Дисертації з теми "Mutational mechanisms"
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Robertson, Scott C. "Mechanisms of protein kinase activation determined by molecular modeling and mutational analysis /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 1999. http://wwwlib.umi.com/cr/ucsd/fullcit?p9938596.
Повний текст джерелаLegler, Patricia Marie. "Kinetic, magnetic, resonance, and mutational studies of the mechanisms of GDP-mannose mannosyl hydrolase, an unusual nudix enzyme." Available to US Hopkins community, 2002. http://wwwlib.umi.com/dissertations/dlnow/3046492.
Повний текст джерелаKennouche, Paul. "New insights into meningococcal pathogenesis : exploring the role of the major pilin PilE in the functions of type IV pili Mechanisms of meningococcal type IV pili multiple functions revealed by deep mutational scanning." Thesis, Sorbonne Paris Cité, 2018. https://wo.app.u-paris.fr/cgi-bin/WebObjects/TheseWeb.woa/wa/show?t=1972&f=12515.
Повний текст джерелаType IV pili (TFP) are multifunctional micrometer-long filaments expressed at the surface of many prokaryotes. In Neisseria meningitidis, TFP are homopolymers of the major pilin PilE. They are crucial for virulence as they mediate interbacterial aggregation and adhesion to host cells although the mechanisms behind these functions remain unclear. During this doctoral work, we simultaneously determined the regions of PilE involved in pili display, auto-aggregation and adhesion to human cells by using deep mutational scanning. Mining of this extensive functional map of the pilin sequence provides new mechanistic insights: first, the hyperconserved 1-domain of PilE was found to be involved in the balance between pili length and number; moreover, we identified an electropositive cluster of residues centered around Lysine 140 necessary for aggregation; finally, we show the importance of the tip of TFP in adhesion. Overall, these results support a direct role of PilE in aggregation and adhesion to host cells and identify these specific functional domains. This doctoral work opens up new perspectives on the pathogenicity mechanisms of Neisseria meningitidis and could help design new therapies to fight meningococcal disease
Kugelberg, Elisabeth. "Mechanisms of adaptive mutations in bacteria /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-446-5/.
Повний текст джерелаKitzenmaier, Alexandra [Verfasser], Carmen [Gutachter] Villmann, and Erhard [Gutachter] Wischmeyer. "GlyT2-Mutationen als zweithäufigste Ursache bei Hyperekplexie – Pathologischer Mechanismus der Mutation P429L / Alexandra Kitzenmaier ; Gutachter: Carmen Villmann, Erhard Wischmeyer." Würzburg : Universität Würzburg, 2020. http://d-nb.info/1208629344/34.
Повний текст джерелаSahlin, Charlotte. "Pathogenic Mechanisms of the Arctic Alzheimer Mutation." Doctoral thesis, Uppsala University, Department of Public Health and Caring Sciences, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7582.
Повний текст джерелаAlzheimer’s disease (AD) is a progressive neurodegenerative disorder, neuropathologically characterized by neurofibrillay tangles and deposition of amyloid-β (Aβ) peptides. Several mutations in the gene for amyloid precursor protein (APP) cause familial AD and affect APP processing leading to increased levels of Aβ42. However, the Arctic Alzheimer mutation (APP E693G) reduces Aβ levels. Instead, the increased tendency of Arctic Aβ peptides to form Aβ protofibrils is thought to contribute to the pathogenesis.
In this thesis, the pathogenic mechanisms of the Arctic mutation were further investigated, specifically addressing if and how the mutation affects APP processing. Evidence of a shift towards β-secretase cleavage of Arctic APP was demonstrated. Arctic APP did not appear to be an inferior substrate for α-secretase, but the availability of Arctic APP for α-secretase cleavage was reduced, with diminished levels of cell surface APP in Arctic cells. Interestingly, administration of the fatty acid docosahexaenoic acid (DHA) stimulated α-secretase cleavage and partly reversed the effects of the Arctic mutation on APP processing.
In contrast to previous findings, the Arctic mutation generated enhanced total Aβ levels suggesting increased Aβ production. Importantly, this thesis illustrates and explains why measures of both Arctic and wild type Aβ levels are highly dependent upon the Aβ assay used, with enzyme-linked immunosorbent assay (ELISA) and Western blot generating different results. It was shown that these differences were due to inefficient detection of Aβ oligomers by ELISA leading to an underestimation of total Aβ levels.
