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University of Illinois – Chicago
1.
Pershad, Kritika.
Directed Evolution of the Forkhead-associated Domain to Generate Anti-Phosphospecific Reagents.
Degree: 2013, University of Illinois – Chicago
URL: http://hdl.handle.net/10027/9800 
► While affinity reagents are valuable tools for monitoring protein phosphorylation and studying signaling events in cells, generating them through immunization of animals with phosphopeptides is…
(more)
▼ While affinity reagents are valuable tools for monitoring protein phosphorylation and studying signaling events in cells, generating them through immunization of animals with phosphopeptides is expensive, laborious and time consuming. An attractive alternative is to use protein evolution techniques and isolate new anti-phosphopeptide binding specificities from a library of variants of a phosphopeptide-binding
domain. To explore this strategy, we attempted to display on the surface of bacteriophage M13, the N-terminal
Forkhead-
associated domain (FHA1) of yeast Rad53p, which is a naturally occurring phosphothreonine (pT)-binding
domain, and found it to be non-functional due to misfolding in the bacterial periplasm. To overcome this limitation, a library of FHA1 variants was constructed by mutagenic PCR and functional variants were isolated after three rounds of affinity selection with its pT peptide ligand. A hydrophobic residue at position 34 in the β1-strand was discovered to be essential for phage-display of a functional FHA1
domain. Additionally, by heating the phage library to 50ºC prior to affinity selection with its cognate pT peptide, we identified a variant (G2) that was ~8ºC more thermal stable than the wild-type
domain. Using G2 as a scaffold, we constructed phage-displayed libraries of FHA1 variants and affinity selected for variants that bound selectively to seven pT peptides. These reagents are renewable and have high protein yields (~20-25 mg/L), when expressed in Escherichia coli. Thus, we have changed the specificity of the FHA1
domain and demonstrated that engineering phosphopeptide-binding domains is an attractive avenue for generating new anti-phosphopeptide binding specificities in vitro by phage-display.
Advisors/Committee Members: Stone, David E. (advisor), Kay, Brian K. (committee member), Jin, Hua (committee member), Orenic, Teresa V. (committee member), Santarsiero, Bernard D. (committee member).
Subjects/Keywords: forkhead-associated domain; anti-phosphospecific reagents; phage display; alanine scanning; phosphothreonine peptides; affinity selection
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APA (6th Edition):
Pershad, K. (2013). Directed Evolution of the Forkhead-associated Domain to Generate Anti-Phosphospecific Reagents. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/9800
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):
Pershad, Kritika. “Directed Evolution of the Forkhead-associated Domain to Generate Anti-Phosphospecific Reagents.” 2013. Thesis, University of Illinois – Chicago. Accessed April 19, 2021.
http://hdl.handle.net/10027/9800.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Pershad, Kritika. “Directed Evolution of the Forkhead-associated Domain to Generate Anti-Phosphospecific Reagents.” 2013. Web. 19 Apr 2021.
Vancouver:
Pershad K. Directed Evolution of the Forkhead-associated Domain to Generate Anti-Phosphospecific Reagents. [Internet] [Thesis]. University of Illinois – Chicago; 2013. [cited 2021 Apr 19].
Available from: http://hdl.handle.net/10027/9800.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Pershad K. Directed Evolution of the Forkhead-associated Domain to Generate Anti-Phosphospecific Reagents. [Thesis]. University of Illinois – Chicago; 2013. Available from: http://hdl.handle.net/10027/9800
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Illinois – Chicago
2.
Venegas, Leon A.
Generating and Characterizing Phosphospecific Affinity Reagents Using the Forkhead-Associated 1 Domain.
Degree: 2018, University of Illinois – Chicago
URL: http://hdl.handle.net/10027/23028
► Phosphorylation is an important post-translational event that has a wide array of functional consequences. With advances in the ability of various technologies in revealing and…
(more)
▼ Phosphorylation is an important post-translational event that has a wide array of functional consequences. With advances in the ability of various technologies in revealing and mapping new phosphosites in proteins, it is equally important to develop affinity reagents that can monitor such posttranslational modifications in eukaryotic cells. While monoclonal and polyclonal antibodies have been shown to be useful in assessing the phosphoproteome, we have expanded our efforts to exploit the
Forkhead-
associated 1 (FHA1)
domain as scaffold for generating recombinant affinity reagents that recognize phosphothreonine-containing peptides. A phage display library of FHA1 variants was screened by affinity selection with 15 phosphothreonine-containing peptides corresponding to various human transcription factors and kinases. The library yielded binding variants against 10 targets (66% success rate); success was largely determined by what residue occurred at the +3 position (C-terminal) to the pThr moiety (i.e., pT+3). Three FHA domains binding transcription factor,c-Myc (Myc), calmodulin-dependent protein kinase II (CaMKII), and extracellular-signal regulated kinases 1 and 2 (ERK1/2) were characterized and compared against commercially available antibodies. All FHA domains were shown to be phosphorylation-dependent and phosphothreonine-specific in their binding, unlike several commercial monoclonal and polyclonal antibodies. The crystal structure of the engineered FHA Myc-pThr-binding
domain (Myc-pTBD) was solved in complex with its cognate ligand. The Myc-pTBD was observed to be structurally similar to the yeast Rad9 FHA1
domain, except that its β4-β5 and β10-β11 loops form a hydrophobic pocket to facilitate the interaction between the
domain and the peptide ligand. Both the pThr and the residue at the pT+3 position were major factors in defining the specificity of the FHA domains. To enhance apparent affinity of the pTBDs, the Myc-pTBD, ERK1/2-pTBD, and CaMKII-pTBD were converted to homodimers by either fusing the domains to a leucine zipper (LZ) dimerizing sequence (to generate pTBD LZs) or linking them in tandem (to generate pTBD-Tandem repeats, TR). To estimate the affinity of the various constructs, the concentration of each that gives the half maximal response (EC50) was measured in an ELISA. Monomers were observed to have an average EC50 value of 10-8 M, whereas pTBD-LZs and pTBD-TRs had EC50 values of 10-9 M and 10-10 M, respectively. Interestingly, there was no apparent loss of specificity for either dimeric form of the three pTBDs tested. The utility of Myc-pTBD LZ was further evaluated by probing western blots of lysates of HEK 293 cells engineered to overexpress Myc-pT58. Curiously, while the Myc-pTBD LZ failed to detect Myc-pT58, it bound to two unrelated, phosphorylated protein species. Future engineering experiments on the FHA scaffold may contribute to enhanced detection of cell signaling events and biomarkers of disease.
Advisors/Committee Members: Kay, Brian (advisor), Morrison, Don (committee member), Mankin, Alexander (committee member), Karginov, Andrei (committee member), Orenic, Teresa (chair).
Subjects/Keywords: Forkhead-associated domain; Phage display; Antibody; Phosphorylation; Phosphothreonine; c-Myc; Leucine zipper; Dimerization
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APA (6th Edition):
Venegas, L. A. (2018). Generating and Characterizing Phosphospecific Affinity Reagents Using the Forkhead-Associated 1 Domain. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/23028
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):
Venegas, Leon A. “Generating and Characterizing Phosphospecific Affinity Reagents Using the Forkhead-Associated 1 Domain.” 2018. Thesis, University of Illinois – Chicago. Accessed April 19, 2021.
http://hdl.handle.net/10027/23028.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Venegas, Leon A. “Generating and Characterizing Phosphospecific Affinity Reagents Using the Forkhead-Associated 1 Domain.” 2018. Web. 19 Apr 2021.
Vancouver:
Venegas LA. Generating and Characterizing Phosphospecific Affinity Reagents Using the Forkhead-Associated 1 Domain. [Internet] [Thesis]. University of Illinois – Chicago; 2018. [cited 2021 Apr 19].
Available from: http://hdl.handle.net/10027/23028.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Venegas LA. Generating and Characterizing Phosphospecific Affinity Reagents Using the Forkhead-Associated 1 Domain. [Thesis]. University of Illinois – Chicago; 2018. Available from: http://hdl.handle.net/10027/23028
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Missouri – Columbia
3.
Ding, Zhaofeng, 1978-.
Kinase-interacting FHA domain of kinase associated protein phosphatase : phosphopeptide interactions and NMR-detected dynamics.
Degree: PhD, 2007, University of Missouri – Columbia
URL: http://hdl.handle.net/10355/4729
► FHA domains are phosphoThr recognition modules found in diverse signaling proteins. Kinase-associated protein phosphatase (KAPP) from Arabidopsis employs its FHA domain in its negative regulation…
(more)
▼ FHA domains are phosphoThr recognition modules found in diverse signaling proteins. Kinase-
associated protein phosphatase (KAPP) from Arabidopsis employs its FHA
domain in its negative regulation of some receptor-like kinase (RLK) signaling pathways. The interactions between the kinase-interacting FHA (KI-FHA)
domain of KAPP and RLK kinase domains have been investigated. Three phosphoThr peptides of KAPP-binding RLKs were found by isothermal titration calorimetry (ITC) and NMR to bind KI-FHA, with Kd values of 8 to 30 [mu]M. Thermodynamics study revealed that their affinities were driven by favorable enthalpy and the hydrophobic effect. Mutagenesis of these three threonine sites suggests Thr546 in the C-lobe of BAK1 kinase
domain to be a principal site of KI-FHA binding. BRI1 kinase
domain interacts with the same 3/4, 4/5, 6/7, 8/9, and 10/11 recognition loops of KI-FHA as do phosphoThr peptides. The backbone mobility of KI-FHA, free and bound to pThr868CLV1 peptide has also been investigated using 15N NMR relaxation at 500 MHz and 600 MHz. Binding of the peptide seems to reduce nsec-scale fluctuations of KI-FHA globally. In the psec to nsec timescale, KI-FHA residues that are critical for phosphopeptide recognitions are rigid. Peptide binding rigidifies KI-FHA at the binding site and remote sites across the [beta-] sandwich. Peptide binding increases flexibility around the periphery of the binding site, perhaps relieving strain from the peptide association.
Advisors/Committee Members: Van Doren, Steven (advisor).
Subjects/Keywords: Forkhead-associated domain.; Forkhead-associated domain; Plants – Development; Phosphoprotein phosphatases; Protein kinases; Nuclear magnetic resonance; Cellular signal transduction; Mutagenesis
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APA (6th Edition):
Ding, Zhaofeng, 1. (2007). Kinase-interacting FHA domain of kinase associated protein phosphatase : phosphopeptide interactions and NMR-detected dynamics. (Doctoral Dissertation). University of Missouri – Columbia. Retrieved from http://hdl.handle.net/10355/4729
Chicago Manual of Style (16th Edition):
Ding, Zhaofeng, 1978-. “Kinase-interacting FHA domain of kinase associated protein phosphatase : phosphopeptide interactions and NMR-detected dynamics.” 2007. Doctoral Dissertation, University of Missouri – Columbia. Accessed April 19, 2021.
http://hdl.handle.net/10355/4729.
MLA Handbook (7th Edition):
Ding, Zhaofeng, 1978-. “Kinase-interacting FHA domain of kinase associated protein phosphatase : phosphopeptide interactions and NMR-detected dynamics.” 2007. Web. 19 Apr 2021.
Vancouver:
Ding, Zhaofeng 1. Kinase-interacting FHA domain of kinase associated protein phosphatase : phosphopeptide interactions and NMR-detected dynamics. [Internet] [Doctoral dissertation]. University of Missouri – Columbia; 2007. [cited 2021 Apr 19].
Available from: http://hdl.handle.net/10355/4729.
Council of Science Editors:
Ding, Zhaofeng 1. Kinase-interacting FHA domain of kinase associated protein phosphatase : phosphopeptide interactions and NMR-detected dynamics. [Doctoral Dissertation]. University of Missouri – Columbia; 2007. Available from: http://hdl.handle.net/10355/4729
4.
Straker, Geburah.
Characterization of the FHA domain involved in Saccharomyces cerevisiae dNTP regulation.
Degree: 2018, University of Waterloo
URL: http://hdl.handle.net/10012/13182
► Over 2000 Forkhead-associated (FHA) domain-containing proteins exhibiting diverse functions, such as kinases, phosphatases, and transcription factors, have been identified to date in both eukaryotic and…
(more)
▼ Over 2000 Forkhead-associated (FHA) domain-containing proteins exhibiting diverse functions, such as kinases, phosphatases, and transcription factors, have been identified to date in both eukaryotic and prokaryotic organisms. Initially characterized as the only known protein-protein interaction motif with phosphothreonine (pThr)-binding specificity, research from the Duncker Lab that characterized the minimal interaction surfaces between the Rad53 FHA1 domain and the Dbf4 H-BRCT domain in the model organism Saccharomyces cerevisiae demonstrated the existence and importance of a conserved non-canonical binding surface on Rad53 FHA1 that does not rely on the phosphothreonine-binding patch. Recent analysis by the Duncker Lab of a Rad53 paralog called DNA damage UNinducible (Dun1), a budding yeast cell cycle checkpoint kinase involved in regulating dNTP synthesis, identified another instance of a conserved non-canonical FHA domain lateral surface interaction patch, located on the Dun1 FHA domain, similar to that of Rad53 FHA1. Continued examination of the Dun1 FHA domain lateral surface interaction patch and pThr-binding site suggested the existence of a differential requirement for the non-canonical FHA domain lateral surface interaction patch and the canonical pThr-binding site during interactions between Dun1 and some of its ligands.
The research presented in this thesis aimed to study the prevalence of protein-protein interactions in S. cerevisiae that operate using this novel non-canonical lateral surface interaction patch of FHA domains as well as their functional significance in cell growth and survival mechanisms in response to genotoxic stress, using the Dun1 FHA domain as an example. In order to investigate the existence and importance of Dun1 non-canonical FHA domain-based protein-protein interactions, bioinformatics analysis was used to identify candidate conserved residues on the FHA domain lateral surface interaction patch, site-directed mutagenesis was used to alter select amino acids and yeast two-hybrid assays were used to compare disruptions and/or the abrogation of protein-protein interactions between wild type and mutant Dun1 FHA domains with ligands involved in dNTP regulation. Analysis of the interaction between the FHA domain of Dun1 and proteins involved in the dNTP regulation pathway illustrated a differential requirement of the FHA domain lateral surface interaction patch and the pThr-binding site as well as a contribution of the kinase domain for the establishment of at least two interactions. Highly conserved residues of the Dun1 FHA domain lateral surface interaction patch contributed to FHA domain-based protein-protein interactions and slight but reproducible genotoxic sensitivity was observed for Dun1 FHA domain mutants. The interaction between Dun1 and Damage-regulated Import Facilitator (Dif1) suggested a contribution of the kinase activity of the Dun1 kinase domain to the establishment of a maximal interaction. In order to observe any interaction between Dun1 and Suppressor of mec1…
Subjects/Keywords: Forkhead-associated domain; Saccharomyces cerevisiae; dNTP regulation; cell cycle
…the
Forkhead-associated (FHA) domain was discovered (Hofmann and Bucher, 1995… …Dithiothreitol
EDTA: Ethylenediaminetetraacetic acid
FHA: Forkhead-associated
FL: Full-length
GAL/RAF… …Forkhead-associated Domains
Forkhead-associated (FHA) domains have historically been… …31
Figure 3.2: Conservation Mapping of the Dun1 FHA Domain… …36
Figure 3.5: Conserved Surface Residues of the Dun1 FHA Domain Canonical pThr-binding…
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APA ·
Chicago ·
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CSE |
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Manager
APA (6th Edition):
Straker, G. (2018). Characterization of the FHA domain involved in Saccharomyces cerevisiae dNTP regulation. (Thesis). University of Waterloo. Retrieved from http://hdl.handle.net/10012/13182
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):
Straker, Geburah. “Characterization of the FHA domain involved in Saccharomyces cerevisiae dNTP regulation.” 2018. Thesis, University of Waterloo. Accessed April 19, 2021.
http://hdl.handle.net/10012/13182.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Straker, Geburah. “Characterization of the FHA domain involved in Saccharomyces cerevisiae dNTP regulation.” 2018. Web. 19 Apr 2021.
