+publisher:"Cornell University" +contributor:("Parrish, Colin Ross")

Cornell University

1. Fischer, Amanda. The Role Of Receptor-Induced Conformational Changes In Feline Calicivirus Infectious Entry.

Degree: M.S., Veterinary Medicine, Veterinary Medicine, 2014, Cornell University

► Despite 30 years of vaccination the prevalence of feline calicivirus (FCV) infection remains the same, at 30%. This is due to the high variability of… (more)

Subjects/Keywords: calicivirus lifecycle; calicivirus biology; non-enveloped viral entry

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APA (6^th Edition):

Fischer, A. (2014). The Role Of Receptor-Induced Conformational Changes In Feline Calicivirus Infectious Entry. (Masters Thesis). Cornell University. Retrieved from http://hdl.handle.net/1813/36046

Chicago Manual of Style (16^th Edition):

Fischer, Amanda. “The Role Of Receptor-Induced Conformational Changes In Feline Calicivirus Infectious Entry.” 2014. Masters Thesis, Cornell University. Accessed March 04, 2021. http://hdl.handle.net/1813/36046.

MLA Handbook (7^th Edition):

Fischer, Amanda. “The Role Of Receptor-Induced Conformational Changes In Feline Calicivirus Infectious Entry.” 2014. Web. 04 Mar 2021.

Vancouver:

Fischer A. The Role Of Receptor-Induced Conformational Changes In Feline Calicivirus Infectious Entry. [Internet] [Masters thesis]. Cornell University; 2014. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1813/36046.

Council of Science Editors:

Fischer A. The Role Of Receptor-Induced Conformational Changes In Feline Calicivirus Infectious Entry. [Masters Thesis]. Cornell University; 2014. Available from: http://hdl.handle.net/1813/36046

Cornell University

2. Tse, Long Ping Victor. Sequence And Structure Of Influenza Hemagglutinin Cleavage Site Modulate Viral Pathogenesis.

Degree: PhD, Microbiology, 2014, Cornell University

URL: http://hdl.handle.net/1813/36116

► Viruses are obligatory intracellular pathogens requiring host machinery for survival and reproduction. Differing from living organisms, which can grow where nutrients are available, viruses absolutely… (more)

▼ Viruses are obligatory intracellular pathogens requiring host machinery for survival and reproduction. Differing from living organisms, which can grow where nutrients are available, viruses absolutely require hijacking of host machineries to complete their life cycle. Enveloped viruses evolved to have dedicated strategies to passively sense environmental cues to ensure that initiation of infection occurs at the correct moment and place. One general strategy used by enveloped viruses is to precisely control activation of their envelope glycoprotein just prior entry into host cells. Influenza A virus (AIV) is the causative agent of influenza illness and causes both economical and public health problems globally and annually. As a successful pathogen infecting a wide range of animals, IAV excels in sensing the environment to ensure efficient infection by employing two sequential activating steps during viral entry: proteolytic cleavage for priming of the hemagglutinin (HA) and low-pH-triggered conformational changes allowing release of the fusion peptide. Proteolytic cleavage of influenza HA controls viral pathogenesis by influencing viral growth rate and viral tropism. The primary sequence and tertiary structure of the HA determine the overall properties of HA activation and hence, viral pathogenesis. Mutations on the primary sequence of the HA cleavage site affect viral activation in two dimensions, 1) HA activation efficiency and 2) alteration in protease repertoire for HA activation. The former modulates viral growth kinetics and the later is important for viral tropism. Mutations that modifies HA tertiary structure also play an important role in viral activation, in particular virus growth. In this thesis, I describe three interrelated studies of mutations on primary and tertiary structure of HA and their consequence on HA cleavage and viral pathogenesis. These mutations also allow influenza virus to interact with prokaryotic pathogens and open up another dimension in virus-bacteria-host interactions and synergy. Advisors/Committee Members: Whittaker, Gary R (chair), Crane, Brian (committee member), Parrish, Colin Ross (committee member).

Subjects/Keywords: Influenza HA activation; Proteases; Pathogenesis

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APA (6^th Edition):

Tse, L. P. V. (2014). Sequence And Structure Of Influenza Hemagglutinin Cleavage Site Modulate Viral Pathogenesis. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/36116

Chicago Manual of Style (16^th Edition):

Tse, Long Ping Victor. “Sequence And Structure Of Influenza Hemagglutinin Cleavage Site Modulate Viral Pathogenesis.” 2014. Doctoral Dissertation, Cornell University. Accessed March 04, 2021. http://hdl.handle.net/1813/36116.

MLA Handbook (7^th Edition):

Tse, Long Ping Victor. “Sequence And Structure Of Influenza Hemagglutinin Cleavage Site Modulate Viral Pathogenesis.” 2014. Web. 04 Mar 2021.

Vancouver:

Tse LPV. Sequence And Structure Of Influenza Hemagglutinin Cleavage Site Modulate Viral Pathogenesis. [Internet] [Doctoral dissertation]. Cornell University; 2014. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1813/36116.

