Dissertations / Theses on the topic 'Model organisms'

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1

Ziehm, Matthias Fritz. "Computational biology of longevity in model organisms." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648888.

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McCarthy, Linda Catherine. "New approaches to genome mapping in model organisms." Thesis, University College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283335.

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Atreya, Ravi Viswanathan. "Drug target prediction in pancreatic cancer using model organisms." Thesis, The University of Arizona, 2009. http://hdl.handle.net/10150/192261.

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Vargas, José Danilo. "Model organisms and human disease : from kyphoscoliosis to neurodegeneration." Thesis, University of Oxford, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275381.

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5

Treitz, Christian [Verfasser]. "Mass Spectrometry based Bioanalytics on Model Organisms / Christian Treitz." Kiel : Universitätsbibliothek Kiel, 2018. http://d-nb.info/1154434133/34.

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6

Nabhan, Ahmed Ragab. "Graph Pattern Mining Techniques to Identify Potential Model Organisms." ScholarWorks @ UVM, 2014. http://scholarworks.uvm.edu/graddis/4.

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Recent advances in high throughput technologies have led to an increasing amount of rich and diverse biological data and related literature. Model organisms are classically selected as subjects for studying human disease based on their genotypic and phenotypic features. A significant problem with model organism identification is the determination of characteristic features related to biological processes that can provide insights into the mechanisms underlying diseases. These insights could have a positive impact on the diagnosis and management of diseases and the development of therapeutic drugs. The increased availability of biological data presents an opportunity to develop data mining methods that can address these challenges and help scientists formulate and test data-driven hypotheses. In this dissertation, data mining methods were developed to provide a quantitative approach for the identification of potential model organisms based on underlying features that may be correlated with disease manifestation in humans. The work encompassed three major types of contributions that aimed to address challenges related to inferring information from biological data available from a range of sources. First, new statistical models and algorithms for graph pattern mining were developed and tested on diverse genres of data (biological networks, drug chemical compounds, and text documents). Second, data mining techniques were developed and shown to identify characteristic disease patterns (disease fingerprints), predict potentially new genetic pathways, and facilitate the assessment of organisms as potential disease models. Third, a methodology was developed that combined the application of graph-based models with information derived from natural language processing methods to identify statistically significant patterns in biomedical text. Together, the approaches developed for this dissertation show promise for summarizing the information about biological processes and phenomena associated with organisms broadly and for the potential assessment of their suitability to study human diseases.
7

Cookson, Natalie Anne. "Single cell growth and gene expression dynamics in model organisms." Diss., [La Jolla] : University of California, San Diego, 2009. http://wwwlib.umi.com/cr/ucsd/fullcit?p3387196.

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Thesis (Ph. D.)--University of California, San Diego, 2009.
Title from first page of PDF file (viewed February 12, 2010). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 104-114).
8

Konieczka, Jay, Kevin Drew, Alex Pine, Kevin Belasco, Sean Davey, Tatiana Yatskievych, Richard Bonneau, and Parker Antin. "BioNetBuilder2.0: bringing systems biology to chicken and other model organisms." BioMed Central, 2009. http://hdl.handle.net/10150/610006.

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BACKGROUND:Systems Biology research tools, such as Cytoscape, have greatly extended the reach of genomic research. By providing platforms to integrate data with molecular interaction networks, researchers can more rapidly begin interpretation of large data sets collected for a system of interest. BioNetBuilder is an open-source client-server Cytoscape plugin that automatically integrates molecular interactions from all major public interaction databases and serves them directly to the user's Cytoscape environment. Until recently however, chicken and other eukaryotic model systems had little interaction data available.RESULTS:Version 2.0 of BioNetBuilder includes a redesigned synonyms resolution engine that enables transfer and integration of interactions across species
this engine translates between alternate gene names as well as between orthologs in multiple species. Additionally, BioNetBuilder is now implemented to be part of the Gaggle, thereby allowing seamless communication of interaction data to any software implementing the widely used Gaggle software. Using BioNetBuilder, we constructed a chicken interactome possessing 72,000 interactions among 8,140 genes directly in the Cytoscape environment. In this paper, we present a tutorial on how to do so and analysis of a specific use case.CONCLUSION:BioNetBuilder 2.0 provides numerous user-friendly systems biology tools that were otherwise inaccessible to researchers in chicken genomics, as well as other model systems. We provide a detailed tutorial spanning all required steps in the analysis. BioNetBuilder 2.0, the tools for maintaining its data bases, standard operating procedures for creating local copies of its back-end data bases, as well as all of the Gaggle and Cytoscape codes required, are open-source and freely available at http://err.bio.nyu.edu/cytoscape/bionetbuilder/ webcite.
9

Simmonds, Michael Patrick. "The stress field in a suspension of swimming model micro-organisms." Thesis, University of Cambridge, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.615714.

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10

Wagih, Omar. "Elucidating the mechanistic impact of single nucleotide variants in model organisms." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/271713.

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Understanding how genetic variation propagate to differences in phenotypes in individuals is an ongoing challenge in genetics. Genome-wide association studies have allowed for the identification of many trait-associated genomic loci. However, they are limited in their inability to explain the altered cellular mechanism. Genetic variation can drive disease by altering a range of mechanisms, including signalling networks, TF binding, and protein folding. Understanding the impact of variants on such processes has key implications in therapeutics, drug development, and more. This thesis aims to utilise computational predictors to shed light on how cellular mechanisms are altered in the context of genetic variation and better understand how they drive both molecular and organism-level phenotypes. Many binding events in the cell are mediated by short stretches of sequence motifs. The ability to discover these underlying rules of binding could greatly aid our understanding of variant impact. Kinase–substrate phosphorylation is one of the most prominent post-translational modifications (PTMs) which is mediated by such motifs. We first describe a computational method which utilises interaction and phosphorylation data to predict sequence preferences of kinases. Our method was applied to 57% of human kinases capturing known well-characterised and novel kinase specificities. We experimentally validate four understudied kinases to show that predicted models closely resemble true specificities. We further demonstrate that this method can be applied to different organisms and can be used for other phospho-recognition domains. The described approach allows for an extended repertoire of sequence specificities to be generated, particularly in organisms for which little data is available. TF-DNA binding is another mechanism driven by sequence motifs, which is key for the tight regulation of gene expression and can be greatly altered by genetic variation. We have comprehensively benchmarked current methods used to predict non-coding variant effects on TF-DNA binding by employing over 20,000 compiled allele-specific ChIP-seq variants across 94 TFs. We show that machine learning-based approaches significantly outperform more rudimentary methods such as the position weight matrix. We further note that models for many TFs with distinct binding specificities were unable to accurately assess the impact of variants. For these TFs, we explore alternative mechanisms underlying TF-binding, such as methylation, co-operative binding, and DNA shape that drive poor performance. Our results demonstrate the complexity of predicting non-coding variant effects and the importance of incorporating alternative mechanisms into models. Finally, we describe a comprehensive effort to compile and benchmark state-of-the-art sequence and structure-based predictors of mutational consequences and predict the effect of coding and non-coding variants in the reference genomes of human, yeast, and E. coli. Predicted mechanisms include the impact on protein stability, interaction interfaces, and PTMs. These variant effects are provided through mutfunc, a fast and intuitive web tool by which users can interactively explore pre-computed mechanistic variant impact predictions. We validate computed predictions by analysing known pathogenic disease variants and provide mechanistic hypotheses for causal variants of unknown function. We further use our predictions to devise gene-level functionality scores in human and yeast individuals, which we then used to perform gene-phenotype associations and uncover novel gene-phenotype associations.
11

Brandt, Annely [Verfasser]. "Insects as model organisms for basic and applied research / Annely Brandt." Gießen : Universitätsbibliothek, 2021. http://d-nb.info/1237274192/34.

