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Paget, Caroline Mary. "Environmental systems biology of temperature adaptation in yeast." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/environmental-systems-biology-of-temperature-adaptation-in-yeast(597a675a-aaf1-43bf-bd6c-143aeefc98be).html.
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Temperature is arguably the leading factor that drives adaptation of organisms and ecosystems. Remarkably, many sister species share the same habitat because of their different temporal or micro-spatial thermal adaptation. In this PhD, the underlying molecular mechanisms of the adaptation of closely related species to different temperatures are sought. A thermodynamic analysis was applied to a genome-scale metabolic model of S. cerevisiae at warm and cold temperatures to identify thermo-dependent reactions. Gene Ontology (GO) analysis of predicted cold-dependent reactions found that redox reactions were significantly enriched. A complementary large scale experimental approach was taken by competing 6,000 mutant strains at 16°C to identify genes that were responsible for the fitness at low temperatures. The experiment was carried out in three different nutritional conditions to test the plasticity of temperature dependency. A list of strains whose copy number significantly increased or decreased in all media conditions was constructed and analysed using Gene Ontology. Vitamin biosynthesis, lipid/fatty acid processes and oxido-reduction reactions were all found to be significantly affected by the cold condition. Combining the data from the two studies a list of candidate genes affected by temperature changes were generated. In particular, two genes, GUT2 and ADH3, were identified as potential cold favouring genes and studied in more detailed. Mutants for these two genes were created in a pair of natural sympatric cryotolerant and thermotolerant Saccharomyces yeasts, namely S. kudriavzevii CA111 and S. cerevisiae 96.2, representing an excellent ecological experimental model for differential temperature adaption. My results showed that when compared to the parental strains, both mutants showed lower fitness at cold temperatures as predicted, and in S. kudriavzevii CA111 these mutations significantly improve growth at warm temperatures. Results from all aspects of this work indicate that oxidation reduction reactions are important for cold acclimation. It is known that heat stress causes redox imbalances which are compensated by increasing glycerol production or cytosolic acetaldehyde. Since GUT2 and ADH3 are involved in these processes, mutations in these genes may not be able to compensate for temperature changes. My data also shows that vitamins may also play an important role in cold acclimation which would be an interesting line of investigation for future work. Overall this PhD thesis has incorporated in silico and in vivo work to identify potential processes and genes involved in the temperature adaptation of sister Saccharomyces yeast species. The approach and results provided in this study support the use of a systems biology framework to studying species adaptation to environmental changes, and show that such models can yield testable predictions that may lead to new biological discoveries.
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Modi, Sheetal. "Systems biology approaches to mechanisms of bacterial stress adaptation." Thesis, Boston University, 2013. https://hdl.handle.net/2144/12822.
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Thesis (Ph.D.)--Boston University
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.Bacteria exhibit highly adaptive behaviors in the face of stress, which poses significant challenges for the eradication of infectious disease as well as for the success of biotechnology efforts to harness microbes as production chassis. Systems biology, which studies interactions between the components of a biological system, presents a framework for using computational strategies to further understand the complexity of bacterial physiology. In this work we use systems biology to elucidate the comprising mechanisms of two facets of bacterial stress adaptation. In the first part of this work, we develop a method to facilitate the characterization of small non-coding RNAs, which are involved in mediating adaptive physiological responses to changing environmental conditions. We implement a network biology approach based on expression profiling to predict the functional and regulatory interactions for small RNAs in Escherichia coli. We experimentally validate functional predictions for three small RNAs in our inferred network and demonstrate that a specific small RNA interacts with a transcription factor in a mutually inhibitory relationship, demonstrating a new cellular regulatory motif in bacteria. In the second part of this work, we investigate the role of phages, viruses which infect bacteria, in the adaptation of the microbiome to stressful environments. Disruption of intestinal homeostasis has been studied at the level of microbial composition; however, investigation of the gut ecosystem has evinced a myriad of resident phages, and it remains unclear how perturbation of the gut environment affects these viral symbionts. Our analysis demonstrates that antibiotic treatment, a prevalent stress for commensal microbes, enriches the phage metagenome for stress-specific and niche-specific functions. We also show that antibiotic treatment expands the interactions between phage and bacterial species, leading to a more highly connected phage-bacterial network for gene exchange. Our work indicates that the adaptive capacity of the phageome may represent a community-based mechanism for protecting the gut microfiora and preserving its functional robustness during antibiotic stress. Systems biology approaches toward understanding bacterial behavior within an environmental and evolutionary context may improve our relationships with microbes, which will be critical in an era where the potential of these organisms remains both promising and incipient.
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Cuthbertson, Charles. "Limits to the rate of adaptation." Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.670176.
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Leiby, Nicholas. "Adaptation and Specialization in the Evolution of Bacterial Metabolism." Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11364.
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Specialization is a balance of evolutionary adaptation and its accompanying costs. Here we focus on the Lenski Long-Term Evolution Experiment, which has maintained cultures of Escherichia coli in the same, defined seasonal environment for 50,000 generations. This dissertation explores the extent and means by which metabolic specialization occurs over an extended period in the same environment.
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Haller, Benjamin. "The role of heterogeneity in adaptation and speciation." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=119621.
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Heterogeneity is at the heart of Darwin's "mystery of mysteries", the origin of species, as both cause and consequence. Heterogeneity within and between environments can lead to genetic and phenotypic heterogeneity within and between populations. This can lead, in turn, to heterogeneity in patterns of mating and reproduction, often called "non-random" or "assortative" mating. Ultimately, this process can lead to speciation – in essence, the development of stable, persistent heterogeneity at the phylogenetic level. A "chain of causation" thus exists along which heterogeneity propagates, from differences among environments to differences among individuals, populations, and ultimately species (Chapter 1). In this thesis I present three models, focused upon three different links in this chain of causation, to study the causes and consequences of heterogeneity in the evolutionary process. The first model (Chapter 2) examines the earliest link in this chain of causation: the process of adaptation within a single population in an environment containing a single resource type. This model demonstrates that stochasticity generates genetic and phenotypic heterogeneity even in a simple environment such as this. Furthermore, that heterogeneity can be maintained and promoted by simple ecological processes such as intraspecific competition that decrease the fitness of common phenotypes. The results of this model help to resolve a long-standing puzzle in evolutionary biology, the "paradox of stasis", by providing a mechanistic explanation for the pattern of selection observed in natural populations. The second model (Chapter 3) explores an intermediate link in the chain of causation: the effects of spatial environmental heterogeneity on divergent adaptation and biodiversification. This model incorporates complex, realistic patterns of environmental heterogeneity not previously studied, and demonstrates a novel "refugium effect" through which such complex environmental heterogeneity can promote biodiversification. In essence, "refugia" generated by patchy environmental heterogeneity can provide stepping-stones through which adaptation to hostile environments can proceed incrementally. Other effects of complex heterogeneity are also demonstrated, and these results are connected to empirical speciation research. The last model presented (Chapter 4) investigates the final links in the chain of causation: the development of reproductive isolation and progress toward speciation. It has previously been hypothesized that a floral syndrome called heterostyly might cause partial reproductive isolation among populations of flowering plants, promoting speciation. This chapter's model is used to test that hypothesis. Results support this hypothesis in some scenarios, because divergent ecological selection on traits involved in heterostyly can pleiotropically produce reproductive isolation. However, this model does not always lead to reproductive isolation. An alternative outcome in which heterostyly leads to asymmetric gene flow points toward a novel mechanism underlying the progression from heterostyly to dioecy, offering a possible resolution of an enduring mystery in plant mating system research. In Chapter 5, the chain of causation discussed above is visualized with a flowchart that depicts the mechanisms that generate and promote heterogeneity at different stages in the process of adaptation and speciation. This flowchart illustrates the unifying idea at the heart of this thesis: that the process of biodiversification involves the propagation of heterogeneity from the environment to individuals, populations, and ultimately new species. The models presented in the preceding chapters are shown at their respective positions along the chain of causation, illustrating which parts of this conceptual framework have been explored in this thesis.L'hétérogénéité est au coeur du «mystère des mystères» de Darwin : l'origine des espèces, comme cause et comme conséquence. L'hétérogénéité à l'intérieur et entre les environnements peut produire de l'hétérogénéité génétique et phénotypique dans une population et entre des populations. Ceci peut produire, à son tour, de l'hétérogénéité dans les patrons d'accouplement et de reproduction, souvent appelé «croisement assortatif». Ultimement, ce processus peut mener à la spéciation – en fait, le développement d'une hétérogénéité stable et persistante au niveau phylogénique. Une «chaîne de causalité» existe au cours duquel l'hétérogénéité se propage, de différences environmentales à des différences entre les individus, les populations, et ultimement aux espèces (premier chapitre). Dans cette thèse, je présente trois modèles, qui portent chacun sur un lien différent de la chaîne de causalité pour étudier les causes et les conséquences de l'hétérogénéité dans les processus évolutifs. Le premier modèle (deuxième chapitre) examine le premier lien de la chaîne de causalité : le processus d'adaptation avec une seule population et un seul environnement ne contenant qu'un seul type de ressource. Ce modèle montre que la stochasticité génère de l'hétérogénéité génétique et phénotypique, même dans un environnement simple. En plus, l'hétérogénéité peut être maintenue et amplifiée par des processus écologiques simples comme la compétition intra-spécifique qui réduit la valeur d'adaptation des phénotypes communs. Ces résultats aident à résoudre une vieille question en biologie de l'évolution, «le paradoxe de la stase», en fournissant une explication pour les mécanismes de sélection que l'on observe dans la nature. Le deuxième modèle (troisième chapitre) explore un lien intermédiaire dans la chaîne de causalité : les effets de l'hétérogénéité environnementale sur l'adaptation divergente et les processus de biodiversification. Ce modèle intègre des patrons complexes d'hétérogénéité qui n'ont pas été étudiés précédemment et montre un nouvel «effet refuge» qui amplifie les processus de biodiversification dans des environnements hétérogènes complexes. En effet, les «refuges» générés par la fragmentation spatiale peuvent devenir des tremplins par lesquels l'adaptation aux environnements hostiles peut procéder séquentiellement. D'autres effets de l'hétérogénéité complexe sont aussi montrés et ces résultats sont liés à la recherche empirique sur la spéciation. Le dernier modèle (quatrième chapitre) étudie le dernier lien de la chaîne de causalité : le développement de l'isolation reproductive et l'évolution vers la spéciation. Il a été suggéré qu'un syndrome floral appelé hétérostylie peut causer une isolation reproductive partielle entre les fleurs, entraînant la spéciation. Le modèle de ce chapitre est utilisé pour tester cette hypothèse. Les résultats appuient cette hypothèse dans certains scénarios, car la sélection écologique divergente sur les traits impliqués dans l'hétérostylie peuvent produire de l'isolement reproductif à cause d'effects pléiotropes. Cependant, ce modèle ne génère pas toujours de l'isolement reproductif. Un autre résultat possible du modèle est que l'hétérostylie produit un flux génique asymmétrique. Ce résultat pointe vers un nouveau mécanisme sous-jacent à la progression de l'hétérostylie vers la diécie, offrant la possibilité de résoudre un mystère persistant à propos du système reproductif des plantes. Dans le cinquième chapitre, la chaîne de causalité est représentée par un organigramme qui présente les mécanismes qui génèrent et amplifient l'hétérogénéité à différents stades du processus d'adaptation et de spéciation. Les modèles présentés dans les chapitres précédents sont positionnés sur la chaîne de causalité, illustrant quelles sont les parties de cet organigramme qui ont été explorées dans cette thèse.
