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1
Istrail, Sorin. „Computational molecular biology /“. Amsterdam [u.a.] : Elsevier, 2003. http://www.loc.gov/catdir/toc/fy037/2003051360.html.
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2
Coffey, Matthew Clayton. „The molecular biology of reovirus“. Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0001/NQ38461.pdf.
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3
King, L. A. „Molecular biology of insect picornaviruses“. Thesis, University of Oxford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.370278.
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4
Garner, Sarah. „The molecular biology of Chp2“. Thesis, University of Southampton, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.398831.
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5
Mossman, Sally Patricia. „Investigations into the biology and molecular biology of alphaherpesvirus saimiri“. Thesis, University of Liverpool, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.291968.
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6
Bantle, Stefan Franz. „The molecular biology of chicken myomesin /“. Zürich, 1997. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=12157.
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7
Fange, David. „Modelling Approaches to Molecular Systems Biology“. Doctoral thesis, Uppsala universitet, Molekylärbiologi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-132864.
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Implementation and analysis of mathematical models can serve as a powerful tool in understanding how intracellular processes in bacteria affect the bacterial phenotype. In this thesis I have implemented and analysed models of a number of different parts of the bacterium E. coli in order to understand these types of connections. I have also developed new tools for analysis of stochastic reaction-diffusion models. Resistance mutations in the E. coli ribosomes make the bacteria less susceptible to treatment with the antibiotic drug erythromycin compared to bacteria carrying wildtype ribosomes. The effect is dependent on efficient drug efflux pumps. In the absence of pumps for erythromycin, there is no difference in growth between wildtype and drug target resistant bacteria. I present a model explaining this unexpected phenotype, and also give the conditions for its occurrence. Stochastic fluctuations in gene expression in bacteria, such as E. coli, result in stochastic fluctuations in biosynthesis pathways. I have characterised the effect of stochastic fluctuations in the parallel biosynthesis pathways of amino acids. I show how the average protein synthesis rate decreases with an increasing number of fluctuating amino acid production pathways. I further show how the cell can remedy this problem by using sensitive feedback control of transcription, and by optimising its expression levels of amino acid biosynthetic enzymes. The pole-to-pole oscillations of the Min-proteins in E. coli are required for accurate mid-cell division. The phenotype of the Min-oscillations is altered in three different mutants: filamentous cells, round cells and cells with changed membrane lipid composition. I have shown that the wildtype and mutant phenotypes can be explained using a stochastic reaction-diffusion model. In E. coli, the transcription elongation rate on the ribosmal RNA operon increases with increasing transcription initiation rate. In addition, the polymerase density varies along the ribosomal RNA operons. I present a DNA sequence dependent model that explains the transcription elongation rate speed-up, and also the density variation along the ribosomal operons. Both phenomena are explained by the RNA polymerase backtracking on the DNA.Felaktigt tryckt som Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology 715
8
Bäckesjö, Carl-Magnus. „Molecular biology of Bruton's tyrosine kinase /“. Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-693-6.
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9
Jelier, Rob. „Text mining applied to molecular biology“. [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2008. http://hdl.handle.net/1765/10866.
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10
Ali, Manir. „The molecular biology of frutose intolerance“. Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.388463.
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11
Essex, Jonathan Wynne. „Free-energy calculations in molecular biology“. Thesis, University of Oxford, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.314884.
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12
Leahy, Michael. „The molecular biology of Thogoto virus“. Thesis, University of Oxford, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268143.
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13
Edwards, T. L. „The molecular cell biology of spartin“. Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.598783.
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This thesis has focused on the protein spartin, which is mutated in a form of autosomal recessive hereditary spastic paraplegia (HSP) called Troyer syndrome. Upon commencement of this project little was known about the likely mechanism of axonopathy in spartin HSP, indeed there was considerable disagreement in the literature as to its precise subcellular localisation. However, a putative role for spartin in endocytosis was proposed due to sequence homology identified with several proteins known to function in this area. This suggested that spartin belonged to an enlarging group of HSP proteins with membrane traffic and transport-related roles. This thesis had three primary aims: to clarify the subcellular localisation of endogenous spartin, to identify proteins that interacted with spartin, and to investigate a possible functional role(s) for spartin. Spartin was found to localise predominantly in the cytoplasm, with a cystosolic pool that was recruited to endosomes. Additionally, a proportion of spartin was found in mitochondria. Furthermore, spartin was shown to undergo multiple monoubiquitination and to interact with ubiquitin, two ankyrin repeat domain-13 family members, and also with the E3 ubiquitin ligase AIP4. Functional assays suggest that spartin is an inhibitor of epidermal growth factor receptor degradation, and negatively regulates bone morphogenetic protein (BMP) signalling. A putative role in BMP signalling is interesting because this pathway is emerging as an important regulator of distal axonal morphology and function, and has been implicated in the pathogenesis of another endosomal HSP protein, NIPA1. This suggests that altered BMP signalling may be a key pathological component of spartin HSP.
14
Vialette, Stéphane. „Algorithmic Contributions to Computational Molecular Biology“. Habilitation à diriger des recherches, Université Paris-Est, 2010. http://tel.archives-ouvertes.fr/tel-00862069.
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15
Chen, Zheng-Yi. „Molecular biology of X-chromosome disease“. Thesis, University of Oxford, 1992. http://ora.ox.ac.uk/objects/uuid:8214a2f6-0bfa-4ea4-8f48-b8a20f29318c.
