Dissertations / Theses on the topic 'RNA pathogenesis'
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Frederick, Madeline Rose. "The role of RNA-editing in viral mediated pathogenesis." Kent State University Honors College / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ksuhonors152545654349718.
Full textAlsomali, Khayria. "Investigating RNA editing in the pathogenesis of amyotrophic lateral sclerosis." Thesis, University of Sheffield, 2015. http://etheses.whiterose.ac.uk/9182/.
Full textTalbot, Kevin. "The molecular pathogenesis of autosomal recessive spinal muscular atrophy." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300137.
Full textFris, Elizabeth Megan. "Small RNA Sibling Pairs RyfA and RyfB in Shigella dysenteriae and their Impact on Pathogenesis." Ohio University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1531480621100282.
Full textFahl, Willian de Oliveira. "Marcadores moleculares para a patogenia de vírus da raiva: relação entre períodos de incubação, carga viral e os genes codificadores das proteínas virais P e L." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/10/10134/tde-24072014-103209/.
Full textRabies is an acute, progressive and infectious disease of the central nervous system of mammals, caused by Rabies virus (RABV). Although preventable by vaccine, it remains a serious public health problem, and is responsible for the death of humans and many other animals, including those of economic interest. This study aimed to assess the relationship between polymorphisms in genes encoding the P and L proteins of RABV samples belonging to antigenic variants 2 and 3 and incubation periods and titers in mice. For this, samples isolated from different mammalian rabies reservoirs of the Orders Carnivora and Chiroptera and samples of cattle from endemic areas for rabies virus were selected. The sequences obtained were used to construct phylogenetic trees to search for the segregation patterns of strains. The results showed that there were no markers or polymorphisms that explain variations in incubation periods and lethality amongst strains belonging to antigenic variants 2 and 3. This information might be used for discussions about the importance of rabies reservoirs, the dynamics of the virus maintenance and evolution of the different forms of this zoonotic disease among infected animals, contributing to further study about the search for molecular markers for pathogenesis.
Zentner, Gabriel Etienne. "Genomic analysis of ribosomal DNA and its application to the investigation of disease pathogenesis." Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1321478238.
Full textSantana, Estevan Alexis. "Identification of a Fur-regulated small regulatory RNA in nontypeable Haemophilus influenzae." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1410472201.
Full textCunyat, Viaplana Francesc. "Changes in the HIV-1 env gene: Implications at the RNA and protein structure levels." Doctoral thesis, Universitat Autònoma de Barcelona, 2012. http://hdl.handle.net/10803/96233.
Full textLa glicoproteína de la envuelta (Env) es una de les proteínas claves del VIH-1 en patogénesis. La secuencia del gen env es importante para codificar la Env pero también para las estructuras secundarias de los RREs presentes en sus tránscritos. La relevancia de estos dos elementos ha sido comprobada extensamente, pese a que ensayos funcionales aún son requeridos en ambos casos para estudiar el impacto de cambios específicos. El tratamiento con el inhibidor de fusión T-20 selecciona virus resistentes después de adquirir cambios en el gen env. Para estudiar variantes funcionalmente relevantes de env que se encontraran in vivo decidimos utilizar mutaciones asociadas a T-20. Las predicciones de las estructuras secundarias de los RRE resultaron alteradas en los cambios que codificaban para G36V/D, V38A, Q40H y L45M, pero no para N43D o Q40H-L45M. Funcionalmente demostramos que sólo los mutantes que presentan el cambio L45M en su secuencia sufren un impacto de unión a la proteína viral Rev cuando ésta se encuentra en bajas concentraciones, sugiriendo que los cambios nucleotídicos que afectan a la formación del aminoácido 45 de gp41 juegan un papel en la unión a Rev. No obstante, la capacidad de transporte al citoplasma de estos RRE no está afectada. Por lo tanto, alteraciones en las estructuras secundarias predictivas a partir de secuencias nucleotídicas no necesariamente implican impactos funcionales y la mutación L45M tampoco se incorpora como mutación secundaria debido a la restauración de las funciones del RRE. Como es importante caracterizar funcionalmente Envs derivadas de pacientes para estudiar su patogenicidad, establecimos una metodología completa basándonos en el papel principal de la subunidad gp41. Los resultados demostraron que la línea celular efectora es esencial para optimizar la sensibilidad de los ensayos. La línea celular 293T debería utilizarse para experimentos de fusión y la HeLa per analizar parámetros de citopaticidad. Estudios clínicos habían sugerido que virus que contenían la mutación V38A y el polimorfismo viral N140I estaban asociados a una fallo virológico y beneficios inmunológicos del paciente debido a que eran menos patogénicos. Para entender estos datos discordantes analizamos Envs derivadas de pacientes y vimos que cuando éstas tenían los cambios V38A-N140I tenían menos capacidad para matar células diana de forma individual pese a no tener alterada su capacidad fusogénica. Estos datos remarcan la importancia del contexto de la Env y el papel central de gp41 en la patogénesis del VIH-1.