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Kane, Nolan C. "The genetic basis of adaptation and speciation in wild sunflowers." [Bloomington, Ind.] : Indiana University, 2007. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3290775.
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Thesis (Ph.D.)--Indiana University, Dept. of Biology, 2007.Title from dissertation home page (viewed May 28, 2008). Source: Dissertation Abstracts International, Volume: 68-11, Section: B, page: 7090. Adviser: Loren H. Rieseberg.
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Friedman, Jonathan Ph D. Massachusetts Institute of Technology. "Microbial adaptation, differentiation, and community structure." Thesis, Massachusetts Institute of Technology, 2013. http://hdl.handle.net/1721.1/81751.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Computational and Systems Biology Program, 2013.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (p. 112-119).
Microbes play a central role in diverse processes ranging from global elemental cycles to human digestion. Understanding these complex processes requires a rm under- standing of the interplay between microbes and their environment. In this thesis, we utilize sequencing data to study how individual species adapt to different niches, and how species assemble to form communities. First, we study the potential temperature and salinity range of 16 marine Vibrio strains. We nd that salinity tolerance is at odds with the strains' natural habitats, and provide evidence that this incongruence may be explained by a molecular coupling between salinity and temperature tolerance. Next, we investigate the genetic basis of bacterial ecological differentiation by analyzing the genomes of two closely related, yet ecologically distinct populations of Vibrio splendidus. We nd that most loci recombine freely across habitats, and that ecological differentiation is likely driven by a small number of habitat-specic alle-les. We further present a model for bacterial sympatric speciation. Our simulations demonstrate that a small number of adaptive loci facilitates speciation, due to the op- posing roles horizontal gene transfer (HGT) plays throughout the speciation process: HGT initially promotes speciation by bringing together multiple adaptive alleles, but later hinders it by mixing alleles across habitats. Finally, we introduce two tools for analyzing genomic survey data: SparCC, which infers correlations between taxa from relative abundance data; and StrainFinder, which extracts strain-level information from metagenomic data. Employing these tools, we infer a rich ecological network connecting hundreds of interacting species across 18 sites on the human body, and show that 16S-defined groups are rarely composed of a single dominant strain.
by Jonathan Friedman.
Ph.D.
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Kettler, Gregory C. (Gregory Carl). "Genetic diversity and its consequences for light adaptation in Prochlorococcus." Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/68428.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2011.Cataloged from PDF version of thesis.
Includes bibliographical references (p. 215-223).
When different cells thrive across diverse environments, their genetic differences can reveal what genes are essential to survival in a particular environment. Prochlorococcus, a cyanobacterium that dominates the open ocean, offers an opportunity to explore such differences. Its diversity is examined here, beginning with an overview and comparison of 12 fully sequenced Prochlorococcus genomes. The Prochlorococcus core genome, that set of genes shared by all cultured Prochlorococcus, appears to be well defined by the set shared by these isolates. The flexible genome, that set of genes found in some isolates but not shared by all Prochlorococcus, was found to be much larger and open-ended. Most laterally-acquired genes were found to be located in highly variable islands such as those described in previous studies of Prochlorococcus. Those lateral gene transfer events can also be placed on the Prochlorococcus phylogenetic tree: each Prochlorococcus isolate possesses a significant number of genes that even its closest sequenced cousin does not. A particular gene family may define a Prochlorococcus ecotype if those genes are possessed by all members of that ecotype, and if their presence gives that ecotype a selective advantage in some circumstance, thus contributing to the determination of its niche. One gene family is conspicuous for appearing in many copies per genome in one Prochlorococcus clade, referred to as eNATL. The sequenced strains belonging to this clade each possess over 40 copies of genes encoding high light inducible proteins (HLIPs), compared to only 9-24 in the other Prochlorococcus genomes. Other studies suggest these genes may be involved in resistance to sudden increases in light intensity, among other stresses. This becomes especially interesting as recent field studies also found that eNATL cells may survive changes in light intensity more easily than other lowlight adapted Prochlorococcus. Here, the effects of light shocks on an eNATL strain and on other Prochlorococcus strains are studied. eNATL cultures do recover from light shock conditions that are lethal to other low light-adapted Prochlorococcus. Measurements of bulk in vivo chlorophyll fluorescence, fluorescence per cell, and variable fluorescence, along with preliminary gene expression data, suggest that the early, rapid response of high light-adapted cells and of eNATL cells distinguish them from other low light-adapted cells, possibly explaining their subsequent survival. The possible role of HLIPs in this response is discussed. The discussion of HLIPs and eNATL is based on the complete sequences of only two eNATL genomes, both sampled from the same part of the ocean at the same time. That dataset is expanded by the inclusion of Global Ocean Survey environmental shotgun reads, from which are identified several thousand HLIP genes. Past work has shown that HLIPs are divided into two distinct clades: the core, freshwater cyanobacteria-like HLIPs and the flexible, phage-like, island-bound copies. That distinction is examined in the metagenomic data, demonstrating that the separate types are consistently found in distinct chromosomal neighborhoods.
(cont.) The evolution of HLIPs is also explored by the analysis of large-insert environmental clones containing islands from a variety of eNATL cells. Here, not even all island-bound, HLIP-encoding genes appear to be alike, as only a subset are consistently found in the same locations across the whole eNATL clade. Ecotype-defining genes are those genes, shared by all members of an ecotype, that provide an ecologically significant advantage, thus helping to define the ecotype's niche. It can be expected that, as environmental data accumulates (including additional measurements of Prochlorococcus abundance and newly sequenced genomes from uncultured cells), additional such genes can be identified. This work should represent a model for searching for and examining such genes. Hopefully, future experiments will be able to test the physiological significance of candidate ecotype-defining genes, while feeding back to the environmental data to verify their importance in the open ocean.
by Gregory C. Kettler.
Ph.D.
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Crispo, Erika. "Interplay among phenotypic plasticity, local adaptation, and gene flow." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:8881/R/?func=dbin-jump-full&object_id=92201.
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Smith, Joel Haviland. "Leveraging Haplotype-Based Inference to Describe Adaptation and Speciation." Thesis, The University of Chicago, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10788183.
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Forward progress in empirical population genetics is closely tied to the development of theory which can accomodate and keep pace with the production of genetic data. In recent years, the ability to survey genetic variation at increasingly greater resolution, across the genomes of a variety of species, has prompted new approaches to use this data for population genetic inference. While many models have historically relied on assuming independence among genetic variants in a sample of chromosomes, there are now a variety of methods which can use the non-independence among variants as a source of information. In particular, the unique combination and co-inheritance of variants on a chromosome can be used to define "haplotypes" of linked genetic variation associated with specific populations, individuals, or variants from which they are descended. The work presented here is a contribution to this class of population genetic models which describes: (1) a method to estimate the timing of adaptation for a beneficial allele, including several applications to recent human evolution, (2) an application of the same method to infer the timing of introgression for coat color alleles in North American wolves and high-altitude adaptation in Tibetans, (3) a model to infer the action of purifying selection against genetic incompatibilities in a hybrid zone, and (4) a reanalysis of genomic data from Heliconius butterflies which confirms the role of hybridization in transfering mimicry phenotypes between species.
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Otchy, Timothy Matthew. "Neural Circuit Mechanisms Underlying Skill Learning, Adaptation, and Maintenance." Thesis, Harvard University, 2016. http://nrs.harvard.edu/urn-3:HUL.InstRepos:33493332.
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Part I
Mastering a motor skill, such as a playing the guitar, requires precisely controlling both spatial and temporal aspects of motor output – that is, what movements to perform when. While it is generally assumed that these aspects are acquired through the same learning processes and in the same circuits, there is also evidence that the brain can control them independently. But if that’s true, how is such modularity in motor control and learning implemented in neural circuitry? To probe this question, we developed a paradigm that ‘trains’ songbirds to change either spatial or temporal aspects of their vocal output and showed that learning in the two domains is implemented in distinct neural circuits. This dissociation extended to premotor nucleus HVC, which we showed encodes changes to temporal but not spectral song structure. Such functional modularity, i.e. different circuits learning and implementing different aspects of motor control, could serve to overcome the limitations of reinforcement learning algorithms in dealing with large task domains.
Having identified key mechanisms by which an acquired motor skill can be modified, we then turned to investigate the mechanisms underlying the formation of circuits during the initial acquisition of a motor skill. The neural circuits controlling learned behaviors develop under genetic constraints and in response to environmental influences. Recent studies have provided an unprecedentedly detailed view of the circuit- and synaptic-level changes that accompany complex motor learning, but have left unexplored how environmental factors influence the formation of the neural circuits underlying motor skills. To address this, we investigated how the lack of a behavioral model affects normal motor circuit development in songbirds, a question with relevance for developmental disorders associated with deficits in imitation. We found that the primary difference in circuit formation was delayed and decreased pruning at a synapse that is a principal locus of learning. We show that this difference in synapse refinement is consistent with it being the principal mechanism driving reduced temporal precision of song and the underlying motor program. Intriguingly, our finding of impaired synapse formation mirrors what has been suggested in previous studies of autism.