Council of Science Editors:

Tse LPV. Sequence And Structure Of Influenza Hemagglutinin Cleavage Site Modulate Viral Pathogenesis. [Doctoral Dissertation]. Cornell University; 2014. Available from: http://hdl.handle.net/1813/36116

Cornell University

3. Ray, Gregory. Arabidopsis Thaliana Syta As A Model To Address Whether Synaptotagmin Proteins Function As Dimers Or Tetramers.

Degree: PhD, Molecular and Cell Biology, 2014, Cornell University

URL: http://hdl.handle.net/1813/37059

► The Arabidopsis thaliana synaptotagmin SYTA (AT2G20990) regulates endocytosis at the plasma membrane and virus movement protein-mediated cellto-cell movement. As with all synaptotagmin proteins, SYTA is… (more)

▼ The Arabidopsis thaliana synaptotagmin SYTA (AT2G20990) regulates endocytosis at the plasma membrane and virus movement protein-mediated cellto-cell movement. As with all synaptotagmin proteins, SYTA is predicted to consist of a transmembrane domain, a cytosolic variable domain, and two calcium/lipid binding domains (C2A and C2B) at its COOH-terminus. Deletion of the C2B domain abolishes SYTA function. The C2B deleted mutant of SYTA also acts as a dominant-negative mutant as evidenced by its interference with endogenous, wild-type SYTA. This finding is consistent with the unproven hypothesis that synaptotagmin proteins in animals potentially function as dimers or tetramers. However, the existence of a SYTA C2B domain in plants that is functionally similar to those in animal synaptotagmins has been questioned by some research groups. In this project, I utilized molecular modeling to predict how a homodimer of SYTA may function, and cell-based functional assays and in vitro biochemical approaches to demonstrate the relevance of the model I created. I modeled SYTA-C2B to explain how the C2B domains from the individual proteins within a dimer could function to bind calcium. I demonstrated that key residues from this model (E430, D431, and E433) were functionally relevant by expressing alanine point mutants of each in protoplasts and observing that they did not localize to endosomes effectively. My research was consistent with the prediction that E430 and D431 are essential for SYTA function, possibly forming the core of a calcium-binding site. Although it is not essential in this activity, I also concluded that E433 may improve the calciumsensing ability of C2B. By utilizing dynamic and static light scattering, I observed that purified SYTA is a dimer, which indicated calcium binding via the C2B domain is not required for the formation of this dimer. This research is the first direct observation of a synaptotagmin protein, plant or animal, forming a dimer. Advisors/Committee Members: Lazarowitz, Sondra Gale (chair), Vogt, Volker M (committee member), Parrish, Colin Ross (committee member).

Subjects/Keywords: Synaptotagmin; Endocytosis; SYTA

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APA (6^th Edition):

Ray, G. (2014). Arabidopsis Thaliana Syta As A Model To Address Whether Synaptotagmin Proteins Function As Dimers Or Tetramers. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/37059

Chicago Manual of Style (16^th Edition):

Ray, Gregory. “Arabidopsis Thaliana Syta As A Model To Address Whether Synaptotagmin Proteins Function As Dimers Or Tetramers.” 2014. Doctoral Dissertation, Cornell University. Accessed March 04, 2021. http://hdl.handle.net/1813/37059.

MLA Handbook (7^th Edition):

Ray, Gregory. “Arabidopsis Thaliana Syta As A Model To Address Whether Synaptotagmin Proteins Function As Dimers Or Tetramers.” 2014. Web. 04 Mar 2021.

Vancouver:

Ray G. Arabidopsis Thaliana Syta As A Model To Address Whether Synaptotagmin Proteins Function As Dimers Or Tetramers. [Internet] [Doctoral dissertation]. Cornell University; 2014. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1813/37059.

Council of Science Editors:

Ray G. Arabidopsis Thaliana Syta As A Model To Address Whether Synaptotagmin Proteins Function As Dimers Or Tetramers. [Doctoral Dissertation]. Cornell University; 2014. Available from: http://hdl.handle.net/1813/37059

Cornell University

4. Dalziel, Benjamin. The Influence Of Collective Animal Movement On Population Dynamics.

Degree: PhD, Ecology, 2014, Cornell University

URL: http://hdl.handle.net/1813/37026

► Many populations exhibit collective behavior, where interactions among nearby individuals scale up to cause emergent patterns in the behavior of groups, as in the coordinated… (more)