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Genomic clones were isolated and characterized using the human monoamine oxidase A (MAOA) cDNA to screen a phage library, constructed from a human 4X cell line (48, XXXX). The genomic contig derived from overlapping phage clones showed that the size of the MAOA gene is over 80 kb. Exon-containing fragments from these phage clones were subcloned and sequenced. The data from this showed that the MAOA gene consists of 15 exons. A YAC (yeast artificial chromosome) isolated using the MAOA cDNA was characterized. This YAC was found to contain both the MAOA and the MAOB genes. Using PFGE (pulsed-field gel electrophoresis) to investigate the YAC, it was found that the MAOA and the MAOB genes are located within 50 kb and adjacent to each other. The two genes are localized in a 3'-to-3' fashion, suggesting their expression may be regulated independently. The analysis of the homology shown by the two genes clearly demonstrated that they were derived from duplication of a common ancestral gene. A CpG island was discovered to be associated with the 5' end of both genes. A restriction map of -2.5 Mb of genomic DMA around the MAO genes was generated by PFGE. Long-range mapping defined the physical relationship between the marker L1.28 and the MAO genes as L1.28_MAOA_MAOB. A number of genetic diseases have been linked to the Xp11.3 region. Strong linkage was known to exist between the Norrie disease locus and L1.28. Studies showed that some of the Norrie patients have deletions encompassing the region which contains L1.28 as well as the MAO genes. Another YAC isolated by using L1.28 as the probe was also characterized. A phage library was constructed from the L1.28 YAC and the end clones were isolated. Studies on some of the Norrie deletion patients showed that the proximal end clone of the YAC was retained in one of the deletion patients. Previous studies had shown that the Norrie disease locus was also localized proximal to the 5' end of the MAOB gene. The combined information placed the disease locus to an interval of 240 kb within the YAC. More phage clones were characterized in order to define further the region for the Norrie locus which was finally localized within 160 kb. A YAC fragment of 160 kb was isolated and used to screen two human retinal cDNA libraries. Among the cDNAs isolated, one group was found to be deleted in some of the Norrie patients previously without any known deletion, which established their candidacy as the transcripts of the Norrie disease locus. Further characterization of the candidate gene showed that it is conserved across species. The expression of the gene was detected in various tissues. The homology shared between the NDP gene and some of the growth factor binding proteins suggests its role in neural cell proliferation and differentiation.
16
Millward-Sadler, Sarah Jane. „The molecular biology of bacterial xylanases“. Thesis, University of Newcastle Upon Tyne, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.318256.
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17
Bicknell, Andrew B. „Molecular biology of the stress axis“. Thesis, University of Reading, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.245319.
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18
Yaacob, Nik Soriani. „Molecular cell biology of peroxisome proliferators“. Thesis, University of Surrey, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244831.
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19
Thomas, Nicholas Simon. „The molecular biology of chlamydial plasmids“. Thesis, University of Southampton, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295857.
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20
Liu, Binlei. „Molecular biology of human enteric caliciviruses“. Thesis, University of Southampton, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.242419.
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21
MACEDO, JOSE ANTONIO FERNANDES DE. „A CONCEPTUAL MODEL FOR MOLECULAR BIOLOGY“. PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO, 2005. http://www.maxwell.vrac.puc-rio.br/Busca_etds.php?strSecao=resultado&nrSeq=7939@1.
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Projetos de genômica e biológica molecular estão gerando
dados cujos volumes e complexidades jamais foram
observados nesta área. Além disso, fontes de dados e de
conhecimento são produzidas e utilizadas por grupos de
pesquisa os quais utilizam terminologias diferentes
(sinônimos, apelido e fórmulas), sintaxes diferentes
(estrutura de arquivos e separadores) e semânticas
diferentes (intra e interdisciplinares homônimos). O
sucesso da pesquisa em biologia dependerá da correta
representação e manipulação dos dados biológicos
permitindo os cientistas criarem, gerenciarem,
manipularem, integrarem e analisarem os dados de forma a
gerar informação e conhecimento. Neste trabalho, estudamos
os problemas para representação de dados biológicos
apresentados nas principais linguagens de modelagem
tradicionais. Em seguida, levantamos os requisitos para um
novo modelo de dados conceitual para biologia molecular.
Finalmente, propomos um novo modelo conceitual contendo
construtores específicos para solucionar alguns dos
problemas estudados. Além disso, formalizamos o modelo
proposto usando lógica de primeira ordem e utilizamos esta
descrição lógica para realizar inferências que auxiliem o
trabalho do projetista de banco de dados durante a criação
de um esquema de banco de dados.Genomic and molecular biology projects are generating knowledge data whose volume and complexity are unparalleled in this research area. In addition, data and knoweledge sources produced and used by research groups have terminological differences (synonyms, aliases and formulae), syntactic differences (file structure, separators and spelling) and semantic differences (intra- and interdisciplinary homonyms). In this context, data management techniques play a fundamental role for biological applications development because it offers adequate abstractions to desing, implement, access and manage data, in order to generate knowledge. In this work, we study the representation problems presentd in traditional languages. Following, we raise the main requiremants for a new conceptual data model specially conceived for molecular biology. Finally, we propose a new conceptual data model with special types of constructor tryng to solve some of the representation problems discurssed before. In addition, we formalize our proposed model using first-order logic and we use this logical description to infer some properties that may help database designer during the elaboration of database schema.
22
Rishi, Arun Kumar. „Molecular biology studies of taeniid cestodes“. Thesis, Imperial College London, 1987. http://hdl.handle.net/10044/1/46314.
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23
Jajesniak, Pawel. „Expanding molecular toolbox for synthetic biology“. Thesis, University of Sheffield, 2017. http://etheses.whiterose.ac.uk/21292/.
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24
Promdonkoy, Boonhiang. „Molecular biology of a microbial toxin“. Thesis, University of Cambridge, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.621541.
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25
Baldridge, Gerald Don. „Molecular biology of Bunyavirus-host interactions“. Diss., The University of Arizona, 1989. http://hdl.handle.net/10150/184934.