Part II
Assigning function to brain areas is a principal aim of neuroscience that is often pursued by rapidly and reversibly manipulating neural activity in behaving animals. An important assumption underlying this experimental regime is that consequent behavioral changes reflect the function of the targeted circuits. In Part II of this dissertation, we demonstrate that this assumption is problematic in that it fails to account for indirect effects on the independent functions of circuits downstream of the targeted area. Transient inactivation of sensorimotor area Nif in songbirds and motor cortex in rats severely disrupts courtship songs and task-specific movement patterns – learned skills that recover spontaneously after permanent lesions of the same areas. How can a brain area be both essential for behavior execution (as assayed by the now preferred method, transient perturbation) and not (as assayed by the traditional method, lesions)? We resolve this seeming paradox in songbirds, showing that sudden silencing of Nif disrupts song and neural dynamics within HVC, a downstream song control nucleus. In parallel with song recovery, the off-target effects resolved within days of lesion, a recovery consistent with homeostatic regulation of neural activity within HVC. These finding have broad implications for how neural circuit manipulations are interpreted and for understanding the mechanisms supporting functional recovery following brain injury.Medical Sciences
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Brauer, Matthew Jonas. "Geometry and genetics of microbial adaptation /." Full text (PDF) from UMI/Dissertation Abstracts International, 2000. http://wwwlib.umi.com/cr/utexas/fullcit?p3004221.
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Lieberman, Tami Danielle. "Genomic insights into bacterial adaptation during infection." Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11312.
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Bacteria evolve during the colonization of human hosts, yet little is known about the selective pressures and evolutionary forces that shape this evolution. Illumination of these processes may inspire new therapeutic directions for combating bacterial infections and promoting healthy bacteria-host interactions. The advent of high-throughput sequencing has enabled the identification of mutations that occur within the human host, and various tools from computational and evolutionary biology can aid in creating biological understanding from these mutations. Chapter 1 describes recent progress in understanding within-patient bacterial adaption, focusing on insights made from genomic studies.
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Kingsley, Evan Prentice. "Adaptation in the forest deer mouse: evolution, genetics, and development." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:17467192.
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Variation in the shape, size, and number of segments along the vertebral column underlies a vast amount of vertebrate diversity. Although the molecular pathways controlling vertebrate segmentation during normal development are well understood, the genetic and developmental underpinnings responsible for the tremendous variation in size and number of vertebrae are relatively unexplored. The main goal of this dissertation is to explore the genetic and developmental mechanisms influencing naturally occurring variation in the vertebral column. To this end, I focus on intraspecific skeletal variation, with an emphasis on tail length, in the deer mouse, Peromyscus maniculatus. In Chapter 1, I employ a phylogeographic framework to show that longer tails have evolved independently in different populations of forest-dwelling mice. Closer investigation of the underlying morphology shows that long-tailed mice have both (1) a greater number of tail vertebrae and (2) individually longer vertebrae, compared to ancestral short-tailed mice. Chapter 2 explores the genetic basis of tail length variation. I use quantitative trait locus mapping to uncover six loci that influence differences in total tail length (3 associated with vertebral length and 3 with vertebrae number). Finally, in Chapter 3 I combine comparative data from quantitative measurements of tissue dynamics during somitogenesis in fixed embryos and ex vivo explant culture to show that embryos of forest mice make more segments because they produce more presomitic mesoderm, and not because of any significant difference in the timing of somitogenesis. Together, this work integrates phylogeographic, genetic, and developmental studies to pinpoint the ways that natural selection modifies development to produce the repeated evolution of an evolutionarily important trait, and suggests that there are a limited number of ways that long tails can evolve.Biology, Organismic and Evolutionary
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Schoenberger, Shirley Ann 1943. "High-temperature adaptation of three Sonoran Desert Bacillus species: Ecological and evolutionary prospects." Thesis, The University of Arizona, 1996. http://hdl.handle.net/10150/278546.
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Growth at high temperature of wild isolates of three species of Bacillus was analyzed to assess potential responses to global warming. Experimental populations were grown at temperatures from 32° to 60° C. The higher temperatures include ones near and above maxima previously reported for laboratory strains. Summer soil temperatures, three centimeters below the ground surface, were recorded at the same site from which the wild isolates came, show that temperatures in the Sonoran Desert often reach 50° to 60° C. The growth data show that the desert isolates of B. subtilis and B. licheniformis have thermal maxima close to those reported by Gordon et al. (1973), while B. megaterium grew well at 2-3°C above the reported maximum. Global Climate Models predict a rise of 1° to 4.5°C over the next 60-100 years. Such a rise could shorten periods of active growth and nutrient cycling by Bacillus decomposers.
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Reyes, Nikolle Susanne. "Marine bacterial isolates utilize unique mercury resistance mechanisms." Thesis, Georgia Institute of Technology, 1999. http://hdl.handle.net/1853/25416.
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Sullivan, Christopher James. "The role of fibroblast growth factor-2 (FGF2) in vascular remodeling and adaptation." Diss., The University of Arizona, 2002. http://hdl.handle.net/10150/284317.
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The goal of this dissertation was to test the hypothesis that fibroblast growth factor-2 (FGF2) is required during diseased-related vascular growth and remodeling in the adult organism. Given previous research, it is generally assumed that FGF2 is an important regulator of vessel growth during various pathophysiological processes (e.g. tissue ischemia, vessel injury, and flow-dependent remodeling). However, such studies only indirectly implicate FGF2 in vascular adaptation and remodeling. In contrast, experiments using mice with a targeted disruption of the Fgf2 gene have allowed direct determination of the biological roles of endogenous FGF2. Thus, experimental models of flow-dependent remodeling and ischemic revascularization were used to compare the responses of Fgf2⁻/⁻ and Fgf2⁺/⁺ mice to directly identify the function of FGF2 during vascular adaptation in the adult animal. Surprisingly, the lack of FGF2 did not appear to affect vascular growth in these models. First, using a novel model of flow-dependent remodeling, Fgf2⁻/⁻ mice had equivalent carotid artery adaptation in response to both high-flow and low-flow was as wildtype counterparts. Second, angiogenesis and arteriogenesis were not different between the ischemic limbs Fgf2⁺/⁺ and Fgf2⁻/⁻ mice, demonstrating that FGF2 is not required for vascular adaptation in response to ischemia. However, these experiments led to the observation that reactive hyperemia was impaired in ischemic limb of Fgf2⁻/⁻ mice. These results indicate that vessel responsiveness is altered in the collateral circulation of the ischemic Fgf2⁻/⁻ limb. This possible identification of FGF2 as a "functional" factor in the collateral circulation suggests a novel, non-mitogenic role for endogenous growth factors. Finally, Fgf2⁻/⁻ mice had altered gene expression in the ischemic limb as evaluated using cDNA microarrays. The significance of differential gene expression in the absence of FGF2 is unknown. It is unclear whether such changes in gene expression are related to the FGF2 hyperemia phenotype or whether they are related to an unknown phenotype present in the ischemic limb of Fgf2⁻/⁻ mice. Overall, this dissertation provides new evidence that endogenous FGF2 has important actions in the remodeling vasculature during ischemic revascularization. Specifically, endogenous FGF2 appears to modulate vascular reactivity of the collateral circulation of the hindlimb.
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Blazek, Alisa D. "Integrative Approach to Understanding the Multimodal Effects of Exercise Adaptation." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1439546709.
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David, Maude. "Bacterial adaptation to the chlorinated compounds." Thesis, Ecully, Ecole centrale de Lyon, 2009. http://www.theses.fr/2009ECDL0026/document.
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Le travail présenté dans cette thèse porte sur l'adaptation bactérienne aux molécules chlorées, tant au niveau des ressources génétiques nécessaires à la mise en place des gênes de dégradation qu'au niveau de la structure de la communauté microbienne observée durant la dégradation de ces composés. La première partie de ce document est une bibliographie qui se focalise sur les mécanismes développés par les bactéries pour répondre aux stress environnementaux, et sur les possibles origines des gènes responsables des premières étapes de dégradation des composés chlorés : les dehalogenases (qui réalisent les étapes de déchloration). Le deuxième chapitre de cette thèse porte sur des essais expérimentaux de remodelage génétique, dans le but de valider les hypothèses présentées lors de la bibliographie quant aux mécanismes qui ont pu conduire à la génération de nouveaux gênes de dégradation. Ces remodelages in vitro et in vivo ont été effectués en utilisant les gènes linB et dhaA. Le chapitre suivant examine la structure de la communauté bactérienne lors de la dégradation réductive du tetrachloroéthylène (PCE). Pour cette étude, des outils de biologie moléculaire, plus spécifiquement des puces phylogénétiques, ont été utilisés pour étudier la structure de la communauté microbienne depuis l'introduction du polluant jusqu'à sa dégradation. Afin d'élucider les fonctions métaboliques qui peuvent être corrélées avec la dégradation du PCE, les résultats des puces phylogénétiques ont été comparés avec un suivi chimique des métabolites de dégradation de ce composé, lors d'une étude en microcosmes. L'objectif du dernier chapitre de la thèse a été de relier la structure de la communauté microbienne avec la cinétique de dégradation des composés chimiques étudiés. Pour cela, une étude globale comportant à la fois un suivi chimique des métabolites de dégradation, une quantification des gènes de dégradation impliqués dans la déchloration réductive du PCE ainsi que l'étude de la structure de la communauté microbienne ont été mis en place. Cette étude a permis de corréler les conditions environnementales nécessaires à la déchloration et la communauté microbienne associée avec l'expression des déhalogénases quantifiées. En résumé, cette thèse explore à la fois les mécanismes mis en place par les bactéries pour dégrader ces composés polluants et la structure de la communauté bactérienne durant la dégradation de ce polluant. Comprendre ces deux étapes dans l'adaptation bactérienne peut contribuer à améliorer l'utilisation des capacités bactériennes utilisées en bioremédiationThis thesis concerns the bacterial adaptation to the chlorinated compounds at both the gene level and the microbial community level. The bibliography will focus on the adaptation mechanisms developed by bacteria to respond to environmental stresses and on the possible origins of the genes responsible for the first steps of chlorinated compound degradation, those encoding for the dehalogenases, which perform the dechlorination or chlorine removal step. The second chapter of the thesis consists of an experimental exploration of the gene shuffling hypothesis presented in the bibliography, using linB and dhaA genes. The next chapter examines the bacterial community structure in relation to compound degradation using the reductive dechlorination of tetrachloroethylene. For this study, molecular biology tools, specifically phylochip microarrays were used to examine bacterial community structure from the moment of pollutant introduction to the environment and during bioremediation. In order to elucidate the metabolic functions, which correlate the PCE degradation, phylogenetic results were compared with functional genes in the microcosms studied. The last chapter of this global study on chlorinated compound degradation genes was to link the microbial community structure kinetics with the chemical degradation kinetics. In order to evaluate the molecular biological parameters of the microbial community, all the genes known to be involved in the entire pathway of PCE reductive dechlorination were quantified. This global study, incorporating chemical monitoring, dehalogenase quantification and microbial community structure, produced correlations between the environmental conditions necessary for dechlorination and the microbial community associated with dehalogenase expression. In summary, both the mechanisms implemented by the bacteria to degrade this compound pollutant and the bacterial community structure during the pollutant degradation were addressed. Improving the understanding of these two steps in bacterial adaptation can contribute to the understanding of bacterial and environmental cleanup capabilities
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Heemstra, Lydia A. "Melatonin, cortisol, and perceived adaptation after working one night shift." Kent State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=kent1461153204.
