subject:(molecular biology)

Universiteit Utrecht

1. Hofman, E.G. Plasma membrane organization during EGFR signaling: a FRET-based analysis.

Degree: 2008, Universiteit Utrecht

URL: http://dspace.library.uu.nl:8080/handle/1874/30336

► Since two decades it has been suggested that the plasma membrane is organized into lipid-separated domains called lipid rafts. A number of functions have been… (more)

▼ Since two decades it has been suggested that the plasma membrane is organized into lipid-separated domains called lipid rafts. A number of functions have been attributed to these domains, including spatially separating or combining functionally linked proteins. Proteins such as the Epidermal Growth Factor Receptor (EGFR) are found to be localized in membrane domains, as well as effector molecules downstream in the signal transduction cascade. The investigation of these structures has mainly been performed by highly invasive techniques such as biochemical analysis, but lacks data on the situation in intact cells. Chapter 2 of this thesis describes the use of Förster Resonance Energy Transfer (FRET) to study the presence and dynamics of membrane domains containing EGFR. To study this receptor we developed fluorescent nanobodies, monovalent domains from cameloid heavy-chain only antibodies. FRET-FLIM analysis revealed that EGFR resides in a subclass of nanodomains including the ganglioside GM1, and is absent in domains composed of GM1 and GPI-linked GFP. Activation of EGFR results in the coalescence of the two domains, suggesting the formation of signaling platforms. Lipid domains are often suggested to promote the local clustering of their constituents. Therefore, a part of this work describes the development of a novel approach to study the oligomerization state of the domain components in intact cells. This technique, confocal time-resolved fluorescence anisotropy imaging microscopy (CTRFAIM), is based on FRET between identical fluorophores (homo-FRET). The anisotropy, defined as the degree of polarization of the fluorescence, is directly related to the degree of oligomerization. In this thesis, a simplification of this approach is described by applying time-gated data acquisition (chapter 3 and 4). An inducible FKBP dimerization and oligomerization system was developed to correlate the anisotropy value to the oligomerization state. Chapter 4 describes an evaluation of different modes of data acquisition. When compared to steady-state anisotropy, CTR-FAIM shows an improved dynamic range of anisotropy values. A further improvement can be obtained with two-photon excitation, although this improvement is diminished by significant higher photobleaching (chapter 4). When subjected to CTRFAIM analysis, the domain components in our study were indeed found to be clustered. By controlled photobleaching, the lipid raft probe GPI-GFP was found to form small nanoclusters of 1-5 molecules. Also EGFR was found to organize into oligomers, depending on the activation state of the receptor. The CTRFAIM data reveal pre-existing dimers of EGFR in the plasma membrane of resting cells. After stimulation with EGF, the receptor oligomerizes in a kinase- and phosphotyrosine-dependent manner, forming clusters of 3 or more receptors (chapter 5). Furthermore, induced receptor clustering enhances receptor internalization speed, which suggests a stimulatory role for EGFR oligomerization in the internalization process. In conclusion, these data… Advisors/Committee Members: Verkleij, A, van Bergen en Henegouwen, P.

Subjects/Keywords: Molecular biology; Life sciences; Cell biology; Biologie/Milieukunde (BIOL); International (English)

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APA (6^th Edition):

Hofman, E. G. (2008). Plasma membrane organization during EGFR signaling: a FRET-based analysis. (Doctoral Dissertation). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/30336

Chicago Manual of Style (16^th Edition):

Hofman, E G. “Plasma membrane organization during EGFR signaling: a FRET-based analysis.” 2008. Doctoral Dissertation, Universiteit Utrecht. Accessed January 16, 2021. http://dspace.library.uu.nl:8080/handle/1874/30336.

MLA Handbook (7^th Edition):

Hofman, E G. “Plasma membrane organization during EGFR signaling: a FRET-based analysis.” 2008. Web. 16 Jan 2021.

Vancouver:

Hofman EG. Plasma membrane organization during EGFR signaling: a FRET-based analysis. [Internet] [Doctoral dissertation]. Universiteit Utrecht; 2008. [cited 2021 Jan 16]. Available from: http://dspace.library.uu.nl:8080/handle/1874/30336.

Council of Science Editors:

Hofman EG. Plasma membrane organization during EGFR signaling: a FRET-based analysis. [Doctoral Dissertation]. Universiteit Utrecht; 2008. Available from: http://dspace.library.uu.nl:8080/handle/1874/30336

2. Verbeeren, Jens. Regulation of the minor spliceosome through alternative splicing and nuclear retention of the U11/U12-65K mRNA.

Degree: Department of Biosciences, 2016, University of Helsinki

URL: http://hdl.handle.net/10138/159362

►

The protein coding information in our genome is located on genes which are very often interrupted by non-coding regions called introns. For proper gene expression,… (more)

▼

The protein coding information in our genome is located on genes which are very often interrupted by non-coding regions called introns. For proper gene expression, introns must be removed accurately and the remaining protein coding parts, the exons, must be rejoined. This reaction, termed splicing, is carried out by an enormous macromolecular machine called the spliceosome, and is one of the most crucial steps in gene expression. Two different intron types have been identified in eukaryotes, each removed by their own dedicated spliceosome; the U2-type (or major) introns, which constitute the majority of introns, and the U12-type (or minor) introns, of which ca. 700-800 have been identified in the human genome. The presence of a second type of intron and spliceosome has always been enigmatic. However, studies investigating U12-type intron removal have provided us with an important clue; it appears that U12-type introns are spliced less efficiently than U2-type introns. This suggests that their removal could be rate-limiting for the expression of the genes that harbor these introns, and it also offers the intriguing possibility that the activity of the minor spliceosome could be altered in response to changing cellular conditions. These implications could offer a valuable explanation for the extraordinary conservation of the U12-type introns and the components that catalyze their excision. There is currently not much known about the regulation of the minor spliceosome and this study aimed to address this issue. I have investigated the characteristics of a negative feedback loop that regulates the expression level of two essential and unique protein components of the minor spliceosome, the U11-48K and the U11/U12-65K proteins. In the genes that encode these proteins, an ultraconserved sequence element can be found which consists of a tandem repeat of U12-type 5ʹ splice sites. We uncovered that binding of U11/U12 di-snRNPs on these elements leads to alternative splicing where an mRNA isoform is produced that is targeted for degradation or nuclear retention. The presence of such enhancer elements is conserved from plants to animals, highlighting an extreme selection pressure for this regulatory mechanism. I further investigated the role of the U11-35K protein, another protein uniquely associated with the minor spliceosome, in alternative splicing, and the functional requirements for enhancer binding. Furthermore, I uncovered the molecular mechanism by which the level of translational-competent U11/U12-65K mRNA is downregulated through U11/U12 di-snRNP enhancer binding.

Genomissamme oleva tieto proteiinien koodaamiseen sijaitsee geeneissä, jotka ovat usein katkonaisia informaation suhteen. Näitä katkoksia koodaavassa tiedossa kutsutaan introneiksi. Asianmukainen geenien ilmentyminen vaatii että intronit poistettaan tarkasti ja proteiinia koodaavan osat eli eksonit liitetään yhteen. Tämän reaktion, jota kutsutaan silmukoimiseksi, suorittaa valtava makromolekyyliyhdisteiden muodostama koneisto nimeltä silmukoimisyksikkö…

Subjects/Keywords: molecular Biology; molecular Biology

4 more images…

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APA (6^th Edition):

Verbeeren, J. (2016). Regulation of the minor spliceosome through alternative splicing and nuclear retention of the U11/U12-65K mRNA. (Doctoral Dissertation). University of Helsinki. Retrieved from http://hdl.handle.net/10138/159362

Chicago Manual of Style (16^th Edition):

Verbeeren, Jens. “Regulation of the minor spliceosome through alternative splicing and nuclear retention of the U11/U12-65K mRNA.” 2016. Doctoral Dissertation, University of Helsinki. Accessed January 16, 2021. http://hdl.handle.net/10138/159362.

MLA Handbook (7^th Edition):

Verbeeren, Jens. “Regulation of the minor spliceosome through alternative splicing and nuclear retention of the U11/U12-65K mRNA.” 2016. Web. 16 Jan 2021.

Vancouver:

Verbeeren J. Regulation of the minor spliceosome through alternative splicing and nuclear retention of the U11/U12-65K mRNA. [Internet] [Doctoral dissertation]. University of Helsinki; 2016. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/10138/159362.

Council of Science Editors:

Verbeeren J. Regulation of the minor spliceosome through alternative splicing and nuclear retention of the U11/U12-65K mRNA. [Doctoral Dissertation]. University of Helsinki; 2016. Available from: http://hdl.handle.net/10138/159362

3. Clarke, Don Lucas. Development of a Stem Cell Gene Therapy for Sanfilippo Syndrome Type B.

Degree: 2017, California State University, Los Angeles

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=10278830

► Sanfilippo syndrome type B (Mucopolysaccharidosis type IIIB; MPS IIIB) is a lysosomal storage disorder affecting primarily the brain and is characterized by profound intellectual… (more)

Subjects/Keywords: Biology; Molecular biology

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APA (6^th Edition):

Clarke, D. L. (2017). Development of a Stem Cell Gene Therapy for Sanfilippo Syndrome Type B. (Thesis). California State University, Los Angeles. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=10278830

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Clarke, Don Lucas. “Development of a Stem Cell Gene Therapy for Sanfilippo Syndrome Type B.” 2017. Thesis, California State University, Los Angeles. Accessed January 16, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=10278830.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Clarke, Don Lucas. “Development of a Stem Cell Gene Therapy for Sanfilippo Syndrome Type B.” 2017. Web. 16 Jan 2021.

Vancouver:

Clarke DL. Development of a Stem Cell Gene Therapy for Sanfilippo Syndrome Type B. [Internet] [Thesis]. California State University, Los Angeles; 2017. [cited 2021 Jan 16]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=10278830.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Clarke DL. Development of a Stem Cell Gene Therapy for Sanfilippo Syndrome Type B. [Thesis]. California State University, Los Angeles; 2017. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=10278830

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – San Diego

4. Fassas, Scott. Functional characterization of proteins essential for de novo peroxisome biogenesis.

Degree: Biology, 2016, University of California – San Diego

URL: http://www.escholarship.org/uc/item/97j475fd

► Recent discoveries suggest a role for the endoplasmic reticulum (ER) in peroxisome formation. Following the intra-ER sorting of peroxisomal membrane proteins (PMPs) to a site… (more)

Subjects/Keywords: Biology; Molecular biology

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APA (6^th Edition):

Fassas, S. (2016). Functional characterization of proteins essential for de novo peroxisome biogenesis. (Thesis). University of California – San Diego. Retrieved from http://www.escholarship.org/uc/item/97j475fd

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Fassas, Scott. “Functional characterization of proteins essential for de novo peroxisome biogenesis.” 2016. Thesis, University of California – San Diego. Accessed January 16, 2021. http://www.escholarship.org/uc/item/97j475fd.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Fassas, Scott. “Functional characterization of proteins essential for de novo peroxisome biogenesis.” 2016. Web. 16 Jan 2021.