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12

Banks, Russell K. "Annotation Tools for Multivariate Gene Set Testing of Non-Model Organisms." DigitalCommons@USU, 2015. https://digitalcommons.usu.edu/etd/4515.

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Many researchers across a wide range of disciplines have turned to gene expression anal- ysis to aid in predicting and understanding biological outcomes and mechanisms. Because genes are known to work in a dependent manner, it’s common for researchers to first group genes in biologically meaningful sets and then test each gene set for differential expression. Comparisons are made across different treatment/condition groups. The meta-analytic method for testing differential activity of gene sets, termed multi-variate gene set testing (mvGST), will be used to provide context for two persistent and problematic issues in gene set testing. These are: 1) gathering organism specific annotation for non-model organisms and 2) handling gene annotation ambiguities. The primary purpose of this thesis is to explore different gene annotation gathering methods in the building of gene set lists and to address the problem of gene annotation ambiguity. Using an example study, three different annotation gathering methods are proposed to construct GO gene set lists. These lists are directly compared, as are the subsequent results from mvGST analysis. In a separate study, an optimization algorithm is proposed as a solution for handling gene annotation ambiguities.
13

Ashwell, Susan. "Mode of action of vitamin B←1←2 : model studies." Thesis, University of Newcastle Upon Tyne, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.329271.

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14

Clark, Francis. "A computational study of gene structure and splicing in model eukaryote organisms /." St. Lucia, Qld, 2003. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe17395.pdf.

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15

Korsisaari, Nina. "Functional analysis of Cdk7-interacting proteins Mat1 and Hint in model organisms." Helsinki : University of Helsinki, 2002. http://ethesis.helsinki.fi/julkaisut/mat/bioti/vk/korsisaari/.

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16

Chen, Jing Andy. "Label Free Chemical Imaging Reveals Novel Metabolic Signatures in Living Model Organisms." Thesis, Purdue University, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10846167.

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Cell and molecular biology often need direct monitoring of the dynamic distribution and interactions of metabolites in living cells and model organisms. However, this task is extremely challenging for a few reasons. Labeling metabolites with markers can potentially interrupt the dynamic cellular events that are aimed to be observed. Moreover, labeling dyes are usually toxic to cells. Lastly, many labeling methods require cell fixation thus cannot be used to study cellular dynamics. Label-free chemical imaging methods such as stimulated Raman scattering (SRS) circumvent these problems by generating signals based on the intrinsic optical property of target biological metabolites. As a result, label-free chemical imaging methods provide huge potential to make new biological discoveries which are not possible with traditional imaging technologies.

This Ph.D. thesis work focuses on applying two label-free chemical imaging methods—SRS and TA microscopy—to studying dynamics of metabolites. In detail, the dynamic distribution of retinoids in C. elegans was studied using SRS microscopy, and it was found that retinoids help C. elegans survive high glucose stress. In the second part of this thesis work, TA microscopy was introduced to image heme, a metabolite invisible to biologists for decades. The dynamic distribution and trafficking of heme was revealed in C. elegans model. In the last part of this thesis work, TA microscopy was expanded to monitoring the growth of hemozoin crystal in malaria parasite at different stages of infection, demonstrating TA microscopy as a powerful tool for studying hemozoin metabolism and anti-malaria drug screening.

17

Paton, Leigh Catherine. "Analysis of novel pathways in neurodegeneration using mouse and fly model organisms." Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:43e6bcfb-47d2-44b2-a10b-81d135ceb824.

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The aim of this project was to understand the molecular mechanisms underlying movement disorders and to identify new genes involved in neurodegeneration. By genetic crossing two mutations identified in the Shakin' Stevens mouse, were separated into individual mouse strains. Both have provided important new insights into two pathways characteristic of neurodegeneration: The autophagy-lysosome pathway, a protein degradation pathway in the Nymphe mouse (nym/nym), and lipid metabolism defects in the Jabber mouse (jab/+). The nym homozygous mouse was identified as a novel mouse model of the lysosomal storage disorder mucolipidosis II (MLII) homozygous for a patient mutation in the GNPTAB gene. The novel mouse model of MLII more fully recapitulates the human pathology than the previously described Gnptab knock-out mouse. Histological analysis of the brain revealed for the first time progressive neurodegeneration in the cerebellum with severe Purkinje cell loss. In addition, based on similar features between Niemann-Pick type C disease and MLII, the nym homozygous mice were treated with 2-hydroxypropyl-β-cyclodextrin, a drug previously reported to rescue Purkinje cell death in a mouse model of NPC disease. No improvement in brain pathology was observed, demonstrating that cerebellar degeneration is not primarily triggered by loss of Npc2 function. The jab mouse model, harbouring a mutation in the small GTPase Arl1, was characterised as a novel model of chylomicron retention disease, a lipoprotein deficiency, and offered the opportunity to study a novel gene involved in the maintenance of lipid homeostasis and neurodegeneration, specifically demyelination in the peripheral nervous system. The jab mutation in Drosophila presented with characteristic features of the jab mouse, highlighting the functional conservation of Arl1 and validated the use of Drosophila for further studies. Interestingly, together with constitutively active and inactive mutants, pathology in lipid droplet formation and defective insulin signalling was associated with defective Arl1 function. Using Drosophila will enable further studies into Arl1's role in tissue specific function and help elucidate molecular pathway leading to demyelination. Thus, this work has highlighted the value of a phenotype-driven approach to investigate novel neurodegenerative pathways and their amenability to therapy.
18

Dieris, Milan [Verfasser], Sigrun [Gutachter] Korsching, and Peter [Gutachter] Kloppenburg. "Amine detection in aquatic organisms: receptor evolution, neuronal circuits and behavior in the model organism zebrafish / Milan Dieris ; Gutachter: Sigrun Korsching, Peter Kloppenburg." Köln : Universitäts- und Stadtbibliothek Köln, 2017. http://d-nb.info/1171422636/34.

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19

Scourfield, Melanie A. "An investigation into the structure and function on model dental plaque communities using a laboratory film fermenter." Thesis, Cardiff University, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337309.

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20

Kuhring, Mathias [Verfasser]. "Computational Methods for Omics Sequence Data with Focus on Non-Model Organisms / Mathias Kuhring." Berlin : Freie Universität Berlin, 2019. http://d-nb.info/1190645181/34.

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21

Khan, Hamza. "De novo annotation of non-model organisms using whole genome and transcriptome shotgun sequencing." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/60152.

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Townsell, Leslie C. "Exploring the effect of sexual recombination on Nascent Multicellular organisms." DigitalCommons@Robert W. Woodruff Library, Atlanta University Center, 2016. http://digitalcommons.auctr.edu/dissertations/3333.

