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Universidade Estadual de Campinas
1.
Vassequi-Silva, Tallita, 1985-.
Avaliação da função da MAGP-1 na trombogênese arterial: Evaluation of MAGP1 function in arterial thrombogenesis.
Degree: 2015, Universidade Estadual de Campinas
URL: http://repositorio.unicamp.br/jspui/handle/REPOSIP/314058
► Abstract: MAGP-1 is a glycoprotein present in the elastic fibers, functioning as part of the microfibrils components. Studies have shown that MAGP-1 expression is critical…
(more)
▼ Abstract: MAGP-
1 is a
glycoprotein present in the elastic fibers, functioning as part of the microfibrils components. Studies have shown that MAGP-
1 expression is critical for vascular development and is
associated with decreased interaction between integrins and the extracellular matrix in zebra fish. Also MAGP-
1 interacts with von Willebrand factor and the active form of TGF-? and BMP. In mice lacking MAGP-
1, thrombus formation is delayed, increasing the occlusion time of carotid artery despite normal blood coagulation in vitro. MAGP-containing microfibrils may play a role in hemostasis and thrombosis. In this work, we evaluated the function of MAGP-
1 and its relation to TGF-? in the arterial thrombosis process. For this purpose, we obtained and analyzed a mutated MAGP1 (VG1) protein, its participation in the arterial thrombosis formation and its interaction with important proteins in the coagulation process. We analyzed thrombus formation time in wild type and MAGP-
1-deficency mice. The potential participation of TGF-? in this process was accessed when we treated both wild type and MAGP-
1-/- mice with losartan and captopril. Besides, we evaluated the gelatinolytic activity in the arterial walls. The MAGP-
1 mutation avoided its thrombus formation time recovery, although the mutated MGP-
1 still interacting with vWF and fibronectin. Losartan and captopril were able to recover the thrombus formation time without changing blood pressure, aPTT and PT, platelet aggregation and adhesion, but increased gelatinases activity. Our results suggest that both treatments are effective in the prevention of the sub-endothelial ECM degradation, allowing the recovery of normal thrombus formation
Advisors/Committee Members: UNIVERSIDADE ESTADUAL DE CAMPINAS (CRUESP), Werneck, Claudio Chrysostomo, 1966- (advisor), Universidade Estadual de Campinas. Instituto de Biologia (institution), Programa de Pós-Graduação em Biologia Funcional e Molecular (nameofprogram), Paschoal, Sisi Marcondes (committee member), Oliva, Maria Luiza Vilela (committee member), Gadelha, Fernanda Ramos (committee member), Felisbino, Sérgio Luis (committee member).
Subjects/Keywords: Glicoproteínas associadas a microfibrila-1; Trombose arterial; Fator de crescimento transformador beta; Losartan; Captopril; Microfibril-associated glycoprotein-1; Arterial thrombosis; Transforming growth factor beta; Losartan; Captopril
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APA (6th Edition):
Vassequi-Silva, Tallita, 1. (2015). Avaliação da função da MAGP-1 na trombogênese arterial: Evaluation of MAGP1 function in arterial thrombogenesis. (Thesis). Universidade Estadual de Campinas. Retrieved from http://repositorio.unicamp.br/jspui/handle/REPOSIP/314058
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Vassequi-Silva, Tallita, 1985-. “Avaliação da função da MAGP-1 na trombogênese arterial: Evaluation of MAGP1 function in arterial thrombogenesis.” 2015. Thesis, Universidade Estadual de Campinas. Accessed January 17, 2021.
http://repositorio.unicamp.br/jspui/handle/REPOSIP/314058.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Vassequi-Silva, Tallita, 1985-. “Avaliação da função da MAGP-1 na trombogênese arterial: Evaluation of MAGP1 function in arterial thrombogenesis.” 2015. Web. 17 Jan 2021.
Vancouver:
Vassequi-Silva, Tallita 1. Avaliação da função da MAGP-1 na trombogênese arterial: Evaluation of MAGP1 function in arterial thrombogenesis. [Internet] [Thesis]. Universidade Estadual de Campinas; 2015. [cited 2021 Jan 17].
Available from: http://repositorio.unicamp.br/jspui/handle/REPOSIP/314058.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Vassequi-Silva, Tallita 1. Avaliação da função da MAGP-1 na trombogênese arterial: Evaluation of MAGP1 function in arterial thrombogenesis. [Thesis]. Universidade Estadual de Campinas; 2015. Available from: http://repositorio.unicamp.br/jspui/handle/REPOSIP/314058
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
2.
Juricek, Ludmila.
Rôles du récepteur aux hydrocarbures aromatiques (AhR) dans la structure de la myéline du système nerveux central de la souris : Roles of the aryl hydrocarbon receptor (AhR) in the myelin structure of the murine central nervous system.
Degree: Docteur es, Toxicologie, 2015, Sorbonne Paris Cité
URL: http://www.theses.fr/2015USPCB166
► Le récepteur aux hydrocarbures aromatiques (AhR) est un facteur de transcription activé par de nombreux xénobiotiques (molécules étrangères à l’organisme) qui régule l’expression d’enzymes et…
(more)
▼ Le récepteur aux hydrocarbures aromatiques (AhR) est un facteur de transcription activé par de nombreux xénobiotiques (molécules étrangères à l’organisme) qui régule l’expression d’enzymes et transporteurs permettant le métabolisme et l’élimination de ces ligands. Cette protéine exprimée dans toutes les cellules chez les vertébrés, joue un rôle majeur dans la détoxication et la protection des organismes vis à vis des molécules toxiques. Des orthologues de celle-ci ont été identifiés chez les invertébrés mais ne semblent pas jouer le même rôle; ils sont exprimés principalement dans des neurones et ne sont pas activés par des polluants. L’absence du AhR chez ces organismes entraîne au niveau cellulaire, des défauts de morphologie dendritique et sur le plan comportemental, des anomalies dans le comportement de nutrition. Malgré ces découvertes, peu de recherches ont été entreprises sur les conséquences d’une invalidation du AhR sur le fonctionnement du système nerveux central chez les vertébrés. Au cours de ma thèse, j’ai étudié ces conséquences au niveau moléculaire, cellulaire et comportemental: les souris AhR KO développent un nystagmus pendulaire horizontal dont l’origine est en partie liée à des défauts structuraux de la gaine de myéline. Au niveau moléculaire, nous avons mis en évidence un changement de la composition lipidique, de l’expression des gènes de la myéline et de l’inflammation, défauts qui sont retrouvés en partie chez des souris dont le AhR a été invalidé spécifiquement dans l’oligodendrocyte, la cellule responsable de la formation de la gaine de myéline. J’ai donc réalisé des études en parallèle sur la lignée murine d’oligodendrocyte, 158N, et montré que l’invalidation du AhR dans cette lignée ainsi que in vivo, modifiait l’expression du gène MAG (Myelin Associated Glycoprotein). Compte tenu du rôle du AhR en tant que récepteur de polluants, nous avons également exposé ou traité nos modèles avec de la TCDD (dioxine de Seveso) et montré que celle-ci modifiait également l’expression du gène MAG. Mes travaux démontrent donc que le AhR joue un rôle au niveau oligodendrocytaire dans la formation de la gaine de myéline. Son rôle connu en tant que récepteur de polluants laisse supposer que certaines contaminations environnementales pourraient jouer un rôle dans l’incidence de pathologies au niveau du système nerveux central, ce qui soulève de nombreuses questions en terme de santé publique.
The aryl hydrocarbon receptor (AhR) is a transcription factor activated by many xenobiotics (foreign molecules) that regulates the expression of enzymes and transporters which allow the metabolism and elimination of these ligands. This protein expressed in all cells in vertebrates, plays a major role in detoxication and protection of the organisms against toxic molecules. Some orthologs have been identified in invertebrates but do not seem to play the same role; they are expressed mainly in neurons and are not activated by pollutants. The absence of the AhR in these organisms causes at the cellular level, defects of…
Advisors/Committee Members: Coumoul, Xavier (thesis director).
Subjects/Keywords: AhR; Myéline; Nerf optique; MAG; Souris; Aryl hydrocarbon receptor; Myelin; Optic nerve; Myelin associated-glycoprotein; Mice; 615.951 1
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Juricek, L. (2015). Rôles du récepteur aux hydrocarbures aromatiques (AhR) dans la structure de la myéline du système nerveux central de la souris : Roles of the aryl hydrocarbon receptor (AhR) in the myelin structure of the murine central nervous system. (Doctoral Dissertation). Sorbonne Paris Cité. Retrieved from http://www.theses.fr/2015USPCB166
Chicago Manual of Style (16th Edition):
Juricek, Ludmila. “Rôles du récepteur aux hydrocarbures aromatiques (AhR) dans la structure de la myéline du système nerveux central de la souris : Roles of the aryl hydrocarbon receptor (AhR) in the myelin structure of the murine central nervous system.” 2015. Doctoral Dissertation, Sorbonne Paris Cité. Accessed January 17, 2021.
http://www.theses.fr/2015USPCB166.
MLA Handbook (7th Edition):
Juricek, Ludmila. “Rôles du récepteur aux hydrocarbures aromatiques (AhR) dans la structure de la myéline du système nerveux central de la souris : Roles of the aryl hydrocarbon receptor (AhR) in the myelin structure of the murine central nervous system.” 2015. Web. 17 Jan 2021.
Vancouver:
Juricek L. Rôles du récepteur aux hydrocarbures aromatiques (AhR) dans la structure de la myéline du système nerveux central de la souris : Roles of the aryl hydrocarbon receptor (AhR) in the myelin structure of the murine central nervous system. [Internet] [Doctoral dissertation]. Sorbonne Paris Cité; 2015. [cited 2021 Jan 17].
Available from: http://www.theses.fr/2015USPCB166.
Council of Science Editors:
Juricek L. Rôles du récepteur aux hydrocarbures aromatiques (AhR) dans la structure de la myéline du système nerveux central de la souris : Roles of the aryl hydrocarbon receptor (AhR) in the myelin structure of the murine central nervous system. [Doctoral Dissertation]. Sorbonne Paris Cité; 2015. Available from: http://www.theses.fr/2015USPCB166

University of Manitoba
3.
Chan, Mable W. S.
Serpin-based SKI-1/S1P inhibitors against Old and New World arenaviruses.
Degree: Medical Microbiology, 2011, University of Manitoba
URL: http://hdl.handle.net/1993/4522
► The importance of arenavirus glycoprotein processing has only been understood within the past decade, with the majority of work focused on the Old World arenaviruses.…
(more)
▼ The importance of arenavirus
glycoprotein processing has only been understood within the past decade, with the majority of work focused on the Old World arenaviruses. Evidence has shown that SKI-
1/S1P (subtilisin kexin isozyme-
1/site
1 protease) is the cellular protease responsible for
glycoprotein cleavage in Old and New World arenaviruses. Furthermore,
glycoprotein cleavage is shown to be necessary for the production of infectious virus particles in Lassa and Junín viruses. In this thesis, evidence is provided that the recently emerged Chapare virus (New World) is also processed by SKI-
1/S1P. Additionally, novel serpin-based SKI-
1 inhibitors were shown to effectively prevent SKI-
1 mediated cleavage. Using a wide panel of recombinant vesicular stomatitis viruses expressing New World arenavirus glycoproteins, these inhibitors were capable of significantly reducing viral titres. This provides strong evidence that SKI-
1 inhibitors can be used as an effective treatment against the majority of New World Clade B arenaviruses and LASV in vivo.
Advisors/Committee Members: Ball, T. Blake (Medical Microbiology) (supervisor), Stetefeld, Jorg (Chemistry) Fowke, Keith (Medical Microbiology) (examiningcommittee).
Subjects/Keywords: arenaviruses; glycoprotein; serpin; SKI-1
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Chan, M. W. S. (2011). Serpin-based SKI-1/S1P inhibitors against Old and New World arenaviruses. (Masters Thesis). University of Manitoba. Retrieved from http://hdl.handle.net/1993/4522
Chicago Manual of Style (16th Edition):
Chan, Mable W S. “Serpin-based SKI-1/S1P inhibitors against Old and New World arenaviruses.” 2011. Masters Thesis, University of Manitoba. Accessed January 17, 2021.
http://hdl.handle.net/1993/4522.
MLA Handbook (7th Edition):
Chan, Mable W S. “Serpin-based SKI-1/S1P inhibitors against Old and New World arenaviruses.” 2011. Web. 17 Jan 2021.
Vancouver:
Chan MWS. Serpin-based SKI-1/S1P inhibitors against Old and New World arenaviruses. [Internet] [Masters thesis]. University of Manitoba; 2011. [cited 2021 Jan 17].
Available from: http://hdl.handle.net/1993/4522.
Council of Science Editors:
Chan MWS. Serpin-based SKI-1/S1P inhibitors against Old and New World arenaviruses. [Masters Thesis]. University of Manitoba; 2011. Available from: http://hdl.handle.net/1993/4522

University of Technology, Sydney
4.
Lu, Jamie Fung.
Microparticles mediate trait dominance in cancer.
Degree: 2015, University of Technology, Sydney
URL: http://hdl.handle.net/10453/44200
► Multidrug resistance (MDR) persists to be a major hindrance to the successful treatment in clinical oncology and is the cause of over 90% of treatment…
(more)
▼ Multidrug resistance (MDR) persists to be a major hindrance to the successful treatment in clinical oncology and is the cause of over 90% of treatment failure in cancer. The two main membrane spanning proteins, P-glycoprotein (ABCB1/P-gp) and Multidrug Resistance-associated protein 1 (ABCC1/MRP1) are responsible for the efflux of a plethora of unrelated anti-cancer drugs out of cells, resulting in MDR. Cancer cells overexpressing these efflux proteins are insensitive to chemotherapeutic treatments by maintaining sub-lethal intracellular cytotoxic drug concentrations. Given their enormous substrate profile, of which there is significant overlap, the expression of either efflux protein would result in a poor prognosis. In some cancers, the overexpression of these proteins is correlated with clinical stage, with early stage tumours expressing one efflux transporter and substituted by another transporter at an advanced stage. Our group has established the transfer and dissemination of ABC-transporter mediated MDR via a subset of extracellular vesicles known as microparticles (MPs). This study investigates the molecular mechanisms governing the alteration and acquisition of MDR traits in cancer cell populations via MPs.
Spontaneously shed MPs from cancer cells represent a prominent modality for intercellular communication by virtue of their capacity to transport and disseminate bioactive cargo through the vasculature. Their ability to carry large membrane spanning proteins and nucleic acids, imparts their capacity to confer MDR among otherwise drug sensitive tumour cells. Herein, the study validates the MP-transfer and functionality of MRP1 in drug sensitive acute leukaemia cells. The study also introduces MP-mediated trait dominance and demonstrate the re-templating of a pre-existing MDR phenotype in recipient cells. To validate the transfer and translation of MP packaged nucleic acids, a novel methodology was developed, abolishing the requirement for labelled probes and interspecies models. Using, surface peptide shaving, detection of MP packaged P-gp was removed and showed transcript translation of transferred ABCB1 in drug sensitive recipient cells after more than 24 h. Finally, the study identifies transcript suppression mechanisms involved in MP-mediated trait dominance and identify a novel relationship between the function of miRNA with a non-target mRNA transcript. Specifically, the presence of a rival transcript ABCB1 facilitates the ABCC1 suppression by miR-326. These findings substantially advance our understanding on the molecular mechanisms leading to the alteration of MDR traits and can be translated into clinical oncology by providing prognostic information and additional therapeutic targets.
Subjects/Keywords: Multidrug resistance (MDR).; P-glycoprotein (ABCB1/P-gp).; Multidrug Resistance-associated protein 1 (ABCC1/MRP1).; Chemotherapeutic treatments.; ABC-transporter mediated MDR.; Microparticles (MPs).; MP-mediated trait dominance .
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lu, J. F. (2015). Microparticles mediate trait dominance in cancer. (Thesis). University of Technology, Sydney. Retrieved from http://hdl.handle.net/10453/44200
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Lu, Jamie Fung. “Microparticles mediate trait dominance in cancer.” 2015. Thesis, University of Technology, Sydney. Accessed January 17, 2021.
http://hdl.handle.net/10453/44200.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Lu, Jamie Fung. “Microparticles mediate trait dominance in cancer.” 2015. Web. 17 Jan 2021.