Vancouver:
Straker G. Characterization of the FHA domain involved in Saccharomyces cerevisiae dNTP regulation. [Internet] [Thesis]. University of Waterloo; 2018. [cited 2021 Apr 19].
Available from: http://hdl.handle.net/10012/13182.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Straker G. Characterization of the FHA domain involved in Saccharomyces cerevisiae dNTP regulation. [Thesis]. University of Waterloo; 2018. Available from: http://hdl.handle.net/10012/13182
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Southern California
5.
Li, Yang.
The polydispersity of human FOXP3 fragment with zinc finger,
leucine zipper and forkhead domain.
Degree: MS, Biochemistry & Molecular Biology, 2010, University of Southern California
URL: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/384355/rec/7108
► Forkhead Box Protein P3 (FOXP3) is essential for the development and maintenance of regulatory T cells (Treg) via regulating the expression of genes involved in…
(more)
▼ Forkhead Box Protein P3 (FOXP3) is essential for the
development and maintenance of regulatory T cells (Treg) via
regulating the expression of genes involved in TCR signaling.
Studies of the homologue of FOXP3, FOXP2, demonstrated that FOXP3
might function as a dimer. However, few papers report the structure
of FOXP3 especially its conformation in the solution. In this
study, hFOXP3S containing a zinc-finger, a leucine zipper and a
forkhead domain, was present as various oligomers in solution.
Light scattering assay suggested that the zinc finger affects the
conformation of oligomers and the precipitation of the protein was
due to the aggregation of large oligomers. DSS is able to crosslink
homodimers of hFOXP3S and
forkhead FOXP3, but
domain-swapping
exchange between hFOXP3S and
forkhead FOXP3 is not observed. The
polydispersity of hFOXP3 solution brings plenty of information for
the advanced structural research of FOXP3.
Advisors/Committee Members: Tokes, Zoltan A. (Committee Chair), Chen, Lin (Committee Member), Ulmer, Tobias (Committee Member).
Subjects/Keywords: forkhead domain; polydispersity; zinc finger; structure
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Manager
APA (6th Edition):
Li, Y. (2010). The polydispersity of human FOXP3 fragment with zinc finger,
leucine zipper and forkhead domain. (Masters Thesis). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/384355/rec/7108
Chicago Manual of Style (16th Edition):
Li, Yang. “The polydispersity of human FOXP3 fragment with zinc finger,
leucine zipper and forkhead domain.” 2010. Masters Thesis, University of Southern California. Accessed April 19, 2021.
http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/384355/rec/7108.
MLA Handbook (7th Edition):
Li, Yang. “The polydispersity of human FOXP3 fragment with zinc finger,
leucine zipper and forkhead domain.” 2010. Web. 19 Apr 2021.
Vancouver:
Li Y. The polydispersity of human FOXP3 fragment with zinc finger,
leucine zipper and forkhead domain. [Internet] [Masters thesis]. University of Southern California; 2010. [cited 2021 Apr 19].
Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/384355/rec/7108.
Council of Science Editors:
Li Y. The polydispersity of human FOXP3 fragment with zinc finger,
leucine zipper and forkhead domain. [Masters Thesis]. University of Southern California; 2010. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/384355/rec/7108
6.
Viscardi, Lucas Henriques.
História evolutiva da subfamília FOXP : análise evolutiva molecular e estrutural em tetrápodes.
Degree: 2015, Brazil
URL: http://hdl.handle.net/10183/150633
► A família gênica Forkhead P {FOXP) tem sido alvo de muitos estudos envolvendo evolução do cérebro e comportamento animal. Destacam-se particularmente as investigações com o…
(more)
▼ A família gênica Forkhead P {FOXP) tem sido alvo de muitos estudos envolvendo evolução do cérebro e comportamento animal. Destacam-se particularmente as investigações com o gene FOXP2, que indicam que mudanças neste gene estariam associadas com a evolução da vocalização em algumas espécies de mamíferos, incluindo o Homo sapiens. Recentemente, estudos de desordem intrínseca de proteínas (IDPs) tem ganhado ênfase no contexto evolut ivo, visto que uma correlação posit iva entre regiões de desordem e altas taxas evolutivas tem sido observada. Através de um conjunto de abordagens que inclui predizer o conteúdo de desordem e os motivos lineares de interação, bem como as taxas evolutivas, buscamos desvendar a historia evolutiva dos genes da subfamília FOXP. Concentramos nossas análises sobre regiões desordenadas das proteínas FOXPl, FOXP2, FOXP3 e FOXP4 encontradas em 77 espécies de tetrápodes. Tais regiões proteicas são normalmente negligenciadas em
estudos dessa natureza, pois se localizam fora de seus tra dicionais domínios conservados, normalmente associados à função principal da proteína. Sít ios apontados estando sob seleção positiva e relaxamento da restrição seletiva mostraram-se hotspots importantes para mudanças que podem impactar na capacidade de interação das proteínas. Encontramos que os maiores valores de w são mais prevalentes em regiões desordenadas que em ordenadas. Ainda, alto e similar valor de desordem (70%) foi encontrado nas 77 proteínas ortólogas de FOXPl , FOXP2, e FOXP4, indicando a manutenção de um "padrão geral" sobre um longo tempo evolutivo. Portanto, a variabilidade tanto de aminoácidos quanto de motivos lineares dentro das regiões de desordem foi marcante. A proteína FOXP3 apresentou menor nível de desordem (30%), mas signif icante sinal de seleção positiva em alguns sítios. Composição idênt ica de resíduo de aminoácido e/ou motivos lineares em espécies filogeneticamente distantes, indica clara
convergência molecular, provavelmente associada a pressões seletivas similares. Sucessivamente, nossos achados mostraram uma clara diferença na composição de motivos lineares entre mamíferos e não mamíferos, dando suporte para a importância dos estudos de evolução da interatividade proteica para as compreensões de características taxa-específicas.
Forkhead Family P (FOXP) has been target of many studies about brain and behavior evo lution among species. FOXP2 receives special attention in academic society, due associations with vocalízation evolution in mammals, including Homo sapiens. Recently, intrinsically disorder proteins studies have gained emphasis in the evolutionary context, as positive correlation between disorder regions and higher evolutionary rate has been observed. Through a set of approaches, including disorder and linear motif predictions, as well as estimate evolutionary rates, we aimed to unveil the evolutionary history of FOXP subfamily genes. We focused our ana
lysis over disordered regions of FOXPl, FOXP2, FOXP3 and FOXP4 proteins retrieved in 77 tetrapods. Such protein regions…
Advisors/Committee Members: Bau, Claiton Henrique Dotto, Bortolini, Maria Cátira.
Subjects/Keywords: Evolução molecular; Tetrapodes; lntrinsica lly disordered protein; Molecular evolution; Linear motifs; Forkhead domain; FOXP gene family
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APA (6th Edition):
Viscardi, L. H. (2015). História evolutiva da subfamília FOXP : análise evolutiva molecular e estrutural em tetrápodes. (Masters Thesis). Brazil. Retrieved from http://hdl.handle.net/10183/150633
Chicago Manual of Style (16th Edition):
Viscardi, Lucas Henriques. “História evolutiva da subfamília FOXP : análise evolutiva molecular e estrutural em tetrápodes.” 2015. Masters Thesis, Brazil. Accessed April 19, 2021.
http://hdl.handle.net/10183/150633.
MLA Handbook (7th Edition):
Viscardi, Lucas Henriques. “História evolutiva da subfamília FOXP : análise evolutiva molecular e estrutural em tetrápodes.” 2015. Web. 19 Apr 2021.
Vancouver:
Viscardi LH. História evolutiva da subfamília FOXP : análise evolutiva molecular e estrutural em tetrápodes. [Internet] [Masters thesis]. Brazil; 2015. [cited 2021 Apr 19].
Available from: http://hdl.handle.net/10183/150633.
Council of Science Editors:
Viscardi LH. História evolutiva da subfamília FOXP : análise evolutiva molecular e estrutural em tetrápodes. [Masters Thesis]. Brazil; 2015. Available from: http://hdl.handle.net/10183/150633
Duke University
7.
Chen, Shiwei.
Regulation of the T Cell Receptor Beta Locus by Nuclear Lamina Association
.
Degree: 2018, Duke University
URL: http://hdl.handle.net/10161/18242
► T lymphocytes of the adaptive immune system recognize antigens using T cell receptors, with each lymphocyte bearing a receptor of unique specificity. T cell…
(more)
▼ T lymphocytes of the adaptive immune system recognize antigens using T cell receptors, with each lymphocyte bearing a receptor of unique specificity. T cell receptors are generated through V(D)J recombination, a process in which gene segments are assembled for the generation of a functional receptor protein via somatic recombination. The T cell receptor β (Tcrb) locus encodes the β chain of the T cell receptor αβ heterodimer. Among antigen receptor loci, the Tcrb locus is unique in that it frequently associates with the nuclear periphery during the developmental stage in which the locus undergoes recombination. Previous work showed that the association of the Tcrb locus with the nuclear periphery was a stochastic process and that the recombination of Tcrb alleles at the nuclear periphery was suppressed compared to Tcrb alleles in the interior of the nucleus. However, the mechanisms that instruct the frequent association of Tcrb alleles with the nuclear periphery remained unknown. We characterized the association of the Tcrb locus with the nuclear lamina (NL) at high resolution using DamID. DamID analysis revealed that the association of the Tcrb locus with the NL was heterogeneous, and that a lamina-
associated domain (LAD) border within the locus segregated the Tcrb recombination center (RC) from RC-proximal chromatin. This LAD border constrains the activity of the Tcrb enhancer (Eβ) to the RC. Accordingly, deletion of the LAD border caused the Eβ-dependent activation of RC-proximal chromatin, resulting in a loss of NL association, increased chromatin looping to the RC, and increased transcription and histone acetylation of genes within the affected 300 kb region. Activated gene segments underwent recombination at higher frequencies, causing a substantial alteration of the Tcrb repertoire. Therefore, our studies identified a LAD border in the Tcrb locus that served to limit the Eβ-dependent activation of RC-proximal gene segments in order to maintain the diversity of the Tcrb repertoire.
Advisors/Committee Members: Krangel, Michael S (advisor).
Subjects/Keywords: Immunology;
DamID;
LAD border;
Lamina-associated domain;
Nuclear lamina;
T cell receptor beta;
Tcrb
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APA (6th Edition):
Chen, S. (2018). Regulation of the T Cell Receptor Beta Locus by Nuclear Lamina Association
. (Thesis). Duke University. Retrieved from http://hdl.handle.net/10161/18242
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):
Chen, Shiwei. “Regulation of the T Cell Receptor Beta Locus by Nuclear Lamina Association
.” 2018. Thesis, Duke University. Accessed April 19, 2021.
http://hdl.handle.net/10161/18242.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Chen, Shiwei. “Regulation of the T Cell Receptor Beta Locus by Nuclear Lamina Association
.” 2018. Web. 19 Apr 2021.
Vancouver:
Chen S. Regulation of the T Cell Receptor Beta Locus by Nuclear Lamina Association
. [Internet] [Thesis]. Duke University; 2018. [cited 2021 Apr 19].
Available from: http://hdl.handle.net/10161/18242.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Chen S. Regulation of the T Cell Receptor Beta Locus by Nuclear Lamina Association
. [Thesis]. Duke University; 2018. Available from: http://hdl.handle.net/10161/18242
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
8.
진, 혜진.
Inhibition of discoidin domain receptor 1 prevents stroma-induced peritoneal metastasis in gastric carcinomas.
Degree: 2017, Ajou University
URL: http://repository.ajou.ac.kr/handle/201003/16429
;
http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000025572
► Although the interactions between cancer cells and the tumor stroma are known to play a role in the peritoneal metastasis of gastric carcinomas (GCs), effective…
(more)
▼ Although the interactions between cancer cells and the tumor stroma are known to play a role in the peritoneal metastasis of gastric carcinomas (GCs), effective targeting agents that block these interactions have never been reported. Discoidin domain receptor 1 (DDR1) is activated by triple-helix collagens, which are major components of tumor stroma: thus, DDR1 might have a key role in the communication between cancer cells and stroma. The aim of this study was to investigate the effect of DDR1 inhibition on stroma-induced peritoneal metastasis in GCs.
METHODS: We analyzed by immunohistochemistry the correlation between DDR1 expression and the pattern of recurrence in GC tissues from a cohort established in a previous study. We also co-cultured human GC cell lines with gastric cancer-associated fibroblasts (CAFs), and investigated DDR1 expression and activation by western blotting. We evaluated the CAF-induced tumorigenic ability of GC cell lines and the effects of a DDR1-specific inhibitor in organotypic cultures and a peritoneal seeding xenograft animal model.
RESULTS: The expression of DDR1 in gastric cancer tissues was significantly positively associated with early recurrence (p = 0.043) and a high incidence of peritoneal recurrence (p = 0.036). We confirmed that co-culture with CAFs elevated DDR1 protein expression in GC cell lines. CAFs also enhanced GC cell line spheroid formation in organotypic cultures in a tumor cell DDR1-dependent manner. Co-implantation of CAFs with GC cells enhanced peritoneal tumor formation in vivo, an effect that was sensitive to pharmacologic inhibition of DDR1.
CONCLUSION: Our findings suggest that the CAF-induced elevation of DDR1 in GC cells enhances their peritoneal tumorigenesis, and that the inhibition of DDR1 signaling is an attractive strategy for the treatment of GC peritoneal metastasis.
암 세포와 종양 기질 세포 사이의 상호작용이 위암의 복막 전이에 관여한다는 사실은 이미 알려져 있지만, 이를 효과적으로 차단할 표적 물질은 아직 밝혀지지 않은 실정이다. Discoidin domain receptor 1 (DDR1)은 종양 기질의 주요한 구성물질인 삼중 나선 구조의 콜라겐에 의해 활성화된다. 그러므로, DDR1은 암 세포와 종양 기질 세포 사이의 커뮤니케이션에 중요한 역할을 할 것으로 생각된다. 본 연구는 DDR1을 억제함에 따라 기질 세포에 의해 유도되는 위암 복막 전이의 개선 여부를 밝혀내고자 하였다. 본 연구에서는 이전 연구에서 설립한 위암 환자들의 집단으로부터 얻은 위암 조직에서의 DDR1 발현과 재발 패턴의 연관성을 면역조직화학염색법을 이용하여 분석하였다. 그 결과, 위암 조직의 DDR1 발현은 짧은 무재발 생존기관과 관련성을 (p = 0.043) 보였고 재발 부위 중 복막 전이의 발생 비율과 의미 있는 연관성을 (p = 0.036) 나타냈다. 이러한 임상데이터 분석 결과를 바탕으로 위암 세포주를 위암 관련 섬유모세포와 동시 배양함으로써 DDR1 단백질의 발현이 증가하는 것을 다양한 실험 기법을 통해 확인하였다. 또한, 위암 관련 섬유모세포가 위암 세포의 DDR1을 통해 기관형 배양에서 스페로이드 형성을 증가시키고, 복막 이종이식 마우스 실험에서 복막의 종양형성 능력을 증가시키는 것을 확인하였다. 더 나아가 이러한 현상들이 DDR1에 특이적으로 작용하는 억제제인 7rh에 의해 저해됨을 확인하였다. 결과적으로, 본 연구에서는 위암 관련 섬유모세포에 의해 유도되는 위암세포의 DDR1 발현 증가가 위암 복막 전이의 악화에 관여함을 밝혔으며, 앞으로 DDR1에 대한 억제가 위암 복막 전이의 치료 전략이 될 수 있을 것으로 기대한다.