Vancouver:

Fassas S. Functional characterization of proteins essential for de novo peroxisome biogenesis. [Internet] [Thesis]. University of California – San Diego; 2016. [cited 2021 Jan 16]. Available from: http://www.escholarship.org/uc/item/97j475fd.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Fassas S. Functional characterization of proteins essential for de novo peroxisome biogenesis. [Thesis]. University of California – San Diego; 2016. Available from: http://www.escholarship.org/uc/item/97j475fd

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

5. Nuhn, Mitchell E. Molecular ecology of Boletinellus merulioides and systematics of the Boletineae.

Degree: 2016, Clark University

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=10090330

► This work focuses on members of the Boletales. This order is comprised of a morphological and ecologically diverse set of species. While the vast… (more)

▼ This work focuses on members of the Boletales. This order is comprised of a morphological and ecologically diverse set of species. While the vast majority of species are pileate-stipitate with pores and have a mutualistic nutritional strategy ectomycorrhal (ECM), there are resupinate and gilled species, and saprotrophs and mycoparasites as well. In the first chapter, we review the ecological niche occupied by Boletinellus merulioides. This species was originally considered to be ECM, the symbiont to Fraxinus americana. This hypothesis was rejected, and replaced by the possibility of a mutualism with an F. americana aphid pest, Prociphilus fraxinifolii. We present the first study that observed all three species, since the original publication, the first molecular data for each species, and isotopic fractionation results for B. merulioides and P. fraxinifolii. Additionally, we describe a new morphology for sclerotia of B. merulioides. In total, we are unable to reject the possibility of a facultative mutualism between B. merulioides and P. fraxinifolii. Chapters two through five review systematics in the Boletineae. Chapter two presents the most comprehensive phylogenetic review of the Boletineae, at the time publication, and remains one of the most inclusive Boletineae phylogenies. Three genes, nuclear large subunit, translation elongation factor 1-alpha, and DNA directed RNA polymerase II largest subunit, were used. This chapter is a summary of Boletineae taxonomy and morphological characteristics, with a clade by clade analysis. We present compelling evidence for the mycoparasitic nutritional mode of Buchwaldoboletus lignicola. Additionally, we found that Chalciporus piperatus, a close relative of B. lignicola, is likely to be a mycoparasite. We present strong evidence that the genus Boletus is limited to single clade that contains approximately 10% of the validly published Boletus species. A subset of the taxa sampled in chapter two was used in the phylogenies presented in chapters three, four, and five. Each of these chapters reviews the phylogenetic placement of traditionally problematic species/genera; Surotius eximius, Harrya chromapes and allies, and the Boletaceae species with longitudinally striated spores. These groups have been in multiple. Our results show that Sutorius and Harrya species are distinct from other Boletacaea species and that the longitudinally striated species have been lumped together. By correcting taxonomic confusion and using a multigene data set we are able to resolve these problematic species, and provide a path for future systematics and evolutionary analysis.

Subjects/Keywords: Biology; Molecular biology

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APA (6^th Edition):

Nuhn, M. E. (2016). Molecular ecology of Boletinellus merulioides and systematics of the Boletineae. (Thesis). Clark University. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=10090330

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Nuhn, Mitchell E. “Molecular ecology of Boletinellus merulioides and systematics of the Boletineae.” 2016. Thesis, Clark University. Accessed January 16, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=10090330.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Nuhn, Mitchell E. “Molecular ecology of Boletinellus merulioides and systematics of the Boletineae.” 2016. Web. 16 Jan 2021.

Vancouver:

Nuhn ME. Molecular ecology of Boletinellus merulioides and systematics of the Boletineae. [Internet] [Thesis]. Clark University; 2016. [cited 2021 Jan 16]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=10090330.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Nuhn ME. Molecular ecology of Boletinellus merulioides and systematics of the Boletineae. [Thesis]. Clark University; 2016. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=10090330

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

6. Guo, Lei. The Molecular Mechanisms of Sex Determination in Vertebrates.

Degree: 2017, The University of North Dakota

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=10274673

► Many reptiles display temperature-dependent sex determination (TSD), in which the primary sex is determined by incubation temperatures rather than sex chromosomes. However, temperature is… (more)

▼ Many reptiles display temperature-dependent sex determination (TSD), in which the primary sex is determined by incubation temperatures rather than sex chromosomes. However, temperature is not the only factor that play critical roles in sex determination in the species with TSD. Previous studies in the snapping turtle, a species with TSD, showed that dihydrotestosterone (DHT) induces ovary development at temperatures that normally produce males or mixed sex ratios. In addition, the feminizing effect of DHT was found to be associated with increased expression of the ovary-determining gene Foxl2, suggesting a potential androgen-Foxl2 regulatory mechanism. This dissertation aims to clarify the molecular mechanisms underlying TSD in several aspects. First, determine the role of androgen in TSD; second, identify novel thermosensitive genes involved in TSD and lastly, reconstruct gene regulatory networks underlying sex determination. To test the hypothetical androgen-Foxl2 interaction, I cloned the proximal promoter (1.6 kb) and coding sequence for snapping turtle Foxl2 (tFoxl2) in frame with mCherry, a red fluorescent protein. The tFoxl2-mCherry fusion plasmid or mCherry plasmid were stably transfected into mouse KK1 granulosa cells. Although expression of tFoxl2-mCherry was not affected by androgen treatment in KK1 cells, androgen inhibited expression of the endogenous mouse Foxl2 gene, suggesting the androgen-Foxl2 interaction does exist but it differs between species. We also found tFoxl2-mCherry potentiated low dose DHT effects on aromatase expression, which has not been reported in any other studies. To identify novel sex-determining genes in TSD, I first de novo assembled and annotated the transcriptome of the snapping turtle using next-generation sequencing (NGS) and then performed RNA-seq analyses on the newly assembled reference transcriptome. With the differential gene expression analyses, I identified 293 thermosensitive genes. Among these genes, I find AEBP2, JARID2, and KDM6B of particular interest because these genes could influence expression of many other genes via epigenetic modifications. To further investigate the molecular mechanisms underlying sex determination, I reconstructed gene regulatory networks using an entropy based network reconstructing algorithm—ARACNE with public microarray experiments in mouse gonads. The subsequent hub gene analyses revealed the basic molecular pathways underlying gonadal development and the master regulator analyses identified 110 candidate sex-determining genes including both known sex-determining genes and novel candidate genes. My findings demonstrate that androgens can influence expression of key ovarian genes but further studies are needed to understand the androgen signaling in TSD. Furthermore, my study provides a first description of the snapping turtle transcriptome and the effects of temperature on transcriptome-wide patterns of gene expression…

Subjects/Keywords: Biology; Molecular biology

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APA (6^th Edition):

Guo, L. (2017). The Molecular Mechanisms of Sex Determination in Vertebrates. (Thesis). The University of North Dakota. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=10274673

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Guo, Lei. “The Molecular Mechanisms of Sex Determination in Vertebrates.” 2017. Thesis, The University of North Dakota. Accessed January 16, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=10274673.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Guo, Lei. “The Molecular Mechanisms of Sex Determination in Vertebrates.” 2017. Web. 16 Jan 2021.

Vancouver:

Guo L. The Molecular Mechanisms of Sex Determination in Vertebrates. [Internet] [Thesis]. The University of North Dakota; 2017. [cited 2021 Jan 16]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=10274673.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Guo L. The Molecular Mechanisms of Sex Determination in Vertebrates. [Thesis]. The University of North Dakota; 2017. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=10274673

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universidade Nova

7. Tavares, Débora A. Studies on non-typeability and molecular identification of the pneumococcus.

Degree: 2016, Universidade Nova

URL: https://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/43668

Pneumococcus(is(a(major(human(pathogen.(Its(main(virulence(factor(is(the(capsule,( which( is( of( polysaccharide( nature.( The( detection( of( the( capsule( using( specific( antisera( is( used( to( identify( pneumococcus.( Also,( differences( in( structural( and( antigenic(properties(of(the(polysaccharides(composing(the(capsule(have(been(used( to(classify(pneumococcus(into(serotypes.(

info:eu-repo/semantics/publishedVersion

Subjects/Keywords: Biology; Molecular Biology

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APA (6^th Edition):

Tavares, D. A. (2016). Studies on non-typeability and molecular identification of the pneumococcus. (Thesis). Universidade Nova. Retrieved from https://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/43668

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Tavares, Débora A. “Studies on non-typeability and molecular identification of the pneumococcus.” 2016. Thesis, Universidade Nova. Accessed January 16, 2021. https://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/43668.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Tavares, Débora A. “Studies on non-typeability and molecular identification of the pneumococcus.” 2016. Web. 16 Jan 2021.

Vancouver:

Tavares DA. Studies on non-typeability and molecular identification of the pneumococcus. [Internet] [Thesis]. Universidade Nova; 2016. [cited 2021 Jan 16]. Available from: https://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/43668.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Tavares DA. Studies on non-typeability and molecular identification of the pneumococcus. [Thesis]. Universidade Nova; 2016. Available from: https://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/43668

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – Santa Cruz

8. Kan, Christopher H. Quantifying Introgression at the Gene Level in Strongylocentrotid Urchins.

Degree: Ecology and Evolutionary Biology, 2018, University of California – Santa Cruz

URL: http://www.escholarship.org/uc/item/6773x4rv

► Introgressive hybridization, the movement of genetic material between species, is increasingly being documented in many taxa. It has largely been studied at 100kb+ level. I… (more)

Subjects/Keywords: Biology; Molecular biology

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APA (6^th Edition):

Kan, C. H. (2018). Quantifying Introgression at the Gene Level in Strongylocentrotid Urchins. (Thesis). University of California – Santa Cruz. Retrieved from http://www.escholarship.org/uc/item/6773x4rv

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kan, Christopher H. “Quantifying Introgression at the Gene Level in Strongylocentrotid Urchins.” 2018. Thesis, University of California – Santa Cruz. Accessed January 16, 2021. http://www.escholarship.org/uc/item/6773x4rv.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kan, Christopher H. “Quantifying Introgression at the Gene Level in Strongylocentrotid Urchins.” 2018. Web. 16 Jan 2021.

