The pace and
importance of improvements in coal-fired power generation
efficiency is projected to halve mainly because, after the
progress already made, China’s current coal-fired power
generation efficiency is already close to the world’s best
practice, but also because slower growth in electricity demand
reduces the scope for expanding the generation fleet with new
world-class plant. The chapter also shows that, going forward,
switching to renewable energy and structural rebalancing will be
more important for achieving China’s emissions targets than
improving coal-fired power generation efficiency. However, fully
achieving China’s 2020 emissions intensity reduction target
will require a combination of all three.
Chapter 4 focuses on the challenge of China’s enormous regional
diversity, and the tool of emissions trading. This chapter uses a
multi-provincial static CGE model of the Chinese economy,
SinoTERM-CO2, to simulate the linking of two provinces through a
single emissions trading scheme. The simulations show that the
richer regions (typified by Guangdong) may benefit from linking
but the poorer regions (typified by Hubei) may lose. This is
because poorer provinces in China tend to be more emissions
intensive and therefore likely to face a carbon price rise upon
linking, the economy-wide costs of which may be only partially
offset by trading, if indeed trading is permitted. The economic
logic behind this is explained by improving on the stylized model
suggested by Adams and Parmenter (2013). China has not yet
decided whether provincial caps will be retained when a national
emissions trading scheme is introduced. This analysis suggests
that they should be retained, and made more generous for poorer
regions in order to ensure that linking is both welfare enhancing
and politically acceptable.
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Berumen, Michael Lee. "Influence of resource availability on lifehistory traits in coral-feeding butterflyfishes (Pisces: Chaetodontidae)." Thesis, 2006. https://researchonline.jcu.edu.au/1258/2/02whole.pdf.
Full textAbstract:
Given the highly stochastic nature of larval supply, coral reef fishes often settle in sub-optimal habitats with limited access to prey or other resources. Variation in the availability and quality of resources among different reef habitats is likely to have significant effects on the physiological condition and subsequent fitness of resident fishes, if not their absolute abundance. The first component of this study compared the abundance, feeding, and condition of two species of coral-feeding butterflyfishes (Chaetodon baronessa and C. lunulatus) across contrasting habitats with markedly different prey availability. Despite differences in prey availability, densities of C. baronessa and C. lunulatus were very similar between locations. However, there was significant spatial variation in their feeding and physiological condition. In front-reef locations, where coral prey was highly abundant, C. baronessa fed preferentially and almost exclusively on the coral Acropora hyacinthus. In contrast, in back-reef locations where coral prey was scarce and A. hyacinthus lacking, C. baronessa was much less selective and consumed a wider range of different coral prey. C. lunulatus was less selective than C. baronessa, but the diet of C. lunulatus also differed significantly between habitats. C. lunulatus consumed mostly A. hyacinthus in front-reef locations, but not in greater proportions than it was available. In back-reef locations, C. lunulatus preferentially consumed A. intermedia and Porites spp.. The physiological condition of both C. baronessa and C. lunulatus was much lower in back-reef locations compared to front-reef locations, which may reflect differences in the quantity and/or quality of prey available in different habitats. This work suggests that small scale (within-reef) differences in prey availability can have significant effects on the physiological condition and subsequent fitness of coral reef fishes. Having established that resource availability may have a significant influence on physiological condition of fishes, I wanted to explore variation in growth and longevity of butterflyfishes associated with variation in resource availability. However, little basic life-history information on chaetodontids exists, so it was first necessary to establish the best model to describe the growth of these fish. von Bertalanffy growth functions were fitted to size-at-age data for four species of chaetodontids from Lizard Island. Special emphasis on juveniles provided detailed information of the early growth period. All four species demonstrated rapid initial growth achieving an average of 92% of maximum theoretical size in the first 2 years of their life. Within the von Bertalanffy growth function, I used various constraints of the theoretical age at length zero (t0) in an analysis of both complete data sets and data sets using only adult fish. An unconstrained value of t0 resulted in the best-fit (maximum r2) curve when juveniles were included. When excluding juveniles, it was necessary to constrain t0 to an approximate settlement size to most closely represent the growth of the species.
