+publisher:"Florida International University" +contributor:("Lidia Kos")

Florida International University

1. Herrington, Joshua A. Effects of Elevated Prenatal Progesterone on Postnatal Emotional Reactivity in Bobwhite Quail (Colinus Virginianus) Neonates.

Degree: MS, Psychology, 2012, Florida International University

URL: https://digitalcommons.fiu.edu/etd/668 ; 10.25148/etd.FI12072701 ; FI12072701

► Non-genetic maternal influences on prenatal development have a significant effect on the development of early life behavior. This study assessed the behavioral effect of… (more)

Subjects/Keywords: Quail; Progesterone; Prenatal; Emotional; Reactivity

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APA (6^th Edition):

Herrington, J. A. (2012). Effects of Elevated Prenatal Progesterone on Postnatal Emotional Reactivity in Bobwhite Quail (Colinus Virginianus) Neonates. (Thesis). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/668 ; 10.25148/etd.FI12072701 ; FI12072701

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

Chicago Manual of Style (16^th Edition):

Herrington, Joshua A. “Effects of Elevated Prenatal Progesterone on Postnatal Emotional Reactivity in Bobwhite Quail (Colinus Virginianus) Neonates.” 2012. Thesis, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/668 ; 10.25148/etd.FI12072701 ; FI12072701.

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

MLA Handbook (7^th Edition):

Herrington, Joshua A. “Effects of Elevated Prenatal Progesterone on Postnatal Emotional Reactivity in Bobwhite Quail (Colinus Virginianus) Neonates.” 2012. Web. 15 Apr 2021.

Vancouver:

Herrington JA. Effects of Elevated Prenatal Progesterone on Postnatal Emotional Reactivity in Bobwhite Quail (Colinus Virginianus) Neonates. [Internet] [Thesis]. Florida International University; 2012. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/668 ; 10.25148/etd.FI12072701 ; FI12072701.

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

Council of Science Editors:

Herrington JA. Effects of Elevated Prenatal Progesterone on Postnatal Emotional Reactivity in Bobwhite Quail (Colinus Virginianus) Neonates. [Thesis]. Florida International University; 2012. Available from: https://digitalcommons.fiu.edu/etd/668 ; 10.25148/etd.FI12072701 ; FI12072701

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

Florida International University

2. Gu, Cong. Superoxide Dismutase C Modulates Macropinocytosis and Phagocytosis in Dictyostelium Discoideum.

Degree: PhD, Biochemistry, 2018, Florida International University

URL: https://digitalcommons.fiu.edu/etd/3887 ; FIDC007020

► Macropinocytosis and phagocytosis, two actin-dependent and clathrin independent events of endocytosis, enable the cells such as macrophages and neutrophils to either internalize pathogens and… (more)

▼ Macropinocytosis and phagocytosis, two actin-dependent and clathrin independent events of endocytosis, enable the cells such as macrophages and neutrophils to either internalize pathogens and initiates the human innate immune response or serve as a direct entry route for productive infection of pathogen. Dictyostelium discoideum, soil-living amoeba, a unicellular eukaryote that could professionally internalize fluid phase or particles several folds more than that of macrophages and neutrophils. Additionally, multiple key signaling pathways are conserved between Dictyostelium and mammalian cells, including pathways affecting small GTPases Ras and Rac and their downstream effectors, and F-Actin remodeling. All these traits makes Dictyostelium an excellent model organism to study the process pf macropinocytosis and phagocytosis. Upon internalization of the prey, these macropinocytes and phagocytes are often in an environment of increased production of superoxide radicals in the prey-containing vesicles, which helps stimulates the downstream signaling pathways to digest the prey inside. However, the mechanism of how superoxide regulates the process of macropinocytosis and phagocytosis is not fully understood. We had previously reported that Dictyostelium cells lacking Superoxide dismutase C (SodC) exhibited aberrantly high level of active RasG, high basal level of Phosphatidylinositol-3,4,5-triphosphate (PIP3), and severe chemotaxis defects. Now we report that sodC^- cells displayed aberrant endosomal vesicle trafficking, significantly compromised particle uptake and defective cell to substratum matrix adhesion compared to that of wild type cells. By using high resolution live imaging microscope we also show that sodC^- cells have defects in F-Actin remodeling at the phagocytic rim extension and F-Actin depolymerization of the nascent phagosome. Interestingly, the introduction of overexpressing of cytoplasmic superoxide dismutase (SodA), redox insensitive RasG (C118A) or treatment of PI3K inhibitor LY294002 in sodC^- cells significantly rescued the defects of endosomal vesicle trafficking, particle uptake and adhesion. This project suggests that superoxide dismutase C regulates the endosomal vesicle trafficking, phagocytosis and cell to substratum matrix adhesion through the RasG/PI3K signaling axis in Dictyostelium cells. Advisors/Committee Members: Lou Kim, Xiaotang Wang, Lidia Kos, Jessica Liberles.

Subjects/Keywords: Superoxide Dismutase C; Macropinocytosis; Phagocytosis; Dictyostelium Discoideum; Biochemistry; Cell Biology; Molecular Biology

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APA (6^th Edition):

Gu, C. (2018). Superoxide Dismutase C Modulates Macropinocytosis and Phagocytosis in Dictyostelium Discoideum. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/3887 ; FIDC007020

Chicago Manual of Style (16^th Edition):

Gu, Cong. “Superoxide Dismutase C Modulates Macropinocytosis and Phagocytosis in Dictyostelium Discoideum.” 2018. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/3887 ; FIDC007020.