Vancouver:

Kan CH. Quantifying Introgression at the Gene Level in Strongylocentrotid Urchins. [Internet] [Thesis]. University of California – Santa Cruz; 2018. [cited 2021 Jan 16]. Available from: http://www.escholarship.org/uc/item/6773x4rv.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kan CH. Quantifying Introgression at the Gene Level in Strongylocentrotid Urchins. [Thesis]. University of California – Santa Cruz; 2018. Available from: http://www.escholarship.org/uc/item/6773x4rv

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Wisconsin – Milwaukee

9. Biswas, Sreya. Characterization and Use of Folate Receptor Isoforms for Targeting of Epithelial and Myeloid Cells.

Degree: PhD, Biological Sciences, 2016, University of Wisconsin – Milwaukee

URL: https://dc.uwm.edu/etd/1352

► ABSTRACT CHARACTERIZATION AND USE OF FOLATE RECEPTOR ISOFORMS FOR TARGETING OF EPITHELIAL AND MYELOID CELLS by Sreya Biswas The University of Wisconsin-Milwaukee, 2016 Under… (more)

▼ ABSTRACT CHARACTERIZATION AND USE OF FOLATE RECEPTOR ISOFORMS FOR TARGETING OF EPITHELIAL AND MYELOID CELLS by Sreya Biswas The University of Wisconsin-Milwaukee, 2016 Under the Supervision of Professor Douglas A. Steeber Folate receptor (FR) is a GPI-anchored glycoprotein with high binding affinity for folic acid. FR has two membrane-associated isoforms, α and β, that are overexpressed on epithelial and myeloid tumors, respectively. Normal cells may also exhibit FR expression at very low levels but interestingly, FR-α on normal cells is restricted to the apical surface i.e., away from the blood stream. This differential expression and orientation of the FR-α isoform on tumor cells has been exploited to selectively target and deliver conjugates (e.g., drugs, nanoparticles, liposomes) to tumor cells without harming neighboring healthy cells. However, the functions and use of FR-β as a potential target have not been explored, and its functions on myeloid cells remain largely unknown. Therefore, we investigated the functions of FR-β to determine its potential as a target in myeloid malignancies using a human myelomonocytic leukemia cell line, U937. FR-α studies were conducted using a murine epithelial breast carcinoma cell line, 4T1, and tumors harvested from 4T1 tumor-bearing mice. The isoforms were found overexpressed on tumor cells and tissues, both in vitro and in vivo, with no expression observed on corresponding normal cells. Studies conducted using folic acid-fluorochrome conjugates to determine intracellular receptor fate indicated that FR-β was not internalized into cells unlike FR-α. However, both isoforms exhibited strong binding to folic acid conjugates (e.g., fluorochromes, nanoparticles) thus indicating that they could be selectively targeted using folic acid-dependent methods. We also determined the potential of a novel histone deacetylase (HDAC) inhibitor (HDACi) as an anti-cancer agent that could be used along with folic acid for achieving better selectivity in targeting tumor cells. Preliminary studies showed that Compound 5 (Cpd5) is stable with strong anti-proliferative activities against human tumor cells. Cpd5 was also able to reduce the rate of 4T1 tumor growth in mice without inducing systemic toxicity in the animals. In addition, Cpd5 exhibited desirable pharmacokinetic properties and showed direct effects on acetylation levels of histone proteins. These studies not only provide insights into the functional differences associated with FR-α and FR-β isoforms, but also highlight the potential of future targeting strategies utilizing these to target both epithelial and myeloid malignancies with improved selectivity. Advisors/Committee Members: Douglas Steeber.

Subjects/Keywords: Biology; Molecular Biology

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APA (6^th Edition):

Biswas, S. (2016). Characterization and Use of Folate Receptor Isoforms for Targeting of Epithelial and Myeloid Cells. (Doctoral Dissertation). University of Wisconsin – Milwaukee. Retrieved from https://dc.uwm.edu/etd/1352

Chicago Manual of Style (16^th Edition):

Biswas, Sreya. “Characterization and Use of Folate Receptor Isoforms for Targeting of Epithelial and Myeloid Cells.” 2016. Doctoral Dissertation, University of Wisconsin – Milwaukee. Accessed January 16, 2021. https://dc.uwm.edu/etd/1352.

MLA Handbook (7^th Edition):

Biswas, Sreya. “Characterization and Use of Folate Receptor Isoforms for Targeting of Epithelial and Myeloid Cells.” 2016. Web. 16 Jan 2021.

Vancouver:

Biswas S. Characterization and Use of Folate Receptor Isoforms for Targeting of Epithelial and Myeloid Cells. [Internet] [Doctoral dissertation]. University of Wisconsin – Milwaukee; 2016. [cited 2021 Jan 16]. Available from: https://dc.uwm.edu/etd/1352.

Council of Science Editors:

Biswas S. Characterization and Use of Folate Receptor Isoforms for Targeting of Epithelial and Myeloid Cells. [Doctoral Dissertation]. University of Wisconsin – Milwaukee; 2016. Available from: https://dc.uwm.edu/etd/1352

Florida State University

10. Sima, Jiao. Genetic Dissection of Cis-Elements in Spatio-temporal Control of DNA Replication.

Degree: PhD, Biological Science, 2018, Florida State University

URL: http://purl.flvc.org/fsu/fd/2018_Sp_Sima_fsu_0071E_14411 ;

►

DNA replication in all Eukaryotes follows a defined temporal order termed replication-timing program (RT), which is coupled with the spatial separation of chromatin distribution inside… (more)

▼

DNA replication in all Eukaryotes follows a defined temporal order termed replication-timing program (RT), which is coupled with the spatial separation of chromatin distribution inside the nucleus. Early or late replicating chromatin self-organizes in 3D into sub-nuclear compartments at the nucleus interior or proximity to nuclear lamina respectively. RT is also highly correlated with multiple other features of the genome including transcriptional activity, chromatin composition, and mutational landscape. The molecular mechanisms regulating RT and linking these events are unclear. To investigate the role of DNA sequences in RT regulation, I adopted two parallel approaches to test the sufficiency and necessity of specific DNA segments in these processes. In the first approach, I developed an extra-chromosomal vector system (E-BAC) to show that determinants for RT and A/B compartmentalization are genetically encoded in ~200kb DNA sequences. In the second approach involving CRISPR (clustered regularly interspaced short palindromic repeats) mediated genome-editing, I identified three “early replication control elements” (ERCEs) internal of the domain that act redundantly and interdependently to give rise to both early replication and A/B compartmentalization of a pluripotency associated domain in mouse embryonic stem cells. The three ERCEs and other ERCE-like elements form the strongest CTCF-independent interactions among each other, which could drive the formation of A/B compartments inside the nucleus. The ERCEs also display a combination of active chromatin features resembling promoters and/or enhancers. They are implicated in gene regulation possibly by mediating the formation of transcription factories. These findings underscore the genetic influence on controlling multiple cellular processes, and highlight the complexity of cis regulation from the linear genome. The discovery of cis regulatory elements offers mechanistic insight linking highly correlated genomic features/activities, and provides opportunities to further dissect their relationship from a 3D perspective. Deeper understanding of genome regulation will hopefully enable the manipulation of these processes in cell function and disease.

A Dissertation submitted to the Department of Biological Science in partial fulfillment of the requirements for the degree of Doctor of Philosophy.

Spring Semester 2018.

April 4, 2018.

Chromatin compartment, Chromatin interactions, cis-elements, DNA replication timing, E-BACs, ERCEs

David M. Gilbert, Professor Directing Dissertation; Akash Gunjan, University Representative; Jonathan H. Dennis, Committee Member; Fanxiu Zhu, Committee Member; Debra A. Fadool, Committee Member.

Advisors/Committee Members: David M. Gilbert (professor directing dissertation), Akash Gunjan (university representative), Jonathan Hancock Dennis (committee member), Fanxiu Zhu (committee member), Debra Ann Fadool (committee member).

Subjects/Keywords: Biology; Molecular biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sima, J. (2018). Genetic Dissection of Cis-Elements in Spatio-temporal Control of DNA Replication. (Doctoral Dissertation). Florida State University. Retrieved from http://purl.flvc.org/fsu/fd/2018_Sp_Sima_fsu_0071E_14411 ;

Chicago Manual of Style (16^th Edition):

Sima, Jiao. “Genetic Dissection of Cis-Elements in Spatio-temporal Control of DNA Replication.” 2018. Doctoral Dissertation, Florida State University. Accessed January 16, 2021. http://purl.flvc.org/fsu/fd/2018_Sp_Sima_fsu_0071E_14411 ;.

MLA Handbook (7^th Edition):

Sima, Jiao. “Genetic Dissection of Cis-Elements in Spatio-temporal Control of DNA Replication.” 2018. Web. 16 Jan 2021.

Vancouver:

Sima J. Genetic Dissection of Cis-Elements in Spatio-temporal Control of DNA Replication. [Internet] [Doctoral dissertation]. Florida State University; 2018. [cited 2021 Jan 16]. Available from: http://purl.flvc.org/fsu/fd/2018_Sp_Sima_fsu_0071E_14411 ;.

Council of Science Editors:

Sima J. Genetic Dissection of Cis-Elements in Spatio-temporal Control of DNA Replication. [Doctoral Dissertation]. Florida State University; 2018. Available from: http://purl.flvc.org/fsu/fd/2018_Sp_Sima_fsu_0071E_14411 ;

Florida State University

11. Li, Jie. Functional Characterization of Protein O-glcnacylation in Plants.

Degree: MS, Biological Science, 2015, Florida State University

URL: http://purl.flvc.org/fsu/fd/FSU_migr_etd-9639 ;

►

O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and dynamic protein modification in eukaryotes, carried out by O-GlcNAc transferases (OGT). Two OGTs from Arabidopsis, SPINDLY (SPY) and… (more)

▼

O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and dynamic protein modification in eukaryotes, carried out by O-GlcNAc transferases (OGT). Two OGTs from Arabidopsis, SPINDLY (SPY) and SECRET AGENT (SEC), play important roles in plant growth and development. The phenotypes of spy and sec single mutants indicate that OGT affects processes including response to hormones and environmental signals, circadian rhythms, root development, and intercellular transport. Interestingly, the spy sec double mutant caused embryonic lethality, suggesting that OGT activity is essential to plant embryogenesis. However, the function of SPY and SEC in protein O-GlcNAc modification remains largely unknown. In animals, there are hundreds of O-GlcNAc modified cytoplasmic and nuclear proteins, participating in diverse cellular processes such as signaling, metabolism, transcriptional regulation, and cell cycle controls. However, there is little evidence that any protein in planta is O-GlcNAc modified. In order to determine the roles of SPY and SEC in protein O-GlcNAcylation, I generated transgenic plants with an inducible RNAi construct (hRNA) to knock down either gene in the mutant background for the other gene, which circumvents the embryonic lethality of the spy sec double mutant. High level expression of the RNAi constructs in the SPY hRNA sec and SEC hRNA spy double mutants caused complete arrest of root growth and death to rosette and shoot, which suggested that SPY and SEC are essential for postembryonic growth. Using O-GlcNAc antibodies, I showed that many proteins are O-GlcNAcylated in Arabidopsis thaliana seedlings. Specifically, I found that RNA polymerase II (Pol II) is modified by O-GlcNAc. In animals, O-GlcNAcylation and phosphorylation compete for the same residues, serine 5 and serine 7, on C-terminal domain of Pol II. Interestingly, I found that O-GlcNAcylation and phosphorylation are mutually exclusive on the 5th serine in the conserved YSPTSPS repeat sequence of Pol II. In animals, O-GlcNAc has recently been shown to also occur on histones as part of the epigenetic marks. I also examined whether O-GlcNAc modification affects other histone modifications, such as H3K36me3, H3K27me3, H3K9me3, H3K4me3 and H3K27me2. These results suggest that SPY and SEC have an overlapping role in plant postembryonic development by O-GlcNAcylating Pol II in plants, which competes phosphorylation of Serine 5 on CTD.

