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University of Rochester
1.
Huang, Chao.
2’-O-methylation of Yeast Telomerase RNA.
Degree: PhD, 2011, University of Rochester
URL: http://hdl.handle.net/1802/14597 
► In Saccharomyces cerevisiae, telomeres can be replenished by the action of telomerase, a specialized reverse transcriptase consisting of a single RNA (TLC1) and a number…
(more)
▼ In Saccharomyces cerevisiae, telomeres can be
replenished by the action of telomerase, a specialized reverse
transcriptase consisting of a single RNA (TLC1) and a number of
proteins. The RNA component is essential for telomerase activity
both in vivo and in vitro.
In eukaryotic cells, box C/D RNPs
introduce 2’-O-methylations in rRNAs and major spliceosomal snRNAs.
The RNA component of box C/D RNP (box C/D RNA) serves as guide that
dictates the 2’-O-methylation site(s).
Here, we show that
artificial box C/D RNAs, when introduced into yeast cells, target
TLC1 RNA for 2’-O-methylation at specific site(s) with an
efficiency of 70~90%. Remarkably, while 2’-O-methylation at A804 or
A805 in the pseudoknot region results in enhanced telomerase
activity and telomere lengthening, 2’-O-methylation at U809 results
in the opposite effect. Further analyses indicate that targeted
2’-O-methylation does not affect the steady-state level of TLC1
RNA, and that 2'-O-methylated TLC1 RNA is efficiently incorporated
into telomerase RNP. Our results demonstrate the effectiveness of a
novel approach for regulating telomerase activity in vivo through
artificial 2’-O-methylation.
We also provide evidence suggesting
that TLC1 RNA is naturally 2’-O-methylated in its 5’ end region,
and that these modifications require Nop1p, the methyltransferase
associated with box C/D RNP. Our results support the notion that a
naturally occurring telomerase regulatory mechanism may already
exist, in which TLC1 RNA is post-transcriptionally modified in
order to fine-tune its role in catalysis.
Subjects/Keywords: 2’-O-methylation; Telomerase RNA; Yeast; snoRNA; RNA guided RNA Modification
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APA (6th Edition):
Huang, C. (2011). 2’-O-methylation of Yeast Telomerase RNA. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/14597
Chicago Manual of Style (16th Edition):
Huang, Chao. “2’-O-methylation of Yeast Telomerase RNA.” 2011. Doctoral Dissertation, University of Rochester. Accessed December 06, 2019.
http://hdl.handle.net/1802/14597.
MLA Handbook (7th Edition):
Huang, Chao. “2’-O-methylation of Yeast Telomerase RNA.” 2011. Web. 06 Dec 2019.
Vancouver:
Huang C. 2’-O-methylation of Yeast Telomerase RNA. [Internet] [Doctoral dissertation]. University of Rochester; 2011. [cited 2019 Dec 06].
Available from: http://hdl.handle.net/1802/14597.
Council of Science Editors:
Huang C. 2’-O-methylation of Yeast Telomerase RNA. [Doctoral Dissertation]. University of Rochester; 2011. Available from: http://hdl.handle.net/1802/14597
University of Utah
2.
Kuttan, Ashani.
Mechanistic insights into editing site specificity of adenosine deaminases that act on RNA: critical role of a conserved loop.
Degree: PhD, Biochemistry, 2012, University of Utah
URL: http://content.lib.utah.edu/cdm/singleitem/collection/etd3/id/2046/rec/1557
► Adenosine deaminases that act on RNA (ADARs) deaminate adenosines in doublestrandedRNA (dsRNA) to produce inosines. The extent an adenosine is edited dependson the sequence context…
(more)
▼ Adenosine deaminases that act on RNA (ADARs) deaminate adenosines in doublestrandedRNA (dsRNA) to produce inosines. The extent an adenosine is edited dependson the sequence context of the target adenosine. Human ADAR2 (hADAR2) has a 5’nearest neighbor preference of U>A>C>G and a 3’ preference of G>C>U«A, but it is notknown which amino acids mediate these preferences. Previous studies show thatpreferences are derived mainly from the catalytic domain. Thus, we adapted a previouslyreported screen in yeast to identify mutations in the hADAR2 catalytic domain that allowediting of an adenosine in context of a disfavored triplet, GAC. A favored triplet, UAG,was used as the positive control. Hairpin substrates containing disfavored GAC andfavored UAG were based on the R/G editing site of GRIA2 (glutamate receptor,ionotropic, AMPA 2) pre-mRNA, a well-studied endogenous substrate for hADAR2.Four mutants that edited GAC more than WT hADAR2 (E488Q, V493T, N597Kand N613K) and one mutant that did not edit GAC (T490A) were further characterizedby determining their binding affinity, catalytic rate, base-flipping and preferences tounderstand the effect of these mutations on ADAR reactivity. Gel-shift assays showedtwo mutants, N597K and N613K, had ~2-fold higher binding affinity compared to WThADAR2, suggesting these mutants may have been selected in the screen due to tighterbinding. Other mutants E488Q, T490A and V493T, which are on a highly conserved loopclose to the active site, showed similar binding affinity as WT hADAR2 for both UAGand GAC, indicating discrimination was not derived from differences in binding affinity.We also determined catalytic rates, and probed base-flipping by substituting thetarget adenosine with the fluorescent base analog 2-aminopurine (2-AP). Remarkably,with both UAG and GAC substrates, mutants with similar binding affinity showed acorrelation between catalytic rate and base-flipping, as indicated by a change in 2-APfluorescence intensity (FI). Our data provide the first information on the residuesimportant for preferences, and point to a conserved loop as key. Unexpectedly, our datasuggest that hADAR2’s preferences are derived from differences in base-flipping, ratherthan direct recognition of the neighboring base.
Subjects/Keywords: 2-aminopurine; ADAR2; Base-flipping; RNA editing
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APA (6th Edition):
Kuttan, A. (2012). Mechanistic insights into editing site specificity of adenosine deaminases that act on RNA: critical role of a conserved loop. (Doctoral Dissertation). University of Utah. Retrieved from http://content.lib.utah.edu/cdm/singleitem/collection/etd3/id/2046/rec/1557
Chicago Manual of Style (16th Edition):
Kuttan, Ashani. “Mechanistic insights into editing site specificity of adenosine deaminases that act on RNA: critical role of a conserved loop.” 2012. Doctoral Dissertation, University of Utah. Accessed December 06, 2019.
http://content.lib.utah.edu/cdm/singleitem/collection/etd3/id/2046/rec/1557.
MLA Handbook (7th Edition):
Kuttan, Ashani. “Mechanistic insights into editing site specificity of adenosine deaminases that act on RNA: critical role of a conserved loop.” 2012. Web. 06 Dec 2019.
Vancouver:
Kuttan A. Mechanistic insights into editing site specificity of adenosine deaminases that act on RNA: critical role of a conserved loop. [Internet] [Doctoral dissertation]. University of Utah; 2012. [cited 2019 Dec 06].
Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd3/id/2046/rec/1557.
Council of Science Editors:
Kuttan A. Mechanistic insights into editing site specificity of adenosine deaminases that act on RNA: critical role of a conserved loop. [Doctoral Dissertation]. University of Utah; 2012. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd3/id/2046/rec/1557
University of Otago
3.
Baker, Estelle Swainson.
Characterisation of the NS1-2 and NS4 proteins of murine norovirus
.
Degree: 2012, University of Otago
URL: http://hdl.handle.net/10523/2320
► Human noroviruses are highly infectious viruses that cause the majority of acute, non-bacterial epidemic gastroenteritis cases worldwide. Noroviruses belong to the family Caliciviridae and have…
(more)
▼ Human noroviruses are highly infectious viruses that cause the majority of acute, non-bacterial epidemic gastroenteritis cases worldwide. Noroviruses belong to the family Caliciviridae and have a positive-sense
RNA genome of around 7.5 kb. Murine norovirus is a useful model for the uncultivable human strains, and has a 7.4 kb genome with four open reading frames (ORFs). Two of these, ORF2 and ORF3, encode structural proteins and ORF4 encodes a virulence factor. The first open reading frame (ORF1) encodes a polyprotein that is cleaved by the viral protease into six nonstructural proteins. There is limited functional and biophysical information available for two of these nonstructural proteins, NS1-
2 and NS4. The aims of this research were to characterise these two proteins.
The NS1-
2 protein lacks any significant sequence similarity to other viral or cellular proteins. Bioinformatic analyses identified an inherently disordered region (residues 1 – 142) in the highly divergent N-terminal region of the NS1-
2 protein. Expression and purification of the NS1-
2 protein of murine norovirus confirmed these predictions by identifying features typical of an inherently disordered protein. These were a biased amino acid composition with enrichment in the disorder promoting residues serine and proline, a lack of predicted secondary structure, a hydrophilic nature, an aberrant electrophoretic migration, an increased Stokes radius similar to that predicted for a protein from the pre-molten globule family, a high sensitivity to thermolysin proteolysis and a circular dichroism spectrum typical of an inherently disordered protein. The purification of the NS1-
2 protein identified the presence of an NS1-
2 dimer when expressed in Escherichia coli, which was also identified in transfected HEK293T cells and MNV-infected RAW264.7 cells.
The NS4 protein is often referred to as the 3A-like protein due to a similar position in the genome as the 3A protein of poliovirus. However, NS4 shares only limited sequence similarity to polio 3A. The NS4 protein of murine norovirus was expressed in Escherichia coli and purified for the generation of a polyclonal antibody.
Whole transcriptome
RNA-Seq analysis was conducted on transfected RAW264.7 cells to provide important leads on functional roles, effects and host cell responses to in vitro transcripts encoding the complete MNV genome, the ORF1 nonstructural polyprotein, the full-length NS1-
2 protein and the disordered region of NS1-
2. Each transfected cell sample showed an upregulation in anti-apoptotic genes and a downregulation of pro-apoptotic genes, suggesting that MNV, and in particular the disordered region of NS1-
2, manipulates the induction of apoptosis. A downregulation of sterol lipid synthesis genes and an upregulation of Th1-type chemokines were observed in MNV- and ORF1-transfected cells. NS1-
2-transfected cells showed an increased expression for genes encoding intercellular junctions and regulatory proteins, indicating that NS1-
2 is likely to have a multi-functional role affecting…
Advisors/Committee Members: Ward, Vernon (advisor).
Subjects/Keywords: Norovirus;
RNA-Seq;
Disorder;
NS1-2;
NS4
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APA ·
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APA (6th Edition):
Baker, E. S. (2012). Characterisation of the NS1-2 and NS4 proteins of murine norovirus
. (Doctoral Dissertation). University of Otago. Retrieved from http://hdl.handle.net/10523/2320
Chicago Manual of Style (16th Edition):
Baker, Estelle Swainson. “Characterisation of the NS1-2 and NS4 proteins of murine norovirus
.” 2012. Doctoral Dissertation, University of Otago. Accessed December 06, 2019.
http://hdl.handle.net/10523/2320.
MLA Handbook (7th Edition):
Baker, Estelle Swainson. “Characterisation of the NS1-2 and NS4 proteins of murine norovirus
.” 2012. Web. 06 Dec 2019.
Vancouver:
Baker ES. Characterisation of the NS1-2 and NS4 proteins of murine norovirus
. [Internet] [Doctoral dissertation]. University of Otago; 2012. [cited 2019 Dec 06].
Available from: http://hdl.handle.net/10523/2320.
Council of Science Editors:
Baker ES. Characterisation of the NS1-2 and NS4 proteins of murine norovirus
. [Doctoral Dissertation]. University of Otago; 2012. Available from: http://hdl.handle.net/10523/2320
Montana Tech
4.
Strong, Christy.
Characterization of 5 UTR splicing and the CGI in HIV-2 RNA.
Degree: PhD, 2011, Montana Tech
URL: https://scholarworks.umt.edu/etd/183
► HIV-2 tightly regulates several steps of its replication cycle via regulatory elements found within the 5 untranslated region of HIV-2 genomic RNA. Two elements…
(more)
▼ HIV-2 tightly regulates several steps of its replication cycle via regulatory elements found within the 5 untranslated region of HIV-2 genomic RNA. Two elements of interest are the 5 UTR intron and the proposed long distance base pairing interaction between the C-box and G-box termed the CGI. This research focuses on the effects of 5 UTR splicing and the CGI in HIV-2 translation and replication. The central hypothesis is that both 5 UTR splicing and the CGI modulate HIV-2 translation and replication. This hypothesis was tested and supported by employing in vitro translation assays, SELEX, and cell culture studies. Results of these experiments demonstrate that splicing of the 5 UTR intron produces an isoform of gag mRNA that is specialized for high translational efficiency. Further, evidence is provided for a novel branched secondary structure within the CGI that is important for HIV-2 replication. In addition, we show that mutation of the C-box alone can enhance RNA encapsidation and mutation of the G-box can alter levels of Gag protein isoforms. These studies suggest coordinated regulation of RNA translation, dimerization, and encapsidation during HIV-2 replication. This research provides new insight into HIV translational mechanisms, in turn identifying potential antiviral targets that may be exploited for antiviral therapeutic strategies.
Subjects/Keywords: CGI; CGI; gag; HIV-2; RNA; translation
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APA ·
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Manager
APA (6th Edition):
Strong, C. (2011). Characterization of 5 UTR splicing and the CGI in HIV-2 RNA. (Doctoral Dissertation). Montana Tech. Retrieved from https://scholarworks.umt.edu/etd/183
Chicago Manual of Style (16th Edition):
Strong, Christy. “Characterization of 5 UTR splicing and the CGI in HIV-2 RNA.” 2011. Doctoral Dissertation, Montana Tech. Accessed December 06, 2019.
https://scholarworks.umt.edu/etd/183.
MLA Handbook (7th Edition):
Strong, Christy. “Characterization of 5 UTR splicing and the CGI in HIV-2 RNA.” 2011. Web. 06 Dec 2019.
Vancouver:
Strong C. Characterization of 5 UTR splicing and the CGI in HIV-2 RNA. [Internet] [Doctoral dissertation]. Montana Tech; 2011. [cited 2019 Dec 06].
Available from: https://scholarworks.umt.edu/etd/183.
Council of Science Editors:
Strong C. Characterization of 5 UTR splicing and the CGI in HIV-2 RNA. [Doctoral Dissertation]. Montana Tech; 2011. Available from: https://scholarworks.umt.edu/etd/183
5.
Αναστασοπούλου, Πανούλα.
Μελέτη του RNA μέσω της σύνθεσης μικρών οργανικών μορίων.
Degree: 2013, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)
URL: http://hdl.handle.net/10442/hedi/37619
► This thesis refers to the development of strategies concerning the synthesis of novel aminoglycoside analogues that are expected to exhibit improved antibiotic activity and binding…
(more)
▼ This thesis refers to the development of strategies concerning the synthesis of novel aminoglycoside analogues that are expected to exhibit improved antibiotic activity and binding selectivity towards the decoding site of the bacterial ribosomal RNA (A-site). After quoting representative examples from the literature, we focused on synthetic strategies of properly substituted 2-deoxystreptamine (2-DOS) analogues, since 2-DOS consists the diaminocycloexitol core of most natural aminoglycosides. Great emphasis was given to the orthogonal protection of all these analogues, in order to achieve higher flexibility in their functionalization. Particularly, we used as starting material the aminoglycoside neomycin B, which demonstrates considerable antibiotic activity, and we examined in detail several suitable combinations of protecting groups regarding the 2-DOS scaffold, in order to accomplish further variability in the ring’s substitution. Furthermore, we applied these orthogonal strategies on the syntheses of novel representative mono-, di-, tri and tetra-substituted 2-DOS analogues. During these syntheses, we utilized oxazolidinones as drug-carrier groups, as well as triazole rings resulting from 1,3-dipolar cycloadditions. To evaluate the antibiotic activity of selected examples of the newly synthesized 2-DOS analogues we employed in vitro assays, concerning both the whole bacterial ribosome and the A-site. The furnished biological results were promising and provided the first useful information for further investigation of the prospective SAR studies (Structure-Activity Relationship).