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Wyatt, Gregory Alan Kenneth. "Coevolutionary adaptation in mutualisms." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:c3318211-a893-432e-a52e-35a6c60b76ce.
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Natural selection favours those individuals that respond best to novel features of their selective environment. For many, a critical challenge is responding to evolutionary change in mutualistic species. These responses create complex feedbacks, so only coevolutionary approaches are able to fully answer key questions about the maintenance or disruption of mutualistic behaviour, and explain the range of mechanisms that allow individuals to benefit from these associations. I first consider the hypothesis that economic models studying multiple classes of traders, where each trader seeks to optimise its own payoffs will yield insights into mutualistic systems. I show that individuals can be favoured to discriminate amongst potential partners based on the price for which they provide resources. Then, I show that market mechanisms can maintain cooperation and drive specialisation in mutualistic systems. I extend this market model to allow individuals to restrict a mutualistic partner's access to resources, and show that this strategy can stabilise cooperation and increase the fitness of both partners. I also explicitly incorporate relatedness in my market model. I show that high relatedness sometimes increases cooperativeness in members of a mutualistic species, but sometimes decreases cooperativeness as it narrow the scope for partner choice to maintain cooperation. Having studied market mechanisms, I consider indiscriminate costly help to members of another species. I discover that this trait can be favoured by natural selection and can be classified as either altruism between or altruism within species. Finally, I consider a framework for analysing coevolved phenotypic responses to a partner's cooperativeness, a challenging process to model. I demonstrate that this framework can yield firm predictions about behaviour whenever partners hold private information about their costs and benefits.
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Jenkins, James E. "Influence of high intensity interval training on pregnancy outcomes and muscle adaptation in rats /." The Ohio State University, 1988. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487596807822376.
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Gonzalez, Jonathan. "Investigations into host-specific interactions and local adaptation in the mycorrhizal symbiosis." ScholarWorks @ UVM, 2014. http://scholarworks.uvm.edu/graddis/324.
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Mycorrhizal fungi are soil-borne organisms that form symbiotic associations with the majority of land plants. These fungi gather and exchange mineral nutrients with plants for photosynthetically derived carbohydrates. Mycorrhizal fungi can also confer other benefits onto plants, e.g. defense against pathogens, improved water relations, tolerance to heavy metal toxicity and herbivory. The influence of mycorrhizal fungi on plant mineral nutrition and response to stress suggests that these organisms may have a role to play sustainable agriculture as well as in bioremediation and ecosystem restoration.
In contributing to this important research, I investigated host-specific interactions between mycorrhizal fungi and the sex morphs of the gynodioecious perennial herb Polemonium foliosissimum (Polemoniaceae) and their mycorrhizal associates in the field. I hypothesized that the genders of this species differed in their associations with mycorrhizal fungi in benefits received. I performed a full factorial simulated herbivory experiment and evaluated the extent of mycorrhizal colonization in the roots as well as the concentrations of nutrients in leaf tissue. Mycorrhizal colonization and leaf nutrient concentrations did not differ between the genders nor were influenced by the experimental treatments. This suggests that the genders of Polemonium foliosissimum do not interact differently with mycorrhizal fungi, and thus do not represent different "hosts".
Also, I investigated local adaptation of mycorrhizal associations by exploring the effect of large herbivore grazing on plant-mycorrhizal associations. I hypothesized that grazing by large herbivores results in locally adapted symbioses that enhance plant response to herbivory. I grew the perennial bunchgrass Themeda triandra (Poaceae) in inoculum prepared from soils collected from three field exclosures with differing histories of large herbivore exclusion in the Kenya Long Term Exclosure Experiment. I conducted a full factorial simulated herbivory experiment in which plants were subject to two clipping events over the course of 5-months, and evaluated plant regrowth as well as mycorrhizal colonization for plants in the experiment. Plants grown in inoculum from exclosures in which large herbivores have had access produced more root mass when mycorrhizal fungi were present. Further, I found equivalent biomass production of clipped and non-clipped plants in inoculum prepared from the exclosure with only native large herbivore access while equivalent biomass production was not found in the substrate prepared from areas with a history of large herbivore exclusion. This suggests that mycorrhizal fungi mediate plant growth and response to herbivory in this system.
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Maldonado, Torres Solvey [Verfasser]. "Force-induced Bone Adaptation: : A Systems Biology Perspective Towards Therapy Design / Solvey Maldonado Torres." Aachen : Shaker, 2012. http://d-nb.info/1069048151/34.
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Manku, Amrik S. "Biology Of Growth Adaptation And Remodelling Of Temporomandibular Joint Structures And Some Orthodontic Implications." Thesis, The University of Sydney, 1985. http://hdl.handle.net/2123/4875.
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Gruionu, Gabriel. "Structural adaptation of arcade arteries to changes in blood flow." Diss., The University of Arizona, 2004. http://hdl.handle.net/10150/280607.
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Arcades are blood vessels that form direct connections between two arteries or arterioles. Because they are supplied with blood from two sources, arcades can function as alternative flow pathways following obstruction of arteries or arterioles, as in coronary and peripheral vascular disease and stroke. In response to changes in blood flow or metabolic conditions, vascular networks undergo structural adaptation or remodeling, which includes structural changes of the existing vessels and growth of new vessels. Following obstruction of a blood supply, arcade vessels may adjust their internal diameters chronically to convert the alternative pathways into main blood distribution vessels. The overall goal of this dissertation was to examine structural changes in the internal diameter of a single arcade artery and the arterioles of an arcade network following changes in blood flow, using experimental and theoretical approaches. Diameter changes of the mouse gracilis arcade artery were observed up to 56 days following resection of one of its two blood supplies. Overall, diameters increased to a maximum around day 21 and then declined. The diameter changes were spatially non-uniform, being largest towards the point of resection, providing transiently increased perfusion to the most affected regions. Observed diameter changes were compared with predictions of a theoretical model, in which diameter varies in response to stimuli derived from local metabolic and hemodynamic conditions. Good agreement was found when effects of a time-delayed growth stimulus in regions of reduced perfusion were included, with a delay of about 7 days. The effectiveness of arcades in maintaining perfusion both immediately following obstruction and after structural adaptation in the arteriolar arcade network between two feed artery branches of the pig triceps brachii muscle was examined. Morphometric data from vascular casting and published data were used to develop a computational model for the hemodynamics and structural adaptation of the network in response to local stimuli. The results show that the arcades provide alternative flow pathways to the region initially supplied by the obstructed branch and that structural adaptation can lead to improved flow restoration following interruption of blood flow.
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Balogh, Gabor. "Role of membranes in mammalian stress response : sensing, lipid signals and adaptation." Thesis, Cardiff University, 2011. http://orca.cf.ac.uk/26933/.
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It was suggested that under heat stress the accumulation of denatured proteins alone triggers the expression of heat shock proteins. However, earlier research suggested that during abrupt temperature fluctuations membranes represent the most thermally-sensitive macromolecular structures. The aim of this thesis to confirm experimentally for the membrane sensor theory in mammalian cells and to explore the mechanisms behind membrane lipid structural reorganizations. The main results are as follows: (i) I provide the first evidence that heat-analogous, chemically-induced membrane perturbation of K562 erythroleukemic cells is indeed capable of activating heat shock protein formation at the growth temperature, without causing measurable protein denaturation; (ii) I showed that the membrane fluidizer benzyl alcohol acts as a chaperone-inducer also in B16(F10) melanoma cells. Furthermore, following both alcohol and heat treatments, condensation of ordered plasma membrane domains was detected by fluorescence microscopy; (iii) lipidomic fingerprints revealed that stress achieved either by heat or benzyl alcohol resulted in pronounced and highly specific alterations of membrane lipids in B16(F10) cells. The loss in polyenes with the concomitant increase in saturated lipid species was shown to be a consequence of activation of phospholipases. The accumulation of lipid species with raft-forming properties may explain the condensation of ordered plasma membrane domains detected previously; (iv) with Laurdan two-photon microscopy it was demonstrated that, in contrast to the formation of ordered domains in surface membranes, the molecular disorder is significantly elevated within the internal membranes of cells preexposed to mild heat stress. These results were compared with those obtained by other probes and visualisation methods. It was found that the structurally different probes revealed substantially distinct alterations in membrane heterogeneity. The results highlight that even subtle changes in membrane microstructure may play a role in temperature sensing and thermal cell killing and, therefore, could have potential in treatment of several diseases.
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Vidanes, Genevieve M. "Suppression of the DNA damage checkpoint by the Saccharomyces cerevisiae polo-like kinase, CDC5, to promote adaptation." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2009. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3352477.
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Räsänen, Katja. "Evolutionary implications of acidification: a frog’s eye view." Doctoral thesis, Uppsala University, Population Biology, 2002. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2873.
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Understanding the diversity of life is one of the main aims of evolutionary biology, and requires knowledge of the occurrence and causes of adaptive genetic differentiation among geographically distinct populations. Environmental stress caused by acidity may cause strong directional selection in natural populations, but is little explored from an evolutionary perspective. In this thesis, a series of laboratory experiments and field data was used to study evolutionary and ecological responses of amphibians to environmental acidity.
Local adaptation to acid stress was studied in the moor frog (Rana arvalis).The results show that acid origin populations have higher acid stress tolerance during the embryonic stages than neutral origin populations, and that acid and neutral origin populations have diverged in embryonic and larval life-histories. The mechanisms underlying adaptive differentiation are partially mediated by maternal effects related to extra-embryonic membranes and egg size. Acid origin females invest in larger eggs and have a stronger egg size-fecundity trade-off than females from neutral areas, likely reflecting adaptive differentiation in maternal investment patterns.