A Thesis submitted to the Department of Biological Science in partial fulfillment of the requirements for the degree of Master of Science.

Summer Semester 2015.

July 14, 2015.

Hongchang Cui, Professor Directing Thesis; George W. Bates, Committee Member; Hank W. Bass, Committee Member; Karen M. McGinnis, Committee Member.

Advisors/Committee Members: Hongchang Cui (professor directing thesis), George W. (George Wesley) Bates (committee member), Hank W. Bass (committee member), Karen M. McGinnis (committee member).

Subjects/Keywords: Biology; Molecular biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Li, J. (2015). Functional Characterization of Protein O-glcnacylation in Plants. (Masters Thesis). Florida State University. Retrieved from http://purl.flvc.org/fsu/fd/FSU_migr_etd-9639 ;

Chicago Manual of Style (16^th Edition):

Li, Jie. “Functional Characterization of Protein O-glcnacylation in Plants.” 2015. Masters Thesis, Florida State University. Accessed January 16, 2021. http://purl.flvc.org/fsu/fd/FSU_migr_etd-9639 ;.

MLA Handbook (7^th Edition):

Li, Jie. “Functional Characterization of Protein O-glcnacylation in Plants.” 2015. Web. 16 Jan 2021.

Vancouver:

Li J. Functional Characterization of Protein O-glcnacylation in Plants. [Internet] [Masters thesis]. Florida State University; 2015. [cited 2021 Jan 16]. Available from: http://purl.flvc.org/fsu/fd/FSU_migr_etd-9639 ;.

Council of Science Editors:

Li J. Functional Characterization of Protein O-glcnacylation in Plants. [Masters Thesis]. Florida State University; 2015. Available from: http://purl.flvc.org/fsu/fd/FSU_migr_etd-9639 ;

Columbia University

12. Lewis, Thera Cathy. Serum Regulation of Inhibitor of DNA Binding/Differentiation 1 Expression by a BMP Pathway and BMP Responsive El.

Degree: 2013, Columbia University

URL: https://doi.org/10.7916/D8Q246NR

► Immediate Early Genes (IEGs) are expressed upon re-entry of quiescent cells into the cell cycle following serum stimulation. These genes are involved in growth control… (more)

Subjects/Keywords: Biology; Molecular biology

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APA (6^th Edition):

Lewis, T. C. (2013). Serum Regulation of Inhibitor of DNA Binding/Differentiation 1 Expression by a BMP Pathway and BMP Responsive El. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/D8Q246NR

Chicago Manual of Style (16^th Edition):

Lewis, Thera Cathy. “Serum Regulation of Inhibitor of DNA Binding/Differentiation 1 Expression by a BMP Pathway and BMP Responsive El.” 2013. Doctoral Dissertation, Columbia University. Accessed January 16, 2021. https://doi.org/10.7916/D8Q246NR.

MLA Handbook (7^th Edition):

Lewis, Thera Cathy. “Serum Regulation of Inhibitor of DNA Binding/Differentiation 1 Expression by a BMP Pathway and BMP Responsive El.” 2013. Web. 16 Jan 2021.

Vancouver:

Lewis TC. Serum Regulation of Inhibitor of DNA Binding/Differentiation 1 Expression by a BMP Pathway and BMP Responsive El. [Internet] [Doctoral dissertation]. Columbia University; 2013. [cited 2021 Jan 16]. Available from: https://doi.org/10.7916/D8Q246NR.

Council of Science Editors:

Lewis TC. Serum Regulation of Inhibitor of DNA Binding/Differentiation 1 Expression by a BMP Pathway and BMP Responsive El. [Doctoral Dissertation]. Columbia University; 2013. Available from: https://doi.org/10.7916/D8Q246NR

Cleveland State University

13. Singh, Savita, Singh. REGULATION OF ANDROGEN SIGNALING AND CHOLESTEROL METABOLISM BY MIR-149-5P IN PROSTATE CANCER.

Degree: PhD, College of Sciences and Health Professions, 2017, Cleveland State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=csu1513271812361131

► Prostate cancer growth and proliferation depend on androgen signaling mediated by transactivation of androgen receptor (AR). Androgen ablation remains the mainstay therapy for treatment of… (more)

Subjects/Keywords: Molecular Biology; Biology

Record Details Similar Records Cite « Share

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APA (6^th Edition):

Singh, Savita, S. (2017). REGULATION OF ANDROGEN SIGNALING AND CHOLESTEROL METABOLISM BY MIR-149-5P IN PROSTATE CANCER. (Doctoral Dissertation). Cleveland State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=csu1513271812361131

Chicago Manual of Style (16^th Edition):

Singh, Savita, Singh. “REGULATION OF ANDROGEN SIGNALING AND CHOLESTEROL METABOLISM BY MIR-149-5P IN PROSTATE CANCER.” 2017. Doctoral Dissertation, Cleveland State University. Accessed January 16, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=csu1513271812361131.

MLA Handbook (7^th Edition):

Singh, Savita, Singh. “REGULATION OF ANDROGEN SIGNALING AND CHOLESTEROL METABOLISM BY MIR-149-5P IN PROSTATE CANCER.” 2017. Web. 16 Jan 2021.

Vancouver:

Singh, Savita S. REGULATION OF ANDROGEN SIGNALING AND CHOLESTEROL METABOLISM BY MIR-149-5P IN PROSTATE CANCER. [Internet] [Doctoral dissertation]. Cleveland State University; 2017. [cited 2021 Jan 16]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=csu1513271812361131.

Council of Science Editors:

Singh, Savita S. REGULATION OF ANDROGEN SIGNALING AND CHOLESTEROL METABOLISM BY MIR-149-5P IN PROSTATE CANCER. [Doctoral Dissertation]. Cleveland State University; 2017. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=csu1513271812361131

Cleveland State University

14. JHA, SUJATA S. Elucidating the Role of Non Random Synonymous Codon Usage in Fine Tuning the Process of Co-translational Protein Folding.

Degree: PhD, College of Sciences and Health Professions, 2014, Cleveland State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=csu1413375693

► After decades of research, the exact path any polypeptide follows to achieve its functional conformation in vivo is still an enigma. Protein folding in vivo… (more)

▼ After decades of research, the exact path any polypeptide follows to achieve its functional conformation in vivo is still an enigma. Protein folding in vivo is a co-translational process. It starts early on, during elongation of the nascent polypeptide in the ribosomal exit tunnel and continues immediately after the chain extrudes out of the ribosome. The rate of elongation during translation is non-uniform and altered rate of elongation can ultimately affect the folding dynamics of the elongating nascent polypeptide. One of the factors that predominantly influences the rate of translation elongation, is the non-uniform usage of synonymous codons along the mRNA (codon usage bias). Codon usage bias exists because genetic code is degenerate and certain synonymous codons are used with higher frequency (frequent codons) than others (rare codons). It is well known that the relative abundance of tRNAs responding to frequently used codons is also high, which further implies that a frequent codon will be translated faster by the ribosome than the rare codon. Thus, mRNA not only codes for amino acid sequence of the synthesized polypeptide, but it also governs the rate at which different parts of the polypeptide will appear out of the ribosome, i.e. it contains a kinetic code for ribosome movement and peptide elongation. Recent experiments support the hypothesis that distribution of rare and frequent codons along mRNA is not random, but it is evolutionarily conserved and positioned strategically along mRNA to influence the rate of translation elongation. This rate fine tunes the co-translational folding, by allowing temporal and spatial separation of different folding events. We have designed synonymous variants of Bovine Gamma-B Crystallin gene that encode proteins with identical amino acid sequences but altered codon usage and expressed them in in vivo in E. coli and in vitro in various cell-free extracts. These variants were designed and used to comprehensively test the role of synonymous codon usage on 1) protein expression 2) kinetics of translation elongation and ultimately on 3) co-translational protein folding. We provide evidence showing that relative distribution of rare and frequent synonymous codons along mRNA plays a pivotal role in dictating translation kinetics and ensures functional and efficient co-translational protein folding. This study for the first time also demonstrates that altered elongation rates affect the conformation of the ribosome bound nascent chains. Advisors/Committee Members: Komar , Anton (Advisor).

Subjects/Keywords: Biology; Molecular Biology

Record Details Similar Records Cite « Share

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

JHA, S. S. (2014). Elucidating the Role of Non Random Synonymous Codon Usage in Fine Tuning the Process of Co-translational Protein Folding. (Doctoral Dissertation). Cleveland State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=csu1413375693

Chicago Manual of Style (16^th Edition):

JHA, SUJATA S. “Elucidating the Role of Non Random Synonymous Codon Usage in Fine Tuning the Process of Co-translational Protein Folding.” 2014. Doctoral Dissertation, Cleveland State University. Accessed January 16, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=csu1413375693.

MLA Handbook (7^th Edition):

JHA, SUJATA S. “Elucidating the Role of Non Random Synonymous Codon Usage in Fine Tuning the Process of Co-translational Protein Folding.” 2014. Web. 16 Jan 2021.

Vancouver:

JHA SS. Elucidating the Role of Non Random Synonymous Codon Usage in Fine Tuning the Process of Co-translational Protein Folding. [Internet] [Doctoral dissertation]. Cleveland State University; 2014. [cited 2021 Jan 16]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=csu1413375693.

Council of Science Editors:

JHA SS. Elucidating the Role of Non Random Synonymous Codon Usage in Fine Tuning the Process of Co-translational Protein Folding. [Doctoral Dissertation]. Cleveland State University; 2014. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=csu1413375693

15. Vinckevicius, Aurimas. Recruitment of HCFC1 to Chromatin by THAP11 and ZNF143 Transcription Factors.

Degree: 2016, Northwestern University

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=10117187

► Control of cell cycle progression is an important aspect of normal cell biology and is frequently disrupted in cancers. HCFC1 has been established as… (more)

▼ Control of cell cycle progression is an important aspect of normal cell biology and is frequently disrupted in cancers. HCFC1 has been established as a critical component of cell cycle regulation, but the mechanism by which it mediates this function is not clearly understood. Recently HCFC1 has been shown to directly interact with the E2F family of proteins, which are key regulators of cell cycle progression, and bind promoters of cell cycle control genes. Interestingly, some of these promoters are also bound by THAP11, another HCFC1-interacting protein, which may be responsible for HCFC1 recruitment to these loci. In this study, we analyzed existing genome-wide data and performed bench experiments at a large number of HCFC1 target genes to determine the mode of HCFC1 recruitment to cell cycle control genes. These analyses revealed that, on a genome-wide scale, HCFC1 is highly associated with THAP11 and ZNF143 transcription factors on chromatin, while the association with E2F1 – a member of the E2F protein family – is significantly weaker. Furthermore, the results of our study indicate that HCFC1 recruitment to chromatin is conditional on THAP11 and ZNF143, but not E2F1. Contrary to current literature, which suggests that THAP11 and ZNF143 may compete for binding to chromatin, our observations indicate that THAP11, ZNF143, and HCFC1 chromatin occupancy is mutually dependent. Genome-wide and in vitro studies demonstrate that THAP11 and ZNF143 recognize overlapping DNA sequences. Given our results above, the mechanism of cooperative binding by these two proteins is unclear and warrants further investigation. To avoid possible artifacts associated with in vitro binding experiments, we used chromosomally-integrated synthetic constructs and CRISPR-Cas9-mediated approaches in intact cells to elucidate the role of DNA sequence in recruitment of the THAP11/ZNF143/HCFC1 complex and to establish its biological relevance. We show that the ACTACA submotif, shared by both THAP11 and ZNF143, directs recruitment of THAP11 and HCFC1 to ZNF143-occupied loci. Importantly, its position, spacing, and orientation relative to the ZNF143 core motif are critical for this action. Biologically, CRISPR-Cas9-mediated alteration of the ACTACA submotif in the endogenous OPHN1 promoter abolished its transcriptional activity and lead to lower RNA Polymerase II and histone H3 lysine 4 tri-methyl levels. Our in vivo approaches provide strong evidence for the molecular role of the ACTACA submotif in THAP11, ZNF143, and HCFC1 cooperative recruitment to chromatin and its biological necessity for target gene expression.