Vancouver:
Lu JF. Microparticles mediate trait dominance in cancer. [Internet] [Thesis]. University of Technology, Sydney; 2015. [cited 2021 Jan 17].
Available from: http://hdl.handle.net/10453/44200.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Lu JF. Microparticles mediate trait dominance in cancer. [Thesis]. University of Technology, Sydney; 2015. Available from: http://hdl.handle.net/10453/44200
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Urbana-Champaign
5.
Peixoto, Phillip.
Characterization of pregnancy-associated glycoproteins and progesterone as a predictor of twins and conceptus loss in high-risk pregnancy Holstein cows.
Degree: MS, VMS-Veterinary Clinical Medcne, 2020, University of Illinois – Urbana-Champaign
URL: http://hdl.handle.net/2142/108415
► Pregnancy loss is a multifactorial condition that compromises reproductive performance in dairy operations. Despite the high oocyte fertilization rate in dairy cows, only 28 %…
(more)
▼ Pregnancy loss is a multifactorial condition that compromises reproductive performance in dairy operations. Despite the high oocyte fertilization rate in dairy cows, only 28 % of those maintain a pregnancy to term. Pregnancy loss is estimated to cost U$600.00 per case. Identification of cows losing the pregnancy as early as possible can be helpful in providing timely opportunities for rebreeding, thus potentially minimizing economic losses. Traditionally, early pregnancy diagnosis is performed via ultrasonography, starting at 30 days, which provides information regarding embryo viability, uterine health, and ovarian structures. In addition, this technique allows the diagnosis of twin pregnancy that is three times more likely to be lost than a singleton. Despite its benefits ultrasonography requires well-trained personnel and incurs additional costs involving equipment purchase and maintenance. The use of biomarkers has been studied throughout the years, based on a demand for an easier, less costly, and more accurate test. Pregnancy-
associated glycoproteins (PAG) is the most common biomarker marker to assess pregnancy status in cows. Produced and secreted on the maternal circulation by binucleate giant cells. Measurement of PAG in the blood has high sensitivity when performed between 25 32 days of gestation, however, the specificity can be as low as 83%. One of the major components that affect test accuracy is pregnancy loss. It has been reported that cows experiencing early pregnancy loss, present lower plasma concentrations of PAG. Another indirect biomarker to detect pregnancy in cows is progesterone. Cows experiencing pregnancy loss showed lower concentrations of this hormone, in comparison to cows keeping the pregnancy. The development of a threshold for PAG and progesterone that can predict pregnancy loss may aid in management decisions to provide earlier rebreeding opportunities. It was hypothesized that the plasma concentration of PAG and progesterone is reduced and can predict pregnancy loss in cows experiencing a high-risk pregnancy. Additionally, it was hypothesized that the concentration of PAG and progesterone are increased and can predict twins. High-risk pregnancy (HR) were characterized using transrectal ultrasonography 37 days post-AI based on the following criteria: small embryo size (SE, embryo < 15 mm, n=10), slow heartbeat (SH, <60 beats per minute, n = 11), extra amniotic membrane (EM, additional amniotic membrane, n=3). A cohort of twins (TW, n = 41) diagnosed at day 37 post-AI was also enrolled. Twins were also subgroups in unilateral (UT, n=17) and bilateral (BT, n=24). Each HR and TW cow was paired with the same parity cow carrying a normal singleton at d 37 post-AI (CON, n = 65). Blood samples were collected to measure PAG and progesterone at 37, 44, and 51 post-AI. Statistical analysis was performed using ANOVA, logistic regression and receiver operation characteristics (ROC) with JMP. Pregnancy loss at day 51 post-AI was greater (P < 0.01) in HR than CON and TW (CON=
1.5%; HR=87.5%;…
Advisors/Committee Members: Lima, Fabio S (advisor), Canisso, Igor F (committee member), Garret, Edgar F (committee member).
Subjects/Keywords: Pregnancy loss; pregnancy-associated glycoprotein; progesterone; high-risk pregnancy; twins
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Peixoto, P. (2020). Characterization of pregnancy-associated glycoproteins and progesterone as a predictor of twins and conceptus loss in high-risk pregnancy Holstein cows. (Thesis). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/108415
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Peixoto, Phillip. “Characterization of pregnancy-associated glycoproteins and progesterone as a predictor of twins and conceptus loss in high-risk pregnancy Holstein cows.” 2020. Thesis, University of Illinois – Urbana-Champaign. Accessed January 17, 2021.
http://hdl.handle.net/2142/108415.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Peixoto, Phillip. “Characterization of pregnancy-associated glycoproteins and progesterone as a predictor of twins and conceptus loss in high-risk pregnancy Holstein cows.” 2020. Web. 17 Jan 2021.
Vancouver:
Peixoto P. Characterization of pregnancy-associated glycoproteins and progesterone as a predictor of twins and conceptus loss in high-risk pregnancy Holstein cows. [Internet] [Thesis]. University of Illinois – Urbana-Champaign; 2020. [cited 2021 Jan 17].
Available from: http://hdl.handle.net/2142/108415.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Peixoto P. Characterization of pregnancy-associated glycoproteins and progesterone as a predictor of twins and conceptus loss in high-risk pregnancy Holstein cows. [Thesis]. University of Illinois – Urbana-Champaign; 2020. Available from: http://hdl.handle.net/2142/108415
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Saskatchewan
6.
Hebbandi Nanjundappa, Roopa.
HIV-1 Glycoprotein 120-Specific Exosome-Targeted CD8+ T Cell Vaccine.
Degree: 2011, University of Saskatchewan
URL: http://hdl.handle.net/10388/ETD-2011-12-275
► Immunosuppression is a hallmark of human immunodeficiency virus-1 (HIV-1) infection. Upon binding to cluster of differentiation (CD) 4 receptor via trimeric glycoprotein (Gp) 120, HIV-1…
(more)
▼ Immunosuppression is a hallmark of human immunodeficiency virus-
1 (HIV-
1) infection. Upon binding to cluster of differentiation (CD) 4 receptor via trimeric
glycoprotein (Gp) 120, HIV-
1 enters and multiplies in CD4+ T cells, leading to the death of these cells. CD4+ T helper (Th) cells are required for the generation and maintenance of CD8+ T cells, which are crucial to control HIV-
1 proliferation. The stimulation of HIV-
1-specific CD8+ T cell responses in CD4-deficient environment is a major scientific challenge. In addition, dendritic cells (DCs) expressing C-type lectin and dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) with high affinity for Gp120, appear to act as “Trojan horses”, facilitating the spread of HIV-
1 from mucosal surfaces to T cells in lymph nodes, and these HIV-
1-infected T cells have been found to be impaired. Currently, highly active antiretroviral therapy (HAART) is the only means to halt progression of acquired immunodeficiency syndrome (AIDS). Although HAART suppresses viral replication and significantly improves prognosis, toxicity and cost of the treatment have become major limitations for its use. In addition, with long-term use, HAART also decreases HIV-
1-specific CD4+ Th1 and CD8+ T cell responses, causing a functional decrease in capacity of HIV-
1-capturing DCs in initiating adaptive immune responses. As a result, HIV patients are unable to eliminate infected cells and proviral latent reservoirs. Therefore, how to stimulate efficient CD8+ T cell responses in AIDS patients is one of the major challenges in HIV-
1 patient therapy.
Previously, it was demonstrated that novel ovalbumin (OVA)-specific exosome (EXO)-targeted CD4+ T cell vaccine (CD4+aTexo) was capable of stimulating CD4+ T cell-independent CD8+ T cell responses and antitumor immunity to a highly metastasizing tumor challenge in wild-type mice. Since CD4+ T cells are killed by HIV-
1, the present study proposed to use active CD8+ T cells rather than active CD4+ T cells for vaccine development. First, OVA-specific CD8+aTexo (OVA-aTexo) vaccine was prepared by pulsing concanavalin A (Con A)-stimulated CD8+ T cells with OVA-pulsed DCs (DCOVA)-released exosomes (EXOOVA). In wild-type mice, OVA-aTexo vaccine stimulated CD4-independent OVA-specific CD8+ T cell responses via CD40L and interleukin (IL)-2 signaling, and exosomal peptide major histo-compatibility complex (pMHC)-I targeting. To further provide insight into whether CD8+aTexo vaccine induces similar cellular immune response in the context of human immune system, transgenic A2-Kb mice expressing α
1 and α2 domains of human leukocyte antigen (HLA)-A2 and α3 domain of mouse H2-Kb were used. Adenovirus (AdVGp120) expressing HIV-
1 envelope protein Gp120 was used to transfect bone-marrow DCs to generate DC expressing Gp120 and DCGp120-released EXO were purified (EXOGp120). EXOGp120 were also purified from the culture supernatant of DC2.4Gp120-transfected cells. Next, Gp120-specific CD8+aTexo (Gp120-aTexo) vaccine was prepared by pulsing…
Advisors/Committee Members: Xiang, Jim, Ziola, Barry, Qualtiere, Lou, Liu, Lixin, Qureshi, Mabood.
Subjects/Keywords: HIV-1 infection; T cell vaccine; glycoprotein-120; adenovirus; exosomes
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Hebbandi Nanjundappa, R. (2011). HIV-1 Glycoprotein 120-Specific Exosome-Targeted CD8+ T Cell Vaccine. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/ETD-2011-12-275
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Hebbandi Nanjundappa, Roopa. “HIV-1 Glycoprotein 120-Specific Exosome-Targeted CD8+ T Cell Vaccine.” 2011. Thesis, University of Saskatchewan. Accessed January 17, 2021.
http://hdl.handle.net/10388/ETD-2011-12-275.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Hebbandi Nanjundappa, Roopa. “HIV-1 Glycoprotein 120-Specific Exosome-Targeted CD8+ T Cell Vaccine.” 2011. Web. 17 Jan 2021.
Vancouver:
Hebbandi Nanjundappa R. HIV-1 Glycoprotein 120-Specific Exosome-Targeted CD8+ T Cell Vaccine. [Internet] [Thesis]. University of Saskatchewan; 2011. [cited 2021 Jan 17].
Available from: http://hdl.handle.net/10388/ETD-2011-12-275.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Hebbandi Nanjundappa R. HIV-1 Glycoprotein 120-Specific Exosome-Targeted CD8+ T Cell Vaccine. [Thesis]. University of Saskatchewan; 2011. Available from: http://hdl.handle.net/10388/ETD-2011-12-275
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
7.
Tan, Su-fern.
Role of Acid Ceramidase in Regulating Survival and Drug Resistance in Acute Myeloid Leukemia.
Degree: 2013, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/19626
► Acute myeloid leukemia (AML) is a heterogeneous disease that affects the differentiation of myeloid precursors. In normal hematopoiesis, hematopoietic stem cells committed to the myeloid…
(more)
▼ Acute myeloid leukemia (AML) is a heterogeneous disease that affects the differentiation of myeloid precursors. In normal hematopoiesis, hematopoietic stem cells committed to the myeloid lineage form platelets, white cells and red cells. AML patients have the characteristic feature of accumulated immature myeloid precursors known as blasts. Prognosis for AML patients depends on several risk factors, including cytogenetic abnormalities, age, prior exposure to chemotherapy, and pre-existing hematological disorder such as myelodysplastic syndrome (MDS). The five-year survival rate for AML patients remains low and drug resistance is also a major problem for relapsed patients. Hence, AML patients require better treatments.
Sphingolipids are a group of sphingoid-based lipids that maintain cellular integrity and mediate signal transduction and gene regulation. Two sphingolipids are important in regulating cell survival: ceramide and sphingosine-
1-phosphate (S1P). The ceramide and S1P balance is known as the “sphingolipid rheostat”, which modulates cell survival. Sphingolipids are dysregulated in many types of cancer, including AML. Acid ceramidase (AC) is a lysosomal enzyme that catalyzes ceramide breakdown into sphingosine and free fatty acids. Sphingosine is then phosphorylated by sphingosine kinases to form S1P. AC is crucial for embryonic development but is found in high levels in several different types of cancer, including prostate, colon and breast cancer.
In this study, we investigated the role of AC in AML blast survival and drug resistance. We show that AC expression and activity is elevated in AML patients. Corresponding to elevated AC activity is the elevation of S1P levels also detected in patient samples. Targeting AC using ceramide analog LCL204 and AC shRNA decreased viability and myeloid cell leukemia differentiation protein-
1(Mcl-
1) expression, a B-cell lymphoma 2 (Bcl-2) family protein essential for AML survival. AC inhibition also decreased the multidrug resistance protein (MDR1)/P-
glycoprotein (P-gp) and sensitized cells to AML chemotherapeutic drugs. Furthermore, AC overexpression in AML cell line HL-60 increased S1P and decreased total ceramide levels. We also found that AC overexpression increased NF-κB activation, a transcription factor responsible for many survival pathways including the regulation of Mcl-
1 and P-gp transcription. We hypothesized that AC overexpression increases NF-κB activation that then serves as a positive feedback loop back to AC. We demonstrate that NF-κB inhibition decreased AC, Mcl-
1 and P-gp expression, supporting the positive feedback loop hypothesis. Pharmacological inhibition of AC in a murine AML model also significantly increased the survival of leukemic mice.
Taken together, we show that AC is important for blast survival and drug resistance in AML. Targeting AC changes the sphingolipid rheostat to increase ceramide and decrease S1P levels, thereby leading to cell death. We also demonstrate for the first time that AC regulates Mcl-
1 and P-gp expression,…
Advisors/Committee Members: Andrew Paul Loughran, Dissertation Advisor/Co-Advisor, "Thomas P Loughran, Jr", Committee Chair/Co-Chair, Charles H Lang, Committee Chair/Co-Chair, Hong Gang Wang, Committee Member, Jin Ming Yang, Committee Member, David F Claxton, Special Member.
Subjects/Keywords: AML; Acid Ceramidase; Mcl-1; P-glycoprotein; NF-kB; sphingolipids
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Tan, S. (2013). Role of Acid Ceramidase in Regulating Survival and Drug Resistance in Acute Myeloid Leukemia. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/19626
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Tan, Su-fern. “Role of Acid Ceramidase in Regulating Survival and Drug Resistance in Acute Myeloid Leukemia.” 2013. Thesis, Penn State University. Accessed January 17, 2021.
https://submit-etda.libraries.psu.edu/catalog/19626.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Tan, Su-fern. “Role of Acid Ceramidase in Regulating Survival and Drug Resistance in Acute Myeloid Leukemia.” 2013. Web. 17 Jan 2021.
Vancouver:
Tan S. Role of Acid Ceramidase in Regulating Survival and Drug Resistance in Acute Myeloid Leukemia. [Internet] [Thesis]. Penn State University; 2013. [cited 2021 Jan 17].
Available from: https://submit-etda.libraries.psu.edu/catalog/19626.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Tan S. Role of Acid Ceramidase in Regulating Survival and Drug Resistance in Acute Myeloid Leukemia. [Thesis]. Penn State University; 2013. Available from: https://submit-etda.libraries.psu.edu/catalog/19626
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Melbourne
8.
Chitas, Andre Marques Lopes.
Structural and functional investigations of a chemokine binding protein from equine herpesvirus-1.
Degree: 2013, University of Melbourne
URL: http://hdl.handle.net/11343/38678
► Equine herpesvirus-1 (EHV-1) and equine herpesvirus-4 (EHV-4) are members of the Alphaherpesvirinae subfamily in the Herpesviridae family. Both EHV-1 and EHV-4 are endemic equine viruses…
(more)
▼ Equine herpesvirus-1 (EHV-1) and equine herpesvirus-4 (EHV-4) are members of the Alphaherpesvirinae subfamily in the Herpesviridae family. Both EHV-1 and EHV-4 are endemic equine viruses worldwide. Infection with EHV-1 has significant health effects for equine populations by causing respiratory disease, abortion, perinatal mortality and severe neurological disease. Equine herpesvirus-4 predominantly causes respiratory disease. Abortion, perinatal mortality and neurological disease are rarely associated with EHV-4 infection. Equine herpesvirus-1 and EHV-4 both encode glycoprotein G (gG). Homologues of this protein are also present in most other alphaherpesviruses. Glycoprotein G encoded by EHV-1 is a chemokine binding protein, although no chemokine-binding activity has been demonstrated for EHV-4 gG.