Potential carry-over effects of low pH, and the effects of UV-b/pH interaction were investigated in the common frog (R. temporaria). The results suggest that amphibian larvae are able to compensate for the negative effects of acidity experienced early in life, if conditions later turn beneficial. R. temporaria populations differed in their sensitivity to synergistic effects of low pH/UV-B, indicating variation in population responses to environmental stress.
In conclusion, these results suggest rapid evolution in response to human induced environmental change, much of which may be mediated via adaptive maternal effects. Acidification may be a powerful selective force shaping life-history evolution.
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Sheeley, Sara Lynn. "Investigating patterns of parallel genetic change in repeated adaptation." Diss., University of Iowa, 2010. https://ir.uiowa.edu/etd/600.
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The phenomenon of repeated evolution runs counter to expectations about the role of contingency in adaptation. However, many examples of independently acquired similar traits show that evolution sometimes does follow the same path. Factors influencing the probability of such an event include selection, trait complexity and relatedness. Previous investigations of repeated adaptation have primarily focused on low-complexity traits subject to strong selection. Studies of systems with varying levels of trait complexity, selection, and relatedness are needed to evaluate the relative contributions of these factors. The series of studies reported here 1) establishes a system for inquiry into the role of parallel adaptation among hosts and parasites and 2) provides an assessment of the role of parallel genetic change in the evolution of a complex trait.
In Chapter 2, I show that all-female broods in a line of Drosophila borealis are caused by infection with a male-killing strain of Wolbachia that is very closely-related to another male-killing strain infecting a geographically and evolutionarily distant species of Drosophila. This host-parasite system, together with two other known male-killing Wolbachia strains infecting Drosophila provides a framework for investigating the role of parallel evolution in the independent acquisition of the male-killing trait among Wolbachia, as well as in the adaptation of divergent hosts to similar male-killing parasites.
In Chapters 3-5, I investigate the role of parallel genetic change in a complex trait in two species of Drosophila by searching for evidence of adaptation in the Drosophila americana homologs of genes thought to underlie adaptation to climate in Drosophila melanogaster. In Chapter 3, I investigate the D. americana homolog of Alcohol dehydrogenase (Adh). In contrast with D. melanogaster, which segregates functionally distinct variants in Adh that represent local adaptation to climate, D. americana segregates little variation. This is surprising, especially because Adh of D. americana is found near a polymorphic chromosomal rearrangement that does segregate geographically-structured alleles across the species' range. In Chapter 4, I report similarities at the Phosphoglucomutase (Pgm) locus in the two species, including a shared excess of nonsynonymous variants and the presence of clinal alleles. However, while variation at Pgm of D. melanogaster is proposed to underlie local adaptation, variation at Pgm of D. americana appears to be predominantly neutral. In Chapter 5, I investigate the role of positive selection in sequence evolution in the D. americana homologs of a group of genes thought to underlie local adaptation to climate in D. melanogaster. The two species share a large geographic range and exhibit levels of sequence variation that indicate a similar effective population size, but D. melanogaster appears to undergo more frequent fixation of advantageous alleles. Approximately half of all amino acid divergence in D. melanogaster is attributable to positive selection, but I find no signs of positive selection in the investigated genes in D. americana. Overall, the results reveal little or no parallel evolution at the single genes analyzed. This lack of parallel evolution is likely a result of the high complexity of adaptation to climate as well as contingency.
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Knapp, Corrine Noel. "Engaging local perspectives for improved conservation and climate change adaptation." Thesis, University of Alaska Fairbanks, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3607055.
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Climate change is a global process that will impact local places in heterogeneous and unpredictable manners. This dissertation considers whose knowledge and observations could contribute to conservation and climate adaptation planning, how perceptions influence social-ecological feedbacks, and how science could be more relevant to decision-makers and local residents. In Chapter 2, I report on interviews (n=36) conducted with ranchers and recreation-based business owners in Colorado to understand their self-perceptions of resilience and vulnerability. I find that ranchers perceive more exposure and sensitivity to climate change and they also demonstrate more adaptive capacity than recreation businesses. In Chapter 3, I convey results from interviews (n=83) completed with various long-term residents of the region surrounding Denali National Park and Preserve. I find that people who have more direct and ongoing experience with natural resources (subsistence users, bus drivers, business owners) have a greater number and more diverse observations of change than Park employees or scientists. In Chapter 4, I describe results from interviews (n=26) with community-defined Gunnison Sage-grouse experts. I find that formal and observational experts had very different explanations of the decline of Gunnison Sage-grouse and disagreed about potential conservation strategies. In Chapter 5, I describe multi-method surveys (41) conducted with ranchers in the Gunnison Basin to understand their perceptions of the potential listing of the Gunnison Sage-grouse under the Endangered Species Act, and their planned responses. I find that ranchers tend to have negative perceptions of the listing and that they plan to take actions, including sales of land and water and decreased participation in conservation efforts, which may result in harm to the Gunnison Sage-grouse. In Chapter 6, I review stakeholder-generated climate change needs assessments (63) to assess the suggestions made to make science more relevant to decision-making. Their suggestions include: interdisciplinary approaches, place-based focus, increased data-sharing and collaboration, and user-driven research. This dissertation demonstrates the importance of understanding perceptions for effective conservation and adaptation, identifies the existence of proactive adaptation strategies, highlights the value of local knowledge in specific situations, and reveals how failure to engage local people may lead to inequitable outcomes.
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Banks, John E. "The effects of landscape heterogeneity on insect populations : a study of pattern and scale /." Thesis, Connect to this title online; UW restricted, 1997. http://hdl.handle.net/1773/5166.
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Whitson, Jeremy A. "Lens Adaptation to Glutathione Deficiency: Implications for Cataract." Case Western Reserve University School of Graduate Studies / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1491482909327594.
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Patitucci, Cecilia. "PPARy, a new player in hepatic metabolic adaptation from mouse model to human liver cancer." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCB056/document.
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La tumorigenèse est influencée par des facteurs génétiques et environmentaux. La surnutrition est une cause d'obésité et d'accumulation pathologique de lipides dans le foie, la stéatose, qui peut évoluer en stéato-hépatite. Obésité et stéato-hépatite contribuent à l'augmentation de l'incidence du diabète dans le monde entier. Le diabète et l'obésité sont des facteurs de risque pour le cancer du foie (El-Serag et al., Clin Gastroenterol Hepatol, 2006). Cet projet de thèse élucide les mécanismes moléculaires liant l'activation de la voie de signalisation de l'insuline, les maladies du foie gras et le développement du cancer du foie, et il propose de nouvelles stratégies thérapeutiques. La délétion hépato-spécifique du gène codant le suppresseur de tumeurs Phosphatase and tensin homolog (PTEN) est un modèle de cancer du foie associé à la stéatose (Horie et al., J Clin Invest, 2004). Nous avons utilisé ce modèle, où la cascade de signalisation PI3K/mTOR est activée, pour démontrer que l'induction de l'expression du facteur de transcription et récepteur nucléaire Peroxysome Proliferator-Activated Receptor gamma (PPARγ) est responsable de la stéatose et de la glycolyse aérobie (effet Warburg). Son activité est spécifiquement dépendente de l'activité d'un effectuer en aval de la voie PI3K/mTOR, la protéine sérine/thréonine kinase, AKT2 (Panasyuk et al., Nat Comm, 2012). Sur la base de ces observations, nous avons construit l'hypothèse que PPARγ est un important régulateur de la croissance pathologique et du développement des adénocarcinomes hépatiques associés aux stéato-hépatites. Avec mon travail de thèse j'ai pu démontrer que l'expression et l'activité de PPARγ sont essentielles pour le développement du cancer du foie dans le modèle de souris invalidées pour PTEN dans les hépatocytes. Par ailleurs, la délétion de PPARγ dans le foie dépourvu de PTEN joue un rôle protecteur de la tumorigenèse, confirmant que PPARγ est effectivement placé en aval de AKT2. De plus, nous avons découvert que PPARγ est induit dans des échantillons de carcinome hépatocellulaire humains. Ces échantillons sont caractérisés par leur agressivité (haut taux prolifératif et bas niveau de différentiation) et aussi par l'activation de la voie PI3K/AKT. L'analyse des échantillons humains au stade pré-carcinome (adénomes) nous a permis de démontrer que l'ARN de PPARγ est le plus exprimé dans les adénomes caractérisés par un haut degré de stéatose. Ils sont caractérisés par la perte de fonction du facteur de transcription Hepatocyte Nuclear Factor 1α (HNF1α). Nous avons identifié HNF1α comment un nouveau régulateur négatif de la transcription de PPARγ. Nous avons aussi découvert que l'expression et l'activité de HNF1α sont inhibées par AKT2, induisant l'expression de PPARγ et son activité pro-tumorigénique. Finalement, la sensitibilité de PPARγ aux ligands, naturels et exogènes, nous a encouragé à tester des traitements pharmacologiques pour moduler son activation. La stimulation de l'activité de PPARγ avec l'agoniste synthétique Pioglitazone a conduit à une aggravation des symptomes dans le foie. Par contre, son inhibition par un antagoniste sélectif, SR2595, était thérapeutique, resultant en une réduction de signes pré-tumoraux et tumoraux dans le foie des souris invalidé par PTEN. En résumé, nos études chez l'humain et la souris, révèlent une nouvelle signature d'interaction entre les facteurs de transcription HNF1α et PPARγ et la voie de signalisation de l'insuline, suggérant de nouvelles stratégies thérapeutiques possibles pour le traitement d'une sous-classe spécifique de cancer du foie lié aux stéato-hépatitesTumorigenesis is influenced by genetic and environmental factors. Overnutrition leads to obesity and fatty liver disease, contributing to increase diabetes incidence worldwide. Diabetes and obesity are independent risk factors for liver cancer development (El-Serag et al., Clin Gastroenterol Hepatol, 2006). This PhD project elucidates the molecular mechanisms linking activated insulin signalling pathway, fatty liver disease and liver cancer development and proposes novel therapeutic strategies. The hepatocytes-specific deletion of tumour suppressor Phosphatase and tensin homolog (PTEN) is a model of steatosis-associated liver cancer (Horie et al., J Clin Invest, 2004). Using this model of activated PI3K/mTOR signalling, our laboratory discovered that the nuclear receptor transcription factor Proliferator-Activated Receptor gamma (PPARγ) is induced in PTEN-null liver. My group demonstrated that in the liver PPARγ contributes to steatosis and aerobic glycolysis. Its activity specifically requires a downstream effector in the PI3K/mTOR pathway, the serine/threonine-specific protein kinase AKT2 (Panasyuk et al., Nat Comm, 2012). Based on these observations, we hypothesized that PPARγ might be an important regulator of pathological growth and development of steatohepatitis-associated liver adenocarcinomas. In my PhD work, I demonstrated that PPARγ expression and activity is essential for liver cancer in PTEN mutants. Moreover, PPARγ is induced in human samples of Hepatocellular Carcinoma (HCC) characterized by poor differentiation accompanied by the activation of PI3K/AKT pathway. We could attribute to PPARγ a specific role in tumour formation as it is required for abnormal liver growth and steatosis in mice at pre-tumoral age. In addition, deletion of PPARγ in PTEN mutants protected animals form liver tumorigenesis placing PPARγ downstream of activated AKT2. Analysing human samples of pre-carcinoma lesions characterized by high steatotic rate, we demonstrated that PPARγ transcript levels are increased in a specific subgroup of adenomas characterized by loss-of-function mutations in the Hepatocyte Nuclear Factor 1α (HNF1α). We identified HNF1α as a novel direct negative regulator of PPARγ transcription. We also revealed HNF1α expression and activity inhibited by AKT2 and thereby inducing PPARγ pro-tumorigenic action. Finally, the sensitivity of PPARγ to natural and exogenous ligands encouraged us to perform treatments to pharmacologically modulate PPARγ activity. Further activation of PPARγ with its synthetic ligand pioglitazione dramatically aggravates liver disease. While PPARγ inhibition by selective antagonist SR2595 allowed to reduce the pre-tumoral and tumoral signs of PTEN-null mice. In sum, our studies in men and mice reveal a novel pro-tumorigenic network of transcription factors HNF1α and PPARγ downstream of activated insulin signalling pathway, suggesting possible strategies for treatment of a subgroup of steatohepatitis-associated liver cancer
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Niswander, Julie M. "Molecular Correlates of Adaptation and Apoptosis: p38 Signaling in Hippocampus." University of Toledo Health Science Campus / OhioLINK, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=mco1085678685.