▼ Many populations exhibit collective behavior, where interactions among nearby individuals scale up to cause emergent patterns in the behavior of groups, as in the coordinated movement of a flock of birds or a school of fish. Populations influenced by collective behavior violate the assumption of mass action that underlies most ecological models, in which individuals are viewed as statistically independent. However, the ecological significance of collective behavior is not well understood, because studies have been limited to populations where high throughput ethological data is available, such as in the laboratory or in computer simulations. This dissertation tests for the signal of collective behavior in ecological data-data on the distribution patterns of organisms collected on a coarser spatial and temporal scale than the underlying processes-and examines the influence of collective behavior on population dynamics. Data on the locations of migratory caribou (collected every five days by satellite tracking collars) are shown to be generated by two distinct processes. The first process creates broad-scale spatiotemporal order in movement patterns, and is likely driven by seasonally and spatially fluctuating environmental and physiological cues. The second process creates finer-scale order that is likely due to behavioral interactions among nearby individuals. The strength of alignment in the velocities of nearby individuals varies systematically with time of year, suggesting that collective behavior can be a dynamic property of migratory populations. The dissertation then considers collective mobility patterns in humans, analyzing census data on the commuting patterns of workers in Canadian cities. The level of order in commuting patterns varies systematically among cities. In particular, in some cities a disproportionate number of workers travel to work in a few focal locations. Simulations of the spread of a respiratory infection in each city predict differences among cities in the risk of an epidemic, due to systematic variation in the level of order in the commuting patterns of workers. In particular, larger cities tend to be more highly organized and, as a result, have a disproportionately higher probability of sparking an epidemic. The dissertation then explores the role of large cities in supporting the emergence of a new strain of influenza in dogs. The analysis combines demographic data on animal shelters in the United States, molecular data from the pathogen and seroprevalence estimates from the literature to show that large animal shelters in major metropolitan areas function as endemic reservoirs for the virus, facilitating sporadic outbreaks in the wider population. In sum the dissertation research shows that collective behavior can sometimes be detected and characterized in ecological data without recourse to fine-scale behavioral observations, and that collective behavior can significantly alter population dynamics at broad spatial and temporal scales. Advisors/Committee Members: Ellner, Stephen Paul (chair), Parrish, Colin Ross (committee member), Hooker, Giles J. (committee member), Geber, Monica Ann (committee member).

Subjects/Keywords: collective behavior; population dynamics; epidemic model

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APA (6^th Edition):

Dalziel, B. (2014). The Influence Of Collective Animal Movement On Population Dynamics. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/37026

Chicago Manual of Style (16^th Edition):

Dalziel, Benjamin. “The Influence Of Collective Animal Movement On Population Dynamics.” 2014. Doctoral Dissertation, Cornell University. Accessed March 04, 2021. http://hdl.handle.net/1813/37026.

MLA Handbook (7^th Edition):

Dalziel, Benjamin. “The Influence Of Collective Animal Movement On Population Dynamics.” 2014. Web. 04 Mar 2021.

Vancouver:

Dalziel B. The Influence Of Collective Animal Movement On Population Dynamics. [Internet] [Doctoral dissertation]. Cornell University; 2014. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1813/37026.

Council of Science Editors:

Dalziel B. The Influence Of Collective Animal Movement On Population Dynamics. [Doctoral Dissertation]. Cornell University; 2014. Available from: http://hdl.handle.net/1813/37026

Cornell University

5. Kim, Boram. The Role Of Mater In Cytoplasmic Lattice Formation, Endoplasmic Reticulum Distribution, And Calcium Homeostasis In Mouse Oocytes.

Degree: PhD, Veterinary Medicine, 2013, Cornell University

URL: http://hdl.handle.net/1813/33817

► Ca2+ oscillation is hallmark of mammalian fertilization that is thought to mediate egg activation process, and dramatic targeting of the endoplasmic reticulum (ER) to the… (more)

▼ Ca2+ oscillation is hallmark of mammalian fertilization that is thought to mediate egg activation process, and dramatic targeting of the endoplasmic reticulum (ER) to the microvillar subcortex, is known to provide calcium pools for subsequent activation and embryo development. While the mechanisms by which Ca2+ oscillation govern later embryonic development are poorly understood, emerging evidences indicate the critical role of Ca2+ oscillation in embryonic development, for example, by regulating recruitment of maternal mRNAs. Mater (Nlrp5) and Padi6 are oocyte-and early embryo-restricted maternal effect genes that are required for embryonic development beyond the 2-cell stage. Interestingly, PADI6 localizes to, and is required for the formation of oocyte-specific structure termed cytoplasmic lattices (CPLs). Based on similarity between MATER and PADI6, we hypothesized that MATER is also required for CPL formation. Indeed, ultrastructural analysis of Matertm/tm oocytes show ~90% reduced volume of CPLs and immuno-EM demonstrates the localization of MATER to CPLs, indicating MATER as a component of CPLs. Interestingly, Tubulin was also identified as a CPL component and that Tubulin interacts with PADI6. Given that Tubulin drives organelle movement, the role of Tubulin-PADI6-CPLs in organelle distribution during oocyte maturation was demonstrated. Given above observations, we further hypothesized that Mater plays a role in ER distribution and function, Ca2+ homeostasis in oocytes. We first investigated ER distribution by microinjecting DiI into oocytes and found that, as opposed to WT oocytes, the ER in metaphase-II Matertm/tm oocytes failed to concentrate around the spindle and cortical clusters were reduced. As cortical clusters are thought to be important for Ca2+ oscillation, then we tested if the pattern of Ca2+ oscillation is altered in Matertm/tm oocytes after in vitro fertilization. Intriguingly, Matertm/tm oocytes show altered Ca2+ oscillation pattern, lower amplitude and higher frequency. Then we demonstrated the reduced amount of intracellular Ca2+ stores in Matertm/tm oocytes, in part, contribute to such phenotype. Finally, the localization of IP3R-I, an essential player in releasing Ca2+ from ER, was altered in supporting of ER distribution. Taken together, this observation support the hypothesis that MATER is required for CPL formation and is involved in ER distribution and Ca2+ homeostasis in oocytes. Advisors/Committee Members: Coonrod, Scott A. (chair), Schimenti, John C. (committee member), Parrish, Colin Ross (committee member), Clark, Theodore G. (committee member).