Η παρούσα διδακτορική διατριβή αφορά σε ανάπτυξη στρατηγικών για τη σύνθεση καινοτόμων αναλόγων αμινογλυκοζιτών που δυνητικά θα έχουν βελτιωμένη αντιβιοτική δράση και εκλεκτικότητα πρόσδεσης στο αποκωδικοποιητικό κέντρο του βακτηριακού ριβοσωματικού RNA (A-site). Αφού αναφερθούν αντιπροσωπευτικά ανάλογα αμινογλυκοζιτών που υπάρχουν ήδη στη βιβλιογραφία, η προσοχή εστιάζεται σε στρατηγικές σύνθεσης κατάλληλα υποκατεστημένων αναλόγων της 2-δεοξυστρεπταμίνης (2-DOS), η οποία και αποτελεί τον κεντρικό διαμινοκυκλοεξιτολικό δακτύλιο στους περισσότερους φυσικούς αμινογλυκοζίτες. Ιδιαίτερη έμφαση δόθηκε στην ορθογωνικότητα των προστατευτικών ομάδων όλων των αναλόγων, ώστε να επιτευχθεί μεγαλύτερη ευελιξία στην υποκατάστασή τους. Συγκεκριμένα, με πρώτη ύλη τον αμινογλυκοζίτη νεομυκίνη Β, ο οποίος έχει σημαντική αντιβιοτική δράση, εξετάστηκαν εκτεταμένα κατάλληλοι συνδυασμοί προστατευτικών ομάδων στο δακτύλιο της 2-DOS, ώστε να μπορεί να προκύψει κατά βούληση περαιτέρω τροποποίησή της. Εν συνεχεία, έγινε εφαρμογή των ορθογωνικών αυτών στρατηγικών στη σύνθεση αντιπροσωπευτικών μονο-, δι-, τρι- και τετρα-υποκατεστημένων αναλόγων της 2-DOS. Παράλληλα κατά τη σύνθεση των νέων αναλόγων της 2-DOS, έγινε χρήση των οξαζολιδινονών ως φαρμακοφόρων ομάδων, αλλά και της 1,3-διπολικής κυκλοπροσθήκης για την εισαγωγή τριαζολικού δακτυλίου. Σε ορισμένα νεοσυντιθέμενα ανάλογα της 2-DOS εξετάστηκε η αντιβιοτική δράση με in vitro πειράματα, τόσο στο σύνολο του…
Subjects/Keywords: Αντιβιοτικά; Αμινογλυκοζίτες; 2-δεοξυστρεπταμίνη (2-DOS); Ανάλογα 2-δεοξυστρεπταμίνης (2-DOS); Antibiotics; Aminoglycosides; RNA; 2-deoxystreptamine (2-DOS); 2-deoxystreptamine (2-DOS) Analogues
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APA ·
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Manager
APA (6th Edition):
Αναστασοπούλου, . . (2013). Μελέτη του RNA μέσω της σύνθεσης μικρών οργανικών μορίων. (Thesis). National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Retrieved from http://hdl.handle.net/10442/hedi/37619
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Αναστασοπούλου, Πανούλα. “Μελέτη του RNA μέσω της σύνθεσης μικρών οργανικών μορίων.” 2013. Thesis, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Accessed December 06, 2019.
http://hdl.handle.net/10442/hedi/37619.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Αναστασοπούλου, Πανούλα. “Μελέτη του RNA μέσω της σύνθεσης μικρών οργανικών μορίων.” 2013. Web. 06 Dec 2019.
Vancouver:
Αναστασοπούλου . Μελέτη του RNA μέσω της σύνθεσης μικρών οργανικών μορίων. [Internet] [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2013. [cited 2019 Dec 06].
Available from: http://hdl.handle.net/10442/hedi/37619.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Αναστασοπούλου . Μελέτη του RNA μέσω της σύνθεσης μικρών οργανικών μορίων. [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2013. Available from: http://hdl.handle.net/10442/hedi/37619
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Universitat Pompeu Fabra
6.
Andrés Aguayo, Luisa de,1975-.
The Role of Msi2 in adult and embryonic hematopoiesis.
Degree: Departament de Ciències Experimentals i de la Salut, 2017, Universitat Pompeu Fabra
URL: http://hdl.handle.net/10803/586094
► La producción de células sanguíneas a lo largo de toda la vida se lleva a cabo gracias a las células madre hematopoyéticas y células progenitoras…
(more)
▼ La producción de células sanguíneas a lo largo de toda la vida se lleva a cabo gracias a las células madre hematopoyéticas y células progenitoras (HSPC) que residen en la médula ósea. El estudio de los genes que controlan cómo estas HSPCs trabajan para sostener la producción continua de las células de la sangre permitirán el desarrollo de nuevos protocolos basados en la expansión ‘in vitro’ de estas células para terapias de transplante. Hemos utilizado un cribado basado en el fenómeno de integración retroviral para buscar nuevos genes que regulan la función de células madre hematopoyéticas (HSC). Uno de los genes encontrados fue Musashi
2 (Msi2), una proteína de unión a ARN que puede actuar como un inhibidor de la traducción. El modelo de ratón desarrollado mediante “gene-trap” y que inactiva el gen, muestra que Msi2 está más expresado en HSCs de largo plazo (LT-HSC) y corto plazo (ST-HSC), así como en los progenitores linfoides-mieloides (LMPP), y su expresión disminuye en progenitores intermedios y células maduras. Los ratones deficientes para Msi2 son completamente viables, pero presentan defectos importantes en los precursores primitivos que se agravan con la edad. El análisis de ciclo celular y de expresión génica sugieren que el principal defecto hematopoyético en ratones con esta deficiencia consiste en una disminución de la capacidad de proliferación de ST-HSCs y LMPPs. Además, las HSCs con déficit de Msi2 no son capaces de repoblar la médula ósea cuando se transplantan junto a médula procedente de ratones “wild-type”. También hemos observado que Msi2 se expresa durante el desarrollo del embrión en las células CD41 + de la Aorta-Gonada Mesonefros (AGM), correspondiendo muy probablemente a las HSCs emergentes. Además los embriones deficientes para Msi2 tienen una disminución en el número de HSPC en hígado fetal. Por último, nuestros experimentos muestran que un déficit de Msi2 en las HSPCs provoca un defecto en las vías Wnt y PTEN / PI3K / Akt; esto podría explicar el fenotipo observado en estos ratones. En conjunto, mi tesis proporciona una nueva perspectiva sobre el papel y el mecanismo de acción de Musashi-
2 en HSPCs de ratón.
Advisors/Committee Members: [email protected] (authoremail), true (authoremailshow), Graf, T. (Thomas) (director), true (authorsendemail).
Subjects/Keywords: RNA-binding protein; Musashi 2; Hematopoiesis; HSC; Proteína de unión a RNA; Musashi-2; Hematopoyesis; 576
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APA ·
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Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Andrés Aguayo, L. d. (2017). The Role of Msi2 in adult and embryonic hematopoiesis. (Thesis). Universitat Pompeu Fabra. Retrieved from http://hdl.handle.net/10803/586094
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Andrés Aguayo, Luisa de,1975-. “The Role of Msi2 in adult and embryonic hematopoiesis.” 2017. Thesis, Universitat Pompeu Fabra. Accessed December 06, 2019.
http://hdl.handle.net/10803/586094.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Andrés Aguayo, Luisa de,1975-. “The Role of Msi2 in adult and embryonic hematopoiesis.” 2017. Web. 06 Dec 2019.
Vancouver:
Andrés Aguayo Ld. The Role of Msi2 in adult and embryonic hematopoiesis. [Internet] [Thesis]. Universitat Pompeu Fabra; 2017. [cited 2019 Dec 06].
Available from: http://hdl.handle.net/10803/586094.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Andrés Aguayo Ld. The Role of Msi2 in adult and embryonic hematopoiesis. [Thesis]. Universitat Pompeu Fabra; 2017. Available from: http://hdl.handle.net/10803/586094
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Penn State University
7.
Wilcox, Jennifer Lynn.
Development and utilization of spectroscopic and chemical
methodologies for investigating pKa shifting in nucleic
acids.
Degree: PhD, Chemistry, 2013, Penn State University
URL: https://etda.libraries.psu.edu/catalog/19229
► RNA has historically been thought to play an intermediary role in the flow of genetic information between DNA and proteins. With its 2’ hydroxyl, RNA…
(more)
▼ RNA has historically been thought to play an
intermediary role in the flow of genetic information between DNA
and proteins. With its 2’ hydroxyl, RNA is much less stable than
DNA, which makes it amenable to a transitional role rather than one
of storage. Proteins are equipped with 20 chemically diverse amino
acid side chains, surpassing the functional potential of the four
heterocycles that make up RNA. However, with the discovery of
catalytic RNA (or ribozymes) in 1982, RNA was no longer limited to
the transitional role it was once believed to have. The discovery
of catalytic RNA shed light on RNA’s potential to actively
participate in biological processes. Proteins can act catalytically
as a result of an electrostatic contribution with pKa’s of amino
acid side chains far from neutrality to form a charged species at
neutrality or with side chain pKa’s near neutrality to allow for
participation through proton transfer. However, the pKa’s of single
stranded nucleobases are far from neutrality, inhibiting
participation in catalysis. Because Watson-Crick base pairing
requires the formation of hydrogen bonds, the pKa’s of the
nucleobases are shifted even further from neutrality, significantly
decreasing the potential for catalytic activity. The pKa’s of the
nucleobases must be shifted towards neutrality in order to act
catalytically in a manner analogous to amino acid side chains. Some
non-canonical interactions shift RNA pKa’s towards neutrality,
enabling the nucleobases to act catalytically. Interactions that
facilitate protonation of nucleobases occur in both secondary and
tertiary motifs and allow RNA to play a much more diverse role than
the intermediary role once thought. Protonated nucleobases
participate in many biological processes such as general acid-base
catalysis of ribozymes, programmed ribosomal frameshifting, miRNA
processing, and RNA editing. We hypothesize that RNA systems can
contain protonated motifs that participate in biological processes
but confirmation of protonation in these systems is limited by
existing methods. To determine the driving forces for pKa shifting,
the development of a new method for determining pKa’s was
essential. Spectroscopic methods currently exist to quantify pKa
shifting in nucleic acid systems; however, spectroscopic analysis
by these methods requires high sample concentration, costly sample
preparation and lengthy experimental time. Additionally, some
existing spectroscopic methods such as UV-Vis spectroscopy and CD
require a large conformational change to produce an observable
signal change between protonated and deprotonated states, therefore
limiting the size of systems that can be analyzed. I developed a
new method using fluorescence spectroscopy to determine pKa’s in
nucleic acids. Development of this method utilized fluorescence
quenching of 2-aminopurine (2AP), a fluorescent isomer of adenine,
when stacked. Positioning the 2AP adjacent to the protonated base
allowed for high fluorescence when the base pair wasn’t formed and
low fluorescence when the base pair was…
Subjects/Keywords: RNA; nucleic acids; 2-aminopurine fluorescence; pKa
shifting
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APA (6th Edition):
Wilcox, J. L. (2013). Development and utilization of spectroscopic and chemical
methodologies for investigating pKa shifting in nucleic
acids. (Doctoral Dissertation). Penn State University. Retrieved from https://etda.libraries.psu.edu/catalog/19229
Chicago Manual of Style (16th Edition):
Wilcox, Jennifer Lynn. “Development and utilization of spectroscopic and chemical
methodologies for investigating pKa shifting in nucleic
acids.” 2013. Doctoral Dissertation, Penn State University. Accessed December 06, 2019.
https://etda.libraries.psu.edu/catalog/19229.
MLA Handbook (7th Edition):
Wilcox, Jennifer Lynn. “Development and utilization of spectroscopic and chemical
methodologies for investigating pKa shifting in nucleic
acids.” 2013. Web. 06 Dec 2019.
Vancouver:
Wilcox JL. Development and utilization of spectroscopic and chemical
methodologies for investigating pKa shifting in nucleic
acids. [Internet] [Doctoral dissertation]. Penn State University; 2013. [cited 2019 Dec 06].
Available from: https://etda.libraries.psu.edu/catalog/19229.
Council of Science Editors:
Wilcox JL. Development and utilization of spectroscopic and chemical
methodologies for investigating pKa shifting in nucleic
acids. [Doctoral Dissertation]. Penn State University; 2013. Available from: https://etda.libraries.psu.edu/catalog/19229
University of Toronto
8.
Sibony, Michal.
Autophagy Regulates Expression of Argonaute 2, a Critical Regulator of the MicroRNA Silencing Pathway.
Degree: 2012, University of Toronto
URL: http://hdl.handle.net/1807/42408
► Genome-wide association studies have implicated autophagy in Crohn’s Disease (CD) pathogenesis. The functional relevance of autophagy in CD remains unknown. I hypothesized that autophagy is…
(more)
▼ Genome-wide association studies have implicated autophagy in Crohn’s Disease (CD) pathogenesis. The functional relevance of autophagy in CD remains unknown. I hypothesized that autophagy is involved in microRNA silencing, another process implicated in CD pathogenesis. MicroRNAs are short non-coding RNAs that are loaded onto RNA-induced silencing complex (RISC) and promote degradation and/or repress translation of target mRNAs. RISC formation and turnover occurs on endosomal membranes. Since autophagosomes and endosomes are closely related and RISC components are downstream effectors of microRNA silencing, I hypothesized that autophagy affects RISC, hence modulates microRNA expression. Using immunoblotting and immunofluorescence, I showed that Ago2, a critical component of RISC, is increased in cells with defective autophagy. Using microarray technology, I discovered 5 microRNAs that are differentially expressed in these cells. Taken together, my results propose a compelling mechanism by which autophagy regulates Ago2, thereby affects miRNA expression, which is implicated in the development of CD.
MAST
Advisors/Committee Members: Jones, Nicola L., Silverberg, Mark, Physiology.
Subjects/Keywords: Autophagy; microRNA; Crohn's Disease; Argonaute 2; RNA-induced Silencing Complex; 0719
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to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sibony, M. (2012). Autophagy Regulates Expression of Argonaute 2, a Critical Regulator of the MicroRNA Silencing Pathway. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/42408
Chicago Manual of Style (16th Edition):
Sibony, Michal. “Autophagy Regulates Expression of Argonaute 2, a Critical Regulator of the MicroRNA Silencing Pathway.” 2012. Masters Thesis, University of Toronto. Accessed December 06, 2019.
http://hdl.handle.net/1807/42408.
MLA Handbook (7th Edition):
Sibony, Michal. “Autophagy Regulates Expression of Argonaute 2, a Critical Regulator of the MicroRNA Silencing Pathway.” 2012. Web. 06 Dec 2019.
Vancouver:
Sibony M. Autophagy Regulates Expression of Argonaute 2, a Critical Regulator of the MicroRNA Silencing Pathway. [Internet] [Masters thesis]. University of Toronto; 2012. [cited 2019 Dec 06].
Available from: http://hdl.handle.net/1807/42408.
Council of Science Editors:
Sibony M. Autophagy Regulates Expression of Argonaute 2, a Critical Regulator of the MicroRNA Silencing Pathway. [Masters Thesis]. University of Toronto; 2012. Available from: http://hdl.handle.net/1807/42408
University of Illinois – Urbana-Champaign
9.