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Bebris, Kristaps. "Local adaptation of Grauer's gorilla gut microbiome." Thesis, Uppsala universitet, Zooekologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-326705.
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The availability of high-throughput sequencing technologies has enabled metagenomicinvestigations into complex bacterial communities with unprecedented resolution andthroughput. The production of dedicated data sets for metagenomic analyses is, however, acostly process and, frequently, the first research questions focus on the study species itself. Ifthe source material is represented by fecal samples, target capture of host-specific sequencesis applied to enrich the complex DNA mixtures contained within a typical fecal DNA extract.Yet, even after this enrichment, the samples still contain a large amount of environmentalDNA that is usually left unanalysed. In my study I investigate the possibility of using shotgunsequencing data that has been subjected to target enrichment for mtDNA from the hostspecies, Grauer’s gorilla (Gorilla beringei graueri), for further analysis of the microbialcommunity present in these samples. The purpose of these analyses is to study the differencesin the bacterial communities present within a high-altitude Grauer’s gorilla, low-altitudeGrauer’s gorilla, and a sympatric chimpanzee population. Additionally, I explore the adaptivepotential of the gut microbiota within these great ape populations.I evaluated the impact that the enrichment process had on the microbial community by usingpre- and post-capture museum preserved samples. In addition to this, I also analysed the effectof two different extraction methods on the bacterial communities.My results show that the relative abundances of the bacterial taxa remain relatively unaffectedby the enrichment process and the extraction methods. The overall number of taxa is,however, reduced by each additional capture round and is not consistent between theextraction methods. This means that both the enrichment and extraction processes introducebiases that require the usage of abundance-based distance measures for biological inferences.Additionally, even if the data cannot be used to study the bacterial communities in anunbiased manner, it provides useful comparative insights for samples that were treated in thesame fashion.With this background, I used museum and fecal samples to perform cluster analysis to explorethe relationships between the gut microbiota of the three great ape populations. I found thatpopulations cluster by species first, and only then group according to habitat. I further foundthat a bacterial taxon that degrades plant matter is enriched in the gut microbiota of all threegreat ape species, where it could help with the digestion of vegetative foods. Another bacterialtaxon that consumes glucose is enriched in the gut microbiota of the low-altitude gorilla andchimpanzee populations, where it could help with the modulation of the host’s mucosalimmune system, and could point to the availability of fruit in the animals diet. In addition, Ifound a bacterial taxon that is linked with diarrhea in humans to be part of the gut microbiotaof the habituated high-altitude gorilla population, which could indicate that this pathogen hasbeen transmitted to the gorillas from their interaction with humans, or it could be indicative ofthe presence of a contaminated water source.
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Maher, Keri Renee. "A geographically constrained molecular phylogeny of Panamanian Aechmea species (Bromeliaceae, subfamily bromelioideae)." CSUSB ScholarWorks, 2007. https://scholarworks.lib.csusb.edu/etd-project/3280.
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This study lends strong support to the idea that members of Bromeliaceae have undergone a recent adaptive radiation, and therefore show that, at least in part, diversity in the tropics is due to a fast speciation rate and that the tropics can be a "cradle" for new diversification and exploitation of varying ecological niches through the diversification of ecophysiological traits within a lineage.
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Rodriguez, Marbelys. "Two Adaptation Mechanisms Regulate Cellular Migration in Dictyostelium discouideum." FIU Digital Commons, 2014. http://digitalcommons.fiu.edu/etd/1144.
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Dictyostelium discoideum is a simple model widely used to study many cellular functions, including differentiation, gene regulation, cellular trafficking and directional migration. Adaptation mechanisms are essential in the regulation of these cellular processes. The misregulation of adaptation components often results in persistent activation of signaling pathways and aberrant cellular responses. Studying adaptation mechanisms regulating cellular migration will be crucial in the treatment of many pathological conditions in which motility plays a central role, such as tumor metastasis and acute inflammation. I will describe two adaptation mechanisms regulating directional migration in Dictyostelium cells.
The Extracellular signal Regulated Kinase 2 (ERK2) plays an essential role in Dictyostelium cellular migration. ERK2 stimulates intracellular cAMP accumulation in chemotaxing cells. Aberrant ERK2 regulation results in aberrant cAMP levels and defective directional migration. The MAP Phosphatase with Leucine-rich repeats (MPL1) is crucial for ERK2 adaptation. Cells lacking, MPL1 (mpl1- cells) displayed higher pre-stimulus and persistent post-stimulus ERK2 phosphorylation, defective cAMP production and reduced cellular migration. Reintroduction of a full length Mpl1 into mpl1- cells restored aggregation, ERK2 regulation, random and directional motility, and cAMP production similar to wild type cells (Wt). These results suggest Mpl1 is essential for proper regulation of ERK2 phosphorylation and optimal motility in Dictyostelium cells.
Cellular polarization in Dictyostelium cells in part is regulated by the activation of the AGC-related kinase Protein Kinase Related B1 (PKBR1). The PP2A regulatory subunit, B56, and the Glycogen Synthase Kinase 3 (GSK3) are necessary for PKBR1 adaptation in Dictyostelium cells. Cells lacking B56, psrA-cells, exhibited high basal and post-stimulus persistent phosphorylation of PKBR1, increased phosphorylation of PKBR1 substrates, and aberrant motility. PKBR1 adaptation is also regulated by the GSK3. When the levels of active GSK3 are reduced in Wt and psrA- cells, high basal levels of phosphorylated PKBR1 were observed, in a Ras dependent, but B56 independent mechanism. Altogether, PKBR1 adaptation is regulated by at least two independent mechanisms: one by GSK3 and another by PP2A/B56.
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Lindgren, Beatrice. "Adaptation Along Environmental Gradients: an Evaluation of Physiological Mechanisms and Ecological Constraints." Doctoral thesis, Uppsala University, Department of Ecology and Evolution, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8310.
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For ectotherms living in seasonal environments, time available for development and growth is often constrained by the length of the growth season. Declining season length towards higher latitudes often select for latitudinal clines in development and growth rates, exhibiting increasing growth and developmental rates towards the north. However, the physiological and ecological factors enabling these clines are poorly understood.
Our study system included eight populations of Rana temporaria along a 1500 km latitudinal gradient. We found increased growth rates in populations at higher latitudes to be the result of higher growth efficiency, partly due to increased relative gut length. Populations with higher growth rates also exhibited lower standard metabolic rates, implying that fast-growing individuals are able to achieve high growth rates by spending less energy on maintenance metabolism under low activity conditions.
Predator densities, and antipredatory defenses in prey, are assumed to decrease towards higher latitudes. While all study populations responded to predator presence by decreasing activity and foraging, high latitude populations maintained higher activity levels in the presence of the predator. In trials with a free-ranging predator, high latitude tadpoles experienced higher mortality than those from the low latitudes. The higher activity level in the northern populations increases mortality under predation risk, but is probably needed to maintain high growth and development rates.
When competing over resources, tadpoles from the low latitude population were inferior competitors, as indicated by their longer development time when raised together with high latitude tadpoles. We found no effect of latitude on size-corrected burst speed. The general effect of predator presence on burst speed depended on food availability, with well fed tadpoles being faster in the absence, and food restricted being faster in the presence of a predator.
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Lapidge, Steven James. "Reintroduction biology of yellow-footed rock wallabies (petrogale xanthopus celeris and P. x. xanthopus." University of Sydney. Biological Sciences, 2002. http://hdl.handle.net/2123/851.
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Based on the recommendations of both the 1993 Reintroduction biology of Australasian Fauna Conference and the 1994 Rock Wallaby Symposium, captive-bred Yellow footed rock wallabies were reintroduced into areas of their former ranges in both South Australia and Queensland
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Martinossi-Allibert, Ivain. "Sexual Selection and Adaptation to Novel Environments." Doctoral thesis, Uppsala universitet, Zooekologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-332119.