Subjects/Keywords: MATER; cytoplasmic lattice; calcium homeostasis

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APA (6^th Edition):

Kim, B. (2013). The Role Of Mater In Cytoplasmic Lattice Formation, Endoplasmic Reticulum Distribution, And Calcium Homeostasis In Mouse Oocytes. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/33817

Chicago Manual of Style (16^th Edition):

Kim, Boram. “The Role Of Mater In Cytoplasmic Lattice Formation, Endoplasmic Reticulum Distribution, And Calcium Homeostasis In Mouse Oocytes.” 2013. Doctoral Dissertation, Cornell University. Accessed March 04, 2021. http://hdl.handle.net/1813/33817.

MLA Handbook (7^th Edition):

Kim, Boram. “The Role Of Mater In Cytoplasmic Lattice Formation, Endoplasmic Reticulum Distribution, And Calcium Homeostasis In Mouse Oocytes.” 2013. Web. 04 Mar 2021.

Vancouver:

Kim B. The Role Of Mater In Cytoplasmic Lattice Formation, Endoplasmic Reticulum Distribution, And Calcium Homeostasis In Mouse Oocytes. [Internet] [Doctoral dissertation]. Cornell University; 2013. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1813/33817.

Council of Science Editors:

Kim B. The Role Of Mater In Cytoplasmic Lattice Formation, Endoplasmic Reticulum Distribution, And Calcium Homeostasis In Mouse Oocytes. [Doctoral Dissertation]. Cornell University; 2013. Available from: http://hdl.handle.net/1813/33817

Cornell University

6. Pennington, Matthew Robert. Repurposing the human immunodeficiency virus (HIV) integrase inhibitor raltegravir for the treatment of felid alphaherpesvirus 1 (FHV-1) ocular infection.

Degree: PhD, Immunology and Infectious Disease, 2018, Cornell University

URL: http://hdl.handle.net/1813/59803

► Herpesviruses infect many species, inducing a wide range of diseases. Herpesvirus-induced ocular disease, which may lead to blindness, commonly occurs in humans, dogs, and cats,… (more)

▼ Herpesviruses infect many species, inducing a wide range of diseases. Herpesvirus-induced ocular disease, which may lead to blindness, commonly occurs in humans, dogs, and cats, and is caused by human alphaherpesvirus 1 (HHV-1), canid alphaherpesvirus (CHV-1), and felid alphaherpesvirus 1 (FHV-1), respectively. Rapid and effective antiviral therapy is of the utmost importance to control infection in order to preserve the vision of infected people or animals. However, current treatment options are suboptimal, in large part due to the difficulty and cost of de novo drug development and the lack of effective models to bridge work in in vitro cell cultures and in vivo. Repurposing currently approved drugs for viral infections is one strategy to more rapidly identify new therapeutics. Furthermore, studying ocular herpesviruses in cats is of particular importance, as this condition is a frequent disease manifestation in these animals and FHV-1 infection of the cat is increasingly being recognized as a valuable natural-host model of herpesvirus-induced ocular infection First, the current models to study ocular herpesvirus infections were reviewed. Next, the efficacy of raltegravir was evaluated using a novel corneal explant model. Raltegravir is a human immunodeficiency virus (HIV) integrase inhibitor that was recently shown to poses antiviral activity against human herpesviruses. Then, electric cell-substrate impedance sensing (ECIS) was evaluated as a novel methodology to study the replication kinetics of herpesviruses. It was also used to characterize a fluorescently labeled FHV-1, created using CRISPR/Cas9 genome. Next, it was found that raltegravir inhibits both viral DNA synthesis initiation and late gene expression, a mechanism consistent with inhibition of viral ICP8. Finally, RNA sequencing was used to explore the indirect effects of raltegravir on the host. It was found that raltegravir treatment promoted the expression of anti-angiogenic factors and altered the metabolism of the host cells, both of which may be beneficial therapeutically. These results, combined with a recent in vivo study in experimentally infected cats, demonstrates that raltegravir is a viable treatment option for FHV-1 and warrants further investigations into its clinical potential against other herpesviruses. Advisors/Committee Members: Van de Walle, Gerlinde (chair), Parrish, Colin Ross (committee member), Wagner, Bettina (committee member), Ledbetter, Eric C. (committee member).

Subjects/Keywords: Veterinary science; electric cell-substrate impedance sensing (ECIS); explant; Felid alphaherpesvirus (FHV-1); ICP8; ocular herpesvirus; raltegravir; Virology

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APA (6^th Edition):

Pennington, M. R. (2018). Repurposing the human immunodeficiency virus (HIV) integrase inhibitor raltegravir for the treatment of felid alphaherpesvirus 1 (FHV-1) ocular infection. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/59803

Chicago Manual of Style (16^th Edition):

Pennington, Matthew Robert. “Repurposing the human immunodeficiency virus (HIV) integrase inhibitor raltegravir for the treatment of felid alphaherpesvirus 1 (FHV-1) ocular infection.” 2018. Doctoral Dissertation, Cornell University. Accessed March 04, 2021. http://hdl.handle.net/1813/59803.