Keever, Marissa R.
Comparison of the molecular phenotypes of pigs carrying different IGF2 alleles at four developmental time points.
Degree: MS, Animal Sciences, 2017, University of Illinois – Urbana-Champaign
URL: http://hdl.handle.net/2142/97301
► A single nucleotide polymorphism in insulin-like growth factor 2 (IGF2 intron3-G3072A) is associated with greater muscle mass and decreased subcutaneous fat deposition in pigs carrying…
(more)
▼ A single nucleotide polymorphism in insulin-like growth factor
2 (IGF2 intron3-G3072A) is associated with greater muscle mass and decreased subcutaneous fat deposition in pigs carrying a paternal copy of the A allele (Apat). While many studies have focused on the differences in between the gross phenotypes of these animals, relatively little has been done to understand how these animals differ at the molecular level. It was the objective of this study to compare the molecular phenotypes of animals carrying the Apat allele and those carrying the Gpat allele in order to gain insight into how those differences may result in the differences seen at the whole-animal level.
RNA was extracted from longissimus (LM) samples taken from six animals of each genotype (Apat and Gpat) at four different time points, fetal day 90 (d90), birth (0d), weaning (21d), and market weight (176d). In total 46 samples were sequenced on the Illumina HiSeq 2000 with a target depth of 20 million reads per sample. Analysis of the
RNA-seq data using tweeDEseq determined differentially expressed genes between Apat and Gpat pigs at each time point. Additionally, IPA analysis was used to determine if there were any differentially activated pathways between the two phenotypes. IGF2 was not found to be upregulated in Apat pigs compared to Gpat at d90 or 0d; however, IGF2 expression was found to be increased in Apat pigs compared to Gpat pigs at 21d and 176d. Though there was not differential expression of IGF2 at d90 and 0d, there was still differential expression of several other genes at these time points. At d90, Apat pigs tended to have an increase in the expression anti-apoptotic genes and a decrease in pro-apoptotic genes, possibly indicating enhanced myoblast survival, while Gpat pigs had greater expression of genes associated with protein synthesis. At 0d, there was an increased expression of genes associated with proliferation and protein synthesis in Apat pigs, and Gpat pigs appeared to have upregulation of genes involved in inflammation. At both 0d and 21d Apat and Gpat pigs had displayed upregulation of markers of myogenesis, suggesting different stages of muscle development. At 176d, Apat animals had decreased expression of genes involved in adipose signaling, including inflammation, stress, and autophagy and greater expression of genes associated with tissue development and the cell cycle. Thus, throughout the developmental timepoints, there appear to be markedly different processes taking place in the muscle tissue of Apat pigs and Gpat pigs.
Advisors/Committee Members: Beever, Jonathan E (advisor), Dilger, Anna C (committee member), Kukekova, Anna V (committee member).
Subjects/Keywords: Insulin-like growth factor 2 (IGF2); Pig; RNA-seq; Muscle
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Keever, M. R. (2017). Comparison of the molecular phenotypes of pigs carrying different IGF2 alleles at four developmental time points. (Thesis). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/97301
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Keever, Marissa R. “Comparison of the molecular phenotypes of pigs carrying different IGF2 alleles at four developmental time points.” 2017. Thesis, University of Illinois – Urbana-Champaign. Accessed December 06, 2019.
http://hdl.handle.net/2142/97301.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Keever, Marissa R. “Comparison of the molecular phenotypes of pigs carrying different IGF2 alleles at four developmental time points.” 2017. Web. 06 Dec 2019.
Vancouver:
Keever MR. Comparison of the molecular phenotypes of pigs carrying different IGF2 alleles at four developmental time points. [Internet] [Thesis]. University of Illinois – Urbana-Champaign; 2017. [cited 2019 Dec 06].
Available from: http://hdl.handle.net/2142/97301.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Keever MR. Comparison of the molecular phenotypes of pigs carrying different IGF2 alleles at four developmental time points. [Thesis]. University of Illinois – Urbana-Champaign; 2017. Available from: http://hdl.handle.net/2142/97301
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Southern California
10.
Tao, Litao.
Investigation of the molecular mechanisms of
ototoxicity.
Degree: PhD, Genetic, Molecular and Cellular Biology, 2014, University of Southern California
URL: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/426847/rec/3645
► Sensory hair cells are essential for transforming the mechanical vibrations of sound into electric signals that our nervous system can interpret. However, sensory hair cells…
(more)
▼ Sensory hair cells are essential for transforming the
mechanical vibrations of sound into electric signals that our
nervous system can interpret. However, sensory hair cells are
sensitive to a variety of stresses, including aminoglycoside
antibiotics, chemotherapy agents, and environmental noise. The
molecular mechanisms of ototoxicity have been under investigation
for several decades, yet little is known about the underlying
signaling pathways. In Chapter
2 and 3 of this study, we adapted an
established technique of organotypic culture of perinatal mouse
cochlea to investigate the ototoxicity. With this culture model, we
found that CDK2 activity was involved in aminoglycoside‐induced
hair cell death and that one consequence of its activity was to
mediate the transcriptional activity of c-Jun. The involvement of
CDK2 was further supported by evidence from utricular cultures and
in vivo experiments. Using knockout mice, we demonstrated that
p19ⁱⁿᵏ⁴ᵈ, p21ᵏⁱᵖ¹ and p53 were not involved in aminoglycoside
ototoxicity. In Chapter 6, we profiled the gene expression changes
in hair cells after aminoglycoside treatment and found altered
expression for genes involved in the general transcription
apparatus, translation machinery, mitochondria, DNA damage and
repair, stress and apoptosis, JNK pathway and NF-κB pathway.
Finally, we found that the sensitivity to ototoxins was changed in
mCherry-H2B positive hair cells. Our results create a framework for
understanding the molecular mechanisms of ototoxicity and the
signaling pathways underlying postmitotic hair cell
apoptosis.
Advisors/Committee Members: Tower, John G. (Committee Chair), Schauwecker, P. Elyse (Committee Member), Segil, Neil (Committee Member), Comai, Lucio (Committee Member).
Subjects/Keywords: aminoglycoside antibiotics; ototoxicity; cyclin-dependent kinase 2; c-Jun; RNA sequencing
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Tao, L. (2014). Investigation of the molecular mechanisms of
ototoxicity. (Doctoral Dissertation). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/426847/rec/3645
Chicago Manual of Style (16th Edition):
Tao, Litao. “Investigation of the molecular mechanisms of
ototoxicity.” 2014. Doctoral Dissertation, University of Southern California. Accessed December 06, 2019.
http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/426847/rec/3645.
MLA Handbook (7th Edition):
Tao, Litao. “Investigation of the molecular mechanisms of
ototoxicity.” 2014. Web. 06 Dec 2019.
Vancouver:
Tao L. Investigation of the molecular mechanisms of
ototoxicity. [Internet] [Doctoral dissertation]. University of Southern California; 2014. [cited 2019 Dec 06].
Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/426847/rec/3645.
Council of Science Editors:
Tao L. Investigation of the molecular mechanisms of
ototoxicity. [Doctoral Dissertation]. University of Southern California; 2014. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/426847/rec/3645
Princeton University
11.
Han, Yuchen.
STRUCTURAL AND BIOCHEMICAL CHARACTERIZATIONS OF THE INNATE IMMUNE SENSOR/EFFECTOR RNASE L
.
Degree: PhD, 2016, Princeton University
URL: http://arks.princeton.edu/ark:/88435/dsp019s1618656
► One of the defensive mechanisms activated by type I interferons in human tissues involves synthesis of 2', 5'-linked oligoadenylates (2-5As) by the oligoadenylate synthetase (OAS)…
(more)
▼ One of the defensive mechanisms activated by type I interferons in human tissues involves synthesis of
2', 5'-linked oligoadenylates (
2-5As) by the oligoadenylate synthetase (OAS) family members and cleavage of intracellular
RNA by the
2-5A-dependent kinase-like endoribonuclease, RNase L. Despite its important roles that extend from innate immunity, the detailed mechanism of activation and cleavage-site selection of RNase L remained poorly known. Here, I have combined X-ray crystallography and biochemical studies to characterize RNase L in solution, elucidate its three-dimensional architecture in the presence of both
2-5A and
RNA substrate, and explain its behavior upon activation.
Our kinetic measurements, cross-linking assays, and size-exclusion chromatography analyses all converge to suggest that human RNase L forms high-order self-assemblies when reaching its fully active state, similar to the mode of activation of the phylogenetically related transmembrane kinase/RNase Ire1. The structural analysis of the N-terminal ankyrin-repeat (ANK) domain of RNase L in the presence and absence of
2-5A reveals that two molecules of
2-5A simultaneously tether two ANK domains to form a head-to-tail dimeric complex. Contrary to previous beliefs, this process does not involve any structural changes in the ANK domain.
To better understand domain interactions of RNase L, we have further obtained two crystal structures of nearly full-length human RNase L in complexes with synthetic or natural
2-5A, adenine nucleotides, and, for the first time, a fragment of
RNA. Overall, RNase L forms a crossed homodimer by exchanging ANK domains, and positions two RNase domains for recognition and cleavage of
RNA. Combined with corroborating biochemical studies, the partial
RNA observed in the active site allowed us to unveil the UN^N (^ denotes the cleavage site) rule that RNase L follows to select cleavage sites: one protomer of RNase L recognizes the identity nucleotide uridine, whereas the other protomer cleaves
RNA between the two nucleotides immediately following the uridine. This mechanism readily explains the requirement of
2-5A-induced dimerization of RNase L for its activation. Furthermore, the UN^N rule is consistent with the UG^C cleavage pattern of Ire1, highlighting similarities between substrate selection and cleavage mechanisms employed by RNase L and Ire1.
Advisors/Committee Members: Korennykh, Alexei V (advisor).
Subjects/Keywords: 2-5A;
RNA Cleavage Mechanism;
RNase L;
Structure
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Han, Y. (2016). STRUCTURAL AND BIOCHEMICAL CHARACTERIZATIONS OF THE INNATE IMMUNE SENSOR/EFFECTOR RNASE L
. (Doctoral Dissertation). Princeton University. Retrieved from http://arks.princeton.edu/ark:/88435/dsp019s1618656
Chicago Manual of Style (16th Edition):
Han, Yuchen. “STRUCTURAL AND BIOCHEMICAL CHARACTERIZATIONS OF THE INNATE IMMUNE SENSOR/EFFECTOR RNASE L
.” 2016. Doctoral Dissertation, Princeton University. Accessed December 06, 2019.
http://arks.princeton.edu/ark:/88435/dsp019s1618656.
MLA Handbook (7th Edition):
Han, Yuchen. “STRUCTURAL AND BIOCHEMICAL CHARACTERIZATIONS OF THE INNATE IMMUNE SENSOR/EFFECTOR RNASE L
.” 2016. Web. 06 Dec 2019.
Vancouver:
Han Y. STRUCTURAL AND BIOCHEMICAL CHARACTERIZATIONS OF THE INNATE IMMUNE SENSOR/EFFECTOR RNASE L
. [Internet] [Doctoral dissertation]. Princeton University; 2016. [cited 2019 Dec 06].
Available from: http://arks.princeton.edu/ark:/88435/dsp019s1618656.
Council of Science Editors:
Han Y. STRUCTURAL AND BIOCHEMICAL CHARACTERIZATIONS OF THE INNATE IMMUNE SENSOR/EFFECTOR RNASE L
. [Doctoral Dissertation]. Princeton University; 2016. Available from: http://arks.princeton.edu/ark:/88435/dsp019s1618656
Duke University
12.
Morgan, Brittany Suzanne.
Towards Guiding Principles for Targeting RNA: Rational Approaches to Design and Synthesize RNA-Biased Small Molecule Libraries
.
Degree: 2018, Duke University
URL: http://hdl.handle.net/10161/17473
► RNA is increasingly recognized as a therapeutic target in many diseases, including viral and bacterial infections, neurodegenerative disease, and cancer. Despite this, no FDA-approved…
(more)
▼ RNA is increasingly recognized as a therapeutic target in many diseases, including viral and bacterial infections, neurodegenerative disease, and cancer. Despite this, no FDA-approved drugs target
RNA, aside from select antimicrobials that recognize highly abundant ribosomal
RNA. Currently, most
RNA-targeted, small molecule screens utilize commercially available libraries; however, these libraries are presumably biased to protein-binding chemotypes, leading to low hit rates for
RNA and/or the identification of promiscuous ligands with limited efficacy in biological systems. Additionally, previous attempts to characterize distinct guiding principles for targeting
RNA were unsuccessful, potentially due to the choice of criteria (e.g. in vitro binding) or the limited selection of parameters (e.g. Lipinski’s rules). As a result, few rationally designed,
RNA-focused libraries have been developed and screened against non-ribosomal RNAs, hindering the identification of chemical probes and the study of disease-causing RNAs. Therefore, the goal of my dissertation work is to elucidate guiding principles for selectively targeting
RNA and utilize the rules to rationally design and synthesize novel
RNA-biased libraries. Toward this goal,
2-oxazolidinone was chosen as the core for small molecule synthesis, as the scaffold is present in FDA-approved antimicrobials that target ribosomal
RNA as well as small molecules that inhibit the T-box riboswitch in vitro. In addition to being diversity-oriented, the developed synthetic scheme utilized commercially available, chiral amino acid derivatives, which allowed for stereochemical control and therefore, the study of stereocenters in
RNA binding and selectivity. Five scaffolds and fifteen bis-substituted small molecules were synthesized, and a preliminary screen identified a secondary structure binding preference for
RNA bulge motifs. In parallel, the
RNA-targeted BIoactive ligaNd Database (R-BIND) was curated, which was comprised of
RNA-binding ligands with activity in cell culture and animal models. The library was compared to in vitro
RNA binders and FDA-approved drugs from which several guiding principles were identified for bioactive
RNA-binding ligands: i) compliance to common medicinal chemistry rules; ii) a statistically significant shift in rod-like character; and iii) a statistically significant increase in nitrogen atom count and ligand rigidity. These rules were utilized to develop a biology-oriented synthesis based on the
2-oxazolidinone core and bioactive
RNA chemical space. The strategy included a novel scaffold design, a subunit library inspired by the building blocks in R-BIND, and a method to select small molecules for synthesis based on similarity to known
RNA bioactives. Future work will include the diversification and expansion of the
2-oxazolidinone-based libraries, screening of the small molecules against secondary structure libraries as well as therapeutically relevant RNAs, and validation and exploration of bioactive
RNA-privileged chemical space. It is…
Advisors/Committee Members: Hargrove, Amanda E (advisor).
Subjects/Keywords: Organic chemistry;
Biochemistry;
2-Oxazolidinone;
Chemical Biology;
Diversity-Oriented Synthesis;
Guiding Principles;
RNA Bulge Motifs;
RNA Recognition
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Morgan, B. S. (2018). Towards Guiding Principles for Targeting RNA: Rational Approaches to Design and Synthesize RNA-Biased Small Molecule Libraries
. (Thesis). Duke University. Retrieved from http://hdl.handle.net/10161/17473
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Morgan, Brittany Suzanne. “Towards Guiding Principles for Targeting RNA: Rational Approaches to Design and Synthesize RNA-Biased Small Molecule Libraries
.” 2018. Thesis, Duke University. Accessed December 06, 2019.
http://hdl.handle.net/10161/17473.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Morgan, Brittany Suzanne. “Towards Guiding Principles for Targeting RNA: Rational Approaches to Design and Synthesize RNA-Biased Small Molecule Libraries
.” 2018. Web. 06 Dec 2019.
