subject:(Biology Cell)

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 April 21, 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. 21 Apr 2021.

Vancouver:

Hofman EG. Plasma membrane organization during EGFR signaling: a FRET-based analysis. [Internet] [Doctoral dissertation]. Universiteit Utrecht; 2008. [cited 2021 Apr 21]. 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

University of Helsinki

2. Puhka, Maija. Morphogenesis of Mammalian Endoplasmic Reticulum and Golgi Apparatus throughout the Cell Cycle.

Degree: Department of Biosciences, Division of Biochemistry, 2011, University of Helsinki

URL: http://hdl.handle.net/10138/23908

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The endoplasmic reticulum (ER) and the Golgi apparatus are organelles that produce, modify and transport proteins and lipids and regulate Ca2+ environment within cells. Structurally… (more)

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The endoplasmic reticulum (ER) and the Golgi apparatus are organelles that produce, modify and transport proteins and lipids and regulate Ca2+ environment within cells. Structurally they are composed of sheets and tubules. Sheets may take various forms: intact, fenestrated, single or stacked. The ER, including the nuclear envelope, is a single continuous network, while the Golgi shows only some level of connectivity. It is often unclear, how different morphologies correspond to particular functions. Previous studies indicate that the structures of the ER and Golgi are dynamic and regulated by fusion and fission events, cytoskeleton, rate of protein synthesis and secretion, and specific structural proteins. For example, many structural proteins shaping tubular ER have been identified, but sheet formation is much more unclear. In this study, we used light and electron microscopy to study morphological changes of the ER and Golgi in mammalian cells. The proportion, type, location and dynamics of ER sheets and tubules were found to vary in a cell type or cell cycle stage dependent manner. During interphase, ER and Golgi structures were demonstrated to be regulated by p37, a cofactor of the fusion factor p97, and microtubules, which also affected the localization of the organelles. Like previously shown for the Golgi, the ER displayed a tendency for fenestration and tubulation during mitosis. However, this shape change did not result in ER fragmentation as happens to Golgi, but a continuous network was retained. The activity of p97/p37 was found to be important for the reassembly of both organelles after mitosis. In EM images, ER sheet membranes appear rough, since they contain attached ribosomes, whereas tubular membranes appear smooth. Our studies revealed that structural changes of the ER towards fenestrated and tubular direction correlate with loss of ER-bound ribosomes and vice versa. High and low curvature ER membranes have a low and high density of ribosomes, respectively. To conclude, both ER and Golgi architecture depend on fusion activity of p97/p37. ER morphogenesis, particularly of the sheet shape, is intimately linked to the density of membrane bound ribosomes.

Endoplasmakalvosto (ER) ja Golgi ovat organelleja, jotka tuottavat, muokkaavat ja kuljettavat proteiineja ja lipidejä sekä säätelevät kalsiumin oikeaa pitoisuutta solun sisällä. Ne koostuvat putkimaisista ja laattarakenteista, jotka voivat olla ehjiä, reikiintyneitä, yksittäisiä tai pinoutuneita. ER, johon kuuluu myös tumakalvo, on yksi yhtenäinen verkosto, kun taas Golgissa on erillisiä alaosastoja ja siis vähemmän verkostoitumista. Erilaisten rakenteiden ajatellaan tukevan erityisiä toimintoja. Useimpien rakenteiden kohdalla on kuitenkin epäselvää, mitkä toiminnot niissä sijaitsevat tai miten rakenne palvelee ko. toimintoa. Aiemmissa tutkimuksissa on todettu, että ER ja Golgi ovat dynaamisia ja niiden rakennetta muovaavat erilaiset kalvoston fuusio- ja fissiotapahtumat, solun tukiranka, proteiinituotanto ja eritys sekä rakenneproteiinit.…

Subjects/Keywords: cell Biology; cell Biology

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

APA (6^th Edition):

Puhka, M. (2011). Morphogenesis of Mammalian Endoplasmic Reticulum and Golgi Apparatus throughout the Cell Cycle. (Doctoral Dissertation). University of Helsinki. Retrieved from http://hdl.handle.net/10138/23908

Chicago Manual of Style (16^th Edition):

Puhka, Maija. “Morphogenesis of Mammalian Endoplasmic Reticulum and Golgi Apparatus throughout the Cell Cycle.” 2011. Doctoral Dissertation, University of Helsinki. Accessed April 21, 2021. http://hdl.handle.net/10138/23908.

MLA Handbook (7^th Edition):

Puhka, Maija. “Morphogenesis of Mammalian Endoplasmic Reticulum and Golgi Apparatus throughout the Cell Cycle.” 2011. Web. 21 Apr 2021.

Vancouver:

Puhka M. Morphogenesis of Mammalian Endoplasmic Reticulum and Golgi Apparatus throughout the Cell Cycle. [Internet] [Doctoral dissertation]. University of Helsinki; 2011. [cited 2021 Apr 21]. Available from: http://hdl.handle.net/10138/23908.

Council of Science Editors:

Puhka M. Morphogenesis of Mammalian Endoplasmic Reticulum and Golgi Apparatus throughout the Cell Cycle. [Doctoral Dissertation]. University of Helsinki; 2011. Available from: http://hdl.handle.net/10138/23908

University of Helsinki

3. Weber-Boyvat, Marion. Functional role of the Mso1p-Sec1p complex in membrane fusion regulation.

Degree: Department of Biosciences, Division of Genetics; Institute of Biotechnology, 2011, University of Helsinki

URL: http://hdl.handle.net/10138/24311

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Sec1/Munc18 (SM) protein family members are evolutionary conserved proteins. They perform an essential, albeit poorly understood function in SNARE complex formation in membrane fusion. In… (more)

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Sec1/Munc18 (SM) protein family members are evolutionary conserved proteins. They perform an essential, albeit poorly understood function in SNARE complex formation in membrane fusion. In addition to the SNARE complex components, only a few SM protein binding proteins are known. Typically, their binding modes to SM proteins and their contribution to the membrane fusion regulation is poorly characterised. We identified Mso1p as a novel Sec1p interacting partner. It was shown that Mso1p and Sec1p interact at sites of polarised secretion and that this localisation is dependent on the Rab GTPase Sec4p and its GEF Sec2p. Using targeted mutagenesis and N- and C-terminal deletants, it was discovered that the interaction between an N-terminal peptide of Mso1p and the putative Syntaxin N-peptide binding area in Sec1p domain 1 is important for membrane fusion regulation. The yeast Syntaxin homologues Sso1p and Sso2p lack the N-terminal peptide. Our results show that in addition to binding to the putative N-peptide binding area in Sec1p, Mso1p can interact with Sso1p and Sso2p. This result suggests that Mso1p can mimic the N-peptide binding to facilitate membrane fusion. In addition to Mso1p, a novel role in membrane fusion regulation was revealed for the Sec1p C-terminal tail, which is missing in its mammalian homologues. Deletion of the Sec1p-tail results in temperature sensitive growth and reduced sporulation. Using in vivo and in vitro experiments, it was shown that the Sec1p-tail mediates SNARE complex binding and assembly. These results propose a regulatory role for the Sec1p-tail in SNARE complex formation. Furthermore, two novel interaction partners for Mso1p, the Rab GTPase Sec4p and plasma membrane phospholipids, were identified. The Sec4p link was identified using Bimolecular Fluorescence Complementation assays with Mso1p and the non-SNARE binding Sec1p(1-657). The assay revealed that Mso1p can target Sec1p(1-657) to sites of secretion. This effect is mediated via the Mso1p C-terminus, which previously has been genetically linked to Sec4p. These results and in vitro binding experiments suggest that Mso1p acts in cooperation with the GTP-bound form of Sec4p on vesicle-like structures prior to membrane fusion. Mso1p shares homology with the PIP2 binding domain of the mammalian Munc18 binding Mint proteins. It was shown both in vivo and in vitro that Mso1p is a phospholipid inserting protein and that this insertion is mediated by the conserved Mso1p amino terminus. In vivo, the Mso1p phospholipid binding is needed for sporulation and Mso1p-Sec1p localisation at the sites of secretion at the plasma membrane. The results reveal a novel layer of membrane fusion regulation in exocytosis and propose a coordinating role for Mso1p in connection with membrane lipids, Sec1p, Sec4p and SNARE complexes in this process.

Sec1/Munc18 (SM) perheen jäsenet ovat hyvin evoluutiossa säilyneitä, mutta toiminnallisesti huonosti tunnettuja solunsisäisille kalvofuusiotapahtumille välttämättömiä proteiineja. SM proteiinit säätelevät…

Subjects/Keywords: cell biology; cell biology

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

APA (6^th Edition):

Weber-Boyvat, M. (2011). Functional role of the Mso1p-Sec1p complex in membrane fusion regulation. (Doctoral Dissertation). University of Helsinki. Retrieved from http://hdl.handle.net/10138/24311

Chicago Manual of Style (16^th Edition):

Weber-Boyvat, Marion. “Functional role of the Mso1p-Sec1p complex in membrane fusion regulation.” 2011. Doctoral Dissertation, University of Helsinki. Accessed April 21, 2021. http://hdl.handle.net/10138/24311.

MLA Handbook (7^th Edition):

Weber-Boyvat, Marion. “Functional role of the Mso1p-Sec1p complex in membrane fusion regulation.” 2011. Web. 21 Apr 2021.

Vancouver:

Weber-Boyvat M. Functional role of the Mso1p-Sec1p complex in membrane fusion regulation. [Internet] [Doctoral dissertation]. University of Helsinki; 2011. [cited 2021 Apr 21]. Available from: http://hdl.handle.net/10138/24311.