MLA Handbook (7^th Edition):

Gu, Cong. “Superoxide Dismutase C Modulates Macropinocytosis and Phagocytosis in Dictyostelium Discoideum.” 2018. Web. 15 Apr 2021.

Vancouver:

Gu C. Superoxide Dismutase C Modulates Macropinocytosis and Phagocytosis in Dictyostelium Discoideum. [Internet] [Doctoral dissertation]. Florida International University; 2018. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/3887 ; FIDC007020.

Council of Science Editors:

Gu C. Superoxide Dismutase C Modulates Macropinocytosis and Phagocytosis in Dictyostelium Discoideum. [Doctoral Dissertation]. Florida International University; 2018. Available from: https://digitalcommons.fiu.edu/etd/3887 ; FIDC007020

Florida International University

3. Pulido, Maria. Mechanism of Superoxide Mediated Regulation of Particle Uptake and Exocytosis by a GPI-anchored Superoxide Dismutase C in Dictyostelium.

Degree: MS, Biology, 2014, Florida International University

URL: https://digitalcommons.fiu.edu/etd/1540 ; 10.25148/etd.FI14071177 ; FI14071177

► Dictyostelium discoideum is a simple model organism that can be used to study endocytic pathways such as phagocytosis and macropinocytosis because of its homology… (more)

Subjects/Keywords: Dictyostelium discoideum; SodC; endocytosis; exocytosis; RasG

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

APA (6^th Edition):

Pulido, M. (2014). Mechanism of Superoxide Mediated Regulation of Particle Uptake and Exocytosis by a GPI-anchored Superoxide Dismutase C in Dictyostelium. (Thesis). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/1540 ; 10.25148/etd.FI14071177 ; FI14071177

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

Chicago Manual of Style (16^th Edition):

Pulido, Maria. “Mechanism of Superoxide Mediated Regulation of Particle Uptake and Exocytosis by a GPI-anchored Superoxide Dismutase C in Dictyostelium.” 2014. Thesis, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/1540 ; 10.25148/etd.FI14071177 ; FI14071177.

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

MLA Handbook (7^th Edition):

Pulido, Maria. “Mechanism of Superoxide Mediated Regulation of Particle Uptake and Exocytosis by a GPI-anchored Superoxide Dismutase C in Dictyostelium.” 2014. Web. 15 Apr 2021.

Vancouver:

Pulido M. Mechanism of Superoxide Mediated Regulation of Particle Uptake and Exocytosis by a GPI-anchored Superoxide Dismutase C in Dictyostelium. [Internet] [Thesis]. Florida International University; 2014. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/1540 ; 10.25148/etd.FI14071177 ; FI14071177.

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

Council of Science Editors:

Pulido M. Mechanism of Superoxide Mediated Regulation of Particle Uptake and Exocytosis by a GPI-anchored Superoxide Dismutase C in Dictyostelium. [Thesis]. Florida International University; 2014. Available from: https://digitalcommons.fiu.edu/etd/1540 ; 10.25148/etd.FI14071177 ; FI14071177

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

Florida International University

4. Lahiri, Debrupa. Hydroxyapatite-Nanotube Composites and Coatings for Orthopedic Applications.

Degree: PhD, Materials Science and Engineering, 2011, Florida International University

URL: https://digitalcommons.fiu.edu/etd/444 ; 10.25148/etd.FI11080203 ; FI11080203

► Hydroxyapatite (HA) has received wide attention in orthopedics, due to its biocompatibility and osseointegration ability. Despite these advantages, the brittle nature and low fracture… (more)

▼ Hydroxyapatite (HA) has received wide attention in orthopedics, due to its biocompatibility and osseointegration ability. Despite these advantages, the brittle nature and low fracture toughness of HA often results in rapid wear and premature fracture of implant. Hence, there is a need to improve the fracture toughness and wear resistance of HA without compromising its biocompatibility. The aim of the current research is to explore the potential of nanotubes as reinforcement to HA for orthopedic implants. HA- 4 wt.% carbon nanotube (CNT) composites and coatings are synthesized by spark plasma sintering and plasma spraying respectively, and investigated for their mechanical, tribological and biological behavior. CNT reinforcement improves the fracture toughness (>90%) and wear resistance (>66%) of HA for coating and free standing composites. CNTs have demonstrated a positive influence on the proliferation, differentiation and matrix mineralization activities of osteoblasts, during in-vitro biocompatibility studies. In-vivo exposure of HA-CNT coated titanium implant in animal model (rat) shows excellent histocompatibility and neobone integration on the implant surface. The improved osseointegration due to presence of CNTs in HA is quantified by the adhesion strength measurement of single osteoblast using nano-scratch technique. Considering the ongoing debate about cytotoxicity of CNTs in the literature, the present study also suggests boron nitride nanotube (BNNT) as an alternative reinforcement. BNNT with the similar elastic modulus and strength as CNT, were added to HA. The resulting composite having 4 wt.% BNNTs improved the fracture toughness (~85%) and wear resistance (~75%) of HA in the similar range as HA-CNT composites. BNNTs were found to be non-cytotoxic for osteoblasts and macrophages. In-vitro evaluation shows positive role of BNNT in osteoblast proliferation and viability. Apatite formability of BNNT surface in ~4 days establishes its osseointegration ability. Advisors/Committee Members: Arvind Agarwal, Lidia Kos, W. Kinzy Jones, Norman D. H. Munroe.