In conclusion, the Arctic APP mutation leads to AD by multiple mechanisms. It facilitates protofibril formation, but it also alters trafficking and processing of APP which leads to increased steady state levels of total Aβ, in particular at intracellular locations. Importantly, these studies highlight mechanisms, other than enhanced production of Aβ peptide monomers, which could be implicated in sporadic AD.
Segditsas, Stefania. "Mechanisms of intestinal tumorigenesis resulting from APC mutations." Thesis, University College London (University of London), 2008. http://discovery.ucl.ac.uk/15923/.
Повний текст джерелаWilliams, Louise Jane. "Recombinational mechanisms in human genetic diversity." Thesis, University of Nottingham, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342483.
Повний текст джерелаRobinson, Alexis Anne. "Molecular Mechanisms of DJ-1 Mutations in Parkinson's Disease." Thesis, University College London (University of London), 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.487292.
Повний текст джерелаRutherford, Jodie. "Germline p53 mutations : characterisation and mechanisms of P53 dysfunction." Thesis, King's College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.252278.
Повний текст джерелаBartolo, Claire. "Novel mutations and molecular mechanisms in muscular dystrophy patients /." The Ohio State University, 1996. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487940665437141.
Повний текст джерелаCheung, Jonathan Yu. "Pathogenic mechanisms of RAPSN mutations in congenital myasthenic syndromes." Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:c343ca03-563e-4b4a-9e35-aac09bfc5ea7.
Повний текст джерелаAlotibi, Raniah Saleem. "Investigating the mechanisms of telomeric mutation in human cells." Thesis, Cardiff University, 2015. http://orca.cf.ac.uk/84320/.
Повний текст джерелаMotley, William Washburn. "Glycyl-tRNA synthetase mutations in neurological disease : mechanisms and models." Thesis, University of Oxford, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558205.
Повний текст джерелаMurray, Lydia Soraya. "Dissecting the mechanisms of disease of COL4A1 and COL4A2 mutations." Thesis, University of Glasgow, 2014. http://theses.gla.ac.uk/5143/.
Повний текст джерелаKoskiniemi, Sanna. "Dynamics of the bacterial genome rates and mechanisms of mutation /." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-111428.
Повний текст джерелаKubica, Barbara. "Fitness Effects and Resistance Mechanisms of Beneficial Mutations in 'Pseudomonas aeruginosa'." Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/23123.
Повний текст джерелаGomes, Cláudia, Puchol Sandra Martínez, Noemí Palma, Gertrudis Horna, Lidia Ruiz-Roldán, Maria J. Pons, and Joaquim Ruiz. "Macrolide resistance mechanisms in Enterobacteriaceae: Focus on azithromycin." Taylor & Francis, 2016. http://hdl.handle.net/10757/620710.
Повний текст джерелаWiberg, Jörgen. "Mechanisms controlling DNA damage survival and mutation rates in budding yeast." Doctoral thesis, Umeå universitet, Institutionen för medicinsk kemi och biofysik, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-54203.
Повний текст джерелаHardwick, Robert John. "Mechanisms of mutation at mouse expanded simple tandem repeat (ESTR) loci." Thesis, University of Leicester, 2007. http://hdl.handle.net/2381/30375.
Повний текст джерелаKingswell, Nicola Jo. "Pathological mechanisms underpinning amelogenesis imperfecta in mice carrying an amelogenin mutation." Thesis, University of Leeds, 2015. http://etheses.whiterose.ac.uk/10619/.
Повний текст джерелаLiquori, Alessandro. "Deciphering molecular mechanisms of unusual variants in Usher Syndrome." Thesis, Montpellier, 2015. http://www.theses.fr/2015MONTT016.