Subjects/Keywords: Molecular biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Vinckevicius, A. (2016). Recruitment of HCFC1 to Chromatin by THAP11 and ZNF143 Transcription Factors. (Thesis). Northwestern University. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=10117187

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Vinckevicius, Aurimas. “Recruitment of HCFC1 to Chromatin by THAP11 and ZNF143 Transcription Factors.” 2016. Thesis, Northwestern University. Accessed January 16, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=10117187.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Vinckevicius, Aurimas. “Recruitment of HCFC1 to Chromatin by THAP11 and ZNF143 Transcription Factors.” 2016. Web. 16 Jan 2021.

Vancouver:

Vinckevicius A. Recruitment of HCFC1 to Chromatin by THAP11 and ZNF143 Transcription Factors. [Internet] [Thesis]. Northwestern University; 2016. [cited 2021 Jan 16]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=10117187.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Vinckevicius A. Recruitment of HCFC1 to Chromatin by THAP11 and ZNF143 Transcription Factors. [Thesis]. Northwestern University; 2016. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=10117187

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

16. Cucullo, Jessica. The role of mammalian WDR1 and its truncated isoform in cell migration and cofilin signalling.

Degree: MS, Biological Sciences, 2010, National Library of Canada

URL: http://scholar.uwindsor.ca/etd/281

► Directed cellular migration is a normal process which involves the actin cytoskeleton and actin-binding proteins such as WDR1 and cofilin. WDR1 promotes actin filament depolymerization… (more)

Subjects/Keywords: Biology; Molecular.

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APA (6^th Edition):

Cucullo, J. (2010). The role of mammalian WDR1 and its truncated isoform in cell migration and cofilin signalling. (Masters Thesis). National Library of Canada. Retrieved from http://scholar.uwindsor.ca/etd/281

Chicago Manual of Style (16^th Edition):

Cucullo, Jessica. “The role of mammalian WDR1 and its truncated isoform in cell migration and cofilin signalling.” 2010. Masters Thesis, National Library of Canada. Accessed January 16, 2021. http://scholar.uwindsor.ca/etd/281.

MLA Handbook (7^th Edition):

Cucullo, Jessica. “The role of mammalian WDR1 and its truncated isoform in cell migration and cofilin signalling.” 2010. Web. 16 Jan 2021.

Vancouver:

Cucullo J. The role of mammalian WDR1 and its truncated isoform in cell migration and cofilin signalling. [Internet] [Masters thesis]. National Library of Canada; 2010. [cited 2021 Jan 16]. Available from: http://scholar.uwindsor.ca/etd/281.

Council of Science Editors:

Cucullo J. The role of mammalian WDR1 and its truncated isoform in cell migration and cofilin signalling. [Masters Thesis]. National Library of Canada; 2010. Available from: http://scholar.uwindsor.ca/etd/281

17. Dhaliwal, Rajdeep. Roles of Cyclin A and Cyclin B in Drosophila Female Meiosis.

Degree: MA, Biological Sciences, 2011, National Library of Canada

URL: http://scholar.uwindsor.ca/etd/67

► Cyclin Dependent Kinase 1 (CDK1) is a key mitotic regulator that associates with Cyclin proteins to form active Cyclin-CDK1 complexes. The mitotic roles of Cyclin-CDK1… (more)

Subjects/Keywords: Molecular biology.

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APA (6^th Edition):

Dhaliwal, R. (2011). Roles of Cyclin A and Cyclin B in Drosophila Female Meiosis. (Masters Thesis). National Library of Canada. Retrieved from http://scholar.uwindsor.ca/etd/67

Chicago Manual of Style (16^th Edition):

Dhaliwal, Rajdeep. “Roles of Cyclin A and Cyclin B in Drosophila Female Meiosis.” 2011. Masters Thesis, National Library of Canada. Accessed January 16, 2021. http://scholar.uwindsor.ca/etd/67.

MLA Handbook (7^th Edition):

Dhaliwal, Rajdeep. “Roles of Cyclin A and Cyclin B in Drosophila Female Meiosis.” 2011. Web. 16 Jan 2021.

Vancouver:

Dhaliwal R. Roles of Cyclin A and Cyclin B in Drosophila Female Meiosis. [Internet] [Masters thesis]. National Library of Canada; 2011. [cited 2021 Jan 16]. Available from: http://scholar.uwindsor.ca/etd/67.

Council of Science Editors:

Dhaliwal R. Roles of Cyclin A and Cyclin B in Drosophila Female Meiosis. [Masters Thesis]. National Library of Canada; 2011. Available from: http://scholar.uwindsor.ca/etd/67

University of South Florida

18. Mitra, Avishek. Sigma Factor N| A Novel Regulator of Acid Resistance and Locus of Enterocyte Effacement in Escherichia coli O157|H7.

Degree: 2014, University of South Florida

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=3617860

► In enterohemorrhagic E. coli (EHEC) sigma factor N (σ^N) regulates glutamate-dependent acid resistance (GDAR) and the locus of enterocyte effacement (LEE), discrete genetic… (more)

Subjects/Keywords: Biology; Molecular

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APA (6^th Edition):

Mitra, A. (2014). Sigma Factor N| A Novel Regulator of Acid Resistance and Locus of Enterocyte Effacement in Escherichia coli O157|H7. (Thesis). University of South Florida. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=3617860

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Mitra, Avishek. “Sigma Factor N| A Novel Regulator of Acid Resistance and Locus of Enterocyte Effacement in Escherichia coli O157|H7.” 2014. Thesis, University of South Florida. Accessed January 16, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=3617860.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Mitra, Avishek. “Sigma Factor N| A Novel Regulator of Acid Resistance and Locus of Enterocyte Effacement in Escherichia coli O157|H7.” 2014. Web. 16 Jan 2021.

Vancouver:

Mitra A. Sigma Factor N| A Novel Regulator of Acid Resistance and Locus of Enterocyte Effacement in Escherichia coli O157|H7. [Internet] [Thesis]. University of South Florida; 2014. [cited 2021 Jan 16]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3617860.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Mitra A. Sigma Factor N| A Novel Regulator of Acid Resistance and Locus of Enterocyte Effacement in Escherichia coli O157|H7. [Thesis]. University of South Florida; 2014. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3617860

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Kansas

19. Bishop, Stephanie Cara. Long primer extension by a novel inverse PCR method.

Degree: 2009, University of Kansas

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=1465374

► An inverse polymerase chain reaction (PCR) was employed to construct an engineered F₁-ATPase by means of inserting the repressor of primer (Rop) DNA sequence… (more)

Subjects/Keywords: Biology; Molecular

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APA (6^th Edition):

Bishop, S. C. (2009). Long primer extension by a novel inverse PCR method. (Thesis). University of Kansas. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=1465374

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bishop, Stephanie Cara. “Long primer extension by a novel inverse PCR method.” 2009. Thesis, University of Kansas. Accessed January 16, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=1465374.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Bishop, Stephanie Cara. “Long primer extension by a novel inverse PCR method.” 2009. Web. 16 Jan 2021.

Vancouver:

Bishop SC. Long primer extension by a novel inverse PCR method. [Internet] [Thesis]. University of Kansas; 2009. [cited 2021 Jan 16]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=1465374.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bishop SC. Long primer extension by a novel inverse PCR method. [Thesis]. University of Kansas; 2009. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=1465374

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California, San Diego

20. Murthy, Nevin. hIws1 structural elucidation and protein interactions.

Degree: 2009, University of California, San Diego

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=1467930

► There are a number of nuclear factors that play an integral role in transcriptional elongation. Once such factor is hIws1, a nuclear protein first… (more)

▼ There are a number of nuclear factors that play an integral role in transcriptional elongation. Once such factor is hIws1, a nuclear protein first characterized to bind the histone H3 chaperone, Spt6. Our lab previously showed that Spt6 binds directly to the phosphorylated C-terminal tail of RNA polymerase II (RNAPII), and recruits Iws1 to control specific events that occur during elongation, including mRNA processing, mRNA export, and histone H3K36 methylation. hIws1 interacts directly with the histone H3K36 methyltransferase, Hypb/Set2, as well as the mRNA export adaptor protein, REF1/Aly. Iws1 is reportedly an essential mammalian protein, but little is know about its structure or functional domains. In the present study, I constructed GST tagged hIws1 protein constructs that were subsequently used in pulldown assays to evaluate its nuclear binding partner proteins. Pulldown assays were performed with either HeLa whole cell extract or HeLa nuclear extract. The N-terminal region of Iws1 (residues 1 through 495) was found to associate with the LEDGF/p75, a protein that has been previously identified to take part in lentiviral genome integration. In addition, I found that the C-terminal region of Iws (residues 522 through 819) binds to the E74-like factor 1 (Elf1). Interestingly, the hIws1 C-terminus contains a novel domain called the LW motif, which is highly conserved in Iws1 proteins from other species, and is also present in two transcription factors, Med26 and TFIIS. To test the role of the LW domain, I created three GST-Iws1 point mutant proteins, which were purified and used in GST-pulldown assays. Two residues (tyrosine-665 and tryptophan-685) contained within the LW motif were found to be crucial for the hIws1-Spt6 interaction. By contrast, Med26 was found to also associate with Iws1, but this interaction was not mediated by the LW motif, and Iws1 also binds to the LEDGF factor through a region outside of the LW sequence. Thus these findings identify a new domain that is likely to be critical for binding of Iws1 to Spt6 and assembly of the RNAPII elongation complex.

Subjects/Keywords: Biology; Molecular

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Murthy, N. (2009). hIws1 structural elucidation and protein interactions. (Thesis). University of California, San Diego. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=1467930

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Murthy, Nevin. “hIws1 structural elucidation and protein interactions.” 2009. Thesis, University of California, San Diego. Accessed January 16, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=1467930.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Murthy, Nevin. “hIws1 structural elucidation and protein interactions.” 2009. Web. 16 Jan 2021.