Several species of corallivorous butterflyfishes are known to have specific feeding preferences. Foraging theory predicts that organisms should specialise on a given resource only if there are tangible fitness benefits, such as increased growth. To assess the influence of different prey types on juvenile growth for two species of highly selective coral-feeding butterflyfish, C. plebeius and C. trifascialis, individuals were held in tanks for one month on an exclusive diet of only one coral species. The feeding habits of both these species have been well documented in the field, and this study utilised existing data to quantify specific feeding preferences. Selection functions revealed that C. plebeius selectively consumes both Pocillopora damicornis and A. hyacinthus, while C. trifascialis selectively consumes A. hyacinthus. To test the fitness consequences of prey preferences, controlled feeding experiments were conducted in which individual butterflyfish were fed exclusively one of three different branching corals (A. hyacinthus, P. damicornis and Porites cylindrica) to compare growth on highly preferred coral species (e.g., A. hyacinthus and P. damicornis), versus coral prey that was never eaten in the field (P. cylindrica). Chaetodon trifascialis grew .053mm per day when feeding on A. hyacinthus, but actually decreased in total length when feeding on both P. damicornis and P. cylindrica. Chaetodon plebeius, meanwhile, grew at .051mm per day on P. damicornis, versus .038mm per day on A. hyacinthus and decreased in total length on P. cylindrica. This study shows that both C. trifascialis and C. plebeius selectively consume the coral prey that maximises juvenile growth and probably increases overall fitness. Variation in the early growth of these fish due to resource availability may explain patterns or anomalies in their large-scale population demographics.
Finally, to directly assess the influence of resource availability on life history traits, I quantified large-scale variation in some life history traits of chaetodontids across reefs with marked differences in the abundance of certain coral species. Samples of four species of chaetodontids (C. citrinellus, C. lunulatus, C. melannotus, and C. trifascialis) were collected at a northern Great Barrier Reef location (Lizard Island) and at a southern Great Barrier Reef location (One Tree Island). Population characteristics were assessed using a re-parameterised von Bertanlanffy growth function, allowing for better comparisons between populations. Although chaetodontids often had measurable variation between populations in growth rates, longevities, and mean maximum sizes, the variations were not consistent among species. These variations could not be consistently explained by preferred resource availability, temperature/latitude, or conspecific abundance. For, it was expected that growth rates would be higher where preferred resources are more abundant, but this was not found. It is likely that a combination of resources, latitude (seasonal temperature variation), and conspecific abundance (including behavioural interactions) ultimately determine the large-scale differences in the demographics of butterflyfish populations.
Overall, this study shows that resources play an important role in determining life history characteristics of butterflyfishes. In particular, access to specific resources during the juvenile stage may have significant implications for life-long fitness and will likely effect survivorship and reproductive output. Ultimately, variation in the availability of resources is also likely to directly impact local abundance of butterflyfishes, especially for highly specialised species. While this was not apparent in this study, it is likely that several confounding factors such as competition, predation, and local environmental conditions may obscure the importance of resources in determining population demographics in complex environments, such as coral reefs. Future studies must therefore attempt to isolate the effects of different factors using further experimentation and well-designed sampling programs.
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Lefèvre, Carine D. "Small cryptic fishes on coral reefs: ecological effects of extreme life history traits." Thesis, 2015. https://researchonline.jcu.edu.au/46686/1/46686-lefevre-2015-thesis.pdf.
Full textAbstract:
On Indo-Pacific coral reefs, small cryptic fishes are extremely diverse, and represent approximately 50 % of individuals in reef fish assemblages. Yet, many of these species have been little studied, particularly in the Indo-Pacific, and the influence of their often extreme life history traits on population dynamics and the broader implications for the composition and resilience of coral reef fish assemblages as a whole, remain unclear. While past research has shown that many of these small species have short and challenging generation times of 47–74 days, we are yet to determine how small cryptic fishes overcome these extreme life history characteristics to successfully persist on coral reefs. The overall goal of this thesis is, therefore, to provide a better understanding of the demographics of short-lived taxa on the Great Barrier Reef (GBR), Australia. More specifically, the present study considers the consequences of extreme life history characteristics, and especially short lifespans, with respect to their ability to recolonise after disturbance, and maintain populations throughout the year. The findings are then discussed in relation to the potential importance of these short-lived species for coral reef trophodynamics.