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The transition to multicellularity is a major step in the evolution of complex life. The first steps in this transition are poorly understood because multicellularity evolved long ago, and transitional forms have been lost to extinction. Previous studies developed a novel microbial model system in which simple multicellularity could be evolved de novo (Ratcliff et al., 2012). By evolving our snowflake yeast to undergo sexual reproduction we hypothesized that sex created variation in key multicellular traits, which spurs multicellular adaptation. In our 'snowflake yeast' model system, two traits are of central importance: cluster size, and programmed cell death (apoptosis). Apoptosis previously evolved to regulate cluster size, by acting as break points within clusters, allowing them to modify the size and number of multicellular propagules they produce. In prior experiments, this only develops after yeast have evolved to form large clusters. Prior experiments in the lab demonstrated that the longer snowflake yeast have been evolving, the greater the fitness benefit provided by sex. Here we examine whether this is due to sex creating greater amounts of diversity in the traits of post-sex offspring in more highly evolved multicellular yeast, allowing post-recombination offspring to 'fine tune' their multicellular traits. By using flow cytometry, we collected data on our multicellular traits. By gathering the biomass mean of the cluster size in each population and staining the cells with propidium iodide to determine the apoptotic tendencies of our cells we were able to compare our outcomes to the pre-sex ancestor, and we determined there was no increase in variation. Although apoptosis did not have an increase in variation due to sex, it created a variation in cluster size; the variation was seen in the population W8. This still supports our hypothesis that sex creates variation in multicellular traits, which allows for rapid adaptation.
23

Jonsson, Micael. "Investigations of species richness effects on ecosystem functioning using stream-living macroinvertebrates as model organisms." Doctoral thesis, Umeå : Univ, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-164.

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Pavlaki, Maria. "Bottom-up contamination in marine systems: model trophic levels to predict cadmium flow in marine organisms." Doctoral thesis, Universidade de Aveiro, 2016. http://hdl.handle.net/10773/16846.

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Doutoramento em Biologia
Cadmium is considered one of the most toxic metals to aquatic organisms. This naturally occurring metal is found in the environment in low concentrations due to natural processes, such as volcanic eruptions, natural crust erosion and also anthropogenic activities, such as mining and smelting. As a by-product of zinc mining, cadmium can reach aquatic environment through leaching or to rainwater runoff from the mine areas. It is a non-essential metal for organisms that even at relatively low concentrations can be toxic and may cause adverse effects due to its high bioaccumulation tendency. Considering this, the objective of this work was to study the toxicity and bioaccumulation potential of cadmium within different model marine trophic levels. To achieve this goal, this work was divided into four studies: i) assess the eco- and genotoxicity of cadmium to three marine test-species, representing different marine trophic levels, ii) determine the bioconcentration potential of cadmium in the calanoid copepod Acartia tonsa under different environmental conditions, such as pH, salinity and temperature, iii) evaluate the uptake and depuration kinetics of cadmium by the estuarine ditch shrimp Palaemon varians considering three different uptake routes: water, diet, water + diet and iv) assess the bioaccumulation patterns of cadmium in the Senegalese sole Solea senegalensis, a final consumer, and the possible risk and implications the consumption of the edible fraction of both shrimps and fish may bear to human health upon Cd exposure. We observed that the toxicity of cadmium is highly influenced by its speciation. Highest sensitivity to cadmium was observed by A. tonsa while the most sensitive endpoint was the Larval Development Ratio (LDR). Cadmium induced DNA damage to all species with increasing concentrations. The bioconcentration of cadmium by A. tonsa is strongly affected by different environmental conditions due to biological processes. The simultaneous exposure of P. varians to cadmium-contaminated water + diet showed that cadmium internal concentration was higher when compared to the individual pathways. Finally, by exposing S. senegalensis for 14 days through contaminated water and diet (supplied as Hediste diversicolor), with another 14 days of depuration phase, it was concluded that the 14 days of exposure were not enough for the fish to reach a steady state on cadmium internal concentration, and neither the 14 days of elimination were sufficient to cause total depuration of the accumulated cadmium in any of the organs. Moreover, a higher concentration of cadmium was found in the intestine of the fish when compared with the rest of the organs, and the elimination rate constant of cadmium in the liver was nule. The Target Hazard Quotient (THQ) and the Estimated Weekly Intake (EWI) values for cadmium for the edible fraction of S. senegalensis were below the acceptable levels set by the European Regulation while for the shrimps both THQ and EWI exceeded the acceptable levels established
O cádmio é considerado um dos metais mais tóxicos para organismos aquáticos, podendo ocorrer naturalmente no ambiente em concentrações muito baixas, devido a processos naturais (e.g., erupções vulcânicas, erosão da crosta natural) mas também devido a atividades antropogénicas, como a atividade mineira. Como um subproduto da exploração mineira de zinco, o cádmio pode ser libertado para o ambiente aquático através de lixiviação ou escorrências. O cádmio é um metal não essencial para os organismos mas, mesmo em concentrações relativamente baixas, pode ser tóxico, provocando efeitos adversos devido à sua elevada tendência para bioacumular. Neste contexto, o objetivo deste trabalho foi estudar a transferência de cádmio em diferentes modelos de níveis tróficos marinhos. O estudo foi dividido em quatro etapas: i) avaliar a eco- e genotoxicidade de cádmio em três espécies marinhas, representando diferentes níveis tróficos marinhos ii) determinar a bioconcentração de cádmio por Acartia tonsa sob diferentes condições ambientais, tais como pH, salinidade e temperatura, iii) a avaliação de toxicocinética de cádmio pelo camarão estuarino Palaemon varians sob três vias de exposição diferentes: água, alimentação e água + alimentação, e iv) avaliar os padrões de bioacumulação de cádmio no linguado Solea senegalensis como consumidor final, e os possíveis riscos e implicações do consumo da fração edível de camarões e peixe que pode ter para a saúde humana, após a exposição a cádmio. Foi observado que a toxicidade de cádmio é influenciada pela sua especiação. A maior sensibilidade ao cádmio foi observada em A. tonsa tendo como parâmetro mas sensível o Índice de Desenvolvimento Larvar (LDR). O cádmio induziu danos no ADN de todas as espécies utilizadas. A bioconcentração de cádmio por A. tonsa é fortemente afetada por diferentes condições ambientais devido a processos biológicos. P. varians foi exposto a cádmio através de diferentes vias de exposição: água ou alimento ou água e alimento. A exposição simultânea de P. varians a água e alimento contaminado com cádmio mostrou que a concentração interna de cádmio foi maior quando comparada com as outras duas vias de exposição. Finalmente, mesmo uma exposição através de água e alimento contaminado (fornecido como Hediste diversicolor) não foi suficiente para que o peixe S. senegalensis atingisse um plateau na concentração interna de cádmio, sendo os 14 dias de depuração insuficientes para que os organismos depurassem totalmente a concentração interna que havia sido acumulada. Adicionalmente, foi encontrada uma maior concentração de cádmio no intestino de S. senegalensis quando comparada com os outros órgãos, e a constante de eliminação de cádmio no fígado foi inexistente. Os valores do Coeficiente de Perigo Alvo (THQ) e o Consumo Semanal Estimado (EWI) para o cádmio estavam abaixo dos níveis aceitáveis estabelecidos em regulamentos europeus para a fração edível de S. senegalensis, enquanto que para P. varians tanto o THQ quanto o EWI excederam os níveis aceitáveis estabelecidos.
25

Davis, Nicholas Gregory. "Application of Next-Generation Transcriptomic Tools for Non-Model Organisms: Gene Discovery and Marker DevelopmentWithin Plecoptera (Insecta)." BYU ScholarsArchive, 2013. https://scholarsarchive.byu.edu/etd/4265.