Vancouver:
Morgan BS. Towards Guiding Principles for Targeting RNA: Rational Approaches to Design and Synthesize RNA-Biased Small Molecule Libraries
. [Internet] [Thesis]. Duke University; 2018. [cited 2019 Dec 06].
Available from: http://hdl.handle.net/10161/17473.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Morgan BS. Towards Guiding Principles for Targeting RNA: Rational Approaches to Design and Synthesize RNA-Biased Small Molecule Libraries
. [Thesis]. Duke University; 2018. Available from: http://hdl.handle.net/10161/17473
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Université Paris-Sud – Paris XI
13.
Boudoukha, Selim.
Étude de la régulation post-transcriptionnelle de l’expression des gènes par la protéine de liaison à l’ARN IMP-2 au cours de la myogenèse : Post-transcriptional regulation of gene expression by IMP-2 during myogenesis.
Degree: Docteur es, Biochimie, Biologie cellulaire et moléculaire, 2011, Université Paris-Sud – Paris XI
URL: http://www.theses.fr/2011PA11T095
► Les rhabdomyosarcomes embryonnaires et aléolaires (RMS) appartiennent aux tumeurs des tissus mous les plus fréquentes chez les enfants dont elles représentent 2/3 des cas. Plusieurs…
(more)
▼ Les rhabdomyosarcomes embryonnaires et aléolaires (RMS) appartiennent aux tumeurs des tissus mous les plus fréquentes chez les enfants dont elles représentent 2/3 des cas. Plusieurs données suggèrent que la dérégulation des cellules progénitrices du muscle squelettique pourrait jouer un rôle dans l'émergence des cellules de RMS qui ont aussi bien perdu le contrôle de la régulation de la prolifération cellulaire que la capacité à se différencier.Néanmoins les mécanismes de développement des RMS restent à caractériser. La famille des IMPs et notamment IMP-2, protéines liant les ARN, sont à la fois fortement exprimées dans le muscle en régénération in vivo mais aussi dans les cellules de RMS.Au cours de ma thèse, j’ai pu mettre en évidence le rôle d’IMP-2 dans la motilité des cellules de RMS et dans les cellules musculaires ainsi que dans le contrôle de l’intégrité du cytosquelette de microtubules (MTs) et dans le remodelage des adhésions focales. En effet, IMP-2 est impliqué à la fois dans la régulation de l’expression de MuRF-3, une protéine lié àla stabilisation des MTs et de Pinch-2, un important médiateur de l’adhésion cellulaire.
The RNA-binding proteins IMPs (IGF-II mRNA binding protein) first discovered in rhabdomyosarcoma cells (RMS) are expressed during embryonic development but their expression is decreased in adult tissues.We showed that IMPs and particularly IMP-2 are strongly expressed in mouse myoblatsts, during early regeneration of skeletal muscle in vivo and in and RMS. IMP-2 loss of function experiments using siRNA have shown that IMP-2 is necessary for microtubules stability(MTs), cell motility and invasion of myoblasts and RMS.Expression of IMP-2 specifically increases MTs stability by an enrichment of detyrosinated tubulin Glu-tubulin. Detyrosination is indispensable for myogenic differentiation and plays substantial role in tumor growth. Additionaly, MTs stabilization play an important role in focal adhesion remodeling, in cytoskeleton integrity, cell adhesion and cell motility.To get new insight into molecular mechanism underlying the function of IMP-2 in MTs stability and cell motility, full ranscriptome analysis was performed between IMP-2 knockdown (KD) myoblasts and control myoblatsts. We have further shown that IMP-2 controls the mRNA levels of many important mediators of cell adhesion such as PINCH-2, as well as multiple cytoskeleton remodeling, such as MuRF-3.We have identified a number of functionally relevant protein partners of IMP-2.Moreover subsequent RNAi screens have revealed the importance of IMP-2 regulated transcripts involved in cell motility and cell adhesion In conclusion, we show that IMP-2 dependent regulation of mRNA such as MuRF3 and PINCH2 largely contributes to the motility –deficient in IMP-2 KD cells. Moreover these results indicate clearly, that further analysis of IMP2 protein partners and RNA targets regulated by IMP-2 will help to characterized the function of IMP-2 and to propose a model of IMP-2 transcriptional regulation of gene expression in myoblasts and…
Advisors/Committee Members: Polesskaya, Anna (thesis director).
Subjects/Keywords: IMP-2; ARN; Myogenèse; MuRf-3; RMS; Pinch-2; Régulation posttranscriptionnelle; IMP-2; RNA; Myogenesis; MuRf-3; RMS; Pinch-2; Post-transcriptional regulation
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APA ·
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MLA ·
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APA (6th Edition):
Boudoukha, S. (2011). Étude de la régulation post-transcriptionnelle de l’expression des gènes par la protéine de liaison à l’ARN IMP-2 au cours de la myogenèse : Post-transcriptional regulation of gene expression by IMP-2 during myogenesis. (Doctoral Dissertation). Université Paris-Sud – Paris XI. Retrieved from http://www.theses.fr/2011PA11T095
Chicago Manual of Style (16th Edition):
Boudoukha, Selim. “Étude de la régulation post-transcriptionnelle de l’expression des gènes par la protéine de liaison à l’ARN IMP-2 au cours de la myogenèse : Post-transcriptional regulation of gene expression by IMP-2 during myogenesis.” 2011. Doctoral Dissertation, Université Paris-Sud – Paris XI. Accessed December 06, 2019.
http://www.theses.fr/2011PA11T095.
MLA Handbook (7th Edition):
Boudoukha, Selim. “Étude de la régulation post-transcriptionnelle de l’expression des gènes par la protéine de liaison à l’ARN IMP-2 au cours de la myogenèse : Post-transcriptional regulation of gene expression by IMP-2 during myogenesis.” 2011. Web. 06 Dec 2019.
Vancouver:
Boudoukha S. Étude de la régulation post-transcriptionnelle de l’expression des gènes par la protéine de liaison à l’ARN IMP-2 au cours de la myogenèse : Post-transcriptional regulation of gene expression by IMP-2 during myogenesis. [Internet] [Doctoral dissertation]. Université Paris-Sud – Paris XI; 2011. [cited 2019 Dec 06].
Available from: http://www.theses.fr/2011PA11T095.
Council of Science Editors:
Boudoukha S. Étude de la régulation post-transcriptionnelle de l’expression des gènes par la protéine de liaison à l’ARN IMP-2 au cours de la myogenèse : Post-transcriptional regulation of gene expression by IMP-2 during myogenesis. [Doctoral Dissertation]. Université Paris-Sud – Paris XI; 2011. Available from: http://www.theses.fr/2011PA11T095
14.
Faustino, Viviane Dias.
Inibição simultânea dos genes antiapoptóticos Bcl-2 e Bcl-XL em células de leucemia linfoide aguda e células de linfoma do manto mediante RNA de interferência.
Degree: Mestrado, Distúrbios do Crescimento Celular, Hemodinâmicos e da Hemostasia, 2012, University of São Paulo
URL: http://www.teses.usp.br/teses/disponiveis/5/5167/tde-22012013-154327/
;
► As estatísticas relacionadas aos cânceres hematológicos indicam que a incidência e mortalidade dessas doenças têm aumentado ao longo dos anos. Embora a maioria dos casos…
(more)
▼ As estatísticas relacionadas aos cânceres hematológicos indicam que a incidência e mortalidade dessas doenças têm aumentado ao longo dos anos. Embora a maioria dos casos de linfomas e leucemias não possua etiologia definida, sugere-se que fatores genéticos possam estar envolvidos. Nesse contexto, destaca-se a família de proteínas Bcl-2, divididas em anti e pró-apoptóticas. Os genes Bcl-2 e Bcl-XL, membros de uma nova classe de oncogenes, que atuam no mecanismo de morte celular das células cancerígenas, sobretudo apoptose, a qual é controlada por numerosos sinais intra e extracelulares. Uma nova estratégia para o tratamento desta doença inclui a terapia gênica mediada por RNA de interferência, que silencia importantes genes, a exemplo dos genes da família Bcl-2. Visto que o silenciamento isolado de um único gene pode não ter resultados expressivos, o presente trabalho teve por objetivo desenhar um RNA de interferência (RNAi) homólogo a dois tipos distintos de RNA mensageiro (RNAm) e inibir simultaneamente os genes Bcl-2 e Bcl-XL,assim como testar a inibição isolada dos mesmos. Amostras de linhagem tumoral Jurkat e Granta-519 foram avaliadas após transfecção com os seguintes RNA:i Bcl-2,Bcl-XL, Bcl-2/Bcl-XL,Bcl-2+Bcl-XL e scramble. Os nossos achados evidenciam que, na linhagem Granta-519, a sequência do RNAi Bcl-2 inibe, isoladamente ou conjugado ao Bcl-XL, o gene Bcl-2. Deste modo, o RNAi Bcl-2 apresenta-se mais eficiente no mecanismo de silenciamento gênico, uma vez que propicia a morte celular frente a toxicidade do quimioterápico etoposide.
The hematological cancer statistics indicates that its incidence and mortality have increased over the years. Although most cases of lymphomas and leukemias has no definite etiology however is suggested that genetic factors may be involved. In this context there is the Bcl-2 proteins family divided into anti-apoptotic and pro-apoptotic which Bcl-2 and Bcl-XL genes are members of a new class of oncogenes that act in cancer cells death mechanisms, especially apoptosis, that is controlled by numerous intra-and extracellular signals. Among new strategies to treat hematological cancer includes gene therapy mediated by RNA interference, which can decrease expression of genes like Bcl-2 family components. Studies of single gene silencing have not shown significant results so this study aimed to design an RNA interference (iRNA) homologous to two distinct types of messenger RNA (mRNA) and inhibit both genes Bcl-2 and Bcl-XL -XL as well as test the inhibition. Commercial cells Jurkat and Granta-519 were evaluated after transfection with iRNA as follows: Bcl-2, Bcl-XL, Bcl-2/Bcl-XL, Bcl-2+Bcl-XL and scramble. Our findings show that in Granta-519 cell line Bcl-2 RNAi sequence inhibits, alone or conjugated to Bcl-XL, Bcl-2 gene. Thus RNAi Bcl-2 appears more effective in gene silencing mechanism as it promotes cell death due chemotherapeutic agent etoposide toxicity.
Advisors/Committee Members: Bydlowski, Sergio Paulo.
Subjects/Keywords: Apoptose; Apoptosis; Bcl-2 gene; Gene therapy; Genes Bcl-2; Inibição simultânea; Interferência de RNA; Neoplasias; Neoplasms; Protein Bcl-XL; Proteína Bcl-XL; RNA interference; Simultaneous inhibition; Terapia de genes
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APA (6th Edition):
Faustino, V. D. (2012). Inibição simultânea dos genes antiapoptóticos Bcl-2 e Bcl-XL em células de leucemia linfoide aguda e células de linfoma do manto mediante RNA de interferência. (Masters Thesis). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/5/5167/tde-22012013-154327/ ;
Chicago Manual of Style (16th Edition):
Faustino, Viviane Dias. “Inibição simultânea dos genes antiapoptóticos Bcl-2 e Bcl-XL em células de leucemia linfoide aguda e células de linfoma do manto mediante RNA de interferência.” 2012. Masters Thesis, University of São Paulo. Accessed December 06, 2019.
http://www.teses.usp.br/teses/disponiveis/5/5167/tde-22012013-154327/ ;.
MLA Handbook (7th Edition):
Faustino, Viviane Dias. “Inibição simultânea dos genes antiapoptóticos Bcl-2 e Bcl-XL em células de leucemia linfoide aguda e células de linfoma do manto mediante RNA de interferência.” 2012. Web. 06 Dec 2019.
Vancouver:
Faustino VD. Inibição simultânea dos genes antiapoptóticos Bcl-2 e Bcl-XL em células de leucemia linfoide aguda e células de linfoma do manto mediante RNA de interferência. [Internet] [Masters thesis]. University of São Paulo; 2012. [cited 2019 Dec 06].
Available from: http://www.teses.usp.br/teses/disponiveis/5/5167/tde-22012013-154327/ ;.
Council of Science Editors:
Faustino VD. Inibição simultânea dos genes antiapoptóticos Bcl-2 e Bcl-XL em células de leucemia linfoide aguda e células de linfoma do manto mediante RNA de interferência. [Masters Thesis]. University of São Paulo; 2012. Available from: http://www.teses.usp.br/teses/disponiveis/5/5167/tde-22012013-154327/ ;
University of Vienna
15.
Kurth, Henriette.
A study of nuclear acting small RNApost-transcriptional modification and nuclear import.
Degree: 2010, University of Vienna
URL: http://othes.univie.ac.at/10548/
► Kleine, ~20-30 Nukleotide (nt) lange RNAs können Genexpression sowohl auf transkriptioneller, als auch auf post-transkriptioneller Ebene regulieren. In Arabidopsis sind alle kleinen RNAs am 3’…
(more)
▼ Kleine, ~20-30 Nukleotide (nt) lange RNAs können Genexpression sowohl auf transkriptioneller, als auch auf post-transkriptioneller Ebene regulieren. In Arabidopsis sind alle kleinen RNAs am 3’ Ende 2’-O-methyliert. In Metazoen hingegen trägt nur ein Teil der kleinen RNAs diese Modifikation. Es ist zwar erwiesen, dass kleine RNAs durch Methylierung stabilisiert werden, die biologische Bedeutung dieser Modifikation ist jedoch unzureichend verstanden. Tetrahymena thermophila exprimiert zwei Klassen von kleinen RNAs. Die erste Klasse setzt sich aus ständig exprimierten ~23–24 nt siRNAs zusammen, während ~28–29 nt scnRNAs die zweite Klasse bilden. Die Funktion der Methylierung von kleinen RNAs in Tetrahymena untersuchte ich im ersten Teil meiner Doktorarbeit. Ich konnte zeigen, dass scnRNAs, aber nicht siRNAs, an ihren 3’ Enden methyliert sind. Das Tetrahymena HEN1 Homolog Hen1p katalysiert diese Reaktion. Das Fehlen von Hen1p hat eine Verkürzung, sowie einen teilweisen Abbau der scnRNAs zur Folge. Diese Destabilisierung führt zu einem Defekt in der DNA Eliminierung, wodurch die Anzahl sexueller Nachkommen stark reduziert wird. Unsere Studie zeigt, dass 2’-O-Methylierung von kleinen RNAs einen spezifischen RNAi Stoffwechselweg in Eukaryoten regulieren kann. Das Argonautprotein Twi1p wird im Zytoplasma mit scnRNA beladen, entfaltet seine Funktion aber im Zellkern. Im zweiten Teil meiner Doktorarbeit untersuchten wir, wie beladene Argonautproteine erkannt und in den Zellkern transportiert werden. Wir identifizierten ein neues Protein, Giw1p, welches mit Twi1p interagiert und für dessen Lokalisation im Zellkern verantwortlich ist. Giw1p bindet weder an unbeladenes, noch an mit doppelsträngiger RNA beladenes Twi1p. Dies deutet darauf hin, dass Giw1p den Zustand des Argonaut-scnRNA Komplexes erkennt und nur den reifen Komplex in den Zellkern transportiert. Ein möglicher Grund für diesen selektiven Transport ist eine Konformationsänderung von Twi1p. Dies ist die erste Beschreibung eines Proteins, welches die Beladung eines Argonauts erkennen kann.