I. INTRODUCTION 1
II. MATERIALS AND METHODS 3
1. Human samples and immunohistochemical staining 3
2. Cell lines and chemicals 3
3. CRISPR/Cas9mediated knockout of DDR1 4
4. Western blot 5
5. Cell viability test 5
6. RTPCR 6
7. Organotypic culture and immunocytochemical staining 6
8. Peritoneal xenograft mouse…
Advisors/Committee Members: 대학원 의생명과학과, 201524519, 진, 혜진.
Subjects/Keywords: Gastric carcinomas; Peritoneal metastasis; Discoidin domain receptor; Cancer-associated fibroblasts; 위암; 복막 전이; 암 관련 섬유모세포
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APA (6th Edition):
진, . (2017). Inhibition of discoidin domain receptor 1 prevents stroma-induced peritoneal metastasis in gastric carcinomas. (Thesis). Ajou University. Retrieved from http://repository.ajou.ac.kr/handle/201003/16429 ; http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000025572
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):
진, 혜진. “Inhibition of discoidin domain receptor 1 prevents stroma-induced peritoneal metastasis in gastric carcinomas.” 2017. Thesis, Ajou University. Accessed April 19, 2021.
http://repository.ajou.ac.kr/handle/201003/16429 ; http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000025572.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
진, 혜진. “Inhibition of discoidin domain receptor 1 prevents stroma-induced peritoneal metastasis in gastric carcinomas.” 2017. Web. 19 Apr 2021.
Vancouver:
진 . Inhibition of discoidin domain receptor 1 prevents stroma-induced peritoneal metastasis in gastric carcinomas. [Internet] [Thesis]. Ajou University; 2017. [cited 2021 Apr 19].
Available from: http://repository.ajou.ac.kr/handle/201003/16429 ; http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000025572.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
진 . Inhibition of discoidin domain receptor 1 prevents stroma-induced peritoneal metastasis in gastric carcinomas. [Thesis]. Ajou University; 2017. Available from: http://repository.ajou.ac.kr/handle/201003/16429 ; http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000025572
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Université de Sherbrooke
9.
Lessard-Beaudoin, Mélissa.
Implication de deux nouveaux partenaires d'interaction de la Caspase-6, DAXX et STK3, dans le vieillissement et la maladie de Huntington.
Degree: 2018, Université de Sherbrooke
URL: http://hdl.handle.net/11143/11831
► La neurodégénérescence fait partie intégrante de la maladie de Huntington (MH) dont les premiers symptômes moteurs et cognitifs apparaissent vers l’âge de 30 à 40…
(more)
▼ La neurodégénérescence fait partie intégrante de la maladie de Huntington (MH) dont les premiers symptômes moteurs et cognitifs apparaissent vers l’âge de 30 à 40 ans. Cette maladie incurable est causée par une mutation dans le gène codant pour la protéine huntingtin (htt). L’activation de la caspase-6 (casp6) est observée au stade présymptomatique chez l’humain et les modèles murins MH faisant de la casp6 un joueur majeur dans la neurodégénérescence précoce associé à la MH. De plus, le clivage de htt mutant par la casp6 produit un fragment N-terminal neurotoxique essentielle au développement de la MH. Des résultats préliminaires ont permis de révéler l’interaction et le clivage des protéines proapoptotiques Serine/Threonine Kinase 3 (STK3), Death-
Domain Associated Protein (DAXX) par la casp6. Des effets proapoptotiques sont associés à leurs fragments et leur production par les caspases pourrait influencer la neurodégénérescence observée dans diverses maladies neurodégénératives et dans le vieillissement normal.
Nos résultats dans les souris C57Bl/6 démontrent que l’expression de DAXX varie fortement avec l’âge selon l’organe analysé. Ses divers fragments ne suivent pas la même tendance d’un organe à l’autre suggérant des fonctions différentielles à travers l’organisme et une importante régulation de ses fonctions par des modifications post-traductionnelles. Chez les modèles murins de la MH, les souris YAC128, nous avons constaté une augmentation des fragments à 65 et 70 kDa dans le cortex et une diminution de DAXX entier et du fragment à 70 kDa dans le cervelet soulignant la possibilité de fonctions spécifiques selon les régions cérébrales. Nous avons aussi démontré pour la première fois le clivage de STK3 par la caspase-7 et la production différentielle de fragments par les caspase-3, 6 et 7. L’expression protéique de STK3 augmente globalement à travers l’organisme avec l’âge et dans le cervelet des souris YAC128. Par contre, une diminution de l’expression de STK3 est observée dans le cortex des individus atteints de la MH et des souris YAC128. Finalement, par l’induction de différents stress cellulaires, nous avons constaté la présence d’un mécanisme adaptatif des neurones modèles de la MH impliquant STK3.
En conclusion, l’expression de DAXX et STK3 varie avec l’âge à travers l’organisme et est altérée dans la maladie de Huntington. Plus particulièrement, STK3semble être impliqué dans un mécanisme protégeant les neurones de la mort cellulaire dans la MH.
Advisors/Committee Members: Graham, Rona (advisor).
Subjects/Keywords: Caspase; Death-domain associated protein 6 (DAXX); Sérine-Thréonine kinase 3 (STK3); Vieillissement; Maladie de Huntington; YAC 128
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Record Details
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lessard-Beaudoin, M. (2018). Implication de deux nouveaux partenaires d'interaction de la Caspase-6, DAXX et STK3, dans le vieillissement et la maladie de Huntington. (Masters Thesis). Université de Sherbrooke. Retrieved from http://hdl.handle.net/11143/11831
Chicago Manual of Style (16th Edition):
Lessard-Beaudoin, Mélissa. “Implication de deux nouveaux partenaires d'interaction de la Caspase-6, DAXX et STK3, dans le vieillissement et la maladie de Huntington.” 2018. Masters Thesis, Université de Sherbrooke. Accessed April 19, 2021.
http://hdl.handle.net/11143/11831.
MLA Handbook (7th Edition):
Lessard-Beaudoin, Mélissa. “Implication de deux nouveaux partenaires d'interaction de la Caspase-6, DAXX et STK3, dans le vieillissement et la maladie de Huntington.” 2018. Web. 19 Apr 2021.
Vancouver:
Lessard-Beaudoin M. Implication de deux nouveaux partenaires d'interaction de la Caspase-6, DAXX et STK3, dans le vieillissement et la maladie de Huntington. [Internet] [Masters thesis]. Université de Sherbrooke; 2018. [cited 2021 Apr 19].
Available from: http://hdl.handle.net/11143/11831.
Council of Science Editors:
Lessard-Beaudoin M. Implication de deux nouveaux partenaires d'interaction de la Caspase-6, DAXX et STK3, dans le vieillissement et la maladie de Huntington. [Masters Thesis]. Université de Sherbrooke; 2018. Available from: http://hdl.handle.net/11143/11831
10.
Corvaisier, Matthieu.
Implication des co-activateurs transcriptionnels YAP/TAZ dans la régulation entre la croissance et la dormance tumorale des cellules du cancer colorectal : mécanismes moléculaires et perspectives thérapeutiques : Involvement of the transcriptional coactivators YAP/TAZ in the regulation of the switch from tumor growth to dormancy : molecular mechanisms et therapeutical perspectives.
Degree: Docteur es, Biologie cellulaire, 2016, Université Lille II – Droit et Santé
URL: http://www.theses.fr/2016LIL2S028
► Le cancer colorectal est la première pathologie cancéreuse de la sphère digestive, tant en terme de fréquence que de mortalité par an. Chaque année, 41…
(more)
▼ Le cancer colorectal est la première pathologie cancéreuse de la sphère digestive, tant en terme de fréquence que de mortalité par an. Chaque année, 41 000 nouveaux cas sont diagnostiqués et 17 000 décès sont dus à ce cancer en France. Deux paramètres cliniques expliquent la mortalité de ce cancer; d'une part le fait qu'un patient sur deux est diagnostiqué au stade métastatique ou va présenter des lésions métastatiques durant l'histoire de sa pathologie, d'autre part le fait que les patients après traitement vont fréquemment présenter une récidive de leur pathologie. L'utilisation de régimes de chimiothérapies avant et après résection métastatique améliore la survie sans récidive à court terme, mais à 2 ans post chirurgie l'avantage apporté est perdu. Ainsi, la compréhension des mécanismes d'échappement à la chimiothérapie et régissant la croissance tumorale est d'intérêt pour tenter de limiter la récidive tumorale. L'objectif de ce travail de thèse a consisté en l'analyse de sous-populations obtenues sous pression de chimiothérapie au 5-Fluorouracile (5FU) dérivées de la lignée cancéreuse colique HT29, ainsi que les mécanismes moléculaires associés. Notre clone le plus chimiorésistant isolé, le modèle cellulaire 5F31, quitte le compartiment prolifératif sous traitement à fortes doses de 5FU, ceci étant associé à une perturbation de la voie de signalisation de la Src kinase c-Yes et de son partenaire, le co-activateur transcriptionnel YAP. Sous traitement, les cellules chimiorésistantes entrent en quiescence, le complexe protéique entre c-Yes et YAP est perdu et la quantité totale et nucléaire de YAP diminue de manière significative (Igoudjil, Touil, Corvaisier et al. 2014 Clinical Cancer Research). Dès lors, la suite des travaux a consisté en l'étude du rôle potentiel de YAP sur la balance quiescence/prolifération sous 5FU. L'inhibition pharmacologique ou l'inhibition transitoire de l'expression de YAP et de son paralogue, la protéine TAZ, dans plusieurs lignées cancéreuses coliques induit l'augmentation de la fraction de cellules quiescentes, associée au ralentissement significatif de la croissance tumorale. A l'inverse, la surexpression d'une forme constitutivement active de YAP demeurant nucléaire sous 5FU maintient les cellules 5F31 en prolifération et sensibilise les cellules à la chimiothérapie. Au niveau des effecteurs protéiques, l'induction de quiescence (par traitement à la chimiothérapie ou inhibition de YAP/TAZ) est associée à la perte d'expression de la Cycline E1 et du facteur de transcription c-Myc. A l'inverse, la surexpression du dominant constitutivement actif de YAP dans les cellules 5F31 conduit à l'expression soutenue de la Cycline E1 sous 5FU, expression nécessitant l'activation du facteur de transcription CREB. L'inhibition de la Cycline E1 permet d'induire la quiescence cellulaire, proposant cette protéine comme l'un des effecteurs des protéines YAP/TAZ dans la régulation entre la quiescence et la prolifération cellulaire (Corvaisier et al, Oncotarget, 2016). En conclusion, nos données…
Advisors/Committee Members: Huet, Guillemette (thesis director).
Subjects/Keywords: Cancer colorectal; Traitement médicamenteux; Récidives; YAP; WWTR1; Transcription regulator containing ww domain); Yes associated protein; Colorectal cancer; Metastatic relapse
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Corvaisier, M. (2016). Implication des co-activateurs transcriptionnels YAP/TAZ dans la régulation entre la croissance et la dormance tumorale des cellules du cancer colorectal : mécanismes moléculaires et perspectives thérapeutiques : Involvement of the transcriptional coactivators YAP/TAZ in the regulation of the switch from tumor growth to dormancy : molecular mechanisms et therapeutical perspectives. (Doctoral Dissertation). Université Lille II – Droit et Santé. Retrieved from http://www.theses.fr/2016LIL2S028
Chicago Manual of Style (16th Edition):
Corvaisier, Matthieu. “Implication des co-activateurs transcriptionnels YAP/TAZ dans la régulation entre la croissance et la dormance tumorale des cellules du cancer colorectal : mécanismes moléculaires et perspectives thérapeutiques : Involvement of the transcriptional coactivators YAP/TAZ in the regulation of the switch from tumor growth to dormancy : molecular mechanisms et therapeutical perspectives.” 2016. Doctoral Dissertation, Université Lille II – Droit et Santé. Accessed April 19, 2021.
http://www.theses.fr/2016LIL2S028.
MLA Handbook (7th Edition):
Corvaisier, Matthieu. “Implication des co-activateurs transcriptionnels YAP/TAZ dans la régulation entre la croissance et la dormance tumorale des cellules du cancer colorectal : mécanismes moléculaires et perspectives thérapeutiques : Involvement of the transcriptional coactivators YAP/TAZ in the regulation of the switch from tumor growth to dormancy : molecular mechanisms et therapeutical perspectives.” 2016. Web. 19 Apr 2021.
Vancouver:
Corvaisier M. Implication des co-activateurs transcriptionnels YAP/TAZ dans la régulation entre la croissance et la dormance tumorale des cellules du cancer colorectal : mécanismes moléculaires et perspectives thérapeutiques : Involvement of the transcriptional coactivators YAP/TAZ in the regulation of the switch from tumor growth to dormancy : molecular mechanisms et therapeutical perspectives. [Internet] [Doctoral dissertation]. Université Lille II – Droit et Santé 2016. [cited 2021 Apr 19].
Available from: http://www.theses.fr/2016LIL2S028.
Council of Science Editors:
Corvaisier M. Implication des co-activateurs transcriptionnels YAP/TAZ dans la régulation entre la croissance et la dormance tumorale des cellules du cancer colorectal : mécanismes moléculaires et perspectives thérapeutiques : Involvement of the transcriptional coactivators YAP/TAZ in the regulation of the switch from tumor growth to dormancy : molecular mechanisms et therapeutical perspectives. [Doctoral Dissertation]. Université Lille II – Droit et Santé 2016. Available from: http://www.theses.fr/2016LIL2S028
Indian Institute of Science
11.
Zaveri, Anisha.
Nucleic Acid-binding Adenylyl Cyclases in Mycobacteria : Studies on Evolutionary & Biochemical Aspects.
Degree: PhD, Faculty of Engineering, 2018, Indian Institute of Science
URL: http://etd.iisc.ac.in/handle/2005/3077
► Mycobacterium tuberculosis is one of the most successful human pathogens, estimated to have infected close to one-third of the global human population. In order to…
(more)
▼ Mycobacterium tuberculosis is one of the most successful human pathogens, estimated to have infected close to one-third of the global human population. In order to survive within its host, M. tuberculosis utilises multiple signalling strategies, one of them being synthesis and secretion of universal second messenger cAMP. This process is enabled by the presence of sixteen predicted adenylyl cyclases in the genome of M. tuberculosis H37Rv, ten of which have been characterised in vitro. The synthesized cAMP is recognised by ten putative cAMP-binding proteins in which the cyclic AMP-binding
domain is
associated with a variety of enzymatic domains. The cAMP signal can be extinguished by degradation by phosphodiesterase’s, secretion into the extracellular milieu or via sequestration of the nucleotide by upregulation of a high-affinity cAMP-binding protein.
Of the sixteen adenylyl cyclases (ACs) encoded by M. tuberculosis H37Rv, a subset of multidomain adenylyl cyclases remain poorly characterised, primarily due to challenges
associated with studying these in vitro. The adenylyl cyclase
domain in these proteins is
associated with an NB-ARC
domain (nucleotide binding
domain common to APAF-1, plant R proteins and CED-4), a TPR
domain (tetratricopeptide repeat) and an LuxR-type HTH motif (helix-turn-helix). This architecture places these multidomain mycobacterial ACs within a larger group of STAND (Signal transduction ATPase’s with numerous domains) proteins, and hence they will be referred to as STAND ACs. The STAND proteins are a recently recognised class of multidomain ATPases which integrate a variety of signals prior to activation. Activation is accompanied by formation of large oligomeric signalling hubs which facilitate downstream signalling events. While most STAND proteins have a single effector
domain followed by an NB-ARC
domain and a scaffolding
domain, the STAND ACs distinguish themselves by retaining two effector domains, the AC
domain and the HTH
domain, at the N- and C- termini respectively.