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Phylogenetic research on non-model organisms has been hindered by limited marker availability. Next generation sequencing techniques are eliminating that barrier. Using Illumina sequencing technology, Trinity assembly software, custom Perl reciprocal BLAST scripts, and Primer3 primer prediction software, we produced and analyzed 7 Plecopteran transcriptomes, representing 7 of the 16 total families, in an attempt to identify and develop conserved orthologous genetic markers. The transcriptomes were used to reconstruct a gene content phylogeny using a simple distance matrix generated from reciprocal blastn data. By producing and filtering a reciprocal blast network we identified and aligned over 450 putative orthologs. Out of these, 25 primer pairs were selected that showed 100% conserved primer sites across all the transcripts from which they were created. Of those 25, 3 loci (PlecSK1, Perl534, and PvC2190) show very positive phylogenetic potential. These 3 markers may also be suitable and even highly useful in population genetic studies in which the populations have had sufficient time to develop significant genetic separation. The rapid and affordable nature of this study demonstrates the ease by which non-model organism phylogenetics can be expanded and made more robust.
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Martí, Solans Josep. "Oikopleura dioica com a model animal per investigar l'impacte de les pèrdues gèniques en l'Evo-Devo: les vies de senyalització de l'àcid retinoic i Wnt com a cas d'estudi." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/663443.

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El creixent nombre de genomes seqüenciats està posant de manifest que la pèrdua gènica és un fenomen recurrent que pot haver generat diversitat al llarg de la història evolutiva dels diferents grups d’organismes. En aquest sentit, un dels grans reptes en el camp de la EvoDevo és entendre l’impacte de la pèrdua gènica en l’evolució dels mecanismes del desenvolupament animal considerant diferents escenaris evolutius. En escenaris de selecció positiva, la pèrdua hauria comportat canvis morfològics o fisiològics que haurien permès l’adaptació de les espècies a noves condicions ambientals. En escenaris de selecció neutre (o quasi neutre), la pèrdua hauria afectat a gens que haurien esdevingut prescindibles per l’existència de robustesa mutacional o perquè les condicions ambientals haurien canviat. Saber si una pèrdua gènica ha estat adaptativa o neutre és generalment molt complex ja que molts cops es difícil establir relacions directes de causalitat entre la pèrdua d’un gen i l’aparició d’una nova característica evolutivament avantatjosa. Malgrat aquesta dificultat, en aquesta tesi doctoral vàrem voler estudiar l’impacte de la pèrdua gènica en l’EvoDevo a partir d’analitzar l’evolució de les vies de senyalització de l’àcid retinoic (RA) i de Wnt -vies essencials pel desenvolupament de tots els cordats- a l’urocordat Oikopleura. dioica com a sistema model de referència. Per establir O. dioica com a model animal, però, a més de les característiques biològiques que la fan atractiva per aquests tipus estudis –desenvolupament embrionari i cicle de vida extremadament ràpid, simplicitat i transparència corporal, genoma reduït i totalment seqüenciat, possibilitat de manipulació gènica per estudis funcionals– ha estat fonamental desenvolupar unes instal·lacions per cultivar-la en el laboratori, així com protocols de manteniment assequibles (low-cost) per qualsevol grup d’investigació. Gràcies a aquest sistema de cultiu, em pogut analitzar els components de la xarxa gènica del metabolisme de l’RA (RA-MGN), així com els lligands de la via de senyalització per Wnt. En referència a la RA-MGN, el nostre treball ens permet concloure que les pèrdues gèniques que han afectat a aquesta via durant l’evolució de O. dioica han tingut lloc en un sistema genètic no robust, on el desballestament de la via no han tingut un impacte dramàtic en el pla corporal típic de cordats que preserva aquest organisme. Per altre banda, l’anàlisi de la família Wnt a cordats, ens ha permès concloure que a més de la duplicació gènica o de la redundància funcional per processos d’evolució convergent, els fenòmens de reassignació de funcions (function shuffling) augmenten també la robustesa mutacional i faciliten les pèrdues gèniques en les famílies de gens. En resum, els resultats d’aquesta tesi doctoral posen de manifest que O. dioica és un model animal atractiu per estudiar tant aspectes bàsics de l’impacte de les pèrdues gèniques en l’evolució dels mecanismes del desenvolupament, com en aspectes aplicats en que certes pèrdues confereixen a O. dioica la condició de knockout evolutiu que pot ser interessant per l’estudi de mecanismes moleculars concrets com la toxicitat de les PUAs en el desenvolupament embrionari d’organismes marins.
The bloom of genomics is revealing gene loss as a pervasive evolutionary force generating genetic diversity that shapes the evolution of species. In this sense, one of the great challenges in the field of EvoDevo is to understand the impact of gene loss on the evolution of animal developmental mechanisms. In this doctoral thesis we wanted to study the impact of gene loss in EvoDevo, using the analysis of the evolution of retinoic acid (RA) and Wnt signaling pathways - essential pathways in the development of all the chordates- in the urochordate Oikopleura. dioica as a model reference system. To establish O. dioica as an animal model, in addition to the biological characteristics that make it attractive for his type of studies-embryonic development and extremely fast life cycle, simplicity and body transparency, reduced and fully sequenced genome, possibility of gene manipulation for functional studies - It has been essential to develop a facility to grow O. dioica in the laboratory, as well as low-cost maintenance protocols affordable for any research group. Thanks to this culture system, we were able to analyze the components of the RA metabolic gene network (RA-MGN), as well as the ligands of the Wnt signaling pathway. In reference to the RA-MGN, our work allows us to conclude that the gene losses that have affected this pathway during the evolution of O. dioica have taken place in a non-robust genetic system, where the dismantling of the network has not had a dramatic impact on the typical body plan of chordates that preserves this organism. On the other hand, the analysis of the Wnt family in chordates, has allowed us to conclude that in addition to gene duplication or functional redundancy due to processes of convergent evolution, function shuffling also increase the mutational robustness and facilitate gene losses in gene families. In summary, the results of this doctoral thesis show that O. dioica is an attractive animal model for studying both basic aspects of the impact of gene losses in the evolution of development mechanisms, and in applied aspects. For instance, certain losses give to O. dioica an evolutionary knockout condition that may be interesting for the study of concrete molecular mechanisms such as the toxicity of PUAs in the embryonic development of marine organisms.
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Stanley, Jacob K. Brooks Bryan William. "Effects of chiral contaminants to aquatic organisms pharmaceuticals as model compounds for enantiomer specific ecological hazard assessment /." Waco, Tex. : Baylor University, 2006. http://hdl.handle.net/2104/5104.

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Finke, Monika [Verfasser]. "Engineering and characterization of RNA-based switches for control of gene expression in model organisms / Monika Finke." Konstanz : KOPS Universität Konstanz, 2021. http://d-nb.info/1230756043/34.

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Strobl, Frederic [Verfasser], Ernst H. K. [Gutachter] Stelzer, and Bernd [Gutachter] Grünewald. "Comparative embryonic morphogenesis of emerging insect model organisms / Frederic Strobl ; Gutachter: Ernst H. K. Stelzer, Bernd Grünewald." Frankfurt am Main : Universitätsbibliothek Johann Christian Senckenberg, 2018. http://d-nb.info/1164077295/34.