Council of Science Editors:

Weber-Boyvat M. Functional role of the Mso1p-Sec1p complex in membrane fusion regulation. [Doctoral Dissertation]. University of Helsinki; 2011. Available from: http://hdl.handle.net/10138/24311

University of Helsinki

4. Dopie, Joseph. Nucleocytoplasmic transport mechanism for actin.

Degree: Department of Biosciences, Genetics, 2014, University of Helsinki

URL: http://hdl.handle.net/10138/44990

► Actin controls numerous nuclear events including transcription factor activity, chromatin remodeling and RNA polymerase activity. As a component of the cytoskeleton in the cytoplasm, actin… (more)

▼ Actin controls numerous nuclear events including transcription factor activity, chromatin remodeling and RNA polymerase activity. As a component of the cytoskeleton in the cytoplasm, actin traditionally influences cell motility, cell division, cell shape and intracellular transport. In the cytoplasm, actin-binding proteins (ABPs) regulate the dynamic interplay between actin polymerization into filaments and depolymerization into monomers, a process that is central to the cytoplasmic functions of actin. Details of the nuclear functions of actin are unclear and it remains unknown whether actin polymerization and depolymerization in the nucleus is directly linked to the nuclear functions of actin. Many cytoplasmic ABPs have also been identified in the nucleus and shown to influence gene expression, yet their nuclear function in relation to actin is not clear. Actin utilizes an active mechanism to exit the nucleus, however, the nuclear import mechanism for actin has not been characterized. This work provides evidence to support an active nuclear shuttling mechanism for actin and identify novel regulators of nuclear actin. Our live cell imaging data show that actin actively and constantly shuttles between the nucleus and the cytoplasm. Using RNA interference (RNAi) mediated loss-of-function analysis, we show that unphosphorylated cofilin, an ABP, and importin 9, a member of the karyopherin β family of transport receptors, are required for nuclear localization of actin. Protein interaction experiments show that importin 9, cofilin and actin form an import complex that mediates nuclear localization of actin to promote efficient transcriptional activity. Our genome-wide RNAi screens have identified novel and conserved regulators of nucleocytoplasmic transport of actin. Notably, we identified cell division cycle (CDC)73, also known as parafibromin, a component of the RNA polymerase II associated factor homolog (PAF)1 complex and cyclin-dependent kinase 13 (CDK13), a protein that controls cell fate, as regulators of nuclear export of actin. On the other hand our data implicate protein kinase activated gamma subunit 1 (PRKAG1), a regulatory subunit of the AMP-activated protein kinase (AMPK) and RAB18, a member of the ras-related protein family, as factors that promote nuclear import of actin. Also, we identify novel regulators of cofilin phosphorylation that influence nuclear localization of actin. These include; Capping protein B (CPB), an actin filament barbed end capping protein; shibire (SHI)/dynamin, involved in endocytosis; BTB and CNC homology 2 (BACH2), a Pox virus and Zinc finger domain-containing transcriptional regulator; receptor for protein kinase C 1 (RACK1) and structure-specific recognition protein (SSRP), a member of the facilitates chromatin transcription (FACT) complex. BACH2 promotes cofilin dephosphorylation via repression of Lim kinase (LIMK) and testis-specific kinase (TESK) expression, while CPB promotes cofilin dephosphorylation via activation of the expression of slingshot. This study has thus…

Subjects/Keywords: cell Biology; cell Biology

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APA (6^th Edition):

Dopie, J. (2014). Nucleocytoplasmic transport mechanism for actin. (Doctoral Dissertation). University of Helsinki. Retrieved from http://hdl.handle.net/10138/44990

Chicago Manual of Style (16^th Edition):

Dopie, Joseph. “Nucleocytoplasmic transport mechanism for actin.” 2014. Doctoral Dissertation, University of Helsinki. Accessed April 21, 2021. http://hdl.handle.net/10138/44990.

MLA Handbook (7^th Edition):

Dopie, Joseph. “Nucleocytoplasmic transport mechanism for actin.” 2014. Web. 21 Apr 2021.

Vancouver:

Dopie J. Nucleocytoplasmic transport mechanism for actin. [Internet] [Doctoral dissertation]. University of Helsinki; 2014. [cited 2021 Apr 21]. Available from: http://hdl.handle.net/10138/44990.

Council of Science Editors:

Dopie J. Nucleocytoplasmic transport mechanism for actin. [Doctoral Dissertation]. University of Helsinki; 2014. Available from: http://hdl.handle.net/10138/44990

Wayne State University

5. Sekhri, Palak. Regulation Of Nuclear Localization Of The Sole Sumo-Conjugating Enzyme, Ubc9.

Degree: MS, Biological Sciences, 2013, Wayne State University

URL: https://digitalcommons.wayne.edu/oa_theses/314

► The covalent and reversible conjugation of small ubiquitin-like modifier (SUMO) proteins to hundreds of different cellular proteins is catalyzed by a cascade of enzymes… (more)

▼ The covalent and reversible conjugation of small ubiquitin-like modifier (SUMO) proteins to hundreds of different cellular proteins is catalyzed by a cascade of enzymes including an E1-activating enzyme (SAE1/SAE2), an E2-conjugating enzyme (Ubc9) and multiple E3 ligases. As the only E2 enzyme for SUMO-conjugation, Ubc9 localizes mainly in the nucleus and plays an essential role in regulation of many cellular processes including cell cycle progression through mitosis, cell migration, genome stability, stress response, transcription, and nuclear transport in eukaryotic cells. It is hypothesized that the nuclear localization of Ubc9 is required for efficient sumoylation inside the nucleus because both the sole SUMO E1 enzyme and SUMO-conjugates are mainly in the nucleus. However, we still have a poor understanding of how Ubc9 is accumulated in the nucleus. Although the nuclear import receptor Importin 13 (Imp13) can mediate the nuclear import of Ubc9 using in vitro nuclear import assays, little is known about how Ubc9 nuclear localization is regulated in vivo. Here, we hypothesize that Imp13 is the major nuclear import receptor for Ubc9 and thus required for efficient global sumoylation in vivo. Consistent with this hypothesis, we found that knockdown of Imp13 by RNA interference (RNAi) causes a decrease of global sumoylation and also an increased cytoplasmic distribution of Ubc9. Furthermore, the Ubc9 mutant (R17E) with a defect in Imp13-interaction showed a significant increase of cytoplasmic distribution when compared to Ubc9 wild-type (WT). Moreover, overexpression of Imp13 greatly enhanced the nuclear localization of Ubc9-WT but not Ubc9-R17E mutant, whereas overexpression of Imp13 mutant (D426R) with a defect in Ubc9 binding could not promote the nuclear accumulation of Ubc9-WT. Lastly, we demonstrated that the Ubc9 mutants (R17E, R13A and H20D) with a defect in SUMO-binding have an elevated cytoplasmic distribution when compared to Ubc9-WT, suggesting that the non-covalent interaction between Ubc9 and SUMO is also important for Ubc9 nuclear accumulation. Hence, our results support a model that both Imp13-mediated nuclear import and the SUMO-binding activity of Ubc9 are critical for Ubc9 nuclear localization and efficient global sumoylation in mammalian cells. Advisors/Committee Members: Xiang-Dong Zhang.

Subjects/Keywords: Biology; Cell Biology

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APA (6^th Edition):

Sekhri, P. (2013). Regulation Of Nuclear Localization Of The Sole Sumo-Conjugating Enzyme, Ubc9. (Masters Thesis). Wayne State University. Retrieved from https://digitalcommons.wayne.edu/oa_theses/314

Chicago Manual of Style (16^th Edition):

Sekhri, Palak. “Regulation Of Nuclear Localization Of The Sole Sumo-Conjugating Enzyme, Ubc9.” 2013. Masters Thesis, Wayne State University. Accessed April 21, 2021. https://digitalcommons.wayne.edu/oa_theses/314.

MLA Handbook (7^th Edition):

Sekhri, Palak. “Regulation Of Nuclear Localization Of The Sole Sumo-Conjugating Enzyme, Ubc9.” 2013. Web. 21 Apr 2021.

Vancouver:

Sekhri P. Regulation Of Nuclear Localization Of The Sole Sumo-Conjugating Enzyme, Ubc9. [Internet] [Masters thesis]. Wayne State University; 2013. [cited 2021 Apr 21]. Available from: https://digitalcommons.wayne.edu/oa_theses/314.

Council of Science Editors:

Sekhri P. Regulation Of Nuclear Localization Of The Sole Sumo-Conjugating Enzyme, Ubc9. [Masters Thesis]. Wayne State University; 2013. Available from: https://digitalcommons.wayne.edu/oa_theses/314

6. Coley, Jacqueline Seki. Dopamine mediates mature monocyte migration in the context of HIV neuropathogenesis and substance abuse.

Degree: 2014, Yeshiva University

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=3580305

► Despite the effectiveness of antiretroviral therapies, CNS complications due to HIV infection persist in a significant number of HIV positive people. HIV enters the… (more)

▼ Despite the effectiveness of antiretroviral therapies, CNS complications due to HIV infection persist in a significant number of HIV positive people. HIV enters the brain within two weeks of peripheral infection by the transmigration of infected monocytes across the blood brain barrier. Once in the brain, virions are produced, which can infect other monocytes, perivascular macrophages, microglia, and astrocytes. Inflammation resulting from viral proteins and host factors continues even in the presence of antiretroviral therapy, and this chronic low level inflammation damages neurons and leads to HIV associated neurocognitive disorders. Monocytes are a major cell type involved in this inflammation, as they are the cells that initiate this neuroinflammation and perpetuate it by their continued influx into the CNS. Drug abuse and HIV infection have long been associated, and many HIV infected drug abusers exhibit worse neurocognitive impairments. A common mechanism by which drugs assert their addictive effects is by increasing extracellular dopamine in the brain. Dopamine, a major neurotransmitter involved in reward and cognition, has been shown to exacerbate and accelerate CNS disease in SIV infected macaques, and this was characterized by increased influx of monocytes into the brain. Our laboratory found that dopamine increases transmigration of monocytes across an in vitro BBB model alone and in combination with CXCL12. We hypothesized that increased dopamine in the brains of HIV infected drug abusers increases the migration of mature CD14+CD16+ monocytes once they are within the CNS. This increased migration is mediated, in part, by the activation of dopamine receptors on CD14+CD16+ monocytes, altering their motility and adhesion. This project focused on characterizing the effects of dopamine on monocyte migration. We demonstrated that monocytes express functional dopamine receptors. We also showed that dopamine increased the migration of monocytes but that the movement is not gradient dependent. Dopamine increased the adhesion of monocytes, as compared to media only. These findings suggest that in HIV infected individuals who take illicit drugs, increased CNS dopamine may increase the accumulation of monocytes around synapses of dopaminergic neurons, damaging these neurons and increasing the severity of neurocognitive impairment in HIV infected drug abusers.

Subjects/Keywords: Biology; Cell

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APA (6^th Edition):

Coley, J. S. (2014). Dopamine mediates mature monocyte migration in the context of HIV neuropathogenesis and substance abuse. (Thesis). Yeshiva University. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=3580305

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):

Coley, Jacqueline Seki. “Dopamine mediates mature monocyte migration in the context of HIV neuropathogenesis and substance abuse.” 2014. Thesis, Yeshiva University. Accessed April 21, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=3580305.

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

MLA Handbook (7^th Edition):

Coley, Jacqueline Seki. “Dopamine mediates mature monocyte migration in the context of HIV neuropathogenesis and substance abuse.” 2014. Web. 21 Apr 2021.

Vancouver:

Coley JS. Dopamine mediates mature monocyte migration in the context of HIV neuropathogenesis and substance abuse. [Internet] [Thesis]. Yeshiva University; 2014. [cited 2021 Apr 21]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3580305.