Повний текст джерелаUsher syndrome (USH) is an autosomal recessive disorder characterized by the association of sensorineural hearing loss (HL) and retinitis pigmentosa (RP), and in some cases, vestibular areflexia. Clinical and genetic heterogeneity are recognised. Indeed, three clinical types can be caused by mutations in one of the 10 known genes and USH2A represents the most frequently involved gene.Approximately 10 % of the USH cases remain genetically unsolved after extensive molecular analysis of the different genes, which includes sequencing of the exons and their intronic boundaries, combined to large rearrangements screening by array CGH. These unsolved cases include patients who do not carry any mutation in any of the known USH genes and patients who carry a single USH mutation. During this thesis we focalised on the study of patients carrying a single mutation in USH2A and PCDH15 gene.First, we have analysed a cohort of well-defined USH2A patients: five patients, for whom a single USH2A heterozygous mutation had been identified and one patient carrying a silent variant in trans to a nonsense mutation. For the 5 patients, we supposed that the second mutation remaining to be found could be localised deep in the introns. Indeed, a deep intronic mutation resulting in the inclusion of a pseudoexon (PE 40) in USH2A transcripts had been identified, following RNA analysis from nasal cells. Unfortunately, analysing USH2A transcripts still represent a challenging approach in a diagnostic settings and it is not always possible. To circumvent this issue, we have developed a DNA-Next Generation Sequencing (NGS) approach to identify deep intronic variants in USH2A and evaluate their consequences on splicing. As a proof of concept and to validate this approach, including the bioinformatics pipeline and the assessment of splicing predictor tools, the patient carrying the PE 40 was analysed at first. Then, the 5 patients were studied using the defined pipeline, which led to the identification of 3 distinct novel deep intronic variants in 4 of them. All were predicted to affect splicing and resulted in the insertion of PEs, as shown by minigene assays. Through this study, we present a new and attractive strategy to identify deep intronic mutations, when RNA analyses are not possible. In addition, the bioinformatics pipeline developed is independent of the gene size, implying the possible application of this approach to any disease-linked gene. Moreover, an antisense morpholino oligonucleotide (AMO) tested in vitro for its ability to restore the splicing alterations caused by one of the identified mutation provided high inhibition rates. These results are indicative of a potential application for molecular therapy.In the second case, we have performed studies on the USH2A c.1377T>A silent variant to investigate its effect on splicing. Analysis of RNA from nasal cells of patients showed that this variant led to the skipping of exon 8 in USH2A transcripts. This was confirmed by minigene assay. Moreover, preliminary studies have been performed using prediction tools and minigene assays to assess the involvement of cis-acting elements in causing the aberrant splicing.In the second part of the thesis, we have analysed an USH1 patient, for whom only one mutation had been identified in the PCDH15 gene. In this case, we combined nasal epithelial cells culture with the analysis of the PCDH15 transcripts. This was performed by sequencing five overlapping RT-PCRs. Through this analysis, we were able to delimit a region within the transcript, which failed to be amplified exclusively in the allele carrying the unidentified mutation. Further analyses have been performed in the corresponding genomic region by NGS-target capture and LongRange PCR associated with Sanger sequencing. However, no evident mutation has been identified so far. Therefore, we suggest the involvement of complex molecular mechanisms that remain to be characterised
Morais, Sara Peres de. "Juvenile Parkinson disease caused by parkin mutations: large deletions and pathogenic mechanisms." Master's thesis, Faculdade de Ciências e Tecnologia, 2011. http://hdl.handle.net/10362/6723.
Повний текст джерелаAutosomal recessive juvenile Parkinson disease (AR-JP) is mainly caused by mutations in PARK2. AR-JP presents with rigidity, bradykinesia and resting tremor, usually before age 40 years. Large PARK2 deletions account for 50% of the mutations identified in patients with AR-JP of Portuguese origin. The PARK2 gene encodes parkin, an E3 ubiquitin ligase, an important part of the cellular machinery that covalently tags target proteins with ubiquitin for degradation by the ubiquitinproteasome system (UPS), the main cellular protein degradation system responsible for targeted degradation of damaged and misfolded proteins. This project aims were: determine the breakpoints of the deletion found in Portuguese patients in order to identify the genomic mechanisms underlying these gene rearrangements and to explore the pathogenic mechanisms of parkin mutations by assessing the dynamics of formation and degradation of aggregates by UPS and also by determining its effects in the UPS degradation capacity and its relation with neuronal death. A successful approach was developed to narrow the deletion breakpoint intronic position. Cellular models expressing wild-type and mutant parkin were developed and characterized regarding mRNA and protein expression, as well as, aggregate formation, cell viability and proteasome activity. Our data show that the different studied mutations do not have an impact on cell viability, although resulted in differences in the number of cell with aggregates for the cells expressing N52MfsX29, L358RfsX77 and R275W mutants as well as in the number of aggregates present in each cell. We were also able to show that proteasome inhibition has as impact both in cell viability and in aggregate formation, resulting in decreased viability and increased aggregate formation. The study of the cellular mechanisms resulting in neuronal dysfunction is crucial for the identification of potential therapeutic targets for Parkinson disease.