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Kimbung, Stanley Mbandi. "A computational framework for transcriptome assembly and annotation in non-model organisms: the case of venturia inaequalis." Thesis, University of the Western Cape, 2014. http://hdl.handle.net/11394/4022.

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Abstract:
Philosophiae Doctor - PhD
In this dissertation three computational approaches are presented that enable optimization of reference-free transcriptome reconstruction. The first addresses the selection of bona fide reconstructed transcribed fragments (transfrags) from de novo transcriptome assemblies and annotation with a multiple domain co-occurrence framework. We showed that selected transfrags are functionally relevant and represented over 94% of the information derived from annotation by transference. The second approach relates to quality score based RNA-seq sub-sampling and the description of a novel sequence similarity-derived metric for quality assessment of de novo transcriptome assemblies. A detail systematic analysis of the side effects induced by quality score based trimming and or filtering on artefact removal and transcriptome quality is describe. Aggressive trimming produced incomplete reconstructed and missing transfrags. This approach was applied in generating an optimal transcriptome assembly for a South African isolate of V. inaequalis. The third approach deals with the computational partitioning of transfrags assembled from RNA-Seq of mixed host and pathogen reads. We used this strategy to correct a publicly available transcriptome assembly for V. inaequalis (Indian isolate). We binned 50% of the latter to Apple transfrags and identified putative immunity transcript models. Comparative transcriptomic analysis between fungi transfrags from the Indian and South African isolates reveal effectors or transcripts that may be expressed in planta upon morphogenic differentiation. These studies have successfully identified V. inaequalis specific transfrags that can facilitate gene discovery. The unique access to an in-house draft genome assembly allowed us to provide preliminary description of genes that are implicated in pathogenesis. Gene prediction with bona fide transfrags produced 11,692 protein-coding genes. We identified two hydrophobin-like genes and six accessory genes of the melanin biosynthetic pathway that are implicated in the invasive action of the appressorium. The cazyome reveals an impressive repertoire of carbohydrate degrading enzymes and carbohydrate-binding modules amongst which are six polysaccharide lyases, and the largest number of carbohydrate esterases (twenty-eight) known in any fungus sequenced to date
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Wood, Hannah Louise. "Assessing the impact of increasing seawater temperature and acidity on marine organisms using ophiuroid brittlestars as an experimental model." Thesis, University of Plymouth, 2009. http://hdl.handle.net/10026.1/2388.

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Abstract:
Ocean acidification is a consequence of rapidly increasing atmospheric levels of carbon dioxide and, in tandem with increasing sea temperature, poses a significant threat to marine life. A series of mesocosm experiments have been conducted at the Plymouth Marine Laboratory (Plymouth, UK) and the Kings Bay Marine Laboratory (Ny-Alesund, Svalbard) where ophiuroid brittlestars were used as a model to investigate the physiological response of marine organisms to ocean acidification and ocean warming. A 'whole organism' approach was adopted to elucidate the primary physiological responses, trade offs and conflicts that occurred. Three ophiuroid species of differing lifestyle and habitats were chosen to give an insight into how such factors influenced a species' response to ocean acidification and warming; the infaunal Amphiura filiformis, the epibenthic Ophiura ophiura, both temperate, and the Arctic epibenthic Ophiocten sericeum. There was a similar physiological response of metabolic upregulation across all three species. All species survived the lowest pH exposures (6.8 for A. filiformis, 7.3 for 0. ophiura and 0. sericeum) and showed signs of synergy between increasing water temperature and ocean acidification with the effects of lowered pH amplified as temperature increased. Beyond this, whilst specific responses differed between species, some similarity was observed between the epibenthic species 0. ophiura and 0. sericeum which both reduced arm regeneration and motility at lowered pH. In contrast, A. filiformis increased arm regeneration and suffered arm muscle wastage that appeared unsustainable. Differences in response and long term vulnerability to ocean acidification related to lifestyle (infaunal versus epibenthic) were consolidated by the Energy Limitation Model whereby the response of a species to ocean acidification is based on the increased cost of maintaining the acid-base balance of extracellular fluids. The ability to do this, and where the energy is taken from to do so, rationalises the variety of physiological responses seen between species. The results of the investigations described in this thesis indicate that even species with low regulatory capacity may survive ocean acidification. However, lifestyle may have a determining role in where energy trade offs are made to maintain acid-base balance and this may ultimately determine species survival.
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Dobbins, Laura L. Brooks Bryan William. "Chemical toxicity distributions in aquatic toxicology relative sensitivities of estrogenicity assays and ecotoxicity of parabens in model freshwater organisms /." Waco, Tex. : Baylor University, 2009. http://hdl.handle.net/2104/5350.

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Fuchs, Beatrix [Verfasser], and Peter Paul [Akademischer Betreuer] Nawroth. "Comparative Study in Various Model Organisms Regarding the Effect of the Loss of Glyoxalase 1 / Beatrix Fuchs ; Betreuer: Peter Paul Nawroth." Heidelberg : Universitätsbibliothek Heidelberg, 2019. http://d-nb.info/1200548582/34.

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Amsel, Daniel [Verfasser]. "Elucidating the potential of microRNAs : towards a functional landscape of microRNAs in the model organisms Tribolium castaneum and Galleria mellonella / Daniel Amsel." Gießen : Universitätsbibliothek, 2021. http://d-nb.info/1233036459/34.

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Thrupp, Tara Joanne. "Effects of pharmaceutical pollutants and their mixtures on aquatic organisms, with particular focus on reproduction and endocrine function in a fish model species." Thesis, Brunel University, 2016. http://bura.brunel.ac.uk/handle/2438/14395.

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Abstract:
A number of pharmaceuticals have been shown to have adverse effects on key biological processes of aquatic organisms at low concentrations (ng/l range). Key questions for chemical risk assessment are whether such pharmaceuticals can produce adverse effects on organisms when present in the environment in combination and at low concentrations, whether these can be classified as additive, and under what circumstances can they be predicted. The main purpose of this study was to assess the potential for combination effects of a multicomponent steroid pharmaceutical mixture of dissimilarly acting compounds on an ecologically relevant end point – reproduction, using the existing predictive toxicity models Concentration Addition (CA) and Independent Action (IA). Concentrations of steroids close to those reported in the environment were shown to produce adverse effects on reproduction when present in combination with other steroids. Clear combination effects significantly larger than the effects of the individual compounds were observed when each compound was present at a concentration below the detection limit of the assay, demonstrating a ‘something from nothing’ mixture effect. Furthermore, IA predicted more pronounced effects on egg production that CA, an observation previously unreported from the literature. Actual observed effects were closer to the IA prediction. Additional biomarker and molecular endpoints were examined in subsequent studies to establish the mechanisms of disrupted reproduction in pair-breeding FHMs exposed to the steroid mixture. Results from this study indicate that reproductive impairment of fish exposed to the steroid mixture is likely due to the masculinisation of female fish due to the androgenic activity of the mixture. These results have implications for chemical risk assessment, and in particular, highlight the need for caution when using CA as a worst-case approximation of mixture effects.
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Mesilaakso, Lauri. "Bioinformatic approaches for detecting homologous genes in the genomes of non-model organisms : A case study of wing development genes in insect genomes." Thesis, Uppsala universitet, Evolutionsbiologi, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-398072.