Vancouver:

Murthy N. hIws1 structural elucidation and protein interactions. [Internet] [Thesis]. University of California, San Diego; 2009. [cited 2021 Jan 16]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=1467930.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Murthy N. hIws1 structural elucidation and protein interactions. [Thesis]. University of California, San Diego; 2009. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=1467930

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Southern California

21. Parakh, Sejal. Genetic engineering of thermally sensitive elastin-like polypeptide and its expression in HEK 293 cells.

Degree: 2010, University of Southern California

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=1479997

► Substantial efforts have been to design drug carriers for targeted drug delivery to tumor sites in order to spare the normal tissue from the… (more)

▼ Substantial efforts have been to design drug carriers for targeted drug delivery to tumor sites in order to spare the normal tissue from the hazardous effects of chemotherapeutic agents and achieve better therapeutic efficacy [2, 4, 37, 39]. One promising approach to reduce chemotoxicity would be to conjugate or encapsulate these potent drugs into nanometer (10–400) sized particles and trigger their release at tumor sites [12, 13, 20]. However, nanoparticulates frequently accumulate in the liver, which leads to high local concentrations of these toxic drugs. This accumulation reduces delivery of the appropriate dose of drugs to the site of action and can generate hepatotoxicity. The aim of this project is to design a nano drug carrier that extends plasma circulation, permits greater tumor accumulation, and reduces hepatotoxicity, which is based on the enhanced permeability and retention effect. To achieve this goal, a novel approach to produce N-glycosylated peptide nanoparticles has been explored. Elastin-like polypeptides are repeated pentameric peptides VPG XG exhibiting a characteristic inverse phase transition temperature T_t, above which they form aggregates from a monodisperse solution. It is hypothesized that on triggering the phase transition of an N-glycosylated-ELP-drug conjugate, it will form nanostructures with insoluble ELP-drug at the core shielded with soluble N-linked carbohydrates. For this purpose, a library of ELP VPGAG consisting of 6, 12, 24, 48, 96, 192 pentamers was constructed. This was followed by biosynthesis of several constructs comprising of ELP A₉₆and A₁₉₂ with Endoplasmic Reticulum Signal and N-glycosylation sequences using recombinant DNA technology. Expression of these constructs and GFP plasmid was optimized into mammalian HEK 293 cells using L-PEI as transfection agent. Successful expression of GFP protein alone and its co-transfection with N-glycosylation + ELP A₁₉₂ and A₉₆ sequences was evaluated using fluorescence microscopy. However, N-glycosylated ELP or ELP (A₁₉₂ and A₉₆) did not exhibit any obvious phase transition in the medium collected before and after HEK293 cell lysis. Thus, expression of N-glycosylated ELP or ELP protein could not be determined.

Subjects/Keywords: Biology; Molecular

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Parakh, S. (2010). Genetic engineering of thermally sensitive elastin-like polypeptide and its expression in HEK 293 cells. (Thesis). University of Southern California. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=1479997

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Parakh, Sejal. “Genetic engineering of thermally sensitive elastin-like polypeptide and its expression in HEK 293 cells.” 2010. Thesis, University of Southern California. Accessed January 16, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=1479997.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Parakh, Sejal. “Genetic engineering of thermally sensitive elastin-like polypeptide and its expression in HEK 293 cells.” 2010. Web. 16 Jan 2021.

Vancouver:

Parakh S. Genetic engineering of thermally sensitive elastin-like polypeptide and its expression in HEK 293 cells. [Internet] [Thesis]. University of Southern California; 2010. [cited 2021 Jan 16]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=1479997.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Parakh S. Genetic engineering of thermally sensitive elastin-like polypeptide and its expression in HEK 293 cells. [Thesis]. University of Southern California; 2010. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=1479997

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

East Carolina University

22. Shah, Maitri Yogen. Effects of 5-fluorouracil drug treatment on the expression profile of microRNAs in MCF7 breast cancer cells.

Degree: 2010, East Carolina University

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=1480459

► Breast cancer is one of the leading causes of deaths in women worldwide. 5-flourouracil (5-FU) is a classic chemotherapeutic drug that has been widely… (more)

▼ Breast cancer is one of the leading causes of deaths in women worldwide. 5-flourouracil (5-FU) is a classic chemotherapeutic drug that has been widely used in the treatment of breast cancer patients. In this study, using several biochemical techniques, we studied the global effects of 5-FU treatment on MCF7 breast cancer cells. The dose-response curve obtained after the treatment of MCF7 cells with 23 different 5-FU concentrations for 48 hours showed an atypical bimodal or biphasic curve, thus indicating a plausible dual mechanism of action for 5-FU. After 48 hours of treatment with 5-FU, the cells were found to be apoptotic, with a distinct reduction in the cell size, compromised anchorage ability but no significant alteration in the cell cycle progression. These findings provided evidence of the global inhibitory effects of 5-FU on human breast cancer cells in vitro and warranted further evaluation to study the molecular basis of aberrant expression of protein-coding genes previously reported after 5-FU treatment. We hypothesized that microRNAs (miRNAs), the newly identified class of small regulatory RNAs, might play a mediator role in inducing the cytotoxicity of 5-FU, by regulating the expression of its target genes. Using a combined advanced microarray and quantitative real time PCR (qRT-PCR) technology, we found for the first time that 5-FU significantly altered the global expression profile of miRNAs in MCF7 breast cancer cells. After 48 hours of treatment with a low dose (0.01µM), 42 miRNAs were differentially expressed in MCF7 cells (23 up-regulated, 19 down-regulated). A majority of these miRNAs have been previously associated with cancer development, and were predicted to potentially target many oncogenes and tumor suppressor genes. To further understand the connection between miRNA dysregulation and 5-FU therapy, we investigated the dose- and time-dependent modification in the miRNA expression levels after 5-FU treatment. Eleven miRNAs (let-7g, miR-10b, miR-15a, miR-16, miR-21, miR-27a, miR-365, miR-374b, miR-483-5p, miR-574-3p and miR-575) previously identified in the microarray to be differentially expressed after treatment were selected to analyze their responsiveness to eight different 5-FU dosages of 0.001, 0.005, 0.01, 0.1, 0.7, 1, 5 and 10µM. Of these, miR-10b, miR-21, miR-365 and miR-483-5p were shown to be significantly regulated in a beneficial way. Time-response data was also generated for miR-10b, miR-21, miR-483-5p, miR-574-3p and miR-575 following 12, 24, 36, 48, 60 and 72 hours treatment with 0.1, 0.7 and 10µM 5-FU. The data obtained suggested that miRNA expression in MCF7 cells is sensitive to 5-FU therapy at low doses and shorter treatment durations. The down-regulation of an important oncomir, miR-21; and alteration in the expression of three new miRNAs with no previous breast cancer association, miR-483-5p, miR-574-3p and miR-575 indicates that miRNA might play an important role in 5-FU therapy. In conclusion, miRNAs were shown to play an important regulatory…

Subjects/Keywords: Biology; Molecular

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Shah, M. Y. (2010). Effects of 5-fluorouracil drug treatment on the expression profile of microRNAs in MCF7 breast cancer cells. (Thesis). East Carolina University. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=1480459

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Shah, Maitri Yogen. “Effects of 5-fluorouracil drug treatment on the expression profile of microRNAs in MCF7 breast cancer cells.” 2010. Thesis, East Carolina University. Accessed January 16, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=1480459.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Shah, Maitri Yogen. “Effects of 5-fluorouracil drug treatment on the expression profile of microRNAs in MCF7 breast cancer cells.” 2010. Web. 16 Jan 2021.

Vancouver:

Shah MY. Effects of 5-fluorouracil drug treatment on the expression profile of microRNAs in MCF7 breast cancer cells. [Internet] [Thesis]. East Carolina University; 2010. [cited 2021 Jan 16]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=1480459.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Shah MY. Effects of 5-fluorouracil drug treatment on the expression profile of microRNAs in MCF7 breast cancer cells. [Thesis]. East Carolina University; 2010. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=1480459

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

23. Susilarini, Ni Ketut. Interaction of Kaposi's sarcoma-associated herpesvirus ORF59 with oriLyt is dependent upon binding with K-Rta.

Degree: 2011, University of Nevada, Reno

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=1484051

► There are six Kaposi Sarcoma-associated Herpesvirus (KSHV/HHV-8) viral-encoded core proteins required for lytic origin-dependent DNA replication. They are: ORF9 (DNA polymerase), ORF6 (single-stranded DNA… (more)

▼ There are six Kaposi Sarcoma-associated Herpesvirus (KSHV/HHV-8) viral-encoded core proteins required for lytic origin-dependent DNA replication. They are: ORF9 (DNA polymerase), ORF6 (single-stranded DNA binding protein), ORF40/41 (primase-associated factor), ORF44 (helicase), ORF56 (primase) and ORF59 (DNA polymerase processivity factor). These six core proteins have a high level of homology to other herpesvirus proteins necessary for oriLyt-dependent DNA replication. In addition to these core proteins, the major transactivator for KSHV, K-Rta, is also required for lytic origin-dependent DNA replication. KSHV/HHV-8 displays two distinct life stages, latency and lytic reactivation. Progression through the lytic cycle and replication of the viral genome is an essential step towards the production of infectious virus and human disease. KSHV K-Rta has been shown to be the major transactivator required for the initiation of lytic reactivation. In the transient cotransfection replication assay, K-Rta is the only non-core protein required for DNA synthesis. K-Rta was shown to interact with both C/EBP&agr; binding motifs and the R response elements (49) within oriLyt. It is postulated that K-Rta acts in part, to facilitate the recruitment of replication factors to oriLyt. In order to define the role of K-Rta in the initiation of lytic DNA synthesis we show an interaction with ORF59, the DNA polymerase processivity factor (PF), one of the eight virally encoded proteins necessary for origin-dependent DNA replication. Using the chromatin immunoprecipitation assay (ChIP), both K-Rta and ORF59 interact with the RRE and C/EBP&agr; binding motifs within oriLyt in cells harboring the KSHV BAC. A transient transfection ChIP assay demonstrated that the interaction of ORF59 with oriLyt is dependent upon binding with K-Rta and ORF59 fails to bind to oriLyt in the absence of K-Rta. Also, using the cotransfection replication assay, over-expression of the interaction domain of K-Rta has a dominant-negative effect on oriLyt amplification, suggesting that the interaction of K-Rta with ORF59 is essential for DNA synthesis and supports the hypothesis that K-Rta facilitates the formation of a replication complex at oriLyt.

Subjects/Keywords: Biology; Molecular

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Susilarini, N. K. (2011). Interaction of Kaposi's sarcoma-associated herpesvirus ORF59 with oriLyt is dependent upon binding with K-Rta. (Thesis). University of Nevada, Reno. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=1484051

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Susilarini, Ni Ketut. “Interaction of Kaposi's sarcoma-associated herpesvirus ORF59 with oriLyt is dependent upon binding with K-Rta.” 2011. Thesis, University of Nevada, Reno. Accessed January 16, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=1484051.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Susilarini, Ni Ketut. “Interaction of Kaposi's sarcoma-associated herpesvirus ORF59 with oriLyt is dependent upon binding with K-Rta.” 2011. Web. 16 Jan 2021.