The Env glycoprotein is one of the key proteins used by HIV-1 to mediate its pathogenicity. The sequence of the env gene is important to encode the Env glycoprotein but also for the secondary structure of the RRE that harbor its transcripts. The relevance of both elements has been extensively proved, although functional assays were needed in both cases to study the impact of specific changes. Treatment with the fusion inhibitor T-20 in patients infected with HIV-1 select resistant viruses to this drug after acquiring changes in their env gene. Therefore, we decided to use T-20-associated changes in order to functionally study relevant in vivo env variants. Predictions of the RRE secondary structures showed alterations when they were encoding for the changes G36V/D, V38A, Q40H and L45M, but not when harboring N43D and Q40H-L45M. Functional data showed that only the mutants harboring the L45M mutation had impairments in their binding capacity to Rev when this protein was at low concentrations, suggesting that the nucleotide changes affecting the encoding of the amino acid 45 in gp41 plays a role in Rev binding. However, none of the RRE variants were affected in their ability to being transported to the cytoplasm. Thus, it was found that alterations in RRE secondary structures predicted from nucleotide sequences might not necessary imply functional impairments and that the L45M change was not incorporated as a secondary mutation due to a restoration of the RRE functions. As it is important to functionally characterize patient-derived Envs to understand their in vivo pathogenesis, we established a complete methodology to study them by focusing on the main role of the subunit gp41. Based on our results, the correct selection of the effector cell line is essential to optimize the sensitivity of the assays. The 293T cell line might be used for fusogenic experiments and the HeLa for analyzing death parameters. Clinical trials had suggested that V38A viral mutants arising in an Env context containing the N140I polymorphism, were low pathogenic due to they were associated with virological failure and immunologic benefits. In order to understand these in vivo discordant data, we used our complete methodology to analyze patient-derived Envs that harbored these changes. We found that the V38A mutant Envs that were arisen in a N140I context were less able to induce single-cell death to target cells despite not having an altered fusogenic capacity. Thus, these data supports the importance of the Env context and the main role of gp41 in HIV-1 pathogenesis.
Wilf, Nabil M. "The role of post-transcriptional regulators in pathogenesis and secondary metabolite production in Serratia sp. ATCC 39006." Thesis, University of Cambridge, 2011. https://www.repository.cam.ac.uk/handle/1810/245284.
Full textDelbianco, Alice. "Molecular mechanisms involved in the pathogenesis of beet soil-borne viruses." Phd thesis, Université de Strasbourg, 2013. http://tel.archives-ouvertes.fr/tel-01017177.
Full textSingla, Meenu. "Occurrence and Relevance of Trans-kingdom RNAi against Phytopathogenic Bacteria." Electronic Thesis or Diss., Sorbonne université, 2019. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2019SORUS375.pdf.
Full textWe first generated and characterized Arabidopsis-based transgenic systems expressing artificial small RNAs directed against key virulence-associated genes from Pto DC3000. Interestingly, we found that these Arabidopsis-encoded small RNAs were competent in repressing the expression of the targeted virulence factors during infection. This Antibacterial Gene Silencing (AGS) phenomenon was associated with a reduced bacterial pathogenesis, which was also observed upon external application of corresponding plant-derived small RNAs onto wild-type Arabidopsis and tomato leaves prior to infection. Furthermore, we demonstrated that these plant small RNA species were causal for both AGS and pathogenesis suppression. This implies that the Gram-negative bacterium Pto DC3000 is capable of taking-up –passively and/or actively– small RNAs despite the presence of a cell wall comprising an intricate double membrane structure, namely the bacterial inner and outer membranes. In addition, we discovered that apoplastic small RNAs, which are competent for AGS, were either embedded into Extracellular Vesicles (EVs) or presumably in a free form. The latter small RNA species have not yet been reported and were referred to as Extracellular Free Small RNAs (efsRNAs). Overall, this thesis work unveils a novel phenomenon of trans-kingdom regulation between a eukaryotic host and a prokaryotic pathogen
Bruch, Daniel Mathias Julius [Verfasser], Günter [Akademischer Betreuer] [Gutachter] Höglinger, Thomas [Gutachter] Misgeld, and Stefan [Gutachter] Lichtenthaler. "New insights into factors affecting the pathogenesis of Progressive Supranuclear Palsy: Tau splicing and the effect of protein kinase RNA-like endoplasmic reticulum kinase (PERK) dysfunction / Daniel Mathias Julius Bruch ; Gutachter: Günter Höglinger, Thomas Misgeld, Stefan Lichtenthaler ; Betreuer: Günter Höglinger." München : Universitätsbibliothek der TU München, 2017. http://d-nb.info/1135385327/34.
Full textDando, Samantha Joan. "Ureaplasma parvum : understanding the complexities of intra-amniotic infection in an ovine model." Thesis, Queensland University of Technology, 2012. https://eprints.qut.edu.au/50958/1/Samantha_Dando_Thesis.pdf.
Full textGonçalves, Carla Aguiar. "The role of polyunsaturated fatty acids in bacterial pathogenesis." Master's thesis, Universidade de Aveiro, 2014. http://hdl.handle.net/10773/13794.
