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Discovery, Phylogenetic Analysis, and Functional Characterization of a Unique Family of Eukaryotic Translation Initiation Factor 4E, eIF4E, From Amphidinium carterae, a Marine DinoflagellateJones, Grant D. 09 June 2016 (has links)
<p> This study investigates the eIF4E family members in Dinoflagellates. Dinoflagellates are eukaryotic algae with large genomes and a minimal role for transcriptional regulation. All mRNA in dinoflagellates is <i>trans </i>-spliced with a 22-nucleotide 5'-spliced-leader sequence bearing a multi-methylated cap. Like other eukaryotes, dinoflagellates encode multiple eIF4E family members that are anticipated to fulfill a range of functions. Three distinct and novel clades of eIF4E have been recognized in dinoflagellates that are separate from the three metazoan classes of eIF4E. The dinoflagellate <i> Amphidinium carterae</i> encodes eight eIF4E family members while <i> Karlodinium veneficum</i> encodes fifteen eIF4E family members. I assayed six of these family members from <i>A. carterae</i> for expression levels, m<sup>7</sup>GTP binding, yeast knockout complementation and affinity for three mRNA cap analogs using surface plasmon resonance (SPR). Transcripts of each are expressed through a diel cycle, but only eIF4E-1 family members and eIF4E-2a are expressed at the level of protein. Recombinant eIF4E-1 family members and eIF4E-3a, but not eIF4E-2a, are able to bind to m<sup> 7</sup>GTP-agarose beads. Of the clade 1 eIF4Es, only eIF4E-1a and -1d1 complement a S. cerevisiae strain conditionally deficient in functional eIF4E, consistent with their function as translation initiation factors. However, only eIF4E-1a can be recovered from <i>A. carterae</i> extracts by m<sup>7</sup>GTP affinity binding. Using SPR analysis, the affinity of <i>A. carterae</i> eIF4E-1a for m<sup>7</sup>GTP is lower than that of murine eIF4E-1A. By the same analysis, <i>A. carterae</i> eIF4E-1a has a higher affinity for m<sup>7</sup>GpppG than m<sup>7</sup>GTP. In addition, <i>K. veneficum</i> eIF4E-1a1 displays many of the same characteristics as <i>A. carterae</i> eIF4E-1a. Four eIF4E-1 and one eIF4E-2 family members from <i>K. veneficum</i> were characterized for m<sup>7</sup>GTP binding capacity, only the eIF4E-1 family members can be pulled down with m<sup>7</sup>GTP. Three eIF4E family members were tested for their ability to interact with a putative eIF4E-interacting protein, although none interacted. Overall, the eIF4E-1a sub-clade emerges with characteristics consistent with the role of a prototypical translation initiation factor. These initial analyses will allow for a better understanding of specific translational control of gene expression through mRNA recruitment in the unique dinoflagellate lineage.</p>
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Transcriptome Analysis of Vaccine Responses to Francisella Tularensis or Venezuelan Equine Encephalitis VirusErwin-Cohen, Rebecca A. 21 December 2016 (has links)
<p>The lack of vaccines for emerging and re-emerging diseases highlights technical gaps and indicates a need for innovative approaches to produce new vaccines. Vaccines may be improved by knowledge of host responses to vaccination, disease pathogenesis, and the effect of age and genetics on vaccine outcome. This study?s purpose was to quantitatively assess the molecular epidemiology of Francisella tularensis (Ft) and Venezuelan Equine Encephalitis Virus (VEEV). Study results support the Epidemiology Nexus model which holds that association of changes in gene expression to vaccination facilitate understanding the mechanisms of immune development and link public health and disease epidemiology. My research questions assessed the relationship between gene expression following vaccination, the relationship between age and vaccine response, and the association between Human Leukocyte Antigen (HLA) allele and vaccine response. The study was a novel secondary analysis of human data subjected to ANOVA to measure association between treatment and outcome, correlation to measure association of age with vaccine outcome, and Mann-Whitney U tests to measure association of HLA allele with vaccine outcome. Both Ft and VEEV vaccination elicited significant changes in gene expression. A highly positive relationship between age and vaccine outcome was shown for VEEV. The results may affect positive social change by contributing to a growing compendium of evidence of vaccine efficacy mechanisms that may function to assure the public of vaccine safety, combat vaccine hesitancy, and promote vaccine acceptance, as well as contribute mechanistic knowledge to reduce developmental costs of novel vaccines.