Small RNAs, ~20–30 nucleotides (nt) in length regulate gene expression at the transcriptional and post-transcriptional levels. In the plant Arabidopsis, all small RNAs are 3’-terminal 2’-O-methylated by HEN1, whereas only a subset of small RNAs carries this modification in metazoans. Methylation is known to stabilize small RNAs, but its biological significance remains unclear. In Tetrahymena, two classes of small RNAs have been identified: 28–29 nt RNAs (scnRNAs), that are expressed only during sexual reproduction, and constitutively expressed 23–24 nt siRNAs. In the first part of my PhD study, I have investigated the role of scnRNA methylation in Tetrahymena. I have demonstrated that scnRNAs, but not siRNAs, are 2’-O-methylated at their 3’ ends. The Tetrahymena HEN1 homolog Hen1p is responsible for scnRNA 2’-O-methylation. Loss of Hen1p causes a gradual reduction in the level and length of scnRNAs, defects in programmed DNA elimination and inefficient production of sexual…
Subjects/Keywords: 30.00 Naturwissenschaften allgemein: Allgemeines; 42.13 Molekularbiologie; kleine RNA / Piwi / Argonautprotein / 2'-O-Methylierung / HEN1 / Import in den Zellkern; small RNA / Piwi / Argonaute / 2'-O-methylation / HEN1 / nuclear import
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APA ·
Chicago ·
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CSE |
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APA (6th Edition):
Kurth, H. (2010). A study of nuclear acting small RNApost-transcriptional modification and nuclear import. (Thesis). University of Vienna. Retrieved from http://othes.univie.ac.at/10548/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Kurth, Henriette. “A study of nuclear acting small RNApost-transcriptional modification and nuclear import.” 2010. Thesis, University of Vienna. Accessed December 06, 2019.
http://othes.univie.ac.at/10548/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Kurth, Henriette. “A study of nuclear acting small RNApost-transcriptional modification and nuclear import.” 2010. Web. 06 Dec 2019.
Vancouver:
Kurth H. A study of nuclear acting small RNApost-transcriptional modification and nuclear import. [Internet] [Thesis]. University of Vienna; 2010. [cited 2019 Dec 06].
Available from: http://othes.univie.ac.at/10548/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Kurth H. A study of nuclear acting small RNApost-transcriptional modification and nuclear import. [Thesis]. University of Vienna; 2010. Available from: http://othes.univie.ac.at/10548/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
16.
Cerutti, Elena.
Nucleotide Excision Repair at the crossroad with transcription : La réparation par excision de nucléotides à la croisée des chemins avec la transcription.
Degree: Docteur es, Réparation de l’ADN, 2019, Lyon
URL: http://www.theses.fr/2019LYSE1057
► L’intégrité de l’ADN est continuellement remise en question par divers agents endogènes et exogènes (p. ex., la lumière ultraviolette, la fumée de cigarette, la pollution…
(more)
▼ L’intégrité de l’ADN est continuellement remise en question par divers agents endogènes et exogènes (p. ex., la lumière ultraviolette, la fumée de cigarette, la pollution de l’environnement, les dommages oxydatifs, etc.) qui causent des lésions de l’ADN qui interfèrent avec les fonctions cellulaires correctes. Le mécanisme de réparation par excision de nucléotides (NER) supprime les adduits d’ADN déformantes l’hélice tels que les lésions induites par les UV et il existe dans deux sous voies distinctes selon l’endroit où les lésions de l’ADN sont situées dans le génome. L’une de ces sous voies est directement liée à la transcription de l’ADN (TCR) par l’ARN Polymérase 2 (ARNP2). Dans la première partie de ce travail, nous avons démontré qu’un mécanisme NER entièrement compétent est également nécessaire pour la réparation de l’ADN ribosomique (ADNr), transcrite par ARN Polymérase 1 (ARNP1) et représentant 60 % de la transcription cellulaire totale. De plus, nous avons identifié et clarifié le mécanisme de deux protéines responsables du repositionnement nucléolaire dépendant des UV de l’ARNP1 et de l’ADNr observé pendant la réparation. Dans la deuxième partie de ce travail, nous avons étudié la fonctionne moléculaire de la protéine XAB2 lors de la réparation NER et nous avons démontré son implication dans le processus TCR. De plus, nous avons également montré la présence de XAB2 dans un complexe d’épissage du pré-ARNm. Enfin, nous avons décrit l’impact de XAB2 sur la mobilité de l’ARNP2 lors des premières étapes de la réparation TCR, suggérant ainsi un rôle de XAB2 dans le processus de reconnaissance des lésions
The integrity of DNA is continuously challenged by a variety of endogenous and exogenous agents (e.g. ultraviolet light, cigarette smoke, environmental pollution, oxidative damage, etc.) that cause DNA lesions which interfere with proper cellular functions. Nucleotide Excision Repair (NER) mechanism removes helix-distorting DNA adducts such as UV-induced lesions and it exists in two distinct sub-pathways depending where DNA lesions are located within the genome. One of these sub pathways is directly linked to the DNA transcription by RNA Polymerase 2 (TCR). In the first part of this work, we demonstrated that a fully proficient NER mechanism is also necessary for repair of ribosomal DNA, transcribed by RNA polymerase 1 and accounting for the 60 % of the total cellular transcription. Furthermore, we identified and clarified the mechanism of two proteins responsible for the UV-dependent nucleolar repositioning of RNAP1 and rDNA observed during repair. In the second part of this work, we studied the molecular function of the XAB2 protein during NER repair and we demonstrated its involvement in the TCR process. In addition, we also shown the presence of XAB2 in a pre-mRNA splicing complex. Finally, we described the impact of XAB2 on RNAP2 mobility during the first steps of TCR repair, thus suggesting a role of XAB2 in the lesion recognition process
Advisors/Committee Members: Giglia-Mari, Giuseppina (thesis director), Mari, Pierre-Olivier (thesis director).
Subjects/Keywords: NER; ARN Polymérase 1; ADN ribosomique; XAB2; Lésions UV; ARN Polymérase 2; Nucléole; NER; RNA Polymerase 1; Ribosomal DNA; XAB2; UV lesions; RNA Polymerase 2; Nucleolus; 570
Record Details
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Cerutti, E. (2019). Nucleotide Excision Repair at the crossroad with transcription : La réparation par excision de nucléotides à la croisée des chemins avec la transcription. (Doctoral Dissertation). Lyon. Retrieved from http://www.theses.fr/2019LYSE1057
Chicago Manual of Style (16th Edition):
Cerutti, Elena. “Nucleotide Excision Repair at the crossroad with transcription : La réparation par excision de nucléotides à la croisée des chemins avec la transcription.” 2019. Doctoral Dissertation, Lyon. Accessed December 06, 2019.
http://www.theses.fr/2019LYSE1057.
MLA Handbook (7th Edition):
Cerutti, Elena. “Nucleotide Excision Repair at the crossroad with transcription : La réparation par excision de nucléotides à la croisée des chemins avec la transcription.” 2019. Web. 06 Dec 2019.
Vancouver:
Cerutti E. Nucleotide Excision Repair at the crossroad with transcription : La réparation par excision de nucléotides à la croisée des chemins avec la transcription. [Internet] [Doctoral dissertation]. Lyon; 2019. [cited 2019 Dec 06].
Available from: http://www.theses.fr/2019LYSE1057.
Council of Science Editors:
Cerutti E. Nucleotide Excision Repair at the crossroad with transcription : La réparation par excision de nucléotides à la croisée des chemins avec la transcription. [Doctoral Dissertation]. Lyon; 2019. Available from: http://www.theses.fr/2019LYSE1057
17.
Alaide Gonçalves.
Estudo comparativo da atividade dos genes ribossômicos em mucosa bucal (gengiva) e leucócitos de indivíduos com Síndrome de Down em relação à idade.
Degree: 2009, Universidade Federal de São Paulo
URL: http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=380
;
http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=381
;
http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=382
;
http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=383
;
http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=384
;
http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=385
► Indivíduos com trissomia do cromossomo 21 ou Síndrome de Down (SD) apresentam envelhecimento prematuro e a maior parte manifesta a Doença de Alzheimer a partir…
(more)
▼ Indivíduos com trissomia do cromossomo 21 ou Síndrome de Down (SD) apresentam envelhecimento prematuro e a maior parte manifesta a Doença de Alzheimer a partir da terceira e quarta décadas de vida. Estudos citogenéticos e moleculares têm mostrado redução associada à idade na atividade dos genes ribossômicos em linfócitos e fibroblastos de indivíduos com trissomia do cromossomo 21, bem como em linfócitos e células do córtex cerebral de pacientes com Doença de Alzheimer (DA). Os objetivos do estudo foram analisar a expressão dos rRNA por meio da relação 28S/18S de células sanguíneas e gengivais de 10 indivíduos com SD jovens (de 6 a 21 anos de idade) e 10 idosos (de 35 a 54 anos de idade) e em controles jovens e idosos sadios de ambos os sexos, investigados por meio da técnica de Northern blotting. As células gengivais e as células neurais compartilham a mesma origem embriológica. As células do sangue, de origem do mesoderma foram comparadas em relação às gengivais. Os níveis de rRNA de células sanguíneas foram também comparados entre os 42 indivíduos com SD e os 42 controles. Nenhum dos indivíduos estudados apresentavam quadro clínico de DA no momento da coleta de material. Os resultados não mostraram diferença estatisticamente significante na relação das frações de rRNA 28S/18S tanto no que se refere aos tecidos analisados (mucosa oral e sangue), quanto à idade entre os indivíduos. Assim, a alteração da expressão dos rRNA em células sanguíneas e gengivais de indivíduos com SD e de controles saudáveis não diferiram (p>0,05). Pode-se assim concluir que a origem embriológica dos dois tecidos (mesoderma e neuroectoderma) bem com as suas diferentes taxas de proliferação não influenciaram os níveis de atividade dos rDNA. A regulação na atividade dos genes ribossômicos na SD e em controles não se configurou como biomarcador do envelhecimento na SD e no processo de envelhecimento natural.
Cytogenetic and molecular studies have shown significant reduction in the ribosomal genes activity in lymphocyte and fibroblasts cells from older Trisomy 21 or Down syndrome (DS) individuals as well as in lymphocyte and neural cortical cells from Alzheimers disease patients. We have proposed the study of rRNA levels in older and younger DS subjects in two different cell tissues, blood and gingival cells. Gingival cells share the same neuroectodermal origin as neural cells and should indicate common properties and/or functions. The aim of the study was to analyze rDNA activity through rRNA 28S/18S ratio levels in blood and gingival cells from younger and older DS subjects. rRNA 28S/18S ratio levels were investigated in both tissues from ten younger (6-21 years old) and ten older DS subjects (35-54 years old) and in the same age and sex controls through the Northern Blotting method. Blood cells rRNA levels were also compared between 42 DS subjects and 42 controls. The results showed no significant difference in rRNA 28S/18S ratios between gingival and blood tissues from younger and older DS as well as from younger and elderly controls.…
Advisors/Committee Members: Marilia de Arruda Cardoso Smith, Spencer Luiz Marques Payao, Bianca Borsatto Galera, Maria Tercilia Vilela de Azeredo Oliveira, Cláudio Aparecido Casatti.
Subjects/Keywords: 1. Síndrome de Down, 2. RNA ribossômico, 3. Genes ribossômicos, 4. Envelhecimento; MORFOLOGIA
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❌
APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Gonçalves, A. (2009). Estudo comparativo da atividade dos genes ribossômicos em mucosa bucal (gengiva) e leucócitos de indivíduos com Síndrome de Down em relação à idade. (Thesis). Universidade Federal de São Paulo. Retrieved from http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=380 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=381 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=382 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=383 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=384 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=385
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Gonçalves, Alaide. “Estudo comparativo da atividade dos genes ribossômicos em mucosa bucal (gengiva) e leucócitos de indivíduos com Síndrome de Down em relação à idade.” 2009. Thesis, Universidade Federal de São Paulo. Accessed December 06, 2019.
http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=380 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=381 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=382 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=383 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=384 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=385.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Gonçalves, Alaide. “Estudo comparativo da atividade dos genes ribossômicos em mucosa bucal (gengiva) e leucócitos de indivíduos com Síndrome de Down em relação à idade.” 2009. Web. 06 Dec 2019.
Vancouver:
Gonçalves A. Estudo comparativo da atividade dos genes ribossômicos em mucosa bucal (gengiva) e leucócitos de indivíduos com Síndrome de Down em relação à idade. [Internet] [Thesis]. Universidade Federal de São Paulo; 2009. [cited 2019 Dec 06].
Available from: http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=380 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=381 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=382 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=383 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=384 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=385.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Gonçalves A. Estudo comparativo da atividade dos genes ribossômicos em mucosa bucal (gengiva) e leucócitos de indivíduos com Síndrome de Down em relação à idade. [Thesis]. Universidade Federal de São Paulo; 2009. Available from: http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=380 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=381 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=382 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=383 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=384 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=385
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Ottawa
18.
Vuong, Nhung.
Molecular Mechanisms by Which Estrogen Causes Ovarian Epithelial Cell Dysplasia
.
Degree: 2018, University of Ottawa
URL: http://hdl.handle.net/10393/37286
► The initiating events of ovarian cancer remain unknown, but an established risk factor is use of estrogen therapy by post-menopausal women where there is a…
(more)
▼ The initiating events of ovarian cancer remain unknown, but an established risk factor is use of estrogen therapy by post-menopausal women where there is a positive correlation between duration of use and risk for disease. Mouse models of ovarian cancer have shown that exposure to exogenous 17β-estradiol (E2) accelerates tumour onset so this study aims to investigate the E2 signalling mechanisms responsible for sensitizing ovarian epithelial cells to transformation. By developing model systems that are responsive to E2 manipulation, we showed that E2 induces the formation of epithelial dysplasias both in vitro and in vivo. microRNA microarray was used to discover that E2 up-regulates microRNA-378 via the ESR1 pathway, resulting in the down-regulation of a tumour suppressor gene called Disabled-2 (Dab2). E2 suppression of Dab2 was found to result in increased proliferation, loss of contact inhibition, epithelial dysplasia, and increased sensitivity to transformation. This mechanism was also found to be active in mouse fallopian tube epithelium and human ovarian cancer cells. Single-cell RNA sequencing and trajectory analysis was subsequently used to explore additional signalling mechanisms that might contribute to the emergence of dysplastic lesions induced by E2. Multiple molecular signalling pathways dysregulated by E2 were identified and this revealed several possible biomarkers to be investigated for early detection of ovarian cancer. In the context of a current lack of strategies for ovarian cancer prevention or early detection, this work represents a significant advance in our understanding of how E2 promotes ovarian cancer initiation.
Subjects/Keywords: Ovarian Cancer;
Estrogen;
Epithelial Cell Dysplasia;
Molecular Signalling;
Disabled-2;
Single-cell RNA Sequencing
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APA (6th Edition):
Vuong, N. (2018). Molecular Mechanisms by Which Estrogen Causes Ovarian Epithelial Cell Dysplasia
. (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/37286
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Vuong, Nhung. “Molecular Mechanisms by Which Estrogen Causes Ovarian Epithelial Cell Dysplasia
.” 2018. Thesis, University of Ottawa. Accessed December 06, 2019.
http://hdl.handle.net/10393/37286.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Vuong, Nhung. “Molecular Mechanisms by Which Estrogen Causes Ovarian Epithelial Cell Dysplasia
.” 2018. Web. 06 Dec 2019.
Vancouver:
Vuong N. Molecular Mechanisms by Which Estrogen Causes Ovarian Epithelial Cell Dysplasia
. [Internet] [Thesis]. University of Ottawa; 2018. [cited 2019 Dec 06].