Full textPolyunsaturated fatty acids (PUFAs) comprise a class of essential micronutrients, which are essential for normal development, cardiovascular health, and immunity. The role of lipids, including long-chain fatty acids, in the immune response is increasingly being recognized as beneficial regulators of the immune systems. However, the mechanisms by which PUFAs modulate innate immunity are yet to be fully clarified. C. elegans has been used in several recent studies as a simple animal model for the study of host-pathogen interactions, generating important insights into both bacterial pathogenesis and host innate immunity. Many of the virulence mechanisms used by bacterial pathogens to cause disease in mammalian hosts have also been shown to be important for pathogenesis in C. elegans and, similarly, important features of the host innate immunity have been evolutionarily conserved between C. elegans and mammals. This project is focused on addressing the role of polyunsaturated fatty acids in bacterial pathogenesis using C. elegans as model system. We find that knockdown of some elongase genes increase the worms’ susceptibility towards infection with the adherent-invasive Escherichia Coli LF82, isolated from a patient suffering from Crohn’s disease. Moreover, dietary supplementation with the fatty acid γ-linolenic acid rescued the enhanced pathogen susceptibility of C. elegans lacking a Δ6 desaturase. The fatty acid profile of the nematode is altered upon infection with pathogenic LF82. qRT-PCR analysis allowed to determine that stress and autophagy genes are induced in C. elegans infected with this particular type of E. coli. Autophagy was found to be increased on C. elegans challenged with LF82, as determined by fluorescence microscopy. Collectively these results suggest an important role for PUFAS in the innate immune response and indicate that autophagy may have a contribution for C. elegans response towards the pathogen E. coli LF82.
Schrick, Katharina [Verfasser]. "Regulation der Genexpression des RNA-bindenden Proteins KSRP und dessen Bedeutung für die Pathogenese von chronisch inflammatorischen Erkrankungen / Katharina Schrick." Mainz : Universitätsbibliothek Mainz, 2018. http://d-nb.info/1173283552/34.
Full textFaissner, Simon Raoul [Verfasser], Andrew [Gutachter] Chan, and Karl [Gutachter] Überla. "Die Pathogenese der HIV-Demenz : HIV-infizierte monozytäre Zellen aktivieren humane Mikroglia abhängig von zytosolischer RNA / Simon Raoul Faissner ; Gutachter: Andrew Chan, Karl Überla ; Medizinische Fakultät." Bochum : Ruhr-Universität Bochum, 2014. http://d-nb.info/1209358875/34.
Full textSamaraweera, Saumya Erandathi. "Double-stranded RNA as a pathogenic agent in a Drosophila model of dominant expanded repeat diseases." Thesis, 2013. http://hdl.handle.net/2440/90755.
Full textThesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 2013
Bruslind, Linda D. "Pathogenic and molecular characterization of three closely related isolates of infectious pancreatic necrosis virus (IPNV)." Thesis, 1997. http://hdl.handle.net/1957/34139.
Full textGraduation date: 1997
Apicco, Daniel. "Emerging roles for RNA binding proteins in the pathogenesis of Alzheimer's disease and frontotemporal dementia." Thesis, 2017. https://hdl.handle.net/2144/23406.
Full textSanchez, Caballero Ignacio. "Using the host immune response to hemorrhagic fever Viruses to understand pathogenesis and improve diagnostics." Thesis, 2016. https://hdl.handle.net/2144/14489.
Full textMahmoudi, Ebrahim. "Study of miRNA and circular RNA role and mechanism in synaptic plasticity and the pathogenesis of schizophrenia." Thesis, 2019. http://hdl.handle.net/1959.13/1412765.
Full textSchizophrenia is a severe psychiatric disorder attributed to neurodevelopmental changes in connectivity and neurotransmission. While the acute psychotic symptoms usually respond to antipsychotic treatment, the chronic negative and cognitive symptoms are less responsive and represent a major unmet need in psychiatry. With a greater understanding of the molecular basis of the disorder, especially the debilitating cognitive symptoms it should be possible to refine the treatment options and improve the outcome for millions of people. With heritability around 80%, genetics has the potential to achieve important new insights into the biology of the disorder. One of the most interesting candidates to emerge from genome wide association studies is MIR137, a gene encoding the microRNA miR-137 whose expression seems essential for neural processes and brain development. As this gene encodes a small non-coding RNA, most of the functionally significant variation is likely to modify transcription and this is supported by postmortem analysis with reduced expression from the risk allele. One of these in close proximity to the miR-137 encoding segment is a 15-bp Variable Number Tandem Repeat (VNTR) (rs58335419). To investigate possible regulatory role of this variant in disease associated changes in cognitive and neuroanatomical features, DNA sequencing was performed on a cohort of schizophrenia and non-psychiatric controls with respect to their neurocognitive and neuroimaging phenotypes established by a battery of cognitive testing and magnetic resonance imaging. The results revealed VNTR was associated with cognitive performance, with the 4-repeat variant enriched in the cognitive deficit subtype of schizophrenia. Surface-based morphometry of imaging data also revealed that the VNTR carriers have significantly thinner grey matter in the left inferior temporal gyrus, deeper right mid-cingulate, and deeper right postcentral sulci relative to non-carrier individuals. These findings suggest that MIR137 VNTR has biological function in the brain development and etiology of schizophrenia, particularly in relation to cognitive symptoms. There is recent evidence to suggest that miRNA expression, more broadly, is important for brain function and synaptic plasticity, and is implicated in schizophrenia. The expression of these molecules is dynamically regulated by environmental exposures, including those associated with psychiatric disorders. Their function can also be modulated by another class of noncoding RNAs, known as circular RNA (circRNA). These transcripts, which are highly enriched in the brain, contain binding sites for miRNA, enabling them to act as endogenous competitors. To establish a more comprehensive model of gene regulatory networks in the neuronal biology, we profiled the expression of circRNA and analyzed their differential expression in neuronal development and aging, neuronal excitation, and in the pathophysiology of schizophrenia using RNA sequencing. Interestingly, the brain showed the highest level of enrichment and expression change during aging with an increased trend detected throughout the life span of the rats. Bioinformatic analysis of the circRNA-miRNA interaction indicated that the age-associated circRNAs might be involved in ageing processes by regulating mRNAs expression through sponging miRNAs. The analysis of circRNA regulation in neuronal depolarization revealed a significant alteration in circRNA abundance which coincided with a change in miRNA and mRNA abundance, suggesting a circRNA-mediated gene regulation mechanism in the cellular response to neural activity. This was supported by both in silico and functional analysis suggesting that circular transcripts have the capacity to impact mRNA expression through interaction with common miRNAs. Finally, exploration of circRNA in neuropsychiatric disorder of schizophrenia revealed a substantial depletion of these transcripts in the disorder. A significant enrichment of neural functions and neurological disorders was observed for the differentially expressed circRNAs host genes in gene set analysis. Many of the depleted circRNAs have the potential to sequester miRNAs that were previously implicated in the neuropathology of schizophrenia, potentially exacerbating the functional impact of their dysregulation via posttranscriptional gene silencing. In summary, the data presented in this thesis provide evidence of miRNA and circRNA association with neuronal development and neuronal activity, and their alteration in the pathogenesis of schizophrenia.