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Ribonuclease T1 oligonucleotide fingerprint (ONF) analysis was used to study genomic stability of La Crosse virus (Bunyaviridae) during vertical and horizontal transmission in the laboratory. No RNA genomic changes were detected in vertebrate cell culture-propagated virus isolated (following oral ingestion and replication) from the natural mosquito host, Aedes triseriatus. Genomic changes were not detected during transovarial passage of virus through two generations of mosquitoes or in virus isolated from suckling mice infected by transovarially infected mosquitoes. These results demonstrate that the La Crosse virus genome can remain relatively stable during transovarial transmission (TOT) in the insect host and during transfer between insect and vertebrate hosts. ONF analysis was used to demonstrate TOT of reassortant California serogroup bunyaviruses in Aedes treiseriatus. Mosquitoes were simultaneously inoculated with temperature sensitive mutants of La Crosse and Snowshoe hare viruses able to replicate at 33°C but not at 40°C. Putative reassortants, selected by replication at 40°C, were isolated from progeny mosquitoes and mice infected by these mosquitoes. ONF analysis confirmed that they were reassortants. Approximately 75% of the M segment and 25% of the L segment nucleotide sequences of Inkoo virus (Bunyaviridae) were determined by Sanger dideoxynucleotide sequencing of cDNA clones. Comparison of the M segment nucleotide and deduced amino acid sequences with those of four other bunyaviruses, representing two serogroups, revealed greater conservation of nucleotide than of amino acid sequence between serogroups. Areas of the sequences representing nonstructural protein(s) were less conserved than glycoprotein regions. The L segment nucleotide sequence begins with the known 3' end of the viral L segment and contains an open reading frame encoding the amino terminal 505 amino acids of the viral L protein. The amino acid sequence contains the glycine-aspartate-aspartate motif which is conserved in many RNA-dependent RNA polymerases. Comparison of the L segment sequences with those in the GEN Bank Data Base revealed no significant similarities with any other sequence.
26
Kilvington, Simon. „The molecular biology of Naegleria fowleri“. Thesis, University of Bath, 1994. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.260220.
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27
Parker, Timothy P. „Integrating Concepts in Modern Molecular Biology into a High School Biology Curriculum“. Thesis, University of North Texas, 2003. https://digital.library.unt.edu/ark:/67531/metadc4255/.
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More so than any other science in the past several decades, Biology has seen an explosion of new information and monumental discoveries that have had a profound impact on much more than the science itself. Much of this has occurred at the molecular level. Many of these modern concepts, ideas, and technologies, as well as their historical context, can be easily understood and appreciated at the high school level. Moreover, it is argued here that the integration of this is critical for making biology relevant as a modern science. A contemporary high school biology curriculum should adequately reflect this newly acquired knowledge and how it has already has already begun to revolutionize medicine, agriculture, and the study of biology itself.
This curriculum provides teachers with a detailed framework for integrating molecular biology into a high school biology curriculum. It is not intended to represent the curriculum for an entire academic year, but should be considered a significant component. In addition to examining key concepts and discoveries, it examines modern molecular techniques, their applications, and their relevance to science and beyond. It also provides several recommended labs and helpful protocols.
28
Ozato, Kenjiro. „Present and future of medaka biology : molecular biology to field surveys“. Laboratory of Freshwater Fish Stocks, Nagoya University, 1992. http://hdl.handle.net/2237/13774.
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29
Lau, Katherine Aik Hee. „Biology and Molecular Biology of New HIV-1 Recombinants from Malaysia“. Thesis, The University of Sydney, 2009. http://hdl.handle.net/2123/4129.
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HIV-1 is the cause of the majority of global HIV infections. Not only being more virulent, and relatively easily transmitted than HIV-2, HIV-1 is also more extensively studied. HIV-1 is known for its highly recombinogenic nature, together with an extreme genetic variety, both attributable to an error-prone reverse transcriptase which gives rise to heterozygous virion. Sequence diversity of HIV-1 has resulted in identification of 9 subtypes of HIV-1 M group, as well as 43 circulating and a number of other unique recombinant forms of HIV-1. The extensive heterogeneity of HIV-1 has become the main consideration in vaccine development, mainly due to the inherent variability of HIV-1 and the frequent generation of new recombinant forms, which subsequently makes the effort to control the HIV-1 pandemic more challenging. The inter-subtype recombination event is a common phenomenon observed in Malaysia whereby there is a co-circulation of multiple HIV-1 subtypes; CRF01_AE and subtype B. Therefore, it becomes crucial to widen the knowledge of currently emerging CRF01_AE/B inter-subtype recombinants, in order to assist the future regional vaccine design and also to prevent wider spread of these strains. Concurrently, with a better understanding on the characteristics of HIV-1 CRF01_AE/B recombinant forms, further diversification of these strains can possibly be thwarted. The objectives of this study included, firstly to study the molecular epidemiology pattern of different HIV-1 strains, as well as to observe their frequency and distribution. Our second aim was to identify possible derivative from CRF33_01B, and also other new CRF01_AE/B inter-subtype recombinant forms in Malaysia. Thirdly, we aimed to identify possible biological advantages of the CRF33_01B isolates over its parental strains; CRF01_AE and subtype B. Currently, the HIV-1 epidemic in Malaysia is in a concentrated phase with evidence of predominance of both CRF01_AE and subtype