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Abstract:
Identifying homologous genes, that is genes from a common ancestor, is important in comparative genomic studies for understanding gene annotation and the predicted function of a gene. Several pieces of software, of which the most well-known is BLAST, have been developed for identifying homologues, but this can be challenging in non-model organisms where sometimes poor quality of genome assemblies and lack of annotation make it difficult to robustly identify homologues. The aim of this project was to build a bioinformatic framework for homology detection using genomes from non-model organisms. The approach developed used genome annotations, annotated polypeptide sequences and genome assembly sequences to detect homologous genes.The framework was applied to identify Drosophila melanogaster homologous wing development genes in the genomes of nine other insect species with the aim to understand the evolution of loss of wings. To identify changes related to wing loss, the homologous protein sequences obtained were aligned and phylogenetic trees were built from them. The aim of creating the multiple protein alignments and phylogenetic trees was to shed light on whether changes in gene sequences can be related to presence or absence of wings. From the set of 21 candidate wing development genes identified with literature and subsequent database searches, I tested eight and was successful in identifying homologues for all of them in eight of the 10 in sectgenomes. This was done using a combination of text searches in genome annotations, searches with Exonerate v. 2.4.0 alignment program in annotated polypeptide sequences and in genome assemblies. The eight genes chosen for testing the framework were based on initial finding of putative homologues in the eight insect genomes when using the first two steps of the framework. For the set of homologous wing development genes examined I was not able to identify any conclusive pattern of potential protein coding changes that correlated with loss of wings in these species. Improvement to the current pipeline could include using query sequences from closer relatives of the 8 test species than D. melanogaster and, of course, testing of the remaining wing development genes as well as further literature study of wing development genes. Together these could improve future studies on the evolution of wing loss in insects.
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Santos, Jorge Miguel Martins. "Understanding the microbial ecology and ecophysiology of enhanced biological phosphorus removal processes through metabolic modelling and experimental studies." Master's thesis, Faculdade de Ciências e Tecnologia, 2013. http://hdl.handle.net/10362/12214.

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Dissertation to obtain the degree of Master in Chemical and Biochemical Engineering
The enhanced biological phosphorus removal (EBPR) process in activated sludge systems has become a widely applied wastewater treatment technology to control eutrophication. The success of this process relies on the sludge enrichment with polyphosphate accumulating organisms (PAOs), while one of the main causes for its failure is due to microbial competition between PAOs and another group of organisms known as the glycogen accumulating organisms (GAOs). The microbial ecology and ecophysiology of these two groups have been investigated through metabolic modelling and experimental studies in order to provide a better understanding of EBPR systems. This thesis focuses on researching the P removal efficiency and metabolic behaviour of an enriched culture containing two PAOs: Tetrasphaera-related organisms and Accumulibacter, which were acclimatized with casamino acids as sole carbon source in a sequencing batch reactor (SBR). Both organisms were identified through fluorescence in situ hybridization (FISH), and this culture demonstrated anaerobic P release, glycogen hydrolysis, a very low poly--hydroxyalkanoates (PHA) synthesis and high casamino acids uptake; followed by aerobic P uptake, glycogen formation and a very low PHA oxidation. Different carbon sources (glucose, acetate, propionate, glutamate, aspartate, glycine and casamino acids) were studied through batch tests inoculated with sludge from the main SBR. Through experimental data, it was suggested that Accumulibacter were responsible for the uptake of volatile fatty acids (VFAs), and Tetrasphaera-related organisms were likely responsible for both glucose and amino acids uptake. This thesis also focuses on the development of a model that combines a PAO-GAO metabolic model with activated sludge model no. 2d (ASM2d) in collaboration with Hydromantis Environmental Software Solutions, Inc.. The combined model was implemented in the GPS-X software and will provide a new and advanced platform for wastewater treatment modelling, which will be available to practitioners.
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Jäger, Ilonka. "Hosts and parasites many ways of interactions ; an approach with two model organisms, the three-spined stickleback (Gasterosteus aculeatus) and its cestode parasite (Schistocephalus solidus) /." [S.l.] : [s.n.], 2006. http://e-diss.uni-kiel.de/diss_1763/d1763.pdf.

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Bens, Martin [Verfasser], Matthias [Gutachter] Platzer, Steve [Gutachter] Hoffmann, and Ingo [Gutachter] Ebersberger. "Development and application of RNA-seq bioinformatic tools to explore non-model organisms in ageing research / Martin Bens ; Gutachter: Matthias Platzer, Steve Hoffmann, Ingo Ebersberger." Jena : Friedrich-Schiller-Universität Jena, 2018. http://d-nb.info/1170396828/34.

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Myklatun, Ahne [Verfasser], Gil G. [Akademischer Betreuer] Westmeyer, Gil G. [Gutachter] Westmeyer, Friedrich C. [Gutachter] Simmel, and Wolfgang [Gutachter] Wurst. "Biophysical and Behavioral Characterization of Magnetoreception in Genetic Model Organisms / Ahne Myklatun ; Gutachter: Gil G. Westmeyer, Friedrich C. Simmel, Wolfgang Wurst ; Betreuer: Gil G. Westmeyer." München : Universitätsbibliothek der TU München, 2018. http://d-nb.info/1183259123/34.

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Sobotta, Jessica [Verfasser], Wolfgang [Akademischer Betreuer] Eisenreich, Dieter [Gutachter] Braun, and Wolfgang [Gutachter] Eisenreich. "Investigations of carbon fixation in model organisms and in cell-free prebiotic transition metal-catalyzed reactions / Jessica Sobotta ; Gutachter: Dieter Braun, Wolfgang Eisenreich ; Betreuer: Wolfgang Eisenreich." München : Universitätsbibliothek der TU München, 2018. http://d-nb.info/1165227533/34.

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Pletzer, Daniel [Verfasser], Helge [Akademischer Betreuer] Weingart, Georgi [Akademischer Betreuer] Muskhelishvili, and Thilo [Akademischer Betreuer] Köhler. "Drug export and nutrient import: Insights from the bacterial model organisms Erwinia amylovora and Pseudomonas aeruginosa / Daniel Pletzer. Betreuer: Helge Weingart. Gutachter: Helge Weingart ; Georgi Muskhelishvili ; Thilo Köhler." Bremen : IRC-Library, Information Resource Center der Jacobs University Bremen, 2014. http://d-nb.info/1087305845/34.

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43

Siddique, Muhammad Asim. "Proteome analysis of tobacco BY-2 cell culture plastids and Capsicum annuum chromoplasts : protein profiling, quantification and novel strategies for the detection of proteins from non- model organisms." kostenfrei, 2007. http://e-collection.ethbib.ethz.ch/view/eth:29321.

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44

Keskiaho-Saukkonen, K. (Katriina). "Prolyl 4-hydroxylase:studies on collagen prolyl 4-hydroxylases and related enzymes using the green alga Chlamydomonas reinhardtii and two Caenorhabditis nematode species as model organisms." Doctoral thesis, University of Oulu, 2007. http://urn.fi/urn:isbn:9789514284731.