Li-Cheng and 劉力誠. "Involvement of the Outer Membrane Proteins in the Pathogenesis of Klebsiella pneumoniae :a role of RNA Chaperone Hfq." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/28138985681911974866.
Full text中山醫學大學
醫學研究所
95
Klebsiella pneumoniae is a common pathogen of hospital- and community-acquired infections, causing urinary tract infections, nosocomial pneumonia, meningitis and pyogenic liver abscess. K. pneumoniae infections tend to occur in immunocompromised individuals, especially diabetic patients with high morbidity and mortality rates. In Taiwan, K. pneumoniae is the primary pathogen for pyogenic liver abscesses; however, its pathogenesis mechanism still remains unclear. Since outer membrane proteins are important for the pathogenesis and physiology of Gram-negative bacteria, in this study, we determined the role of outer membrane proteins in the pathogenesis of K. pneumoniae as well as the possible regulatory mechanism controlling the expression of these proteins. Inoculation with BALB/c mice with outer membrane fractions of K. pneumoniae was found to provide mice immunity against the wild type infection after six weeks, indicating that outer membrane proteins played a crucial role during K. pneumoniae infections. Given Guillier, et. al in 2006 reported that expression of outer membrane proteins is controlled by small regulatory RNAs via mediation with the RNA chaperone Hfq, in order to examine the possible role of Hfq in the outer membrane expression, a hfq deletion mutant was initially constructed with allelic exchange technique. In our BALB/c infectious model via the GI route, the deletion of hfq gene slightly increased bacterial virulence of K. pneumoniae. Besides, the deletion of hfq gene also affected the physiology of K. pneumoniae in many aspects including bacterial growth curves upon different conditions, production of capsular polysaccharides mucoviscosity of colony, and the expression profiles of outer membrane proteins. Moreover, this deletion slightly increased the protein level of outer membrane protein OmpA. Based on a proteomics analysis, several outer membrane proteins were found to express differentially in the hfq deletion mutant when compared with the wild type strain. Characterization of these Hfq-dependent outer membrane proteins and determination of the underlying regulatory circuits require further studies.
"MicroRNA profiling of human hepatocytes induced by HBx in hepatocarcinogenesis." 2009. http://library.cuhk.edu.hk/record=b5894144.
Full textThesis (M.Phil.)--Chinese University of Hong Kong, 2009.
Includes bibliographical references (leaves 100-119).
Abstract also in Chinese.
Abstract (English version) --- p.i
Abstract (Chinese version) --- p.iii
Acknowledgments --- p.v
Table of Contents --- p.vii
List of Tables --- p.x
List of Figures --- p.xi
List of Abbreviations --- p.xiii
Chapter CHAPTER 1 --- INTRODUCTION --- p.1
Chapter 1.1 --- Hepatocellular Carcinoma --- p.1
Chapter 1.1.1 --- Epidermiology --- p.1
Chapter 1.1.2 --- Etiology --- p.1
Chapter 1.2 --- Hepatitis B Virus --- p.3
Chapter 1.2.1 --- The Epidermiology of Hepatitis B Virus Infection --- p.3
Chapter 1.2.2 --- The Morphology and Genome of Hepatitis B Virus --- p.4
Chapter 1.2.3 --- HBV Genotypes and Their Significance --- p.8
Chapter 1.3 --- Hepatitis B Virus X Protein --- p.9
Chapter 1.3.1 --- HBx Alters Various Signal Transduction Pathways --- p.10
Chapter 1.3.2 --- HBx Interacts with Various Transcription Factors and Co-activators --- p.12
Chapter 1.3.3 --- HBx Induces Epigenetic Alterations --- p.14
Chapter 1.3.4 --- Identification of COOH-terminal Truncated HBx in Liver Tumors --- p.15
Chapter 1.4 --- MicroRNAs --- p.17
Chapter 1.4.1 --- Transcriptional Regulation and Biogenesis of MicroRNAs --- p.18
Chapter 1.4.2 --- MicroRNAs and Cancer --- p.21
Chapter 1.4.3 --- MicroRNAs and HCC --- p.25
Chapter 1.5 --- Hypothesis and Aims of the Study --- p.29
Chapter CHAPTER 2 --- MATERIALS and METHODS --- p.30
Chapter 2.1 --- Patients --- p.30
Chapter 2.2 --- Cell Lines --- p.30
Chapter 2.3 --- Cloning of Various HBx Constructs --- p.32
Chapter 2.3.1 --- PCR Amplification of HBx Fragments --- p.32
Chapter 2.3.2 --- Cloning of HBx Fragments into TA-vectos --- p.33
Chapter 2.3.3 --- Heat Shock Transformation --- p.33
Chapter 2.3.4 --- Sub-cloning of HBx Fragments into Lentiviral Vectors --- p.34
Chapter 2.4 --- Generation of Lentivirus --- p.37
Chapter 2.4.1 --- Lentivirus Infection --- p.37
Chapter 2.5 --- RNA Extraction --- p.38
Chapter 2.6 --- Western Blot Analysis --- p.39
Chapter 2.7 --- MiRNA Microarray --- p.40
Chapter 2.7.1 --- Cyanine3-pCp Labeling of RNA Samples --- p.40