Subjects/Keywords: Orthpedic; Bioceramic; Carbon Nanotube; Boron Nitride Nanotube; Hydroxyapatite; Osseointegration; Osteoblast; Cell Adhesion; Biocompatibility; Nano Indentation

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

APA (6^th Edition):

Lahiri, D. (2011). Hydroxyapatite-Nanotube Composites and Coatings for Orthopedic Applications. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/444 ; 10.25148/etd.FI11080203 ; FI11080203

Chicago Manual of Style (16^th Edition):

Lahiri, Debrupa. “Hydroxyapatite-Nanotube Composites and Coatings for Orthopedic Applications.” 2011. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/444 ; 10.25148/etd.FI11080203 ; FI11080203.

MLA Handbook (7^th Edition):

Lahiri, Debrupa. “Hydroxyapatite-Nanotube Composites and Coatings for Orthopedic Applications.” 2011. Web. 15 Apr 2021.

Vancouver:

Lahiri D. Hydroxyapatite-Nanotube Composites and Coatings for Orthopedic Applications. [Internet] [Doctoral dissertation]. Florida International University; 2011. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/444 ; 10.25148/etd.FI11080203 ; FI11080203.

Council of Science Editors:

Lahiri D. Hydroxyapatite-Nanotube Composites and Coatings for Orthopedic Applications. [Doctoral Dissertation]. Florida International University; 2011. Available from: https://digitalcommons.fiu.edu/etd/444 ; 10.25148/etd.FI11080203 ; FI11080203

Florida International University

5. Wang, Zhonghua. Proton Nuclear Magnetic Resonance Investigation of the Native and Modified Active Site Structure of Heme Proteins.

Degree: PhD, Chemistry, 2011, Florida International University

URL: https://digitalcommons.fiu.edu/etd/513 ; 10.25148/etd.FI11120706 ; FI11120706

► Hemoproteins are a very important class of enzymes in nature sharing the essentially same prosthetic group, heme, and are good models for exploring the… (more)

▼ Hemoproteins are a very important class of enzymes in nature sharing the essentially same prosthetic group, heme, and are good models for exploring the relationship between protein structure and function. Three important hemoproteins, chloroperoxidase (CPO), horseradish peroxidase (HRP), and cytochrome P450cam (P450cam), have been extensively studied as archetypes for the relationship between structure and function. In this study, a series of 1D and 2D NMR experiments were successfully conducted to contribute to the structural studies of these hemoproteins. During the epoxidation of allylbenzene, CPO is converted to an inactive green species with the prosthetic heme modified by addition of the alkene plus an oxygen atom forming a five-membered chelate ring. Complete assignment of the NMR resonances of the modified porphyrin extracted and demetallated from green CPO unambiguously established the structure of this porphyrin as an N_III-alkylated product. A novel substrate binding motif of CPO was proposed from this concluded regiospecific N-alkylation structure. Soybean peroxidase (SBP) is considered as a more stable, more abundant and less expensive substitute of HRP for industrial applications. A NMR study of SBP using 1D and 2D NOE methods successfully established the active site structure of SBP and consequently fills in the blank of the SBP NMR study. All of the hyperfine shifts of the SBP-CN^- complex are unambiguously assigned together with most of the prosthetic heme and all proximal His170 resonances identified. The active site structure of SBP revealed by this NMR study is in complete agreement with the recombinant SBP crystal structure and is highly similar to that of the HRP with minor differences. The NMR study of paramagnetic P450cam had been greatly restricted for a long time. A combination of 2D NMR methods was used in this study for P450cam-CN^- complexes with and without camphor bound. The results lead to the first unequivocal assignments of all heme hyperfine-shifted signals, together with certain correlated diamagnetic resonances. The observed alternation of the assigned novel proximal cysteine β-CH₂ resonances induced by camphor binding indicated a conformational change near the proximal side. Advisors/Committee Members: Xiaotang Wang, Fenfei Leng, Watson Lees, Kathleen Rein, Lidia Kos.

Subjects/Keywords: NMR; Heme; P450cam; Chloroperoxidase; Soybean Peroxidase

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

APA (6^th Edition):

Wang, Z. (2011). Proton Nuclear Magnetic Resonance Investigation of the Native and Modified Active Site Structure of Heme Proteins. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/513 ; 10.25148/etd.FI11120706 ; FI11120706

Chicago Manual of Style (16^th Edition):

Wang, Zhonghua. “Proton Nuclear Magnetic Resonance Investigation of the Native and Modified Active Site Structure of Heme Proteins.” 2011. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/513 ; 10.25148/etd.FI11120706 ; FI11120706.

MLA Handbook (7^th Edition):

Wang, Zhonghua. “Proton Nuclear Magnetic Resonance Investigation of the Native and Modified Active Site Structure of Heme Proteins.” 2011. Web. 15 Apr 2021.

Vancouver:

Wang Z. Proton Nuclear Magnetic Resonance Investigation of the Native and Modified Active Site Structure of Heme Proteins. [Internet] [Doctoral dissertation]. Florida International University; 2011. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/513 ; 10.25148/etd.FI11120706 ; FI11120706.