MLA Handbook (7^th Edition):

Pennington, Matthew Robert. “Repurposing the human immunodeficiency virus (HIV) integrase inhibitor raltegravir for the treatment of felid alphaherpesvirus 1 (FHV-1) ocular infection.” 2018. Web. 04 Mar 2021.

Vancouver:

Pennington MR. Repurposing the human immunodeficiency virus (HIV) integrase inhibitor raltegravir for the treatment of felid alphaherpesvirus 1 (FHV-1) ocular infection. [Internet] [Doctoral dissertation]. Cornell University; 2018. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1813/59803.

Council of Science Editors:

Pennington MR. Repurposing the human immunodeficiency virus (HIV) integrase inhibitor raltegravir for the treatment of felid alphaherpesvirus 1 (FHV-1) ocular infection. [Doctoral Dissertation]. Cornell University; 2018. Available from: http://hdl.handle.net/1813/59803

Cornell University

7. Ortved, Kyla. Aav-Mediated Dual-Axis Gene Therapy To Enhance Cartilage Repair.

Degree: PhD, Veterinary Medicine, 2014, Cornell University

URL: http://hdl.handle.net/1813/38859

► The aim of this thesis project was to investigate the use of a recombinant adenoassociated virus (rAAV) as a gene therapy vector to target both… (more)

▼ The aim of this thesis project was to investigate the use of a recombinant adenoassociated virus (rAAV) as a gene therapy vector to target both the anabolic and catabolic axes of cartilage homeostasis in order to enhance cartilage repair capabilities and prevent joint degradation. The specific aims of the research were to 1) evaluate healing of full-thickness chondral defects in femoral trochlear ridges repaired with autologous chondrocytes transduced ex vivo with an rAAV5 vector overexpressing the anabolic protein, insulin-like growth factor I (IGF-I); 2) investigate the impact of post-transcriptional silencing of interleukin-1[beta] (IL-1[beta]) mediated by rAAV2 expressing a short hairpin IL-1[beta] silencing motif in chondrocytes cultured in an osteoarthritic model and; 3) elucidate the humoral and cellmediated immune response, and its impact on transgene expression, following direct intraarticular (IA) injection of rAAV2 and rAAV5 overexpressing IGF-I. Autologous chondrocytes transduced ex vivo with rAAV5-IGF-I were arthroscopically implanted, in a fibrin vehicle, into 15mm diameter full-thickness chondral defects created in the lateral trochlear ridges of horses. Transgene expression was assessed by serially quantifying IGF-I concentration in the synovial fluid. Defect healing was assessed arthroscopically at 8 weeks post-implantation. Long-term healing at 8 months post- implantation was assessed using gross, histological, immunohistochemical, and biochemical parameters. rAAV5-IGF-I treated defects had improved short and long-term healing with improved tissue architecture and collagen type II content compared to defects repaired with naïve chondrocytes. Transduction of chondrocytes with rAAV2 expressing a short hairpin IL-1[beta] led to significantly reduced IL-1[beta] mRNA expression following stimulation with lipopolysaccharide (LPS). Down-regulation of additional key catabolic cytokines and degradative enzymes, including tumor necrosis factor (TNF)-[alpha] and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, was also seen in transduced cultures. Posttranscriptional silencing of IL-1[beta] appeared to limit the catabolic cascade seen in cartilage following LPS simulation. Direct intra-articular injection of rAAV2- and rAAV5-IGF-I led to prolonged transgene expression without any significant local joint inflammation. Carpal joints injected with rAAV5-IGF-I had significantly higher levels of IGF-I in the synovial fluid compared to rAAV2-IGF-I despite a more robust and diverse humoral immune response to AAV5. A cellmediated immune response was not noted in either treatment group. Advisors/Committee Members: Nixon, Alan J (chair), Wagner, Bettina (committee member), Brooks, Samantha A. (committee member), Mohammed, Hussni Omar (committee member), Parrish, Colin Ross (committee member).

Subjects/Keywords: Gene therapy; Cartilage repair; Adeno-associated virus

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APA (6^th Edition):

Ortved, K. (2014). Aav-Mediated Dual-Axis Gene Therapy To Enhance Cartilage Repair. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/38859

Chicago Manual of Style (16^th Edition):

Ortved, Kyla. “Aav-Mediated Dual-Axis Gene Therapy To Enhance Cartilage Repair.” 2014. Doctoral Dissertation, Cornell University. Accessed March 04, 2021. http://hdl.handle.net/1813/38859.

MLA Handbook (7^th Edition):

Ortved, Kyla. “Aav-Mediated Dual-Axis Gene Therapy To Enhance Cartilage Repair.” 2014. Web. 04 Mar 2021.