The cyclase, NB-ARC, TPR and HTH domains have widely divergent taxonomic distributions making the presence of these four domains in a single polypeptide rare. In fact, proteins with cyclase-NB-ARC-TPR-HTH (C-A-T-H)
domain organisation were found to be encoded almost exclusively by slow growing mycobacterial species, a clade that harbours most mycobacterial pathogens, such as M. tuberculosis and M. leprae. Notably, one of the STAND ACs, Rv0386, is the only mycobacterial AC shown till date to be required for virulence of M. tuberculosis in mice.
Using phylogenetic, the evolutionary underpinnings of this
domain architecture were examined. The STAND ACs appear to have most likely evolved via a
domain gain event from a cyclase-ATPase-TPR progenitor encoded by a strain ancestral to M. marina. Subsequently, the genes duplicated and diverged, sometimes leading to frameshift mutations splitting the cyclase
domain from the C-terminal domains. Consequently, M. tuberculosis encodes for three ‘full-length’ STAND ACs, namely, Rv0386,…
Advisors/Committee Members: Visweswariah, Sandhya S (advisor).
Subjects/Keywords: Adenylyl Cyclases; Mycobacteria; Cyclic AMP in Mycobacteria; STAND Proteins; TPR Domain; HTH Domain; Nucleoid Associated Proteins; Mycobacterium tuberculosis; M. tuberculosis; H37Rv; Biochemistry
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zaveri, A. (2018). Nucleic Acid-binding Adenylyl Cyclases in Mycobacteria : Studies on Evolutionary & Biochemical Aspects. (Doctoral Dissertation). Indian Institute of Science. Retrieved from http://etd.iisc.ac.in/handle/2005/3077
Chicago Manual of Style (16th Edition):
Zaveri, Anisha. “Nucleic Acid-binding Adenylyl Cyclases in Mycobacteria : Studies on Evolutionary & Biochemical Aspects.” 2018. Doctoral Dissertation, Indian Institute of Science. Accessed April 19, 2021.
http://etd.iisc.ac.in/handle/2005/3077.
MLA Handbook (7th Edition):
Zaveri, Anisha. “Nucleic Acid-binding Adenylyl Cyclases in Mycobacteria : Studies on Evolutionary & Biochemical Aspects.” 2018. Web. 19 Apr 2021.
Vancouver:
Zaveri A. Nucleic Acid-binding Adenylyl Cyclases in Mycobacteria : Studies on Evolutionary & Biochemical Aspects. [Internet] [Doctoral dissertation]. Indian Institute of Science; 2018. [cited 2021 Apr 19].
Available from: http://etd.iisc.ac.in/handle/2005/3077.
Council of Science Editors:
Zaveri A. Nucleic Acid-binding Adenylyl Cyclases in Mycobacteria : Studies on Evolutionary & Biochemical Aspects. [Doctoral Dissertation]. Indian Institute of Science; 2018. Available from: http://etd.iisc.ac.in/handle/2005/3077
University of Gothenburg / Göteborgs Universitet
12.
Landgren, Henrik.
Forkhead Genes in Mammalian Development.
Degree: 2008, University of Gothenburg / Göteborgs Universitet
URL: http://hdl.handle.net/2077/18403
► This thesis concerns aspects of Forkhead gene biology and it’s relation to mammalian development. Genes from three subclasses are discussed, Foxj3, Foxf1 and f2, and…
(more)
▼ This thesis concerns aspects of Forkhead gene biology and it’s relation to mammalian
development. Genes from three subclasses are discussed, Foxj3, Foxf1 and f2, and Foxe3.
We have identified and characterized a novel forkhead gene, FoxJ3, that is expressed in
neuroectoderm, neural crest and mytome, suggesting possible function in the nervous system
and muscle. The myotome, which will develop into muscle, along with the mesenchyme lining
the intestinal gut, originates from embryonic mesoderm.
Forkhead factors, Foxf1 and Foxf2, are expressed in intestinal mesenchyme derived from
splanchnic mesoderm. Foxf function is important for patterning of the gut tube. Removal of
Foxf results in a range of intestinal phenotypes, such as agangliosis and megacolon. Both Foxf1
and Foxf2 are regulated by hedgehog signaling, Foxf mutants display mesenchymal increase in
Wnt5a expression, and reduction in Bmp4 expression. The extracellular matrix is depleted of
collagens, and together with altered paracrine factors, this leads to a phenotype where
epithelial cells lose polarization and become resistant to apoptosis.
The ocular lens develops from the head ectoderm and a critical factor in its formation is
Foxe3. Foxe3 is, after secondary fiber differentiation starts, expressed exclusively in the lens
epithelium. These cells provide the precursors for lens fibers. Fiber cells are elongated,
terminally differentiated cells that provide the specialized optical properties of the lens. Ectopic
expression of Foxe3 in the fiber compartment interferes with several aspects of fiber
differentiation. The cytoskeletal remodeling and organelle degradation is blocked in transgenic
lenses, whereas fiber cell specific expression of crystallins seems to be undisturbed.
Foxe3 is also involved in patterning of the anterior segment of eye. Heterozygous Foxe3
mutants show defects in differentiation of the cornea, iris and filtration angle. The anterior
segment similarities in Foxe3 and Pax6 heterozygous mutants provide, along with Foxe3
expression being dependent on Pax6 gene dosage, an indication that Foxe3 is a major
contributor to the phenotype of Pax6 mutants.Foxe3 can interact with many signaling pathways active in the eye. Foxe3 expression can be altered by changes in growth factor ligands. Furthermore, components of different growth factor pathways can be controlled by Foxe3. Taken together, Foxe3 biology is regulated on many cellular levels in the ocular lens.
Subjects/Keywords: Development; Forkhead
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APA (6th Edition):
Landgren, H. (2008). Forkhead Genes in Mammalian Development. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/18403
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):
Landgren, Henrik. “Forkhead Genes in Mammalian Development.” 2008. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed April 19, 2021.
http://hdl.handle.net/2077/18403.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Landgren, Henrik. “Forkhead Genes in Mammalian Development.” 2008. Web. 19 Apr 2021.
Vancouver:
Landgren H. Forkhead Genes in Mammalian Development. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 2008. [cited 2021 Apr 19].
Available from: http://hdl.handle.net/2077/18403.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Landgren H. Forkhead Genes in Mammalian Development. [Thesis]. University of Gothenburg / Göteborgs Universitet; 2008. Available from: http://hdl.handle.net/2077/18403
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Indian Institute of Science
13.
Kumar, Sushant.
Structural Studies on DNA Damage Inducible Protein 1 (Ddi1) of Leishmania and the Rotavirus Nonstructural Protein NSP4.
Degree: PhD, Faculty of Science, 2018, Indian Institute of Science
URL: http://etd.iisc.ac.in/handle/2005/3018
► Structuraj investigations on the Ddi1 (DNA-damage inducible protein 1) of Leishmania major and on the rotavirus nonstructural protein NSP4 were carried out. Ddi1 belongs to…
(more)
▼ Structuraj investigations on the Ddi1 (DNA-damage inducible protein 1) of Leishmania major and on the rotavirus nonstructural protein NSP4 were carried out. Ddi1 belongs to the ubiquitin receptor family of proteins. One of its domains is similar to the retroviral aspartic proteinases. It has been shown that this
domain is the target of HIV-protease inhibitors that were being used in the treatment of AIDS and it was observed that these drugs effectively controlled opportunistic diseases caused by many parasitic protozoa such as Leishmania and Plasmodium species. The retroviral protease-like domains present in Ddi1 proteins of these organisms were identified as the targets of these drugs. Structural studies on Ddi1 from L. major have been carried out, in an attempt to provide a platform for the design of anti-protozoal compounds. Rotavirus NSP4, the first viral enterotoxin to be identified, is a multifunctional glycoprotein that plays critical roles in viral pathogenesis and morphogenesis. As part of an ongoing project on the structural characterization of NSP4, we determined the structure of the diarrhea-inducing region of this protein from the rotavirus strain MF66.
Chapter 1 presents an overview of Ddi1 and NSP4 of the rotavirus with an emphasis on their structural features. The methods employed during the course of the present work are described in Chapter 2.
Structural studies on the retroviral protease-like
domain of Ddi1 (Ddi1-RVP) of L. major is presented in Chapter 3. Apart from this
domain, Ddi1 of L. major also has a ubiquitin-
associated and ubiquitin-like domains whereas P. falciparum has only the ubiquitin-
associated domain. Activity of the full length Ddi1 of L. major and the retroviral protease
domain of P. falciparum using an HIV protease substrate was shown to be inhibited by an HIV protease inhibitor, saquinavir. Binding of saquinavir to the proteins was also confirmed by Biolayer Interferometry studies. The crystal structure of the retroviral protease
domain of L. major Ddi1 has been determined. It forms a homodimeric structure similar to that of HIV protease and the reported structure of the same
domain from Saccharomyces cerevisiae. The loops in Ddi1-RVP are similar to the 'flap' regions of the HIV protease which close-in upon substrate/inhibitor binding; they are visible in the electron density maps, unlike the case of the S. cerevisiae protein. Though the native form of the
domain shows an open dimeric structure, normal mode analysis reveals that it can take up a closed conformation resulting from relative movements of the subunits. The present structure of Ddi1-RVP of L. major with the defined 'flap'-like loops will be helpful in the design of effective drugs against protozoal diseases, starting with HIV protease inhibitors as the lead compounds.
Chapter 4 describes the structural investigations carried out on the diarrhea-inducing region of the nonstructural protein NSP4 of the rotavirus strain MF66 which forms an α-helical coiled-coil structure. Crystal structures of a synthetic…
Advisors/Committee Members: Suguna, K (advisor).
Subjects/Keywords: Rotavirus Nonstructural Protein NSP4; DNA Damage Inducible Protein (Ddi1); Retroviral Protease Domain (RVP); Ubiquitin-Like Domain (UBL); Ubiquitin Associated Domain (UBA); Nonstructural Protein 4; Rotavirus Strain MF66; Leishmania Major; Molecular Biophysics
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APA (6th Edition):
Kumar, S. (2018). Structural Studies on DNA Damage Inducible Protein 1 (Ddi1) of Leishmania and the Rotavirus Nonstructural Protein NSP4. (Doctoral Dissertation). Indian Institute of Science. Retrieved from http://etd.iisc.ac.in/handle/2005/3018
Chicago Manual of Style (16th Edition):
Kumar, Sushant. “Structural Studies on DNA Damage Inducible Protein 1 (Ddi1) of Leishmania and the Rotavirus Nonstructural Protein NSP4.” 2018. Doctoral Dissertation, Indian Institute of Science. Accessed April 19, 2021.
http://etd.iisc.ac.in/handle/2005/3018.
MLA Handbook (7th Edition):
Kumar, Sushant. “Structural Studies on DNA Damage Inducible Protein 1 (Ddi1) of Leishmania and the Rotavirus Nonstructural Protein NSP4.” 2018. Web. 19 Apr 2021.
Vancouver:
Kumar S. Structural Studies on DNA Damage Inducible Protein 1 (Ddi1) of Leishmania and the Rotavirus Nonstructural Protein NSP4. [Internet] [Doctoral dissertation]. Indian Institute of Science; 2018. [cited 2021 Apr 19].
Available from: http://etd.iisc.ac.in/handle/2005/3018.
Council of Science Editors:
Kumar S. Structural Studies on DNA Damage Inducible Protein 1 (Ddi1) of Leishmania and the Rotavirus Nonstructural Protein NSP4. [Doctoral Dissertation]. Indian Institute of Science; 2018. Available from: http://etd.iisc.ac.in/handle/2005/3018
University of Illinois – Urbana-Champaign
14.
Shen, Zhen.
ORCA/LRWD1, a novel player in the initiation of eukaryotic DNA replication.
Degree: PhD, 4094, 2013, University of Illinois – Urbana-Champaign
URL: http://hdl.handle.net/2142/42431
► Accurate DNA replication is key to maintaining genome stability in all living species. In eukaryotes, the duplication process starts with the formation of the pre-replicative…
(more)
▼ Accurate DNA replication is key to maintaining genome stability in all living species. In eukaryotes, the duplication process starts with the formation of the pre-replicative complex (pre-RC) prior to S phase, followed by the transition to the pre-initiation complex (pre-IC) that is required for DNA synthesis. The conserved canonical model of the pre-RC assembly includes an ordered recruitment of ORC, Cdt1, Cdc6, and the helicase MCMs to replication origins, and is strictly governed by replication licensing system. As the complexity increases dramatically from yeast to human cells, additional replication regulators have been identified in higher eukaryotes. In Chapter I, I review how the canonical pre-RC components were identified; what are the novel players; and our current understanding of how the replication licensing dictates proper DNA synthesis.
While how ORC is recruited to specific origins has been studied explicitly in lower organisms, it remains unclear in higher eukaryotes. To understand whether additional factors enable the recruitment of ORC to origins and/or specific chromatin sites in human cells, our lab conducted ORC immunoprecipitations followed by mass spectrometric analysis in order to find novel ORC interactors. In Chapter II, I describe the identification of a highly conserved protein in human cells, leucine-rich repeats and WD40 repeat
domain-containing protein 1 (LRWD1) or ORC-
associated (ORCA). It interacts with ORC and modulates its chromatin association. ORCA co-localizes with ORC, shows similar cell cycle dynamics, and efficiently recruits ORC to chromatin. Depletion of ORCA in human primary cells and embryonic stem cells results in the loss of ORC association to chromatin, concomitant reduction of MCM binding, and a subsequent accumulation of cells in G1 phase. I therefore propose the model where ORCA-mediated association of ORC to chromatin is critical for pre-RC assembly in G1.
In addition to ORC, I describe the interaction of ORCA with replication factor Cdt1 and its inhibitor Geminin in Chapter III. I demonstrate the stoichiometry of these associations via single-molecule pull-down experiments that each molecule of ORCA can bind to one molecule of ORC, one molecule of Cdt1, and two molecules of Geminin. Further, ORCA directly interacts with the N-terminus of Orc2, and this association is essential for ORCA stability. ORCA associates with Orc2 throughout the cell cycle, with Cdt1 during mitosis and G1, and with Geminin in post-G1 cells. Interestingly, overexpression of Geminin results in the loss of interaction between ORCA and Cdt1, suggesting that the increased levels of Geminin in post-G1 cells titrate Cdt1 away from ORCA. Based on these data, I propose that the dynamic association of ORCA with pre-RC components modulates the assembly of its interacting partners on chromatin and plays a key role in replication initiation.
ORCA exhibits cell cycle-regulated protein levels that peak in G1; and it can only be stabilized when it is in a complex with Orc2. In Chapter IV, I show that…
Advisors/Committee Members: Prasanth, Supriya G. (advisor), Belmont, Andrew S. (Committee Chair), Prasanth, Supriya G. (committee member), Freeman, Brian C. (committee member), Yau, Peter M. (committee member), Cann, Isaac K. (committee member).
Subjects/Keywords: ORC-associated (RCA); origin recognition complex; pre-replicative complex; DNA replication; leucine-rich repeats and WD40 repeat domain-containing protein 1 (LRWD1)
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APA ·
Chicago ·
MLA ·
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Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Shen, Z. (2013). ORCA/LRWD1, a novel player in the initiation of eukaryotic DNA replication. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/42431
Chicago Manual of Style (16th Edition):
Shen, Zhen. “ORCA/LRWD1, a novel player in the initiation of eukaryotic DNA replication.” 2013. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 19, 2021.
http://hdl.handle.net/2142/42431.