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

Council of Science Editors:

Coley JS. Dopamine mediates mature monocyte migration in the context of HIV neuropathogenesis and substance abuse. [Thesis]. Yeshiva University; 2014. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3580305

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

7. Tsang, Matthew. Modulation of retinal pigmented epithelium phagocytosis by taurine.

Degree: 2008, University of the Sciences in Philadelphia

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=1458203

► Impaired phagocytic ability of the retinal pigmented epithelial (RPE) cells and cellular swelling of the retina is a noted condition seen in disease states… (more)

Subjects/Keywords: Biology; Cell

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

APA (6^th Edition):

Tsang, M. (2008). Modulation of retinal pigmented epithelium phagocytosis by taurine. (Thesis). University of the Sciences in Philadelphia. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=1458203

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):

Tsang, Matthew. “Modulation of retinal pigmented epithelium phagocytosis by taurine.” 2008. Thesis, University of the Sciences in Philadelphia. Accessed April 21, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=1458203.

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

MLA Handbook (7^th Edition):

Tsang, Matthew. “Modulation of retinal pigmented epithelium phagocytosis by taurine.” 2008. Web. 21 Apr 2021.

Vancouver:

Tsang M. Modulation of retinal pigmented epithelium phagocytosis by taurine. [Internet] [Thesis]. University of the Sciences in Philadelphia; 2008. [cited 2021 Apr 21]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=1458203.

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

Council of Science Editors:

Tsang M. Modulation of retinal pigmented epithelium phagocytosis by taurine. [Thesis]. University of the Sciences in Philadelphia; 2008. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=1458203

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

8. Applewhite, Derek Anthony. Barbed end regulation and the formation of actin protrusive structures.

Degree: 2008, Northwestern University

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=3278031

► Barbed end regulation is critical to the formation of the actin-based protrusive structures, lamellipodia and filopodia. In this body of work we have chosen… (more)

▼ Barbed end regulation is critical to the formation of the actin-based protrusive structures, lamellipodia and filopodia. In this body of work we have chosen to focus on two main activities, filament termination by the heterodimeric Capping protein (CP) and continued filament elongation by the Ena/VASP family of proteins. We demonstrate that the transition from lamellipodia-to-filopodia is elegantly controlled by the activities of these two proteins whereby depletion of CP via siRNA leads to a hyper-filopodial phenotype but only under conditions where at least single member of the Ena/VASP family of proteins is expressed. In addition, depletion of CP led to diminution of the lamellipodia, concomitant displacement of the Arp2/3 complex, and abrogated rates lamellipodial protrusion. Through rescue experiments we demonstrated that it is the specific depletion of CP that leads these phenotypes. Furthermore we demonstrated that Ena/VASP proteins function beyond that of an anti-capper and play a key role in filopodia formation through oligomerization and capture of actin barbed ends. In doing so, we also determined that the C-terminal Ena-VASP homology-2 (EVH2) domain is the minimal domain of filiopodia formation. Furthermore, we determined that upon lamellipodial-to-filopodial transition Ena/VASP proteins change kinetics, becoming "static" at filopodia tips. Despite this "static" association with the barbed ends, Ena/VASP still allow for continuous polymerization suggesting insertional polymerization. Finally, we putatively uncovered new roles for CP and twinfilin. Localization and kinetics indicate that CP has a discrete lamellipodial distribution and short lifetime on actin barbed ends. There is also a discrepancy between CP's distribution and that of the actin barbed ends. Through perturbation of CP localization by cytochalasin D, as well as a RNAi screen we have uncovered a role for twinfilin as a "global capper" terminating the actin barbed ends not actively engaged in protrusion, while CP functions more locally.

Subjects/Keywords: Biology; Cell

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APA (6^th Edition):

Applewhite, D. A. (2008). Barbed end regulation and the formation of actin protrusive structures. (Thesis). Northwestern University. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=3278031

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):

Applewhite, Derek Anthony. “Barbed end regulation and the formation of actin protrusive structures.” 2008. Thesis, Northwestern University. Accessed April 21, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=3278031.

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

MLA Handbook (7^th Edition):

Applewhite, Derek Anthony. “Barbed end regulation and the formation of actin protrusive structures.” 2008. Web. 21 Apr 2021.

Vancouver:

Applewhite DA. Barbed end regulation and the formation of actin protrusive structures. [Internet] [Thesis]. Northwestern University; 2008. [cited 2021 Apr 21]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3278031.

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

Council of Science Editors:

Applewhite DA. Barbed end regulation and the formation of actin protrusive structures. [Thesis]. Northwestern University; 2008. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3278031

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

9. Nokes, Rita L. Rab13 regulates membrane trafficking between the trans-Golgi network and recycling endosomes in polarized epithelial cells.

Degree: 2009, Northwestern University

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=3336529

► To maintain polarity, epithelial cells continuously sort transmembrane proteins to the apical or basolateral membrane domains during biosynthetic delivery or after internalization. This thesis… (more)

Subjects/Keywords: Biology; Cell

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

APA (6^th Edition):

Nokes, R. L. (2009). Rab13 regulates membrane trafficking between the trans-Golgi network and recycling endosomes in polarized epithelial cells. (Thesis). Northwestern University. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=3336529

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):

Nokes, Rita L. “Rab13 regulates membrane trafficking between the trans-Golgi network and recycling endosomes in polarized epithelial cells.” 2009. Thesis, Northwestern University. Accessed April 21, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=3336529.

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

MLA Handbook (7^th Edition):

Nokes, Rita L. “Rab13 regulates membrane trafficking between the trans-Golgi network and recycling endosomes in polarized epithelial cells.” 2009. Web. 21 Apr 2021.

Vancouver:

Nokes RL. Rab13 regulates membrane trafficking between the trans-Golgi network and recycling endosomes in polarized epithelial cells. [Internet] [Thesis]. Northwestern University; 2009. [cited 2021 Apr 21]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3336529.

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

Council of Science Editors:

Nokes RL. Rab13 regulates membrane trafficking between the trans-Golgi network and recycling endosomes in polarized epithelial cells. [Thesis]. Northwestern University; 2009. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3336529

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

10. Frey, Tiffany Albright. Inhibition of the cholesterol biosynthetic pathway modulates the innate immune response.

Degree: 2009, The Johns Hopkins University

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=3340038

► Sepsis, which is the product of a poorly controlled inflammatory response, is a major health problem in the United States. There is not adequate… (more)

▼ Sepsis, which is the product of a poorly controlled inflammatory response, is a major health problem in the United States. There is not adequate therapy for sepsis and patient care is mainly supportive. Human clinical studies have indicated that statins, which are widely used for the treatment of hypercholesterolemia, may be beneficial in sepsis. We investigated the effect of statins on macrophage (M&phis;) CD14 expression. CD14 is the major binding site for bacterial lipopolysaccharide (LPS), which is an important mediator of gram-negative sepsis. This glycoprotein is found in both a membrane-bound form on the cell surface (mCD14) and in a soluble variant in circulation (sCD14). Treatment of RAW 264.7 M&phis;s with lovastatin resulted in elevated mCD14 levels and decreased sCD14 levels following LPS stimulation. The increase in mCD14 was dependent on depletion of the isoprenoid intermediate geranylgeranylpyrophosphate (GGPP) and subsequent inhibition of Rho GTPases, whereas the effect of lovastatin on sCD14 was not dependent on GGPP depletion alone. While increased mCD14 expression in the presence of lovastatin correlated with increased tumor necrosis factor (TNF) -α secretion, decreased release of sCD14 may result in a diminished systemic response to LPS and therefore provide a benefit to septic patients. Another inhibitor of cholesterol biosynthesis is itraconazole (ICZ), which blocks the pathway downstream of the isoprenoid intermediates, acting on lanosterol 14-α demethylase. ICZ altered both the expression and glycosylation of CD14 in RAW 264.7 M&phis;s. The effect of ICZ on glycosylation was not due to trafficking since the protein was delivered to the cell surface and released as the soluble variant. Moreover, the alternately glycosylated form of CD14 appears to be functional as indicated by increased LPS-induced TNF-α release at a CD14-specific concentration of LPS. Metabolic labeling with [2-³H]-mannose revealed that no glycoproteins with complex-modified N-glycans are being made in the presence of ICZ. This effect is not likely to be dependent on inhibition of the cholesterol biosynthetic pathway since other azole antifungals that block the cholesterol pathway did not affect glycosylation. Therefore, alterations in the glycosylation process are a novel effect of ICZ on macrophages that may have consequences for immune function.

Subjects/Keywords: Biology; Cell

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

APA (6^th Edition):

Frey, T. A. (2009). Inhibition of the cholesterol biosynthetic pathway modulates the innate immune response. (Thesis). The Johns Hopkins University. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=3340038

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):

Frey, Tiffany Albright. “Inhibition of the cholesterol biosynthetic pathway modulates the innate immune response.” 2009. Thesis, The Johns Hopkins University. Accessed April 21, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=3340038.

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

MLA Handbook (7^th Edition):

Frey, Tiffany Albright. “Inhibition of the cholesterol biosynthetic pathway modulates the innate immune response.” 2009. Web. 21 Apr 2021.

Vancouver:

Frey TA. Inhibition of the cholesterol biosynthetic pathway modulates the innate immune response. [Internet] [Thesis]. The Johns Hopkins University; 2009. [cited 2021 Apr 21]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3340038.

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

Council of Science Editors:

Frey TA. Inhibition of the cholesterol biosynthetic pathway modulates the innate immune response. [Thesis]. The Johns Hopkins University; 2009. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3340038

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

11. Brauchle, Michael. Evolution of embryonic phenotypes in rhabditid nematodes.

Degree: 2009, New York University

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=3342425

► The cell biological events that guide early embryonic development occur with great precision within species but can be quite diverse across species. How these… (more)

▼ The cell biological events that guide early embryonic development occur with great precision within species but can be quite diverse across species. How these cellular processes evolve and which molecular components underlie these changes is poorly understood. To begin to address these questions, we used two approaches. In the first approach, we systematically investigated early embryogenesis in 35 nematode species by time-lapse microscopy. We found 40 cell-biological characters that displayed phenotypic differences among the species. By tracing the evolutionary changes on the species phylogeny, we found that these characters evolved multiple times and independently of one another. Comparisons with genome-wide RNAi data from C. elegans revealed that individual aspects of the observed inter-species diversity are mirrored by single-gene phenotypes in C. elegans, thus leading to hypotheses about the specific molecular subnetworks that may have been altered during the evolution of early embryogenesis. For example, we predicted that a cell polarity module was altered during the evolution of the Protorhabditis group and showed that PAR-1, a kinase localized asymmetrically in C. elegans early embryos and many other cell types, is symmetrically localized in the one-cell stage of Protorhabditis group species. In the second approach, we used RNAi in C. briggsae, a species that displays no major phenotypic difference when compared with C. elegans during wild-type development. We tested the C. briggsae role of genes belonging to the par-network by RNAi and identified several cases where the resulting phenotypes differed between the two species. This approach identified hidden genetic variability only visible by comparing the effect of gene perturbations. Together, these results are consistent with the idea that the molecular networks underlying early embryogenesis are evolving significantly, even in cases where wild-type phenotypes are similar. They also suggest that embryogenesis comprises loosely interconnected functional modules that allow cellular events to evolve independently of one another thereby facilitating the exploration of phenotypic space.