Council of Science Editors:

Wang Z. Proton Nuclear Magnetic Resonance Investigation of the Native and Modified Active Site Structure of Heme Proteins. [Doctoral Dissertation]. Florida International University; 2011. Available from: https://digitalcommons.fiu.edu/etd/513 ; 10.25148/etd.FI11120706 ; FI11120706

Florida International University

6. Goldina, Anna. Endocrine Regulation of Dynamic Communication Signals in Gymnotiform Fish.

Degree: PhD, Biology, 2011, Florida International University

URL: https://digitalcommons.fiu.edu/etd/521 ; 10.25148/etd.FI11120803 ; FI11120803

► Communication signals are shaped by the opposing selection pressures imposed by predators and mates. A dynamic signal might serve as an adaptive compromise between… (more)

▼ Communication signals are shaped by the opposing selection pressures imposed by predators and mates. A dynamic signal might serve as an adaptive compromise between an inconspicuous signal that evades predators and an extravagant signal preferred by females. Such a signal has been described in the gymnotiform electric fish, Brachyhypopomus gauderio, which produces a sexually dimorphic electric organ discharge (EOD). The EOD varies on a circadian rhythm and in response to social cues. This signal plasticity is mediated by the slow action of androgens and rapid action of melanocortins. My dissertation research tested the hypotheses that (1) signal plasticity is related to sociality levels in gymnotiform species, and (2) differences in signal plasticity are regulated by differential sensitivity to androgen and melanocortin hormones. To assess the breadth of dynamic signaling within the order Gymnotiformes, I sampled 13 species from the five gymnotiform families. I recorded EODs to observe spontaneous signal oscillations after which I injected melanocortin hormones, saline control, or presented the fish with a conspecific. I showed that through the co-option of the ancient melanocortin pathway, gymnotiforms dynamically regulate EOD amplitude, spectral frequency, both, or neither. To investigate whether observed EOD plasticities are related to species-specific sociality I tested four species; two territorial, highly aggressive species, Gymnotus carapo and Apteronotus leptorhynchus, a highly gregarious species, Eigenmannia cf. virescens, and an intermediate short-lived species with a fluid social system, Brachyhypopomus gauderio. I examined the relationship between the androgens testosterone and 11-ketotestosterone, the melanocortin a-MSH, and their roles in regulating EOD waveform. I implanted all fish with androgen and blank silicone implants, and injected with a-MSH before and at the peak of implant effect. I found that waveforms of the most territorial and aggressive species were insensitive to hormone treatments; maintaining a static, stereotyped signal that preserves encoding of individual identity. Species with a fluid social system were most responsive to hormone treatments, exhibiting signals that reflect immediate condition and reproductive state. In conclusion, variation in gymnotiform signal plasticity is hormonally regulated and seems to reflect species-specific sociality. Advisors/Committee Members: Philip Stoddard, Maureen Donnelly, Matthew Grober, Lidia Kos, Robert Lickliter.

Subjects/Keywords: Gymnotiformes; Adrenocorticotropic hormone (ACTH); alpha-melanocyte stimulating hormone (alpha-MSH); 11-Ketotestosterone (11-KT); Testosterone (T); electric communication signals; plasticity; EOD; sociality

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

APA (6^th Edition):

Goldina, A. (2011). Endocrine Regulation of Dynamic Communication Signals in Gymnotiform Fish. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/521 ; 10.25148/etd.FI11120803 ; FI11120803

Chicago Manual of Style (16^th Edition):

Goldina, Anna. “Endocrine Regulation of Dynamic Communication Signals in Gymnotiform Fish.” 2011. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/521 ; 10.25148/etd.FI11120803 ; FI11120803.

MLA Handbook (7^th Edition):

Goldina, Anna. “Endocrine Regulation of Dynamic Communication Signals in Gymnotiform Fish.” 2011. Web. 15 Apr 2021.

Vancouver:

Goldina A. Endocrine Regulation of Dynamic Communication Signals in Gymnotiform Fish. [Internet] [Doctoral dissertation]. Florida International University; 2011. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/521 ; 10.25148/etd.FI11120803 ; FI11120803.

Council of Science Editors:

Goldina A. Endocrine Regulation of Dynamic Communication Signals in Gymnotiform Fish. [Doctoral Dissertation]. Florida International University; 2011. Available from: https://digitalcommons.fiu.edu/etd/521 ; 10.25148/etd.FI11120803 ; FI11120803

Florida International University

7. Sun, Tong. Glycogen Synthase Kinase 3 Influences Cell Motility and Chemotaxis by Regulating Phosphatidylinositol 3 Kinase Localization in Dictyostelium discoideum.

Degree: PhD, Biology, 2013, Florida International University

URL: https://digitalcommons.fiu.edu/etd/807 ; 10.25148/etd.FI13040103 ; FI13040103

► Glycogen Synthase Kinase 3 (GSK3), a serine/threonine kinase initially characterized in the context of glycogen metabolism, has been repeatedly realized as a multitasking protein… (more)