An understanding of the responses of fish assemblages to disturbance events is central to the on-going management of coral reefs habitats. Recovery of fish communities can occur by movement of fishes or recruitment processes. However, small cryptobenthic fishes have extremely limited post-settlement mobility, with home ranges often less than 2 m² and their responses to habitat disturbance has been seldom investigated. In order to understand the patterns of recovery of short-lived taxa, and in particular, to assess their ability to recover after a disturbance, the recolonisation of populations of small cryptic fishes was examined following experimental removal. After removing resident cryptobenthic reef fish assemblages from otherwise undisturbed coral rubble areas, a rapid recovery was observed. Within 8 weeks fish assemblages were similar to their pre-removal structure in terms of fish abundance, species diversity and species richness. However, species differed in the speed and nature of their return. The return of larger species (e.g. Parapercis cylindrica) was largely mediated by recolonisation through movement of adults, while smaller, less mobile, species (e.g. Eviota spp. and Enneapterygius spp.) relied primarily on recruitment from the plankton. Although patterns of settlement and recruitment are ultimately responsible for the replenishment of local populations, this study suggests that mobility may play a strong role in restoring fish assemblages in the short-term.
The majority of coral reef goby species are short-lived, with a large proportion of small taxa, such as Eviota, living less than 100 days. Despite these exceptionally short lifespans presenting the demographic challenges of very little time to mature and reproduce, these sub-annual taxa persist and are highly abundant on reefs. To understand the role and consequences of extreme life history in shaping coral reef fish populations, the structure of small reef fish populations was quantitatively documented over a 26 month study period (> 14 short-lived fish generations). Fish density varied over time, but species richness did not change significantly. These patterns were driven by the differential trends in density shown among species within the fish community. Most species with lifespans > 1 year, such as pomacentrids, exhibited a peak in recruitment during the Austral summer. In contrast, despite exceptionally short lifespans, species of Eviota showed consistent densities of both adults and newly settled recruits over the 26 months. These different temporal patterns among taxa drove changes in the overall fish community composition among seasons but there were few apparent differences in the composition of the Eviota populations over time. These results provide evidence of on-going recruitment of these small cryptic fishes, which appears to compensate for an exceptionally short life span on the reef. This study suggests that gobiid populations are able to overcome demographic limitations, and by maintaining reproduction, larval survival and recruitment throughout the year, they may avoid population bottlenecks. These findings also underline the potential trophodynamic importance of these small species; because of extremely high turn-over, and year-round recruitment, Eviota species and other short-lived fishes may be particularly valuable contributors to the flow of energy on coral reefs, underpinning the year-round trophic structure.
In examining previously unstudied aspects of the demography of small cryptic fishes on the GBR, this thesis presents evidence of a rapid recruitment of small cryptic fishes to reefs after a disturbance event. Furthermore, this thesis highlights temporal stability (over 26 months) in the size structure of short-lived taxa, specifically for the gobiid genus Eviota. These findings have significant implications for the proposal that small cryptic fishes play an important, yet often forgotten, role in coral reef energetics. Sub-annual taxa provide a constant food resource and supply of reproductive energy to coral reefs trophodynamics throughout the year via predatory pathways. Although not as conspicuous as other coral reef fishes, the unique life-history of short-lived fishes and their proposed important contribution to coral reef trophodynamics suggests these taxa warrant further studies. Two important future research directions are: teasing apart the relative effects of larval supply and post-settlement mortality on abundance of recruits, and assessing the generality of these results for other short-lived taxa. Coral reef ecosystems operate over a broad range of temporal and spatial scales. The exceptional life history features and resulting population dynamics of short-lived species form an integral part of the diversity and dynamics of reef systems and thus are an important research focus.