This project studied the ability of EHV-1 gG to bind to various recombinant chemokines, cytokines and defensins. The binding activity of full length and truncated foms of recombinant EHV-1 gG were compared using enzyme linked immunosorbant assays (ELISAs). The study also investigated the ability of recombinant EHV-1 gG to function as an immunomodulator in a mouse model using influenza virus. The immunomodulatory properties of recombinant EHV-1 gG were compared to those of recombinant EHV-4 gG and recombinant infectious laryngotracheitis virus (ILTV) which is an alphaherpesvirus of chickens.
Equine herpesvirus-1 gG bound to recombinant chemokines from various species (human, mouse, equine), as well as recombinant human and mouse cytokines, and recombinant equine alpha-defensin-1. The chemokine binding of the truncated form of EHV-1 gG was similar to that of the full length recombinant EHV-1 gG. In mice, no significant difference in immunoglobulin levels was observed in animals that received infectious or inactivated influenza, compared to those that received infectious or inactivated influenza along with recombinant EHV-1, EHV-4 or ILTV gG. Recombinant ILTV gG co-delivered with infectious influenza resulted in a significant decrease in CD8 cells compared to infectious influenza alone. The co-delivery of EHV-4 gG resulted in a significant decrease in CD8 cells in infectious influenza studies and a significant increase in CD8 cells in inactivated influenza studies. No inflammatory cytokine or chemokine responses were detected in these studies using cytometric bead arrays. The results showed an influence on the cell mediated immune response.
This project improves our understanding of the role of gG and the effect of its ability to bind to chemokines, cytokines and defensins. This project contributes to our understanding of the disease pathogenesis of EHV-1 and other alphaherpesviruses that encode gG. This project also brings potential benefits through the characterisation of an immunomodulatory compound that may have therapeutic application.
Subjects/Keywords: equine herpesvirus-1; glycoprotein G; chemokine binding protein
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Chitas, A. M. L. (2013). Structural and functional investigations of a chemokine binding protein from equine herpesvirus-1. (Masters Thesis). University of Melbourne. Retrieved from http://hdl.handle.net/11343/38678
Chicago Manual of Style (16th Edition):
Chitas, Andre Marques Lopes. “Structural and functional investigations of a chemokine binding protein from equine herpesvirus-1.” 2013. Masters Thesis, University of Melbourne. Accessed January 17, 2021.
http://hdl.handle.net/11343/38678.
MLA Handbook (7th Edition):
Chitas, Andre Marques Lopes. “Structural and functional investigations of a chemokine binding protein from equine herpesvirus-1.” 2013. Web. 17 Jan 2021.
Vancouver:
Chitas AML. Structural and functional investigations of a chemokine binding protein from equine herpesvirus-1. [Internet] [Masters thesis]. University of Melbourne; 2013. [cited 2021 Jan 17].
Available from: http://hdl.handle.net/11343/38678.
Council of Science Editors:
Chitas AML. Structural and functional investigations of a chemokine binding protein from equine herpesvirus-1. [Masters Thesis]. University of Melbourne; 2013. Available from: http://hdl.handle.net/11343/38678

Louisiana State University
9.
Saied, Ahmad.
The Role of Herpes Simplex Virus Type 1 Glycoprotein K in Neuroinvasion and Immunopathogenesis of Herpes Keratitis.
Degree: PhD, Veterinary Pathology and Pathobiology, 2015, Louisiana State University
URL: etd-04012015-164717
;
https://digitalcommons.lsu.edu/gradschool_dissertations/3640
► ABSTRACT Herpes simplex virus type 1 is a common neurotropic pathogen responsible for a multitude of human diseases ranging from mucocutaneous lesions, keratitis to life-threatening…
(more)
▼ ABSTRACT Herpes simplex virus type 1 is a common neurotropic pathogen responsible for a multitude of human diseases ranging from mucocutaneous lesions, keratitis to life-threatening encephalitis. The hallmark of the HSV-1 life cycle is infection of sensory neurons, where the virus establishes a latent infection for the life of the host. Viral envelope glycoproteins play important roles in viral life cycle and virus-host interaction. Viral glycoproteins gK, gM, gE and the membrane protein UL11 have been shown to be important for virus assembly, egress and virus spread. To investigate the relative importance of each of gK, gM, gE and UL11 in infection of ganglionic neurons following ocular inoculation, recombinant viruses were constructed, characterized and used to infect mice via the ocular route. Results showed that gK plays the most important role in infection of ganglionic neurons following ocular inoculation in the mouse model. gK null viruses exhibited major defects in replication and cell to cell spread in tissue culture. To further investigate the role of gK in the pathogenesis of herpes keratitis and to delineate gK domains responsible for replication and neuroinvasion, recombinant viruses lacking the amino-terminus of gK were constructed. Characterization of the constructed viruses revealed that the amino terminus of gK is dispensable for replication in tissue culture; however, it is required for neuroinvasion and cell to cell spread. Moreover, the virus lacking the amino terminus in gK was unable to infect corneal epithelium and establish latency in the trigeminal ganglia after ocular inoculation of mice. In the above mentioned investigation, we have observed that lack of the amino terminus of gK is associated with lack of ocular disease in infected mice. Further investigation of this observation (still in progress) revealed a potential role for gK in the immunopathogenesis of keratitis. The research work presented in this dissertation is of paramount importance as it identifies gK as an important neurotropic determinant, and it delineates gK domains responsible for neuroinvasion and immunopathogenesis in vivo. This work may lead to the development of replication competent, safe vaccine vectors, and paves the way for the discovery of new therapeutics for herpes keratitis.
Subjects/Keywords: HSV-1; Glycoprotein K; Neuroinvasion; Immunopathogenesis; Herpes Keratitis
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Saied, A. (2015). The Role of Herpes Simplex Virus Type 1 Glycoprotein K in Neuroinvasion and Immunopathogenesis of Herpes Keratitis. (Doctoral Dissertation). Louisiana State University. Retrieved from etd-04012015-164717 ; https://digitalcommons.lsu.edu/gradschool_dissertations/3640
Chicago Manual of Style (16th Edition):
Saied, Ahmad. “The Role of Herpes Simplex Virus Type 1 Glycoprotein K in Neuroinvasion and Immunopathogenesis of Herpes Keratitis.” 2015. Doctoral Dissertation, Louisiana State University. Accessed January 17, 2021.
etd-04012015-164717 ; https://digitalcommons.lsu.edu/gradschool_dissertations/3640.
MLA Handbook (7th Edition):
Saied, Ahmad. “The Role of Herpes Simplex Virus Type 1 Glycoprotein K in Neuroinvasion and Immunopathogenesis of Herpes Keratitis.” 2015. Web. 17 Jan 2021.
Vancouver:
Saied A. The Role of Herpes Simplex Virus Type 1 Glycoprotein K in Neuroinvasion and Immunopathogenesis of Herpes Keratitis. [Internet] [Doctoral dissertation]. Louisiana State University; 2015. [cited 2021 Jan 17].
Available from: etd-04012015-164717 ; https://digitalcommons.lsu.edu/gradschool_dissertations/3640.
Council of Science Editors:
Saied A. The Role of Herpes Simplex Virus Type 1 Glycoprotein K in Neuroinvasion and Immunopathogenesis of Herpes Keratitis. [Doctoral Dissertation]. Louisiana State University; 2015. Available from: etd-04012015-164717 ; https://digitalcommons.lsu.edu/gradschool_dissertations/3640
10.
Dias, Carlos André Ribeiro.
Possible emodepside toxicosis in a Collie with MDR1 gene mutation.
Degree: 2014, RCAAP
URL: https://www.rcaap.pt/detail.jsp?id=oai:comum.rcaap.pt:10400.26/16628
► The multi-drug resistance gene 1 (MDR1) is responsible for encoding an efflux transport protein designated P-glycoprotein (P-gp). The P-gp is expressed in various tissues such…
(more)
▼ The multi-drug resistance gene 1 (MDR1) is responsible for encoding an efflux transport protein designated P-glycoprotein (P-gp). The P-gp is expressed in various tissues such as the capillary endothelial cells of the brain, renal tubular cells, intestinal cells, skin, among others. It is also present in some types of neoplastic cells, where it is often overexpressed. It is a glycosylated transmembrane protein that transports several amphipathic and hydrophobic molecules, such as toxins and xenobiotics, including drugs commonly used in veterinary practice. A mutation in MDR1 gene is frequent in some dog breeds, and encodes the synthesis of a non-functional P-gp. The absence of P-gp in the blood-brain barrier may originate the accumulation of its substrates in the central nervous system, leading to neurotoxicity. Currently, a wide variety of molecules are known to be substrates of P-gp. This mutation has been classically associated with ivermectin neurotoxicity in dogs of Collie breeds. However, this mutation has been described in several other dog breeds, mainly herding breeds, and associated with toxicity of other drugs and toxins. This paper reports a clinical case of a strong suspicion of neurotoxicity associated with an overdose of emodepside in a Collie dog carrier of an homozygous mutation in the MDR1 gene. Although the neurotoxicity associated with the overdose of emodepside is recognized by the European Medicines Agency, this is, to our best knowledge, the first clinical report of a possible emodepside toxicosis. Considering the relevance of P-gp function in drug metabolism, it is of paramount importance to screen the MDR1 gene mutation, especially in dogs breeds where this mutation is frequent, so that safe drugs are used in the treatment of these animals
O gene da multirresistência aos fármacos 1 (MDR1) é responsável por codificar uma proteína transportadora, designada glicoproteína-P (P-gp). A P-gp encontra-se presente em diferentes tecidos, tais como, células endoteliais dos vasos cerebrais, células dos túbulos renais, intestino, pele, entre outros. Está também presente em alguns tipos de células neoplásicas, onde se encontra frequentemente sobre-expressa. É uma proteína transmembranar glicosada, que tem a função de transportar para o exterior das células diversos compostos anfipáticos e hidrofóbicos tais como toxinas e xenobióticos, entre os quais vários fármacos usados correntemente na prática veterinária. Em algumas raças de cães é frequente a existência de uma mutação do gene MDR1, que origina a síntese de uma P-gp não funcional. A ausência da P-gp na barreira hematoencefálica permite a acumulação dos seus substratos no sistema nervoso central, originando neurotoxicidade. Atualmente são reconhecidas várias moléculas como substratos da P-gp. Esta mutação é classicamente associada à neurotoxicidade por ivermectina em cães das raças Collie e seus cruzamentos. No entanto, esta mutação está também descrita em diversas outras raças de cães, maioritariamente de pastoreio, e tem sido associada a toxicidade…
Advisors/Committee Members: Francisco, Anabela Maduro de Almeida, Vilhena, Hugo Corte-Real.
Subjects/Keywords: Collie; Emodepside; Adverse Drug Reactions; MDR 1 gene mutation; ABCB 1 gene; P Glycoprotein
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Dias, C. A. R. (2014). Possible emodepside toxicosis in a Collie with MDR1 gene mutation. (Thesis). RCAAP. Retrieved from https://www.rcaap.pt/detail.jsp?id=oai:comum.rcaap.pt:10400.26/16628
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Dias, Carlos André Ribeiro. “Possible emodepside toxicosis in a Collie with MDR1 gene mutation.” 2014. Thesis, RCAAP. Accessed January 17, 2021.
https://www.rcaap.pt/detail.jsp?id=oai:comum.rcaap.pt:10400.26/16628.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Dias, Carlos André Ribeiro. “Possible emodepside toxicosis in a Collie with MDR1 gene mutation.” 2014. Web. 17 Jan 2021.
Vancouver:
Dias CAR. Possible emodepside toxicosis in a Collie with MDR1 gene mutation. [Internet] [Thesis]. RCAAP; 2014. [cited 2021 Jan 17].
Available from: https://www.rcaap.pt/detail.jsp?id=oai:comum.rcaap.pt:10400.26/16628.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Dias CAR. Possible emodepside toxicosis in a Collie with MDR1 gene mutation. [Thesis]. RCAAP; 2014. Available from: https://www.rcaap.pt/detail.jsp?id=oai:comum.rcaap.pt:10400.26/16628
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Indian Institute of Science
11.
Das, Raksha.
Effects of Cyclic Permutation, Glycan Removal and Aspartate Mutagenesis on Conformation of HIV-1 Envelope.
Degree: PhD, Faculty of Science, 2018, Indian Institute of Science
URL: http://etd.iisc.ac.in/handle/2005/4169
► It has been decades since Human Immunodeficiency Virus-1 (HIV-1) was discovered. The virus has created havoc worldwide. According to the UNAIDS 2014 Gap report, 35million…
(more)
▼ It has been decades since Human Immunodeficiency Virus-
1 (HIV-
1) was discovered. The virus has created havoc worldwide. According to the UNAIDS 2014 Gap report, 35million people worldwide are infected with HIV-
1 and yet there is no vaccine. The most abundant and exposed protein on the HIV-
1 virion surface is Envelope (Env)
glycoprotein. HIV-
1 uses its Env
glycoprotein to infect host cells. HIV-
1 Env
glycoprotein exists as a trimer of heterodimers of gp120 and gp41. gp120 is the surface exposed and gp41 the membrane anchored subunit. gp120, being surface exposed, is the primary target of neutralizing antibodies and therefore is an important candidate for immunogen design. The generation of an effective HIV-
1 vaccine is a challenging job because the HIV-
1 virus has acquired many immune evasive mechanisms. The HIV-
1 virus has high sequence variability, because of which it is difficult to make a vaccine that can effectively act against all viral strains. HIV-
1 gp120 is extensively glycosylated and thus much of the surface is concealed from the host immune system. It also has immunodominant loops that are highly exposed in shed gp120 and can drive the immune focus towards a non-neutralizing response. There are different strategies that have been employed in the search for an HIV-
1 vaccine. Chapter
1, contains a brief introduction of HIV-
1, the difficulties in eliciting neutralizing antibodies and the strategies employed so far in Env based immunogen design. In Chapter 2, we describe the use of cyclic permutation as a strategy to trimerize gp120 in the absence of gp41. Normally, the Env trimer present on the cell surface exists as a trimer of gp120 and gp41 heterodimers. The trimerization is largely mediated by gp41 and assisted by V1V2 loops on gp120 that form the apex of the trimer. The antibodies generated against gp41 are autoreactive and more often non-neutralizing. To avoid that, only gp120 was used as an immunogen and to trimerize gp120 in the absence of gp41, a cyclic permutant of gp120 was made. The original N and C termini were joined by a linker and new N and C termini were generated in the V1 loop region. The V1 loop is a flexible region in gp120 and can tolerate insertions at the chosen location between residues 143 and 144. The trimerization domain, human cartilage matrix protein (hCMP), was linked at the new N terminus of the V1 loop. In a separate construct, hCMP was also linked to the C terminus of gp120 as a negative control. We found that the resulting V1 cyclic permutants JRCSF-hCMP-V1cyc and JRFL-hCMP-V1cyc improved the binding of gp120 to broadly neutralizing antibodies like VRC01 and VRCPG04 (CD4 binding site antibodies) and reduced the binding to non-neutralizing antibodies like b6 and F105. These cyclic permutants showed ~ 10-20 fold increase in binding to the quaternary epitope specific broadly neutralizing antibodies PGT145, PG9, PG16, and PGDM 1400. The gp120 cyclic permutants showed an increased thermal stability by 4˚C compared to Wtgp120 and were shown to be trimeric by negative stain EM. On…
Advisors/Committee Members: Varadarajan, Raghavan (advisor).
Subjects/Keywords: HIV-1 Envelope; HIV-1 Envelope Glycoprotein; HIV-1 Cyclic Mutant; HIV-1 gp41; Human Immunodeficiency Virus-1; HIV-1 gp120; Human Cartilage Matrix Protein (hCMP); Molecular Biophysics
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Das, R. (2018). Effects of Cyclic Permutation, Glycan Removal and Aspartate Mutagenesis on Conformation of HIV-1 Envelope. (Doctoral Dissertation). Indian Institute of Science. Retrieved from http://etd.iisc.ac.in/handle/2005/4169
Chicago Manual of Style (16th Edition):
Das, Raksha. “Effects of Cyclic Permutation, Glycan Removal and Aspartate Mutagenesis on Conformation of HIV-1 Envelope.” 2018. Doctoral Dissertation, Indian Institute of Science. Accessed January 17, 2021.
http://etd.iisc.ac.in/handle/2005/4169.