▼ Glycogen Synthase Kinase 3 (GSK3), a serine/threonine kinase initially characterized in the context of glycogen metabolism, has been repeatedly realized as a multitasking protein that can regulate numerous cellular events in both metazoa and protozoa. I recently found GSK3 plays a role in regulating chemotaxis, a guided cell movement in response to an external chemical gradient, in one of the best studied model systems for chemotaxis - Dictyostelium discoideum. It was initially found that comparing to wild type cells, gsk3^- cells showed aberrant chemotaxis with a significant decrease in both speed and chemotactic indices. In Dictyostelium, phosphatidylinositol 3,4,5-triphosphate (PIP3) signaling is one of the best characterized pathways that regulate chemotaxis. Molecular analysis uncovered that gsk3^- cells suffer from high basal level of PIP3, the product of PI3K. Upon chemoattractant cAMP stimulation, wild type cells displayed a transient increase in the level of PIP3. In contrast, gsk3^- cells exhibited neither significant increase nor adaptation. On the other hand, no aberrant dynamic of phosphatase and tensin homolog (PTEN), which antagonizes PI3K function, was observed. Upon membrane localization of PI3K, PI3K become activated by Ras, which will in turn further facilitate membrane localization of PI3K in an F-Actin dependent manner. The gsk3^- cells treated with F-Actin inhibitor Latrunculin-A showed no significant difference in the PIP3 level. I also showed GSK3 affected the phosphorylation level of the localization domain of PI3K1 (PI3K1-LD). PI3K1-LD proteins from gsk3^- cells displayed less phosphorylation on serine residues compared to that from wild type cells. When the potential GSK3 phosphorylation sites of PI3K1-LD were substituted with aspartic acids (Phosphomimetic substitution), its membrane localization was suppressed in gsk3^- cells. When these serine residues of PI3K1-LD were substituted with alanine, aberrantly high level of membrane localization of the PI3K1-LD was monitored in wild type cells. Wild type, phosphomimetic, and alanine substitution of PI3K1-LD fused with GFP proteins also displayed identical localization behavior as suggested by the cell fraction studies. Lastly, I identified that all three potential GSK3 phosphorylation sites on PI3K1-LD could be phosphorylated in vitro by GSK3. Advisors/Committee Members: Lou W. Kim, Lidia Kos, Ophelia Weeks, DeEtta Mills, Xiaotang Wang.

Subjects/Keywords: Glycogen Synthase Kinase 3; Ras; phosphatidylinositol 3; 4; 5-triphosphate; phosphatidylinositol-3-kinase; chemotaxis; Dictyostelium discoideum

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

APA (6^th Edition):

Sun, T. (2013). Glycogen Synthase Kinase 3 Influences Cell Motility and Chemotaxis by Regulating Phosphatidylinositol 3 Kinase Localization in Dictyostelium discoideum. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/807 ; 10.25148/etd.FI13040103 ; FI13040103

Chicago Manual of Style (16^th Edition):

Sun, Tong. “Glycogen Synthase Kinase 3 Influences Cell Motility and Chemotaxis by Regulating Phosphatidylinositol 3 Kinase Localization in Dictyostelium discoideum.” 2013. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/807 ; 10.25148/etd.FI13040103 ; FI13040103.

MLA Handbook (7^th Edition):

Sun, Tong. “Glycogen Synthase Kinase 3 Influences Cell Motility and Chemotaxis by Regulating Phosphatidylinositol 3 Kinase Localization in Dictyostelium discoideum.” 2013. Web. 15 Apr 2021.

Vancouver:

Sun T. Glycogen Synthase Kinase 3 Influences Cell Motility and Chemotaxis by Regulating Phosphatidylinositol 3 Kinase Localization in Dictyostelium discoideum. [Internet] [Doctoral dissertation]. Florida International University; 2013. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/807 ; 10.25148/etd.FI13040103 ; FI13040103.

Council of Science Editors:

Sun T. Glycogen Synthase Kinase 3 Influences Cell Motility and Chemotaxis by Regulating Phosphatidylinositol 3 Kinase Localization in Dictyostelium discoideum. [Doctoral Dissertation]. Florida International University; 2013. Available from: https://digitalcommons.fiu.edu/etd/807 ; 10.25148/etd.FI13040103 ; FI13040103

Florida International University

8. Sagar, Vidya. Magnetic Nanoparticle-based Targeted Drug Delivery for Treatment of Neuro-AIDS and Drug Addiction.

Degree: PhD, Biology, 2013, Florida International University

URL: https://digitalcommons.fiu.edu/etd/909 ; 10.25148/etd.FI13080525 ; FI13080525

► Brain is one of the safe sanctuaries for HIV and, in turn, continuously supplies active viruses to the periphery. Additionally, HIV infection in brain… (more)

▼ Brain is one of the safe sanctuaries for HIV and, in turn, continuously supplies active viruses to the periphery. Additionally, HIV infection in brain results in several mild-to-severe neuro-immunological complications termed neuroAIDS. One-tenth of HIV-infected population is addicted to recreational drugs such as opiates, alcohol, nicotine, marijuana, etc. which share common target-areas in the brain with HIV. Interestingly, intensity of neuropathogenesis is remarkably enhanced due to exposure of recreational drugs during HIV infection. Current treatments to alleviate either the individual or synergistic effects of abusive drugs and HIV on neuronal modulations are less effective at CNS level, basically due to impermeability of therapeutic molecules across blood-brain barrier (BBB). Despite exciting advancement of nanotechnology in drug delivery, existing nanovehicles such as dendrimers, polymers, micelles, etc. suffer from the lack of adequate BBB penetrability before the drugs are engulfed by the reticuloendothelial system cells as well as the uncertainty that if and when the nanocarrier reaches the brain. Therefore, in order to develop a fast, target-specific, safe, and effective approach for brain delivery of anti-addiction, anti-viral and neuroprotective drugs, we exploited the potential of magnetic nanoparticles (MNPs) which, in recent years, has attracted significant importance in biomedical applications. We hypothesize that under the influence of external (non-invasive) magnetic force, MNPs can deliver these drugs across BBB in most effective manner. Accordingly, in this dissertation, I delineated the pharmacokinetics and dynamics of MNPs bound anti-opioid, anti-HIV and neuroprotective drugs for delivery in brain. I have developed a liposome-based novel magnetized nanovehicle which, under the influence of external magnetic forces, can transmigrate and effectively deliver drugs across BBB without compromising its integrity. It is expected that the developed nanoformulations may be of high therapeutic significance for neuroAIDS and for drug addiction as well. Advisors/Committee Members: Madhavan Nair, Sakhrat Khizroev, Ravi Pottathil, Alejandro Barbieri, Lidia Kos.