Vancouver:

Ortved K. Aav-Mediated Dual-Axis Gene Therapy To Enhance Cartilage Repair. [Internet] [Doctoral dissertation]. Cornell University; 2014. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1813/38859.

Council of Science Editors:

Ortved K. Aav-Mediated Dual-Axis Gene Therapy To Enhance Cartilage Repair. [Doctoral Dissertation]. Cornell University; 2014. Available from: http://hdl.handle.net/1813/38859

Cornell University

8. Cavatorta, Derek. Phenotypic And Functional Characterization Of Equine Monocyte-Derived Dendritic Cells.

Degree: PhD, Immunology, 2012, Cornell University

URL: http://hdl.handle.net/1813/31007

► This dissertation was motivated by the desire to further our understanding of the immune response to vaccination and with the hope of promoting the development… (more)

▼ This dissertation was motivated by the desire to further our understanding of the immune response to vaccination and with the hope of promoting the development of improved vaccine strategies. These studies have focused on the equine dendritic cell (DC) because of the important role this cell plays in initiating the immune response; DCs are unique in their ability to optimally sensitize naïve T cells and are capable of promoting the development of a range of effector T cell phenotypes. In particular, the phenotypic and functional characteristics of the equine monocytederived DC were characterized. Monocyte-derived DCs and macrophages were stimulated with UV-inactivated Escherichia coli (E. coli) and monitored for cell surface marker expression, cytokine production, and endocytic capacity. The resulting alterations in DC activation state were characterized, and the differences between DCs and macrophages were further defined. These findings contribute to our knowledge of equine DCs and demonstrate that, although non-stimulated DCs consist of a mixed population of mature and immature cells, DC maturation can be measured following induction by bacterial stimuli. A method for characterizing DC function was also developed. Relatively pure populations of equine monocyte-derived DCs were co-cultured with autologous, 5,6carboxyfluorescein diacetate succinimidyl ester (CFSE)-stained peripheral blood T cells. Multi- color flow cytometry was used to measure antigen-specific T cell proliferation, surface-marker expression, and cytokine production. The DC-induced T cell response was characterized in response to both self-antigen and vaccine antigen. These experiments confirmed the potent antigen-presenting capabilities of equine DCs, which validates their immunotherapeutic potential and supports their use as a cellular vaccine adjuvant. This system also permitted the use of DCs to study fundamental immunological processes in vitro. These findings contribute to our knowledge of the equine immune system and demonstrate the value of DCs as a research tool. A lymphoscintigraphic procedure for identifying the vaccine-draining lymph node in the horse was also established. This technique will facilitate the study of the anti-vaccine immune response and encourage the development of improved vaccination strategies, such as those using DC-based adjuvants. Advisors/Committee Members: Flaminio, Maria Julia Bevilaqua Felippe (chair), Holowka, David Allan (committee member), Clark, Theodore G. (committee member), Parrish, Colin Ross (committee member).

Subjects/Keywords: Equine Immunology; Dendritic Cell; Lymphoscintigraphy

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APA (6^th Edition):

Cavatorta, D. (2012). Phenotypic And Functional Characterization Of Equine Monocyte-Derived Dendritic Cells. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/31007

Chicago Manual of Style (16^th Edition):

Cavatorta, Derek. “Phenotypic And Functional Characterization Of Equine Monocyte-Derived Dendritic Cells.” 2012. Doctoral Dissertation, Cornell University. Accessed March 04, 2021. http://hdl.handle.net/1813/31007.

MLA Handbook (7^th Edition):

Cavatorta, Derek. “Phenotypic And Functional Characterization Of Equine Monocyte-Derived Dendritic Cells.” 2012. Web. 04 Mar 2021.

Vancouver:

Cavatorta D. Phenotypic And Functional Characterization Of Equine Monocyte-Derived Dendritic Cells. [Internet] [Doctoral dissertation]. Cornell University; 2012. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1813/31007.

Council of Science Editors:

Cavatorta D. Phenotypic And Functional Characterization Of Equine Monocyte-Derived Dendritic Cells. [Doctoral Dissertation]. Cornell University; 2012. Available from: http://hdl.handle.net/1813/31007

Cornell University

9. Callaway, Heather. PARVOVIRUS CAPSID STRUCTURES, LIGAND BINDING INTERACTIONS, AND ENDOGENOUS VIRAL ELEMENTS.

Degree: PhD, Immunology and Infectious Disease, 2018, Cornell University

URL: http://hdl.handle.net/1813/59633

► Parvoviruses are among the simplest of viruses, with capsids composed of variants of a single structural protein. These capsids mediate many of the processes required… (more)