MLA Handbook (7th Edition):
Das, Raksha. “Effects of Cyclic Permutation, Glycan Removal and Aspartate Mutagenesis on Conformation of HIV-1 Envelope.” 2018. Web. 17 Jan 2021.
Vancouver:
Das R. Effects of Cyclic Permutation, Glycan Removal and Aspartate Mutagenesis on Conformation of HIV-1 Envelope. [Internet] [Doctoral dissertation]. Indian Institute of Science; 2018. [cited 2021 Jan 17].
Available from: http://etd.iisc.ac.in/handle/2005/4169.
Council of Science Editors:
Das R. Effects of Cyclic Permutation, Glycan Removal and Aspartate Mutagenesis on Conformation of HIV-1 Envelope. [Doctoral Dissertation]. Indian Institute of Science; 2018. Available from: http://etd.iisc.ac.in/handle/2005/4169

University of Rochester
12.
Chivatakarn, Onanong.
Semaphorin 5A (Sema5A) functions in neocortical
development In vivo.
Degree: PhD, 2009, University of Rochester
URL: http://hdl.handle.net/1802/8459
► Proper nervous system function critically depends upon the proper assembly of an intricate network of neuronal connections. A limited number of axon guidance cues have…
(more)
▼ Proper nervous system function critically depends
upon the proper assembly of an intricate
network of neuronal
connections. A limited number of axon guidance cues have been
identified that
regulates growth cone guidance and directly
participate in neural network development and patterning. A
key
question in developmental neurobiology is: How can a limited number
of axon guidance cues create
such an enormous complexity of
neuronal connections? Emerging new concepts include
“contextdependent” function of guidance cues, hierarchies among
guidance cues, and bi-functionality (i.e. attracting or repelling
growth cones by the same guidance cue depending on the presence of
different co-receptors).
Understanding how specific axon guidance
cues exert their diverse function at the cellular and molecular
level is of considerable interest both biologically and
clinically.
The focus of my thesis work was on Semaphorin 5A
(Sema5A), a type-1 transmembrane protein
with a large ectodomain
composed of a Sema-domain followed by 7 type-1 thrombospondin
repeats. I will show that Sema5A is a bi-functional axon guidance
cue that is essential for the proper formation of the fasciculus
retroflexus (FR) in vitro. Sema5A bi-functional activity is
regulated in a proteoglycan-dependent manner. In the presence of
heparan sulfate proteoglycans (HSPGs), Sema5A exerts an attractive
response towards habenular neurons. Conversely, in the presence of
chondroitin sulfate proteoglycans (CSPGs), Sema5A exerts an
inhibitory response towards the same population of neurons.
Structural and functional analyses indicate that HSPGs and CSPGs
interact with Sema5A directly. Proteoglycans mediate Sema5A
bi-functional responses via interaction with its first four type-1
thrombospondin repeats. Further work has also identified the
neuronal heparan sulfate proteoglycan, syndecan-3, as a direct
binding partner for Sema5A.
In order to study the role of Sema5A
in vivo, a Sema5A conditional mutant mouse was generated
using
cre-loxP technology. Western blot analysis and immunohistochemistry
of Sema5A homozygous
mutant mice revealed that Sema5A-/- are null
for Sema5A protein. Detailed expression analyses indicate that
during embryogenesis, Sema5A is prominently expressed in the
ventricular zone of the dorsal telencephalon. Sema5A shows a
lateral-high to medial-low gradient of expression across the
ventricular/subventricular zone (VZ/SVZ) between E11-E16 in the
mouse. Furthermore, robust expression of Sema5A is seen in the
dentate gyrus (DG) postnatally and continues throughout adulthood.
Both the VZ/SVZ and the DG are areas known for their neurogenic
potential. During normal cortical development, neurons are born in
the VZ/SVZ, migrate up into the cortex along radial glia scaffolds,
and subsequently colonize their appropriate laminar layer within
the cortex. BrdU birthdating studies reveal that mice lacking
Sema5A exhibit abnormal corticogenesis owing to impaired radial
migration. Sema5A null mice demonstrate delayed migration of
newborn cortical neurons towards…
Subjects/Keywords: Semaphorin; Sema5A; Proteoglycan; Myelin-Associated Glycoprotein; Cortical; Migration
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Chivatakarn, O. (2009). Semaphorin 5A (Sema5A) functions in neocortical
development In vivo. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/8459
Chicago Manual of Style (16th Edition):
Chivatakarn, Onanong. “Semaphorin 5A (Sema5A) functions in neocortical
development In vivo.” 2009. Doctoral Dissertation, University of Rochester. Accessed January 17, 2021.
http://hdl.handle.net/1802/8459.
MLA Handbook (7th Edition):
Chivatakarn, Onanong. “Semaphorin 5A (Sema5A) functions in neocortical
development In vivo.” 2009. Web. 17 Jan 2021.
Vancouver:
Chivatakarn O. Semaphorin 5A (Sema5A) functions in neocortical
development In vivo. [Internet] [Doctoral dissertation]. University of Rochester; 2009. [cited 2021 Jan 17].
Available from: http://hdl.handle.net/1802/8459.
Council of Science Editors:
Chivatakarn O. Semaphorin 5A (Sema5A) functions in neocortical
development In vivo. [Doctoral Dissertation]. University of Rochester; 2009. Available from: http://hdl.handle.net/1802/8459

University of Oulu
13.
Päiväläinen-Jalonen, S. (Satu).
Expression and stability of myelin-associated elements.
Degree: 2007, University of Oulu
URL: http://urn.fi/urn:isbn:9789514285714
► Abstract The function of the nervous system is based on the targeted transmission of electrical impulses assuring the coordinated function of tissues and organs. Myelination…
(more)
▼ Abstract
The function of the nervous system is based on the targeted transmission of electrical impulses assuring the coordinated function of tissues and organs. Myelination of the neuronal axons allows the fast saltatory conduction by producing repetitive sites where sodium channels cluster on the axolemma. In the peripheral nervous system (PNS), myelin is formed by differentiation of the Schwann cell plasma membrane. The cells form myelin by first wrapping consecutive layers of the plasma membrane around the axons and then excluding almost all of the cytoplasm from the structure, forming compacted and non-compacted membrane compartments.
The myelin-associated glycoprotein (MAG) is located in all of the non-compacted regions of the PNS myelin sheath. Its two isoforms, L-MAG and S-MAG, differ only by the carboxy-terminal tails of their respective cytoplasmic domains. Both of the MAG isoforms are found in PNS myelin. They are differentially expressed during development and, until now, it has been thought that L-MAG is not present in the mature PNS myelin sheaths of murines. This study shows that both MAG isoforms can be found in different non-compacted membrane compartments in the mature PNS myelin sheaths in dorsal root ganglia (DRG)/Schwann cell cocultures.
Early myelin development and myelin maturation were analyzed by means of a study of the expression of two early myelin markers, MAG and galactosyl cerebrosides (Gal-CB), believed to play roles in both myelin formation and maintenance. In order to allow the exploitation of the full potential of the DRG/Schwann cell coculture model through the use of mouse mutants, a coculture method was developed in which mouse DRGs and Schwann cells are able, for the first time, to produce significant amounts of myelin. To further explore the role of MAG in myelin maintenance and stability, the stability of purified MAG was studied through extensive degradation experiments.
Subjects/Keywords: Schwann cell; culture model; myelin; myelin-associated glycoprotein; protease
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
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APA (6th Edition):
Päiväläinen-Jalonen, S. (. (2007). Expression and stability of myelin-associated elements. (Doctoral Dissertation). University of Oulu. Retrieved from http://urn.fi/urn:isbn:9789514285714
Chicago Manual of Style (16th Edition):
Päiväläinen-Jalonen, S (Satu). “Expression and stability of myelin-associated elements.” 2007. Doctoral Dissertation, University of Oulu. Accessed January 17, 2021.
http://urn.fi/urn:isbn:9789514285714.
MLA Handbook (7th Edition):
Päiväläinen-Jalonen, S (Satu). “Expression and stability of myelin-associated elements.” 2007. Web. 17 Jan 2021.
Vancouver:
Päiväläinen-Jalonen S(. Expression and stability of myelin-associated elements. [Internet] [Doctoral dissertation]. University of Oulu; 2007. [cited 2021 Jan 17].
Available from: http://urn.fi/urn:isbn:9789514285714.
Council of Science Editors:
Päiväläinen-Jalonen S(. Expression and stability of myelin-associated elements. [Doctoral Dissertation]. University of Oulu; 2007. Available from: http://urn.fi/urn:isbn:9789514285714

Vanderbilt University
14.
Perdigoto, Ana Luisa Jordao.
Mechanisms of neurite outgrowth inhibition by Myelin-associated glycoprotein.
Degree: PhD, Biochemistry, 2010, Vanderbilt University
URL: http://hdl.handle.net/1803/15014
► Axonal regeneration in the central nervous system is prevented, in part, by inhibitory proteins expressed by myelin, including Myelin-associated glycoprotein (MAG). Although injury to the…
(more)
▼ Axonal regeneration in the central nervous system is prevented, in part, by inhibitory proteins expressed by myelin, including Myelin-
associated glycoprotein (MAG). Although injury to the corticospinal tract can result in permanent disability, little is known regarding the mechanisms by which MAG affects cortical neurons. Here, we demonstrate that cortical neurons plated on MAG expressing CHO cells, exhibit a striking reduction in process outgrowth. Interestingly, none of the receptors previously implicated in MAG signaling, including the p75 neurotrophin receptor or gangliosides, contributed significantly to MAG-mediated inhibition. However, blocking the small GTPase Rho or its downstream effector kinase, ROCK, partially reversed the effects of MAG on the neurons. In addition, we identified the lipid phosphatase PTEN as a mediator of MAG’s inhibitory effects on neurite outgrowth. Knockdown or gene deletion of PTEN or over expression of activated AKT in cortical neurons resulted in significant, although partial, rescue of neurite outgrowth on MAG-CHO cells. PTEN knockout and Rho inactivation resulted in an additive effect on reversal of neurite outgrowth inhibition by MAG, suggesting that both molecules contribute to inhibition of cortical neurite outgrowth by MAG. Moreover, MAG decreased the levels of phospho-Akt, suggesting that it activates PTEN in the neurons. Taken together, these results suggest a novel pathway activated by MAG in cortical neurons involving the PTEN/PI3K/AKT axis.
Advisors/Committee Members: graham carpenter (committee member), scott heibert (committee member), Jennifer Pietenpol (committee member), Donna Webb (committee member), Bruce Carter (Committee Chair).
Subjects/Keywords: cortical neurons; PTEN; Myelin-associated glycoprotein; neurite outgrowth; AKT
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Perdigoto, A. L. J. (2010). Mechanisms of neurite outgrowth inhibition by Myelin-associated glycoprotein. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/15014
Chicago Manual of Style (16th Edition):
Perdigoto, Ana Luisa Jordao. “Mechanisms of neurite outgrowth inhibition by Myelin-associated glycoprotein.” 2010. Doctoral Dissertation, Vanderbilt University. Accessed January 17, 2021.
http://hdl.handle.net/1803/15014.
MLA Handbook (7th Edition):
Perdigoto, Ana Luisa Jordao. “Mechanisms of neurite outgrowth inhibition by Myelin-associated glycoprotein.” 2010. Web. 17 Jan 2021.
Vancouver:
Perdigoto ALJ. Mechanisms of neurite outgrowth inhibition by Myelin-associated glycoprotein. [Internet] [Doctoral dissertation]. Vanderbilt University; 2010. [cited 2021 Jan 17].
Available from: http://hdl.handle.net/1803/15014.
Council of Science Editors:
Perdigoto ALJ. Mechanisms of neurite outgrowth inhibition by Myelin-associated glycoprotein. [Doctoral Dissertation]. Vanderbilt University; 2010. Available from: http://hdl.handle.net/1803/15014
15.
佐藤, 翔.
Pre-operative evaluation of circulating KL-6 levels as a biomarker for epithelial ovarian carcinoma and its correlation with tumor MUC1 expression. : KL-6の上皮性卵巣癌のバイオマーカーとしての有用性と腫瘍MUC1発現との相関性の検討.
Degree: 博士(医学), 2018, Saitama Medical University / 埼玉医科大学
URL: http://id.nii.ac.jp/1386/00000613/
► Krebs von den Lungen-6 (KL-6), a mucinous sialylated sugar chain on human mucin-1 glycoprotein (MUC1), is a diagnostic marker for interstitial lung diseases. Furthermore, elevated…
(more)
▼ Krebs von den Lungen-6 (KL-6), a mucinous sialylated sugar chain on human mucin-1 glycoprotein (MUC1), is a diagnostic marker for interstitial lung diseases. Furthermore, elevated serum KL-6 levels have been observed in certain malignant tumor types of epithelial origin. The expression of MUC1 has been observed in patients with epithelial ovarian cancer (EOC) and is considered a potential therapeutic target. In the present study, KL-6 serum levels were investigated in patients clinically suspected of having malignant ovarian tumors. A total of 219 patients were enrolled in the study, which analyzed their serum KL-6 levels in addition to tumor expression of MUC1 using immunohistochemistry. High serum KL-6 levels were predominantly observed in patients with EOC, and did not occur in patients with benign or borderline tumors. The level of serum KL-6 was highly correlated with tumor stage, grade and histological type, and demonstrated superior sensitivity for the detection of ovarian cancer compared with that of serum cancer antigen 125. High serum KL-6 was significantly associated with shorter progression-free survival. In addition, tumor MUC1 expression status was significantly correlated with serum KL-6 levels. These data suggest that serum KL-6 may be a useful, non-invasive biomarker surrogate for tumor MUC1 expression in future clinical trials of MUC1-targeted therapy.
平成29年度
Subjects/Keywords: Krebs von den Lungen-6; diagnostic marker; human mucin-1 glycoprotein; ovarian cancer; serum biomarker
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
佐藤, . (2018). Pre-operative evaluation of circulating KL-6 levels as a biomarker for epithelial ovarian carcinoma and its correlation with tumor MUC1 expression. : KL-6の上皮性卵巣癌のバイオマーカーとしての有用性と腫瘍MUC1発現との相関性の検討. (Thesis). Saitama Medical University / 埼玉医科大学. Retrieved from http://id.nii.ac.jp/1386/00000613/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
佐藤, 翔. “Pre-operative evaluation of circulating KL-6 levels as a biomarker for epithelial ovarian carcinoma and its correlation with tumor MUC1 expression. : KL-6の上皮性卵巣癌のバイオマーカーとしての有用性と腫瘍MUC1発現との相関性の検討.” 2018. Thesis, Saitama Medical University / 埼玉医科大学. Accessed January 17, 2021.
http://id.nii.ac.jp/1386/00000613/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
佐藤, 翔. “Pre-operative evaluation of circulating KL-6 levels as a biomarker for epithelial ovarian carcinoma and its correlation with tumor MUC1 expression. : KL-6の上皮性卵巣癌のバイオマーカーとしての有用性と腫瘍MUC1発現との相関性の検討.” 2018. Web. 17 Jan 2021.
Vancouver:
佐藤 . Pre-operative evaluation of circulating KL-6 levels as a biomarker for epithelial ovarian carcinoma and its correlation with tumor MUC1 expression. : KL-6の上皮性卵巣癌のバイオマーカーとしての有用性と腫瘍MUC1発現との相関性の検討. [Internet] [Thesis]. Saitama Medical University / 埼玉医科大学; 2018. [cited 2021 Jan 17].
Available from: http://id.nii.ac.jp/1386/00000613/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
佐藤 . Pre-operative evaluation of circulating KL-6 levels as a biomarker for epithelial ovarian carcinoma and its correlation with tumor MUC1 expression. : KL-6の上皮性卵巣癌のバイオマーカーとしての有用性と腫瘍MUC1発現との相関性の検討. [Thesis]. Saitama Medical University / 埼玉医科大学; 2018. Available from: http://id.nii.ac.jp/1386/00000613/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Toronto
16.