Bohman, Lova. "Pathological Mechanisms of Sarcomere Mutations in the Disease Hypertrophic Cardiomyopathy : A Review." Thesis, Linköpings universitet, Institutionen för fysik, kemi och biologi, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-176045.
Повний текст джерелаOonthonpan, Lalita. "Two human Mitochondrial Pyruvate Carrier mutations reveal distinct mechanisms of molecular pathogenesis." Diss., University of Iowa, 2019. https://ir.uiowa.edu/etd/7006.
Повний текст джерелаStarker, Lee. "New Insights in Genetic and Epigenetic Mechanisms Involved in Parathyroid Tumorigenesis." Doctoral thesis, Uppsala universitet, Institutionen för kirurgiska vetenskaper, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-205587.
Повний текст джерелаBall, Nathan B. "Design and characterization of a gel loading mechanism for an ultra-high throughput mutational spectrometer." Thesis, Massachusetts Institute of Technology, 2005. http://hdl.handle.net/1721.1/32881.
Повний текст джерелаIncludes bibliographical references (leaf 51).
A process known as Constant Denaturant Capillary Electrophoresis is used to separate mutant from wild-type DNA at fractions down to 10-7. A device known as an Ultra-high Throughput Mutational Spectrometer is being created to run 10,000 parallel channels of CDCE in order to correlate multiple point mutations in DNA with the diseases that they can cause, such as cancer. By separating the DNA in large populations, the underlying causes of such diseases can be identified. To successfully run CDCE, a high viscosity polymer gel must be loaded into each of the 10,000 channels, each of which are composed of an individual glass capillary with a 75 m inner diameter. A mechanism was designed and tested which loaded gel into 8 channels simultaneously. The mechanism was used to test the relationship between gel loading time in relation to varied pressure and capillary length, through 45 total runs, with 8 channels per run. The relationships were characterized, resulting in two equations that enable an accurate prediction of the fill time necessary to load 10,000 parallel channels simultaneously under varied conditions.
by Nathan B. Ball.
S.B.
Harris, Reuben Stewart. "On a molecular mechanism of adaptive mutation in Escherichia coli." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/nq21574.pdf.
Повний текст джерелаFrida, Jonsson. "Underlying genetic mechanisms of hereditary dystrophies in retina and cornea." Doctoral thesis, Umeå universitet, Institutionen för medicinsk biovetenskap, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-130538.
Повний текст джерелаLiu, Ping. "Structural, Kinetic and Mutational Analysis of Two Bacterial Carboxylesterases." Digital Archive @ GSU, 2007. http://digitalarchive.gsu.edu/biology_diss/26.
Повний текст джерелаDonnelly, Steven. "Molecular mechanisms underlying mutations in Connexin 26 associated with genetically inherited skins disorders." Thesis, Glasgow Caledonian University, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.688293.
Повний текст джерелаKawanishi, Masanobu. "Molecular mechanisms of mutations induced by environmental pollutants, 3-nitrobenzanthrone, crotonaldehyde and acrolein." Kyoto University, 1998. http://hdl.handle.net/2433/157051.
Повний текст джерелаKyoto University (京都大学)
0048
新制・課程博士
博士(工学)
甲第7521号
工博第1762号
新制||工||1124(附属図書館)
UT51-98-W265
京都大学大学院工学研究科環境地球工学専攻
(主査)教授 松井 三郎, 教授 森澤 眞輔, 教授 齋藤 烈
学位規則第4条第1項該当
Lorenzi, Roberto. "Studies on gene conversion as a mutational mechanism in the evolution of major histocompatibility complex genes." Thesis, University of Cambridge, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336766.
Повний текст джерелаMoens, Thomas Grover. "Molecular mechanisms of pathogenesis in Drosophila models of C9orf72 mutation associated ALS/FTD." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10046295/.
Повний текст джерелаWang, Zhibin. "Molecular mechanism of Arabidopsis CBF mediated plant cold-regulated gene transcriptional activation." Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1158600906.