MLA Handbook (7th Edition):
Shen, Zhen. “ORCA/LRWD1, a novel player in the initiation of eukaryotic DNA replication.” 2013. Web. 19 Apr 2021.
Vancouver:
Shen Z. ORCA/LRWD1, a novel player in the initiation of eukaryotic DNA replication. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2013. [cited 2021 Apr 19].
Available from: http://hdl.handle.net/2142/42431.
Council of Science Editors:
Shen Z. ORCA/LRWD1, a novel player in the initiation of eukaryotic DNA replication. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2013. Available from: http://hdl.handle.net/2142/42431
University of Cincinnati
15.
Conrady, Deborah.
The role of zinc-dependent intercellular adhesion in biofilm
formation in <i>Staphylococcus epidermidis</i>.
Degree: PhD, Medicine : Molecular Genetics, Biochemistry, and
Microbiology, 2010, University of Cincinnati
URL: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1275920539
► Healthcare associated (HA) infections affect 1.5 to 2 million people annually in the United States, with approximately 99,000 fatalities. One third of all HA…
(more)
▼ Healthcare
associated (HA) infections affect
1.5 to 2 million people annually in the United States, with
approximately 99,000 fatalities. One third of all HA infections and
more than one half of all HA-bloodstream infections are caused by
the staphylococcal species <i>S. aureus</i> and
coagulase-negative staphylococcus (CoNS), of which <i>S.
epidermidis</i> is the most frequent isolate. This normally
benign commensal bacterial species infects devices and compromised
tissues, as well as immunocompromised hosts. Its pathogenesis in
these cases is based on its ability to form biofilms. A biofilm is
a specialized bacterial colony that is adherent to abiotic and
biotic substrates, in which bacteria are protected from
environmental hazards such as antibiotics and host immune
defenses. Biofilm formation in <i>S.
epidermidis</i> occurs through three major processes: initial
adhesion, accumulation, and maturation. Initial adhesion to a
surface is achieved through the exposure of hydrophobic interfaces
on dividing cells by autolysin, and by interactions with specific
host proteins via MSCRAMMs (microbial surface components
recognizing adhesive matrix molecules). After adhesion, bacteria
are recruited to the nascent biofilm in the process of
accumulation. The protein Aap plays a role during accumulation, but
also is responsible for maturation of biofilms of some strains.
Other strains secrete the poly-N-acetylglucosamine (PNAG) during
the process of maturation. Cloning and expression studies of SdrF
(an MSCRAMM), various
domain-lengths of Aap, and several Ica
proteins (responsible for PNAG synthesis) form the basis for future
studies on various aspects of staphylococcal biofilm
formation. The protein Aap is of particular
importance to biofilm formation, since it can independently mediate
biofilm maturation. Its role in the accumulation phase of
polysaccharide-secreting isolates make it very biologically
important for both protein and polysaccharide modes of maturation.
We have determined that the molecular mechanism of Aap-dependent
intercellular adhesion is based on the ability of the tandem
repeated G5
domain B-repeat region to self-associate along its
length in a zinc-dependent fashion. Chelation of zinc prevents
biofilm formation in both <i>S. epidermidis</i> and
<i>S. aureus</i>. The structure of
zinc-bound Brpt is of great interest, since it will yield further
insight into the mechanism of zinc binding and the nature of the
dimerization interface. We have crystallized both native and
seleno-methionine-labeled B-repeat point mutants and have attempted
molecular replacement and experimental phasing. The diffraction
data from these crystals suffer from high anisotropy, leading to a
poor signal-to-noise ratio and precluding the determination of
initial phases. Future efforts will focus on the improvement of
diffraction quality.
Advisors/Committee Members: Herr, Andrew (Committee Chair).
Subjects/Keywords: Biochemistry; biofilm; staphylococcus; accumulation associated protein; bacterial pathogenesis; G5 domain; biophysics
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APA ·
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MLA ·
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APA (6th Edition):
Conrady, D. (2010). The role of zinc-dependent intercellular adhesion in biofilm
formation in <i>Staphylococcus epidermidis</i>. (Doctoral Dissertation). University of Cincinnati. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=ucin1275920539
Chicago Manual of Style (16th Edition):
Conrady, Deborah. “The role of zinc-dependent intercellular adhesion in biofilm
formation in <i>Staphylococcus epidermidis</i>.” 2010. Doctoral Dissertation, University of Cincinnati. Accessed April 19, 2021.
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1275920539.
MLA Handbook (7th Edition):
Conrady, Deborah. “The role of zinc-dependent intercellular adhesion in biofilm
formation in <i>Staphylococcus epidermidis</i>.” 2010. Web. 19 Apr 2021.
Vancouver:
Conrady D. The role of zinc-dependent intercellular adhesion in biofilm
formation in <i>Staphylococcus epidermidis</i>. [Internet] [Doctoral dissertation]. University of Cincinnati; 2010. [cited 2021 Apr 19].
Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1275920539.
Council of Science Editors:
Conrady D. The role of zinc-dependent intercellular adhesion in biofilm
formation in <i>Staphylococcus epidermidis</i>. [Doctoral Dissertation]. University of Cincinnati; 2010. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1275920539
University of Michigan
16.
Harper, Scott Quenton.
Structural flexibilty of the dystrophin rod domain: Implications for gene therapy of Duchenne muscular dystrophy using adeno -associated viral vectors.
Degree: PhD, Molecular biology, 2002, University of Michigan
URL: http://hdl.handle.net/2027.42/131967
► Duchenne muscular dystrophy (DMD), the most common form of muscular dystrophy, is a degenerative, lethal disorder caused by mutations in the dystrophin gene. The full-length…
(more)
▼ Duchenne muscular dystrophy (DMD), the most common form of muscular dystrophy, is a degenerative, lethal disorder caused by mutations in the dystrophin gene. The full-length muscle isoform of dystrophin is composed of N-terminal actin-binding, central rod, cysteine rich, and C-terminal domains. Large deletions that remove portions of the rod
domain can yield truncated, yet functional dystrophin proteins, leading to the milder Becker muscular dystrophy (BMD) in humans. The feasibility of gene therapy for DMD was demonstrated by prevention of the development of dystrophy by expression of the muscle isoform of dystrophin in skeletal muscles of transgenic mdx mice, a model for DMD. However, available viral vectors that can carry the full-length dystrophin cDNA (14 kilobases) and regulatory elements are difficult to grow and may not persist after delivery to immunocompetent mice. Adeno-
associated viral (AAV) vectors are promising shuttles for DMD gene therapy because they readily infect muscle, direct long-term gene expression, and do not elicit a detectable cellular immune response in normal muscle. However, the small (<5 kilobases) cloning capacity of AAV precludes packaging of large genes. The primary goal of this dissertation research was to elucidate the minimal functional elements of the dystrophin rod
domain to develop gene therapy for DMD using AAV vectors. We generated three different transgenic mdx mouse lines that expressed truncated 'micro-dystrophins' and examined their ability to prevent the development of dystrophic changes in skeletal muscle. One of the constructs completely prevented the development of morphological features
associated with muscular dystrophy in mdx mice and afforded significant protection from contraction-induced injury to mdx muscles. When delivered to mdx muscle using AAV serotype 2 (AAV-2) vectors, this micro-dystrophin effected a reversal of the histopathological features
associated with dystrophy. The efficiency of muscle transduction by AAV-2 indicated that enormous quantities of virus would be required to achieve a significant clinical benefit in patients. To improve transduction, we tested gene delivery to mouse muscle using AAV serotype 6 (AAV-6). We found that AAV-6 significantly increased the scope and magnitude of gene delivery. It is hoped that these studies may someday contribute to successful treatment for this devastating disease.
Advisors/Committee Members: Chamberlain, Jeffrey S. (advisor).
Subjects/Keywords: Adeno-associated Viral Vectors; Adeno-associated Virus; Domain; Duchenne Muscular Dystrophy; Dystrophin; Gene Therapy; Implications; Rod; Structural Flexibilty; Using
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APA ·
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MLA ·
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Export
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APA (6th Edition):
Harper, S. Q. (2002). Structural flexibilty of the dystrophin rod domain: Implications for gene therapy of Duchenne muscular dystrophy using adeno -associated viral vectors. (Doctoral Dissertation). University of Michigan. Retrieved from http://hdl.handle.net/2027.42/131967
Chicago Manual of Style (16th Edition):
Harper, Scott Quenton. “Structural flexibilty of the dystrophin rod domain: Implications for gene therapy of Duchenne muscular dystrophy using adeno -associated viral vectors.” 2002. Doctoral Dissertation, University of Michigan. Accessed April 19, 2021.
http://hdl.handle.net/2027.42/131967.
MLA Handbook (7th Edition):
Harper, Scott Quenton. “Structural flexibilty of the dystrophin rod domain: Implications for gene therapy of Duchenne muscular dystrophy using adeno -associated viral vectors.” 2002. Web. 19 Apr 2021.
Vancouver:
Harper SQ. Structural flexibilty of the dystrophin rod domain: Implications for gene therapy of Duchenne muscular dystrophy using adeno -associated viral vectors. [Internet] [Doctoral dissertation]. University of Michigan; 2002. [cited 2021 Apr 19].
Available from: http://hdl.handle.net/2027.42/131967.
Council of Science Editors:
Harper SQ. Structural flexibilty of the dystrophin rod domain: Implications for gene therapy of Duchenne muscular dystrophy using adeno -associated viral vectors. [Doctoral Dissertation]. University of Michigan; 2002. Available from: http://hdl.handle.net/2027.42/131967
Ruhr Universität Bochum
17.
Schmitz, Caroline Doris.
Absolute Anzahl und altersabhängige Veränderung der
Anzahl regulatorischer T-Zellen bei gesunden und an atopischer
Dermatitit erkrankten Kindern und Jugendlichen.
Degree: 2009, Ruhr Universität Bochum
URL: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-25553
► Regulatorische T-Zellen zeichnen sich durch die Oberflächenproteine CD4 und CD25 aus, entwickeln sich teilweise FOXP3- abhängig und werden anhand von CD45RA und CD45RO in naive-like…
(more)
▼ Regulatorische T-Zellen zeichnen sich durch die
Oberflächenproteine CD4 und CD25 aus, entwickeln sich teilweise
FOXP3- abhängig und werden anhand von CD45RA und CD45RO in
naive-like und memory-like regulatorische T-Zellen unterschieden.
Sie spielen eine zentrale Rolle in der Immunhomöostase. Ihre Rolle
im Krankheitsbild der atopischen Dermatitis ist wenig erforscht.
Mit Hilfe durchflusszytometrischer Untersuchungen wurde in der
vorliegenden Studie erstmalig vergleichend die absolute Anzahl und
die altersabhängige Veränderung der Anzahl regulatorischer T-Zellen
bei gesunden und an atopischer Dermatitis erkrankten Kindern und
Jugendlichen untersucht. Patienten mit atopischer Dermatitis wiesen
höhere, vor allem in den ersten vier Lebensjahren deutlich höhere
Anzahlen regulatorischer T-Zellen auf. Die Anzahl naive-like
regulatorischer T-Zellen verringerte sich in beiden
Probandengruppen mit dem Alter statistisch signifikant, umgekehrt
stieg die Anzahl der memory-like regulatorischen
T-Zellen.
Advisors/Committee Members: Medizin.
Subjects/Keywords: Immunologie; Lymphozyt; Forkhead-Gen; Endogenes Ekzem;
Durchflusszytometrie
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APA ·
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MLA ·
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Export
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Manager
APA (6th Edition):
Schmitz, C. D. (2009). Absolute Anzahl und altersabhängige Veränderung der
Anzahl regulatorischer T-Zellen bei gesunden und an atopischer
Dermatitit erkrankten Kindern und Jugendlichen. (Thesis). Ruhr Universität Bochum. Retrieved from http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-25553
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):
Schmitz, Caroline Doris. “Absolute Anzahl und altersabhängige Veränderung der
Anzahl regulatorischer T-Zellen bei gesunden und an atopischer
Dermatitit erkrankten Kindern und Jugendlichen.” 2009. Thesis, Ruhr Universität Bochum. Accessed April 19, 2021.
http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-25553.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Schmitz, Caroline Doris. “Absolute Anzahl und altersabhängige Veränderung der
Anzahl regulatorischer T-Zellen bei gesunden und an atopischer
Dermatitit erkrankten Kindern und Jugendlichen.” 2009. Web. 19 Apr 2021.
Vancouver:
Schmitz CD. Absolute Anzahl und altersabhängige Veränderung der
Anzahl regulatorischer T-Zellen bei gesunden und an atopischer
Dermatitit erkrankten Kindern und Jugendlichen. [Internet] [Thesis]. Ruhr Universität Bochum; 2009. [cited 2021 Apr 19].
Available from: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-25553.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Schmitz CD. Absolute Anzahl und altersabhängige Veränderung der
Anzahl regulatorischer T-Zellen bei gesunden und an atopischer
Dermatitit erkrankten Kindern und Jugendlichen. [Thesis]. Ruhr Universität Bochum; 2009. Available from: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-25553
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Texas Southwestern Medical Center
18.
Goertz, Meredith Johanna.
Foxo Transcription Factors Control Spermatogonial Stem Cell Self-Renewal and the Initiation of Spermatogenesis.
Degree: 2013, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/1247
► Spermatogonial stem cells (SSCs), as the foundation for spermatogenesis, must maintain a balance of both self-renewal and differentiation. Although several factors important for these processes…
(more)
▼ Spermatogonial stem cells (SSCs), as the foundation for spermatogenesis, must maintain a balance of both self-renewal and differentiation. Although several factors important for these processes have been identified, the fundamental mechanisms regulating SSC self-renewal and differentiation remain essentially unknown. The work presented here describes the discovery of a role for the Foxo
forkhead transcription factors in mouse spermatogenesis and SSCs. Foxo1 was found to specifically mark mouse gonocytes, and its cytoplasmic-to-nuclear translocation delineated the gonocyte-to-SSC transition in neonatal testes. In adults, Foxo1 is specifically expressed within a subset of undifferentiated spermatogonia with stem cell potential. Genetic analyses showed that Foxo1 was required for both SSC maintenance as well as the initiation of spermatogenesis, with limited contributions from Foxo3 and Foxo4. Conditional inactivation of PI3K/Akt pathway components in the male germ line confirmed that PI3K signaling regulates Foxo1 stability and subcellular localization, revealing that the Foxos are crucial effectors of PI3K/Akt signaling in SSCs. The nuclear localization of Foxo1, indicating functional activation, was found to correlate with Gfralpha1 expression and thus stem cell potential. Subsequent gene expression analyses identified a complex network of Foxo gene targets that rationalized both the maintenance of SSCs and initiation of differentiation by the Foxos. Taken together, these findings demonstrate that the Foxos, particularly Foxo1, are essential in maintaining the spermatogonial stem cell population, and regulation of the Foxos through the PI3K/Akt signaling pathway is a critical process underlying SSC self-renewal versus differentiation.
Advisors/Committee Members: Castrillon, Diego H..
Subjects/Keywords: Forkhead Transcription Factors; Spermatogenesis; Stem Cells
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APA (6th Edition):
Goertz, M. J. (2013). Foxo Transcription Factors Control Spermatogonial Stem Cell Self-Renewal and the Initiation of Spermatogenesis. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/1247
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):
Goertz, Meredith Johanna. “Foxo Transcription Factors Control Spermatogonial Stem Cell Self-Renewal and the Initiation of Spermatogenesis.” 2013. Thesis, University of Texas Southwestern Medical Center. Accessed April 19, 2021.
http://hdl.handle.net/2152.5/1247.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Goertz, Meredith Johanna. “Foxo Transcription Factors Control Spermatogonial Stem Cell Self-Renewal and the Initiation of Spermatogenesis.” 2013. Web. 19 Apr 2021.