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The Efficacy of Maternity Waiting Homes in Decreasing Maternal and Perinatal Mortality in Low-Income Countries – A Systematic ReviewEkunwe, Akua Boatemaa 23 May 2017 (has links)
A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Maternal and perinatal mortality remains significantly high in low‐income countries with over 800 deaths per day of women around childbirth. Greater than 90% of such deaths occur in low‐income countries. The concept of maternity waiting homes (MWH) was reintroduced to aid in decreasing maternal and perinatal mortality. Since the previous Cochrane Review in 2012 on maternity waiting homes, there have not been any published randomized controlled studies. Do observational studies on MWHs demonstrate decreased maternal and perinatal mortality in low‐income countries when compared with the standard of care? We searched for primary articles that reported maternal and perinatal deaths as major outcomes in studies who compared MWHs to other methods such as direct hospital admits, we also investigated cesarean delivery rates. Search engines used were: Cochrane Review, Medline and CINAHL. Meta‐analyses and forests plots were formulated using MedCalc Software. Systematic review was drafted using MOOSE guidelines for meta‐analysis and systematic reviews of observation. Seven articles met criteria for this study. The maternal mortality rate for MWH was 105/100,000 and 1,066/100,000 for non‐MWH, Relative Risk (RR) 0.145 (95% Confidence Interval (CI) 0.062 to 0.204). Perinatal mortality rate was 60/1,000 in MWH compared to 65/1,000, RR 0.782 (CI 0.602 to 1.120) in non‐MWH. Stillbirth rate was 18/1,000 in MWH and 184/1,000 in non‐MWH, RR 0.204 (CI 63.88 to 94.08). Neonatal mortality rates were 16/1,000 in MWH and 15/1,000 in non‐MWH, RR 0.862 (CI 0.392 to 1.628). Cesarean deliveries rate was 24/100 for MWH and 18/100 in non‐MWH, RR 1.229 (CI 1.226‐1.555). MHWs statistically decreased maternal death, stillbirths and increased cesarean delivery rates. Overall, the observation nature of the study designs introduces selection biases that may have altered the results of the studies. No randomized trials have been done to date. We suggest cluster‐randomized studies to further evaluate the effect of MWHs.
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Marijuana Smoking and the Risk of Developing COPD, Lung Cancer, And/or Chronic Respiratory Symptoms: A Systematic ReviewByers, Chris 01 June 2017 (has links)
A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / The aim of this study is to conduct a systematic review of the existing evidence on marijuana use and its association, or the absence of an association, with an increased risk of developing chronic obstructive pulmonary disease (COPD), lung cancer, and/or chronic respiratory symptoms. We hypothesize that a systematic review will not demonstrate sufficient evidence to determine that marijuana use increases the risk of developing COPD, lung cancer, and/or chronic respiratory symptoms. The term “chronic respiratory symptoms” encompasses the following: cough, sputum production, wheeze, shortness of breath, acute bronchitis, and chest tightness. The following databases were searched for the topics of marijuana smoking, COPD, lung cancer, and chronic respiratory symptoms: MEDLINE (PubMed/OvidSP), the Cochrane Controlled Trials Register, the Cochrane Database of Systematic Reviews, PsycINFO, the Database of Abstracts of Reviews of Effects, and Google Scholar. The search ended September 7th, 2016. Studies were initially limited only by the requirement that they were based upon human research and published in English. Studies were included if they were systematic reviews, randomized controlled trials (RCTs), prospective or retrospective cohort studies, case control studies, or cross‐sectional studies. A total of 739 articles were screened for eligibility, 17 unique studies met the inclusion criteria and underwent qualitative analysis1‐17. The quality of systematic reviews was evaluated using the AMSTAR criteria18; cohort, case‐control, and cross sectional studies were evaluated based upon the Newcastle‐Ottawa Quality Assessment Scale (NOS) 19. No RCTs were identified. The overall quality of the evidence for each outcome was determined by utilizing the GRADE