B found among heterosexuals and injecting drug users, respectively. There is urgent necessity to apply a more detailed and continuous molecular characterization and epidemiological monitoring of these recombinant forms in Malaysia. We obtained plasma samples from 115 HIV-1-infected patients who attended HIV clinic at the University Malaya Medical Centre in Kuala Lumpur, Malaysia. The HIV-1 PR-RT, gp120-env and gp41-env genes were amplified and sequenced from 50 samples, while the remaining 65 samples were successfully studied at either one or two HIV-1 specific genomic regions. Cloning, phylogenetic analyses, together with bootscanning methods were employed to assign subtypes and to identify inter-subtype recombination based on all three genomic regions. From the plasma-derived sequences of 50 patients, 46% were found to harbour CRF01_AE, 10% and 6% had subtype B and B’, and a total of 18% of the patients were infected with CRF33_01B, while the remaining 18% of patients was found to have unique recombinant forms. As for the other 65 patients, majority of them harboured CRF01_AE and subtype B. This study shows that co-circulation of multiple HIV-1 subtypes and their recombinant strains are frequent in the Malaysian population, while capable of spreading to different HIV-1 risk groups. Possible recombination hotspots in CRF01_AE/B recombinants are suggested to be within the HIV-1 PR-RT gene region. Further, this study highlights the need to characterize and monitor the molecular epidemiology of these recombinant forms. The ideal environment for the inter-subtype recombination event to take place is created by the co-circulation and dual infections of both CRF01_AE and subtype B. With more HIV-1 CRF01_AE/B recombinant forms emerging and shaping the nature of HIV epidemic in Malaysia, certainly it will complicate the timely diagnosis of these molecularly altered HIV-1 forms. The recent identification of the novel CRF33_01B suggests the emergence of other new CRF01_AE/B inter-subtype recombinant forms in Malaysia, as preliminarily demonstrated in some HIV-1 patients identified in the first part of this study. The peripheral blood mononuclear cells (PBMCs) of these HIV-1 patients were co-cultured with those of healthy donors, which we then isolated the proviral genomic DNA. The nested long-range PCR was performed to obtain seven overlapping viral genome fragments that made up the whole viral genome. The detailed phylogenetic, as well as bootscan analyses confirmed the mosaic compositions and recombinant structures of the newly emerging CRF01_AE/B recombinant forms derived from CRF01_AE and subtype B. One of them in particular; HIV-1 isolate 06MYKLD46 is structurally similar to CRF33_01B, except for an extra subtype B fragment within the env region. It also has close phylogenetic relationship and similar breakpoints with CRF33_01B, mainly at the PR-RT region. Furthermore, the other three distinct HIV-1 recombinants; isolates 07MYKLD47, 07MYKLD48 and 07MYKLD49 also display near full-length genomes composed of the backbone of CRF01_AE, with insertions of subtype B fragments at different gene regions. These results indicate the high possibility of second generation of minor recombinant forms derived from CRF33_01B, as well as the continuous evolution and rapid dispersal of CRF01_AE/B recombinants in Malaysia. The high prevalence of newly emerging CRF33_01B (CRF01_AE/B inter-subtype recombinant) may cause a possible epidemiologic shift, attributable to its altered virologic characteristics and possible transmission advantages compared to its parental strains. Two major determinants; the viral factor and host factor have influenced the progress of a productive HIV-1 infection upon virus entry into the host cells. We have assessed the two main viral factors; the in vitro viral replication capacity and the viral fitness of the circulating HIV-1 strains in Malaysia. We have determined that CRF33_01B primary isolate (07MYKLVik) replicates better in activated whole PBMCs and CD4+ T-lymphocytes and is ‘fitter’ than one of its parental strain; CRF01_AE (07MYKLNBL) but not subtype B (07MYKLAfik). Subtype B has more advanced ability to produce a progressive infection in all cell types, including MDMs, and has a comparable viral fitness to that of CRF33_01B. We also investigated the role of host factors in a productive HIV-1 infection, by determining the viral effect on the host cell morphological features. We found that CRF33_01B (07MYKLVik) culture displayed more large syncytia (multinucleated giant cells) with multiple nuclei compared to subtype B (07MYKLAfik) culture, while no snycytia was observed in CRF01_AE (07MYKLNBL) culture. Generally, the cells within CRF33_01B and subtype B cultures appeared to be morphologically distinct from CRF01_AE cultures. This may indicate a more productive HIV-1 infection of CRF33_01B and subtype B, similar to our finding from the in vitro viral replicative capacity and viral fitness assays of these HIV-1 strains. We also studied the effect of different HIV-1 strain infections on host differential gene expression profiles, by using the PCR Array, which detects a total of 84 genes known to be involved in the host response to HIV-1 infection. It was observed that the in vitro infection with CRF33_01B isolates resulted in a more damaging effect on host cells and caused more apoptotic death within the infected cultures, compared to the isolates of its parental subtypes. Moreover, subtype B isolates resulted in a poorer cell response upon viral infection, compared to CRF01_AE/B isolate. Concurrently, it also gave less productive spread of viral infection within the infected cultures, in comparison to CRF01_AE/B isolate. We speculate that if the same scenario is reflected in vivo, CRF01_AE/B inter-subtype recombinant including CRF33_01B would have a better survival rate within the host upon their infection, in comparison to their parental strains. This again strengthens our presumption that CRF33_01B has potential ability to disseminate widely in the Malaysian population and gives a progressive change of the current molecular epidemiological trend by gradually replacing the current predominance of CRF01_AE in the country.
30
Lau, Katherine Aik Hee. „Biology and Molecular Biology of New HIV-1 Recombinants from Malaysia“. University of Sydney, 2009. http://hdl.handle.net/2123/4129.