Vancouver:
Goertz MJ. Foxo Transcription Factors Control Spermatogonial Stem Cell Self-Renewal and the Initiation of Spermatogenesis. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2013. [cited 2021 Apr 19].
Available from: http://hdl.handle.net/2152.5/1247.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Goertz MJ. Foxo Transcription Factors Control Spermatogonial Stem Cell Self-Renewal and the Initiation of Spermatogenesis. [Thesis]. University of Texas Southwestern Medical Center; 2013. Available from: http://hdl.handle.net/2152.5/1247
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Texas Southwestern Medical Center
19.
Hickey, Stephanie Lepp.
Understanding the Conserved and Species-Specific Functions of FOXP2, a Gene Implicated in Speech and Language Development.
Degree: 2018, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/8795
► During my dissertation work I sought to better understand the conserved and human-specific functions of FoxP2. Intrigued by the enrichment of FOXP2 in the human…
(more)
▼ During my dissertation work I sought to better understand the conserved and human-specific functions of FoxP2. Intrigued by the enrichment of FOXP2 in the human subplate layer, I hypothesized that FOXP2 regulates evolutionarily distinct subplate gene expression patterns and tested this theory by performing RNA-seq in human differentiating neurons and leveraging publically available developmental expression data from human, macaque, and mouse cortex in order to identify human specific, primate specific, and conserved subplate genes regulated by FOXP2. This study not only identified human specific targets in this expanded, transient region, but it may also inspire research of the conserved, non-cell-autonomous role of FoxP2 in the maturation of thalamocortical circuitry. Additionally, I performed ChIP-seq and RNA-seq in human neural progenitor cells and found evidence that FOXP2 may actively modify the chromatin landscape. This lead me to hypothesize that by modifying the chromatin landscape of neural progenitors FOXP2 turns off cellular programs that maintain an undifferentiated state while turning on programs that drive a cell towards a neuronal fate. To test this hypothesis, I identified areas of nucleosomal depletion using ATAC-seq and correlated epigenetic changes caused by FOXP2 expression to changes in gene expression in proliferating and differentiating human neurons. This allowed me to define two separate molecular mechanisms by which FOXP2 regulates gene expression in human neurons, even finding a potential FOXP2 co-activator. Together, these studies push forward our understanding of the function of FoxP2, especially in human neurons, and provide a source of data from which the next hypotheses concerning FoxP2 and human language formation may be derived.
Advisors/Committee Members: Roberts, Todd, Powell, Craig M., Huber, Kimberly M., Takahashi, Joseph.
Subjects/Keywords: Forkhead Transcription Factors; Language; Neurons; Speech
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APA ·
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CSE |
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APA (6th Edition):
Hickey, S. L. (2018). Understanding the Conserved and Species-Specific Functions of FOXP2, a Gene Implicated in Speech and Language Development. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/8795
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):
Hickey, Stephanie Lepp. “Understanding the Conserved and Species-Specific Functions of FOXP2, a Gene Implicated in Speech and Language Development.” 2018. Thesis, University of Texas Southwestern Medical Center. Accessed April 19, 2021.
http://hdl.handle.net/2152.5/8795.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Hickey, Stephanie Lepp. “Understanding the Conserved and Species-Specific Functions of FOXP2, a Gene Implicated in Speech and Language Development.” 2018. Web. 19 Apr 2021.
Vancouver:
Hickey SL. Understanding the Conserved and Species-Specific Functions of FOXP2, a Gene Implicated in Speech and Language Development. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2018. [cited 2021 Apr 19].
Available from: http://hdl.handle.net/2152.5/8795.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Hickey SL. Understanding the Conserved and Species-Specific Functions of FOXP2, a Gene Implicated in Speech and Language Development. [Thesis]. University of Texas Southwestern Medical Center; 2018. Available from: http://hdl.handle.net/2152.5/8795
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Université Laval
20.
Grobs, Yann.
Étude de l'implication du facteur de transcription FoxO3
en hypertension artérielle pulmonaire.
Degree: 2021, Université Laval
URL: http://hdl.handle.net/20.500.11794/68243
► INTRODUCTION : Comme dans le cancer, l’hypertension artérielle pulmonaire (HTAP) est caractérisée par un phénotype pro-prolifératif et résistant à l’apoptose lié à une altération du…
(more)
▼ INTRODUCTION : Comme dans le cancer, l’hypertension
artérielle pulmonaire (HTAP) est caractérisée par un phénotype
pro-prolifératif et résistant à l’apoptose lié à une altération du
métabolisme (effet Warburg) des cellules. Dans le cas de l’HTAP les
cellules affectées sont les cellules musculaires lisses des artères
pulmonaires (CMLAP). L’obstruction vasculaire des petites artères
pulmonaires qui en résulte est responsable de l’augmentation des
résistances pulmonaires menant à l’insuffisance cardiaque droite et
à la mort prématurée des patients. La protéine FoxO3 est un facteur
de transcription dont l’activité et la localisation cellulaire sont
modulables, entre autres, par phosphorylation. Dans les cellules
cancéreuses, la localisation nucléaire de FoxO3 quand elle n’est
pas exclue par phosphorylation a été largement étudiée comme une
protéine cruciale pour son rôle suppresseur de tumeur via la
régulation de gènes impliqués dans l’apoptose et l’arrêt du cycle
cellulaire comme les protéines BIM et P27. En plus de ces fonctions
de facteur de transcription, FoxO3 joue un rôle dans le maintien du
métabolisme cellulaire, connu pour être reprogrammé en HTAP,
notamment en stimulant la synthèse de SOD2, une enzyme responsable
de la détoxification mitochondriale. Ainsi FoxO3 est un candidat
sérieux pour contrôler le phénotype de type cancer des CMLAP-HTAP.
Fait intéressant, AKT et AMPK connus pour être impliqué en HTAP
exercent des effets antagonistes sur FoxO3; AKT promeut son
exclusion nucléaire tandis que AMPK favorise son accumulation
nucléaire et mitochondriale. HYPOTHÈSE : Nous avons ainsi émis
l'hypothèse que l'exclusion nucléaire de FoxO3 (secondaire au
déséquilibre AKT / AMPK) favorise la reprogrammation métabolique
vers la glycolyse conduisant au phénotype pro-prolifératif /
résistant à l'apoptose des CMLAP-HTAP et au remodelage vasculaire.
MÉTHODES ET RÉSULTATS : Par Western blot (WB) et immunofluorescence
sur des CMLAP isolées à la fois de patients HTAP et de patients
témoins, nos résultats suggèrent que l'exclusion nucléaire (et
mitochondriale) de FoxO3 en raison de sa phosphorylation est une
caractéristique des CMLAP-HTAP. In vitro, nous avons démontré que
l'activation pharmacologique (localisation nucléaire) de FoxO3 à
l'aide d'un adénovirus exprimant une forme constitutivement active
et non phosphorylable de FoxO3 ou de la trifluopérazine (TFP)
entraînait une réduction de la prolifération des CMLAP-HTAP
(marquage Ki67) et de la résistance à l'apoptose (dosage de
l'Annexine V). Ces effets sont accompagnés d'une expression
potentiellement augmentée de P27 et de SOD2 ainsi qu’une expression
diminuée de Survivin. In vivo, nous avons montré que l'activation
de FoxO3 à l'aide de la TPF améliore l’HTAP induite chez le rat
monocrotaline (diminution de la Pression systolique du ventricule
droit (RVSP) et des résistances pulmonaires totales (TPR) et
augmentation du volume d’éjection (Sv) et du débit cardiaque (CO)).
CONCLUSION : Nos résultats suggèrent que FoxO3 est impliquée dans
le remodelage vasculaire pulmonaire.…
Advisors/Committee Members: Paulin, Roxane.
Subjects/Keywords: Facteurs de transcription Forkhead.; Hypertension pulmonaire.
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Grobs, Y. (2021). Étude de l'implication du facteur de transcription FoxO3
en hypertension artérielle pulmonaire. (Thesis). Université Laval. Retrieved from http://hdl.handle.net/20.500.11794/68243
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):
Grobs, Yann. “Étude de l'implication du facteur de transcription FoxO3
en hypertension artérielle pulmonaire.” 2021. Thesis, Université Laval. Accessed April 19, 2021.
http://hdl.handle.net/20.500.11794/68243.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Grobs, Yann. “Étude de l'implication du facteur de transcription FoxO3
en hypertension artérielle pulmonaire.” 2021. Web. 19 Apr 2021.
Vancouver:
Grobs Y. Étude de l'implication du facteur de transcription FoxO3
en hypertension artérielle pulmonaire. [Internet] [Thesis]. Université Laval; 2021. [cited 2021 Apr 19].
Available from: http://hdl.handle.net/20.500.11794/68243.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Grobs Y. Étude de l'implication du facteur de transcription FoxO3
en hypertension artérielle pulmonaire. [Thesis]. Université Laval; 2021. Available from: http://hdl.handle.net/20.500.11794/68243
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Universidade Estadual de Campinas
21.
Katashima, Carlos Kiyoshi, 1976-.
Caracterização da s-nitrosação dos fatores de transcrição FOXO1/FOXO3A em músculo esquelético em diferentes modelos experimentais de atrofia.
Degree: Faculdade de Ciências Médicas; Programa de Pós-Graduação em Clínica Médica, 2016, Universidade Estadual de Campinas
URL: http://repositorio.unicamp.br/jspui/handle/REPOSIP/332277
► Orientador: Eduardo Rochete Ropelle
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-09-11T19:37:01Z (GMT). No. of bitstreams:…
(more)
▼ Orientador: Eduardo Rochete Ropelle
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-09-11T19:37:01Z (GMT). No. of bitstreams: 1 Katashima_CarlosKiyoshi_D.pdf: 3770041 bytes, checksum: 6dad30f3362bf6048acc17b992626ad2 (MD5) Previous issue date: 2016
Resumo: A atrofia é um fenômeno clínico complexo que ocorre no músculo esquelético como resultado de uma multiplicidade de causas como danos às conexões neurais, inflamação, estresse oxidativo, desuso dentre outros. Coletivamente, a perda da massa muscular possui estreita relação com uma variedade de condições fisiopatológicas que interferem na qualidade de vida em pacientes com câncer, sepse e diabetes mellitus tipo1 (DM1). Recentes achados, sublinham o papel central dos fatores de transcrição da família Forkhead Box subgroup O (FoxO) na regulação da massa muscular. Durante o estado de catabolismo muscular, esses fatores são
translocados para o núcleo celular e iniciam a transcrição de moléculas relacionadas à proteólise muscular como a muscle-specific RING finger protein 1 (MuRF-1) e atrogin-1/muscle atrophy Fbox protein (Atrogin-1/MAFbx). Embora evidências recentes tenham elucidado que a acetilação, a fosforilação, e a poliubiquitinação governa mecanismos pós-traducionais envolvidos na inibição da atividade desses fatores de transcrição, pouco se sabe como essas moléculas são ativadas. Nos últimos anos, a óxido nítrico sintase induzível (iNOS) foi descrita como principal molécula produtora de óxido nítrico (NO) e responsável por modular a atividade de diversas proteínas durante o processo inflamatório através da S-nitrosação de proteínas. Neste sentido, o objetivo foi avaliar o papel da iNOS sobre a S-nitrosação das proteínas FoxO1 e FOXO3A em modelos experimentais de atrofia muscular induzida por sepse, tumor e DM1. Desse modo, nossos achados mostraram que a atrofia aumentou a expressão de iNOS e a
S-nitrosação dos fatores de transcrição FoxO1 e FoxO3A. Por outro lado, camundongos nocaute para a molécula iNOS, ficaram protegidos da S-nitrosação e parcialmente da perda de peso no estado fisiopatológico da sepse, tumor e DM1. Coletivamente, estes dados sugerem que a atrofia muscular é mediada através da iNOS e da S-nitrosação de proteínas FoxO1 e FOXO3A envolvidas no tumor, sepse e DM1
The atrophy is a clinical complex phenomenon that occurs in skeletal muscle as a result of a multiplicity of causes such as damage to neural connections, inflammation, oxidative stress, disuse, fasting and others. Muscle atrophy has close relationship with a variety of pathophysiological conditions that affect the quality of life in patients with cancer, sepsis and type 1 diabetes mellitus. Recent studies highlight the central role of transcription factors Forkhead Box family subgroup O (FOXO) in the regulation of muscle mass. During the state of muscle catabolism, these transcription factors
are translocated to the nucleus and initiate transcription of molecules related to muscle proteolysis such as…
Advisors/Committee Members: UNIVERSIDADE ESTADUAL DE CAMPINAS, Ropelle, Eduardo Rochete, 1976-, Cintra, Angélica Rossi Sartori, Silva, Adelino Sanchéz Ramos da, Cintra, Dennys Esper, Pauli, José Rodrigo.
Subjects/Keywords: S-nitrosação; Proteína forkhead box O1; Proteína forkhead box O3; Atrofia; Músculos; S-nitrosation; Forkhead Box protein O1; Forkhead Box protein O3; Atrophy; Muscles
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Katashima, Carlos Kiyoshi, 1. (2016). Caracterização da s-nitrosação dos fatores de transcrição FOXO1/FOXO3A em músculo esquelético em diferentes modelos experimentais de atrofia. (Doctoral Dissertation). Universidade Estadual de Campinas. Retrieved from http://repositorio.unicamp.br/jspui/handle/REPOSIP/332277
Chicago Manual of Style (16th Edition):
Katashima, Carlos Kiyoshi, 1976-. “Caracterização da s-nitrosação dos fatores de transcrição FOXO1/FOXO3A em músculo esquelético em diferentes modelos experimentais de atrofia.” 2016. Doctoral Dissertation, Universidade Estadual de Campinas. Accessed April 19, 2021.
http://repositorio.unicamp.br/jspui/handle/REPOSIP/332277.
MLA Handbook (7th Edition):
Katashima, Carlos Kiyoshi, 1976-. “Caracterização da s-nitrosação dos fatores de transcrição FOXO1/FOXO3A em músculo esquelético em diferentes modelos experimentais de atrofia.” 2016. Web. 19 Apr 2021.
Vancouver:
Katashima, Carlos Kiyoshi 1. Caracterização da s-nitrosação dos fatores de transcrição FOXO1/FOXO3A em músculo esquelético em diferentes modelos experimentais de atrofia. [Internet] [Doctoral dissertation]. Universidade Estadual de Campinas; 2016. [cited 2021 Apr 19].
Available from: http://repositorio.unicamp.br/jspui/handle/REPOSIP/332277.
Council of Science Editors:
Katashima, Carlos Kiyoshi 1. Caracterização da s-nitrosação dos fatores de transcrição FOXO1/FOXO3A em músculo esquelético em diferentes modelos experimentais de atrofia. [Doctoral Dissertation]. Universidade Estadual de Campinas; 2016. Available from: http://repositorio.unicamp.br/jspui/handle/REPOSIP/332277
Addis Ababa University
22.
Genet, Haileyesus.
Work Related Stress among Anesthetists in Addis Ababa Hospitals: Prevalence and Associated Factors
.