Chapter 2.7.2 --- Sample Hybridization --- p.41
Chapter 2.7.3 --- Microarray Wash --- p.41
Chapter 2.7.4 --- Array Slide Scanning and Processing --- p.41
Chapter 2.8 --- Detection of HBx Gene Deletion by PCR --- p.43
Chapter 2.9 --- Immunohistochemistry --- p.44
Chapter 2.10 --- Quantitative Real-time PCR --- p.45
Chapter 2.11 --- Proliferation Assay --- p.47
Chapter 2.12 --- Cell Cycle Analysis --- p.48
Chapter 2.13 --- Annexin V Apoptosis Assay --- p.49
Chapter 2.14 --- Colony Formation Assay --- p.50
Chapter 2.15 --- Statistical Analysis --- p.51
Chapter CHAPTER 3 --- RESULTS --- p.52
Chapter 3.1 --- Detection of Full-length and COOH-terminal Truncated HBx in HCC Tissues --- p.52
Chapter 3.2 --- Confirmation of HBx Expression in HCC Tissues --- p.55
Chapter 3.3 --- Comparison of HBx from Different HBV Genotypes for Study --- p.61
Chapter 3.4 --- Functional Characterization of COOH-tterminal Truncated HBx --- p.64
Chapter 3.4.1 --- Selection of COOH-terminal Truncated HBx --- p.64
Chapter 3.4.2 --- Generation of Various HBx-expressing Hepatocyte Cell Lines --- p.66
Chapter 3.4.3 --- Effect of Full-length and COOH-terminal Truncated HBx on Cell Proliferation --- p.69
Chapter 3.4.4 --- Effect of Full-length and COOH-terminal Truncated HBx Cell Cycle --- p.34
Chapter 3.4.5 --- Effect of Full-length and COOH-terminal Truncated HBx on Apoptosis --- p.45
Chapter 3.5 --- MicroRNA Profiling of Various HBx-expressing Hepatocyte Cell Lines --- p.76
Chapter 3.5.1 --- Identification of Deregulated MicroRNAs by Microarray --- p.76
Chapter 3.5.2 --- Validation of Deregulated MicroRNAs by Real-time PCR Analysis --- p.80
Chapter 3.5.3 --- Confirmation of Deregulated MiRNAs in HCC and Adjacent Non-tumor Tissues --- p.84
Chapter 3.5.4 --- Potential Downstream Targets of the HBx-deregulated MiRNAs --- p.87
Chapter CHAPTER 4 --- DISCUSSION --- p.91
Chapter 4.1 --- The Impact of COOH-terminal Truncated HBx in HCC --- p.91
Chapter 4.2 --- The Biological Significance of COOH-terminal Truncated HBx Induced MiRNAs --- p.94
Chapter 4.3 --- Limitations of the Present Study --- p.97
Chapter 4.4 --- Future Studies --- p.98
Chapter CHAPTER 5 --- CONCLUSION --- p.99
REFERENCES --- p.100
Shwetha, S. "Host-Pathogen Interactions in Hepatitis C Virus Infection : Deciphering the Role of Host Proteins and MicroRNAs." Thesis, 2015. http://etd.iisc.ernet.in/2005/3858.
Full textHolley, Concerta Leigh. "Relative contributions of the stringent response mediators (p)ppGpp and DksA to Haemophilus ducreyi virulence in humans." 2015. http://hdl.handle.net/1805/7388.
Full textHaemophilus ducreyi causes chancroid, a sexually transmitted genital ulcerative disease that facilitates the transmission of HIV-1. H. ducreyi also causes non-sexually transmitted cutaneous ulcers in children in tropical regions. During human infection, H. ducreyi is subject to a variety of stresses. The stringent response is a bacterial stress response system induced by nutrient limiting conditions and mediated by guanosine tetra- and pentaphosphate [(p)ppGpp] and the transcriptional regulator DksA. (p)ppGpp and DksA jointly interact with RNA polymerase to regulate genes critical for bacterial survival. We hypothesized that the stringent response is required for H. ducreyi virulence in humans. A ΔrelAΔspoT mutant, which is unable to synthesize (p)ppGpp, was partially attenuated for abscess formation in human volunteers. Loss of (p)ppGpp increased bacterial resistance to phagocytosis and stationary phase survival; however, the mutant was more sensitive to oxidative stress. A ΔdksA mutant was also partially attenuated in humans. The ΔdksA mutant behaved like the (p)ppGpp mutant in stationary phase survival and sensitivity to oxidative stress, but exhibited decreased resistance to phagocytosis. Both mutants had decreased adherence to fibroblasts, but the mechanisms underlying the adherence defect were distinct. To better understand the roles of (p)ppGpp and DksA in regulating gene expression, we performed transcriptome analysis of the parent and mutant strains. (p)ppGpp and DksA deficiency resulted in dysregulation of multiple genes including several known virulence determinants. At stationary phase, (p)ppGpp and DksA targets were not identical but significantly overlapped; as the mutants were phenotypically distinct, this finding underscores both the unique and joint roles DksA and (p)ppGpp play in regulation of H. ducreyi virulence. We conclude that (p)ppGpp and DksA play significant roles in H. ducreyi pathogenesis. This is the first study to show that the stringent response has a direct role in the ability of a bacterial pathogen to cause disease in humans.