Available from: http://hdl.handle.net/10393/37286.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Vuong N. Molecular Mechanisms by Which Estrogen Causes Ovarian Epithelial Cell Dysplasia
. [Thesis]. University of Ottawa; 2018. Available from: http://hdl.handle.net/10393/37286
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Ottawa
19.
Pastic, Alyssa.
LRRK2 Phosphorylates HuD to Affect the Post-Transcriptional Regulation of Parkinson's Disease-Linked mRNA Targets
.
Degree: 2018, University of Ottawa
URL: http://hdl.handle.net/10393/38593
► Parkinson's Disease (PD) is a late-onset neurodegenerative disease characterized by progressive motor dysfunction caused by a loss of dopaminergic neurons for which there is no…
(more)
▼ Parkinson's Disease (PD) is a late-onset neurodegenerative disease characterized by progressive motor dysfunction caused by a loss of dopaminergic neurons for which there is no known cure. Among the most common genetic causes of PD are mutations in the leucine-rich repeat kinase 2 gene (LRRK2), encoding a multi-domain protein with kinase activity. The LRRK2 G2019S mutation causes hyperactivity of the kinase domain and is the most frequent LRRK2 mutation in patients with familial PD, though its role in PD pathology remains unclear. Preliminary data from the lab of our collaborator, Dr. David Park, demonstrated through a genetic screen in Drosophila melanogaster that the deletion of rbp9 encoding an RNA-binding protein prevented pathology induced by PD-relevant mutations in the LRRK2 kinase domain. The neuronal homolog of RBP9 in humans is HuD, a member of the Hu family of RNA-binding proteins that regulates the expression of many transcripts involved in neuronal development, plasticity, and survival. In addition, HuD has been shown to modify the age-at-onset or risk of developing PD. Here, we studied the effect of LRRK2 on the post-transcriptional regulation of mRNAs bound by HuD in the context of PD. Our findings showed that HuD is a substrate for LRRK2 phosphorylation in vitro, and that LRRK2 G2019S hyperphosphorylates HuD. We demonstrated that LRRK2 kinase activity is required for the binding of several transcripts by HuD that encode PD-relevant proteins such as α-synuclein and neuronal survival factor BDNF. Our findings in human neuroblastoma cells indicated that LRRK2 regulates the protein levels of HuD mRNA targets α-synuclein and BDNF in a mechanism that can by modified by HuD. Finally, we showed that the combination of HuD knockout with LRRK2 G2019S expression in mice rescues aberrant expression of HuD targets in mice with only the LRRK2 G2019S mutation or the knockout of HuD alone. Together, our findings demonstrate that LRRK2 affects the post-transcriptional regulation of HuD-bound mRNAs, and suggest the use of HuD as a potential therapeutic target in patients with PD caused by the LRRK2 G2019S mutation.
Subjects/Keywords: RNA-binding protein;
Leucine-rich repeat kinase 2 (LRRK2);
Parkinson's disease;
post-transcriptional regulation
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APA (6th Edition):
Pastic, A. (2018). LRRK2 Phosphorylates HuD to Affect the Post-Transcriptional Regulation of Parkinson's Disease-Linked mRNA Targets
. (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/38593
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Pastic, Alyssa. “LRRK2 Phosphorylates HuD to Affect the Post-Transcriptional Regulation of Parkinson's Disease-Linked mRNA Targets
.” 2018. Thesis, University of Ottawa. Accessed December 06, 2019.
http://hdl.handle.net/10393/38593.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Pastic, Alyssa. “LRRK2 Phosphorylates HuD to Affect the Post-Transcriptional Regulation of Parkinson's Disease-Linked mRNA Targets
.” 2018. Web. 06 Dec 2019.
Vancouver:
Pastic A. LRRK2 Phosphorylates HuD to Affect the Post-Transcriptional Regulation of Parkinson's Disease-Linked mRNA Targets
. [Internet] [Thesis]. University of Ottawa; 2018. [cited 2019 Dec 06].
Available from: http://hdl.handle.net/10393/38593.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Pastic A. LRRK2 Phosphorylates HuD to Affect the Post-Transcriptional Regulation of Parkinson's Disease-Linked mRNA Targets
. [Thesis]. University of Ottawa; 2018. Available from: http://hdl.handle.net/10393/38593
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Colorado
20.
Wang, Xueyin.
The Molecular Basis of RNA Recognition and Transcriptional Regulation by FUS and PRC2.
Degree: PhD, 2018, University of Colorado
URL: https://scholar.colorado.edu/chem_gradetds/271
► RNA and protein interact with each other in the cell nucleus to form RNP (ribonucleoprotein) complexes. These RNPs play key roles in various steps…
(more)
▼ RNA and protein interact with each other in the cell nucleus to form RNP (ribonucleoprotein) complexes. These RNPs play key roles in various steps of gene expression. This thesis focuses on two nuclear
RNA-binding proteins: Fused in Sarcoma (FUS) and Polycomb Repressive Complex
2 (PRC2). The normal functions of FUS are not fully understood, but
RNA binding has been suggested to be crucial for FUS function and many
RNA targets have been identified. Yet the features of RNAs necessary for FUS binding had not been systematically characterized. FUS bound all five published
RNA motifs and other RNAs tightly, including fragments of an <i>Escherichia coli</i> mRNA, suggesting that FUS has a wide range of nucleic-acid binding ability. Additional pull-down experiments reveal that FUS binds the C-terminal domain (CTD) of
RNA polymerase II in an
RNA-dependent manner, providing insight into its function. PRC2 has been shown to interact with RNAs promiscuously <i>in vitro</i> and <i>in vivo</i>, as evidenced by the broad spectrum of transcripts that it binds. Detailed quantitative binding experiments with RNAs of defined sequence and length, coupled with analysis of fRIP-seq and ChIP-seq data, show that PRC2 preferentially binds G-tracts in
RNA. The G-tracts can be either single-stranded or, preferably, folded G-quadruplexes, which are ubiquitous in the transcriptome. This explains the promiscuous nature of PRC2 targeting to
RNA. Additional binding and histone methyltransferase assays showed that
RNA is not a methyltransferase inhibitor; rather it sequesters PRC2 away from nucleosomes. More surprisingly, human PRC2 has robust DNA-binding activity, and
RNA inhibits PRC2 binding to nucleosome by competing PRC2 off the linker region of nucleosomes. Collectively, findings presented in this thesis offer new insights into the mechanistic details underlying the recognition of RNAs by FUS protein and the PRC2 methyltransferase. It is clear that the dysregulation of FUS is linked to neurodegenerative diseases, and that PRC2 is dysregulated in some types of cancers. Thus, understanding the mechanism by which these nuclear
RNA-binding proteins recognize RNAs helps pave new avenues towards developing novel therapeutics to treat
RNA-dominant diseases.
Advisors/Committee Members: Thomas R. Cech, Roy Parker, Rob T. Batey, Karolin Luger, Rui Yi.
Subjects/Keywords: rna; protein; fused in sarcoma; polycomb repressive complex 2; methyltransferase; Biochemistry; Molecular Biology
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APA (6th Edition):
Wang, X. (2018). The Molecular Basis of RNA Recognition and Transcriptional Regulation by FUS and PRC2. (Doctoral Dissertation). University of Colorado. Retrieved from https://scholar.colorado.edu/chem_gradetds/271
Chicago Manual of Style (16th Edition):
Wang, Xueyin. “The Molecular Basis of RNA Recognition and Transcriptional Regulation by FUS and PRC2.” 2018. Doctoral Dissertation, University of Colorado. Accessed December 06, 2019.
https://scholar.colorado.edu/chem_gradetds/271.
MLA Handbook (7th Edition):
Wang, Xueyin. “The Molecular Basis of RNA Recognition and Transcriptional Regulation by FUS and PRC2.” 2018. Web. 06 Dec 2019.
Vancouver:
Wang X. The Molecular Basis of RNA Recognition and Transcriptional Regulation by FUS and PRC2. [Internet] [Doctoral dissertation]. University of Colorado; 2018. [cited 2019 Dec 06].
Available from: https://scholar.colorado.edu/chem_gradetds/271.
Council of Science Editors:
Wang X. The Molecular Basis of RNA Recognition and Transcriptional Regulation by FUS and PRC2. [Doctoral Dissertation]. University of Colorado; 2018. Available from: https://scholar.colorado.edu/chem_gradetds/271
Syracuse University
21.
Gong, Yifan.
IDENTIFYING THE GENETIC MECHANISMS IN SEIZURE THRESHOLD REGULATION.
Degree: PhD, Biology, 2018, Syracuse University
URL: https://surface.syr.edu/etd/968
► Epilepsy is a brain disease defined by having recurrent and spontaneous seizures. The susceptibility to seizure is determined by seizure threshold, which describes the…
(more)
▼ Epilepsy is a brain disease defined by having recurrent and spontaneous seizures. The susceptibility to seizure is determined by seizure threshold, which describes the balance between excitatory and inhibitory neurotransmission in the brain. Epileptogenesis, the transition from normal brain to epileptic brain, is accompanied by a progressive reduction of seizure threshold and has been shown to have genetic influences. Expression of neuronal cyclooxygenase-
2 (COX-
2) gene, PTGS2, a primary gene that regulates prostaglandin synthesis in the normal brain, is enhanced by excitatory neurotransmission and is under tight regulation of N-Methyl-D-Aspartate type glutamate receptor (NMDAR) activity in cortical neurons. The 3’ untranslated region (3’UTR) of PTGS2 gene was found to be a key site of post-transcriptional regulation by NMDAR activity. However, deletion of T-cell intracellular antigen-1 (TIA-1), an
RNA binding protein of COX-
2 mRNA 3’UTR, did not affect COX-
2 protein expression in mouse brain. Although TIA-1 deletion did not alter innate seizure threshold, it facilitated the acquisition of epilepsy and enhanced epileptogenesis-associated mortality. Further investigation revealed that TIA-1 knockout mice have an altered transcriptome in their hippocampi. Together, my findings illustrate an NMDAR-dependent regulatory mechanism of a known modulator of seizure threshold (COX-
2) in neurons, and provide insight into the regulation of epileptogenesis by a novel genetic modifier (TIA-1).
Advisors/Committee Members: James A. Hewett.
Subjects/Keywords: COX-2; Epilepsy; NMDA; RNA binding protein; Seizure; TIA-1; Life Sciences
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APA ·
Chicago ·
MLA ·
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CSE |
Export
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Manager
APA (6th Edition):
Gong, Y. (2018). IDENTIFYING THE GENETIC MECHANISMS IN SEIZURE THRESHOLD REGULATION. (Doctoral Dissertation). Syracuse University. Retrieved from https://surface.syr.edu/etd/968
Chicago Manual of Style (16th Edition):
Gong, Yifan. “IDENTIFYING THE GENETIC MECHANISMS IN SEIZURE THRESHOLD REGULATION.” 2018. Doctoral Dissertation, Syracuse University. Accessed December 06, 2019.
https://surface.syr.edu/etd/968.
MLA Handbook (7th Edition):
Gong, Yifan. “IDENTIFYING THE GENETIC MECHANISMS IN SEIZURE THRESHOLD REGULATION.” 2018. Web. 06 Dec 2019.
Vancouver:
Gong Y. IDENTIFYING THE GENETIC MECHANISMS IN SEIZURE THRESHOLD REGULATION. [Internet] [Doctoral dissertation]. Syracuse University; 2018. [cited 2019 Dec 06].
Available from: https://surface.syr.edu/etd/968.
Council of Science Editors:
Gong Y. IDENTIFYING THE GENETIC MECHANISMS IN SEIZURE THRESHOLD REGULATION. [Doctoral Dissertation]. Syracuse University; 2018. Available from: https://surface.syr.edu/etd/968
22.
Καργιώτης, Οδυσσέας.
Αγγειογένεση και διεισδυτικότητα στα γλοιώματα.
Degree: 2009, University of Ioannina; Πανεπιστήμιο Ιωαννίνων
URL: http://hdl.handle.net/10442/hedi/17709
► Invasive tumors, including gliomas, utilize proteinases to degrade extracellular matrix components and diffuse into the adjacent tissues or migrate towards distant ones. In addition, proteinase…
(more)
▼ Invasive tumors, including gliomas, utilize proteinases to degrade extracellular matrix components and diffuse into the adjacent tissues or migrate towards distant ones. In addition, proteinase activity is required for the formation of new blood vessels within the tumor. Levels of the proteinase matrix metalloproteinase-2 (MMP-2) are highly increased in gliomas. In the present study, we examined the effect of the down-regulation of MMP-2 via adenovirus-mediated siRNA in gliomas. Here, we show that siRNA delivery significantly decreased levels of MMP-2 in the glioblastoma cell lines U-87 and U-251. U-87 and U-251 cells showed impaired invasion through matrigel as well as decreased migration from tumor spheroids. In addition, tumor-induced angiogenesis was decreased in in vitro experiments in cultured human endothelial cells (HMEC) and co-cultures of glioma cells with HMEC and VEGF excretion by tumor cells was reduced, whereas the addition of recombinant MMP-2 and VEGF significantly reversed the anti-angiogenic effect of the MMP-2 siRNA at the co-cultures. We also observed decreased angiogenesis in the in vivo dorsal skin-fold chamber model. After we applied irradiation at 10 Gray, MMP-2 was up-regulated by tumor cells and we observed an induction of tumor angiogenesis by approximately 10% at the co-cultures that the tumor cells were pre-irradiated. siRNA against MMP-2 efficiently inhibited the expression of MMP-2 in the irradiated tumor cells and blocked angiogenesis after irradiation in vitro. Down-regulation of MMP-2 interfered with the activity of intracellular signaling molecules and reduced phosphorylated levels of pI3K, pAKT and p38, even in the irradiated glioma cells, where we observed enhanced activity of p38. Moreover, MMP-2 inhibition induced apoptotic cell death in vitro, and suppressed tumor growth of pre-established U-251 intracranial xenografts in nude mice, whereas pre-infected with the adenovirus carrying the MMP-2 siRNA, U-251 glioblastoma cells failed to develop intracranial tumors after 6 weeks. Thus, specific targeting of MMP-2 may provide a novel, efficient approach for the treatment of gliomas and may contribute to the improvement of the poor outcomes of patients with these brain tumors.
Οι έντονα διεισδυτικοί όγκοι, συμπεριλαμβανομένων των γλοιοβλαστωμάτων, χρησιμοποιούν πρωτεϊνάσες για να αποικοδομήσουν τα συστατικά του εξωκυττάριου υποστρώματος και να διηθήσουν τους παρακείμενους ιστούς ή να μεταναστεύσουν προς απομακρυσμένους. Επιπλέον, η δραστηριότητα των πρωτεϊνασών είναι απαραίτητη για το σχηματισμό των νεόπλαστων αιμοφόρων αγγείων στο εσωτερικό του όγκου. Τα επίπεδα της μεταλλοπρωτεϊνάσης του διάμεσου υποστρώματος-2 (MMP-2) ανιχνεύονται αυξημένα στα γλοιώματα. Στην παρούσα μελέτη, εξετάσαμε την επίδραση της καταστολής της MMP-2 στα γλοιοβλαστώματα, μέσω της αδενοϊικής μεταφοράς siRNA. Τα αποτελέσματα των πειραμάτων φανερώνουν ότι οι κυτταρικές σειρές γλοιωβλατώματος U-87 και U-251 που διαμολύνθηκαν με το αδενοϊικό κατασκεύασμα-μεταφορέα των siRNA εμφάνισαν σημαντική μείωση των…
Subjects/Keywords: Γλοιώματα; Διεισδυτικότητα; Αγγειογένεση; Μεταλλοπρωτεϊνάση του διάμεσου υποστρώματος-2 (mmp-2); RNA αλληλεπίδραση (rnai); Αγγειακός ενδοθηλιακός αυξητικός παράγοντας (VEGF); Αθυμικά ποντίκια; Ιονίζουσα ακτινοβολία; Gliomas; Invasion; Angiogenesis; Matrix Metalloproteinase-2 (Mmp-2); RNA Interference (Rnai); Vascular endothelial growth factor (VEGF); Athymic Mice; Ionizing Irradiation
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APA ·
Chicago ·
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CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Καργιώτης, . . (2009). Αγγειογένεση και διεισδυτικότητα στα γλοιώματα. (Thesis). University of Ioannina; Πανεπιστήμιο Ιωαννίνων. Retrieved from http://hdl.handle.net/10442/hedi/17709
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Καργιώτης, Οδυσσέας. “Αγγειογένεση και διεισδυτικότητα στα γλοιώματα.” 2009. Thesis, University of Ioannina; Πανεπιστήμιο Ιωαννίνων. Accessed December 06, 2019.
http://hdl.handle.net/10442/hedi/17709.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Καργιώτης, Οδυσσέας. “Αγγειογένεση και διεισδυτικότητα στα γλοιώματα.” 2009. Web. 06 Dec 2019.