methodology20‐21. Studies were primarily assessed by a single reviewer, with random validation of assessments on a limited number of studies by a second reviewer. Overall, there is very low quality evidence that assesses for an association between marijuana smoking and an increased risk of developing lung cancer, COPD, and/or chronic respiratory symptoms. There was no conclusive finding for lung cancer and COPD. However, seven of eight studies concluded that there was an association between marijuana use and chronic respiratory symptoms. The totality of evidence describing any associations between marijuana smoking and the risk of developing lung cancer, COPD, and/or chronic respiratory symptoms is not strong enough to confidently state that marijuana use is associated with any of these chronic pulmonary conditions. Of all the evidence examined in this systematic review, the most convincing appears to be that relating to a potential positive association between marijuana smoking and the risk of developing chronic respiratory symptoms. Unfortunately, the overall quality of evidence was very low due to significant methodological weaknesses within the studies. Thus, there is insufficient evidence in the current literature to make a definitive statement regarding this possible association.
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New Observations and Phylogeny of the Entomopathogenic Fungus Desmidiospora myrmecophilaSaltamachia, Stephen J. 12 April 2019 (has links)
<p> The genus <i>Ophiocordyceps</i> contains the most diverse assemblage of fungi attacking ants worldwide and are remarkably well adapted to the specific ecologies of their hosts. <i>Desmidiospora myrmecophila</i> is closely related to ant-pathogenic species within <i>Ophiocordyceps</i>, possibly specific to queens, but the sheer infrequency of encounters and previously unsuccessful attempts to culture this fungus has precluded any meaningful assessment until now. A new record of <i>Desmidiospora myrmecophila</i> from Louisiana was found infecting a foundress <i>Camponotus pennsylvanicus </i> queen, the same host species favored by the more common and ubiquitous ant-pathogenic <i>Ophiocordyceps</i> unilateralis found in the same geographic locality. To evaluate a long-held assumption that these fungi represent synanamorphs of a single species, we sampled our Desmidiospora specimen along with the local <i>O. unilateralis</i> population for molecular comparison. We are able to present for the first time the <i>in vitro </i> characteristics and morphology of <i>Desmidiospora myrmecophila</i> as well as a phylogenetic context for this fungus based on combined molecular analysis of representative members of the Ophiocordycipitaceae. Our results place the <i>Desmidiospora myrmecophila</i> lineage within the genus <i>Ophiocordyceps</i> but with a basal affiliation to the ant-pathogen clade. These results further implicate <i>Desmidiospora myrmecophila</i> as an important and quintessential example of cryptic diversity among an already taxonomically diverse and ecologically important group of fungi.</p><p>
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Methods for Exploring Heterogeneity in Systematic Reviews of Randomized Controlled TrialsGagnier, Joel 12 August 2010 (has links)
This thesis consisted of three major components: 1. A sample of randomized controlled trials of herbal medicines was collected and assessed with a recently developed extension of the CONSORT statement for herbal medicine trials. 2. A methodological review of proposed methods of assessing clinical heterogeneity in meta-analyses of randomized controlled trials, 3. The application of permutation based resampling in meta-regression
of multiple covariates. An analysis of 406 RCTs of herbal medicine interventions
revealed that these trials are regularly under reporting important aspects of the
intervention. Next, the second project showed that there are many resources providing suggestions for investigating clinical heterogeneity in systematic reviews of controlled clinical trials and though there is minimal consensus some recommendations are common across sources. Finally, the third project found that permutation tests result in more
conservative, larger, p-values potentially reducing the rate of false positive findings when exploring multiple covariates.