▼ Parvoviruses are among the simplest of viruses, with capsids composed of variants of a single structural protein. These capsids mediate many of the processes required for infection and are remarkably stable. However, antibody binding or mutations to the capsid can disrupt these processes and block infection. This dissertation discusses mutations to the canine parvovirus (CPV) capsid that result in loss of infection, the interaction between CPV and the transferrin receptor (TfR), and parvovirus endogenous viral elements (EVEs), which contain ancient parvovirus gene sequences. I found that point mutations to CPV VP2 residues 270, 272, 273, and 299/300 result in loss of viral infectivity. Mutation of residue 270 results in loss of a sub-molar proteolytic cleavage event in VP2 and increases capsid stability, residue 272 mutation causes loss of capsid assembly, and residue 273 mutation results in assembled capsids being trapped in the nucleus. Mutation of VP2 residues 299 and 300, which are associated with TfR binding, to lysine disrupts the interaction between CPV and the TfR, inhibiting infection but still allowing receptor binding and uptake into cells. I also found that CPV has different interactions with TfRs from different host species, binding strongly to some TfRs and very weakly to others, even though each TfR can mediate a successful infection. TfRs from different species also had varying levels of occupancy on CPV capsids, with up to 12 black-backed jackal TfRs, but only 1-2 feline TfRs binding to each capsid, and it is possible that the feline TfR induces a conformational change in CPV that inhibits binding of additional TfRs. Antibody binding could also disrupt the CPV/TfR binding interaction, suggesting a possible mechanism of virus neutralization. To examine the structure and function of ancient parvovirus capsids, I expressed the VP2 gene from three different parvovirus EVEs. VP2 expressed from an EVE in the M. spretus genome assembled into capsids, and I determined that these capsids were highly stable, could bind to N-Acetylneuraminic acid, and were endocytosed into murine cells. The results in this dissertation provide new information about parvovirus infection, receptor binding interactions, and evolution, and further the understanding of how infection occurs and may be disrupted. Advisors/Committee Members: Parrish, Colin Ross (chair), Whittaker, Gary R. (committee member), Nicholson, Linda K. (committee member), Wagner, Bettina (committee member).

Subjects/Keywords: Biophysics; Biochemistry; canine parvovirus; endogenous viral element; parvovirus; receptor binding; transferrin receptor; virus structure; Virology

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

APA (6^th Edition):

Callaway, H. (2018). PARVOVIRUS CAPSID STRUCTURES, LIGAND BINDING INTERACTIONS, AND ENDOGENOUS VIRAL ELEMENTS. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/59633

Chicago Manual of Style (16^th Edition):

Callaway, Heather. “PARVOVIRUS CAPSID STRUCTURES, LIGAND BINDING INTERACTIONS, AND ENDOGENOUS VIRAL ELEMENTS.” 2018. Doctoral Dissertation, Cornell University. Accessed March 04, 2021. http://hdl.handle.net/1813/59633.

MLA Handbook (7^th Edition):

Callaway, Heather. “PARVOVIRUS CAPSID STRUCTURES, LIGAND BINDING INTERACTIONS, AND ENDOGENOUS VIRAL ELEMENTS.” 2018. Web. 04 Mar 2021.

Vancouver:

Callaway H. PARVOVIRUS CAPSID STRUCTURES, LIGAND BINDING INTERACTIONS, AND ENDOGENOUS VIRAL ELEMENTS. [Internet] [Doctoral dissertation]. Cornell University; 2018. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1813/59633.

Council of Science Editors:

Callaway H. PARVOVIRUS CAPSID STRUCTURES, LIGAND BINDING INTERACTIONS, AND ENDOGENOUS VIRAL ELEMENTS. [Doctoral Dissertation]. Cornell University; 2018. Available from: http://hdl.handle.net/1813/59633

Cornell University

10. Harbison, Carole. Receptor Binding And Early Steps Of Cellular Infection By Parvoviruses.

Degree: PhD, Veterinary Medicine, 2011, Cornell University

URL: http://hdl.handle.net/1813/29255

► Parvoviruses are small, non-enveloped, single stranded DNA viruses. The specific attributes of the capsid and genome dictate how the virus interacts with the environment and… (more)

▼ Parvoviruses are small, non-enveloped, single stranded DNA viruses. The specific attributes of the capsid and genome dictate how the virus interacts with the environment and the host cell in terms of transmission, tissue tropism, anti-viral immunity, and disease states. A major focus of these studies is viral entry into host cells. During infection, the parvovirus capsid hijacks cellular pathways to reach the nucleus for genome replication. Receptor binding is critical for determining host range and tissue tropism, and various receptors are utilized by different parvoviruses. However, the intracellular trafficking pathways followed by viruses after endocytosis are poorly understood. Chapter 2 examines the dynamic nature of parvoviral uptake and entry by wild type viruses, while chapter 3 examines the ability of these viruses to use variant receptors for uptake and infection. In addition to successfully navigating entry into host cells, parvoviruses must survive in the environment and evade host defenses. Humoral immunity plays a particularly important role in the control of these viruses. This is a benefit as vaccination is generally successful in controlling parvoviral disease, but is a challenge that must be overcome in the development of adeno-associated viruses as gene therapy vectors. The studies that follow expand our knowledge about the interaction of antibodies with a newly described variant of CPV in raccoons, RPV-2 (Chapter 4) and the adenoassociated virus capsid (Chapter 5). One final aspect of parvoviral biology addressed in this work is how changes in host range, antigenicity, and receptor interactions have evolved with small numbers of capsid changes in these closely related viruses. The trafficking studies in chapters 2 and 3 were performed within this contextual framework to examine the differences in the interactions of FPV and CPV with host cells. Chapter 4 describes the phylogenetic origin, host range, and receptor binding properties of several recently characterized parvovirus strains isolated from raccoons, and places this animal as an important intermediate host in the evolution of CPV. Finally, two of the more dissimilar serotypes of AAV were examined in Chapter 5 to look at the interaction of antibodies with capsids displaying somewhat different surface features. Advisors/Committee Members: Parrish, Colin Ross (chair), Brown, William J (committee member), Flaminio, Maria Julia Bevilaqua Felippe (committee member), Denkers, Eric Young (committee member).