Vancouver:
Καργιώτης . Αγγειογένεση και διεισδυτικότητα στα γλοιώματα. [Internet] [Thesis]. University of Ioannina; Πανεπιστήμιο Ιωαννίνων; 2009. [cited 2019 Dec 06].
Available from: http://hdl.handle.net/10442/hedi/17709.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Καργιώτης . Αγγειογένεση και διεισδυτικότητα στα γλοιώματα. [Thesis]. University of Ioannina; Πανεπιστήμιο Ιωαννίνων; 2009. Available from: http://hdl.handle.net/10442/hedi/17709
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
23.
Chaveles, Ioannis.
Μελέτη της αναγεννητικής ικανότητας του ήπατος μετά από μερική ηπατεκτομή.
Degree: 2012, University of Patras; Πανεπιστήμιο Πατρών
URL: http://hdl.handle.net/10442/hedi/27943
► Liver regeneration is a unique ability, because of the way it proceeds, i.e. the proliferation of all categories of all mature liver cell types. It…
(more)
▼ Liver regeneration is a unique ability, because of the way it proceeds, i.e. the proliferation of all categories of all mature liver cell types. It is highly possible that this ability is known to human kind since the ancient times, as pictured in Prometheus’ myth. The great scientific interest towards deciphering this complex process is, of course, highly justified. The most common model for the study of the process of regeneration is the surgical model of the 2/3 partial hepatectomy (PHx) in small rodents, predominantly the rat. 2/3 partial hepatectomy leads to a highly synchronized hepatocyte cell-cycle entry and progression. The first phase, known as the ‘priming phase’, occurs in the first hours after PH and poises the hepatocytes to enter the G1 phase and to become receptive to growth factors. The second phase corresponds to an increased metabolic demand imposed on the remnant liver. During this phase, among other metabolic changes, transient hypoglycemia is suggested to induce systemic lipolysis followed by a lipid droplets accumulation in the hepatocytes. During this phase, am major role is played by the autocrine intercellular network. In rodents, this phase is completed in 4 days post-PHx and is followed by the termination phase. Ending the regenerative process is an equally complex, multiparameter process. The weight of the liver is regulated proportionally to the animal’s body weight with remarkable accuracy, sometimes employing an apoptotic wave. The termination phase of the regenerative process ends with normal hepatic histological structure restoration and matrix remodeling. Liver regeneration is a phenomenon that has been thoroughly studied in the past. Nevertheless, a point of emerging research interest has been adopted in the present study: the possible regulatory role of microRNAs in liver regeneration. MicroRNAs are small non-coding RNA molecules (approx. 22 nts long), which have been discovered quite recently but through research they are quickly emerging as cornerstone regulatory means in a large number of cellular functions. In the beginning of this study, data existed implicating microRNAs in the regeneration of zebrafish fins, regeneration in planarian worms and wound healing. The hypothesis that they may have a role in liver regeneration was made and a large part of this study is concerned with investigating the existence of such a role. The researchers began with revising and standardizing the method for anesthesia and surgical procedure, which, at the time (2007), were not satisfactory enough in the case of mice (as opposed to the widely used rats), possibly because of the difficulty of operating on a 20 gram animal. Many alterations were made upon the previous techniques. As a result, a procedure was standardized, as described herein, that guarantees a fast procedure (12-15 minutes) accompanied by excellent animal survival (95-100%). Using the above described technique, the first surgical experiment in this study was conducted: 56 animals (wild-type mice) were used, half of which were…
Subjects/Keywords: Μερική ηπατεκτομή; Πειραματική χειρουγική; Αναγέννηση ήπατος; Πειραματόζωο ποντικός; Μύες; Προμηθέας; Μίκρο-RNA; Ρυθμιστικά μόρια RNA; Liver regeneration; mi-RNA; Micro RNA; Partial hepatectomy; Experimental surgery; 2/3 hepatectomy; Mouse; Prometheus; Murine
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Chaveles, I. (2012). Μελέτη της αναγεννητικής ικανότητας του ήπατος μετά από μερική ηπατεκτομή. (Thesis). University of Patras; Πανεπιστήμιο Πατρών. Retrieved from http://hdl.handle.net/10442/hedi/27943
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Chaveles, Ioannis. “Μελέτη της αναγεννητικής ικανότητας του ήπατος μετά από μερική ηπατεκτομή.” 2012. Thesis, University of Patras; Πανεπιστήμιο Πατρών. Accessed December 06, 2019.
http://hdl.handle.net/10442/hedi/27943.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Chaveles, Ioannis. “Μελέτη της αναγεννητικής ικανότητας του ήπατος μετά από μερική ηπατεκτομή.” 2012. Web. 06 Dec 2019.
Vancouver:
Chaveles I. Μελέτη της αναγεννητικής ικανότητας του ήπατος μετά από μερική ηπατεκτομή. [Internet] [Thesis]. University of Patras; Πανεπιστήμιο Πατρών; 2012. [cited 2019 Dec 06].
Available from: http://hdl.handle.net/10442/hedi/27943.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Chaveles I. Μελέτη της αναγεννητικής ικανότητας του ήπατος μετά από μερική ηπατεκτομή. [Thesis]. University of Patras; Πανεπιστήμιο Πατρών; 2012. Available from: http://hdl.handle.net/10442/hedi/27943
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Universidade do Rio Grande do Sul
24.
Colli, Máikel Luís.
Papel do PTPN2 e MDA5, dois genes candidatos para diabete melito tipo 1, nas respostas das células beta pancreáticas a citocinas pró-‐inflamatórias e ao RNA de fita dupla intracelular.
Degree: 2010, Universidade do Rio Grande do Sul
URL: http://hdl.handle.net/10183/26121
► Na patogênese do diabete melito tipo 1 (DM1) vários genes e fatores ambientais, como as infecções virais, interagem para iniciar um ataque autoimune contra as…
(more)
▼ Na patogênese do diabete melito tipo 1 (DM1) vários genes e fatores ambientais, como as infecções virais, interagem para iniciar um ataque autoimune contra as células beta pancreáticas. Durante a fase inicial desse processo, as células beta desempenham um papel importante através da promoção de um “diálogo” com o sistema imune. Recentemente, o uso de técnicas de genotipagem em larga escala proporcionou um aumento significativo no número de genes conhecidos potencialmente associados ao desenvolvimento do DM1. Para compreender como esses novos genes candidatos modificam as respostas das células beta pancreáticas a mediadores inflamatórios e aos vírus, nós analisamos os dados de estudos prévios de array e um banco de dados online (www.t1dbase.org) para identificar os genes expressos nas células beta e modificados por citocinas ou pelo subproduto da replicação viral,
RNA de fita dupla (RNAfd). Dois genes foram selecionados para serem estudados nesta tese, PTPN2 e MDA5. PTPN2 é uma proteína tirosina fosfatase que tem entre os seus alvos o STAT1, um fator de transcrição chave no processo de morte das células beta. Inicialmente, confirmamos a presença de PTPN2 pela quantificação do seu RNAm e produto protéico em uma linhagem de células beta (INS-1E), células beta primárias de rato purificadas por FACS e ilhotas humanas. Tratamento com citocinas ou RNAfd intracelular significativamente aumentou a sua expressão. O knockdown específico deste gene pela técnica de
RNA de interferência aumentou significativamente a apoptose das células beta expostas a uma combinação de citocinas (interleucina-1! (IL-1!) + interferon-" (IFN-")) ou RNAfd intracelular, e converteu IFN-" isoladamente em um estímulo pró-apoptótico. O silenciamento do PTPN2 amplificou a fosforilação do STAT1. O duplo knockdown, PTPN2 + STAT1, protegeu as células beta contra a apoptose induzida por citocinas, sugerindo que PTPN2 age como um regulador negativo dos efeitos pró-apoptóticos do STAT1. Contudo, o silenciamento do PTPN2 não produziu nenhuma alteração maior na expressão de citocinas e quimiocinas. O segundo gene candidato, MDA5, é uma helicase associada com o reconhecimento de ácidos nucléicos virais intracelulares. A principal função do MDA5 é a detecção de infecções virais; sendo assim, esse gene foi avaliado apenas no contexto do mimético viral RNAfd. A transfecção de células INS-1E e células beta primárias de rato purificadas por FACS com RNAfd induziu um aumento significativo no RNAm codificando MDA5. O silenciamento do MDA5 e do RIG-I (outra helicase envolvida no reconhecimento do RNAfd intracelular) não modificou a frequência da apoptose induziu por RNAfd. Por outro lado, o knockdown do MDA5, mas não do RIG-I, significativamente reduziu a expressão de várias citocinas/quimiocinas produzidas pelas células beta expostas ao RNAfd intracelular. Concluindo, os dados apresentados sugerem que esses dois genes candidatos, através de suas funções nas células beta, podem ter importantes papéis no desenvolvimento do DM1. PTPN2 aparentemente previne a apoptose das…
Advisors/Committee Members: Canani, Luis Henrique Santos.
Subjects/Keywords: Diabetes mellitus tipo 1; Proteína tirosina fosfatase não receptora tipo 2; RNA helicases; Células secretoras de insulina; Proteínas de ligação a RNA
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APA (6th Edition):
Colli, M. L. (2010). Papel do PTPN2 e MDA5, dois genes candidatos para diabete melito tipo 1, nas respostas das células beta pancreáticas a citocinas pró-‐inflamatórias e ao RNA de fita dupla intracelular. (Thesis). Universidade do Rio Grande do Sul. Retrieved from http://hdl.handle.net/10183/26121
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Colli, Máikel Luís. “Papel do PTPN2 e MDA5, dois genes candidatos para diabete melito tipo 1, nas respostas das células beta pancreáticas a citocinas pró-‐inflamatórias e ao RNA de fita dupla intracelular.” 2010. Thesis, Universidade do Rio Grande do Sul. Accessed December 06, 2019.
http://hdl.handle.net/10183/26121.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Colli, Máikel Luís. “Papel do PTPN2 e MDA5, dois genes candidatos para diabete melito tipo 1, nas respostas das células beta pancreáticas a citocinas pró-‐inflamatórias e ao RNA de fita dupla intracelular.” 2010. Web. 06 Dec 2019.
Vancouver:
Colli ML. Papel do PTPN2 e MDA5, dois genes candidatos para diabete melito tipo 1, nas respostas das células beta pancreáticas a citocinas pró-‐inflamatórias e ao RNA de fita dupla intracelular. [Internet] [Thesis]. Universidade do Rio Grande do Sul; 2010. [cited 2019 Dec 06].
Available from: http://hdl.handle.net/10183/26121.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Colli ML. Papel do PTPN2 e MDA5, dois genes candidatos para diabete melito tipo 1, nas respostas das células beta pancreáticas a citocinas pró-‐inflamatórias e ao RNA de fita dupla intracelular. [Thesis]. Universidade do Rio Grande do Sul; 2010. Available from: http://hdl.handle.net/10183/26121
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
25.
Wahlgren, Jessica.
Intercellular communication via exosomes.
Degree: 2014, University of Gothenburg / Göteborgs Universitet
URL: http://hdl.handle.net/2077/34427
► Exosomes are small membrane bound vesicles between 30-100 nm in diameter of endocytic origin that are secreted into the extracellular environment by many different cell…
(more)
▼ Exosomes are small membrane bound vesicles between 30-100 nm in diameter of endocytic origin that are secreted into the extracellular environment by many different cell types. They play a role in intercellular communication by transferring proteins, lipids and RNA to recipient cells. The overall aim of this work has been to further investigate the mechanisms by which cells communicate with each other via exosomes.
In Paper I we hypothesized that exosomes from human cells could be used as vectors to provide cells with therapeutic RNA. Herein, exogenous short interfering RNAs were successfully introduced into various kinds of human exosomes using electroporation. Flow cytometry, confocal microscopy and northern blot confirmed the presence of siRNA inside the exosomes. The results showed that exosomes from blood plasma could deliver the siRNA to human monocytes and lymphocytes. The siRNA delivered to the target cells was shown to be functional causing selective gene silencing of mitogen activated protein kinase 1. Our results imply that exosomes from human cells could be used as vectors for delivery of therapeutic exogenous nucleic acids to cells.
In paper II we investigated if exosomes from activated CD3+ T cells could play a role in an immunological response by conveying signals from their secreting cells to recipient resting T cells in an in vitro autologous setting. The role of these exosomes was explored in IL-2 mediated T cell proliferation. The results showed that neither exosomes nor IL-2 alone could stimulate proliferation in resting T cells. However, exosomes from stimulated T cells together with IL-2 were able to induce proliferation. T cell cultures stimulated with exosomes and IL-2 showed a higher proportion of CD8+ T cells than cultures without exosomes. Moreover, a cytokine array showed significant changes in the levels of cytokines and chemokines when exosomes were present. The results indicate that activated CD3+ cells communicate with resting autologous T cells via exosomes.
The main focus in paper III was to study the cellular mechanism by which esRNA is selectively packaged into exosome vesicles during their biosynthesis. Using RNA gel mobility shift assay, we showed the presence of RNA-binding proteins (RBPs) in exosomes. Moreover, we developed a method for the identification of exosomal RBPs able to bind to the esRNA and cellular microRNA. Using this method, we could identify 31 different RBPs in exosomes and 78 in cells. To evaluate the possible role of the identified RBPs in the transfer mechanism of RNA into intraluminal vesicles, five gene transcripts from the identified RBPs were silenced. The results revealed that a selective gene silencing of hnRNPA2B1 caused a reduction of RNA present in the extracellular vesicles. Thus, a novel transport mechanism was suggested for the packaging of esRNA into the exosomes.
In conclusion, the studies presented in this thesis have implications for better understanding the RNA and protein transfer mechanism that occurs between cells via exosomes. The…
Subjects/Keywords: exosomes; electroporation; RNA; IL-2; RNA binding proteins
…P, Valadi H.
Plasma exosomes can deliver exogenous short interfering RNA to
monocytes and… …secrete exosomes that participate in IL-2
mediated immune response signaling.
PLoS One, 2012; 7… …Exosomes contain RNA-binding proteins involved in the transfer
mechanism of esRNA
In manuscript… …2
Extracellular vesicles… …2
Exosomes…
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APA (6th Edition):
Wahlgren, J. (2014). Intercellular communication via exosomes. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/34427
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Wahlgren, Jessica. “Intercellular communication via exosomes.” 2014. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed December 06, 2019.
http://hdl.handle.net/2077/34427.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Wahlgren, Jessica. “Intercellular communication via exosomes.” 2014. Web. 06 Dec 2019.