Subjects/Keywords: drug treatment; nanotechnology; drug addition; neuro-AIDS; Life Sciences; Medicine and Health Sciences

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APA (6^th Edition):

Sagar, V. (2013). Magnetic Nanoparticle-based Targeted Drug Delivery for Treatment of Neuro-AIDS and Drug Addiction. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/909 ; 10.25148/etd.FI13080525 ; FI13080525

Chicago Manual of Style (16^th Edition):

Sagar, Vidya. “Magnetic Nanoparticle-based Targeted Drug Delivery for Treatment of Neuro-AIDS and Drug Addiction.” 2013. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/909 ; 10.25148/etd.FI13080525 ; FI13080525.

MLA Handbook (7^th Edition):

Sagar, Vidya. “Magnetic Nanoparticle-based Targeted Drug Delivery for Treatment of Neuro-AIDS and Drug Addiction.” 2013. Web. 15 Apr 2021.

Vancouver:

Sagar V. Magnetic Nanoparticle-based Targeted Drug Delivery for Treatment of Neuro-AIDS and Drug Addiction. [Internet] [Doctoral dissertation]. Florida International University; 2013. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/909 ; 10.25148/etd.FI13080525 ; FI13080525.

Council of Science Editors:

Sagar V. Magnetic Nanoparticle-based Targeted Drug Delivery for Treatment of Neuro-AIDS and Drug Addiction. [Doctoral Dissertation]. Florida International University; 2013. Available from: https://digitalcommons.fiu.edu/etd/909 ; 10.25148/etd.FI13080525 ; FI13080525

Florida International University

9. Pino, Javier. Transgneic Endothelin 3 Regulates Murine Pigment Production and Coat Color.

Degree: PhD, Biology, 2017, Florida International University

URL: https://digitalcommons.fiu.edu/etd/3533 ; 10.25148/etd.FIDC004033 ; FIDC004033

► Pigmentation plays a protective role against damage caused by ultraviolet (UV) irradiation. Humans with fair skin and light hair have a higher susceptibility to… (more)

▼ Pigmentation plays a protective role against damage caused by ultraviolet (UV) irradiation. Humans with fair skin and light hair have a higher susceptibility to UV-induced DNA damage that can lead to the development of skin cancers. The melanocytes found in the skin and hair follicles depend on different signaling molecules for their proper development and pigment production. α-Melanocyte Stimulating Hormone (α-msh) binds to the Melanocortin 1 receptor (Mc1r) to regulate pigment production and the switch between eumelanin and pheomelanin. Lethal yellow mice (A^y) overexpress the agouti signaling protein, which inhibits the binding of α-msh, resulting in a yellow coat color phenotype. Endothelin 3 (Edn3) encodes for a ligand involved in melanocyte development by regulating the differentiation, proliferation and migration of melanocyte precursors. A tetracycline inducible transgenic mouse in which Edn3 was placed under the keratin 5 promoter (K5-tTA;TRE-Edn3-lacZ) displays a hyperpigmentation phenotype due to the accumulation of melanocytes in the skin and an increase in hair pigment. Comparative analysis of dorsal hairs from A^y and A^y; K5-tTA;TRE-Edn3-lacZ mice using high performance liquid chromatography showed that transgenic Edn3 expression significantly increased both eumelanin and pheomelanin. No significant difference in the number of follicular melanocytes between Edn3 transgenic and non-transgenic mice was evidenced by immunofluorescence using an antibody against Tyrosinase related protein 1. Gene expression analysis of hair follicles showed that Edn3 upregulates the expression of melanogenic genes. Deactivation of transgenic Edn3 is possible with doxycycline (dox) treatment. To test if transgenic Edn3 expression is required to rescue and maintain a dark pigmentation phenotype in A^ymice, dox was administered during embryonic and postnatal development to manipulate transgenic Edn3 expression. Results showed that transgenic Edn3 expression is required to maintain a dark pigmentation phenotype after birth but is independent of a developmental requirement. Transgenic Edn3 expression in Mc1r^e/e mice also resulted in a darkened coat color. Our results indicate that the paracrine expression of Edn3 from keratinocytes is capable of generating and maintaining a dark coat color by the regulation of melanogenic genes independent of Mc1r signaling. The results of this study may open new approaches to the treatment of hypopigmentation disorders. Advisors/Committee Members: Lidia Kos, Manuel Barbieri, Marcus Cooke, Yuan Liu, Jose Eirin-Lopez.

Subjects/Keywords: endothelin; pigment; murine; mammalian pigmentation; endothelin receptor b; pigment; eumelanin; pheomelanin; mouse; melanocyte; Biology; Cell Biology; Developmental Biology; Genetics; Other Cell and Developmental Biology

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APA (6^th Edition):

Pino, J. (2017). Transgneic Endothelin 3 Regulates Murine Pigment Production and Coat Color. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/3533 ; 10.25148/etd.FIDC004033 ; FIDC004033

Chicago Manual of Style (16^th Edition):

Pino, Javier. “Transgneic Endothelin 3 Regulates Murine Pigment Production and Coat Color.” 2017. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/3533 ; 10.25148/etd.FIDC004033 ; FIDC004033.