Kearney, Samantha.
The Role of Sphingosine-1-Phosphate in Regulation of Multidrug Resistance at the Developing Blood-brain Barrier.
Degree: 2015, University of Toronto
URL: http://hdl.handle.net/1807/97272
► P-glycoprotein (P-gp) is an efflux transporter on brain endothelial cells (BECs) that protects the developing brain. Sphingosine-1-phosphate (S1P) can modify P-gp function in the adult…
(more)
▼ P-glycoprotein (P-gp) is an efflux transporter on brain endothelial cells (BECs) that protects the developing brain. Sphingosine-1-phosphate (S1P) can modify P-gp function in the adult blood- brain barrier (BBB). This thesis determined the effect of S1P on the developing BBB. We hypothesized that S1P reduces P-gp function in primary cultured guinea pig BECs dependent on developmental age. Treatment of BECs with exogenous S1P or FTY720P (S1P analog) had no effect on P-gp function. BECs treated with high doses of FTY720 (precursor of FTY720P and inhibitor of S1P production) decreased cellular S1P and decreased P-gp function. Extended incubation with the highest dose of FTY720 or SKi II (inhibitor of S1P production) increased P- gp function. These results indicate that S1P is important for maintaining P-gp activity and disruption of the S1P-ceramide rheostat can change P-gp function at the BBB, altering brain exposure to P-gp substrates and potentially adversely affecting brain development.
M.Sc.
2019-11-10 00:00:00
Advisors/Committee Members: Matthews, Stephen G, Physiology.
Subjects/Keywords: Brain development; Endothelial; Multidrug resistance; P-glycoprotein; Sphingolipids; Sphingosine-1-phosphate; 0719
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kearney, S. (2015). The Role of Sphingosine-1-Phosphate in Regulation of Multidrug Resistance at the Developing Blood-brain Barrier. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/97272
Chicago Manual of Style (16th Edition):
Kearney, Samantha. “The Role of Sphingosine-1-Phosphate in Regulation of Multidrug Resistance at the Developing Blood-brain Barrier.” 2015. Masters Thesis, University of Toronto. Accessed January 17, 2021.
http://hdl.handle.net/1807/97272.
MLA Handbook (7th Edition):
Kearney, Samantha. “The Role of Sphingosine-1-Phosphate in Regulation of Multidrug Resistance at the Developing Blood-brain Barrier.” 2015. Web. 17 Jan 2021.
Vancouver:
Kearney S. The Role of Sphingosine-1-Phosphate in Regulation of Multidrug Resistance at the Developing Blood-brain Barrier. [Internet] [Masters thesis]. University of Toronto; 2015. [cited 2021 Jan 17].
Available from: http://hdl.handle.net/1807/97272.
Council of Science Editors:
Kearney S. The Role of Sphingosine-1-Phosphate in Regulation of Multidrug Resistance at the Developing Blood-brain Barrier. [Masters Thesis]. University of Toronto; 2015. Available from: http://hdl.handle.net/1807/97272

University of Georgia
17.
Cato, David Allen.
Chemical synthesis of the O-linked oligosaccharide of P-Selectin Glycoprotein Ligand-1.
Degree: 2014, University of Georgia
URL: http://hdl.handle.net/10724/22609
► P-Selectin Glycoprotein Ligand-1 (PSGL-1) is the key ligand for selectins involved in the inflammatory cascade. This glycoprotein is necessary for the initial steps of the…
(more)
▼ P-Selectin Glycoprotein Ligand-1 (PSGL-1) is the key ligand for selectins involved in the inflammatory cascade. This glycoprotein is necessary for the initial steps of the inflammation process, and the absence of this ligand from leukocytes
eliminates transmigration of white blood cells into injured tissue. Also blocking P-selectins on the endothelial cell wall leads to decreases in transmigration of leukocytes. The key feature of PSGL-1 s binding to selectins is an 18 amino acid signal
sequence that contains 3 tyrosine sulfate residues and a glycosylated threonine residue. This sulfated glycoprotein has been chemoenzymatically synthesized on several occasions, but has never before been completely chemically synthesized. Chemical
synthesis will give this compound on a preparative scale that will allow for increased and improved biological studies on the blocking of P-selectins.
Subjects/Keywords: Inflammatory Cascade; Chronic Inflammation; P-Selectins; P-Selectin Glycoprotein Ligand-1; Leukocyte Transmigration
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Cato, D. A. (2014). Chemical synthesis of the O-linked oligosaccharide of P-Selectin Glycoprotein Ligand-1. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/22609
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Cato, David Allen. “Chemical synthesis of the O-linked oligosaccharide of P-Selectin Glycoprotein Ligand-1.” 2014. Thesis, University of Georgia. Accessed January 17, 2021.
http://hdl.handle.net/10724/22609.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Cato, David Allen. “Chemical synthesis of the O-linked oligosaccharide of P-Selectin Glycoprotein Ligand-1.” 2014. Web. 17 Jan 2021.
Vancouver:
Cato DA. Chemical synthesis of the O-linked oligosaccharide of P-Selectin Glycoprotein Ligand-1. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Jan 17].
Available from: http://hdl.handle.net/10724/22609.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Cato DA. Chemical synthesis of the O-linked oligosaccharide of P-Selectin Glycoprotein Ligand-1. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/22609
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of New South Wales
18.
Edmonds, Judith Helen.
Functional characterisation of the HIV-1 glycoprotein-41 cytoplasmic tail.
Degree: Clinical School - St Vincent's Hospital, 2009, University of New South Wales
URL: http://handle.unsw.edu.au/1959.4/44099
;
https://unsworks.unsw.edu.au/fapi/datastream/unsworks:7008/SOURCE02?view=true
► The unusually long Cytoplasmic tail (CT) of Human Immunodeficiency Virus Type-1 (HIV-1) glycoprotein-41 (gp41) is highly conserved and engineered large truncations often render the virus…
(more)
▼ The unusually long Cytoplasmic tail (CT) of Human Immunodeficiency Virus Type-1 (HIV-1) glycoprotein-41 (gp41) is highly conserved and engineered large truncations often render the virus non-infectious in a cell-type dependent manner. While large CT truncations occur infrequently in natural isolates, little is known about the mechanisms involved in infectious virions harbouring a large CT truncation. This thesis characterises RFgp34, a replication competent laboratory HIV-1 isolate with an acquired 100 amino acid CT truncation, and how it diverged from wildtype RF. The CT truncation and two possible compensatory mutations in Matrix (E40K and F44I) were introduced into the HIV-1 isolate NL4-3. These mutants were tested for infectivity, syncytia formation and glycoprotein incorporation into virions, alternative co-receptor usage and sensitivity to the fusion inhibitor T-20.Compared with RFwt, RFgp34-infected cultures displayed delayed viral replication kinetics in all cell types. Similar sized (MT-4 cells, PBMC) or larger and more numerous syncytia (Hut78 cells) were detected in RFgp34-infected cultures. Similar (Hut78 cells) or decreased (MT-4 cells, PBMC) amounts of glycoprotein was incorporated into RFgp34 virions, compared with RFwt virions. The increased syncytia in RFgp34-infected Hut78 cultures and the reduced glycoprotein incorporation into RFgp34 virions from MT-4 cells and PBMCs may explain the delayed RFgp34 replication kinetics. The Matrix E40K and F44I mutations were not able to directly compensate for the CT truncation to restore infectivity in Hut78 and MT-4 cells, as secondary mutations or the reversion of the CT truncation to a full-length CT were observed. In PBMCs the Matrix mutations alone were able to partially restore infectivity, suggesting specific mutations may compensate for the CT truncation in different cell types.None of the viruses utilised alternative HIV-1 co-receptors, nor were more resistant to T-20 than wildtype HIV-1 suggesting that the CT does not directly play a role in these viral functions. This thesis suggests that the sequence of mutations acquired by RFgp34 to compensate for the CT truncation and restore infectivity in multiple cell types may have occurred in a specific order and the evolution of RFgp34 to out-compete RFwt occurred over many passages.
Subjects/Keywords: HIV-1; Glycoprotein-41; Cytoplasmic tail
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Edmonds, J. H. (2009). Functional characterisation of the HIV-1 glycoprotein-41 cytoplasmic tail. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/44099 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:7008/SOURCE02?view=true
Chicago Manual of Style (16th Edition):
Edmonds, Judith Helen. “Functional characterisation of the HIV-1 glycoprotein-41 cytoplasmic tail.” 2009. Doctoral Dissertation, University of New South Wales. Accessed January 17, 2021.
http://handle.unsw.edu.au/1959.4/44099 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:7008/SOURCE02?view=true.
MLA Handbook (7th Edition):
Edmonds, Judith Helen. “Functional characterisation of the HIV-1 glycoprotein-41 cytoplasmic tail.” 2009. Web. 17 Jan 2021.
Vancouver:
Edmonds JH. Functional characterisation of the HIV-1 glycoprotein-41 cytoplasmic tail. [Internet] [Doctoral dissertation]. University of New South Wales; 2009. [cited 2021 Jan 17].
Available from: http://handle.unsw.edu.au/1959.4/44099 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:7008/SOURCE02?view=true.
Council of Science Editors:
Edmonds JH. Functional characterisation of the HIV-1 glycoprotein-41 cytoplasmic tail. [Doctoral Dissertation]. University of New South Wales; 2009. Available from: http://handle.unsw.edu.au/1959.4/44099 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:7008/SOURCE02?view=true

Kansas State University
19.
Brown, William.
Association
of acute-phase proteins with feed intake in transition dairy cows,
and factors affecting feed quality and digestibility.
Degree: PhD, Department of Animal Sciences
and Industry, 2020, Kansas State University
URL: http://hdl.handle.net/2097/40873
► Production performance of livestock is dependent upon adequate feed intake to meet metabolic demands, yet variations in health, metabolism, feed quality and feed digestibility can…
(more)
▼ Production performance of livestock is dependent upon
adequate feed intake to meet metabolic demands, yet variations in
health, metabolism, feed quality and feed digestibility can greatly
influence an animal’s ability to consume and digest feedstuffs in
order to reach their full potential. Using a large dataset in the
first study, we analyzed plasma alpha-
1-acid
glycoprotein (AGP), an
acute-phase protein, in 434 transition dairy cows to determine its
association with dry matter intake (DMI), common blood inflammatory
and metabolic biomarkers, and transition cow health disorders with
an overarching goal of evaluating AGP as a diagnostic tool. The
plasma AGP concentration increased after parturition to a peak at
14 d postpartum. There was a strong negative association between
AGP and DMI, metritis, retained placenta, hyperketonemia and
haptoglobin in the postpartum period, but overall diagnostic
ability of AGP was marginal based on receiver operating
characteristic analysis. Nonetheless, the ease of quantifying
plasma AGP and the lack of association with metabolic biomarkers
suggest it may be a useful tool to evaluate transition status in
dairy cows. In the second study, a novel high-protein corn product
(HPCP) was fed to high-producing, mid-lactation dairy cows and
compared with canola and soybean meals, and all diets were balanced
for lysine and methionine requirements. The HPCP decreased milk and
milk component yields through reduced total tract apparent dry
matter and crude protein digestibility, potentially due to Maillard
product formation. However, confirming previous research, the
canola meal performed similarly to soybean meal when lysine and
methionine requirements were met. Finally, forage quality is of
utmost importance in ruminant diets, and harvesting practices
influence the quality of the forage delivered to the animals. In
the third study, an innovative round hay baler equipped with knives
that cut the hay as it enters the baling chamber was employed,
reducing the particle size and potentially facilitating easier
incorporation of hay into total mixed rations. In this study,
pre-cutting alfalfa hay bales increased bale weight and density,
but also slightly, but significantly, increased neutral- and
acid-detergent fiber and lignin. When processing the pre-cut bales
in a mixer wagon, time to reduce particle size was greater compared
with tub-grinding normal bales, but less shrink occurred. The
determining factor for impacts of pre-cutting hay bales is
evaluation of the chemical composition of the processed hay which
could be fed to livestock, and data analysis is currently underway.
The fourth project seeks to understand factors impacting silage
hygiene that potentially have health implications for ruminants.
Soil contains numerous micro-organisms, including Clostridia spp.,
which is implicated in enteric diseases in ruminants. The study
evaluates whether drive-over silage piles stored on soil introduce
soil from equipment during the packing process, which may
inadvertently introduce pathogens. Of primary…
Advisors/Committee Members: Barry J. Bradford.
Subjects/Keywords: alpha-1-acid glycoprotein; pre-cut
hay; silage
hygiene;
high-protein corn product
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Brown, W. (2020). Association
of acute-phase proteins with feed intake in transition dairy cows,
and factors affecting feed quality and digestibility. (Doctoral Dissertation). Kansas State University. Retrieved from http://hdl.handle.net/2097/40873
Chicago Manual of Style (16th Edition):
Brown, William. “Association
of acute-phase proteins with feed intake in transition dairy cows,
and factors affecting feed quality and digestibility.” 2020. Doctoral Dissertation, Kansas State University. Accessed January 17, 2021.
http://hdl.handle.net/2097/40873.
MLA Handbook (7th Edition):
Brown, William. “Association
of acute-phase proteins with feed intake in transition dairy cows,
and factors affecting feed quality and digestibility.” 2020. Web. 17 Jan 2021.
Vancouver:
Brown W. Association
of acute-phase proteins with feed intake in transition dairy cows,
and factors affecting feed quality and digestibility. [Internet] [Doctoral dissertation]. Kansas State University; 2020. [cited 2021 Jan 17].
Available from: http://hdl.handle.net/2097/40873.
Council of Science Editors:
Brown W. Association
of acute-phase proteins with feed intake in transition dairy cows,
and factors affecting feed quality and digestibility. [Doctoral Dissertation]. Kansas State University; 2020. Available from: http://hdl.handle.net/2097/40873

Virginia Tech
20.
Glaros, Trevor Griffiths.
Molecular Mechanisms Governing Persistent Induction of Pro-Inflammatory Genes by Lipopolysaccharide.
Degree: PhD, Biology, 2011, Virginia Tech
URL: http://hdl.handle.net/10919/73001
► Low dose endotoxemia is caused by several health conditions including smoking, alcohol abuse, high fat diets, and aging. Several studies have correlated low dose endotoxemia…
(more)
▼ Low dose endotoxemia is caused by several health conditions including smoking, alcohol abuse, high fat diets, and aging. Several studies have correlated low dose endotoxemia with increased risks of atherosclerosis, diabetes, and Parkinson's disease. Unlike high doses of endotoxin which induce a strong but transient induction of pro-inflammatory mediators, low doses of endotoxin result in a mild but chronic induction of pro-inflammatory genes. The central hypothesis of our study was that if low doses of endotoxin are capable of inducing mild prolonged inflammation, then a unique signaling circuit must be utilized.
In the first study, the molecular mechanisms for the persistent induction of lipocalin 2 (LCN2) in response to 100 ng/mL of lipopolysaccharide (LPS) in kidney fibroblasts was examined. It appears that the intracellular signaling network responsible for the persistent induction of LCN2 requires both activator protein-
1 (AP-
1) and CCAAT/enhancer binding protein delta (C/ebpδ). Interleukin-
1 receptor-
associated kinase
1 (IRAK-
1) is critical for LCN2 expression.
In the second study, the molecular mechanisms governing the persistent induction of interleukin 6 (IL-6) upon a 50 pg/mL challenge of LPS in macrophages was examined. At this dose, only the persistent activation of cJun N-terminal kinase (JNK) and C/ebpδ was observed. IL-6 transcription requires the transient recruitment of activating transcription factor 2 (ATF2) and the persistent recruitment of C/ebpδ to the IL-6 promoter.
In the third study, the molecular mechanisms that mediate LPS-induced priming was examined. The results demonstrate that macrophages are able to sense their prior history of exposure to LPS that result in either a priming or tolerance phenotype upon a secondary challenge of LPS. Results suggest that this sensing mechanism involves cross-talk between IRAK-
1 and phosphoinositide-3-kinase (PI3K).