Subjects/Keywords: Biology; Cell

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

APA (6^th Edition):

Brauchle, M. (2009). Evolution of embryonic phenotypes in rhabditid nematodes. (Thesis). New York University. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=3342425

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):

Brauchle, Michael. “Evolution of embryonic phenotypes in rhabditid nematodes.” 2009. Thesis, New York University. Accessed April 21, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=3342425.

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

MLA Handbook (7^th Edition):

Brauchle, Michael. “Evolution of embryonic phenotypes in rhabditid nematodes.” 2009. Web. 21 Apr 2021.

Vancouver:

Brauchle M. Evolution of embryonic phenotypes in rhabditid nematodes. [Internet] [Thesis]. New York University; 2009. [cited 2021 Apr 21]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3342425.

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

Council of Science Editors:

Brauchle M. Evolution of embryonic phenotypes in rhabditid nematodes. [Thesis]. New York University; 2009. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3342425

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

12. Ashworth, Todd. Differential roles for TFII-I in the cell cycle.

Degree: 2009, Sackler School of Graduate Biomedical Sciences (Tufts University)

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=3350322

► TFII-I is a ubiquitously expressed, signal induced transcription factor. TFII-I contains a number of unique structural properties that include a leucine zipper, nuclear localization… (more)

▼ TFII-I is a ubiquitously expressed, signal induced transcription factor. TFII-I contains a number of unique structural properties that include a leucine zipper, nuclear localization signal and six helix-loop-helix repeats that are conserved across species and family members. In humans, a hemizygous deletion within chromosome 7q11.23, a region that encodes for TFII-I and its structurally related family member, BEN, is associated with a neurodevelopmental disorder known as William-Beurens syndrome (WBS). While TFII-I’s role in growth factor induced proliferation is well characterized, TFII-I was recently identified as a phosphorylated constituent in a TGF-β1 phosphoproteomic screen, suggesting that it performs additional hitherto unidentified functions in a signal dependent manner. To determine if TFII-I contributes to growth arrest, we made use of the WEHI-231 B lymphoma cell line which undergoes growth arrest in response to both TGF-β1 and antigenic signaling. Due to intrinsic pathway specific mutations, WEHI-231 cells are characterized by increased nuclear levels of NFκB thereby exhibiting similar transformation characteristics as a subset of ABC derived Diffuse Large B cell Lymphomas. TFII-I knockdown results in a growth arrest defect characterized by elevated c-myc expression, decreased expression of the cell cycle inhibitory proteins p21 and p27, and defects in NFκB regulation. Therefore, TFII-I performs a crucial function in controlling NFκB specific pathways in response to cytostatic signals and further suggests that a TFII-I-NFκB regulatory network intersect during proliferation. Furthermore, given our interest in understanding how TFII-I contributes to cellular proliferation, we sought to identify additional functions and transcriptional targets during the S-G₂/M phase of the cell cycle. Posttranscriptional silencing of TFII-I results in delayed cell cycle progression throughout the S phase whereas TFII-I is dispensable for successful entry and execution of mitosis. Whole genome microarray profiling indicates that TFII-I does not transcriptionally regulate the expression of G₂/M specific genes suggesting that TFII-I performs a nontranscriptional role to promote S phase progression.

Subjects/Keywords: Biology; Cell

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

APA (6^th Edition):

Ashworth, T. (2009). Differential roles for TFII-I in the cell cycle. (Thesis). Sackler School of Graduate Biomedical Sciences (Tufts University). Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=3350322

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):

Ashworth, Todd. “Differential roles for TFII-I in the cell cycle.” 2009. Thesis, Sackler School of Graduate Biomedical Sciences (Tufts University). Accessed April 21, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=3350322.

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

MLA Handbook (7^th Edition):

Ashworth, Todd. “Differential roles for TFII-I in the cell cycle.” 2009. Web. 21 Apr 2021.

Vancouver:

Ashworth T. Differential roles for TFII-I in the cell cycle. [Internet] [Thesis]. Sackler School of Graduate Biomedical Sciences (Tufts University); 2009. [cited 2021 Apr 21]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3350322.

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

Council of Science Editors:

Ashworth T. Differential roles for TFII-I in the cell cycle. [Thesis]. Sackler School of Graduate Biomedical Sciences (Tufts University); 2009. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3350322

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

13. Hesketh, Geoffrey Graham. Cellular and molecular mechanisms of gap junction traffic in the heart.

Degree: 2009, The Johns Hopkins University

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=3357169

► Effective contraction of the heart depends on ordered action potential (AP) propagation throughout the myocardium. Disturbances in AP propagation can produce cardiac arrhythmias, which… (more)

▼ Effective contraction of the heart depends on ordered action potential (AP) propagation throughout the myocardium. Disturbances in AP propagation can produce cardiac arrhythmias, which under certain conditions can lead to cardiac arrest, and sudden cardiac death. Determination of the fundamental cellular and molecular mechanisms that contribute to disturbances in AP propagation is critical to developing a full understanding of the pathophysiology of sudden cardiac death, and rational development of novel therapeutic strategies. Most structural heart diseases are associated with increased risk of developing lethal cardiac arrhythmias. Frequently reported in cardiac disease is remodeling of cardiomyocyte gap junctions (GJs), both in number and localization. GJs are responsible for the passage of electrical current between cardiomyocytes, and are a critical parameter in determining the speed of AP propagation throughout the myocardium, also known as conduction velocity (CV). Heterogeneous changes in CV can enhance the risk of reentrant arrhythmias, a common form of arrhythmia associated with disease. Characterizing the cellular and molecular bases for GJ remodeling in structural heart disease is likely to reveal novel insights into the mechanisms of reentrant arrhythmia formation. This dissertation deals with mechanisms of GJ traffic, specifically as it may relate to the remodeling of connexin43 (Cx43)-based GJs associated with heart failure (HF). The first chapter introduces GJ structure and function, and outlines our current mechanistic understanding of GJ trafficking. The second chapter specifically deals with ultrastructural, cellular and biochemical aspects of GJ remodeling in a canine model of rapid pacing induced non-ischemic cardiomyopathy. In the third chapter, in vivo phosphorylation sites are identified within Cx43 in both normal and failing hearts. One novel phosphorylation site, Thr326, is further characterized and shown to regulate the turnover of GJs. The fourth chapter examines the functional significance of another phosphorylation site, Ser373, which is shown to regulate the targeting of Cx43 to GJs. Overall, this dissertation identifies and functionally characterizes fundamental aspects of GJ function in normal and diseased hearts. From these studies will stem further work aimed at determining the contribution of these described phenomena in arrhythmogenesis associated with cardiac disease.

Subjects/Keywords: Biology; Cell

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

APA (6^th Edition):

Hesketh, G. G. (2009). Cellular and molecular mechanisms of gap junction traffic in the heart. (Thesis). The Johns Hopkins University. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=3357169

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):

Hesketh, Geoffrey Graham. “Cellular and molecular mechanisms of gap junction traffic in the heart.” 2009. Thesis, The Johns Hopkins University. Accessed April 21, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=3357169.

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

MLA Handbook (7^th Edition):

Hesketh, Geoffrey Graham. “Cellular and molecular mechanisms of gap junction traffic in the heart.” 2009. Web. 21 Apr 2021.

Vancouver:

Hesketh GG. Cellular and molecular mechanisms of gap junction traffic in the heart. [Internet] [Thesis]. The Johns Hopkins University; 2009. [cited 2021 Apr 21]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3357169.

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

Council of Science Editors:

Hesketh GG. Cellular and molecular mechanisms of gap junction traffic in the heart. [Thesis]. The Johns Hopkins University; 2009. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3357169

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

Columbia University

14. Morris, Edward. The role of Kif4 in microtubule stabilization.

Degree: 2010, Columbia University

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=3400628

► Microtubules (MTs) are important for cell migration and differentiation. A subset of microtubules that are selectively stabilized are found in cells and these MTs… (more)

▼ Microtubules (MTs) are important for cell migration and differentiation. A subset of microtubules that are selectively stabilized are found in cells and these MTs are highly polarized. Wounded NIH-3T3 cells orient these stable microtubules towards the wound edge, in the direction of migration. The precise proteins that directly stabilize MTs are unclear but certain features are apparent. The MT-stabilization protein(s) function at the end of a stable microtubule and not along their length since the rest of the stabilized microtubule is fully able to grow and shrink when the tip of the microtubule is severed, for instance by calcium treatment. This gave rise to the model that there is a microtubule cap at the plus ends of stable microtubules in NIH-3T3 fibroblasts. Based on biochemical characterization, it was determined the cap was sensitive to ATP and this ATP sensitivity could be blocked by AMP-PNP and high concentrations of vanadate. Both of these inhibitors are weakly selective for kinesins so a kinesin was suggested to be involved. The homolog of the kinesin Kif4 in Xenopus, XKLP1, was shown to have the ability in vitro to cap MTs. I tested whether Kif4 functioned to stabilize MT in vivo. I found that Kif4 was both necessary and sufficient for microtubule stabilization in NIH-3T3 fibroblasts and that it partially localized to the ends of stable microtubules. This encouraged me to conduct further explorations. A pathway that regulates microtubule stabilization in response to lysophosphatidic acid (LPA) has been discovered in NIH-3T3 fibroblasts. LPA, acting through its receptor, activates Rho GTPase which activates the formin mDia to stabilize MTs mDia appears to act with the MT tip proteins EB1 and APC in the MT-stabilization pathway. I found that Kif4 interacted with EB1 and that knockdown of Kif4 blocked EB1 and mDia mediated microtubule stabilization, suggesting Kif4 is downstream of these two proteins, perhaps directly acting on the microtubule. I also explored the localization and dynamics of GFP-Kif4 with live cell imaging. I observed that GFP-Kif4 moved in a fashion consistent with its localization on MT plus ends and that GFP-Kif4 puncta localized to the cell periphery in a MT-dependent manner. These behaviors are consistent with the idea that Kif4 may use its motor activity to move to the ends of MTs to stabilize them. In addition I found that another kinesin, Kif3a, played a role in the other major microtubule rearrangement during cell polarization: centrosome polarization. I showed that Kif3a, but not other members of the Kinesin-II complex, was essential for centrosome polarization. The centrosome polarization activity by Kif3a and the microtubule stabilizing activity of Kif4 reveal the potential diversity of function in kinesin family members.

Subjects/Keywords: Biology; Cell

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

APA (6^th Edition):

Morris, E. (2010). The role of Kif4 in microtubule stabilization. (Thesis). Columbia University. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=3400628

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):

Morris, Edward. “The role of Kif4 in microtubule stabilization.” 2010. Thesis, Columbia University. Accessed April 21, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=3400628.

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

MLA Handbook (7^th Edition):

Morris, Edward. “The role of Kif4 in microtubule stabilization.” 2010. Web. 21 Apr 2021.