Повний текст джерелаLiu, Fengling. "Kinetic and Crystallographic Studies of Drug-Resistant Mutants of HIV-1 Protease: Insights into the Drug Resistance Mechanisms." Digital Archive @ GSU, 2007. http://digitalarchive.gsu.edu/biology_diss/19.
Повний текст джерелаFearon, Abbie Elizabeth. "Dissection of drug resistance mechanisms in FGFR2 mutant endometrial cancer." Thesis, Queen Mary, University of London, 2015. http://qmro.qmul.ac.uk/xmlui/handle/123456789/9027.
Повний текст джерелаVerkerk, Johanna Maria Henriëtta. "The molecular basis of the fragile X syndrome expansion of a trinucleotide repeat, a new mutational mechanism /." [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 1994. http://hdl.handle.net/1765/13739.
Повний текст джерелаThornburg, Adrienne. "Resolving the molecular mechanisms of inherited deafness caused by missense mutations in cadherin 23." The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1461284758.
Повний текст джерелаSanjuan, Ruiz Inmaculada. "Pathophysiological mechanisms involved in amyotrophic lateral sclerosis caused by mutations in the FUS gene." Thesis, Strasbourg, 2019. http://www.theses.fr/2019STRAJ056.
Повний текст джерелаAmyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two untreatable neurodegenerative diseases. Even thought they are two distinctive diseases, they share a series of clinical, genetic and histological hallmarks, thus defining the ALS-FTD continuum. Mutations in the FUS gene have been linked with ALS, whereas alterations in FUS proteins have been detected in FTD patients. Both diseases are characterized by the presence of cytosolic FUS aggregates.We have studied the autoregulation mechanisms of FUS in a mouse model via de activation of an alternative splicing pathway by the insertion of a human wild-type FUS transgene, which has allowed us to potentially elucidate new therapeutic approaches by gene therapy. Furthermore, our mice develop FTD-like symptoms. Our results suggest an alteration in cortical synapses which could originate the observed cognitive and behavioural deficits, accompanied by alterations in the cholinergic system
Segovia, Ugarte Romulo M. "Synthetic hypermutation : gene-drug mutation rate synergy reveals a translesion synthesis mechanism." Thesis, University of British Columbia, 2017. http://hdl.handle.net/2429/61269.
Повний текст джерелаMedicine, Faculty of
Medical Genetics, Department of
Graduate
Moloney, Dominique Martine. "What is the mechanism of the high mutation rate in Apert syndrome." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.284421.
Повний текст джерелаSun, Song. "Dynamics and Mechanisms of Adaptive Evolution in Bacteria." Doctoral thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-172786.
Повний текст джерелаZorzet, Anna. "Mechanisms of Adaptation to Deformylase Inhibitors." Doctoral thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-123242.
Повний текст джерелаJamieson, Quentin. "The Inactivation Mechanisms of Shaker IR and Kv2.1 Potassium Channels: Lessons from Pore Mutation." Case Western Reserve University School of Graduate Studies / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=case1396357775.
Повний текст джерелаHassan, A. Quamrul. "Molecular complementation of mutant thyroid hormone receptors that disrupt transactivation mechanism." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file 9.11 Mb., 175 p, 2006. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:3205433.
Повний текст джерелаChatron, Nolan. "VKORC1 et résistance aux antivitamines K : étude par modélisation moléculaire." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLN008/document.