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The work included in this thesis aims at exploring the environmental sensitivity of benefits and costs of sexual selection through a combined empirical and theoretical effort, to increase our understanding of the impact of environmental change on sexually reproducing populations.Can sexual selection promote adaptation to novel environments? Sexual selection for good genes should accelerate adaptation by granting higher reproductive success to individuals of high genetic quality. However, sexual conflict is a frequent outcome of sexual reproduction and may often be detrimental to population fitness. Experimental evolution has shown that the role of sexual selection in adaptation is variable, because of a complex balance between the detrimental and beneficial effects described above.The present thesis is investigating the role of sexual selection in adaptation by focusing on the sex-specific strength of selection and the intensity of intralocus sexual conflict (IaSC) in ancestral and novel environments. The sex-specific strength of selection is a valuable proxy for the benefits of sexual reproduction, since a male-bias in selection caused by sexual selection should allow efficient purging of deleterious alleles with little impact on female fecundity and cost to population fitness.This thesis investigates both sex-specific selection and IaSC across benign and novel environments in two species of seed beetles, Callosobruchus maculatus and Acanthoscelides obtectus, and includes a theoretical model of the effect of environmental change on of sexual selection. The empirical part of my results indicates that, generally, selection at the adult stage is male biased but that this male bias may be reduced under stress, pointing towards reduced benefits of sexual selection under rapid environmental change. Additional simulations suggest that the frequency dependent nature of sexual selection alone could explain this trend. No empirical support was found for the reduction of IaSC under stress.It is becoming crucial today to understand the impact of environmental change on natural populations. This thesis brings new material adding to our understanding of the role of sexual selection within that particular issue. The outcome of sexual selection is dependent on a variety of mechanisms, such as good genes processes and sexual conflict, which are very likely to be dependent on ecological factors and specificity of the system studied. For that reason, carefully controlled experiments on laboratory systems and mathematical modelling are necessary steps that should ultimately lead to the study of similar questions in natural systems.
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Khawaja, Farhan A. "Ca²+-dependent K+ currents and spike-frequency adaptation in medial entorhinal cortex layer II stellate cells." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=101151.
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We hypothesized that stellate cells (SCs) from layer II of the medial entorhinal cortex (MEC) may express currents that underlie spike-frequency adaptation (SFA) and that inhibitory modulation of these currents may permit the non-adapting nature of pulse-evoked post-burst after-discharges, a possible neuronal correlate of the post-stimulus delay firing seen in-vivo during working memory (WM) tasks. It was revealed that SCs contain medium (mIK(Ca)) and slow (sIAHP) Ca2+-dependent K+ currents. Furthermore, it was determined that mIK(Ca) is not mediated by apamin-sensitive SK channels in SCs, whereas it was found to be is apamin-sensitive in MEC layer II non-SCs. In addition, the results indicated that mIK(Ca) and sIAHP may underlie SFA in SCs and that mIK(Ca), sIAHP and SFA are subject to inhibitory modulation by PKA-activation. Therefore, PKA modulation may be important for SCs to exhibit post-burst after-discharges. Future work is required to determine whether PKA modulation of MEC layer II SCs plays an important role during WM tasks.
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Mena, Paulina Alejandra. "The Role of chromosomal rearrangements in adaptation in Drosophila americana." Diss., University of Iowa, 2009. https://ir.uiowa.edu/etd/310.
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Natural environments expose organisms to multifarious selective pressures involving numerous aspects of the overall phenotype, therefore eliciting a response from multiple correlated loci. It has been hypothesized that chromosomal rearrangements can play a role in facilitating local adaptation by establishing new linkage relationships and modifying the recombination patterns between the different chromosomal forms, allowing coordinated adaptation of several loci. The central aim of the work presented here is to test this hypothesis using Drosophila americana as a model system. This species segregates several inversions and an X-4 centromeric fusion which makes it an excellent model to study the role of chromosomal rearrangements on local adaptation.
This hypothesis was tested using several approaches. The geographic distribution of the chromosomal rearrangements was determined through sampling of wild populations from a broad geographic range. It was found that several of the chromosomal rearrangements exhibit clinal variation. Furthermore, many of these are found in high linkage disequilibrium. The X-4 fusion is highly associated with inversions on the X and 4th chromosome. Also, two inversions on chromosome 5 are in strong negative linkage disequilibrium.
The sequence variation associated with rearrangements of the X was studied using inbred lines. The results show that the inversion and the fusion strongly influence variation on this chromosome. Regions of significant population differentiation and linkage with the rearrangements are found interspersed with loci showing neutral variation indicating that in spite of recombination, allelic associations are maintained on this chromosome.
The analysis was also extended to flies directly collected from the wild sampled from a region encompassing a large part of the species' range. Loci throughout chromosome X and 4 were genotyped. Sites in high linkage disequilibrium with the rearrangements and with other assayed sites were found in close proximity with sites that did not show this pattern.
In conclusion, the clinal distribution of chromosomal rearrangements and associated genetic variation in conjunction with the detection of islands of linkage disequilibrium among the rearrangements and loci on both chromosomes indicate that chromosomal rearrangements are facilitating local adaptation in D. americana.
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Bonvini, Lauren A. "Jumping behavior and the effects of caudal autotomy on performance in Anolis carolinensis /." Connect to online version, 2007. http://ada.mtholyoke.edu/setr/websrc/pdfs/www/2007/215.pdf.
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Davidsen, Peter Kåre. "Understanding skeletal muscle adaptation in health and chronic disease : a multi-omics based systems biology perspective." Thesis, University of Birmingham, 2016. http://etheses.bham.ac.uk//id/eprint/6563/.
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Mammalian skeletal muscle has a major impact on whole-body metabolic homeostasis. Hence, maintenance of a metabolically active muscle mass is key for optimal health. Notably, both muscle function and mass are profoundly negatively affected by environmental factors such as chronic smoking and physical inactivity. RNA abundance integrates genetic, epigenetic and environmental influences. Therefore, while true understanding of physiological adaptation likely require the integration between multi-level datasets, the transcriptome represents a powerful investigative tool in determining the underlying molecular mechanisms behind complex phenotypic traits. The overarching aim of this thesis was to evaluate, using omics-based systems biology approaches, the global regulation of RNAs during exogenous modulation of mammalian muscle phenotype in order to characterize local homeostatic processes as well as identify robust biomarker signatures. The first part of this thesis deals with smoke-induced peripheral muscle wasting. Initially, biological domain knowledge is used to validate a pre-clinical smoking model. Then, specific cytokines are statistically linked to limb muscle energy metabolism; a testable hypothesis supported by both animal and human data. The second part deals with the development of ‘molecular predictors’ of endurance training adaptability. Two complex clinically relevant traits are considered, namely whole-body insulin sensitivity and plasma triglyceride content. Promisingly, quantitative multi-gene predictors of response to training for both traits of interest were developed.
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Kwan, Lucia. "Adaptation to desiccation resistance fails to generate pre- and postmating isolation in Drosophila melanogaster." Thesis, University of Ottawa (Canada), 2009. http://hdl.handle.net/10393/28210.
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Many laboratory speciation experiments have raised allopatric populations in different environments to determine whether reproductive isolation evolves as a by-product of adaptation. Few, however, have controlled for the effects of genetic drift, addressed the evolution of both pre- and postmating isolation, or investigated the conditions that promote or hamper the process. I present results of a long-term evolution experiment in which 12 replicate populations of Drosophila melanogaster independently evolved for more than 57 generations under alternative desiccation treatments (six control and six desiccation-selected populations). Specifically, I demonstrate the divergence between the desiccation and control populations of cuticular hydrocarbons, key traits that have been implicated in mate choice and sexual isolation in Drosophila. Despite this divergence, there was no detectable pre- or postmating isolation between the desiccation and control populations. Novel environments are generally thought to promote the evolution of reproductive isolation. Understanding the conditions that favour or hamper this remains a key challenge for speciation research.
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Smith, Jeramiah James. "AMBYSTOMA: PERSPECTIVES ON ADAPTATION AND THE EVOLUTION OF VERTEBRATE GENOMES." Lexington, Ky. : [University of Kentucky Libraries], 2007. http://lib.uky.edu/ETD/ukybiol2007d00627/JJSmith_Dissertation.pdf.
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Thesis (Ph. D.)--University of Kentucky, 2007.Title from document title page (viewed on September 4, 2007). Document formatted into pages; contains: vii, 182 p. : ill. (some col.). Includes abstract and vita. Includes bibliographical references (p. 164-180).
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Kleinjan, Hetty. "The influence of bacteria on the adaptation to changing environments in Ectocarpus : a systems biology approach." Thesis, Sorbonne université, 2018. http://www.theses.fr/2018SORUS267.
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Ectocarpus dépend de bactéries associées pour croitre en eau douce, ce qui souligne l'importance de l'holobionte lors de stress abiotique. Le but de ma thèse est d'élucider les mécanismes moléculaires qui sous-tendent ce phénomène. Les expériences de co-culture ciblées nécessitent des organismes cultivables. Par conséquent, j'ai caractérisé 388 bactéries associées à Ectocarpus, réparties en 33 genres. Aucune des bactéries cultivées testées n'a eu d'effet bénéfique sur la croissance des algues dans l'eau douce. J'ai continué à travailler avec des holobionts, traités aux antibiotiques doux, qui différaient dans leur réponse à l'eau douce. Le métatranscriptome/métabolome de ces holobionts ont été analysés pendant l'acclimatation. L'analyse approfondie est en cours, mais les premières indications indiquent un changement dans le microbiome en ce qui concerne l'assimilation de l'azote et la virulence. Concomitamment et complémentaire à ce qui précède, les interactions algues/bactéries potentiellement bénéfiques ont été prédites in silico à l'aide d'une analyse de réseau métabolique et les prédictions ont été vérifiées expérimentalement à l'aide de co-cultures. Ensemble, ces résultats contribuent à mieux comprendre comment l'holobiont d'Ectocarpus réagit au stress abiotique et surtout comment les bactéries sont impliquées dans ce processusEctocarpus subulatus depends on its associated bacteria for growth in fresh water, which stresses the significance of the “holobiont” during abiotic stress. The aim of my thesis is to elucidate the molecular mechanisms that underlie this phenomenon. Targeted co-culture experiments require cultivable organisms. Therefore, I have cultivated and characterized 388 Ectocarpus-associated bacteria, which belong to 33 different genera. None of the cultivated bacteria tested had a beneficial effect on algal growth in fresh water. For functional studies, I continued to work with mild antibiotic-treated holobionts that differed in their response to fresh water. The metatranscriptome and metabolome of these holobionts were analyzed during acclimation. In-depth analysis is ongoing, but first indications point towards a change in the microbiome regarding nitrogen assimilation and virulence. In parallel and complementary to the above, potentially beneficial algal-bacterial cross-talk was predicted in silico using metabolic network analysis on a subset of cultivated bacteria, and the predictions were experimentally verified using co-culture experiments. Together, these results contribute to a better understanding of how the Ectocarpus holobiont responds during abiotic stress and especially how bacteria are involved in this process
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Grobbelaar, Melanie. "Adaptation of the Mycobacterium tuberculosis transcriptome in response to rifampicin." Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/20387.