MLA Handbook (7^th Edition):

Pino, Javier. “Transgneic Endothelin 3 Regulates Murine Pigment Production and Coat Color.” 2017. Web. 15 Apr 2021.

Vancouver:

Pino J. Transgneic Endothelin 3 Regulates Murine Pigment Production and Coat Color. [Internet] [Doctoral dissertation]. Florida International University; 2017. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/3533 ; 10.25148/etd.FIDC004033 ; FIDC004033.

Council of Science Editors:

Pino J. Transgneic Endothelin 3 Regulates Murine Pigment Production and Coat Color. [Doctoral Dissertation]. Florida International University; 2017. Available from: https://digitalcommons.fiu.edu/etd/3533 ; 10.25148/etd.FIDC004033 ; FIDC004033

Florida International University

10. Wang, Yingsong. Investigating the In Vitro Oxidative Folding Pathways of Bovine Pancreatic Trypsin Inhibitor (BPTI).

Degree: PhD, Chemistry, 2013, Florida International University

URL: https://digitalcommons.fiu.edu/etd/1029 ; 10.25148/etd.FI13121203 ; FI13121203

► The oxidative folding pathway of the disulfide containing protein bovine pancreatic trypsin inhibitor (BPTI) was one of the first to be elucidated and has… (more)

▼ The oxidative folding pathway of the disulfide containing protein bovine pancreatic trypsin inhibitor (BPTI) was one of the first to be elucidated and has served as a basis for understanding the folding pathways of other proteins. During the oxidative folding of reduced BPTI, two intermediates (N' and N*) accumulate in significant amounts and act as kinetic traps. Both N' and N* bury their two remaining free thiols in their hydrophobic cores, which inhibits further oxidation. Historically, the rate limiting step was considered to be the intramolecular rearrangements of N' and N* to another intermediate with two free thiols, N^SH. The two free thiols in N^SH are solvent-exposed and easily oxidized to a disulfide, producing native protein (N). Nevertheless, our research using reduced BPTI indicated that the folding rate of N* to N was proportional to the concentration of added glutathione disulfide (GSSG), inconsistent with the slow intramolecular rearrangement of N* to N^SH. To confirm our initial results, the intermediate N* was purified and refolded in the presence of GSSG. The conversion of N* to N was dependent upon the disulfide concentration and singly mixed disulfide N*(SG) was observed during folding. These results emphasize that the folding of N* can proceed via a growth type pathway, direct oxidation of the two remaining thiols in N* by an exogenous small molecule disulfide, such as GSSG, to form N. Folding of reduced BPTI via N* was performed under changing concentrations of GSSG and GSH as a function of time. The folding was improved dramatically in terms of rate and yield. Aromatic disulfides and thiols have been demonstrated to improve the folding efficiency of disulfide containing proteins including ribonuclease A (RNase A) and lysozyme. Herein, N* and N' were refolded in the presence of aromatic disulfides. Folding of the two kinetic traps with aromatic disulfides indicated that folding proceed via a growth type pathway. The singly and doubly mixed disulfide intermediates were observed during most folding reactions. The oxidative folding of reduced BPTI with aromatic disulfides and thiols were also investigated. Reduced BPTI can be folded to disulfide intermediates rapidly. Advisors/Committee Members: Watson J. Lees, Konstantinos Kavallieratos, Lidia Kos, Kevin O'Shea, Xiaotang Wang.

Subjects/Keywords: BPTI; folding pathway; protein folding; GSSG and GSH; aromatic disulfides; HPLC; Biochemistry; Other Chemistry

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APA (6^th Edition):

Wang, Y. (2013). Investigating the In Vitro Oxidative Folding Pathways of Bovine Pancreatic Trypsin Inhibitor (BPTI). (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/1029 ; 10.25148/etd.FI13121203 ; FI13121203

Chicago Manual of Style (16^th Edition):

Wang, Yingsong. “Investigating the In Vitro Oxidative Folding Pathways of Bovine Pancreatic Trypsin Inhibitor (BPTI).” 2013. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/1029 ; 10.25148/etd.FI13121203 ; FI13121203.

MLA Handbook (7^th Edition):

Wang, Yingsong. “Investigating the In Vitro Oxidative Folding Pathways of Bovine Pancreatic Trypsin Inhibitor (BPTI).” 2013. Web. 15 Apr 2021.

Vancouver:

Wang Y. Investigating the In Vitro Oxidative Folding Pathways of Bovine Pancreatic Trypsin Inhibitor (BPTI). [Internet] [Doctoral dissertation]. Florida International University; 2013. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/1029 ; 10.25148/etd.FI13121203 ; FI13121203.

Council of Science Editors:

Wang Y. Investigating the In Vitro Oxidative Folding Pathways of Bovine Pancreatic Trypsin Inhibitor (BPTI). [Doctoral Dissertation]. Florida International University; 2013. Available from: https://digitalcommons.fiu.edu/etd/1029 ; 10.25148/etd.FI13121203 ; FI13121203

11. Nagesetti, Abhignyan. The Effect of Hyperthermia on Doxorubicin Therapy and Nanoparticle Penetration in Multicellular Ovarian Cancer Spheroids.