Vancouver:

Morris E. The role of Kif4 in microtubule stabilization. [Internet] [Thesis]. Columbia University; 2010. [cited 2021 Apr 21]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3400628.

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

Council of Science Editors:

Morris E. The role of Kif4 in microtubule stabilization. [Thesis]. Columbia University; 2010. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3400628

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

University of Pittsburgh

15. Yoder, Michael D. Characterization of the Shroom protein family member, Shroom4, and its role in cytoskeletal rearrangements.

Degree: 2008, University of Pittsburgh

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=3284660

► The ability of an organism to adapt to its surrounding environment is at the essence of survival. In metazoa, this ability starts at the… (more)

▼ The ability of an organism to adapt to its surrounding environment is at the essence of survival. In metazoa, this ability starts at the level of the individual cell, which utilizes a specialized set of cytoskeletal proteins to determine their overall shape and the organization of their intracellular protein complexes and organelles. During embryonic development, the dynamic nature of the actin cytoskeleton is critical for virtually all morphogenic events requiring changes in cell shape, migration, adhesion, and division. The behavior of the actin cytoskeleton is modulated by a myriad of accessory proteins. Shroom3 (Shrm3) is an actin binding protein that regulates neural tube morphogenesis by eliciting changes in cell shape through a myosin II-dependent pathway. The Shroom-related gene SHROOM4 (formerly called KIAA1202) has also been implicated in neural development, as mutations in this gene are associated with human X-linked mental retardation. To better understand the function of Shrm4 in embryonic development, the mouse Shrm4 gene was cloned and its protein product was characterized both in vivo and in vitro. Shrm4 is expressed in a wide range of tissue types during mouse development, including the vascular endothelium of the lung and the polarized epithelium of the neural tube and kidney. In endothelial cells and embryo fibroblasts, endogenous Shrm4 co-distributes with myosin II to a distinct cytoplasmic population of F-actin and ectopic expression of Shrm4 in multiple cell types enhances or induces the formation of this actin-based structure. This localization is mediated, at least in part, by the direct interaction of Shrm4 and F-actin. The actin-binding motif of mShrm4 defines a novel actin-binding element that has not yet been described in other proteins. The results described here suggest that mShrm4 is a regulator of the actin cytoskeleton and may play an important role during vertebrate development, particularly in the developing vasculature.

Subjects/Keywords: Biology; Cell

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

APA (6^th Edition):

Yoder, M. D. (2008). Characterization of the Shroom protein family member, Shroom4, and its role in cytoskeletal rearrangements. (Thesis). University of Pittsburgh. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=3284660

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):

Yoder, Michael D. “Characterization of the Shroom protein family member, Shroom4, and its role in cytoskeletal rearrangements.” 2008. Thesis, University of Pittsburgh. Accessed April 21, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=3284660.

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

MLA Handbook (7^th Edition):

Yoder, Michael D. “Characterization of the Shroom protein family member, Shroom4, and its role in cytoskeletal rearrangements.” 2008. Web. 21 Apr 2021.

Vancouver:

Yoder MD. Characterization of the Shroom protein family member, Shroom4, and its role in cytoskeletal rearrangements. [Internet] [Thesis]. University of Pittsburgh; 2008. [cited 2021 Apr 21]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3284660.

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

Council of Science Editors:

Yoder MD. Characterization of the Shroom protein family member, Shroom4, and its role in cytoskeletal rearrangements. [Thesis]. University of Pittsburgh; 2008. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3284660

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

Harvard University

16. Korol, Oksana. Dkk1 domains in heart induction and axial development in Xenopus laevis.

Degree: 2008, Harvard University

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=3312602

► This thesis investigates mechanisms of Dickkopf-1 (Dkk1) action in heart development. Dkk1 is notable for being able to initiate heart development in normally non-cardiogenic… (more)

▼ This thesis investigates mechanisms of Dickkopf-1 (Dkk1) action in heart development. Dkk1 is notable for being able to initiate heart development in normally non-cardiogenic mesoderm of Xenopus laevis and recapitulate normal program up to and including formation of a beating heart tube. Although Dkk1 is a secreted antagonist of canonical Wnt signaling pathway, its heart-forming ability may require additional signaling. Since Wnt-antagonism of Dkk1 is mediated by the C-terminal cysteine-rich domain of Dkk1 (C1), we focused in particular on Dkk1's other cysteine-rich domain, the N-terminal domain (N1). In a quantitative assay measuring Wnt activity, N1 interfered with signaling of some canonical Wnts, such as Wnt8, but much less efficiently than C1. N1's ability to interfere with Wnt8 signaling, however, did not extend to all canonical Wnts: Wnt3a was not antagonized by N1. In contrast to intact Dkk1, C1 domain alone also differentially antagonized Wnt8 and Wnt3a. Dkk1 was shown to activate cJun terminal kinase (JNK), both in Xenopus embryos and in tumor cell lines. Our studies indicate that both domains of Dkk1 can induce JNK activation in Xenopus. Previous studies have shown that injection of N1 domain did not alter gross morphology of the embryo, suggesting that N1 may be inert. In Chapter 3, I show that N1 possesses biological activity in the embryo. First, N1 cooperated with truncated bone morphogenetic protein receptor (tBR) to maintain markers of axial and prechordal mesoderm. N1 also cooperated with several Wnt antagonists in the context of BMP inhibition to expand the expression domain of markers of axial and prechordal mesoderm, as well as to increase the frequency of heart marker expression. N1 also cooperated with Wnt antagonists Crescent and C1 to increase the extent of heart marker induction in ventral marginal zone (VMZ) explants. During early stages of gastrulation, N1 altered some markers of the dorsal-ventral patterning, either alone or in combination with BMP inhibition. These data suggest that N1 possesses novel activity and that Dkk1 has to be considered not a simple Wnt antagonist but a dual-function protein.

Subjects/Keywords: Biology; Cell

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

APA (6^th Edition):

Korol, O. (2008). Dkk1 domains in heart induction and axial development in Xenopus laevis. (Thesis). Harvard University. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=3312602

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):

Korol, Oksana. “Dkk1 domains in heart induction and axial development in Xenopus laevis.” 2008. Thesis, Harvard University. Accessed April 21, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=3312602.

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

MLA Handbook (7^th Edition):

Korol, Oksana. “Dkk1 domains in heart induction and axial development in Xenopus laevis.” 2008. Web. 21 Apr 2021.

Vancouver:

Korol O. Dkk1 domains in heart induction and axial development in Xenopus laevis. [Internet] [Thesis]. Harvard University; 2008. [cited 2021 Apr 21]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3312602.

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

Council of Science Editors:

Korol O. Dkk1 domains in heart induction and axial development in Xenopus laevis. [Thesis]. Harvard University; 2008. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3312602

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

Stanford University

17. Brandman, Onn. Feedback loops shape cellular signals in space and time.

Degree: 2008, Stanford University

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=3313809

► Positive and negative feedback loops are common regulatory elements in biological signaling systems. This thesis includes a comprehensive description of feedback loops in signaling… (more)

Subjects/Keywords: Biology; Cell

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APA (6^th Edition):

Brandman, O. (2008). Feedback loops shape cellular signals in space and time. (Thesis). Stanford University. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=3313809

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):

Brandman, Onn. “Feedback loops shape cellular signals in space and time.” 2008. Thesis, Stanford University. Accessed April 21, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=3313809.

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

MLA Handbook (7^th Edition):

Brandman, Onn. “Feedback loops shape cellular signals in space and time.” 2008. Web. 21 Apr 2021.

Vancouver:

Brandman O. Feedback loops shape cellular signals in space and time. [Internet] [Thesis]. Stanford University; 2008. [cited 2021 Apr 21]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3313809.

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

Council of Science Editors:

Brandman O. Feedback loops shape cellular signals in space and time. [Thesis]. Stanford University; 2008. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3313809

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

18. O'Brien, Xian M. Innate immune functions of human polymorphonuclear leukocytes as mediated by the beta2 integrin, CR3, and modulated by beta-glucan, a fungal pathogen associated molecular pattern.

Degree: 2010, Brown University

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=3430205

► Invasive fungal infections are emerging as a significant cause of morbidity and mortality, especially among the increasing immunosuppressed patient populations. Transition to a filamentous… (more)

▼ Invasive fungal infections are emerging as a significant cause of morbidity and mortality, especially among the increasing immunosuppressed patient populations. Transition to a filamentous hyphal morphology, which is not easily cleared by phagocytosis, correlates strongly with invasiveness and virulence. This dissertation explored the effects of β-glucan, a component of the pathogenic yeast cell wall, on human polymorphonuclear leukocyte (PMN) respiratory burst, migration and mechanosensing as mediated through the β2 integrin, CR3 (αM β2 ). CR3 is a known β-glucan receptor via a lectin-like domain. These and other studies from our laboratory have shown that β-glucan accelerates chemotaxis of PMNs when added to a fibronectin (Fn) matrix. We show that immobilized β-glucan stimulates plasma membrane-associated respiratory burst, which is inhibited by Fn. β-glucan was shown to exhort its PMN priming effects through CR3 modulated in part through a system of β1-to-β2 integrin cross talk with VLA3 (α3β1) and VLA5 (α5β1). A putative mechanism through p38 MAPK and Lyn PTK is proposed. We show that PMN migration on the CR3 ligand fibrinogen is independent of substrate stiffness, unlike the β1-mediated migration of PMNs on Fn. Migration in the presence of soluble β-glucan significantly increased PMN polarity index and significantly reduced the percentage of PMNs that initiated a respiratory burst before reaching the chemoattractant source. Taken together, these data suggest that activation of β1 integrins and priming by β-glucan elaborated by a fungal infection may determine an inflammatory cell phenotype that is well suited to eliminate the virulent, filamentous form of fungi by accelerating chemotaxis towards the foci of infection while suppressing the premature release of oxidants until the neutrophil establishes direct multifocal contact with hyphae. Additionally, fluorescence resonance energy transfer (FRET) based reporter constructs for CR3 activation and avidity were generated that provide evidence for conformational changes in the cytoplasmic domains of CR3 during physiologic activation, as well priming with soluble β-glucan. We also extended this by developing a differentiated HL-60 system that allows for the tracking of CR3 dynamic regulation during relevant PMN cellular functions.

Subjects/Keywords: Biology; Cell

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APA (6^th Edition):

O'Brien, X. M. (2010). Innate immune functions of human polymorphonuclear leukocytes as mediated by the beta2 integrin, CR3, and modulated by beta-glucan, a fungal pathogen associated molecular pattern. (Thesis). Brown University. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=3430205

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):

O'Brien, Xian M. “Innate immune functions of human polymorphonuclear leukocytes as mediated by the beta2 integrin, CR3, and modulated by beta-glucan, a fungal pathogen associated molecular pattern.” 2010. Thesis, Brown University. Accessed April 21, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=3430205.