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PhDHIV-1 is the cause of the majority of global HIV infections. Not only being more virulent, and relatively easily transmitted than HIV-2, HIV-1 is also more extensively studied. HIV-1 is known for its highly recombinogenic nature, together with an extreme genetic variety, both attributable to an error-prone reverse transcriptase which gives rise to heterozygous virion. Sequence diversity of HIV-1 has resulted in identification of 9 subtypes of HIV-1 M group, as well as 43 circulating and a number of other unique recombinant forms of HIV-1. The extensive heterogeneity of HIV-1 has become the main consideration in vaccine development, mainly due to the inherent variability of HIV-1 and the frequent generation of new recombinant forms, which subsequently makes the effort to control the HIV-1 pandemic more challenging. The inter-subtype recombination event is a common phenomenon observed in Malaysia whereby there is a co-circulation of multiple HIV-1 subtypes; CRF01_AE and subtype B. Therefore, it becomes crucial to widen the knowledge of currently emerging CRF01_AE/B inter-subtype recombinants, in order to assist the future regional vaccine design and also to prevent wider spread of these strains. Concurrently, with a better understanding on the characteristics of HIV-1 CRF01_AE/B recombinant forms, further diversification of these strains can possibly be thwarted. The objectives of this study included, firstly to study the molecular epidemiology pattern of different HIV-1 strains, as well as to observe their frequency and distribution. Our second aim was to identify possible derivative from CRF33_01B, and also other new CRF01_AE/B inter-subtype recombinant forms in Malaysia. Thirdly, we aimed to identify possible biological advantages of the CRF33_01B isolates over its parental strains; CRF01_AE and subtype B. Currently, the HIV-1 epidemic in Malaysia is in a concentrated phase with evidence of predominance of both CRF01_AE and subtype B found among heterosexuals and injecting drug users, respectively. There is urgent necessity to apply a more detailed and continuous molecular characterization and epidemiological monitoring of these recombinant forms in Malaysia. We obtained plasma samples from 115 HIV-1-infected patients who attended HIV clinic at the University Malaya Medical Centre in Kuala Lumpur, Malaysia. The HIV-1 PR-RT, gp120-env and gp41-env genes were amplified and sequenced from 50 samples, while the remaining 65 samples were successfully studied at either one or two HIV-1 specific genomic regions. Cloning, phylogenetic analyses, together with bootscanning methods were employed to assign subtypes and to identify inter-subtype recombination based on all three genomic regions. From the plasma-derived sequences of 50 patients, 46% were found to harbour CRF01_AE, 10% and 6% had subtype B and B’, and a total of 18% of the patients were infected with CRF33_01B, while the remaining 18% of patients was found to have unique recombinant forms. As for the other 65 patients, majority of them harboured CRF01_AE and subtype B. This study shows that co-circulation of multiple HIV-1 subtypes and their recombinant strains are frequent in the Malaysian population, while capable of spreading to different HIV-1 risk groups. Possible recombination hotspots in CRF01_AE/B recombinants are suggested to be within the HIV-1 PR-RT gene region. Further, this study highlights the need to characterize and monitor the molecular epidemiology of these recombinant forms. The ideal environment for the inter-subtype recombination event to take place is created by the co-circulation and dual infections of both CRF01_AE and subtype B. With more HIV-1 CRF01_AE/B recombinant forms emerging and shaping the nature of HIV epidemic in Malaysia, certainly it will complicate the timely diagnosis of these molecularly altered HIV-1 forms. The recent identification of the novel CRF33_01B suggests the emergence of other new CRF01_AE/B inter-subtype recombinant forms in Malaysia, as preliminarily demonstrated in some HIV-1 patients identified in the first part of this study. The peripheral blood mononuclear cells (PBMCs) of these HIV-1 patients were co-cultured with those of healthy donors, which we then isolated the proviral genomic DNA. The nested long-range PCR was performed to obtain seven overlapping viral genome fragments that made up the whole viral genome. The detailed phylogenetic, as well as bootscan analyses confirmed the mosaic compositions and recombinant structures of the newly emerging CRF01_AE/B recombinant forms derived from CRF01_AE and subtype B. One of them in particular; HIV-1 isolate 06MYKLD46 is structurally similar to CRF33_01B, except for an extra subtype B fragment within the env region. It also has close phylogenetic relationship and similar breakpoints with CRF33_01B, mainly at the PR-RT region. Furthermore, the other three distinct HIV-1 recombinants; isolates 07MYKLD47, 07MYKLD48 and 07MYKLD49 also display near full-length genomes composed of the backbone of CRF01_AE, with insertions of subtype B fragments at different gene regions. These results indicate the high possibility of second generation of minor recombinant forms derived from CRF33_01B, as well as the continuous evolution and rapid dispersal of CRF01_AE/B recombinants in Malaysia. The high prevalence of newly emerging CRF33_01B (CRF01_AE/B inter-subtype recombinant) may cause a possible epidemiologic shift, attributable to its altered virologic characteristics and possible transmission advantages compared to its parental strains. Two major determinants; the viral factor and host factor have influenced the progress of a productive HIV-1 infection upon virus entry into the host cells. We have assessed the two main viral factors; the in vitro viral replication capacity and the viral fitness of the circulating HIV-1 strains in Malaysia. We have determined that CRF33_01B primary isolate (07MYKLVik) replicates better in activated whole PBMCs and CD4+ T-lymphocytes and is ‘fitter’ than one of its parental strain; CRF01_AE (07MYKLNBL) but not subtype B (07MYKLAfik). Subtype B has more advanced ability to produce a progressive infection in all cell types, including MDMs, and has a comparable viral fitness to that of CRF33_01B. We also investigated the role of host factors in a productive HIV-1 infection, by determining the viral effect on the host cell morphological features. We found that CRF33_01B (07MYKLVik) culture displayed more large syncytia (multinucleated giant cells) with multiple nuclei compared to subtype B (07MYKLAfik) culture, while no snycytia was observed in CRF01_AE (07MYKLNBL) culture. Generally, the cells within CRF33_01B and subtype B cultures appeared to be morphologically distinct from CRF01_AE cultures. This may indicate a more productive HIV-1 infection of CRF33_01B and subtype B, similar to our finding from the in vitro viral replicative capacity and viral fitness assays of these HIV-1 strains. We also studied the effect of different HIV-1 strain infections on host differential gene expression profiles, by using the PCR Array, which detects a total of 84 genes known to be involved in the host response to HIV-1 infection. It was observed that the in vitro infection with CRF33_01B isolates resulted in a more damaging effect on host cells and caused more apoptotic death within the infected cultures, compared to the isolates of its parental subtypes. Moreover, subtype B isolates resulted in a poorer cell response upon viral infection, compared to CRF01_AE/B isolate. Concurrently, it also gave less productive spread of viral infection within the infected cultures, in comparison to CRF01_AE/B isolate. We speculate that if the same scenario is reflected in vivo, CRF01_AE/B inter-subtype recombinant including CRF33_01B would have a better survival rate within the host upon their infection, in comparison to their parental strains. This again strengthens our presumption that CRF33_01B has potential ability to disseminate widely in the Malaysian population and gives a progressive change of the current molecular epidemiological trend by gradually replacing the current predominance of CRF01_AE in the country.