Collectively, these studies indicate that JNK and C/ebpδ are the primary players responsible for the persistent expression of pro-inflammatory genes during low dose endotoxemia. IRAK-
1 is a key intracellular signaling kinase that mediates signaling at low doses of LPS. IRAK-
1 is not only critical for low dose induced expression, but also for LPS-induced priming. This research has revealed a novel signaling pathway that could provide new molecular targets for drug development against chronic inflammatory diseases.
Advisors/Committee Members: Li, Liwu (committeechair), Capelluto, Daniel G. S. (committee member), Liu, Dongmin (committee member), Tyson, John J. (committee member).
Subjects/Keywords: Endotoxemia; Inflammation; Interleukin-1 Receptor-Associated Kinase 1; Lipopolysaccharide; Low Dose; Macrophage; Priming
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Glaros, T. G. (2011). Molecular Mechanisms Governing Persistent Induction of Pro-Inflammatory Genes by Lipopolysaccharide. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/73001
Chicago Manual of Style (16th Edition):
Glaros, Trevor Griffiths. “Molecular Mechanisms Governing Persistent Induction of Pro-Inflammatory Genes by Lipopolysaccharide.” 2011. Doctoral Dissertation, Virginia Tech. Accessed January 17, 2021.
http://hdl.handle.net/10919/73001.
MLA Handbook (7th Edition):
Glaros, Trevor Griffiths. “Molecular Mechanisms Governing Persistent Induction of Pro-Inflammatory Genes by Lipopolysaccharide.” 2011. Web. 17 Jan 2021.
Vancouver:
Glaros TG. Molecular Mechanisms Governing Persistent Induction of Pro-Inflammatory Genes by Lipopolysaccharide. [Internet] [Doctoral dissertation]. Virginia Tech; 2011. [cited 2021 Jan 17].
Available from: http://hdl.handle.net/10919/73001.
Council of Science Editors:
Glaros TG. Molecular Mechanisms Governing Persistent Induction of Pro-Inflammatory Genes by Lipopolysaccharide. [Doctoral Dissertation]. Virginia Tech; 2011. Available from: http://hdl.handle.net/10919/73001

Washington State University
21.
[No author].
Molecular Biology And Epidemiology of Grapevine Leafroll-Associated Viruses
.
Degree: 2016, Washington State University
URL: http://hdl.handle.net/2376/12097
► Studies were conducted on molecular biology and epidemiology of grapevine leafroll-associated viruses infecting wine grape (Vitis vinifera) cultivars in Washington State. In the first objective,…
(more)
▼ Studies were conducted on molecular biology and epidemiology of grapevine leafroll-
associated viruses infecting wine grape (Vitis vinifera) cultivars in Washington State. In the first objective, the complete genome sequence of two isolates of Grapevine leafroll-
associated virus
1 (GLRaV-
1, genus: Ampelovirus, family Closteroviridae) was determined to be 18,731 and 18,946 nucleotides. The genome of GLRaV-
1 isolates contain nine open reading frames with long 5’ and 3’ non-translated regions (NTRs). The sequence differences in the 5’NTR was used to develop a restriction fragment length polymorphism assay for distinguishing GLRaV-
1 variants in vineyards. Northern blot hybridization revealed the presence of three of the eight putative 3' co-terminal subgenomic (sg) RNAs at higher levels in virus infected grapevine samples. The 5’ termini of five sgRNAs were mapped and their leader sequences determined. The results provided a foundation to further elucidate the comparative molecular biology of grapevine-infecting members of the family Closteroviridae.
In the second objective, the spread of grapevine leafroll disease (GLD) was monitored for several seasons in vineyard blocks planted with three red-berried wine grape cultivars. Grapevines exhibiting GLD symptoms in these blocks were tested positive for Grapevine leafroll-
associated virus 3 (GLRaV-3, genus: Ampelovirus, family Closteroviridae). The temporal spread of GLD indicated higher number of symptomatic vines in each season compared to previous seasons, suggesting increased incidence of the disease during successive seasons. The spatial distribution of symptomatic vines in all three blocks indicated a disease gradient in which the highest percentage of symptomatic vines were present in rows closest to old vineyard blocks showing GLD symptoms. Spatial autocorrelation (dependence) analysis indicated random distribution of symptomatic vines during initial years of post-planting suggesting primary spread and clustering of symptomatic vines during subsequent years suggesting secondary spread of GLD. Sequence analysis of a portion of the heat-shock protein 70 homolog gene encoded by GLRaV-3 revealed predominance of one of the several genetic variants of the virus in the three vineyard blocks. These results provided for the first time science-based knowledge on nature of the spread of GLD in young vineyards to pursue site-specific disease management strategies under conditions prevailing in Washington State.
Advisors/Committee Members: Rayapati, Naidu A (advisor).
Subjects/Keywords: Plant pathology;
Virology;
Complete genome;
GLRaV-1;
Epidemiology of GLD;
Grapevine leafroll-associated virus 1;
Grapevine leafroll-associated virus 3;
Grapevine leafroll-associated viruses;
Grapevine leafroll disease
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
author], [. (2016). Molecular Biology And Epidemiology of Grapevine Leafroll-Associated Viruses
. (Thesis). Washington State University. Retrieved from http://hdl.handle.net/2376/12097
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
author], [No. “Molecular Biology And Epidemiology of Grapevine Leafroll-Associated Viruses
.” 2016. Thesis, Washington State University. Accessed January 17, 2021.
http://hdl.handle.net/2376/12097.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
author], [No. “Molecular Biology And Epidemiology of Grapevine Leafroll-Associated Viruses
.” 2016. Web. 17 Jan 2021.
Vancouver:
author] [. Molecular Biology And Epidemiology of Grapevine Leafroll-Associated Viruses
. [Internet] [Thesis]. Washington State University; 2016. [cited 2021 Jan 17].
Available from: http://hdl.handle.net/2376/12097.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
author] [. Molecular Biology And Epidemiology of Grapevine Leafroll-Associated Viruses
. [Thesis]. Washington State University; 2016. Available from: http://hdl.handle.net/2376/12097
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Boston University
22.
Huiting, Leah.
Functional and mechanistic characterization of ubiquitin fusion degradation 1 in MYC-driven leukemogenesis.
Degree: PhD, Pharmacology, 2018, Boston University
URL: http://hdl.handle.net/2144/32980
► Tumor cells often hijack endoplasmic reticulum (ER) mediated signaling to facilitate tumor progression by adapting to the cellular stress evoked by oncogene overexpression and adverse…
(more)
▼ Tumor cells often hijack endoplasmic reticulum (ER) mediated signaling to facilitate tumor progression by adapting to the cellular stress evoked by oncogene overexpression and adverse microenvironment. Despite the prevalence of MYC-driven cancers, how the MYC oncoprotein regulates ER stress response pathways during tumorigenesis remains incompletely understood. Here we show that MYC drives continuous upregulation of ubiquitin fusion degradation
1 (UFD1) during T-cell acute lymphoblastic leukemia (T-ALL) development. As the E2 component of an ER-
associated degradation (ERAD) complex, UFD1 facilitates the elimination of misfolded/unfolded proteins from the ER. We found that genetic and pharmacological disruption of UFD1 function exacerbates ER stress and activates the unfolded protein response (UPR). Specifically, UFD1 knockdown in human T-ALL cells impairs ERAD and promotes the proapoptotic UPR through the PERK-CHOP-BCL2 axis. This effect is demonstrated by an upregulation of PERK, phospho-PERK and its downstream effector CHOP, as well as a downregulation of BCL2 and BCLxL. Indeed, CHOP inactivation or BCL2 overexpression is sufficient to rescue tumor-cell apoptosis induced by UFD1 knockdown. Allelic loss of ufd1 in zebrafish similarly induces tumor-cell apoptosis and impairs MYC-driven T-ALL progression without affecting general animal health. These studies establish the UFD1-mediated ER stress response as an important mediator of MYC-driven tumor progression and suggest strategies for targeted therapy in T-ALL, and perhaps other MYC-driven cancers. Although UFD1-specific inhibitors have yet to be developed, inhibitors that target the p97 co-factor in UFD1-mediated ERAD are readily available. Importantly, we show that treatment with CB-5083, a selective and oral bioactive inhibitor of p97, can effectively kill human MYC-overexpressing T-ALL patient cells ex vivo and inhibits tumor progression in zebrafish models of MYC-driven T-ALL. Thus, CB-5083 treatment may represent an effective targeted therapy for T-ALL, especially relapsed/refractory ones with gain-of-function NOTCH1 mutations and thus MYC-overexpression.
Advisors/Committee Members: Feng, Hui (advisor), Singh, Anurag (advisor).
Subjects/Keywords: Pharmacology; Zebrafish; Endoplasmic reticulum associated degradation; Ubiquitin fusion degradation 1
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Huiting, L. (2018). Functional and mechanistic characterization of ubiquitin fusion degradation 1 in MYC-driven leukemogenesis. (Doctoral Dissertation). Boston University. Retrieved from http://hdl.handle.net/2144/32980
Chicago Manual of Style (16th Edition):
Huiting, Leah. “Functional and mechanistic characterization of ubiquitin fusion degradation 1 in MYC-driven leukemogenesis.” 2018. Doctoral Dissertation, Boston University. Accessed January 17, 2021.
http://hdl.handle.net/2144/32980.
MLA Handbook (7th Edition):
Huiting, Leah. “Functional and mechanistic characterization of ubiquitin fusion degradation 1 in MYC-driven leukemogenesis.” 2018. Web. 17 Jan 2021.
Vancouver:
Huiting L. Functional and mechanistic characterization of ubiquitin fusion degradation 1 in MYC-driven leukemogenesis. [Internet] [Doctoral dissertation]. Boston University; 2018. [cited 2021 Jan 17].
Available from: http://hdl.handle.net/2144/32980.
Council of Science Editors:
Huiting L. Functional and mechanistic characterization of ubiquitin fusion degradation 1 in MYC-driven leukemogenesis. [Doctoral Dissertation]. Boston University; 2018. Available from: http://hdl.handle.net/2144/32980

Duke University
23.
Cho, Jang-Eun.
Topoisomerase 1-dependent Mutagenesis in Saccharomyces cerevisiae
.
Degree: 2015, Duke University
URL: http://hdl.handle.net/10161/11386
► Topoisomerase 1 (Top1) resolves transcription-associated supercoils by generating transient single-strand breaks in DNA and is a major source of transcription-associated mutagenesis in Saccharomyces cerevisiae.…
(more)
▼ Topoisomerase
1 (Top1) resolves transcription-
associated supercoils by generating transient single-strand breaks in DNA and is a major source of transcription-
associated mutagenesis in Saccharomyces cerevisiae. Top1 generates a distinctive mutation signature characterized by deletions in short, tandem repeats, and a similar signature is
associated with ribonucleoside monophosphates (rNMPs) in DNA. DNA polymerases incorporate rNMPs into genomic DNA, and such rNMPs are efficiently removed in an error-free manner by ribonuclease (RNase) H2. In the absence of RNase H2, persistent rNMPs give rise to short deletions via a mutagenic process initiated by a Top1 incision at an rNMP. There is only partial overlap, however, between Top1-dependent deletion hotspots identified in highly transcribed DNA and those
associated with rNMPs, suggesting the existence of both rNMP-dependent and rNMP-independent events. Here I present evidence that rNMP-independent hotspots reflect processing of a trapped Top1 cleavage complex (Top1cc), and that rNMP-dependent hotspots reflect sequential Top1 reactions. A sequential-cleavage model for rNMP-dependent deletions is tested in vivo and in vitro, employing Top1 cleavage and ligation assays. In addition, I report that rNMP-dependent hotspot activity is significantly enhanced when Top1 incises the non-transcribed strand of an actively transcribing reporter gene. Finally, I describe a novel type of mutagenesis that reflects repair of multiple Top1ccs. Specifically, expression of a mutant Top1 with reduced ligation activity (Top1-T722A) caused large deletion mutations that are distinct from Top1-dependent short deletions. Genetic data indicates that Top1-T722A-dependent large deletions are non-homologous end joining events.
Advisors/Committee Members: Jinks-Robertson, Sue (advisor).
Subjects/Keywords: Genetics;
Molecular biology;
Biology;
Ribonucleotide;
rNMP;
Topoisomerase 1;
Transcription-associated Mutagenesis
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Cho, J. (2015). Topoisomerase 1-dependent Mutagenesis in Saccharomyces cerevisiae
. (Thesis). Duke University. Retrieved from http://hdl.handle.net/10161/11386
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Cho, Jang-Eun. “Topoisomerase 1-dependent Mutagenesis in Saccharomyces cerevisiae
.” 2015. Thesis, Duke University. Accessed January 17, 2021.
http://hdl.handle.net/10161/11386.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Cho, Jang-Eun. “Topoisomerase 1-dependent Mutagenesis in Saccharomyces cerevisiae
.” 2015. Web. 17 Jan 2021.
Vancouver:
Cho J. Topoisomerase 1-dependent Mutagenesis in Saccharomyces cerevisiae
. [Internet] [Thesis]. Duke University; 2015. [cited 2021 Jan 17].
Available from: http://hdl.handle.net/10161/11386.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Cho J. Topoisomerase 1-dependent Mutagenesis in Saccharomyces cerevisiae
. [Thesis]. Duke University; 2015. Available from: http://hdl.handle.net/10161/11386
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Canterbury
24.
Cotter, Rachel.
Trace amine associated receptors : a new target for medications in drug addiction.
Degree: MS, Psychology, 2012, University of Canterbury
URL: http://dx.doi.org/10.26021/5624
► The abuse of stimulant drugs, such as methamphetamine (METH), has become a major source of public concern in New Zealand. Specific medications for treating METH…
(more)
▼ The abuse of stimulant drugs, such as methamphetamine (METH), has become a major source of public concern in New Zealand. Specific medications for treating METH addiction are not available at present. The newly discovered trace amine- associated receptor 1 (TAAR1) constitutes a novel receptor target for medication development in neuropsychiatry. TAAR1 regulates monoamine systems in the brain, especially dopamine, and is activated directly by psychomotor stimulants, including METH. This study examined the effects of the newly developed TAAR1 partial agonist, RO5203648, in rat models of METH abuse. In experiment 1 rats were administered different doses of RO5203648 (0, 1.67, 5mg/kg i.p.) followed by METH (0, 0.75, 2mg/kg i.p.). Locomotor activity was monitored via automated video tracking system in an open field. The results revealed that RO5203648 dose- dependently reduced acute METH-induced stimulation and prevented long-term sensitization following chronic exposure. Paradoxically, in experiment 2, RO5203648 and METH treatment increased c-Fos protein expression in the nucleus accumbens and dorsal striatum. In experiment 3 rats were trained to consistently self-administer METH (0.5mg/kg/infusion) and were then pre-treated with RO5203648 (0, 3, 10mg/kg i.p.). The data showed that RO5203648 drastically reduced METH intake. Next, RO5203648 was substituted (0.25, 0.5, 1.0 mg/kg/infusion) for METH in the same paradigm. Remarkably, RO5203648 exhibited no reinforcing efficacy compared with METH. Taken together, these observations showed that RO5203648 is able to attenuate METH-related behaviours, including locomotor stimulation, sensitization and self-administration, and highlight the great potential of TAAR1-based medications for the treatment of METH addiction.
Subjects/Keywords: Drug Addiction; Methamphetamine; Medication; Trace Amine Associated Receptor 1; animal model
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Cotter, R. (2012). Trace amine associated receptors : a new target for medications in drug addiction. (Masters Thesis). University of Canterbury. Retrieved from http://dx.doi.org/10.26021/5624
Chicago Manual of Style (16th Edition):
Cotter, Rachel. “Trace amine associated receptors : a new target for medications in drug addiction.” 2012. Masters Thesis, University of Canterbury. Accessed January 17, 2021.
http://dx.doi.org/10.26021/5624.
MLA Handbook (7th Edition):
Cotter, Rachel. “Trace amine associated receptors : a new target for medications in drug addiction.” 2012. Web. 17 Jan 2021.
Vancouver:
Cotter R. Trace amine associated receptors : a new target for medications in drug addiction. [Internet] [Masters thesis]. University of Canterbury; 2012. [cited 2021 Jan 17].