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Abstract:
Abstract Collagen prolyl 4-hydroxylases (C-P4Hs) and related enzymes catalyze the hydroxylation of certain proline residues in animal collagens and plant hydroxyproline-rich proteins, respectively. Animal C-P4Hs and their isoenzymes have been characterized to date from humans, rodents, insects and nematodes. Most of the animal C-P4Hs are α2β2 tetramers in which protein disulphide isomerase (PDI) serves as the β subunit, but the nematode C-P4Hs characterized so far have unique molecular compositions. Two P4Hs have been cloned from the plant Arabidopsis thaliana and one from the Paramecium bursaria Chlorella virus-1, these being monomeric enzymes. This thesis reports on the identification of a large P4H family in the green alga Chlamydomonas reinhardtii and the cloning and characterization of one member, Cr-P4H-1. This is a soluble monomer that hydroxylates in vitro several peptides representing sequences found in C. reinhardtii cell wall proteins. Lack of its activity led to a defective cell wall structure, indicating that Cr-P4H-1 is essential for proper cell wall assembly and that the other P4Hs cannot compensate for the lack of its activity. Two C. elegans genes, Y43F8B.4 and C14E2.4, predicted to code for C-P4H α subunit-like polypeptides were analyzed. Three transcripts were generated from Y43F8B.4, one of them coding for a functional C-P4H α subunit named PHY-4.1. C14E2.4 turned out not to be a C-P4H α subunit gene, as a frame-shift led to the omission of codons for two catalytically critical residues. PHY-4.1 formed active tetramers and dimers with PDI-2 and had unique substrate requirements in that it hydroxylated certain other proline-rich sequences besides collagen-like peptides. Inactivation of the Y43F8B.4 gene led to no obvious morphological abnormalities. Spatial expression of the phy-4.1 transcript and PHY-4.1 polypeptide was localized to the pharynx and the excretory duct. Taken together, these data indicate that PHY-4.1 is not involved in the hydroxylation of cuticular collagens but is likely to have other substrates in vivo. Cloning and characterization of the PHY-1 and PHY-2 subunits from the closely related nematode Caenorhabditis briggsae revealed distinct differences in assembly properties between the C. elegans and C. briggsae PHY-2 subunits in spite of their high amino acid sequence identity. Genetic disruption of C. briggsae phy-1 resulted in a less severe phenotype than that observed in C. elegans, evidently on account of its more efficient assembly of the C. briggsae PHY-2 to an active C-P4H explaining the milder phenotype. Rescue of C. elegans and C. briggsae phy-1 mutants was achieved by injection of a wild-type phy-1 gene from either species.
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Zhou, Hong [Verfasser], and Klaus von [Akademischer Betreuer] Schwartzenberg. "Towards establishment of model organisms for conjugating green algae – Zygnematophyceae and studies on the evolution of the regulatory network of the plant hormone cytokinin / Hong Zhou ; Betreuer: Klaus von Schwartzenberg." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2020. http://d-nb.info/1217409122/34.

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46

Boontian, Nittaya. "Using the activated sludge model 2d (ASM2d) to understand and predict the phosphorus accumulating organisms mechanism in enhanced biological phosphorus removal in relation to disintegrated sludge as a carbon source." Thesis, Cranfield University, 2012. http://dspace.lib.cranfield.ac.uk/handle/1826/7864.

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Carbon sources are considered as one of the most important factors in the performance of enhanced biological phosphorus removal (EBPR). Disintegrated sludge (DS) can act as carbon source to increase the efficiency of EBPR. This research explores the influence of DS upon phosphorus removal efficiency using mathematical simulation modeling. Activated Sludge Model No. 2d (ASM2d) is one of the most useful of activated sludge (AS) models. This is because ASM2d can express the integrated mechanisms of phosphorus accumulating organisms (PAOs) under aerobic, anaerobic and anoxic conditions. Cont/d.
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Klütsch, Cornelya F. C. "Evolutionary history of Southern Arabian faunal elements with a special focus on habitat fragmentation of two model organisms, Reissita simonyi (REBEL, 1899; Lepidoptera: Zygaenidae) and Hyla savignyi (AUDOUIN, 1827; Amphibia: Hylidae)." [S.l.] : [s.n.], 2006. http://deposit.ddb.de/cgi-bin/dokserv?idn=980248132.

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Loira, Nicolas. "Scaffold-based reconstruction method of genome-scale metabolic models." Thesis, Bordeaux 1, 2012. http://www.theses.fr/2012BOR14484/document.

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Abstract:
La compréhension des organismes vivant a été une quête pendant longtemps. Depuisles premiers progrès des derniers siècles, nous sommes arrivés jusqu’au point où desquantités massives de données et d’information sont constamment générées. Bien que,jusqu’au présent la plupart du travail a été concentré sur la génération d’un catalogued’éléments biologiques, ce n’est pas que récemment qu’un effort coordonné pour découvrirles réseaux de relations entre ces parties a été constaté. Nous nous sommes intéressésà comprendre non pas seulement ces réseaux, mais aussi la façon dont, à partir de sesconnexions, émergent des fonctions biologiques.Ce travail se concentre sur la modélisation et l’exploitation d’un de ces réseaux :le métabolisme. Un réseau métabolique est un ensemble des réactions biochimiquesinterconnectées qui se produisent à l’intérieur, ou dans les proximité d’une cellulevivante. Une nouvelle méthode de découverte, ou de reconstruction des réseaux métaboliquesest proposée dans ce travail, avec une emphase particulière sur les organismeseucaryotes.Cette nouvelle méthode est divisée en deux parties : une nouvelle approche pour lamodélisation de la reconstruction basée sur l’instanciation des éléments d’un modèlesquelette existant, et une nouvelle méthode de réécriture d’association des gènes. Cetteméthode en deux parties permet des reconstructions qui vont au-delà de la capacitédes méthodes de l’état de l’art, permettant la reconstruction de modèles métaboliquesdes organismes eucaryotes, et fournissant une relation détaillée entre ses réactions etses gènes, des connaissances cruciales pour des applications biotechnologiques.Les méthodes de reconstruction développées dans ce travail, ont été complétéespar un workflow itératif d’édition, de vérification et d’amélioration du modèle. Ceworkflow a été implémenté dans un logiciel, appelé Pathtastic.Comme une étude de cas de la méthode développée et implémentée dans le présenttravail, le réseau métabolique de la levure oléagineuse Yarrowia lipolytica, connucomme contaminant alimentaire et utilisé pour la biorestauration et comme usinecellulaire, a été reconstruit. Une version préliminaire du modèle a été générée avecPathtastic, laquelle a été améliorée par curation manuelle, à travers d’un travail avecdes spécialistes dans le domaine de cette espèce. Les données expérimentales, obtenuesà partir de la littérature, ont été utilisées pour évaluer la qualité du modèle produit.La méthode de reconstruction chez les eucaryotes, et le modèle reconstruit deY. lipolytica peuvent être utiles pour les communautés scientifiques respectives, lepremier comme un pas vers une meilleure reconstruction automatique des réseauxmétaboliques, et le deuxième comme un soutien à la recherche, un outil pour desapplications biotechnologiques et comme un étalon-or pour les reconstructions futures
Understanding living organisms has been a quest for a long time. Since the advancesof the last centuries, we have arrived to a point where massive quantities of data andinformation are constantly generated. Even though most of the work so far has focusedon generating a parts catalog of biological elements, only recently have we seena coordinated effort to discover the networks of relationships between those parts. Notonly are we trying to understand these networks, but also the way in which, from theirconnections, emerge biological functions.This work focuses on the modeling and exploitation of one of those networks:metabolism. A metabolic network is a net of interconnected biochemical reactionsthat occur inside, or in the proximity of, a living cell. A new method of discovery, orreconstruction, of metabolic networks is proposed in this work, with special emphasison eukaryote organisms.This new method is divided in two parts: a novel approach to reconstruct metabolicmodels, based on instantiation of elements of an existing scaffold model, and a novelmethod of assigning gene associations to reactions. This two-parts method allows reconstructionsthat are beyond the capacity of the state-of-the-art methods, enablingthe reconstruction of metabolic models of eukaryotes, and providing a detailed relationshipbetween its reactions and genes, knowledge that is crucial for biotechnologicalapplications.The reconstruction methods developed for the present work were complementedwith an iterative workflow of model edition, verification and improvement. This workflowwas implemented as a software package, called Pathtastic.As a case study of the method developed and implemented in the present work,we reconstructed the metabolic network of the oleaginous yeast Yarrowia lipolytica,known as food contaminant and used for bioremediation and as a cell factory. A draftversion of the model was generated using Pathtastic, and further improved by manualcuration, working closely with specialists in that species. Experimental data, obtainedfrom the literature, were used to assess the quality of the produced model.Both, the method of reconstruction in eukaryotes, and the reconstructed model ofY. lipolytica can be useful for their respective research communities, the former as astep towards better automatic reconstructions of metabolic networks, and the latteras a support for research, a tool in biotechnological applications and a gold standardfor future reconstructions
49