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Methods for Exploring Heterogeneity in Systematic Reviews of Randomized Controlled TrialsGagnier, Joel 12 August 2010 (has links)
This thesis consisted of three major components: 1. A sample of randomized controlled trials of herbal medicines was collected and assessed with a recently developed extension of the CONSORT statement for herbal medicine trials. 2. A methodological review of proposed methods of assessing clinical heterogeneity in meta-analyses of randomized controlled trials, 3. The application of permutation based resampling in meta-regression
of multiple covariates. An analysis of 406 RCTs of herbal medicine interventions
revealed that these trials are regularly under reporting important aspects of the
intervention. Next, the second project showed that there are many resources providing suggestions for investigating clinical heterogeneity in systematic reviews of controlled clinical trials and though there is minimal consensus some recommendations are common across sources. Finally, the third project found that permutation tests result in more
conservative, larger, p-values potentially reducing the rate of false positive findings when exploring multiple covariates.
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Pradinės matematikos užduočių sistematika ir uždavinių sprendimo optimizavimas 3-4 klasėse / The Systematic and Optimization of Exercises Solution Of Primary Mathematics Exercises in 3-4 ClassesMedeikis, Algirdas 05 June 2006 (has links)
The purpose of my job “The Systematic and Optimization of Exercises Solution Of Primary Mathematics Exercises in 3-4 Classes” was to overlook newly and to value mathematic exercises, which was given in mathematic textbooks. To reach this purpose, I chose and analyzed B. Balchychio, A. Kiseliovo ir D. Kiseliovos bei D. Shalnienes ir L. Hoshteterienės mathematic textbooks of 3-4 classes. I made three problems for this job: to detect peculiarities of mathematics exercises systematic; to analyze mathematic textbooks of different authors of 3-4 classes; to analyze derivation ways of 3-4 mathematic exercises in different ways. When I was writing my job I used these methods: the analyze of different literature derivations, questionnaire poll, the analyze of mathematic textbooks and mathematic statistics.
I ascertained which exercises authors render a lot in their textbooks, which sort is textual and geometric exercises, which are most arithmetic operations. I made the questionnaire poll of nine exercises of chosen textbooks too, I gave three geometric, three arithmetic and three textual exercises in this questionnaire poll. There was chosen one by one from all kinds of exercises from different textbooks. The poll was given to pupils of 4 classes on purpose to see are the pupils able to solve exercises of different authors, do the authors give not difficult or not easy exercises. In this investigation pupils were from 12 schools: main school of Pryshmanchiai, secondary school of... [to full text]
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The evolution of carotenoid coloration and pigmentation in the New World blackbirdsFriedman, Nicholas R. 18 July 2013 (has links)
<p> Plumage color evolution in birds has been the focus of theoretical and empirical research on sexual selection since Darwin. Many of the yellow, orange, and red hues seen in bird plumage are the result of carotenoid pigmentation. While a great number of recent studies have examined the functions of carotenoid-based plumage coloration in a single species, few have examined the evolutionary history of this trait in a comparative phylogenetic context. Using the New World blackbirds as a model clade, I focus on two questions that a comparative phylogenetic approach can uniquely address. First, what is the history of evolutionary change in carotenoid color that led to the colors seen in extant blackbird taxa? Second, by what proximate mechanisms have carotenoid pigments evolved? In Chapter 1, I present an ancestral state reconstruction of carotenoid-based plumage coloration across the Icterid phylogeny, based on reflectance measurements of museum skins. My results show robust evidence that red coloration was gained repeatedly from a yellow common ancestor. In Chapter 2, I used pigment biochemistry of meadowlark (<i>Sturnella</i>) and Cacique (<i>Cacicus</i>) feathers to test whether independent gains of red coloration are the result of parallel or convergent metabolic