Available from: http://dx.doi.org/10.26021/5624.
Council of Science Editors:
Cotter R. Trace amine associated receptors : a new target for medications in drug addiction. [Masters Thesis]. University of Canterbury; 2012. Available from: http://dx.doi.org/10.26021/5624
25.
Gasser, Romain.
Comprendre la flexibilité génétique de la protéine d’enveloppe de VIH-1 à travers l’étude du réseau de coévolution de ses acides aminés : Understanding the genetic flexibility of the HIV-1 envelope protein through the study of the network of its coevolving amino acids.
Degree: Docteur es, Virologie : aspects moléculaires et médicaux, 2016, Université de Strasbourg
URL: http://www.theses.fr/2016STRAJ026
► Une des caractéristiques du Virus de l’Immunodéficience Humaine de type 1 (VIH-1) est sa diversification génétique extensive, qui lui permet d’échapper au système immunitaire. Néanmoins,…
(more)
▼ Une des caractéristiques du Virus de l’Immunodéficience Humaine de type 1 (VIH-1) est sa diversification génétique extensive, qui lui permet d’échapper au système immunitaire. Néanmoins, il est nécessaire que le taux de mutation requis pour à cette évolution rapide ne compromette pas la fonctionnalité de ses protéines. Les travaux présentés ici ont eu pour objectif l’étude des réseaux de coévolution qui composent les glycoprotéines d’enveloppe (Env) afin de comprendre les règles qui sous-tendent leur évolution. Il a été mis en évidence que les régions variables de ces protéines, grâce à leur flexibilité structurelle, peuvent aussi servir à faciliter l’incorporation de mutations touchant les régions plus constantes. De plus, un réseau de coévolution impliqué dans les changements de conformations nécessaires à l’activité de Env a été identifié, soutenant le fait que ces régions variables ont un rôle central dans ces changements. Ces études démontrent le rôle crucial joué par les régions variables en dévoilant un nouvel aspect de leur contribution à l’évolution du VIH-1.
The Human Immunodeficiency Virus type 1 (HIV-1) is characterized by an extensive genetic diversification of its strains that allows the virus to escape the immune system. However, the mutation rate needed for this rapid evolution must not compromise the functionality of the viral proteins. The aim of the work presented here has been to study the coevolution networks that constitute the envelope glycoproteins (Env) in order to understand the rules driving their evolution. The results have highlighted that variable regions, thanks to their structural freedom, can facilitate the incorporation of mutations in more constant regions. Moreover, a coevolution network involved in the conformational changes required for the activity of Env has been identified, underlining the central role played by variable regions in these processes. Besides underscoring the crucial role played by variable regions in the functionality of Env, these studies unveil a new aspect of their contribution to HIV-1 evolution.
Advisors/Committee Members: Negroni, Matteo (thesis director).
Subjects/Keywords: VIH-1; Glycoprotéine d’enveloppe; Réseau de coévolution; Fonctionnalité; HIV-1; Envelope glycoprotein; Coevolution network; Functionality; 572.8; 616.97
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Gasser, R. (2016). Comprendre la flexibilité génétique de la protéine d’enveloppe de VIH-1 à travers l’étude du réseau de coévolution de ses acides aminés : Understanding the genetic flexibility of the HIV-1 envelope protein through the study of the network of its coevolving amino acids. (Doctoral Dissertation). Université de Strasbourg. Retrieved from http://www.theses.fr/2016STRAJ026
Chicago Manual of Style (16th Edition):
Gasser, Romain. “Comprendre la flexibilité génétique de la protéine d’enveloppe de VIH-1 à travers l’étude du réseau de coévolution de ses acides aminés : Understanding the genetic flexibility of the HIV-1 envelope protein through the study of the network of its coevolving amino acids.” 2016. Doctoral Dissertation, Université de Strasbourg. Accessed January 17, 2021.
http://www.theses.fr/2016STRAJ026.
MLA Handbook (7th Edition):
Gasser, Romain. “Comprendre la flexibilité génétique de la protéine d’enveloppe de VIH-1 à travers l’étude du réseau de coévolution de ses acides aminés : Understanding the genetic flexibility of the HIV-1 envelope protein through the study of the network of its coevolving amino acids.” 2016. Web. 17 Jan 2021.
Vancouver:
Gasser R. Comprendre la flexibilité génétique de la protéine d’enveloppe de VIH-1 à travers l’étude du réseau de coévolution de ses acides aminés : Understanding the genetic flexibility of the HIV-1 envelope protein through the study of the network of its coevolving amino acids. [Internet] [Doctoral dissertation]. Université de Strasbourg; 2016. [cited 2021 Jan 17].
Available from: http://www.theses.fr/2016STRAJ026.
Council of Science Editors:
Gasser R. Comprendre la flexibilité génétique de la protéine d’enveloppe de VIH-1 à travers l’étude du réseau de coévolution de ses acides aminés : Understanding the genetic flexibility of the HIV-1 envelope protein through the study of the network of its coevolving amino acids. [Doctoral Dissertation]. Université de Strasbourg; 2016. Available from: http://www.theses.fr/2016STRAJ026

University of Cambridge
26.
Ren, Yudan.
Glycoprotein M and ESCRT in herpes simplex virus type 1 assembly.
Degree: PhD, 2012, University of Cambridge
URL: http://www.dspace.cam.ac.uk/handle/1810/241516https://www.repository.cam.ac.uk/bitstream/1810/241516/2/license.txt
;
https://www.repository.cam.ac.uk/bitstream/1810/241516/3/license_url
;
https://www.repository.cam.ac.uk/bitstream/1810/241516/4/license_text
;
https://www.repository.cam.ac.uk/bitstream/1810/241516/5/license_rdf
;
https://www.repository.cam.ac.uk/bitstream/1810/241516/8/PhD_Ren2011.pdf.txt
;
https://www.repository.cam.ac.uk/bitstream/1810/241516/9/PhD_Ren2011.pdf.jpg
► Herpes simplex virus type 1 (HSV-1) has a large linear double-stranded DNA genome in an icosahedral capsid shell, a cell-derived lipid envelope and a proteinaceous…
(more)
▼ Herpes simplex virus type 1 (HSV-1) has a large linear double-stranded DNA genome in an icosahedral capsid shell, a cell-derived lipid envelope and a proteinaceous tegument layer. There are over fifty viral proteins and many host proteins identified in HSV-1 virions. The final formation of mature virus particles requires the membrane wrapping of tegumented capsids in the cytoplasm, a process termed secondary envelopment. This process involves the coordination of numerous viral and cellular proteins and results in double-membrane structures with enveloped virions contained within cellular vesicles. Mature viruses are then released through the fusion of these virion-containing vesicles and plasma membranes. This thesis describes investigation into the functions of viral glycoprotein M (gM) and the cellular Endosomal Sorting Complexes Required for Transport (ESCRT) in secondary envelopment.
Firstly, it has been reported that gH/L can be efficiently internalised and targeted to the TGN by the co-expression of gM in transfection assays. In order to examine the role of gM in guiding the localisation of viral proteins in infected cells, a HSV-1 gM deletion virus (∆gM), and its revertant virus were constructed. The major phenotype demonstrated was that the absence of gM caused the internalisation of cell surface gH/L to be inhibited and higher levels of gH/L to be observed on the cell surface. Further, lower levels of gH/L were detected in purified ∆gM virions, which was in agreement with the delayed entry kinetics, smaller plaque sizes and greater replication deficits at low multiplicity of infection observed in ∆gM infected cells. Over all the results presented in this thesis demonstrate that in infected cells the efficient incorporation of gH/L into virions relies on the function of gM in HSV-1.
Secondly, during HSV-1 secondary envelopment the budding and scission of the viral envelope from the host membrane share topological similarities with the formation of intraluminal vesicle in multivesicular bodies, retrovirus budding, and abscission at the end of cytokinesis, processes that require the cellular ESCRT machinery. There are four multiprotein ESCRT complexes and many associated proteins involved in their regulation. It has been previously shown that the ESCRT-III complex and a functional ATPase VPS4 are required for HSV-1 secondary envelopment, but different from the strategy utilised by HIV-1, the recruitment of ESCRT during HSV-1 infection is independent of TSG101 and/or ALIX. Data presented in this thesis demonstrate that CHMP4A/B/C proteins of the ESCRT-III complex are specifically crucial for HSV-1 secondary envelopment. Simultaneous depletion of CHMP4A/B/C proteins significantly inhibited HSV-1 replication. Ultrastructure analysis revealed that there were virtually no extracellular virions in CHMP4A/B/C depleted samples while more free capsids were observed in the cytoplasm, although the nuclear capsids and primary envelopment events appeared to be normal. In order to identify interactions between HSV-1 and…
Subjects/Keywords: Herpes simplex virus type 1 (HSV-1); Tegument; Assembly; Glycoprotein M; Endosomal sorting complexes required for transport (ESCRT); Viral-host interaction
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ren, Y. (2012). Glycoprotein M and ESCRT in herpes simplex virus type 1 assembly. (Doctoral Dissertation). University of Cambridge. Retrieved from http://www.dspace.cam.ac.uk/handle/1810/241516https://www.repository.cam.ac.uk/bitstream/1810/241516/2/license.txt ; https://www.repository.cam.ac.uk/bitstream/1810/241516/3/license_url ; https://www.repository.cam.ac.uk/bitstream/1810/241516/4/license_text ; https://www.repository.cam.ac.uk/bitstream/1810/241516/5/license_rdf ; https://www.repository.cam.ac.uk/bitstream/1810/241516/8/PhD_Ren2011.pdf.txt ; https://www.repository.cam.ac.uk/bitstream/1810/241516/9/PhD_Ren2011.pdf.jpg
Chicago Manual of Style (16th Edition):
Ren, Yudan. “Glycoprotein M and ESCRT in herpes simplex virus type 1 assembly.” 2012. Doctoral Dissertation, University of Cambridge. Accessed January 17, 2021.
http://www.dspace.cam.ac.uk/handle/1810/241516https://www.repository.cam.ac.uk/bitstream/1810/241516/2/license.txt ; https://www.repository.cam.ac.uk/bitstream/1810/241516/3/license_url ; https://www.repository.cam.ac.uk/bitstream/1810/241516/4/license_text ; https://www.repository.cam.ac.uk/bitstream/1810/241516/5/license_rdf ; https://www.repository.cam.ac.uk/bitstream/1810/241516/8/PhD_Ren2011.pdf.txt ; https://www.repository.cam.ac.uk/bitstream/1810/241516/9/PhD_Ren2011.pdf.jpg.
MLA Handbook (7th Edition):
Ren, Yudan. “Glycoprotein M and ESCRT in herpes simplex virus type 1 assembly.” 2012. Web. 17 Jan 2021.
Vancouver:
Ren Y. Glycoprotein M and ESCRT in herpes simplex virus type 1 assembly. [Internet] [Doctoral dissertation]. University of Cambridge; 2012. [cited 2021 Jan 17].
Available from: http://www.dspace.cam.ac.uk/handle/1810/241516https://www.repository.cam.ac.uk/bitstream/1810/241516/2/license.txt ; https://www.repository.cam.ac.uk/bitstream/1810/241516/3/license_url ; https://www.repository.cam.ac.uk/bitstream/1810/241516/4/license_text ; https://www.repository.cam.ac.uk/bitstream/1810/241516/5/license_rdf ; https://www.repository.cam.ac.uk/bitstream/1810/241516/8/PhD_Ren2011.pdf.txt ; https://www.repository.cam.ac.uk/bitstream/1810/241516/9/PhD_Ren2011.pdf.jpg.
Council of Science Editors:
Ren Y. Glycoprotein M and ESCRT in herpes simplex virus type 1 assembly. [Doctoral Dissertation]. University of Cambridge; 2012. Available from: http://www.dspace.cam.ac.uk/handle/1810/241516https://www.repository.cam.ac.uk/bitstream/1810/241516/2/license.txt ; https://www.repository.cam.ac.uk/bitstream/1810/241516/3/license_url ; https://www.repository.cam.ac.uk/bitstream/1810/241516/4/license_text ; https://www.repository.cam.ac.uk/bitstream/1810/241516/5/license_rdf ; https://www.repository.cam.ac.uk/bitstream/1810/241516/8/PhD_Ren2011.pdf.txt ; https://www.repository.cam.ac.uk/bitstream/1810/241516/9/PhD_Ren2011.pdf.jpg
27.
Buttler, Carmen Anne.
Superresolved Three-Dimensional Analysis of the Spatial Arrangement of the Human Immunodeficiency Virus Type-1 (HIV-1) Envelope Glycoprotein at Sites of Viral Assembly.
Degree: MS, Biological Sciences, 2018, U of Denver
URL: https://digitalcommons.du.edu/etd/1449
► Human Immunodeficiency Virus type 1 (HIV-1) replicates by forcing infected host cells to produce new virus particles, which assemble form protein components on the…
(more)
▼ Human Immunodeficiency Virus type 1 (HIV-
1) replicates by forcing infected host cells to produce new virus particles, which assemble form protein components on the inner leaflet of the host cell's plasma membrane. This involves incorporation of the essential viral envelope
glycoprotein (Env) into a structural lattice of viral Gag proteins. The mechanism of Env recruitment and incorporation is not well understood. To better define this process, we seek to describe the timing of Env-Gag encounters during particle assembly by measuring angular positions of Env proteins about the surfaces of budding particles. Using three-dimensional superresolution microscopy, we show that Env distributions are biased toward the necks of budding particles, indicating incorporation of Env late in the assembly of the lattice. We show that this behavior is dependent on the host cell type and on the long cytoplasmic tail of Env. We propose a model wherein Env incorporation is regulated by opposing mechanisms: Gag lattice trapping of Env cytoplasmic tails, and intracellular sequestering of Env during lattice assembly.
Advisors/Committee Members: Schuyler B. Van Engelenburg, Ph.D..
Subjects/Keywords: HIV-1; HIV type 1; HIV; Env; Envelope glycoprotein; iPALM; Interferometric PALM; Superresolution; Virus assembly; Cell Biology; Molecular Biology; Virology
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Buttler, C. A. (2018). Superresolved Three-Dimensional Analysis of the Spatial Arrangement of the Human Immunodeficiency Virus Type-1 (HIV-1) Envelope Glycoprotein at Sites of Viral Assembly. (Thesis). U of Denver. Retrieved from https://digitalcommons.du.edu/etd/1449
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Buttler, Carmen Anne. “Superresolved Three-Dimensional Analysis of the Spatial Arrangement of the Human Immunodeficiency Virus Type-1 (HIV-1) Envelope Glycoprotein at Sites of Viral Assembly.” 2018. Thesis, U of Denver. Accessed January 17, 2021.
https://digitalcommons.du.edu/etd/1449.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Buttler, Carmen Anne. “Superresolved Three-Dimensional Analysis of the Spatial Arrangement of the Human Immunodeficiency Virus Type-1 (HIV-1) Envelope Glycoprotein at Sites of Viral Assembly.” 2018. Web. 17 Jan 2021.
Vancouver:
Buttler CA. Superresolved Three-Dimensional Analysis of the Spatial Arrangement of the Human Immunodeficiency Virus Type-1 (HIV-1) Envelope Glycoprotein at Sites of Viral Assembly. [Internet] [Thesis]. U of Denver; 2018. [cited 2021 Jan 17].
Available from: https://digitalcommons.du.edu/etd/1449.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Buttler CA. Superresolved Three-Dimensional Analysis of the Spatial Arrangement of the Human Immunodeficiency Virus Type-1 (HIV-1) Envelope Glycoprotein at Sites of Viral Assembly. [Thesis]. U of Denver; 2018. Available from: https://digitalcommons.du.edu/etd/1449
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
28.
Bouvin-Pley, Mélanie.
Dérive de la glycoprotéine d'enveloppe du VIH-1 au cours de l'épidémie : augmentation de sa résistance aux anticorps neutralisants et amélioration de ses propriétés fonctionnelles : Drift of the envelope glycoprotein of HIV-1 over the course of the epidemic : enhanced resistance to neutralizing antibodies and improved functionality.