Bastos, Juliana Cristina Santiago 1985. "Atividade antiviral de organismos marinhos frente ao vírus da diarreia viral bovina, modelo para o vírus da hepatite C." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/316637.

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Abstract:
Orientadores: Clarice Weis Arns, Luciana Konecny Kohn
Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: O vírus da Hepatite C (família Flaviviridae, gênero Hepacivirus) é causador de infecções crônicas em humanos, que podem evoluir para quadros de cirrose hepática e carcinoma hepatocelular. Até o momento, não há vacina disponível contra essa infecção e o tratamento disponível é caro, tem eficácia limitada e gera uma vasta gama de efeitos secundários, o que dificulta a continuidade do tratamento. Como esse vírus não replica eficientemente em cultura de células e em animais, o vírus da diarréia viral bovina é utilizado como modelo substituto para ensaios de avaliação de atividade antiviral e em ensaios de mecanismo de ação. A partir de invertebrados e micro-organismos marinhos, foram preparados extratos e frações, e algumas substâncias foram isoladas para a avaliação da sua possível atividade antiviral. Dos 422 testados, 5% foram considerados promissores e, destes, 20% mostraram-se ativos apresentando uma proteção de mais de 97% às células frente ao vírus. Os melhores resultados foram obtidos dos extratos produzidos a partir das amostras de esponjas Hyrtios sp. (BA07ES-56: PI=99%, IS=25), Aaptos sp. (BA07ES-59: PI=99%, IS=8,25) e de bactérias Bacillus sp. (555: PI=98%, IS>18; 584: PI=98%, IS=27) isoladas da esponja Petromica citrina. Os extratos e compostos promissores foram capazes de atuar em diversas etapas do ciclo replicativo viral (adsorção, penetração, etapas intracelulares do ciclo replicativo e também inativação da partícula viral), levando à sua interrupção quase completa nas condições analisadas. Desse modo, diversas substâncias presentes nesses organismos estudados são ativas e podem levar ao desenvolvimento de fármacos que garantam uma terapia alternativa para o tratamento da hepatite C
Abstract: The Hepatitis C virus (family Flaviviridae, genus Hepacivirus) causes chronic infections in humans, which can develop to liver cirrhosis and hepatocellular carcinoma. This represents a major public health problem worldwide. To this moment, there is no vaccine available against this infection and the treatment available is expensive, has limited efficacy and generates a wide range of side effects, making it difficult to continue the treatment. All this reflects the need to seek new agents with antiviral action against this virus. As this virus does not replicate efficiently in cell culture and in animals, bovine viral diarrhea virus is used as a surrogate model for screening assays of antiviral activity, and mechanism of action assays. From marine invertebrates and micro-organisms isolated from them, extracts and fractions were prepared, and substances were isolated for assessment of their possible antiviral activity. Of the 422 tested, 5% were considered promising, and of these, 20% were active presenting a protection percentage of more than 97%. The best results were obtained from the extracts produced from the samples of sponge Hyrtios sp. (BA07ES-56: IP=99%, SI=25), Aaptos sp. (BA07ES-59: IP=99%, SI=8,25) and bacteria Bacillus sp. (555: IP=98%, SI>18; 584: IP=98%, SI=27) isolated from the sponge Petromica citrina. The promising extracts and compounds acted in several stages of viral replicative cycle (adsorption, penetration, intracellular steps of the replicative cycle and also inactivation of the viral particle). Thus, various substances are active and may lead to the development of drugs which ensure an alternative therapy for the treatment of hepatitis C
Mestrado
Microbiologia
Mestra em Genética e Biologia Molecular
50

Forrester, Marie Leanne. "Epidemic models and inference for the transmission of hospital pathogens." Queensland University of Technology, 2006. http://eprints.qut.edu.au/16419/.

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The primary objective of this dissertation is to utilise, adapt and extend current stochastic models and statistical inference techniques to describe the transmission of nosocomial pathogens, i.e. hospital-acquired pathogens, and multiply-resistant organisms within the hospital setting. The emergence of higher levels of antibiotic resistance is threatening the long term viability of current treatment options and placing greater emphasis on the use of infection control procedures. The relative importance and value of various infection control practices is often debated and there is a lack of quantitative evidence concerning their effectiveness. The methods developed in this dissertation are applied to data of methicillin-resistant Staphylococcus aureus occurrence in intensive care units to quantify the effectiveness of infection control procedures. Analysis of infectious disease or carriage data is complicated by dependencies within the data and partial observation of the transmission process. Dependencies within the data are inherent because the risk of colonisation depends on the number of other colonised individuals. The colonisation times, chain and duration are often not visible to the human eye making only partial observation of the transmission process possible. Within a hospital setting, routine surveillance monitoring permits knowledge of interval-censored colonisation times. However, consideration needs to be given to the possibility of false negative outcomes when relying on observations from routine surveillance monitoring. SI (Susceptible, Infected) models are commonly used to describe community epidemic processes and allow for any inherent dependencies. Statistical inference techniques, such as the expectation-maximisation (EM) algorithm and Markov chain Monte Carlo (MCMC) can be used to estimate the model parameters when only partial observation of the epidemic process is possible. These methods appear well suited for the analysis of hospital infectious disease data but need to be adapted for short patient stays through migration. This thesis focuses on the use of Bayesian statistics to explore the posterior distributions of the unknown parameters. MCMC techniques are introduced to overcome analytical intractability caused by partial observation of the epidemic process. Statistical issues such as model adequacy and MCMC convergence assessment are discussed throughout the thesis. The new methodology allows the quantification of the relative importance of different transmission routes and the benefits of hospital practices, in terms of changed transmission rates. Evidence-based decisions can therefore be made on the impact of infection control procedures which is otherwise difficult on the basis of clinical studies alone. The methods are applied to data describing the occurrence of methicillin-resistant Staphylococcus aureus within intensive care units in hospitals in Brisbane and London

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