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

MLA Handbook (7^th Edition):

O'Brien, Xian M. “Innate immune functions of human polymorphonuclear leukocytes as mediated by the beta2 integrin, CR3, and modulated by beta-glucan, a fungal pathogen associated molecular pattern.” 2010. Web. 21 Apr 2021.

Vancouver:

O'Brien XM. Innate immune functions of human polymorphonuclear leukocytes as mediated by the beta2 integrin, CR3, and modulated by beta-glucan, a fungal pathogen associated molecular pattern. [Internet] [Thesis]. Brown University; 2010. [cited 2021 Apr 21]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3430205.

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

Council of Science Editors:

O'Brien XM. Innate immune functions of human polymorphonuclear leukocytes as mediated by the beta2 integrin, CR3, and modulated by beta-glucan, a fungal pathogen associated molecular pattern. [Thesis]. Brown University; 2010. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3430205

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

19. Lee, Joon S. Biophysical analysis of the zebrafish morphogen Squint.

Degree: 2009, New York University

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=3368986

► The Nodal signal Squint (Sqt) acts as a morphogen during early zebrafish embryogenesis. Quantitative live imaging of fluorescently tagged Sqt was used to investigate… (more)

Subjects/Keywords: Biology; Cell

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APA (6^th Edition):

Lee, J. S. (2009). Biophysical analysis of the zebrafish morphogen Squint. (Thesis). New York University. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=3368986

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):

Lee, Joon S. “Biophysical analysis of the zebrafish morphogen Squint.” 2009. Thesis, New York University. Accessed April 21, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=3368986.

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

MLA Handbook (7^th Edition):

Lee, Joon S. “Biophysical analysis of the zebrafish morphogen Squint.” 2009. Web. 21 Apr 2021.

Vancouver:

Lee JS. Biophysical analysis of the zebrafish morphogen Squint. [Internet] [Thesis]. New York University; 2009. [cited 2021 Apr 21]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3368986.

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

Council of Science Editors:

Lee JS. Biophysical analysis of the zebrafish morphogen Squint. [Thesis]. New York University; 2009. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3368986

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

Harvard University

20. Ebina, Wataru. Combinatorial Pathway Modulation Toward Ex Vivo Maintenance and Propagation of Hematopoietic Stem Cells.

Degree: PhD, 2016, Harvard University

URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:33493367

► Hematopoietic stem cells (HSCs) sustain continuous turnover and maintenance of all blood lineages through organismal lifespan. The extensive regenerative potential of HSCs has been harnessed… (more)

▼ Hematopoietic stem cells (HSCs) sustain continuous turnover and maintenance of all blood lineages through organismal lifespan. The extensive regenerative potential of HSCs has been harnessed in transplantation medicine to enable curative therapies for numerous life-threatening conditions that require hematological reconstitution. However, the rarity of HSCs combined with the limited availability of immunologically matched donors have constrained the utility of HSC transplantation whose success and safety depend critically on the quantity donor HSCs; therefore, ex vivo expansion of HSCs has been a highly sought after goal in HSC research. In this thesis, I present a hypothesis driven approach toward identifying cocktails of small molecules that enable ex vivo maintenance and propagation of mouse and human HSCs. Specifically, using HSCs isolated from Fgd5ZsGreen HSC-specific fluorescent reporter mice along with previously identified immunophenotypic markers, I conducted a small scale combinatorial chemical screen of developmental signaling modulators to determine a condition that would preserve immunophenotypic HSCs ex vivo. The screen led to the discovery that murine HSCs can be maintained for at least 14 days ex vivo when the basal media was supplemented with cytokines and the minimal combination of a small molecule inhibitor of TGF-β signaling and two epigenetic inhibitors, namely LSD1 inhibitor and HDAC inhibitor, which were selected based on reports that they may derepress Notch target gene expression. Additionally, metabolic optimizations led to the identification of putrescine as a critical culture supplement for promoting HSC propagation. The three chemicals identified in the murine screen were conserved in their ability to promote the ex vivo preservation of primary human HSCs. However, as presence of the two epigenetic inhibitors caused substantial growth suppression, alternative, more specific means to activate the Notch pathway were sought. To this end, I hypothesized that inhibition of IKAROS transcription factor, a repressor of Notch target gene expression, would be able to derepress Notch pathway activity and hence replace the growth suppressive epigenetic inhibitors. Indeed, substitution of the epigenetic inhibitors with an IKAROS inhibitor rescued immunophenotypic HSC propagation, and additional supplementation with UM171, a recently identified small molecule enhancer of human HSC expansion, further improved HSC yield as well as the durability of immunophenotypic preservation over prolonged culture; in sum, three compounds, namely a TGF-β inhibitor, pomalidomide, and UM171, were found to be necessary for robust ex vivo maintenance and propagation of human HSCs. At the time of writing, xenotransplantation is underway to assess the in vivo function of ex vivo cultured human HSCs. Collectively, this body of work contributed to identifying chemically defined ex vivo culture conditions supportive of murine and human HSCs while underscoring the importance of combinatorial pathway modulation for… Advisors/Committee Members: Rossi, Derrick xmlui.authority.confidence.description.cf_uncertain (advisor), Scadden, David (committee member), Ebert, Benjamin (committee member), Goodell, Margaret (committee member), Dymecki, Susan (committee member), Cardozo, David L. (committee member).

Subjects/Keywords: Biology; Cell

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APA (6^th Edition):

Ebina, W. (2016). Combinatorial Pathway Modulation Toward Ex Vivo Maintenance and Propagation of Hematopoietic Stem Cells. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:33493367

Chicago Manual of Style (16^th Edition):

Ebina, Wataru. “Combinatorial Pathway Modulation Toward Ex Vivo Maintenance and Propagation of Hematopoietic Stem Cells.” 2016. Doctoral Dissertation, Harvard University. Accessed April 21, 2021. http://nrs.harvard.edu/urn-3:HUL.InstRepos:33493367.

MLA Handbook (7^th Edition):

Ebina, Wataru. “Combinatorial Pathway Modulation Toward Ex Vivo Maintenance and Propagation of Hematopoietic Stem Cells.” 2016. Web. 21 Apr 2021.

Vancouver:

Ebina W. Combinatorial Pathway Modulation Toward Ex Vivo Maintenance and Propagation of Hematopoietic Stem Cells. [Internet] [Doctoral dissertation]. Harvard University; 2016. [cited 2021 Apr 21]. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:33493367.

Council of Science Editors:

Ebina W. Combinatorial Pathway Modulation Toward Ex Vivo Maintenance and Propagation of Hematopoietic Stem Cells. [Doctoral Dissertation]. Harvard University; 2016. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:33493367

Harvard University

21. Zeid, Rhamy. Characterization and Disruption of Cis Regulatory Elements in Cancer.

Degree: PhD, 2016, Harvard University

URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:33493536

►

Enhancers are cis regulatory elements that play key roles in the control of cell-type specific gene expression programs. In cancer, enhancer deregulation plays a key… (more)

▼

Enhancers are cis regulatory elements that play key roles in the control of cell-type specific gene expression programs. In cancer, enhancer deregulation plays a key role in maintaining gene regulatory programs that underlie an oncogenic state. This dissertation focuses on understanding and modulating aberrant enhancer activity to identify potential vulnerabilities in human cancers. These studies were empowered by evolving technologies in genome-wide measurements of enhancer factors, computational approaches, and chemical and genetic tools to disrupt enhancer function. In high-risk pediatric neuroblastoma, the transcription factor MYCN is frequently amplified and treatment options for these patients are largely ineffective thus establishing the need for improved therapeutic options. To identify previously unrecognized dependencies in neuroblastoma, we generated genome-wide maps of the active enhancer gene regulatory landscape leading to the identification of ID1 as an uncharacterized dependency in neuroblastoma. These results outline a strategy to identify alternative therapeutic avenues based on a holistic understanding of aberrant enhancer activity. While MYCN amplification is the defining feature of high-risk neuroblastoma, a detailed mechanistic understanding of oncogenic transcriptional rewiring has been stalled by a lack of genome-wide binding data. Here we present the dynamic and temporally resolved landscape of genome-wide MYCN occupancy in neuroblastoma. We find that deregulated MYCN binding at enhancers (termed enhancer invasion) is critical to maintaining the oncogenic station and identify the lineage specific transcription factor TWIST1 as a key collaborator and synthetic lethality of oncogenic MYCN. These data suggest that MYCN enhancer invasion shapes transcriptional amplification in neuroblastoma to promote tumorigenesis. The development of small molecule inhibitors of the bromodomain and extra-terminal (BET) family of proteins provides a pharmacological strategy to inhibit enhancer activity. The efficacy of BET inhibition in several cancers has prompted efforts to predict and understand mechanisms of resistance to BET inhibition. Here, we use a newly developed class of small molecules to pharmacologically induce targeted degradation of the BET family. In triple negative breast cancer, we demonstrate that targeted BET family degradation effectively overcomes BET inhibitor resistance. These studies suggest BET degradation as a strategy to overcome BET inhibitor resistance and further disrupt and dissect enhancer activity in cancer.

Medical Sciences

Advisors/Committee Members: Koehler, Angela (advisor).

Subjects/Keywords: Biology; Cell

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

APA (6^th Edition):

Zeid, R. (2016). Characterization and Disruption of Cis Regulatory Elements in Cancer. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:33493536

Chicago Manual of Style (16^th Edition):

Zeid, Rhamy. “Characterization and Disruption of Cis Regulatory Elements in Cancer.” 2016. Doctoral Dissertation, Harvard University. Accessed April 21, 2021. http://nrs.harvard.edu/urn-3:HUL.InstRepos:33493536.

MLA Handbook (7^th Edition):

Zeid, Rhamy. “Characterization and Disruption of Cis Regulatory Elements in Cancer.” 2016. Web. 21 Apr 2021.

Vancouver:

Zeid R. Characterization and Disruption of Cis Regulatory Elements in Cancer. [Internet] [Doctoral dissertation]. Harvard University; 2016. [cited 2021 Apr 21]. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:33493536.

Council of Science Editors:

Zeid R. Characterization and Disruption of Cis Regulatory Elements in Cancer. [Doctoral Dissertation]. Harvard University; 2016. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:33493536

Harvard University

22. Weglarz, Meredith. Evaluation of Voltration Approaches for Optimal Data Acquisition in Flow Cytometry.

Degree: 2018, Harvard University

URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:37945126

►

Flow cytometry is a technology widely used to analyze biophysical and biochemical characteristics of cells and small particles quickly with high sensitivity at the single… (more)

Subjects/Keywords: Biology; Cell

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APA (6^th Edition):

Weglarz, M. (2018). Evaluation of Voltration Approaches for Optimal Data Acquisition in Flow Cytometry. (Thesis). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:37945126

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):

Weglarz, Meredith. “Evaluation of Voltration Approaches for Optimal Data Acquisition in Flow Cytometry.” 2018. Thesis, Harvard University. Accessed April 21, 2021. http://nrs.harvard.edu/urn-3:HUL.InstRepos:37945126.

