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Aggressive Phenotypes in Malawi Cichlids Associated with V1AR Variant

2016-12 , Schappaugh, Nicholas A.

The cichlid model provides a great opportunity to explore diversity in behavioral phenotypes. Different groups of Malawi cichlids exhibit distinct patterns of behavior for a variety of scenarios, including aggressive encounters. These cichlids, characterized by the rocky or sandy habitats they occupy, exhibit strong genetic divergence, possessing large numbers of alternatively fixed variants between them. One such variant exists in the gene avpr1a, also known as V1aR, a major receptor for vasopressin in humans. This gene has been linked to behavioral effects across a variety of animal species, with this specific variant likely to have significant structural implications for the receptor product. Here we investigate the aggressive behaviors of a set of rock and sand hybrid fish for their association with the variant observed in V1aR. While specific metrics of aggression showed similar trends in these hybrids compared to those observed in the parental rock and sand species, ultimately these trends were not significant and were inconclusive. However, these results serve as a preliminary investigation of this gene’s involvement in cichlid aggressive behavior. In future work, further examination of the locus will be conducted utilizing more precise and powerful methods in order to draw stronger conclusions.

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The influence of wheelchair mechanical parameters and human physical fitness on propulsion effort

2016-11-15 , Lin, Jui-Te

The majority of wheelchair studies that attempt to evaluate propulsion efforts across wheelchair configurations examines long and steady propulsion. However, the results of these studies cannot represent performance during daily maneuvers, which include changes in speed and direction. Although each component of wheelchair configuration was widely studied, the knowledge has a limitation to describe the mechanical properties of wheelchairs systematically. Physical fitness was proved to be related to health status and exercise performance. In addition, the biomechanical characteristics of the user were shown to influence wheelchair maneuvers. However, it is still unknown how these human factors would influence wheelchair propulsions together. Therefore, the overall objective of the study is to define the relative influence of mechanical wheelchair parameters as well as individual physical and biomechanical variables on propulsion efforts during over-ground maneuvers. The first aim is to develop and validate a test that quantifies the impact of wheelchair configurations on frictional energy loss, particularly loss related to turning trajectories. The second aim is to develop and validate a testing protocol designed to measure maximum propulsion strength, which will test subjects in a realistic condition – while seated in their wheelchairs. The third aim is to identify the impact of the mechanical parameters of wheelchairs as well as the physical and biomechanical variables of operators on propulsion efforts during over-ground maneuvers. Mechanical parameters include both inertial and frictional measurements. Operator factors include shoulder position, propulsion strength, and aerobic capacity. To evaluate the performance of daily maneuvering, we designed a repeatable maneuver consisting of several momentum changes. Because of the breadth of wheelchair configurations and variance in user physical capacity, it is necessary to define the effects of wheelchair configurations and user fitness on propulsion with a systematic approach. The study results demonstrated that shoulder position and weight distribution had a significant influence on the frictional energy loss and propulsion efforts. However, aerobic capacity and muscle strength had less influence on daily wheelchair maneuver. Clinicians can use our finding, which covers wheelchair designs and human fitness, to select equipment and prescribe exercise to wheelchair users. Manufacturers can also improve their wheelchair design by understanding the importance of shoulder position and weight distribution.

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Environmental niche partitioning of microbial community genomic diversity, gene expression, and metabolism in a marine oxygen minimum zone

2016-11-14 , Ganesh, Sangita

Oxygen Minimum Zones (OMZs) serve as habitats to diverse assemblages of microorganisms that play an important role in mediating global biogeochemical cycles. OMZ microbial communities have not been extensively characterized, and the linkages between microbial community structure, and ecological and biogeochemical processes are still unclear. OMZs act as model systems to study partitioning of microbial niches and biogeochemical transformations owing to their steep vertical gradients of oxygen, nutrient, and redox substrates. This thesis combined genomic tools with environmental measurements of nitrogen transformation rates to characterize how microbial community structure, function and ecological diversity vary at the microscale between free-living (planktonic) and particle-associated microbial communities and over vertical and longitudinal gradients in two of the world’s largest permanent OMZs. The results show an important role for particle-association as a major driver of OMZ microbial community metabolic potential and genome content, and identify wide variation in nitrogen transformation rates in the presence versus absence of particles. These results highlight the dependence of free-living microorganisms on particles for substrates and nutrients, as well as selective partitioning of genes facilitating key steps of an important nitrogen loss pathway, denitrification, in the particle-associated microbial fraction. Finally, this thesis describes the genomic composition and gene expression variation of an important OMZ bacterium, Candidatus Scalindua sp., responsible for anaerobic ammonia oxidation (anammox), the second major nitrogen loss pathway in OMZs. Combining single cell genomics, transcriptome profiling, and rate measurements, this study identifies high metabolic plasticity of OMZ anammox bacteria in different niches along the OMZ redoxcline, including a potential for use of diverse nitrogen substrates to drive anammox. Collectively, these studies enhance our understanding of the environmental determinants of microbial diversity and biochemical activity in low oxygen marine systems.