Vancouver:
Wahlgren J. Intercellular communication via exosomes. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 2014. [cited 2019 Dec 06].
Available from: http://hdl.handle.net/2077/34427.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Wahlgren J. Intercellular communication via exosomes. [Thesis]. University of Gothenburg / Göteborgs Universitet; 2014. Available from: http://hdl.handle.net/2077/34427
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Uppsala University
26.
Kristoffersson, Anders.
Rolling circle transcription on smallest size double stranded DNA minicircles.
Degree: Biology Education Centre, 2010, Uppsala University
URL: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-134082
► The RNA polymerase T7 is utilized as a component of motor complexes in DNA nanotechnology due to its high promotor specificity, the lack of…
(more)
▼ The RNA polymerase T7 is utilized as a component of motor complexes in DNA nanotechnology due to its high promotor specificity, the lack of external transcription factors and its very high processivity, but there is no experience of its application on small double stranded DNA circles. Circular templates from 210 to 126 bp in circumference sharing a common promotor termination motif were synthesized and transcription was monitored at end point on gel and in real time with a 2’ O methyl RNA molecular beacon. The RNAP T7 was found to be able to utilize circular dsDNA templates down to 126 bp with moderate impact on transcription rate for saturated systems and rolling circle transcription products were evident with denaturizing PAGE gel electrophoresis for templates down to 167 bp.
Subjects/Keywords: RNA polymerase; RNAP T7; DNA nanotechnology; molecular motor; real time monitoring of transcription; 2’ O methyl RNA; molecular beacon; minicircle; Other bioengineering; Övrig bioteknik
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APA (6th Edition):
Kristoffersson, A. (2010). Rolling circle transcription on smallest size double stranded DNA minicircles. (Thesis). Uppsala University. Retrieved from http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-134082
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Kristoffersson, Anders. “Rolling circle transcription on smallest size double stranded DNA minicircles.” 2010. Thesis, Uppsala University. Accessed December 06, 2019.
http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-134082.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Kristoffersson, Anders. “Rolling circle transcription on smallest size double stranded DNA minicircles.” 2010. Web. 06 Dec 2019.
Vancouver:
Kristoffersson A. Rolling circle transcription on smallest size double stranded DNA minicircles. [Internet] [Thesis]. Uppsala University; 2010. [cited 2019 Dec 06].
Available from: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-134082.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Kristoffersson A. Rolling circle transcription on smallest size double stranded DNA minicircles. [Thesis]. Uppsala University; 2010. Available from: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-134082
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Iowa State University
27.
Jia, Yi.
Analysis of differences in gene expression and the genetic and epigenetic regulation of transcript accumulation in maize.
Degree: 2010, Iowa State University
URL: https://lib.dr.iastate.edu/etd/11302
► Much of phenotypic variation is the result of alteration in gene expression patterns. Maize exhibits extremely high levels of diversity in DNA sequences, gene expression…
(more)
▼ Much of phenotypic variation is the result of alteration in gene expression patterns. Maize exhibits extremely high levels of diversity in DNA sequences, gene expression and phenotypes. Transcript profiling studies were conducted to explore the relationship between genotype and gene expression patterns. Consistent with prior reports these studies demonstrated that gene expression can be controlled not only by genetic but also epigenetic determinants. Importantly, the identified widespread natural antisense transcripts (NATs) and hundreds of the NAT-eQTL regulating the expression of NATs further increase the complexity of gene expression. These observations and conclusions enhance our understanding of various fundamental biology questions. For example, heterosis is the phenomenon that the progeny of particular inbred lines exhibit superior performance as compared to both parents. We have hypothesized that such extreme phenotypic variations between inbred and hybrid are explained by multiple factors, including epigenetic factors such as those studied here.
Subjects/Keywords: hybrid vigor; maize shoot apical meristem; mop1; Natural antisense transcripts; paramutation; RNA-dependent RNA polymerase 2; Cell and Developmental Biology; Genetics and Genomics
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APA ·
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APA (6th Edition):
Jia, Y. (2010). Analysis of differences in gene expression and the genetic and epigenetic regulation of transcript accumulation in maize. (Thesis). Iowa State University. Retrieved from https://lib.dr.iastate.edu/etd/11302
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Jia, Yi. “Analysis of differences in gene expression and the genetic and epigenetic regulation of transcript accumulation in maize.” 2010. Thesis, Iowa State University. Accessed December 06, 2019.
https://lib.dr.iastate.edu/etd/11302.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Jia, Yi. “Analysis of differences in gene expression and the genetic and epigenetic regulation of transcript accumulation in maize.” 2010. Web. 06 Dec 2019.
Vancouver:
Jia Y. Analysis of differences in gene expression and the genetic and epigenetic regulation of transcript accumulation in maize. [Internet] [Thesis]. Iowa State University; 2010. [cited 2019 Dec 06].
Available from: https://lib.dr.iastate.edu/etd/11302.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Jia Y. Analysis of differences in gene expression and the genetic and epigenetic regulation of transcript accumulation in maize. [Thesis]. Iowa State University; 2010. Available from: https://lib.dr.iastate.edu/etd/11302
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Illinois – Urbana-Champaign
28.
Knowlton, Aaron.
Enhancement of Dicer as a personalized anticancer strategy.
Degree: MS, 0318, 2012, University of Illinois – Urbana-Champaign
URL: http://hdl.handle.net/2142/34568
► Normal miRNA production is essential for regulating protein expression and cellular fate. Misregulation of miRNA production is emerging as a key factor in the development…
(more)
▼ Normal miRNA production is essential for regulating protein expression and cellular fate. Misregulation of miRNA production is emerging as a key factor in the development of many disease states, including most forms cancer. A global downregulation of miRNA processing is common among cancers and has been shown to drive tumorogenesis. This global downregulation of miRNA biogenesis is caused by the disruption of key enzymes in the miRNA biogenesis pathway like Dicer, TAR
RNA-binding protein (TRBP) and Drosha. Herein, the enhancement of miRNA processing as a therapeutic strategy is explored. Developing small molecule or peptide based therapeutics that mimic TRBP, an endogenous activator of Dicer, to enhance miRNA processing in cancers with reduced miRNA production may lead to safe and effective treatments for a number of cancer patients. Identification of direct activators of Dicer will be explored using in vitro kinetic assays with fluorescent probes. Expression of Dicer, TRBP and a peptide-mapping library of TRBP are also described. Since miRNA biogenesis is such a critical pathway in tumorogenesis, activation of this pathway may prove to be an effective target in the battle against cancer.
Advisors/Committee Members: Hergenrother, Paul J. (advisor).
Subjects/Keywords: Dicer; transactivating response RNA-binding protein (TRBP); Dicer1; transactivating response RNA-binding protein 2 (tarbp2); micro ribonucleic acid (miRNA); cancer; Hereditary nonpolyposis colorectal cancer (HNPCC); aptamer; Malachite green
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APA ·
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APA (6th Edition):
Knowlton, A. (2012). Enhancement of Dicer as a personalized anticancer strategy. (Thesis). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/34568
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Knowlton, Aaron. “Enhancement of Dicer as a personalized anticancer strategy.” 2012. Thesis, University of Illinois – Urbana-Champaign. Accessed December 06, 2019.
http://hdl.handle.net/2142/34568.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Knowlton, Aaron. “Enhancement of Dicer as a personalized anticancer strategy.” 2012. Web. 06 Dec 2019.
Vancouver:
Knowlton A. Enhancement of Dicer as a personalized anticancer strategy. [Internet] [Thesis]. University of Illinois – Urbana-Champaign; 2012. [cited 2019 Dec 06].
Available from: http://hdl.handle.net/2142/34568.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Knowlton A. Enhancement of Dicer as a personalized anticancer strategy. [Thesis]. University of Illinois – Urbana-Champaign; 2012. Available from: http://hdl.handle.net/2142/34568
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Toronto
29.
Shao, Peng.
Novel Gene Regulation Mechanisms of Aryl Hydrocarbon Receptor: A ChIP-seq and RNA-seq Study of Ahrdbd/dbd Mice Expressing an Aryl Hydrocarbon Receptor with Mutated DNA-binding Domain.
Degree: 2019, University of Toronto
URL: http://hdl.handle.net/1807/98361
► Aryl hydrocarbon receptor (AHR) is a transcription factor known for mediating the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and regulating many physiological and pathological processes. In…
(more)
▼ Aryl hydrocarbon receptor (AHR) is a transcription factor known for mediating the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and regulating many physiological and pathological processes. In its canonical signalling pathway, ligand-activated AHR translocates into nucleus, associates with its heterodimerization partner, and binds the cognate aryl hydrocarbon response element (AHRE) to regulate transcription. Based on recent evidence, we hypothesize that AHR may mediate gene regulation through unrevealed mechanisms, namely indirect DNA binding via tethering to other transcription factors, or direct DNA binding to regions not containing any AHRE. To explore this, Ahrdbd/dbd mice whose AHR is incapable of binding AHRE were used. ChIP-seq showed Ahrdbd/dbd mice indeed had an increased number of AHR-bound regions across the genome upon activation by TCDD. However, RNA-seq found almost no alteration in gene expression. These results support the presence but refute the physiological significance of AHR tethering to other transcription factors or non-AHRE binding to DNA.
M.Sc.
Advisors/Committee Members: Grant, Denis M, Matthews, Jason, Pharmacology.
Subjects/Keywords: 2; 3; 7; 8-tetrachlorodibenzo-p-dioxin (TCDD); Aryl Hydrocarbon Receptor (AHR); Aryl Hydrocarbon Response Element (AHRE); Chromatin Immunoprecipitation Sequencing (ChIP-Seq); DNA Binding; RNA sequencing (RNA-Seq); 0419
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APA ·
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MLA ·
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Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Shao, P. (2019). Novel Gene Regulation Mechanisms of Aryl Hydrocarbon Receptor: A ChIP-seq and RNA-seq Study of Ahrdbd/dbd Mice Expressing an Aryl Hydrocarbon Receptor with Mutated DNA-binding Domain. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/98361
Chicago Manual of Style (16th Edition):
Shao, Peng. “Novel Gene Regulation Mechanisms of Aryl Hydrocarbon Receptor: A ChIP-seq and RNA-seq Study of Ahrdbd/dbd Mice Expressing an Aryl Hydrocarbon Receptor with Mutated DNA-binding Domain.” 2019. Masters Thesis, University of Toronto. Accessed December 06, 2019.
http://hdl.handle.net/1807/98361.
MLA Handbook (7th Edition):
Shao, Peng. “Novel Gene Regulation Mechanisms of Aryl Hydrocarbon Receptor: A ChIP-seq and RNA-seq Study of Ahrdbd/dbd Mice Expressing an Aryl Hydrocarbon Receptor with Mutated DNA-binding Domain.” 2019. Web. 06 Dec 2019.
Vancouver:
Shao P. Novel Gene Regulation Mechanisms of Aryl Hydrocarbon Receptor: A ChIP-seq and RNA-seq Study of Ahrdbd/dbd Mice Expressing an Aryl Hydrocarbon Receptor with Mutated DNA-binding Domain. [Internet] [Masters thesis]. University of Toronto; 2019. [cited 2019 Dec 06].
Available from: http://hdl.handle.net/1807/98361.
Council of Science Editors:
Shao P. Novel Gene Regulation Mechanisms of Aryl Hydrocarbon Receptor: A ChIP-seq and RNA-seq Study of Ahrdbd/dbd Mice Expressing an Aryl Hydrocarbon Receptor with Mutated DNA-binding Domain. [Masters Thesis]. University of Toronto; 2019. Available from: http://hdl.handle.net/1807/98361
University of Alberta
30.
El-Yazbi, Amira F.
Novel Spectroscopic Probes for Detecting DNA Damage.
Degree: PhD, Department of Chemistry, 2013, University of Alberta
URL: https://era.library.ualberta.ca/files/hm50tt27s
► Absorption of UV light by nucleic acids can result in the formation of molecular lesions leading to mutagenesis, carcinogenesis, and cell death. Thus, understanding DNA…
(more)
▼ Absorption of UV light by nucleic acids can result in
the formation of molecular lesions leading to mutagenesis,
carcinogenesis, and cell death. Thus, understanding DNA damage is
important for elucidating the molecular mechanisms of disease. Much
effort has been focused on developing methods for detecting DNA
damage. However, almost all of the proposed methods consist of
multi-step procedures, are limited to a specific type of damage,
require expensive instruments, and/or suffer from a high level of
interference. In this thesis, I present some novel simple,
mix-and-read fluorescent assays for the detection of DNA damage.
The goal is to design probes that are superior to conventional
fluorescent molecular beacons (MBs) in detecting DNA damage. The
first approach was to design MBs with modified DNA backbones. For
this purpose, locked nucleic acid (LNA) and chimeric RNA-DNA (chMB)
MBs were designed. The results show that chMBs are more sensitive
and selective for DNA damage than LNA MBs that have comparable
selectivity to conventional MBs. However, these probes show a
signal that is inversely proportional to the amount of damage.
Therefore, the second approach was to design probes that give
signals directly proportional to the amount of damage. For this
purpose, probes with 2-aminopurine (2AP) were designed. Such probes
show no fluorescence for undamaged DNA and fluorescence for damaged
DNA. 2AP probes offer high sensitivity and selectivity comparable
to MBs, but are expensive, especially with an increasing number of
2APs in the probe to increase sensitivity. Thus, the hypochromism
probe was designed. For this probe, the absorbance signal increases
with increasing amount of damage. Results show that the
hypochromism probe is more selective and more than ten times
cheaper than conventional MBs, but less sensitive. The need for a
sensitive, selective and inexpensive probe was the motivation to
design the Tb3+/hairpin probe. Single-stranded DNA greatly enhances
the Tb3+ emission, but duplex DNA does not. Undamaged DNA targets
will hybridize with the hairpin with no emission. The Tb3+/DNA
hairpin probe proves to be the cheapest, most sensitive and
selective probe for the quantification of DNA damage of all the
probes presented here.
Subjects/Keywords: Fluorescence; Terbium; Chimeric RNA DNA probe; LNA probe; Hypochromism; 2-aminopurine; Nucleic acid detection; Hybridization; Ultraviolet light; Molecular beacon; DNA damage
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APA ·
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Export
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APA (6th Edition):
El-Yazbi, A. F. (2013). Novel Spectroscopic Probes for Detecting DNA Damage. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/hm50tt27s
Chicago Manual of Style (16th Edition):
El-Yazbi, Amira F. “Novel Spectroscopic Probes for Detecting DNA Damage.” 2013. Doctoral Dissertation, University of Alberta. Accessed December 06, 2019.
https://era.library.ualberta.ca/files/hm50tt27s.
MLA Handbook (7th Edition):
El-Yazbi, Amira F. “Novel Spectroscopic Probes for Detecting DNA Damage.” 2013. Web. 06 Dec 2019.
Vancouver:
El-Yazbi AF. Novel Spectroscopic Probes for Detecting DNA Damage. [Internet] [Doctoral dissertation]. University of Alberta; 2013. [cited 2019 Dec 06].
Available from: https://era.library.ualberta.ca/files/hm50tt27s.
Council of Science Editors:
El-Yazbi AF. Novel Spectroscopic Probes for Detecting DNA Damage. [Doctoral Dissertation]. University of Alberta; 2013. Available from: https://era.library.ualberta.ca/files/hm50tt27s
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Open Access Theses and Dissertations