Degree: Docteur es, Sciences de la vie et de la santé, spécialité Virologie, 2015, Université François-Rabelais de Tours
URL: http://www.theses.fr/2015TOUR3803
► Lors de la primo-infection, la plupart des patients infectés par le VIH-1 développent des anticorps neutralisants autologues dirigés contre la glycoprotéine d’enveloppe virale. Ces anticorps…
(more)
▼ Lors de la primo-infection, la plupart des patients infectés par le VIH-1 développent des anticorps neutralisants autologues dirigés contre la glycoprotéine d’enveloppe virale. Ces anticorps exercent une pression de sélection conduisant à l’apparition de variants d’échappement. Nous avons montré que cette pression de sélection se répercute à l’échelle populationnelle, le VIH-1 en tant qu’espèce s’étant adapté au cours de l’épidémie à la réponse immunitaire de la population humaine en devenant de moins en moins sensible aux anticorps neutralisants. Cette adaptation du VIH‐1 a un impact sur les propriétés fonctionnelles de l’enveloppe. Nous avons ainsi observé une augmentation de l’infectivité associée à une augmentation de la cinétique d’entrée des virus qui circulent actuellement. Les virus contemporains montrent également une plus grande résistance à l’enfuvirtide, un inhibiteur de fusion, associée à une meilleure utilisation du co-récepteur CCR5 ainsi qu’une résistance accrue à l’inhibiteur du CD4 M48U1. L’ensemble de nos résultats est en faveur d’une adaptation progressive de l’espèce virale du VIH-1 à son hôte au cours de l’épidémie.
Most of HIV-1 infected patients develop autologous neutralizing antibodies against the viral envelope glycoprotein during primary infection. These antibodies exert a selective pressure that leads to the selection of escape variants. We showed that HIV-1 evolved at the population level towards an enhanced resistance to antibody neutralization over the course of the epidemic, subsequently to the selective pressure exerted by the individual autologous neutralizing antibodies responses. This antigenic drift has an impact on the functional properties of the viral envelope. We showed an increasing infectivity associated with an increasing entry kinetic of the most recently transmitted viruses. The contemporary viruses are also more resistant to the inhibitor of fusion enfuvirtide, related to a better use of the CCR5 co-receptor as well as a progressive increasing resistance to the CD4 inhibitor M48U1. Together our results are in favor of a progressive adaptation of HIV-1 species to humans over the course of the epidemic.
Advisors/Committee Members: Braibant, Martine (thesis director).
Subjects/Keywords: VIH-1; Glycoprotéine d’enveloppe; Propriétés fonctionnelles; Entrée; Anticorps neutralisants; HIV-1; Envelope glycoprotein; Functional properties; Entry; Neutralizing antibodies
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Bouvin-Pley, M. (2015). Dérive de la glycoprotéine d'enveloppe du VIH-1 au cours de l'épidémie : augmentation de sa résistance aux anticorps neutralisants et amélioration de ses propriétés fonctionnelles : Drift of the envelope glycoprotein of HIV-1 over the course of the epidemic : enhanced resistance to neutralizing antibodies and improved functionality. (Doctoral Dissertation). Université François-Rabelais de Tours. Retrieved from http://www.theses.fr/2015TOUR3803
Chicago Manual of Style (16th Edition):
Bouvin-Pley, Mélanie. “Dérive de la glycoprotéine d'enveloppe du VIH-1 au cours de l'épidémie : augmentation de sa résistance aux anticorps neutralisants et amélioration de ses propriétés fonctionnelles : Drift of the envelope glycoprotein of HIV-1 over the course of the epidemic : enhanced resistance to neutralizing antibodies and improved functionality.” 2015. Doctoral Dissertation, Université François-Rabelais de Tours. Accessed January 17, 2021.
http://www.theses.fr/2015TOUR3803.
MLA Handbook (7th Edition):
Bouvin-Pley, Mélanie. “Dérive de la glycoprotéine d'enveloppe du VIH-1 au cours de l'épidémie : augmentation de sa résistance aux anticorps neutralisants et amélioration de ses propriétés fonctionnelles : Drift of the envelope glycoprotein of HIV-1 over the course of the epidemic : enhanced resistance to neutralizing antibodies and improved functionality.” 2015. Web. 17 Jan 2021.
Vancouver:
Bouvin-Pley M. Dérive de la glycoprotéine d'enveloppe du VIH-1 au cours de l'épidémie : augmentation de sa résistance aux anticorps neutralisants et amélioration de ses propriétés fonctionnelles : Drift of the envelope glycoprotein of HIV-1 over the course of the epidemic : enhanced resistance to neutralizing antibodies and improved functionality. [Internet] [Doctoral dissertation]. Université François-Rabelais de Tours; 2015. [cited 2021 Jan 17].
Available from: http://www.theses.fr/2015TOUR3803.
Council of Science Editors:
Bouvin-Pley M. Dérive de la glycoprotéine d'enveloppe du VIH-1 au cours de l'épidémie : augmentation de sa résistance aux anticorps neutralisants et amélioration de ses propriétés fonctionnelles : Drift of the envelope glycoprotein of HIV-1 over the course of the epidemic : enhanced resistance to neutralizing antibodies and improved functionality. [Doctoral Dissertation]. Université François-Rabelais de Tours; 2015. Available from: http://www.theses.fr/2015TOUR3803
29.
Beretta, Maxime.
Etude des propriétés fonctionnelles de la glycoprotéine d'enveloppe des variants transmis du VIH-1 et de leur évolution à l'échelle individuelle et populationnelle : Functional properties of envelope glycoproteins of transmitted HIV-1 variants and their evolution during the infection or over the course of the epidemic.
Degree: Docteur es, Sciences de la vie et de la santé, spécialité Virologie, 2018, Université François-Rabelais de Tours
URL: http://www.theses.fr/2018TOUR4019
► Lors de la transmission sexuelle du VIH-1, un seul ou un nombre très limité de variants viraux sont transmis parmi ceux présents chez le donneur.…
(more)
▼ Lors de la transmission sexuelle du VIH-1, un seul ou un nombre très limité de variants viraux sont transmis parmi ceux présents chez le donneur. Il est important de comprendre si le variant transmis est sélectionné aléatoirement parmi ceux présents chez le donneur ou s’il possède un avantage sélectif qui le prédispose à établir plus efficacement une nouvelle infection. Lors de nos différents travaux, nous avons pu observer chez quatre patients une évolution parallèle des propriétés génétiques, antigéniques et fonctionnelles de la glycoprotéine d’enveloppe au cours de l’infection. L’évolution de certaines propriétés est répercutée à l’échelle populationnelle. Néanmoins nous avons montré que malgré ces évolutions, les virus transmis au sein d’une même chaîne de transmission présentent des propriétés biologiques conservées. L’ensemble de nos résultats vont en faveur d’une sélection d’un variant viral avec des propriétés particulières lors de la transmission. De plus le variant transmis possède une région V3 particulièrement conservée associée à un tropisme CCR5, une sensibilité au Maraviroc et semble avoir besoin d’un taux élevé de CD4 à la surface de la cellule cible.
During HIV-1 sexual transmission, a single virus among the numerous viral variants present in the donor is transmitted most often. The key question is to understand if transmitted variants are randomly selected among variants from the donor or they have biological properties that predispose them to establish more efficiently a new infection. We observed a parallel evolution of genetic, antigenic and functional properties of the envelope glycoprotein in four patients during the infection. In addition, the evolution of some properties is also observed at the populational level. However, we showed that transmitted variants from a same transmission chain share similar biological properties. Together our results suggest that the transmission bottleneck is mainly non-stochastic and involves the selection viral variants harboring specific phenotypic properties. Despite transmitted variants have a conserved V3 region associated with a CCR5 tropism, sensitivity to Maraviroc and seem to require high level of CD4 to efficiently infect target cells.
Advisors/Committee Members: Braibant, Martine (thesis director).
Subjects/Keywords: VIH-1; Variant transmis; Glycoprotéine d’enveloppe; Propriétés fonctionnelles; Antigénicité; HIV-1; Transmitted variant; Envelope glycoprotein; Functional properties; Entry; Antigenicity
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Beretta, M. (2018). Etude des propriétés fonctionnelles de la glycoprotéine d'enveloppe des variants transmis du VIH-1 et de leur évolution à l'échelle individuelle et populationnelle : Functional properties of envelope glycoproteins of transmitted HIV-1 variants and their evolution during the infection or over the course of the epidemic. (Doctoral Dissertation). Université François-Rabelais de Tours. Retrieved from http://www.theses.fr/2018TOUR4019
Chicago Manual of Style (16th Edition):
Beretta, Maxime. “Etude des propriétés fonctionnelles de la glycoprotéine d'enveloppe des variants transmis du VIH-1 et de leur évolution à l'échelle individuelle et populationnelle : Functional properties of envelope glycoproteins of transmitted HIV-1 variants and their evolution during the infection or over the course of the epidemic.” 2018. Doctoral Dissertation, Université François-Rabelais de Tours. Accessed January 17, 2021.
http://www.theses.fr/2018TOUR4019.
MLA Handbook (7th Edition):
Beretta, Maxime. “Etude des propriétés fonctionnelles de la glycoprotéine d'enveloppe des variants transmis du VIH-1 et de leur évolution à l'échelle individuelle et populationnelle : Functional properties of envelope glycoproteins of transmitted HIV-1 variants and their evolution during the infection or over the course of the epidemic.” 2018. Web. 17 Jan 2021.
Vancouver:
Beretta M. Etude des propriétés fonctionnelles de la glycoprotéine d'enveloppe des variants transmis du VIH-1 et de leur évolution à l'échelle individuelle et populationnelle : Functional properties of envelope glycoproteins of transmitted HIV-1 variants and their evolution during the infection or over the course of the epidemic. [Internet] [Doctoral dissertation]. Université François-Rabelais de Tours; 2018. [cited 2021 Jan 17].
Available from: http://www.theses.fr/2018TOUR4019.
Council of Science Editors:
Beretta M. Etude des propriétés fonctionnelles de la glycoprotéine d'enveloppe des variants transmis du VIH-1 et de leur évolution à l'échelle individuelle et populationnelle : Functional properties of envelope glycoproteins of transmitted HIV-1 variants and their evolution during the infection or over the course of the epidemic. [Doctoral Dissertation]. Université François-Rabelais de Tours; 2018. Available from: http://www.theses.fr/2018TOUR4019
30.
Chaillon, Antoine.
Glycoprotéines d'enveloppe du virus de l'immunodéficience humaine (VIH) : contribution à l'étude des propriétés biologiques et des mécanismes de protection par anticorps neutralisants : HIV env glycoproteins : contribution to the study of biological properties and protection mechanisms by neutralizing antibodies.
Degree: Docteur es, Sciences de la Vie et de la Santé, 2012, Université François-Rabelais de Tours
URL: http://www.theses.fr/2012TOUR3312
► La problématique de la neutralisation par les anticorps constitue un enjeu majeur dans la perspective de la conception d’un vaccin efficace contre le VIH et…
(more)
▼ La problématique de la neutralisation par les anticorps constitue un enjeu majeur dans la perspective de la conception d’un vaccin efficace contre le VIH et les connaissances récemment acquises conforte NT l’absolue nécessité de maintenir une recherche cognitive fondamentale sur le sujet. L’un des objectifs de ce travail de thèse a été de documenter les propriétés biologiques en terme de sensibilité à la neutralisation de variants présents chez certains patients asymptomatiques à long terme (ALT) et présentant des caractéristiques particulières. Nous avons pu identifié certains déterminants moléculaires associés à la sensibilité ou à la résistance à l’anticorps monoclonal 2G12 tels le site potentiel de glycosylation (PNGS) en position N302 et la longueur de la boucle V1V2 du gène env. Nous avons ensuite caractérisé la relation entre l’évolution du gène env et la sensibilité à la neutralisation dans un contexte d’évolution tardive chez un patient ALT. Ces travaux ont permis de mettre en évidence une poursuite de l’évolution du gène env plus de 10 ans après l’infection et ceci malgré la présence d’anticorps largement neutralisants et d’une réponse autologue croissante au cours du temps. Le contexte de la transmission mère enfant (TME) constitue un modèle de choix afin d’étudier le rôle des anticorps neutralisants. Afin d’identifier d’éventuels corrélats de protection, mon travail a consisté à étudier la réponse neutralisante dans une population de 114 couples mères-enfants. Nous avons pu confirmer que le spectre de neutralisation des sérums maternels n’était pas associé à une moindre TME du VIH-1, mais que les anticorps neutralisant certains isolats pourraient constituer des indicateurs d’intérêt associé à un moindre risque de transmission. L’ensemble de ces travaux souligne à nouveau la complexité et la pertinence à poursuivre les investigations relatives à l’identification d’éventuels corrélats de protection.
Basic research on neutralizing antibodies. still remains relevant in term of HIV vacccine development. One of the aim of this thesis was to document the neutralization sensitivity of particular HIV-1variants from long term non progressor (LTNP) patients. We first identified molecular signatures associated with sensitivity to 2G12, such as a potential N-linked glycosylation site (PNGS) at N302 and a longer V1V2 loop of gp120. We also studied the relationship between long-term evolution of the virus and neutralization sensitivity in a LTNP patient. We showed that HIV-1 may continue to evolve in presence of both broadly neutralizing antibodies and increasing autologous neutralizing activity more than 10 years post-infection. Mother-to-child transmission provides a natural model for studying the role of neutralizing antibodies. In previous studies, we showed that the presence or high titers of neutralizing antibodies against a CRF01_AE strain, MBA, was associated with a lower rate of HIV-1 intrapartum transmission in Thailand (Barin et al., 2006; Samleerat et al., 2009). In order to confirm this observation and…
Advisors/Committee Members: Barin, Francis (thesis director), Braibant, Martine (thesis director).
Subjects/Keywords: VIH-1; Anticorps neutralisants; Glycoprotéines d’enveloppe; Transmission mère-enfant; Évolution; HIV-1; Neutralizing antibodies; Envelope glycoprotein; Mother-to-child transmission; Evolution
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Chaillon, A. (2012). Glycoprotéines d'enveloppe du virus de l'immunodéficience humaine (VIH) : contribution à l'étude des propriétés biologiques et des mécanismes de protection par anticorps neutralisants : HIV env glycoproteins : contribution to the study of biological properties and protection mechanisms by neutralizing antibodies. (Doctoral Dissertation). Université François-Rabelais de Tours. Retrieved from http://www.theses.fr/2012TOUR3312
Chicago Manual of Style (16th Edition):
Chaillon, Antoine. “Glycoprotéines d'enveloppe du virus de l'immunodéficience humaine (VIH) : contribution à l'étude des propriétés biologiques et des mécanismes de protection par anticorps neutralisants : HIV env glycoproteins : contribution to the study of biological properties and protection mechanisms by neutralizing antibodies.” 2012. Doctoral Dissertation, Université François-Rabelais de Tours. Accessed January 17, 2021.
http://www.theses.fr/2012TOUR3312.
MLA Handbook (7th Edition):
Chaillon, Antoine. “Glycoprotéines d'enveloppe du virus de l'immunodéficience humaine (VIH) : contribution à l'étude des propriétés biologiques et des mécanismes de protection par anticorps neutralisants : HIV env glycoproteins : contribution to the study of biological properties and protection mechanisms by neutralizing antibodies.” 2012. Web. 17 Jan 2021.
Vancouver:
Chaillon A. Glycoprotéines d'enveloppe du virus de l'immunodéficience humaine (VIH) : contribution à l'étude des propriétés biologiques et des mécanismes de protection par anticorps neutralisants : HIV env glycoproteins : contribution to the study of biological properties and protection mechanisms by neutralizing antibodies. [Internet] [Doctoral dissertation]. Université François-Rabelais de Tours; 2012. [cited 2021 Jan 17].
Available from: http://www.theses.fr/2012TOUR3312.
Council of Science Editors:
Chaillon A. Glycoprotéines d'enveloppe du virus de l'immunodéficience humaine (VIH) : contribution à l'étude des propriétés biologiques et des mécanismes de protection par anticorps neutralisants : HIV env glycoproteins : contribution to the study of biological properties and protection mechanisms by neutralizing antibodies. [Doctoral Dissertation]. Université François-Rabelais de Tours; 2012. Available from: http://www.theses.fr/2012TOUR3312
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