Vancouver:

Susilarini NK. Interaction of Kaposi's sarcoma-associated herpesvirus ORF59 with oriLyt is dependent upon binding with K-Rta. [Internet] [Thesis]. University of Nevada, Reno; 2011. [cited 2021 Jan 16]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=1484051.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Susilarini NK. Interaction of Kaposi's sarcoma-associated herpesvirus ORF59 with oriLyt is dependent upon binding with K-Rta. [Thesis]. University of Nevada, Reno; 2011. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=1484051

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Southern California

24. Si, Yuchen. Determination of the causal potential of histone modifications on transcription and chromatin structure.

Degree: 2012, University of Southern California

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=1529054

► Histone modification is a major epigenetic regulatory mechanism that controls chromatin structure and gene expression potential. However, the causal potential of individual histone modifications… (more)

Subjects/Keywords: Biology; Molecular

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Si, Y. (2012). Determination of the causal potential of histone modifications on transcription and chromatin structure. (Thesis). University of Southern California. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=1529054

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Si, Yuchen. “Determination of the causal potential of histone modifications on transcription and chromatin structure.” 2012. Thesis, University of Southern California. Accessed January 16, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=1529054.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Si, Yuchen. “Determination of the causal potential of histone modifications on transcription and chromatin structure.” 2012. Web. 16 Jan 2021.

Vancouver:

Si Y. Determination of the causal potential of histone modifications on transcription and chromatin structure. [Internet] [Thesis]. University of Southern California; 2012. [cited 2021 Jan 16]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=1529054.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Si Y. Determination of the causal potential of histone modifications on transcription and chromatin structure. [Thesis]. University of Southern California; 2012. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=1529054

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

25. Pao, Christina S. Mechanism of G protein-coupled receptor kinase binding and activation by G protein-coupled receptors.

Degree: 2007, Thomas Jefferson University

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=3240653

► G protein-coupled receptors (GPCRs) are regulated through the process of desensitization, where the receptor becomes refractory to agonist stimulation. The first step in desensitization… (more)

▼ G protein-coupled receptors (GPCRs) are regulated through the process of desensitization, where the receptor becomes refractory to agonist stimulation. The first step in desensitization is phosphorylation of the receptor by G protein-coupled receptor kinases (GRKs). GRK2 is one of seven mammalian GRKs and is the best characterized of the family. In order to define the mechanism of interaction between the receptor and GRKs, we studied the molecular determinants involved in GRK2 binding and how this binding plays a critical role for receptor phosphorylation as well as kinase activity. We also characterized the role of the extreme amino terminus of GRK2 in receptor phosphorylation. To determine the molecular interaction between GRKs and receptor, we used the α_2A-adrenergic receptor (α_2A-AR) as our model GPCR to identify regions that interact with GRK2. We generated glutathione S-transferase (GST) fusion proteins of various regions of the α_2A-AR and used them in direct binding assays with purified GRK2. Through these studies we identified four direct binding sites to GRK2; the second intracellular loop and three regions in the third intracellular loop of the α_2A-AR. Truncation and site-directed mutagenesis studies revealed that basic residues on the receptor are important for binding to GRK2. GRK2 utilizes a number of co-factors to mediate GPCR phosphorylation including acidic phospholipids and G protein subunits. In addition, GRK2 can be stimulated by binding to the agonist-occupied form of receptors. Disruption of GRK binding resulted in decreased activation of the kinase and attenuated phosphorylation of the receptor. The x-ray crystal structure of the inactive form of GRK2 has been solved, revealing an equilateral triangle formed by the three main domains: RGS, kinase and pleckstrin homology domain. Residues 1-29 were unstructured. The amino terminus of GRKs has been implicated in receptor phosphorylation. Here we further characterized the extreme amino terminus of GRK2, which suggested a novel role for this region in regulating kinase activity. Mutations in the first 10 residues of GRK2 impairs its ability to phosphorylate a receptor substrate. Upon further characterization of three mutants, D3K, L4A and D10A, we found that these mutants were severely impaired in β₂-adrenergic receptor phosphorylation, however phosphorylation of a non-receptor substrate, tubulin, was not affected. The mutants were similar to the wild-type in their ability to bind to β₂-adrenergic receptor, however they were not activated by the receptor. We generated a synthetic peptide of the first 14 amino acids of GRK2. A secondary structure prediction program and circular dichroism suggested that the peptide forms an amphipathic alpha helix. In vitro, increasing concentrations of the peptide inhibited receptor phosphorylation by full-length GRK2 and enhanced phospholipid binding of GRK2. Kinetic studies with the…

Subjects/Keywords: Biology; Molecular

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Pao, C. S. (2007). Mechanism of G protein-coupled receptor kinase binding and activation by G protein-coupled receptors. (Thesis). Thomas Jefferson University. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=3240653

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Pao, Christina S. “Mechanism of G protein-coupled receptor kinase binding and activation by G protein-coupled receptors.” 2007. Thesis, Thomas Jefferson University. Accessed January 16, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=3240653.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Pao, Christina S. “Mechanism of G protein-coupled receptor kinase binding and activation by G protein-coupled receptors.” 2007. Web. 16 Jan 2021.

Vancouver:

Pao CS. Mechanism of G protein-coupled receptor kinase binding and activation by G protein-coupled receptors. [Internet] [Thesis]. Thomas Jefferson University; 2007. [cited 2021 Jan 16]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3240653.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Pao CS. Mechanism of G protein-coupled receptor kinase binding and activation by G protein-coupled receptors. [Thesis]. Thomas Jefferson University; 2007. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3240653

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of South Florida

26. Shor, Audrey Cathryn. Src kinase inhibitors for the treatment of sarcomas| Cellular and molecular mechanisms of action.

Degree: 2007, University of South Florida

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=3260112

► Sarcomas are rare mesenchymally-derived tumors with limited treatment options. Tyrosine kinases may serve as potential targets for sarcoma therapy because many are mutated or… (more)

▼ Sarcomas are rare mesenchymally-derived tumors with limited treatment options. Tyrosine kinases may serve as potential targets for sarcoma therapy because many are mutated or overexpressed in sarcomas and cell lines. One potential molecular target for sarcoma treatment is the Src tyrosine kinase. Three independently synthesized Src kinase inhibitors were evaluated in human sarcoma cell lines. Of the three, dasatinib, provided promising results as a potential sarcoma therapy. Until this study, dasatinib activity had not been characterized in sarcoma cells. Based on our previous findings of Src activation in human sarcomas, we evaluated the effects of dasatinib in twelve sarcoma cell lines. Dasatinib inhibited Src activity and downstream signaling at nanomolar concentrations. Inhibition of Src signaling was accompanied by blockade of cell migration and invasion. Moreover, apoptosis was induced in a subset of bone sarcomas at nanomolar concentrations of dasatinib. Inhibition of Src protein expression by siRNA also induced apoptosis, indicating that these bone sarcoma cell lines are dependent on Src activity for survival. These results demonstrate that dasatinib inhibits migration and invasion of diverse sarcoma cell types, and selectively blocks the survival of bone sarcoma cells. Therefore dasatinib may provide therapeutic benefit by preventing the growth and metastasis of sarcomas. Microarray analysis of the sarcoma cell lines lead to the identification of a molecular signature that successfully predicts response to dasatinib by induction of apoptosis. Components of this molecular signature are expressed in primary human sarcomas. Furthermore, expression of the molecular signature in sarcomas can be utilized to cluster tumors based on theoretical response to dasatinib. While the prediction of response in tumors is theoretical, there is encouraging evidence to support further endeavors into validating the potential of this molecular signature to predict response in patients. Together, these studies reveal that, in cell lines, both constitutive Src activation and the presence of a molecular signature that predicts response to dasatinib are important parameters to consider when selecting dasatinib as a treatment for. Furthermore, novel therapeutic approaches that inhibit Src signaling may selectively induce apoptosis in tumor cells and sensitize to chemotherapy those tumors that contain the relevant molecular signature.

Subjects/Keywords: Biology; Molecular

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Shor, A. C. (2007). Src kinase inhibitors for the treatment of sarcomas| Cellular and molecular mechanisms of action. (Thesis). University of South Florida. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=3260112

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Shor, Audrey Cathryn. “Src kinase inhibitors for the treatment of sarcomas| Cellular and molecular mechanisms of action.” 2007. Thesis, University of South Florida. Accessed January 16, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=3260112.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Shor, Audrey Cathryn. “Src kinase inhibitors for the treatment of sarcomas| Cellular and molecular mechanisms of action.” 2007. Web. 16 Jan 2021.

Vancouver:

Shor AC. Src kinase inhibitors for the treatment of sarcomas| Cellular and molecular mechanisms of action. [Internet] [Thesis]. University of South Florida; 2007. [cited 2021 Jan 16]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3260112.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Shor AC. Src kinase inhibitors for the treatment of sarcomas| Cellular and molecular mechanisms of action. [Thesis]. University of South Florida; 2007. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3260112

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

27. He, Ti. Molecular regulation of Pax5-mediated biological functions.

Degree: 2009, The University of Alabama at Birmingham

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=3339168

► B lineage cells are major players in the adaptive immune system. Pax5 is essential for B lineage cell development and function. Pax5 controls B… (more)

▼ B lineage cells are major players in the adaptive immune system. Pax5 is essential for B lineage cell development and function. Pax5 controls B lineage cell developmental progression by regulating expression of many B lineage specific genes and the B lineage specific V_H to DJ_H recombination; and the meantime, Pax5 also represses the transcription of lineage- and developmental stage-inappropriate genes to restrict the B lineage developmental pathway. It is not clear how Pax5-mediated function can be regulated to fulfill its role in different biological reactions. In this dissertation, we focused on the study of the molecular regulation of Pax5-mediated functions. In part I, our results showed that Pax5-mediated transcriptional activation can be dramatically elevated by overexpression of histone acetyltransferase p300. We found that p300 directly interacts with Pax5 and acetylates multiple lysine residues within the N-terminal regions of the Pax5 protein. Mutation of the lysine 67, 87, 89, 103, or 142 residues into alanine diminished p300 mediated enhancement of Pax5 function in activation of Luc-Cd19 reporter gene expression. Moreover, mutations of lysine 67, 87/89 in Pax5 impaired Pax5-mediated activation of endogenous Pax5 target genes in Pax5^-/- mouse pro B cells, indicating that acetylation of Pax5 provides an important regulation for Pax5-mediated biological functions during B lineage cell development. In part II, to understand how Pax5 mediates global effects during B cell development, we analyzed the nuclear sub-localization of Pax5. It has long been hypothesized that transcription in cells occurs on the discrete loci associated with the nuclear matrix inside the nucleus. We found that most endogenous Pax5 in human or mouse B lineage cells associates with the nuclear matrix. In addition, Pax5 co-localizes with the basal transcriptional machinery. We found that the partial homeodomain and its flanking regions contain signals to target Pax5 to the nuclear matrix. Deletion of the partial homeodomain of Pax5 compromises Pax5-mediated transcriptional activation of many target genes. These results indicate that the association with the nuclear matrix is essential for Pax5 to fully activate endogenous B lineage specific genes. Taken together, the results presented in this dissertation uncovered two novel mechanisms that regulate Pax5-mediated transcription function.