Hsieh, Yi-Cheng. "PROPERTIES OF THE TOMBUSVIRUS MOVEMENT PROTEIN AND RNAi SUPPRESSOR THAT INFLUENCE PATHOGENESIS." 2008. http://hdl.handle.net/1969.1/ETD-TAMU-2008-08-33.
Full textRoos, Helena Johanna. "Suppression of African horse sickness virus NS1 protein expression in mammalian cells by short hairpin RNAs." Diss., 2009. http://hdl.handle.net/2263/28937.
Full textDissertation (MSc)--University of Pretoria, 2011.
Microbiology and Plant Pathology
unrestricted
Eggert, Christian. "Untersuchungen zur Biogenese spleißosomaler UsnRNPs und ihrer Bedeutung für die Pathogenese der SMA." Doctoral thesis, 2005. https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-15334.
Full textThe neurodegenerative disease spinal muscular atrophy (SMA) is caused by unsufficient production of the survival motor neuron protein (SMN). This study shows in a SMA-model in Hela cells that SMN deficiency results in reduced de novo synthesis of spliceosomal UsnRNPs (U-rich small nuclear ribonucleoprotein particles). A zebrafish model for SMA revealed that the impaired synthesis of UsnRNPs is a direct cause for the degeneration of axons in motor neurons. This is the first link between a cellular function of SMN and the pathogenesis of SMA
Guerreiro, Soraia Isabel da Silva. "Contribution to unveiling the roles played by small non-coding RNAs in the biology and pathogenesis of Burkholderia cepacia complex bacteria." Master's thesis, 2017. http://hdl.handle.net/10451/27264.
Full textThe development of high-throughput sequencing techniques and continued decrease of associated costs, together with advances in bioinformatics and increasing availability of powerful software for nucleotide and amino acid sequence analyses contributed to the exponential increase of available microbial genomes. These developments have unveiled several novel sequences presenting a size within the range of 50-500 nucleotides (nt) and encoding the now called small non-coding regulatory RNAs (sRNAs). These sRNAs are frequently encoded in intergenic regions, often partially overlapping with the 5’ or 3’ untranslated regions of the vicinal genes or annotated-opening reading frames (ORFs). The current known function for some sRNAs comprises the gene expression regulation through interference RNA mechanisms, mainly at the posttranscriptional level. Bacterial sRNAs may regulate their targets (messenger RNAs) through positive or negative regulation mechanisms. To carry out a negative regulation, the sRNA base pairs with its target in the region containing the initiation codon and/or the ribosome-binding site (RBS), precluding the ribosome binding and consequently preventing the mRNA translation. The Burkholderia cepacia (Bcc) complex comprises nowadays 20 validated and phylogenetically-related species of Gram-negative bacteria. These bacteria are phenotypically similar and genotypically distinct, being widely distributed in different ecological niches such as soil, water, plants, animals and in humans. Some Bcc bacteria have potential application as bioremediation and biocontrol/biopesticides agents due to their unusual metabolic abilities, which include xenobiotics metabolism, production of antifungal compounds and promotion of plant growth. However, Burkholderia species have emerged in 1980s as important opportunistic pathogens, especially to cystic fibrosis (CF) patients. Bcc bacteria have gained the attention of medical and scientific community because they can cause in CF patients a rapid evolving clinical state known as the cepacia syndrome, which can cause a fast and necrotizing pneumonia, septicemia and ultimately results in the patient early death. Bcc bacteria produce a wide variety of virulence factors, possessing intrinsic resistance mechanisms to different antibiotics which lead to a difficult eradication. Over the last years, some Bcc species have also been recognized as emerging nosocomial pathogenic agents in hospitalized non-CF patients, particularly in cancer patients. To identify potential genes involved in the Bcc bacteria virulence, researchers from iBB (Instituto de Bioengenharia e Biociências) prepared mutant libraries derived from B. contaminans IST408 and B. cenocepacia J2315 by random plasposon mutagenesis. This work aims to characterize a mutant derived from B. cenocepacia J2315, identified in an attenuated virulence screening using as model of infection the nematode Caenorhabditis elegans. This mutant, B. cenocepacia SJ2, contains the plasposon inserted in the intergenic region of B. cenocepacia J2315 chromosome 1, located between the coding gene of DNA gyrase subunit A (GyrA) enzyme and the coding gene of an outer membrane protein of the OmpA family. Bioinformatic and Southern blot analyses allowed the identification of the plasposon insertion in the mutant B. cenocepacia SJ2. The plasposon is located 8 nucleotides (nt) after the predicted 5’ UTR beginning of the B. cenocepacia J2315 OmpA-like protein. Therefore, the presence and functionality of the transcript ompA were evaluated by RT-PCR and Western blot, respectively. The results obtained indicated that the plasposon insertion did not affect ompA mRNA transcription or functionality. Bioinformatic analyses also led to the identification of a possible opening reading frame (ORF) in the complementary strand (named ORF3) and encoding a 93 amino acids protein. The presence of this ORF was supported by Northern blot assays previously performed. These assays allowed the identification of a transcript from the complementary strand. However, the amplification of complementary DNA ends (5’ and 3’ RACE) using specific primers for ORF3 region demonstrated that the transcript in study has a 5’ end with a lower size than the expected transcript of the potential protein (ORF3). A transcript containing approximately 179 base pairs and non-interrupted by the plasposon was identified. In the presence of these results, primers for the potential DNA sequence of ORF3 were designed and the results showed that this is the region interrupted by the plasposon. Due to the absence of initiation and termination codons in the region closer to the 179 base pairs transcript, it was hypothesized that the transcript corresponds to a sRNA (MavA). In this work, the presence of two genetic elements, a sRNA and a protein, in the intergenic region of B. cenocepacia J2315 chromosome 1 is described. The coding sequences of both the sRNA and protein are overlapped in, at least, 100 nucleotides. Bioinformatic analysis of the genetic elements showed that they are conserved among the Burkholderia genus. Moreover, the sequence of ORF3 protein also showed to be identical to the sequence of one protein encoded by an annotated ORF in the B. multivorans genome and to five proteins of B. pseudomallei. The assays performed with the strain containing the ORF3 interrupted by the plasposon revealed the involvement of this protein in the resistance of B. cenocepacia J2315 strain to heat-shock stress (50 ºC), susceptibility to the detergent sodium dodecyl sulphate (SDS), biofilms formation, cellular hydrophobicity and antibiotics resistance (imipenem, ceftazidime and tetracycline). In general, these results suggest that this protein is likely involved in the maintenance of the outer membrane integrity and virulence of B. cenocepacia J2315 towards the nematode C. elegans. MavA sRNA identified in the work herein presented was predicted to be a functional homologue of IstR-2 sRNA of Escherichia coli K-12 MG1655. Preliminary results of the MavA sRNA overexpression characterization indicate a possible direct or indirect role in the overexpression of ribosomal protein S12. Phenotypic analysis also showed the involvement in the swimming motility of B. cenocepacia J2315 strain and in resistance to thermal (50 ºC) stress. In addition, this sRNA is not involved in the virulence of B. cenocepacia J2315 towards the C. elegans nematode. Overall, the results presented in this study contribute to a better knowledge of the intergenic region under study and to the identification of a putative ORF and a sRNA, contributing to a better understanding of the biology of Bcc bacteria and the role of sRNAs in the regulation of the expression of putative virulence factors. The identification of MavA sRNA and ORF3 protein highlight the importance of these studies in identifying genetic elements that might be exploited as targets for the development of effective treatments to the B. cenocepacia J2315 strain infections.
O recente desenvolvimento de técnicas de elevado rendimento para sequenciar genomas e a diminuição contínua do custo associado, conjuntamente com os avanços na bioinformática e a disponibilidade de número crescente de ferramentas bioinformáticas para análise de sequências nucleotídicas e aminoacídicas, tornou possível o aumento exponencial dos genomas microbianos disponíveis. Consequentemente, têm vindo a ser descobertos diversos pequenos transcritos com ação regulatória denominados de pequenos RNAs reguladores não codificantes (sRNAs), com tamanhos compreendidos entre 50-500 nucleótidos. Estes sRNAs têm sido identificados essencialmente em regiões intergénicas, junto a genes ou grelhas de leitura (ORFs) anotadas. A função conhecida de um grupo importante desses sRNAs consiste na regulação da expressão génica, principalmente ao nível pós-transcricional, por mecanismos de interferência de RNA. Os sRNAs bacterianos podem exercer nos seus alvos (RNAs mensageiros) uma regulação positiva ou negativa. No caso de ser exercida uma regulação negativa o sRNA estabelece com o seu alvo um emparelhamento na região que contém o codão de iniciação e/ou a região de ligação do ribossoma (RBS), tornando este local inacessível para a ligação do ribossoma e impedindo, assim, a tradução do mRNA. O complexo Burkholderia cepacia (Bcc) é atualmente constituído por 20 espécies de bactérias Gram-negativas validadas e filogeneticamente próximas. As bactérias que compõem este grupo são fenotipicamente semelhantes e genotipicamente distintas, podendo ser isoladas de várias fontes. São exemplo de fontes o solo, a água, a rizosfera de plantas, animais e Humanos. Devido às suas capacidades metabólicas invulgares, algumas estirpes do Bcc apresentam um elevado potencial de aplicação ao nível do biocontrolo, biorremediação e agricultura, pois são capazes de metabolizar xenobióticos, produzir compostos com atividade antifúngica e promover o crescimento de plantas. Contudo, na década de 80 as bactérias incluídas no género Burkholderia, incluindo as englobadas no complexo Bcc, emergiram como agentes patogénicos oportunistas em indivíduos com fibrose quística (FQ). O facto de as bactérias deste complexo produzirem vários fatores de virulência, apresentarem mecanismos de resistência a um largo espetro de antibióticos sendo difíceis de erradicar e de causarem em doentes com FQ infeções por vezes acompanhadas por um estado clínico de evolução rápida que inclui pneumonia necrotizante e septicémia, levando à morte do doente – síndrome cepacia -, faz com que tenham merecido uma elevada atenção da comunidade médica e científica. Acresce que algumas espécies do Bcc têm vindo a ser reconhecidas nos últimos