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Effects of competition, disturbance and productivity on the dynamics of inducible trophic polymorphism in tetrahymena vorax

2016-08-01 , Yin, Yi

Inducible trophic polymorphism enables organisms to alter their trophic level when facing environmental changes, and therefore can ameliorate the intensity of competition. The freshwater ciliated protist Tetrahymena vorax was found to have three distinct phenotypic morphs with two trophic levels. Its carnivorous macrostomes consume intraspecific competitors and its bacterivorous pyriform microstome morph and tailed microstome morph indiscriminately. Cannibalism here indicates an extreme case of niche differentiation and resource utilization via phenotypic plasticity and significantly affects the dynamic equilibrium of T. vorax’s three morphs. By manipulating productivity level, disturbance frequency and the presence or absence of an interspecific competitor species Colpdium striatum, I demonstrated the dynamic transformations of T. vorax’s three morphs and endeavored to explain the underlying mechanisms. In this study, I also tested some classic assumptions about phenotypic tradeoffs in T. vorax and hence clarified some misunderstandings and proposed novel hypotheses.

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Generalizing Disease Associations to Non-Studied Populations

2016-12 , Patel, Kane

This study determines whether risk allele frequencies (RAFs) for common diseases can be generalized in genome wide association surveys (GWAS) that are done in different populations other than the original study population. To test this, the study compares RAFs gathered from the NHRI-EBI GWAS Catalog and 1000 Genomes Project by study population and checks if there is bias towards the study population. If the trend is present, the study looks to answer the question of whether or not this is due to an inherent bias from the study population, or a pre-ascertained bias in the genotyping single nucleotide polymorphism (SNP) chip array. To test bias in the technology, the study compares allele frequencies for disease SNPs and non-disease SNPs on Illumina1M and Affymetrix 6.0 genotyping arrays. If the bias still persists, then there is an inherent bias due to the study population alone. At this point, the study will examine the role of other contributing factors to differences in disease allele frequencies across populations. These include: type of disease, number of participants in the GWAS, whether alleles have a large effect, etc. This study potentially contributes the overall field of population genetics and personalized medicine. Essentially, the goal is to ensure that the information attained can be used to create models that could correct potential bias in GWAS studies.

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Population genomics of human polymorphic transposable elements

2016-11-15 , Rishishwar, Lavanya

Transposable element (TE) activity has had a major impact on the human genome; more than two-thirds of the sequence is derived from TE insertions. Several families of human TEs – primarily Alu, L1 and SVA – continue to actively transpose, thereby generating insertion polymorphisms between individuals. Until very recently, it has not been possible to characterize the genetic variation generated by the activity of these TE families at the scale of whole genomes for multiple individuals within and between human populations. For this reason, the impact of recent TE activity on human evolution has yet to be fully appreciated. My dissertation research leverages novel technologies in data science to investigate the role that recent TE activity has played in shaping human population genetic variation. Specifically, my dissertation addresses three problems: 1) evaluation of the computational techniques used to characterize human polymorphic TE insertion sites from whole genome, next-generation sequence data, 2) characterization of the population genomic variation of human polymorphic TEs and evaluation of their effectiveness as markers of human genetic ancestry and admixture, and 3) analysis of the effects that natural selection (negative and positive) has exerted on human polymorphic TE insertions. I close by presenting a broad prospectus on the implications of genome-scale analyses of human polymorphic TE insertions for population and clinical genetic studies. The results reported in this dissertation represent the dawn of the population genomics era for human TEs.

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Gene expression profiling approach towards enhancement of malaria vaccine development

2016-08-24 , Rojas Pena, Monica Lisseth

Malaria continues to be one of the highest morbidity and mortality infectious diseases in the world, posing an enormous public health burden with significant economic consequences. The development of vaccines that provide sterile protection against pathogenic infection by the Plasmodium parasites that cause malaria is thus a major global public health priority. This dissertation describes three gene expression profiling experiments using RNA sequencing technology (RNASeq) applied to samples collected during clinical trials performed at the CAUCASECO research center in Cali, Colombia. In each case, peripheral blood samples from volunteers and patients enrolled in studies addressing different aspects of immunity against P. vivax malaria were studied, namely the effect of prior exposure, the efficacy of an attenuated parasite vaccine, and resolution of complicated disease. The results presented explore how gene expression profiling of the complex mixture of cells present in whole blood can nevertheless reveal the cellular nature and duration of the immune response to P. vivax infection, while also highlighting subsets of genes that may mediate adaptive immunity. These results demonstrate the potential value of RNASeq for studying the response of the host transcriptome of a malaria infection, and represent a step toward genomic profiling as a component of personalized clinical diagnostics for malaria treatment.