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

MLA Handbook (7^th Edition):

Weglarz, Meredith. “Evaluation of Voltration Approaches for Optimal Data Acquisition in Flow Cytometry.” 2018. Web. 21 Apr 2021.

Vancouver:

Weglarz M. Evaluation of Voltration Approaches for Optimal Data Acquisition in Flow Cytometry. [Internet] [Thesis]. Harvard University; 2018. [cited 2021 Apr 21]. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:37945126.

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

Council of Science Editors:

Weglarz M. Evaluation of Voltration Approaches for Optimal Data Acquisition in Flow Cytometry. [Thesis]. Harvard University; 2018. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:37945126

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

Harvard University

23. Amin, Palak Prakash. Regulation of RIPK1 Dependent Apoptosis and Necroptosis.

Degree: 2017, Harvard University

URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:37944967

►

RIPK1 is a Ser/Thr kinase critically involved in mediating multiple signaling pathways activated by TNFa. When cells are stimulated by TNFa, RIPK1 is rapidly recruited… (more)

▼

RIPK1 is a Ser/Thr kinase critically involved in mediating multiple signaling pathways activated by TNFa. When cells are stimulated by TNFa, RIPK1 is rapidly recruited to the intracellular domain of TNFR1 to form the TNF-RSC (TNF receptor signaling complex). When survival signals are limited, RIPK1 transitions to form a pro-apoptotic cytosolic complex, independently of its kinase activity. Under apoptosis-deficient conditions, RIPK1 may be activated to mediate necroptosis. On the other hand, when TNF-RSC members TAK1 or cIAP1/2 are inhibited, cells may activate a form of apoptosis mediated by RIPK1 kinase activity, termed RIPK1 dependent apoptosis, or RDA. Most studies of RIPK1 focus on its role in necroptosis, while the mechanism that mediates the activation of RIPK1 in RDA is not well understood. Here, I investigated and compared the mechanism of RIPK1 activation in RDA, apoptosis, and necroptosis and identified a unique RIPK1 activation profile in RDA. To characterize the regulation of this unique profile, I carried out a targeted siRNA screen of post-translational modification genes, including kinases, phosphatases, ubiquitin ligases and deubiquitinating enzymes for protectors and sensitizers of RDA. I identified a set of genes which selectively promoted RDA, but not TNFa/cycloheximide-induced apoptosis or necroptosis. In particular, I identified a novel E3 ligase which was recruited to the TNF-RSC to promote the modification and activation of RIPK1 in RDA. Further, I demonstrated that several known TNF-RSC components and a novel E3 ligase play a role in limiting RDA. Finally, my data revealed the existence of two distinct necroptosis initiation pathways by TNFa. Taken together, my study provides important insights into the mechanism of RIPK1 activation in RDA, and identifies a set of enzymes that uniquely modulate RIPK1 activity in RDA but not necroptosis.

Medical Sciences

Apoptosis; necroptosis; RIPK1; TNF

Advisors/Committee Members: Finley, Daniel, Wu, Hao, Fitzgerald, Katherine.

Subjects/Keywords: Biology; Cell

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APA (6^th Edition):

Amin, P. P. (2017). Regulation of RIPK1 Dependent Apoptosis and Necroptosis. (Thesis). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:37944967

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):

Amin, Palak Prakash. “Regulation of RIPK1 Dependent Apoptosis and Necroptosis.” 2017. Thesis, Harvard University. Accessed April 21, 2021. http://nrs.harvard.edu/urn-3:HUL.InstRepos:37944967.

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

MLA Handbook (7^th Edition):

Amin, Palak Prakash. “Regulation of RIPK1 Dependent Apoptosis and Necroptosis.” 2017. Web. 21 Apr 2021.

Vancouver:

Amin PP. Regulation of RIPK1 Dependent Apoptosis and Necroptosis. [Internet] [Thesis]. Harvard University; 2017. [cited 2021 Apr 21]. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:37944967.

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

Council of Science Editors:

Amin PP. Regulation of RIPK1 Dependent Apoptosis and Necroptosis. [Thesis]. Harvard University; 2017. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:37944967

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

Harvard University

24. Christie, Amanda Leigh. Pre-Clinical Assessment of MCL-1 as a Therapeutic Target in T-Cell Lymphomas.

Degree: 2018, Harvard University

URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:37945088

►

Patients with T-cell non-Hodgkin lymphoma (T-NHL) face a particularly poor prognosis and are in desperate need of improved targeted therapies and rational combination strategies, especially… (more)

Subjects/Keywords: Biology; Cell

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APA (6^th Edition):

Christie, A. L. (2018). Pre-Clinical Assessment of MCL-1 as a Therapeutic Target in T-Cell Lymphomas. (Thesis). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:37945088

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):

Christie, Amanda Leigh. “Pre-Clinical Assessment of MCL-1 as a Therapeutic Target in T-Cell Lymphomas.” 2018. Thesis, Harvard University. Accessed April 21, 2021. http://nrs.harvard.edu/urn-3:HUL.InstRepos:37945088.

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

MLA Handbook (7^th Edition):

Christie, Amanda Leigh. “Pre-Clinical Assessment of MCL-1 as a Therapeutic Target in T-Cell Lymphomas.” 2018. Web. 21 Apr 2021.

Vancouver:

Christie AL. Pre-Clinical Assessment of MCL-1 as a Therapeutic Target in T-Cell Lymphomas. [Internet] [Thesis]. Harvard University; 2018. [cited 2021 Apr 21]. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:37945088.

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

Council of Science Editors:

Christie AL. Pre-Clinical Assessment of MCL-1 as a Therapeutic Target in T-Cell Lymphomas. [Thesis]. Harvard University; 2018. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:37945088

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

25. Griner, Nicholas B. The Role of the SUPRMAM1 Locus in Responses to Ionizing Radiation and Susceptibility to Mammary Tumors.

Degree: PhD, Molecular and Cellular Biology, 2011, U of Massachusetts : PhD

URL: https://scholarworks.umass.edu/open_access_dissertations/392

► Loss of p53 function can lead to a variety of cancers, including breast cancer. Mice heterozygous for the p53 gene (designated Trp53+/-) develop spontaneous… (more)

▼ Loss of p53 function can lead to a variety of cancers, including breast cancer. Mice heterozygous for the p53 gene (designated Trp53+/-) develop spontaneous mammary tumors, but this depends on the strain background and has been linked to a locus on chromosome 7 (designated SuprMam1). Mammary tumors are common in BALB/c-Trp53+/-females, but are rare in C57BL/6-Trp53+/- mice. Prevalence of genomic instability appears to contribute to the phenotype as loss of heterozygosity (LOH) is significantly more common among tumors arising in BALB/c-Trp53+/- mice compared to C57BL/6J-Trp53+/- mice. This increased LOH in BALB/c-Trp53+/- tumors was shown to be due to recombination events. The BALB/c strain has been shown to have a deficiency in non-homologous end joining (NHEJ) of DNA double strand breaks (dsb), however, this does not account for the increase of LOH events in tumors. Our hypothesis was that BALB/c-Trp53+/- mice are more susceptible to mammary tumors due to impaired Homologous Recombination Repair (HRR) leading to LOH. Using the COMET assay, we demonstrate that dsbs persist longer in BALB/c-Trp53+/- mouse embryonic fibroblasts (MEFs) compared to C57BL/6J-Trp53+/- MEFs. Similarly, co-localization of H2AX and the homologous recombination protein RAD51 remain at dsbs longer in BALB/c-Trp53+/- MEFs compared to C57BL/6-Trp53+/- MEFs. Palb2, a gene that lies within the SuprMam1 interval and has been shown to contribute to heritable breast cancer, was chosen as an initial candidate gene. No coding SNPs or expression differences of Palb2 were found in the mammary glands between the two strains. Additional fine mapping and use of a filtering criteria in the SuprMam1 region yielded an additional 34 candidate genes. We demonstrate no significant differences in any of these genes in whole mammary glands and primary mammary epithelial cells between the two strains. Finally, using a congenic mouse strain, we demonstrate the lack of irradiation (IR) sensitivity alleles within the SuprMam1 region. These results suggest a possible defect in HRR in the BALB/c strain that is unlikely related to Palb2. The gene or genes respsonsible for increased mammary tumor incidence in the BALB/c-Trp53+/- remain to be identified. vii Advisors/Committee Members: D. Joseph Jerry, Sallie Smith Schneider, Steven J. Sandler.

Subjects/Keywords: Cell Biology

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APA (6^th Edition):

Griner, N. B. (2011). The Role of the SUPRMAM1 Locus in Responses to Ionizing Radiation and Susceptibility to Mammary Tumors. (Doctoral Dissertation). U of Massachusetts : PhD. Retrieved from https://scholarworks.umass.edu/open_access_dissertations/392

Chicago Manual of Style (16^th Edition):

Griner, Nicholas B. “The Role of the SUPRMAM1 Locus in Responses to Ionizing Radiation and Susceptibility to Mammary Tumors.” 2011. Doctoral Dissertation, U of Massachusetts : PhD. Accessed April 21, 2021. https://scholarworks.umass.edu/open_access_dissertations/392.

MLA Handbook (7^th Edition):

Griner, Nicholas B. “The Role of the SUPRMAM1 Locus in Responses to Ionizing Radiation and Susceptibility to Mammary Tumors.” 2011. Web. 21 Apr 2021.

Vancouver:

Griner NB. The Role of the SUPRMAM1 Locus in Responses to Ionizing Radiation and Susceptibility to Mammary Tumors. [Internet] [Doctoral dissertation]. U of Massachusetts : PhD; 2011. [cited 2021 Apr 21]. Available from: https://scholarworks.umass.edu/open_access_dissertations/392.

Council of Science Editors:

Griner NB. The Role of the SUPRMAM1 Locus in Responses to Ionizing Radiation and Susceptibility to Mammary Tumors. [Doctoral Dissertation]. U of Massachusetts : PhD; 2011. Available from: https://scholarworks.umass.edu/open_access_dissertations/392

University of Minnesota

26. Jaberansari, Ziba. Decellularized lung matrix as a scaffold for mouse lung stem cells.

Degree: MS, Cell biology, 2012, University of Minnesota

URL: http://purl.umn.edu/131047

►

University of Minnesota M.S. thesis. May 2012. Major: Cell biology. Advisor: Dr. Angela-Panoskaltsis-Mortari. 1 computer file (PDF);vii, 48 pages.

Decellularized tissue allows scientists to be… (more)

Subjects/Keywords: Cell biology

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

APA (6^th Edition):

Jaberansari, Z. (2012). Decellularized lung matrix as a scaffold for mouse lung stem cells. (Masters Thesis). University of Minnesota. Retrieved from http://purl.umn.edu/131047

Chicago Manual of Style (16^th Edition):

Jaberansari, Ziba. “Decellularized lung matrix as a scaffold for mouse lung stem cells.” 2012. Masters Thesis, University of Minnesota. Accessed April 21, 2021. http://purl.umn.edu/131047.