anos como sendo agentes patogénicos nosocomiais emergentes em doentes hospitalizados, principalmente em doentes oncológicos. Com o objetivo de identificar possíveis genes envolvidos na virulência de bactérias do Bcc, investigadores do iBB (Instituto de Bioengenharia e Biociências) construíram bibliotecas de mutantes de B. contaminans IST408 e B. cenocepacia J2315 utilizando plasposões. As bibliotecas de mutantes foram rastreadas tendo como objetivo a identificação de mutantes que exibiam virulência atenuada, utilizando como modelo de infeção o nemátodo Caenorhabditis elegans. O trabalho aqui apresentado teve como objetivo a caracterização de um mutante identificado no rastreio acima mencionado, contendo um plasposão inserido na região intergénica do cromossoma 1 de B. cenocepacia J2315, localizada entre o gene codificante da subunidade A da enzima ADN girase (GyrA) e o gene codificante de uma proteína da membrana externa do tipo A (OmpA). Através de análises bioinformáticas e experimentais, foi possível localizar no mutante B. cenocepacia SJ2 a inserção do plasposão 8 nucleótidos (nt) após o início da região 5’ não traduzida (5’ UTR) do gene que codifica a proteína do tipo OmpA. Neste sentido, foram avaliados a presença e a funcionalidade do transcrito ompA por ensaios de RT-PCR e Western blot, respetivamente. Os resultados obtidos confirmaram que a inserção do plasposão não afetou a transcrição nem a funcionalidade do transcrito correspondente ao gene ompA. As análises bioinformáticas realizadas permitiram ainda a identificação de uma possível grelha de leitura aberta (ORF) na cadeia complementar da região intergénica (designada de ORF3), codificando para uma proteína de aproximadamente 93 aminoácidos. A confirmação da presença desta ORF foi suportada por ensaios de Northern blot realizados anteriormente e que permitiram a identificação de um transcrito a partir da cadeia complementar. No entanto, análises de amplificação em cadeia pela polimerase (PCR) das extremidades do ADN complementar (5’ e 3’ RACE) com sequências oligonucleotídicas iniciadoras específicas para a região da ORF3 demonstraram que o transcrito em causa possui uma extremidade 5’ menor que o esperado para o transcrito da possível proteína (ORF3), permitindo assim a identificação de um transcrito com cerca de 179 pares de bases que se verificou não ser interrompido pelo plasposão. Deste modo, tendo em conta os resultados aqui apresentados foram desenhadas sequências oligonucleotídicas iniciadoras específicas para a sequência de ADN da possível ORF3, tendo-se verificado que esta era a região interrompida pelo plasposão. Devido à ausência de codões de iniciação e de terminação na região próxima do transcrito de 179 pares de base, colocou-se a hipótese deste transcrito corresponder a outro elemento genético, nomeadamente um sRNA, que se denominou de MavA. Neste trabalho é descrita a existência de dois elementos genéticos na região intergénica do cromossoma 1 de B. cenocepacia J2315, um sRNA e um gene que codifica uma proteína, sendo que as sequências codificantes de ambos encontram-se parcialmente sobrepostas em, pelo menos, 100 nucleótidos. As análises bioinformáticas realizadas dos elementos genéticos permitiram a sua identificação como sendo ambos conservados no género Burkholderia. Além disso, demonstraram também que a proteína ORF3 é idêntica à sequência de uma proteína codificada por uma ORF anotada no genoma de B. multivorans e à de cinco proteínas de B. pseudomallei. Ensaios realizados com a estirpe contendo o plasposão a interromper a ORF3 demonstraram que esta proteína está envolvida na resistência da estirpe B. cenocepacia J2315 a choque térmico (50 ºC), suscetibilidade à presença do detergente dodecil sulfato de sódio (SDS), capacidade para formação de biofilmes e hidrofobicidade das células, bem como na resistência a antibióticos (imipeneme, ceftazidima e tetraciclina). De um modo geral, estes resultados apontam para que esta proteína esteja envolvida na manutenção da integridade da membrana externa e virulência da estirpe B. cenocepacia J2315 para o nemátodo C. elegans. O sRNA MavA identificado neste trabalho foi bioinformaticamente previsto como tendo como seu homólogo funcional o sRNA IstR-2 de Escherichia coli K-12 MG1655. Os resultados preliminares da caracterização do sRNA MavA através da sua sobrexpressão demonstram um possível envolvimento direto ou indireto na sobrexpressão da proteína ribossomal S12. As análises fenotípicas mostraram ainda o seu envolvimento na mobilidade da estirpe B. cenocepacia J2315 por swimming e na resistência ao choque térmico (50 ºC). Os resultados obtidos, baseados em ensaios de morte lenta do nemátodo C. elegans sugerem que este sRNA não está envolvido na virulência de B. cenocepacia J2315 neste modelo animal de infeção. Os resultados obtidos no presente trabalho contribuem para um conhecimento mais aprofundado da região intergénica estudada, tendo permitido identificar 2 elementos genéticos parcialmente sobrepostos que codificam uma proteína e um sRNA. Este trabalho constitui assim um contributo para o melhor conhecimento da biologia das bactérias do complexo Bcc e do papel dos sRNAs na regulação da expressão de fatores de virulência. A identificação do sRNA MavA e da proteína ORF3 realça a importância deste tipo de estudos na identificação de elementos genéticos que possam ser explorados como alvos para o desenvolvimento de estratégias terapêuticas mais eficazes com vista ao tratamento das infeções causadas pela estirpe B. cenocepacia J2315.
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