Degree: 2014, Addis Ababa University
URL: http://etd.aau.edu.et/dspace/handle/123456789/7007
► The major purpose of this study was to assess the prevalence and associated factors of work related stress among anesthetists in Addis Ababa Hospitals. The…
(more)
▼ The major purpose of this study was to assess the prevalence and
associated factors of work related stress among anesthetists in Addis Ababa Hospitals. The research employed a cross-sectional research design using Job Content Questionnaire (JCQ) and turnover intention scale as research instruments. Out of ten government run hospitals in which surgery is performed, four hospitals were selected through the use of the lottery method of simple random sampling as the target population has the same job roles and the available professionals are very limited. Informed consents were obtained from the participants and fifty one anesthetists working in selected hospitals filled out the questionnaire. The findings showed that the prevalence of high level of work related stress was 96.1% among participant anesthetists. Moreover, all the participants had low level of job satisfaction and 84.3% had turnover intention. Generally, this study suggests that the job control and demand of anesthetists and lack of social support increased work stress experience of anesthetists since the results indicated that the participant anesthetists job control and demand positively and significantly correlated with their work stress level, job satisfaction score was negatively and significantly correlated with turnover intention and social support was negatively and significantly correlated with job satisfaction
Advisors/Committee Members: Dr. Moges Ayele (advisor).
Subjects/Keywords: associated factors
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APA ·
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MLA ·
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APA (6th Edition):
Genet, H. (2014). Work Related Stress among Anesthetists in Addis Ababa Hospitals: Prevalence and Associated Factors
. (Thesis). Addis Ababa University. Retrieved from http://etd.aau.edu.et/dspace/handle/123456789/7007
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):
Genet, Haileyesus. “Work Related Stress among Anesthetists in Addis Ababa Hospitals: Prevalence and Associated Factors
.” 2014. Thesis, Addis Ababa University. Accessed April 19, 2021.
http://etd.aau.edu.et/dspace/handle/123456789/7007.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Genet, Haileyesus. “Work Related Stress among Anesthetists in Addis Ababa Hospitals: Prevalence and Associated Factors
.” 2014. Web. 19 Apr 2021.
Vancouver:
Genet H. Work Related Stress among Anesthetists in Addis Ababa Hospitals: Prevalence and Associated Factors
. [Internet] [Thesis]. Addis Ababa University; 2014. [cited 2021 Apr 19].
Available from: http://etd.aau.edu.et/dspace/handle/123456789/7007.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Genet H. Work Related Stress among Anesthetists in Addis Ababa Hospitals: Prevalence and Associated Factors
. [Thesis]. Addis Ababa University; 2014. Available from: http://etd.aau.edu.et/dspace/handle/123456789/7007
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Alberta
23.
Fetterman, Christina.
Forkhead evolution and the FOXC1 inhibitory domain.
Degree: PhD, Medical Sciences - Medical Genetics, 2011, University of Alberta
URL: https://era.library.ualberta.ca/files/kh04dq90r
► Forkhead (Fox) proteins are transcription factors that function in many processes including development, metabolism and cell cycle regulation. This gene family is divided into subfamilies…
(more)
▼ Forkhead (Fox) proteins are transcription factors that
function in many processes including development, metabolism and
cell cycle regulation. This gene family is divided into subfamilies
that appear to originate from a common ancestor. I have identified
the evolutionary selection pressures acting on individual amino
acid positions in the FoxA, FoxC, FoxD, FoxI, FoxO and FoxP
subfamilies. The patterns of selection observed allowed for the
prediction of residue function and identification of residues that
differentiate orthologs and paralogs. The subfamily structure and
negative selection found within the subfamilies indicates that
after gene duplication, differentiation of subfamilies through
amino acid changes and subsequent negative selection on these
changes has occurred. Meanwhile, the observed neutral changes and
positive selection allow for further protein differentiation.
Within the FoxC subfamily, positive selection was identified at one
amino acid site in the inhibitory domain. Mutation of this site in
FOXC1 alters transactivation activity and the effects of mutants on
transactivation activity are different on different reporters. The
mutant effects were consistent with those of known disease causing
mutations, supporting the predicted positive selection. The
inhibitory domain is known to function in reducing FOXC1
transactivation activity and influences protein stability. Here I
additionally show that loss of the inhibitory domain and mutation
of the positively selected site can reduce FOXC1 DNA binding.
Co-transfection of FOXC1 and TLE4, a repressor protein that can
potentially bind to the inhibitory domain, was shown to increase
FOXC1 transactivation activity. The effects of a novel disease
causing FOXC1 inhibitory domain mutation on FOXC1 function were
also assessed. The mutation reduced FOXC1 transactivation activity
and increased protein half-life both of which may lead to disease.
Regulation of FOXC1 activity is critical for normal function and
this work has furthered our knowledge of how the inhibitory domain
influences FOXC1 activity. I have provided biological evidence for
the theory that positive selection acts at the amino acid level to
optimize protein function. I have also shown that both changes in
transcription factor proteins and the cis-regulatory region of
target genes have the potential to contribute to evolutionary
adaptation.
Subjects/Keywords: anterior segment dysgenesis; evolution; genetics; transcription factor; forkhead; disease
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APA ·
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Export
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Manager
APA (6th Edition):
Fetterman, C. (2011). Forkhead evolution and the FOXC1 inhibitory domain. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/kh04dq90r
Chicago Manual of Style (16th Edition):
Fetterman, Christina. “Forkhead evolution and the FOXC1 inhibitory domain.” 2011. Doctoral Dissertation, University of Alberta. Accessed April 19, 2021.
https://era.library.ualberta.ca/files/kh04dq90r.
MLA Handbook (7th Edition):
Fetterman, Christina. “Forkhead evolution and the FOXC1 inhibitory domain.” 2011. Web. 19 Apr 2021.
Vancouver:
Fetterman C. Forkhead evolution and the FOXC1 inhibitory domain. [Internet] [Doctoral dissertation]. University of Alberta; 2011. [cited 2021 Apr 19].
Available from: https://era.library.ualberta.ca/files/kh04dq90r.
Council of Science Editors:
Fetterman C. Forkhead evolution and the FOXC1 inhibitory domain. [Doctoral Dissertation]. University of Alberta; 2011. Available from: https://era.library.ualberta.ca/files/kh04dq90r
University of Manchester
24.
Chen, Xi.
THE DNA-BINDING SPECIFICITY OF FORKHEAD TRANSCRIPTION
FACTORS.
Degree: 2012, University of Manchester
URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:182817
► The healthy development of a living cell requires precise spatial-temporal gene expression. The code that dictates when and where genes are expressed is stored in…
(more)
▼ The healthy development of a living cell requires
precise spatial-temporal gene expression. The code that dictates
when and where genes are expressed is stored in a pattern of
specific sequence motifs, which can be recognised by transcription
factors. Understanding the interaction between these DNA sequence
motifs and transcription factors will help to elucidate how genomic
sequences build transcriptional control networks. However, the
DNA-binding specificities of ~1400 human transcription factors are
largely unknown. The in vivo DNA-binding events of transcription
factors involve great subtlety, because most transcription factors
recognise degenerate sequence motifs and related transcription
factors often prefer similar or even identical sequences. Forkhead
transcription factors exemplify these challenges. To understand how
members within the Forkhead transcription factor family gain their
binding and functional specificities, we used chromatin
immunoprecipitation coupled with high-throughput sequencing
(ChIP-seq) to interrogate the genome-wide chromatin binding events
of three Forkhead transcription factors: FOXM1, FOXO3 and FOXK2. We
find that FOXM1 specifically binds to the promoters of a large
array of genes whose activities peak at the G2 and M phases of the
cell cycle. The canonical Forkhead consensus GTAAACA is not
enriched within the FOXM1 cistrome. It gains its own specific
binding events and biological functions by interacting and
cooperating with the MMB complex. FOXO3 and FOXK2 are recruited to
chromatin by the canonical Forkhead consensus GTAAACA, and they
bind both shared and specific regions in the genome. FOXO3 mostly
binds to the regions which are also bound by FOXK2, but no
competitive or assisted binding between FOXO3 and FOXK2 is detected
within those regions. Overall, these results help explain how
individual members of the Forkhead transcription factor family gain
binding specificity within the genome yet raises new questions of
how functional specificity is achieved by other family
members.
Supplementary_table_1.xlsx - Summary of FOXM1
ChIP-seq analysesSupplementary_table_2.xlsx - Summary of FOXO3
ChIP-seq analyses
Advisors/Committee Members: WHITMARSH, ALAN AJ, Sharrocks, Andrew, Whitmarsh, Alan.
Subjects/Keywords: Forkhead; Transcription factor; ChIP-seq; FOXM1; FOXK2; FOXO3
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APA (6th Edition):
Chen, X. (2012). THE DNA-BINDING SPECIFICITY OF FORKHEAD TRANSCRIPTION
FACTORS. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:182817
Chicago Manual of Style (16th Edition):
Chen, Xi. “THE DNA-BINDING SPECIFICITY OF FORKHEAD TRANSCRIPTION
FACTORS.” 2012. Doctoral Dissertation, University of Manchester. Accessed April 19, 2021.
http://www.manchester.ac.uk/escholar/uk-ac-man-scw:182817.
MLA Handbook (7th Edition):
Chen, Xi. “THE DNA-BINDING SPECIFICITY OF FORKHEAD TRANSCRIPTION
FACTORS.” 2012. Web. 19 Apr 2021.
Vancouver:
Chen X. THE DNA-BINDING SPECIFICITY OF FORKHEAD TRANSCRIPTION
FACTORS. [Internet] [Doctoral dissertation]. University of Manchester; 2012. [cited 2021 Apr 19].
Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:182817.
Council of Science Editors:
Chen X. THE DNA-BINDING SPECIFICITY OF FORKHEAD TRANSCRIPTION
FACTORS. [Doctoral Dissertation]. University of Manchester; 2012. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:182817
Vanderbilt University
25.
Plank, Jennifer Lynn.
Cell autonomous and non-cell autonomous regulation of beta cell mass expansion.
Degree: PhD, Cell and Developmental Biology, 2011, Vanderbilt University
URL: http://hdl.handle.net/1803/15146
► Diabetes mellitus affects approximately 150 million people worldwide. This disease is characterized by hyperglycemia resulting from dysfunctional pancreatic beta cells. Current treatments for diabetics are…
(more)
▼ Diabetes mellitus affects approximately 150 million people worldwide. This disease is characterized by hyperglycemia resulting from dysfunctional pancreatic beta cells. Current treatments for diabetics are inadequate because they often do not prevent complications
associated with the disease; therefore, considerable efforts are focused on derivation of beta cells from embryonic stem cells. Accomplishing this requires a precise understanding of beta cell development and the molecular control of beta cell expansion in vivo. We addressed these approaches in two ways: first, we analyzed the requirement for neural crest (NC) derivatives in regulating beta cell maturation and second, we determined that the transcription factor Foxd3 is required for beta cell mass expansion during pregnancy.
The pancreas develops through a coordinated system of signals from both the endoderm and surrounding mesoderm. Little effort has been devoted to analyzing the role of ectodermally-derived NC that innervates the pancreas during embryogenesis. Our work illustrated that NC enters the pancreatic primordium around 10.25 dpc, shortly after pancreatic evagination from the foregut epithelium. Using a genetic ablation of NC derivatives in the pancreas, we showed, in agreement with published data, increased beta cell proliferation and insulin-positive area. Additionally, our work illustrated a novel requirement for this lineage; NC derivatives are required for beta cell maturation.
Beta cell proliferation in adult mice is rare unless the mice are metabolically challenged, such as during pregnancy. Therefore, I chose to analyze the requirement for Foxd3 during pregnancy. Foxd3 is expressed in the pancreatic primordium beginning at 10.5 dpc and is localized predominantly to beta cells after birth. Virgin mice carrying a pancreas-specific deletion of Foxd3 are euglycemic; however, during pregnancy these mice become glucose intolerant. Several genes required for cell proliferation are misregulated in the absence of Foxd3 resulting in decreased beta cell proliferation and beta cell mass during pregnancy.
Together, my thesis research illustrated the requirement for NC derivatives in controlling beta cell maturation and demonstrated a novel role for Foxd3 in beta cell mass expansion during pregnancy. The findings from both studies can be applied to cell-based therapies to treat diabetics.
Advisors/Committee Members: Patricia Labosky (committee member), David Piston (committee member), Roland Stein (committee member), Maureen Gannon (committee member), Christopher Wright (Committee Chair).
Subjects/Keywords: pancreas development; Forkhead transcription factors; stem cells; beta cell mass
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APA (6th Edition):
Plank, J. L. (2011). Cell autonomous and non-cell autonomous regulation of beta cell mass expansion. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/15146
Chicago Manual of Style (16th Edition):
Plank, Jennifer Lynn. “Cell autonomous and non-cell autonomous regulation of beta cell mass expansion.” 2011. Doctoral Dissertation, Vanderbilt University. Accessed April 19, 2021.
http://hdl.handle.net/1803/15146.
MLA Handbook (7th Edition):
Plank, Jennifer Lynn. “Cell autonomous and non-cell autonomous regulation of beta cell mass expansion.” 2011. Web. 19 Apr 2021.
Vancouver:
Plank JL. Cell autonomous and non-cell autonomous regulation of beta cell mass expansion. [Internet] [Doctoral dissertation]. Vanderbilt University; 2011. [cited 2021 Apr 19].
Available from: http://hdl.handle.net/1803/15146.
Council of Science Editors:
Plank JL. Cell autonomous and non-cell autonomous regulation of beta cell mass expansion. [Doctoral Dissertation]. Vanderbilt University; 2011. Available from: http://hdl.handle.net/1803/15146
University of Texas Southwestern Medical Center
26.
Hoover, Ashley Renae.
Characterization of Non-Coding RNAs in Regulating Thymic Epithelial Cell Responses to Pathophysiological Stress.
Degree: 2016, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/5743
► The thymus is uniquely sensitive to several forms of stress. Stress initiates a transient involution that can reduce overall thymic volume up to 90%. The…
(more)
▼ The thymus is uniquely sensitive to several forms of stress. Stress initiates a transient involution that can reduce overall thymic volume up to 90%. The thymus is predominantly composed of developing thymocytes and specialized epithelial cells. The type of stress predicates whether the thymocytes or epithelial cells initiate the involutionary response. MicroRNAs (miRs) are small non-coding RNAs ~18-22 nucleotides in length that maintain cellular homeostasis and regulate stress responses. Previous work in the laboratory identified several microRNAs involved in regulating thymocyte responses to stress. Thymocytes have been the main population studied in response to stress. However, it has become increasingly clear that the epithelial cells play a critical role in thymus involution and the subsequent recovery of thymopoiesis. The work presented in this thesis characterizes an epithelial specific miR, miR-205, and its surrounding long noncoding RNA, MIR205.001 in regulating TEC functions.
A deficiency of miR-205 specifically in TECs renders these cells more susceptible to stress mediated thymic involution. This is revealed by a significant loss in developing thymocytes, altered migration, delayed recovery of single positive thymocyte selection, and proliferative defects in cortical TECs. Gene expression comparisons revealed miR-205 deficient TECs had reduced levels of the TEC master transcriptional regulator, Foxn1, as well as the expression of multiple chemokines. MiR-205 mimics introduced into miR-205 deficient fetal thymic organ cultures were able to restore the levels of Foxn1 and selected chemokines. This work demonstrates that miR-205 positively regulates Foxn1 and chemokine expression following stress.
MiR-205 resides within a putative long noncoding RNA (lncRNA), MIR205.001. TECs deficient in this lncRNA are also sensitive to stress, but do not experience a delay in thymopoiesis nor cortical TEC proliferation defects. This suggests these noncoding RNAs have non-overlapping functions within the TECs. Mice deficient in MIR205.001 also have distinct phenotypes, displaying reduced mendelian ratios indicative of a lethality. The surviving animals display reduced body size, weight, and fat mass. Current experiments are addressing whether this is a metabolic defect or due to changes in feeding behavior.
Advisors/Committee Members: Hooper, Lora V., van Oers, Nicolai S. C., Cleaver, Ondine, Mendell, Joshua T..