Subjects/Keywords: Biology; Molecular

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

He, T. (2009). Molecular regulation of Pax5-mediated biological functions. (Thesis). The University of Alabama at Birmingham. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=3339168

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

He, Ti. “Molecular regulation of Pax5-mediated biological functions.” 2009. Thesis, The University of Alabama at Birmingham. Accessed January 16, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=3339168.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

He, Ti. “Molecular regulation of Pax5-mediated biological functions.” 2009. Web. 16 Jan 2021.

Vancouver:

He T. Molecular regulation of Pax5-mediated biological functions. [Internet] [Thesis]. The University of Alabama at Birmingham; 2009. [cited 2021 Jan 16]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3339168.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

He T. Molecular regulation of Pax5-mediated biological functions. [Thesis]. The University of Alabama at Birmingham; 2009. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3339168

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California, Riverside

28. Karr, Stephen John. A novel approach to functional genomic studies of the superfamily of receptor-like kinases (RLKs) in Arabidopsis thaliana.

Degree: 2009, University of California, Riverside

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=3345263

► Receptor-like kinases (RLKs) form a large monophyletic gene family of approximately 600 members in Arabidopsis. They consist of proteins that contain a single extracellular… (more)

▼ Receptor-like kinases (RLKs) form a large monophyletic gene family of approximately 600 members in Arabidopsis. They consist of proteins that contain a single extracellular domain that is thought to be the site of ligand binding, connected to a single kinase domain, via a single transmembrane domain. Upon ligand binding the kinase is capable of generating a phosphorylation cascade. Because of the size of this gene family and of functional redundancy among closely related members, not much is known about the function of many of these important signaling genes. What little that is known shows that RLKs have many diverse roles in plants such as, hormone perception, plant defense, plant development and cell growth. My objective is to elucidate the function of these genes using a dominant negative approach, circumventing functional redundancy-associated difficulties in gene functional analysis. I constructed a library of dominant negative mutations that encompasses approximately 50% of all the RLKs in Arabidopsis. This library was then screened for morphological, developmental and conditional phenotypes and two strong candidates emerged. The first belongs to the wall-associated kinase-like (WAKL) subfamily, and its dominant mutant altered senescence associated gene expression under various nutrient and light conditions. Further exploration into this gene family may lead to an understanding of nutrient sensing and signaling via the cell wall in plants. The other belongs to the STRUBBELIG RECEPTOR FAMILY (SRF), and its dominant negative mutant altered cell wall composition when examined using Fourier Transform Infrared (FT-IR) microspectroscopy and gas chromatography. In this gene subfamily there is also altered cellulose synthase (CesA) gene expression and morphological phenotypes that suggest that this gene subfamily is important in directing the composition of the plant cell wall. The ramification of this research is that these genes may be important to a future cellulose based fuel economy.

Subjects/Keywords: Biology; Molecular

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Karr, S. J. (2009). A novel approach to functional genomic studies of the superfamily of receptor-like kinases (RLKs) in Arabidopsis thaliana. (Thesis). University of California, Riverside. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=3345263

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Karr, Stephen John. “A novel approach to functional genomic studies of the superfamily of receptor-like kinases (RLKs) in Arabidopsis thaliana.” 2009. Thesis, University of California, Riverside. Accessed January 16, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=3345263.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Karr, Stephen John. “A novel approach to functional genomic studies of the superfamily of receptor-like kinases (RLKs) in Arabidopsis thaliana.” 2009. Web. 16 Jan 2021.

Vancouver:

Karr SJ. A novel approach to functional genomic studies of the superfamily of receptor-like kinases (RLKs) in Arabidopsis thaliana. [Internet] [Thesis]. University of California, Riverside; 2009. [cited 2021 Jan 16]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3345263.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Karr SJ. A novel approach to functional genomic studies of the superfamily of receptor-like kinases (RLKs) in Arabidopsis thaliana. [Thesis]. University of California, Riverside; 2009. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3345263

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Stanford University

29. Truong, Amy Bidong. Control of epidermal proliferation and differentiation by p63.

Degree: 2009, Stanford University

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=3351495

► p63 is a p53 family member consisting of six isoforms, broadly characterized by the presence (TA) or absence (ΔN) or an amino-terminal transactivation domain.… (more)

▼ p63 is a p53 family member consisting of six isoforms, broadly characterized by the presence (TA) or absence (ΔN) or an amino-terminal transactivation domain. The generation of p63 null mice revealed the importance of p63 function in the development of ectodermally-derived structures and stratified epithelial tissue, including the epidermis. However, less is known about the requirement for p63 in tissue regeneration and the mechanisms by which p63 functions to promote cell proliferation. To investigate p63 function in a post-developmental context, we used siRNAs directed against p63 to downregulate p63 expression in regenerating human epidermis. Loss of p63 resulted in severe tissue hypoplasia and inhibited both stratification and differentiation in a cell-autonomous manner. Isoform-specific knockdown revealed that ΔNp63 isoforms are the main mediators of p63 effects; however, TAp63 isoforms may contribute to late differentiation. p63-deficient cells exhibited hypo-proliferation that was accompanied by an increase in p53 activity. Simultaneous p63 and p53 knockdown rescued the hypoplasia of p63-deficient tissue, suggesting that p63 and p53 antagonize each other to control keratinocyte proliferation. Combined p63 and p53 loss failed to restore differentiation, however, indicating that p63's effects on epidermal proliferation and differentiation are controlled by distinct mechanisms. To discover other potential downstream mediators of p63 function, we integrated expression profiling of p63-deficient cells with chromatin immunoprecipitation data characterizing direct p63 targets on a genome-wide scale. This approach identified c-Myc as a novel mediator of p63 function, and we confirmed that p63 binds within the c-Myc promoter to directly regulate its expression. Downregulation of c-Myc recapitulated the proliferation defect and a subset of gene expression changes observed with p63 knockdown, whereas overexpression of c-Myc in the context of p63 loss was able to partially rescue these effects. We determined that p53 and c-Myc function in distinct pathways downstream of p63 in regulating cell proliferation. Our results extend the importance of p63 in maintaining the proliferative and differentiation potential of developmentally mature human keratinocytes and identify two downstream mediators of p63 function.

Subjects/Keywords: Biology; Molecular

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Truong, A. B. (2009). Control of epidermal proliferation and differentiation by p63. (Thesis). Stanford University. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=3351495

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Truong, Amy Bidong. “Control of epidermal proliferation and differentiation by p63.” 2009. Thesis, Stanford University. Accessed January 16, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=3351495.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Truong, Amy Bidong. “Control of epidermal proliferation and differentiation by p63.” 2009. Web. 16 Jan 2021.

Vancouver:

Truong AB. Control of epidermal proliferation and differentiation by p63. [Internet] [Thesis]. Stanford University; 2009. [cited 2021 Jan 16]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3351495.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Truong AB. Control of epidermal proliferation and differentiation by p63. [Thesis]. Stanford University; 2009. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3351495

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Georgetown University

30. Thomas, Kelly Jean. Pten-induced kinase 1 (PINK1) and its role in mitochondrial function and dynamics.

Degree: 2009, Georgetown University

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=3356110

► Parkinson disease (PD) is a neurodegenerative disorder with progressive loss of dopaminergic neurons in the substantia nigra. The majority of PD cases involve the… (more)

▼ Parkinson disease (PD) is a neurodegenerative disorder with progressive loss of dopaminergic neurons in the substantia nigra. The majority of PD cases involve the sporadic form with unknown etiology, but mitochondrial dysfunction and oxidative stress are considered to play a role in disease pathogenesis. The discoveries of the genes parkin, PINK1 and DJ-1 that are linked to familial forms of parkinsonism have provided insight into the molecular mechanisms that cause disease. Recent findings implicate mitochondrial dysfunction associated with oxidative damage as a key molecular mechanism that compromises dopaminergic neurons in familial parkinsonism. Studies within this thesis characterize the mitochondrial function of PINK1 in human neuroblastoma cells. PINK1 prevents cell death mediated by mitochondrial toxins that inhibit complex one of the respiratory chain, which in turn contributes to oxidative stress. PINK1 protects against oxidative stress and secondary mitochondrial dysfunction; therefore, the role of PINK1 in mitochondrial function and morphology was further investigated. Mitochondria are dynamic organelles that undergo the antagonizing events of fusion and fission. While fusion of mitochondrial membranes promotes cell survival, mitochondrial fission is associated with apoptosis. Defects in mitochondrial membrane potential influence mitochondrial morphology in PINK1 deficient cells shifting phenotypes towards Dynamin-related protein 1 (Drp1)-mediated fission. PINK1 silencing results in mitochondrial fission by enhancing calcineurin activity, which promotes mitochondrial fragmentation via Drp1 dephosphorylation and increased Drp1 GTPase activity. Exogenous expression of parkin in PINK1 deficient cells rescues mitochondrial fission, which confirms that PINK1 and parkin genetically interact to regulate mitochondrial morphology. Cells deficient in parkin or DJ-1 phenocopy PINK1 silencing and exhibit mitochondrial fission. Dephosphorylation of Drp1 is enhanced in DJ-1 deficient cells, suggesting that modulation of fission machinery may be dependent upon the generation of oxidative stress. PINK1, parkin and DJ-1 all act individually to limit the effects of agents that induce oxidative stress and trigger mitochondrial fission. Expression of PINK1 or parkin in DJ-1 deficient cells rescues mitochondrial phenotypes associated with DJ-1 silencing, which suggests DJ-1 lies upstream of the PINK1/parkin pathway to inhibit mitochondrial fission. These studies suggest that oxidative stress can influence mitochondrial shape, structure and function, which might contribute to parkinsonian phenotypes.

Subjects/Keywords: Biology; Molecular

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Thomas, K. J. (2009). Pten-induced kinase 1 (PINK1) and its role in mitochondrial function and dynamics. (Thesis). Georgetown University. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=3356110

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Thomas, Kelly Jean. “Pten-induced kinase 1 (PINK1) and its role in mitochondrial function and dynamics.” 2009. Thesis, Georgetown University. Accessed January 16, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=3356110.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Thomas, Kelly Jean. “Pten-induced kinase 1 (PINK1) and its role in mitochondrial function and dynamics.” 2009. Web. 16 Jan 2021.

Vancouver:

Thomas KJ. Pten-induced kinase 1 (PINK1) and its role in mitochondrial function and dynamics. [Internet] [Thesis]. Georgetown University; 2009. [cited 2021 Jan 16]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3356110.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Thomas KJ. Pten-induced kinase 1 (PINK1) and its role in mitochondrial function and dynamics. [Thesis]. Georgetown University; 2009. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3356110

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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Open Access Theses and Dissertations