MLA Handbook (7^th Edition):

Jaberansari, Ziba. “Decellularized lung matrix as a scaffold for mouse lung stem cells.” 2012. Web. 21 Apr 2021.

Vancouver:

Jaberansari Z. Decellularized lung matrix as a scaffold for mouse lung stem cells. [Internet] [Masters thesis]. University of Minnesota; 2012. [cited 2021 Apr 21]. Available from: http://purl.umn.edu/131047.

Council of Science Editors:

Jaberansari Z. Decellularized lung matrix as a scaffold for mouse lung stem cells. [Masters Thesis]. University of Minnesota; 2012. Available from: http://purl.umn.edu/131047

27. Al Sorkhy, Mohammad. The Role of Spy1 Protein Regulation In Breast Cancer.

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

URL: http://scholar.uwindsor.ca/etd/379

► Cell growth and proliferation are tightly controlled by the cyclic regulation of the cyclin dependent kinases (Cdks). Cdks are positively regulated through interactions with regulatory… (more)

Subjects/Keywords: Biology; Cell.

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

APA (6^th Edition):

Al Sorkhy, M. (2011). The Role of Spy1 Protein Regulation In Breast Cancer. (Doctoral Dissertation). National Library of Canada. Retrieved from http://scholar.uwindsor.ca/etd/379

Chicago Manual of Style (16^th Edition):

Al Sorkhy, Mohammad. “The Role of Spy1 Protein Regulation In Breast Cancer.” 2011. Doctoral Dissertation, National Library of Canada. Accessed April 21, 2021. http://scholar.uwindsor.ca/etd/379.

MLA Handbook (7^th Edition):

Al Sorkhy, Mohammad. “The Role of Spy1 Protein Regulation In Breast Cancer.” 2011. Web. 21 Apr 2021.

Vancouver:

Al Sorkhy M. The Role of Spy1 Protein Regulation In Breast Cancer. [Internet] [Doctoral dissertation]. National Library of Canada; 2011. [cited 2021 Apr 21]. Available from: http://scholar.uwindsor.ca/etd/379.

Council of Science Editors:

Al Sorkhy M. The Role of Spy1 Protein Regulation In Breast Cancer. [Doctoral Dissertation]. National Library of Canada; 2011. Available from: http://scholar.uwindsor.ca/etd/379

Temple University

28. Zhang, Xuemei. Src Kinase Signaling Regulates Connective Tissue Growth Factor (CTGF/CCN2) Induction by Transforming Growth Factor-Beta 1 (TGF-b1) in Osteoblasts.

Degree: PhD, 2010, Temple University

URL: http://digital.library.temple.edu/u?/p245801coll10,63095

►

Anatomy

Connective tissue growth factor (CTGF/CCN2) is a cysteine rich, extracellular matrix protein that acts as an anabolic growth factor to regulate osteoblast differentiation and… (more)

▼

Anatomy

Connective tissue growth factor (CTGF/CCN2) is a cysteine rich, extracellular matrix protein that acts as an anabolic growth factor to regulate osteoblast differentiation and function. In osteoblasts, CTGF is induced by transforming growth factor beta 1 (TGF-β1) where it acts as a downstream mediator of TGF-β1 induced extracellular matrix production. The molecular mechanisms that control CTGF induction by TGF-β1 in osteoblasts are not understood. We have previously demonstrated the requirement of Src, Erk and Smad signaling for TGF-β1 induced CTGF promoter activity in primary osteoblasts, however the potential interaction among these signaling pathways in osteoblasts remains unknown. In this study, we demonstrate that CTGF is induced by TGF-β1 in rat osteosarcoma osteoblast like cells (ROS17/2.8). TGF-β1 activates Src and blocking of Src family kinases by PP2 abrogates TGF-β1 induced CTGF up-regulation. Western blot analysis revealed that primary osteoblasts and ROS 17/2.8 cells express not only Src, but also other Src family members, such as Fyn, Yes and Hck. In order to determine whether CTGF up-regulation is controlled by Src or other members, we used either kinase-dead dominant negative Src constructs in primary osteoblasts or Src siRNA in ROS17/2.8 cells to block Src function. Inactivation of Src by both kinase-dead and siRNA prevented TGF-β1 induced CTGF induction, demonstrating that TGF-β1 induced CTGF up-regulation is mediated only by Src not by other members. In addition, we also demonstrated that Erk is activated by TGF-β1 and that blocking of Erk activation using pharmacological inhibitors, PD98059 and U0126, prevents TGF-β1 induced CTGF induction, demonstrating the requirement of Erk for CTGF induction. These results prompted us to further explore the cross-talk between Src, Erk and Smads in ROS17/2.8 cells. Inhibition of Src using PP2 prevented Erk activation, demonstrating that Src is upstream of Erk. To investigate how Src and Erk regulate the canonical TGF-β1 signaling pathway, including Smad2/3 phosphorylation and nuclear translocation of activated Smads, we treated cells with TGF-β1 in the presence or absence of the Src inhibitor, PP2, or the Erk inhibitors, PD98059 or U0126. PP2 pre-treatment prevented the phosphorylation of Smad2/3 at both the SSXS motif and the linker region and consequently blocked their nuclear translocation, demonstrating that Src can regulate Smad signaling. In contrast, the Erk inhibitors did not have any effects on Smad phosphorylation and/or nuclear translocation. To examine whether Erk can modulate Smad signaling indirectly through the activation/ inactivation of required nuclear coactivators/ co-repressors that mediate Smad DNA binding, we used electro-mobility shift assays. These experiments showed that inhibition of Erk activation impaired transcriptional complex formation on the Smad binding element (SBE) and TGF- β responsive element (TRE) of the CTGF promoter, demonstrating that Erk activation is required for SBE and TRE transactivation. Taking together,…

Advisors/Committee Members: Popoff, Steven N., Barbe, Mary F., Owen, Thomas A., Safadi, Fayez F., Sanjay, Archana.

Subjects/Keywords: Biology; Cell

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

APA (6^th Edition):

Zhang, X. (2010). Src Kinase Signaling Regulates Connective Tissue Growth Factor (CTGF/CCN2) Induction by Transforming Growth Factor-Beta 1 (TGF-b1) in Osteoblasts. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,63095

Chicago Manual of Style (16^th Edition):

Zhang, Xuemei. “Src Kinase Signaling Regulates Connective Tissue Growth Factor (CTGF/CCN2) Induction by Transforming Growth Factor-Beta 1 (TGF-b1) in Osteoblasts.” 2010. Doctoral Dissertation, Temple University. Accessed April 21, 2021. http://digital.library.temple.edu/u?/p245801coll10,63095.

MLA Handbook (7^th Edition):

Zhang, Xuemei. “Src Kinase Signaling Regulates Connective Tissue Growth Factor (CTGF/CCN2) Induction by Transforming Growth Factor-Beta 1 (TGF-b1) in Osteoblasts.” 2010. Web. 21 Apr 2021.

Vancouver:

Zhang X. Src Kinase Signaling Regulates Connective Tissue Growth Factor (CTGF/CCN2) Induction by Transforming Growth Factor-Beta 1 (TGF-b1) in Osteoblasts. [Internet] [Doctoral dissertation]. Temple University; 2010. [cited 2021 Apr 21]. Available from: http://digital.library.temple.edu/u?/p245801coll10,63095.

Council of Science Editors:

Zhang X. Src Kinase Signaling Regulates Connective Tissue Growth Factor (CTGF/CCN2) Induction by Transforming Growth Factor-Beta 1 (TGF-b1) in Osteoblasts. [Doctoral Dissertation]. Temple University; 2010. Available from: http://digital.library.temple.edu/u?/p245801coll10,63095

Vanderbilt University

29. Broderick, Sarah M. Genetic Analysis of Ninjurin A, A stress-regulated potein that induces nonapoptotic cell death.

Degree: PhD, Cell and Developmental Biology, 2013, Vanderbilt University

URL: http://hdl.handle.net/1803/12192

► Ninjurins are a conserved family of transmembrane proteins that increase expression in response to injury and stress. There are few in vivo studies of Ninjurin,… (more)

Subjects/Keywords: Cell Biology

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

APA (6^th Edition):

Broderick, S. M. (2013). Genetic Analysis of Ninjurin A, A stress-regulated potein that induces nonapoptotic cell death. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/12192

Chicago Manual of Style (16^th Edition):

Broderick, Sarah M. “Genetic Analysis of Ninjurin A, A stress-regulated potein that induces nonapoptotic cell death.” 2013. Doctoral Dissertation, Vanderbilt University. Accessed April 21, 2021. http://hdl.handle.net/1803/12192.

MLA Handbook (7^th Edition):

Broderick, Sarah M. “Genetic Analysis of Ninjurin A, A stress-regulated potein that induces nonapoptotic cell death.” 2013. Web. 21 Apr 2021.

Vancouver:

Broderick SM. Genetic Analysis of Ninjurin A, A stress-regulated potein that induces nonapoptotic cell death. [Internet] [Doctoral dissertation]. Vanderbilt University; 2013. [cited 2021 Apr 21]. Available from: http://hdl.handle.net/1803/12192.

Council of Science Editors:

Broderick SM. Genetic Analysis of Ninjurin A, A stress-regulated potein that induces nonapoptotic cell death. [Doctoral Dissertation]. Vanderbilt University; 2013. Available from: http://hdl.handle.net/1803/12192

30. Vonderfecht, Tyson Reid. The two human centrin homologues in Tetrahymena have similar but distinct functions at basal bodies.

Degree: 2013, University of Colorado at Boulder

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=3598515

► The basal body is a microtubule-organizing center responsible for nucleating the cilium, a cellular structure important for a wide variety of cellular functions such… (more)

Subjects/Keywords: Biology; Cell

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

APA (6^th Edition):

Vonderfecht, T. R. (2013). The two human centrin homologues in Tetrahymena have similar but distinct functions at basal bodies. (Thesis). University of Colorado at Boulder. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=3598515

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):

Vonderfecht, Tyson Reid. “The two human centrin homologues in Tetrahymena have similar but distinct functions at basal bodies.” 2013. Thesis, University of Colorado at Boulder. Accessed April 21, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=3598515.

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

MLA Handbook (7^th Edition):

Vonderfecht, Tyson Reid. “The two human centrin homologues in Tetrahymena have similar but distinct functions at basal bodies.” 2013. Web. 21 Apr 2021.

Vancouver:

Vonderfecht TR. The two human centrin homologues in Tetrahymena have similar but distinct functions at basal bodies. [Internet] [Thesis]. University of Colorado at Boulder; 2013. [cited 2021 Apr 21]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3598515.

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

Council of Science Editors:

Vonderfecht TR. The two human centrin homologues in Tetrahymena have similar but distinct functions at basal bodies. [Thesis]. University of Colorado at Boulder; 2013. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=3598515

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