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Silva, Josimar Fernando da. „Energia eletrônica e polarizabilidade da mólecula de hidrogênio ionizada confinada /“. São José do Rio Preto, 2014. http://hdl.handle.net/11449/127625.
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Orientador: Elso Drigo FilhoBanca: João Ruggiero Neto
Banca: Frederico Vasconcellos Prudente
Resumo: No presente trabalho estudamos a energia eletrônica e a polarizabilidade da molécula de hidrogênio ionizada confinada em cavidades de diferentes volumes. Usamos o Método Variacional para realizar os cálculos de energia. O objetivo principal deste trabalho é ampliar o tratamento matemático já existente na literatura. Introduzimos uma função de onda molecular alternativa, que faz uso de apenas um parâmetro variacional para resolver o problema da molécula de hidrogênio ionizada confinada numa cavidade elíptica
Abstract: In this work, we study the electronic energy and the polarizability of ion hydrogen molecule under confinement in different volumes of cavities. We use the Variational Method for estimate the energy. The aim of this work is to extend the mathematical treatment reported in the existing literature. We introduce an alternative molecular wave function, this wave function has only a variational parameter to solve the problem of ion hydrogen molecule under confinement in an elliptical cavity
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Souza, Carolina Penhavel de. „Desenvolvimento de modelos para flavonoides e cumarinas utilizando o campo de força CGenFF /“. São José do Rio Preto, 2014. http://hdl.handle.net/11449/128160.
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Orientador: Alexandre Suman de AraujoBanca: Ernesto Raul Caffarena
Banca: Marinônio Lopes Cornélio
Resumo: A utilização de simulações computacionais como ferramenta no estudo dos mais variados sistemas biomoleculares nos traz a possibilidade de observar o comportamento, organização e interação de seus componentes em nível atômico/molecular. Dentre as inúmeras técnicas de simulação computacional existentes, a mais difundida atualmente é a Dinâmica Molecular (DM). A DM tem um papel importante no que diz respeito à determinação da estrutura, dinâmica e função de um sistema molecular graças à simplicidade de sua função potencial. Essa função potencial e sua respectiva parametrização são chamadas, genericamente, de campo de forças. Dentre os diversos campos de forças propostos na literatura, o CHARMM é um dos mais utilizados e aperfeiçoados atualmente. Com o objetivo de modelar moléculas de interesse farmacológico que interagem com biomoléculas, foi desenvolvida recentemente uma extensão desse campo de forças, o CHARMM General Force Field (CGenFF). A construção da versão inicial do CGenFF foi baseada em moléculas componentes do CHARMM como, por exemplo, o fenol, parametrizado como um precursor para a tirosina. Todos os parâmetros já disponíveis no CHARMM são convertidos e combinados de modo a produzir novos tipos de átomos. Mesmo assim, o CGenFF deve ser usado apenas para moléculas farmacológicas; as macromoléculas biológicas devem ser representadas pelo campo de forças CHARMM original. O estudo de moléculas de interesse farmacológico provenientes de fontes naturais (vegetais, animais ou minerais) sempre resultou no desenvolvimento de fármacos de grande eficiência para o combate de inúmeras doenças. Aproximadamente 50% dos fármacos introduzidos no mercado, durante os últimos 20 anos, são derivados de pequenas moléculas biogênicas. Dentre os compostos naturais com grande potencial para uso como fármacos podemos destacar os flavonoides: eles são...
Abstract: The use of computational simulations as a tool in the study of biomolecular systems creates the possibility to observe the behavior, organization and interaction of the components at atomic/molecular level. Among several computational simulation techniques, the most used is Molecular Dynamics (MD). MD plays an important role in structure determination, dynamics and function of molecular systems due to the simplicity of its potential function. This and their respective parameterization are generically known as force fields. Among the existing force fields, CHARMM is one of the most used and improved today. In order to model molecules of pharmaceutical interest that interact with biomolecules, an extension of this force field, the CHARMM General Force Field (CGenFF), was developed. The construction of the initial version of the CgenFF was based in molecules which compose CHARMM, such as phenol, parameterized as a precursor for tyrosine. All the parameters already available in the CHARMM are converted and combined to produce new types of atoms. Nevertheless, the CGenFF should be used only for pharmacological molecules; the biological molecules should be represented by the original CHARMM force field. The study of molecules of pharmacological interest from natural sources (vegetable, animal or mineral) always resulted in the development of drugs highly efficient to fight several diseases. Approximately 50% of the drugs introduced on the market, during the last 20 years, are derived from small biogenic molecules. Among the natural components with great potential for use as drugs we can highlight flavonoids, our study object: they are polyphenolic compounds naturally present in vegetables, fruit, seeds, nuts and drinks like tea and red wine. These molecules are derived from benzo-γ-pirone and present a wide range of biological activity (antiallergenic, anti-inflammatory, antioxidant, antiviral and...