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Thesis (MScMedSc)--Stellenbosch University, 2012.ENGLISH ABSTRACT: Anti-tuberculosis drugs target specific essential cellular processes and structural components. The first line drug, rifampicin (RIF) is a RNA polymerase inhibitor which targets the β-subunit and subsequently inhibits the initiation of transcription. Previous proteomic and transcriptomic analyses have shown that exposure to RIF for 24hrs significantly increased the abundance of proteins involved in energy metabolism in clinical isolates. No studies have been done to describe the transcriptional responses to RIF in an in vitro RIF resistant M. tuberculosis isolate. Application of in vitro mutants is novel since it will exclude most of the confounding factors which may be present in clinical isolates obtained from patients where the bacterium may have been incubated for several weeks or even years. This study aimed to determine the effect of prolonged exposure to RIF and the effect of the rpoB Ser531Leu mutation on the expression of energy metabolism genes, sigma factors and a regulator in RIF mono-resistant in vitro mutants with different levels of RIF resistance (minimum inhibitory concentration (MIC): 40μg/ml and 70μg/ml). RIF mono-resistant in vitro mutants were generated from a pan susceptible Beijing cluster 208 progenitor using the Luria Delbruck assay. In vitro RIF mono-resistant mutants harbouring the Ser531Leu rpoB mutation and which displayed different levels of RIF resistance were selected. To assess the effect of prolonged RIF exposure on the expression of candidate genes, the in vitro mutants were cultured in liquid media and exposed to RIF for 1, 7 and 14 days. High quality RNA was extracted from these cultures at each time point and Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) was done on the selected candidate genes. The results indicate that limited expression of energy metabolism genes and sigma factors was observed after prolonged RIF exposure. In addition, the activity of the regulator (Rv1846c) was down-regulated in the presence of RIF explaining the up-regulated state of energy metabolism genes. To assess the effect of the rpoB Ser531Leu mutation on the candidate genes, RNA was extracted from the RIF unexposed culture at mid-log phase. RT-qPCR was done for each in vitro mutant in addition to the wild-type progenitor isolate. These results show that energy metabolism genes and sigma factors were significantly up-regulated in the RIF resistant mutantss harbouring an rpoB Ser531Leu mutation. This suggests that the mutation had a significant effect on the cellular energy cost due to the up-regulated state of the energy metabolism genes. In addition, an increase in the expression of sigma factors may be required to compensate for the rpoB mutation by enforcing the binding of the RNA polymerase and sigma factors to the promoter for transcription to be initiated. It is therefore important to assess these candidate genes for their potential as novel candidates for future drug design as this is an important aspect to influence tuberculosis control.
AFRIKAANSE OPSOMMING: Teen-tuberkulose middels teiken essensiële sellulêre prosesse en strukturele komponente. Die eerste linie teen-tuberkulose middel, rifampisien (RIF) is ʼn RNS polimerase inhibeerder wat die β-subeenheid teiken en daarna die inisiasie van transkripsie onderdruk. Vorige proteomiese en transkriptomiese analises het getoon dat blootstelling aan RIF vir 24 uur beduidende styging in sekere protiene wat verband hou met energie metabolisme in kliniese isolate veroorsaak. Die huidige studie poog om die effek van langdurige RIF blootstelling, asook die effek van die rpoB Ser531Leu mutasie op die uitdrukking van energie metabolisme gene, sigma faktore en reguleerders op RIF-enkel weerstandige in vitro mutante by verskillende vlakke van RIF weerstandigheid (Minimum Inhiberende Konsentrasie (MIK): 40μg/ml en 70μg/ml) te ondersoek. RIF-enkelweerstandige in vitro mutante isolate is gegenereer van ʼn sensitiewe Beijing 208 stamfamilielid deur die Luria Delbruck metode. In vitro RIF enkelweerstandige mutante met die rpoB Ser531Leu mutasie en verskillende vlakke van RIF weerstandigheid is geselekteer. Om die langdurige effek van RIF blootstelling op kandidaat geen uitdrukking te ondersoek, is in vitro mutante isolate gegroei in vloeibare medium en blootgestel aan RIF vir 1, 7 en 14 dae. Goeie kwaliteit RNS is geëkstraheer van hierdie kulture by elke tydpunt om Werklike-tyd Kwantitatiewe Polimerase Ketting Reaksie (RT-qPCR) op die kandidaat gene uit te voer. Die resultate toon dat ʼn beperkte aantal energie metabolisme en sigma faktor gene uitgedruk was na RIF blootstelling. Verder is die uitdrukking van die reguleerder (Rv1846c) af gereguleer in die teenwoordigheid van RIF en dit verduidelik die op gereguleerde energie metaboliese geen patroon. Om die effek van die rpoB Ser531Leu mutasie op die kandidaat gene te evalueer, is RNS geëkstraheer van ʼn weerstandige en RIF sensitiewe kultuur wat nie blootgestel was aan RIF nie. RT-qPCR is uit gevoer op elke in vitro mutante isolaat asook op ʼn sensitiewe isolaat sonder ʼn mutasie. Hierdie resultate toon dat energie metabolisme gene en sigma faktore beduidend opreguleer word in die isolate met ʼn rpoB Ser531Leu mutasie. Dit dui daarop dat die mutasie ʼn beduidende effek op die sellulêre energie koste het, omdat die energie metabolisme gene op gereguleer is. Verder kan ʼn toename in die uitdrukking van sigma faktore benodig word om die effek van die rpoB mutasie te oorkom deur binding van die RNS polimerase en die sigma faktore aan die promotor om transkripsie inisiasie te forseer. Dit is daarom belangrik om hierdie kandidaat gene verder te ondersoek vir toekomstige ontwikkeling van teenmiddels teen tuberkulose.
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Sadeghi, Ghandehari Navid. "The effects of adaptation and attention on temporal perception in the Middle Temporal area of behaving primate." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=114266.
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Neurons in sensory areas of our nervous system respond to sensory stimuli, but they are also modulated at the same time by both feed-forward and feed-back mechanisms. The history of prior sensory stimulation shapes the way neurons respond to future stimuli, a bottom-up plasticity effect known as adaptation. In addition, we can willfully employ top-down attention, which affects the activity of sensory neurons in a way that enables us to focus on a relevant task at hand. In this thesis, adaptation and attention are studied predominantly in the context of time and timing. Time is an elusive phenomenon perceived by the brain that plays an important role in many cognitive functions. Understanding bottom-up and top-down effects in a temporal context is a less studied area of neuroscience that is needed for a better understanding of brain's function, cognition, and possibly consciousness. An important feature of our study was to observe both phenomena in awake animals that were engaged in a relevant behavioral task.In addition to the usual characterization of the effects for spikes, we also analyzed the lower frequency voltage modulations in the brain known as the local field potentials (LFPs). Knowledge about the meaning of the LFPs provides a broader understanding of how the brain works. One advantage of LFPs is that they sum all kinds of neural activity for many neurons in the vicinity of the electrode tip, and hence they have the potential to be informative about the correlations among the activity of those neurons.In the first chapter, a brief introduction is presented on background information with a focus on choice-related modulations of neural activity. In the second chapter, the methods used in our experiments are introduced. In the third chapter, the neural correlates of detecting dysrhythmia is studied by analyzing the spiking activity of neurons in area MT. In the fourth chapter, the effects of adaptation and attention on the LFPs and also on the relationship between LFPs and spikes is presented. In the fifth chapter, the effects of adaptation on temporal dynamics of neural response in area MT and its possible role in a temporal illusion in humans is addressed. In the final chapter, the implications of our findings and future perspectives are briefly discussed.Les neurones dans les zones sensorielles de notre système nerveux répondrent aux stimuli sensoriels, mais dans le même temps ils sont aussi modulés à la fois par des mécanismes feed-forward et feed-back. L'histoire de la stimulation sensorielle affecte la façon dont les neurones répondent à des stimuli à venir, un effet de plasticité connu sous le nom d'adaptation. En outre, nous pouvons employer volontairement l'attention, ce qui affecte l'activité des neurones sensoriels d'une manière qui nous permet de concentrer sur une tâche pertinente à portée de main.Dans cette thèse, l'adaptation et l'attention sont étudiés surtout dans le contexte de temps et le calendrier. Le temps est un phénomène insaisissable perçue par le cerveau qui joue un rôle important dans de nombreuses fonctions cognitives. Modulation neuronal dans un contexte temporel est un domaine moins étudié des neurosciences qui est nécessaire pour une meilleure compréhension de la fonction cérébrale, la cognition, et peut-être la conscience. Une caractéristique importante de notre étude était d'observer les deux phénomènes chez les animaux éveillés qui ont été engagés dans une tâche pertinente du comportement.En plus de la caractérisation usuelle des effets de potentiels d'action, nous avons également analysé les modulations de fréquence inférieure de tension dans le cerveau connue sous le nom des potentiels de champs locaux (LFP). La connaissance de la signification des LFP offre une plus large compréhension de la façon dont le cerveau fonctionne. Un avantage de LFP est qu'ils résument toutes sortes d'activités de neurones pour de nombreux neurones dans le voisinage de l'extrémité de l'électrode, et donc ils ont le potentiel pour être informatif sur les corrélations entre l'activité de ces neurones.Dans le premier chapitre, une brève introduction est présentée sur des informations d'arrière-plan avec un accent sur les modulations de l'activité neuronale liée à la décision. Dans le deuxième chapitre, les méthodes utilisées au cours de nos expériences sont introduits. Dans le troisième chapitre, les corrélats neuraux de la détection des troubles du rythme est étudié par l'analyse de l'activité neuronale dans l'aire MT. Dans le quatrième chapitre, les effets de l'adaptation et l'attention sur les LFP et aussi sur la relation entre LFP et les potentiels d'action est présenté. Dans le cinquième chapitre, les effets de l'adaptation sur la dynamique temporelle de la réponse neuronale dans l'aire MT et son rôle possible dans une illusion temporelle chez l'homme est présenté. Dans le dernier chapitre, les implications de nos résultats et perspectives d'avenir sont brièvement discutées.