Subjects/Keywords: Epithelial Cells; Forkhead Transcription Factors; Gene Expression Regulation; MicroRNAs; Thymocytes
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MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Hoover, A. R. (2016). Characterization of Non-Coding RNAs in Regulating Thymic Epithelial Cell Responses to Pathophysiological Stress. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/5743
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):
Hoover, Ashley Renae. “Characterization of Non-Coding RNAs in Regulating Thymic Epithelial Cell Responses to Pathophysiological Stress.” 2016. Thesis, University of Texas Southwestern Medical Center. Accessed April 19, 2021.
http://hdl.handle.net/2152.5/5743.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Hoover, Ashley Renae. “Characterization of Non-Coding RNAs in Regulating Thymic Epithelial Cell Responses to Pathophysiological Stress.” 2016. Web. 19 Apr 2021.
Vancouver:
Hoover AR. Characterization of Non-Coding RNAs in Regulating Thymic Epithelial Cell Responses to Pathophysiological Stress. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2016. [cited 2021 Apr 19].
Available from: http://hdl.handle.net/2152.5/5743.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Hoover AR. Characterization of Non-Coding RNAs in Regulating Thymic Epithelial Cell Responses to Pathophysiological Stress. [Thesis]. University of Texas Southwestern Medical Center; 2016. Available from: http://hdl.handle.net/2152.5/5743
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Manchester
27.
Chen, Xi.
The DNA-binding specificity of forkhead transcription factors.
Degree: PhD, 2012, University of Manchester
URL: https://www.research.manchester.ac.uk/portal/en/theses/the-dnabinding-specificity-of-forkhead-transcription-factors(bc02fd29-30d0-47da-9b4f-448687504463).html
;
http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.677718
► The healthy development of a living cell requires precise spatial-temporal gene expression. The code that dictates when and where genes are expressed is stored in…
(more)
▼ The healthy development of a living cell requires precise spatial-temporal gene expression. The code that dictates when and where genes are expressed is stored in a pattern of specific sequence motifs, which can be recognised by transcription factors. Understanding the interaction between these DNA sequence motifs and transcription factors will help to elucidate how genomic sequences build transcriptional control networks. However, the DNA-binding specificities of ~1400 human transcription factors are largely unknown. The in vivo DNA-binding events of transcription factors involve great subtlety, because most transcription factors recognise degenerate sequence motifs and related transcription factors often prefer similar or even identical sequences. Forkhead transcription factors exemplify these challenges. To understand how members within the Forkhead transcription factor family gain their binding and functional specificities, we used chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) to interrogate the genome-wide chromatin binding events of three Forkhead transcription factors: FOXM1, FOXO3 and FOXK2. We find that FOXM1 specifically binds to the promoters of a large array of genes whose activities peak at the G2 and M phases of the cell cycle. The canonical Forkhead consensus GTAAACA is not enriched within the FOXM1 cistrome. It gains its own specific binding events and biological functions by interacting and cooperating with the MMB complex. FOXO3 and FOXK2 are recruited to chromatin by the canonical Forkhead consensus GTAAACA, and they bind both shared and specific regions in the genome. FOXO3 mostly binds to the regions which are also bound by FOXK2, but no competitive or assisted binding between FOXO3 and FOXK2 is detected within those regions. Overall, these results help explain how individual members of the Forkhead transcription factor family gain binding specificity within the genome yet raises new questions of how functional specificity is achieved by other family members.
Subjects/Keywords: 572.8; Forkhead; Transcription factor; ChIP-seq; FOXM1; FOXK2; FOXO3
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Chen, X. (2012). The DNA-binding specificity of forkhead transcription factors. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/the-dnabinding-specificity-of-forkhead-transcription-factors(bc02fd29-30d0-47da-9b4f-448687504463).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.677718
Chicago Manual of Style (16th Edition):
Chen, Xi. “The DNA-binding specificity of forkhead transcription factors.” 2012. Doctoral Dissertation, University of Manchester. Accessed April 19, 2021.
https://www.research.manchester.ac.uk/portal/en/theses/the-dnabinding-specificity-of-forkhead-transcription-factors(bc02fd29-30d0-47da-9b4f-448687504463).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.677718.
MLA Handbook (7th Edition):
Chen, Xi. “The DNA-binding specificity of forkhead transcription factors.” 2012. Web. 19 Apr 2021.
Vancouver:
Chen X. The DNA-binding specificity of forkhead transcription factors. [Internet] [Doctoral dissertation]. University of Manchester; 2012. [cited 2021 Apr 19].
Available from: https://www.research.manchester.ac.uk/portal/en/theses/the-dnabinding-specificity-of-forkhead-transcription-factors(bc02fd29-30d0-47da-9b4f-448687504463).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.677718.
Council of Science Editors:
Chen X. The DNA-binding specificity of forkhead transcription factors. [Doctoral Dissertation]. University of Manchester; 2012. Available from: https://www.research.manchester.ac.uk/portal/en/theses/the-dnabinding-specificity-of-forkhead-transcription-factors(bc02fd29-30d0-47da-9b4f-448687504463).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.677718
University of Texas Southwestern Medical Center
28.
Lan, Qing.
Transcriptional Regulation of Intestinal Stem Cell Lineage in Drosophila.
Degree: 2017, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/7091
► The general metadata – e.g., title, author, abstract, subject headings, etc. – is publicly available, but access to the submitted files is restricted to UT…
(more)
▼ The general metadata – e.g., title, author, abstract, subject headings, etc. – is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.
The question of how somatic stem cells respond to tissue needs is always intriguing, since aberrant somatic stem cell behaviors may lead to adult tissue degeneration or tumorigenesis. Here, this thesis focuses on the transcriptional regulation of a somatic stem cell lineage: the intestinal stem cell in Drosophila adult gut. The Drosophila adult gut is a dynamic organ. It is maintained by hundreds of somatic gut stem cell evenly distributed throughout the gut epithelium. These multi-potent somatic stem cells undergo self-renewal and differentiation to replenish two mature gut cell types: the absorptive enterocytes and secretory entero-endocrine cells. Through an RNAi screen targeting transcription factors required for stem cell-mediated acute gut regeneration, two novel transcription factors, the FoxA family Fork head (Fkh) and SoxE family sox100b (dSox9), were uncovered and functionally characterized in this thesis. During gut regeneration, transcription factor Fkh and dSox9 are required for stem cell proliferation. During gut homeostasis, Fkh maintains stemness and prevents progenitor from precocious differentiation; dSox9 controls lineage differentiation through Jak-Stat pathway. To further probe mechanisms underlying gut stem cell physiology, ChIP-Seq technique was applied to map chromatin binding sites of gut stem cell regulators (HA tagged) in stem/progenitor cells of dissected fly guts, including transcription factors (FoxA family/Fkh, SoxE family/dSox9, bHLH family/Da), niche pathway downstream factors (Jak-Stat pathway/Stat92E, BMP pathway/Mad, Notch pathway/Su(H), JNK pathway/Kay), and transcriptional regulators (Mediator/Med20, p300/Nej). A set of shared ChIP-Seq peak regions likely functions as enhancers to drive gene expression in gut stem/progenitor cells. This thesis leads to the speculation of a transcriptional network that maintains gut stem/progenitor cell normal physiology in adult Drosophila.
Advisors/Committee Members: Jiang, Jin, Kraus, W. Lee, Sadek, Hesham A., Jiang, Huaqi.
Subjects/Keywords: Chromatin Immunoprecipitation; Drosophila; Forkhead Transcription Factors; Intestines; Stem Cells
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lan, Q. (2017). Transcriptional Regulation of Intestinal Stem Cell Lineage in Drosophila. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/7091
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):
Lan, Qing. “Transcriptional Regulation of Intestinal Stem Cell Lineage in Drosophila.” 2017. Thesis, University of Texas Southwestern Medical Center. Accessed April 19, 2021.
http://hdl.handle.net/2152.5/7091.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Lan, Qing. “Transcriptional Regulation of Intestinal Stem Cell Lineage in Drosophila.” 2017. Web. 19 Apr 2021.
Vancouver:
Lan Q. Transcriptional Regulation of Intestinal Stem Cell Lineage in Drosophila. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2017. [cited 2021 Apr 19].
Available from: http://hdl.handle.net/2152.5/7091.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Lan Q. Transcriptional Regulation of Intestinal Stem Cell Lineage in Drosophila. [Thesis]. University of Texas Southwestern Medical Center; 2017. Available from: http://hdl.handle.net/2152.5/7091
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Saskatchewan
29.
MacAusland-Berg, Josh 1993-.
FRK cancer-related mutations: Effect on enzymatic activity and cellular processes.
Degree: 2019, University of Saskatchewan
URL: http://hdl.handle.net/10388/12357
► Cancer-associated FRK mutations have not been thoroughly studied however, a previous study analyzed six cancer related mutations of BRK L16F, R131L, V253M, N317S, L343F, P450L;…
(more)
▼ Cancer-
associated FRK mutations have not been thoroughly studied however, a previous study analyzed six cancer related mutations of BRK L16F, R131L, V253M, N317S, L343F, P450L; and it was found that there are similar residues in FRK. We identified R64P, K87N, S145R, K265R, N359I, del V378-F379 (VF) found in breast cancer, large intestine cancer, ovarian cancer, and liver cancer. This study analyzes the effect of the mutation of these similar residues in the BRK study, as well as uncharacterized cancer related mutations of FRK. Mutating two of the similar residues maintained the same effects in BRK and FRK whereas the remaining mutants in FRK had no effect on activity. The uncharacterized cancer related mutations of FRK produced interesting results where the mutations in kinase
domain (K265R, N359I, del VF) reduced, inactivated and increased kinase activity respectively. Proliferation, migration and invasion assays were also performed with the R64P, K265R, N358I and VF mutations. The proliferation data revealed that the cell line expressing wild type FRK reduced cell growth which is consistent with past findings. The other mutations also resulted in reduced cell growth in MDA-MB-231 breast cancer cells but were not significantly different to wild type FRK. The invasion assay results show that the wild type FRK significantly reduced invasion compared to the MDA-MB-231 cells compared to parental controls. Differing from the proliferation assay, the mutations R64P, K265R, N359I, and VF showed no reduction in cell invasiveness compared to the parental. The mutations expressed transiently in HEK293 were found to only impact STAT3 phosphorylation where all FRK constructs induced STAT3 phosphorylation except for N359I. Binding experiments were performed using rotational anisotropy and four peptides derived from FRK C terminus (ETDSS(pY)SDANN), SH2 consensus binding sequence (HF(pY)ENI), PTEN (PNVEEPSNPEASSS), and BRCA1 (DTYLIPQIPHSHY). The wild type SH2
domain was able of binding to both peptides from the FRK C terminus and the SH2 consensus binding sequence with a Kd of 2.5 M and 0.4 M respectively. The S145R SH2
domain was also capable of interacting with both peptides with a Kd of 1.4 M with the FRK C terminus and 0.8 M with the SH2 consensus binding sequence. Unfortunately, the SH3
domain was unable to bind to the sequences selected.
Advisors/Committee Members: Lukong, Erique, Bonham, Keith, Luo, Yu, Uppalapati, Maruti.
Subjects/Keywords: Cancer associated mutations
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
MacAusland-Berg, J. 1. (2019). FRK cancer-related mutations: Effect on enzymatic activity and cellular processes. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/12357
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):
MacAusland-Berg, Josh 1993-. “FRK cancer-related mutations: Effect on enzymatic activity and cellular processes.” 2019. Thesis, University of Saskatchewan. Accessed April 19, 2021.
http://hdl.handle.net/10388/12357.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
MacAusland-Berg, Josh 1993-. “FRK cancer-related mutations: Effect on enzymatic activity and cellular processes.” 2019. Web. 19 Apr 2021.
Vancouver:
MacAusland-Berg J1. FRK cancer-related mutations: Effect on enzymatic activity and cellular processes. [Internet] [Thesis]. University of Saskatchewan; 2019. [cited 2021 Apr 19].
Available from: http://hdl.handle.net/10388/12357.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
MacAusland-Berg J1. FRK cancer-related mutations: Effect on enzymatic activity and cellular processes. [Thesis]. University of Saskatchewan; 2019. Available from: http://hdl.handle.net/10388/12357
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
30.
Poston, Chloe N.
Mass Spectrometry-Based Global Proteomic Analysis of
Endoplasmic Reticulum and Mitochondria Contact Sites.
Degree: PhD, Chemistry, 2013, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:320610/
► Mass spectrometry has been a long-standing analytical tool for chemists. Tandem mass spectrometry-based proteomics capitalizes on the sensitivity, accuracy, and efficiency of this classic technique…
(more)
▼ Mass spectrometry has been a long-standing analytical
tool for chemists. Tandem mass spectrometry-based proteomics
capitalizes on the sensitivity, accuracy, and efficiency of this
classic technique in order to investigate the protein content of
specific sub-cellular regions. In this work we apply tandem mass
spectrometry (MS/MS) to the analysis of mitochondria-
associated
endoplasmic reticulum membranes (MAMs). MAMs are a point of
communication between the ER and the mitochondria that facilitate
Ca2+ trafficking, protein folding, and energy metabolism. They have
been implicated in the regulation of apoptosis and more recently
neurodegenerative disorders including Alzheimer's disease and
Parkinson's. The involvement of the MAM in these diseases has yet
to be determined, largely because proteins localized to the MAM
have yet to be elucidated. We address this gap in knowledge with
our tandem mass spectrometry-based global characterization of MAMs
from mouse brain tissue. We employ a gel-based LC/LC-MS/MS method
that allows for the analysis of hydrophobic membrane proteins. Our
analysis reveals 1,212 unique proteins in the MAM that are involved
in cell signaling, small molecule trafficking, and protein
processing. Bio-informatic analysis of our identified MAM proteins
supports postulates that the MAM may play a role in the pathology
of Alzheimer's disease, schizophrenia, and dyskinesia. Our data
also suggests that lipid rafts within the MAM are involved in
signaling and transport within the region, and may play a role in
the MAM's relationship to neurodegenerative disease. The completion
of this work provides a much-anticipated catalog of proteins at the
MAM, which can be used for targeted studies to elucidate pathways
and novel therapeutic targets in the region.
Advisors/Committee Members: Bazemore-Walker, Carthene (Director), Delaney, Sarah (Reader), Suggs, John (Reader).
Subjects/Keywords: Mitochondria-Associated Membranes
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Poston, C. N. (2013). Mass Spectrometry-Based Global Proteomic Analysis of
Endoplasmic Reticulum and Mitochondria Contact Sites. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:320610/
Chicago Manual of Style (16th Edition):
Poston, Chloe N. “Mass Spectrometry-Based Global Proteomic Analysis of
Endoplasmic Reticulum and Mitochondria Contact Sites.” 2013. Doctoral Dissertation, Brown University. Accessed April 19, 2021.
https://repository.library.brown.edu/studio/item/bdr:320610/.
MLA Handbook (7th Edition):
Poston, Chloe N. “Mass Spectrometry-Based Global Proteomic Analysis of
Endoplasmic Reticulum and Mitochondria Contact Sites.” 2013. Web. 19 Apr 2021.
Vancouver:
Poston CN. Mass Spectrometry-Based Global Proteomic Analysis of
Endoplasmic Reticulum and Mitochondria Contact Sites. [Internet] [Doctoral dissertation]. Brown University; 2013. [cited 2021 Apr 19].
Available from: https://repository.library.brown.edu/studio/item/bdr:320610/.
Council of Science Editors:
Poston CN. Mass Spectrometry-Based Global Proteomic Analysis of
Endoplasmic Reticulum and Mitochondria Contact Sites. [Doctoral Dissertation]. Brown University; 2013. Available from: https://repository.library.brown.edu/studio/item/bdr:320610/
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Open Access Theses and Dissertations