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Lindqvist, Lisa Margareta. „The molecular dissection of protein synthesis via small molecules“. Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=96682.
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Protein synthesis is a highly regulated process and it is vital to life. If the rate of translation is too slow, proteins will not be replaced fast enough causing an imbalance in protein turnover and eventual cell death. On the other hand, if the rate of translation is too fast, it can lead to uncontrolled growth and potential tumorigenesis. The scientific community is now trying to exploit this concept to create novel anticancer therapies using inhibitors of translation. These inhibitors have also been invaluable to dissecting the mechanism of translation.Hippuistanol is an inhibitor of translation initiation which inhibits eIF4A:RNA interaction. Herein I characterize the binding site of hippuristanol on eIF4A and develop hippuristanol-resistant mutants to demonstrate that both helicase activity and eIF4G:eIF4A interaction are absolutely required for eIF4A to function in translation. As well, I utilize this compound to determine that eIF4B, eIF4H, and eIF3a cross-link to RNA in an eIF4A-dependent manner up to 52 nucleotides downstream from cap structure of the mRNA. We also demonstrate that eIF4E only cross-links to RNA within a few nucleotides of the cap structure and is not visible at 12 nucleotides downstream of the cap structure. These results shed light on the positioning of initiation factors within the 5'UTR.Herein I also present that cytotrienin A, an inducer of apoptosis in leukemia cell lines, as a novel inhibitor of translation elongation. The compound inhibits proper eEF1A function and inhibits translocation when aminoacyl-tRNA is loaded onto the ribosome in an eEF1A-dependent fashion. Cytotrienin A also hindered growth in several models of angiogenesis indicating that this compound has potential as an anticancer therapeutic. These results strengthen the idea that inhibitors of translation have great potential as anticancer agents as well as being great tools to dissect the mechanism of protein synthesis.La synthèse protéique ou traduction est un processus hautement régulé et essentiel à la vie. Si le rythme de synthèse protéique est trop lent, les protéines ne sont pas remplacées assez rapidement créant un débalancement du taux de renouvellement protéique ce qui entraîne la mort cellulaire. À l'opposé, si le rythme de synthèse est trop rapide, ceci peut engendrer une croissance cellulaire anarchique et potentiellement initier la tumorigenèse. La communauté scientifique cherche à exploiter ce concept afin de créer de nouvelles thérapies anticancéreuses utilisant des inhibiteurs de la traduction. Ces inhibiteurs sont également des outils inestimables pour disséquer les mécanismes de la traduction.L'hippuristanol est un inhibiteur de la traduction qui bloque l'interaction entre eIF4A er l'ARN. Ici, j'ai caractérisé le site de liaison de l'hippuristanol sur eIF4A et j'ai développé des mutants résistant à l'hippuristanol qui ont servis à démontrer que la fonction d'hélicase et l'interaction eIF4G:eIF4A sont toutes deux requises pour que eIF4A soit fonctionnel dans la traduction. De plus, j'ai utilisé ce composé pour déterminer que eIF4B, eIF4H et eIF3a sont tous liés à l'ARN par chimio-pontage et ces interactions qui peuvent être détectées jusqu'à 52 nucléotides en aval de la coiffe requièrent eIF4A. Nous avons également démontré que l'association de eIF4E à l'ARNm n'est détectée par chimio-pontage qu'avec les quelques nucléotides immédiatement en aval de la coiffe et n'est pas détectable au niveau du douzième nucléotide. Ces résultats ont éclaircis le positionnement des facteurs d'initiation au niveau du 5'NTR.Ici, je démontre également que la cytotriénine A, un inducteur d'apoptose dans les cellules leucémiques, est un nouvel inhibiteur de l'élongation lors de a traduction. Ce composé inhibe le fonctionnement du facteur eEF1A et inhibe l'étape de translocation dépendante de eEF1A qui ensuit le chargement du complexe aminoacyl-tRNA sur le ribosome. Le cytotriène A empêche également la croissance dans plusieurs modèles d'angiogenèse, indiquant que ce composé possède un potentiel comme agent anticancéreux. Ces résultats renforcent l'idée que les inhibiteurs de la traduction possèdent un énorme potentiel en tant qu'agent anticancéreux, ainsi que comme outils afin de décortiquer les mécanismes gouvernant la synthèse protéique.
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au, M. Wheeler@murdoch edu, und Margaret Wheeler. „Reproductive and Molecular Biology of Eucalyptus marginata“. Murdoch University, 2004. http://wwwlib.murdoch.edu.au/adt/browse/view/adt-MU20040723.140250.
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This thesis examined aspects of the reproductive and molecular biology of Eucalyptus marginata (jarrah). The aims were to develop protocols for controlled pollination, that could be used in clonal orchard trees to breed jarrah seedlings that have a known genetic resistance to Phytophthora cinnamomi (dieback), for use in rehabilitation after mining and logging. An intimate knowledge of the breeding biology of jarrah was necessary to achieve this aim. The project also aimed to increase knowledge of the genetic diversity and structure of jarrah, in order to make informed decisions regarding the collection of material to be used for clonal propagation. Previous research has had little success in producing viable seed from any controlled pollinations, but clonal material resistant to P. cinnamomi has been produced using tissue culture. The question posed in this thesis was Can we improve breeding and propagation techniques of jarrah?