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Catalytic abilities of the Schistosoma mansoni hammerhead ribozyme with mutated substrates in ice

2016-12 , Calvird, Audrey

The synthesis of biomolecules in an environment similar to a pre-biotic Earth within the field of evolutionary chemistry has applications in understanding abiogenesis and the evolution of early biological systems on Earth. The RNA world is a prebiotic environment proposed and subsequently heavily studied in effort to better understand how biochemical reactions started on Earth. This study proposes to assess the catalytic ability of a Hammerhead Ribozyme (HHRz) isolated from the protozoa Schistosoma mansoni (Schist HHRz). It has been previously shown that the Schist HHRz can catalyze the synthesis of extended sequences of ribonucleic acid (RNA) by ligating two RNA substrates in ice, as well as cleave the same substrate back to the original separate substrates in the presence of Mg2+ (Lie et al. 2016). The same study showed that the Schist HHRz is able to catalyze the ligation with mutated substrates (Lie et al. 2016). This study aims to evaluate Schist HHRz’s ability to ligate a mutated substrate in comparison to the wild type substrate in ice, as well as compare the kinetics of the Schist HHRz to cleave the mutated and wild type substrates in the presence of Mg2+. This study will utilize the techniques specified by Lie et al. (2016) to further investigate the extent of the ligation of a mutated substrate catalyzed by the Schist HHRz compared to that of the wild type substrate. This study also assays the kinetics of the cleavage reaction catalyzed by the same Schist HHRz of both the wild type substrate and mutated substrate. This study hopes to improve the understanding of pre-biotic biochemistry in efforts to identify possible mechanisms or models for RNA polymerization by ribozymes on early Earth.

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Bioinformatic tools for testing microbial ecology theory in natural environments through metagenomics

2016-11-14 , Rodriguez Rojas, Luis Miguel

Metagenomics offers unique opportunities to close the gaps that exist between theory and empirical testing in microbial ecology given the windows it can provide into the large fraction of yet-unculturable organisms and species-level resolution. However, realizing the full potential of metagenomics requires the advancement of computational and statistical techniques for data analyses. In the first part of this dissertation I will present a general overview of the current state of quantitative methods for comparative metagenomics and introduce novel algorithms developed for these purposes. Particular emphasis will be placed on the issue of metagenomic coverage, i.e., what fraction of the microbial community was characterized by the sequencing effort, discussing its practical impact on metagenomic analyses and study design, and proposing a novel method for its accurate estimation, Nonpareil (Rodriguez-R and Konstantinidis, Bioinformatics 2014; –, ISME J 2014). Further, the Nonpareil approach can be leveraged for the estimation of extant diversity using a novel metric of sequence diversity, Nd, independent of databases, and with little impact of sequencing effort. In the second part of this dissertation, I will apply the computational and statistical toolbox described above to the characterization of community assembly processes in natural environments. First, I will describe the post-disturbance successional patterns following the deposition of large amounts of hydrocarbons in the shoreline of Florida following the 2010 Macondo Oil Spill in the Gulf of Mexico. We demonstrated that this secondary succession had only minor lasting effects in community composition post-recovery, and was mainly driven by hydrocarbon degradation and nutrient scavenging metabolic potentials in concert with the degree of specialization of community members (Rodriguez-R et al., ISME 2015). I will discuss these results as evidence in support of the specialization-disturbance ecologic hypothesis. Finally, I’ll describe variations within the meta-community of a freshwater interconnected system without recent major documented disturbances composed of five lakes and two estuarine locations along the Chattahoochee River (Southeast USA) monitored for a span of six years. Our results revealed strong seasonal patterns together with significant distance decay and minor landscape effects, indicating that both historic and contemporary factors shape the community assembly within this system in similar proportions. I will discuss these results in the framework of classic (macro-organismal) biogeographic theory, and illustrate in which ways they contradict the contemporary view of the now classic Baas-Becking dictum: “everything is everywhere, and the environment selects”.

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The interactive effects of environmental warming and habitat fragmentation on the structure of experimental protist communities

2016-08-01 , Tsai, Meng-Hsiu

Global biodiversity is threatened by substantial and increasing human activity, such as human-induced environmental warming and habitat fragmentation. The effects of warming and fragmentation on biodiversity have been carefully studied, yet their potential interactive effects are less understood. Using freshwater protist communities subject to warming and fragmentation, I present the first experimental evidence of the interactive effects of warming and fragmentation on biodiversity. Somewhat unexpectedly, I found that fragmentation positively affected biodiversity. The magnitude of the effects of fragmentation, however, varied with the warming treatments. In one of our experimental communities (Combination B), fragmentation showed a much stronger positive effect on protist richness when warming was not conducted, but it showed a weaker but significant positive effect under a warming scenario. In other communities (from Combination C), however, fragmentation showed a stronger positive effect on richness when warming was present than when it was absent in experimental treatments. I further show that these long-term effects may be due to the alternation of individual species growth rate affected by warming, fragmentation and their interaction in short-term projections. Moreover, these findings of positive effects of fragmentation and interactions with warming can be useful for understanding conservation strategies, especially in areas where biodiversity is currently threatened or will be in the future.

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