Subjects/Keywords: Virus Entry; Virus Evolution; Anti-viral Immunity

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

APA (6^th Edition):

Harbison, C. (2011). Receptor Binding And Early Steps Of Cellular Infection By Parvoviruses. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/29255

Chicago Manual of Style (16^th Edition):

Harbison, Carole. “Receptor Binding And Early Steps Of Cellular Infection By Parvoviruses.” 2011. Doctoral Dissertation, Cornell University. Accessed March 04, 2021. http://hdl.handle.net/1813/29255.

MLA Handbook (7^th Edition):

Harbison, Carole. “Receptor Binding And Early Steps Of Cellular Infection By Parvoviruses.” 2011. Web. 04 Mar 2021.

Vancouver:

Harbison C. Receptor Binding And Early Steps Of Cellular Infection By Parvoviruses. [Internet] [Doctoral dissertation]. Cornell University; 2011. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1813/29255.

Council of Science Editors:

Harbison C. Receptor Binding And Early Steps Of Cellular Infection By Parvoviruses. [Doctoral Dissertation]. Cornell University; 2011. Available from: http://hdl.handle.net/1813/29255

11. Dick, Robert. Interaction Between Retroviral Gag Proteins And Membranes.

Degree: PhD, Biochemistry, 2013, Cornell University

URL: http://hdl.handle.net/1813/34182

► Assembly of an infectious retroviral particle (virion) involves a set of events, including multimerization of thousands of Gag proteins, packaging of two copies of genomic… (more)

▼ Assembly of an infectious retroviral particle (virion) involves a set of events, including multimerization of thousands of Gag proteins, packaging of two copies of genomic RNA, and Gag interaction with the plasma membrane. While each of these events can be thought of as discrete, they are dependent on one another. The Gag polyprotein has three major domains: the N-terminal membrane-binding domain (MA), the central assembly domain (CA), and the C-terminal nucleic acid (or genomic RNA) binding domain (NC). According to one model for formation of virions, NC binds to genomic RNA, which promotes Gag multimerization, which in turn enhances membrane interactions. The work described in this thesis focuses on two aspects of this model, the response of Gag to lipids with different head groups and acyl chains, and the effect of multimerization of Gag on its interaction with membranes. In a comparative study of Rous sarcoma virus (RSV) and human immunodeficiency virus type-1 (HIV-1) Gag, we found that, unlike HIV-1 Gag, RSV Gag was not dependent on the lipid phosphatidylinositol-4,5-phosphate (PI(4,5)P2) for membrane interaction and virus release in vivo. However, both Gag proteins had a similar response to mono-, di, and tri-phosphorylated phosphatidylinositols (PIPs) by an in vitro liposome flotation assay. I interpret these findings to suggest that in addition to the specific interaction reported for HIV-1 Gag, PIPs enhance Gag membrane binding electrostatically. In a follow-up study I found that increasing the concentration of phosphatidylserine (PS) in the membrane resulted in dramatically more HIV-1 Gag binding, and this response to PS was modulated by the lipid acyl chains. Also, the presence of cholesterol in the membrane significantly increased the amount of Gag associated with the liposomes. I interpret these results to mean that Gag can sense the hydrophobic core of the lipid bilayer. To determine the effect of Gag multimerization on its binding to membranes, monomeric, dimeric, and hexameric MA chimeras were tested. In vivo and in vitro, increasing the multimeric state of MA increased its localization to the plasma membrane and to liposomes. These findings suggest that Gag binding to the plasma membrane is enhanced by multimerization. Advisors/Committee Members: Vogt, Volker M (chair), Parrish, Colin Ross (committee member), Ke, Ailong (committee member).

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

APA (6^th Edition):

Dick, R. (2013). Interaction Between Retroviral Gag Proteins And Membranes. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/34182

Chicago Manual of Style (16^th Edition):

Dick, Robert. “Interaction Between Retroviral Gag Proteins And Membranes.” 2013. Doctoral Dissertation, Cornell University. Accessed March 04, 2021. http://hdl.handle.net/1813/34182.

MLA Handbook (7^th Edition):

Dick, Robert. “Interaction Between Retroviral Gag Proteins And Membranes.” 2013. Web. 04 Mar 2021.

Vancouver:

Dick R. Interaction Between Retroviral Gag Proteins And Membranes. [Internet] [Doctoral dissertation]. Cornell University; 2013. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1813/34182.

Council of Science Editors:

Dick R. Interaction Between Retroviral Gag Proteins And Membranes. [Doctoral Dissertation]. Cornell University; 2013. Available from: http://hdl.handle.net/1813/34182

Open Access Theses and Dissertations