Techniques were developed for testing of in vitro pollen viability and pollen storage, pollination and fertilisation success after controlled pollinations, including determination of stigma receptivity and development of bud isolation techniques using alfoil. The variation in female fertility between genotypes was examined. The use of paclobutrazol was explored as a method of increasing the level of viable seed production in clonal orchard trees. The use of fertiliser as well as the growth retardant was also explored to see if it increased the level of seed production even more. Genetic diversity, genetic differentiation and phylogeny within Eucalyptus marginata were examined using nuclear and chloroplast DNA analysis with Restricted Fragment Length Polymorphisms.
While it was first thought that the fertilisation rate was quite low, it was confirmed that the fertilisation rate is similar to other eucalypt species. The zygote abortion rate was quite high in one clone, but one wild tree had a similar seed production rate to other eucalypt species. The zygote and endosperm appeared to be different in the clone and the wild tree observed. The level of seed production was examined in clones and wild trees and it was found that the level was often quite low, particularly in the clones (0 13% in clones, 0 18% in wild trees) in comparison with other Eucalyptus species, and varied between genotypes. The use of a growth retardant such as paclobutrazol may increase the production of viable seed, if it is applied during autumn. The results were inconclusive for the fertiliser/paclobutrazol experiment, since the paclobutrazol was applied during spring which was the worst time of year for increasing seed production. There were differences between genotypes in reaction to both the paclobutrazol and the fertiliser/paclobutrazol. Genetic diversity was moderate in comparison with other Eucalyptus species, and there was a low level of genetic differentiation between populations in the nuclear genome. No differentiation was observed between the morphologically recognised subspecies in the nuclear genome, but differentiation between the populations on the Swan Coastal Plain and populations on the Darling Plateau was seen in the chloroplast genome, indicating that there was historical separation of these two areas.
The conclusions arising from this work are that while controlled pollinations are possible in Eucalyptus marginata the clones that were used in these experiments have often behaved differently to the wild trees in the time of anthesis and levels of viable seed production, and in one clone (5J119) the zygote and endosperm nuclei appeared to be very different to the zygote and endosperm nuclei of a wild tree. Further investigation is necessary to see if these differences are related to the low level of seed production observed in the clonal populations. Paclobutrazol may be worth exploring further as a means of increasing seed production. Material to be used for rehabilitation and seed orchards can be collected from a wide area in the main distribution of the species, although trees on the Swan Coastal Plain are distinct from the trees in the main forest area in the chloroplast genome.
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Liptack, Michael Keith. „Contributions to the molecular biology of kelp“. Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/NQ51890.pdf.
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Pettersson, Fredrik. „A multivariate approach to computational molecular biology“. Doctoral thesis, Umeå : Univ, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-609.
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Crokett, Nigel. „Molecular biology and enzymology of porphyrin biosynthesis“. Thesis, University of Cambridge, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.334167.
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Partington, Joanna Clair. „Biochemistry and molecular biology of potato bruising“. Thesis, Royal Holloway, University of London, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265182.
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Cohen, Niaz. „Molecular biology of X-linked dilated cardiomyopathy“. Thesis, Imperial College London, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.409407.
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Palmer, Christohper Paul. „Molecular biology of the Amsacta moorei enotmopoxvirus“. Thesis, Oxford Brookes University, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241253.
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Strittmatter, Martina. „Molecular biology of the Ectocarpus / Eurychasma pathosystem“. Thesis, University of Aberdeen, 2011. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=165789.
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Ectocarpus siliculosus is commonly challenged by the intracellular oomycete pathogen Eurychasma dicksonii and unlike most other pathogens affecting algae, it is available in a laboratory-controlled pathosystem. In the context of this PhD project, the molecular processes of algal response to pathogen infection has for the first time been studied on a pathosystem using genome-enabled approaches. The proteomic investigation of the compatible (disease-causing) interaction between E. siliculosus and Eu. dicksonii via comparative two-dimensional electrophoresis elucidated 21 differentially expressed proteins. A number of proteins, identified in this course, have been associated with various stress responses (e.g. heat shock proteins, superoxide dismutases) including defence response in previous studies on macroalgae. Most important, some results of this study uncovered molecular aspects of the host response to biotic stress which have not been documented with elicitor-based studies so far, stressing the biological value of this pathosystem. The identification of a Eurychasma-resistant Ectocarpus strain via a qPCR assay, specifically developed for this pathosystem, will allow future applications of the proteomic approach in the investigation of the incompatible (resistant) interaction. Furthermore, in-silico analysis of the E. siliculosus genome identified homologues of plant defence-related genes, coding for so-called pathogenesis-related (PR) proteins. Taken together, these results open new routes for the understanding of algal host pathogen interactions.
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趙崇諾 und Sung-nok Chiu. „Stochastic models of molecular mechanisms in biology“. Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1992. http://hub.hku.hk/bib/B31210752.
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Gossage, Sharon Marie. „Molecular and cellular biology of Leishmania development“. Thesis, University of Liverpool, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.405059.
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Harris, Neil. „The molecular biology of tomato leaf abscission“. Thesis, University of Nottingham, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241090.
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Alrokayan, Salman A. H. „Molecular biology of cholesterol metabolism in humans“. Thesis, University of Nottingham, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.261424.
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46
Asmara, Widya. „Molecular biology of two 2-haloacid halidohydrolases“. Thesis, University of Kent, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293909.
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Yasmin, Mahmuda. „Molecular biology of fulminant hepatitis B viruses“. Thesis, University of Glasgow, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.360121.
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Rao, Srinath Krishna. „The molecular biology of plant phosphoglycerate kinases“. Thesis, King's College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244128.
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Robinson, Jayne. „The molecular biology of human enteric caliciviruses“. Thesis, University of Southampton, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.302313.
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Ryan, Lucy Anne. „The molecular biology of plant growth control“. Thesis, De Montfort University, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.328065.
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