Повний текст джерелаVKORC1 is an endoplasmic reticulum membrane-resident enzyme, responsible for vitamin K epoxide reduction to vitamin K quinone that activates coagulation factors synthesis. VKORC1 is thus a prominent target of vitamin K agonists (VKAs) in anticoagulant therapies. However, some VKORC1 mutations lead to physiological dysregulation and/or VKAs resistance. No VKORC1 structural data is available, and postulated topological models are based on biochemical and biophysical experimental observations frequently contradicting. Topology of VKORC1 and involvement of cysteines residues (highly conserved in VKORs) in the protein enzymatic mechanism remain unclear. We built an in silico 3D model of the wild-type human VKORC1 (hVKORC1WT) at the atomistic scale. Molecular dynamics simulations of the protein model, carrying all the cysteines residues in their oxidized form (SH), were used for identification of cysteines residues which may plausibly form disulfide bridges. We thus described hVKORC1WT metastable conformations depicting the functionally relevant states of protein. Study of the vitamin K (in epoxide and in reduced forms) recognition by the predicted conformations of hVKORC1WT revealed their reciprocal selectivity. The hVKORC1WT conformations targeted by each vitamin K form were established and their role in the reduction mechanism of this molecule was explained. Using our results, we postulated the comprehensive enzymatic mechanism of hVKORC1WT and we proposed the 3D structure as the VKAs target. Interactions between the predicted target - hVKORC1WT active state - and three different VKAs were characterized. The obtained affinities (free binding energy) were in good correlation with in vivo measured inhibition constants (Ki), thus validating our theoretical predictions. Our protocol developed for hVKORC1WT is suitable for a study of its mutants. Description of the enzymatic mechanisms of mutated hVKORC1 will lead to understanding of the modified reductase activity or/and to explaining of its resistance to VKAs. Such data are crucial for the development of novel strategies in the design of a new generation of inhibitors overcoming VKAs resistance. Our concept and the established in silico protocol can be extended to analysis of mammalian VKORs and other oxidoreductases family proteins
Sander, Max [Verfasser]. "Die molekularen Mechanismen des angeborenen Wachstumshormonmangels verursacht durch Cystein-Mutationen / Max Sander." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2021. http://d-nb.info/1228860483/34.
Повний текст джерелаThibodeau, Isabelle. "Mutations in Connexin43 and Connexin40 Associated with Human Atrial Fibrillation; Physiology and Mechanism." Thesis, University of Ottawa (Canada), 2010. http://hdl.handle.net/10393/28834.
Повний текст джерелаLasser, Micaela Cari. "Using Xenopus laevis to investigate developmental mechanisms underlying human neurodevelopmental disorders and intellectual disabilities:." Thesis, Boston College, 2020. http://hdl.handle.net/2345/bc-ir:108957.
Повний текст джерелаThesis advisor: Sarah McMenamin
Development of the central nervous system (CNS) is a complex process that requires the proper function of many genes in order for neurons to proliferate and divide, differentiate, and subsequently migrate long distances to form connections with one another. Abnormalities in any one of these cellular processes can lead to detrimental developmental defects. Growing evidence suggests that genetic mutations caused by rare copy number variants (CNVs) are associated with neurodevelopmental disorders including intellectual disabilities (ID), Autism spectrum disorder (ASD), and schizophrenia. Additionally, these pathogenic CNVs are characterized by extensive phenotypic heterogeneity, as affected individuals often present with microcephaly, craniofacial and heart defects, growth retardation, and seizures. Despite their strong association as risk factors towards neurodevelopmental disorders, the developmental role of individual CNV-affected genes and disrupted cellular mechanisms underlying these mutations remains poorly understood. Moreover, it is unclear as to how the affected genes both individually and combinatorially contribute to the phenotypes associated with pathogenic CNVs. Thus, in this thesis, we explore the functional basis of phenotypic variability of pathogenic CNVs linked to neurodevelopmental disorders. In particular, we focus on the 3q29 deletion and 16p12.1 deletion, to provide insight towards the convergent cellular, molecular, and developmental mechanisms associated with decreased dosage of the affected gene homologs using two complementary model systems, Xenopus laevis and Drosophila melanogaster. First, we examine the role of individual homologs of several CNV-affected genes at chromosome 3q29 and their interactions towards cellular processes underlying the deletion. We find that multiple 3q29-affected genes, including NCBP2, DLG1, FBXO45, PIGZ, and BDH1, contribute to disruptions in apoptosis and cell cycle pathways, leading to neuronal and developmental defects. We then expand further upon this work by discerning the individual contribution of four CNV-affected genes at chromosome 16p12.1, POLR3E, MOSMO, UQCRC2, and CDR2, towards neurodevelopment and craniofacial morphogenesis. We demonstrate that several of these genes affect multiple phenotypic domains during neurodevelopment leading to brain size alterations, abnormal neuronal morphology, and cellular proliferation defects. We then explore their functions during vertebrate craniofacial morphogenesis and demonstrate that some 16p12.1-affected genes are enriched in migratory neural crest, and contribute to early craniofacial patterning and formation of cartilaginous tissue structures. Together, these data are the first to suggest that signature neurodevelopmental phenotypes demonstrated in the 3q29 deletion and 16p12.1 deletion may stem from convergent cellular mechanisms including aberrations in neuronal proliferation, apoptosis and cell cycle regulation, and neural crest cell development
Thesis (PhD) — Boston College, 2020
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Biology