mechanisms. Meadowlarks have evolved red coloration using a different set of carotenoids than caciques, but the caciques have evolved the same set of carotenoids twice. This suggests that red coloration evolved by convergent evolution among different blackbird clades, but evolved by parallel evolution within the caciques. Lastly, in Chapter 3 I examine the relationship between color and carotenoid pigmentation in orioles, a blackbird clade in which orange has been gained at least twice independently from a yellow common ancestor. I found red-producing keto-carotenoids only in orange species and never in yellow species. This result is a striking contrast to our expectation for a continuous gradient of a carotenoid pigment concentration. These results suggest that repeated gains of C4-oxygenation ability best explain evolutionary changes in orange coloration in orioles. To summarize, I showed using phylogenetic comparative methods that blackbirds have repeatedly evolved towards redder carotenoid coloration. Using HPLC biochemistry, I showed that each of these gains of orange and red coloration is likely the result of a gain of C4-oxygenation ability. The prevalence of gains of orange and red coloration suggests that there may be a directional bias towards evolving longer-wavelength carotenoid plumage. The research presented in these chapters provides the phylogenetic framework necessary for future studies to examine the functional causes underlying the repeated evolution of carotenoid-based coloration.</p>
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Taxonomia e distribuição das lagostas (Crustacea: Decapoda: Achelata e Polychelida) no Oceano AtlânticoDall'Occo, Paola Lupianhes [UNESP] 09 June 2010 (has links) (PDF)
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dallocco_pl_dr_rcla.pdf: 5863771 bytes, checksum: 49ba9f956f11d73624a21071be6a09c2 (MD5) / Universidade Estadual Paulista (UNESP) / O presente estudo aborda aspectos sistemáticos e biogeográficos das lagostas pertencentes as infraordens Achelata Scholtz & Richter, 1995 e Polychelida De Haan, 1841 que ocorrem no Oceano Atlântico. Constituindo um relevante recurso ecológico, comercial e científico, são encontradas em uma grande variedade de habitats e profundidades desde a região intertidal até a região abissal, ultrapassando os 5000m. De acordo com os dados obtidos através da literatura e da análise de exemplares provenientes de coleções carcinológicas nacionais e internacionais a fauna de lagostas (Achelata e Polychelida) do Oceano Atlântico é composta por 50 espécies, distribuídas em 3 famílias, 3 subfamílias e 18 gêneros. Para os táxons são fornecidas diagnoses e chaves de identificação, sendo que o tratamento formal de cada espécie inclui sinonímia, tipo(s), localidade-tipo, descrição, tamanho, coloração, hábitat, distribuição geográfica, observações, mapa de distribuição e ilustrações. O estudo biogeográfico realizado caracteriza e discute os padrões distribucionais encontrados, juntamente, com os fatores abióticos que influenciam na distribuição das espécies. São ainda analisados os graus de valência ecológica das espécies em relação aos tipos de substratos ocupados e gradientes batimétricos / This study addresses aspects of the systematics and biogeography of lobsters belonging to the infraorders Achelata Scholtz & Richter, 1995 and Polychelida De Haan, 1841 that occur in the Atlantic Ocean. Constituting an important ecological, commercial, and scientific resource, these lobsters are found in a wide variety of habitats and depths from the intertidal zone to the abyssal zone below 5000 m. According to published information and the analysis of specimens from carcinological collections within and outside Brazil, the lobster fauna (Achelata and Polychelida) in the Atlantic Ocean is composed of 50 species, belonging to 3 families, 3 subfamilies, and 18 genera. For the taxa, diagnoses and identification keys are provided. The formal treatment of each species includes the synonymy, type(s), type-locality, description, size, coloration, habitat, geographical distribution, notes, distribution map, and illustrations. The biogeographical study conducted characterizes and discusses the distributional patterns, along with the abiotic factors that influence the distributions of the species. The degrees of ecological valence of the species in relation to the types of substrates occupied and the bathymetric gradients are also analyzed
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