Degree: PhD, Biomedical Engineering, 2017, Florida International University

URL: https://digitalcommons.fiu.edu/etd/3183 ; 10.25148/etd.FIDC001791 ; FIDC001791

► The efficient treatment of cancer with chemotherapy is challenged by the limited penetration of drugs into the tumor. Nanoparticles (10 – 100 nanometers) have… (more)

▼ The efficient treatment of cancer with chemotherapy is challenged by the limited penetration of drugs into the tumor. Nanoparticles (10 – 100 nanometers) have emerged as a logical choice to specifically deliver chemotherapeutics to tumors, however, their transport into the tumor is also impeded owing to their bigger size compared to free drug moieties. Currently, monolayer cell cultures, as models for drug testing, cannot recapitulate the structural and functional complexity of in-vivo tumors. Furthermore, strategies to improve drug distribution in tumor tissues are also required. In this study, we hypothesized that hyperthermia (43°C) will improve the distribution of silica nanoparticles in three-dimensional multicellular tumor spheroids. Tumor spheroids mimic the functional and histomorphological complexity of in-vivo avascular tumors and are therefore valuable tools to study drug distribution. Ovarian cancer (Skov3) and uterine sarcoma (MES-SA/Dx5) spheroids were generated using the liquid overlay method. The growth ratio and cytotoxicity assays showed that the application of adjuvant hyperthermia with Doxorubicin (DOX) did not yield higher cell killing compared to DOX therapy alone. These results illustrated the role of spheroids in resistance to heat and DOX. In order to study the cellular uptake kinetics of nanoparticles under hyperthermia conditions, the experimental measurements of silica nanoparticle uptake by cells were fitted using a novel inverse estimation method based on Bayesian estimation. This was coupled with advection reaction transport to model nanoparticle transport in spheroids. The model predicted an increase in Area Under the Curve (AUC) and penetration distance (W_1/2) that were validated with in-vitro experiments in spheroids. Based on these observations, a novel multifunctional theranostic nanoparticle probe was created for generating highly localized hyperthermia by encapsulating a Near Infrared (NIR) dye, IR820 (for imaging and hyperthermia) and DOX in Organically modified silica nanoparticles (Ormosil). Pegylated Ormosil nanoparticles had an average diameter of 58.2±3.1 nm, zeta potential of -6.9 ± 0.1 mV and high colloidal stability in physiological buffers. Exposure of the IR820 within the nanoparticles to NIR laser led to the generation of hyperthermia as well as release of DOX which translated to higher cell killing in Skov3 cells, deeper penetration of DOX into spheroids and complete destruction of the spheroids. In-vivo bio-distribution studies showed higher fluorescence from organs and increased plasma elimination life of IR820 compared to free IR820. However, possible aggregation of particles on laser exposure and accumulation in lungs still remain a concern. Advisors/Committee Members: Anthony J.McGoron, Chenzhong Li, Sharan Ramaswamy, Lidia Kos, George Dulikravich.

Subjects/Keywords: Theranostics; Nanoparticles; Hyperthermia; Chemotherapy; Doxorubicin; Spheroids; Ovarian Cancer; Near Infrared; Bioimaging and Biomedical Optics; Biological Engineering; Biomaterials; Biomechanics and Biotransport; Molecular, Cellular, and Tissue Engineering; Other Biomedical Engineering and Bioengineering

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APA (6^th Edition):

Nagesetti, A. (2017). The Effect of Hyperthermia on Doxorubicin Therapy and Nanoparticle Penetration in Multicellular Ovarian Cancer Spheroids. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/3183 ; 10.25148/etd.FIDC001791 ; FIDC001791

Chicago Manual of Style (16^th Edition):

Nagesetti, Abhignyan. “The Effect of Hyperthermia on Doxorubicin Therapy and Nanoparticle Penetration in Multicellular Ovarian Cancer Spheroids.” 2017. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/3183 ; 10.25148/etd.FIDC001791 ; FIDC001791.

MLA Handbook (7^th Edition):

Nagesetti, Abhignyan. “The Effect of Hyperthermia on Doxorubicin Therapy and Nanoparticle Penetration in Multicellular Ovarian Cancer Spheroids.” 2017. Web. 15 Apr 2021.

Vancouver:

Nagesetti A. The Effect of Hyperthermia on Doxorubicin Therapy and Nanoparticle Penetration in Multicellular Ovarian Cancer Spheroids. [Internet] [Doctoral dissertation]. Florida International University; 2017. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/3183 ; 10.25148/etd.FIDC001791 ; FIDC001791.

Council of Science Editors:

Nagesetti A. The Effect of Hyperthermia on Doxorubicin Therapy and Nanoparticle Penetration in Multicellular Ovarian Cancer Spheroids. [Doctoral Dissertation]. Florida International University; 2017. Available from: https://digitalcommons.fiu.edu/etd/3183 ; 10.25148/etd.FIDC001791 ; FIDC001791

Florida International University

12. Brown, Tanya. Phenomenological and Molecular Basis of the Cnidarian Immune System.

Degree: PhD, Biology, 2017, Florida International University

URL: https://digitalcommons.fiu.edu/etd/3468 ; 10.25148/etd.FIDC001928 ; FIDC001928

► Coral reefs are one of the most diverse ecosystems on the planet due partially to the habitat structure provided by corals. Corals are long… (more)

▼ Coral reefs are one of the most diverse ecosystems on the planet due partially to the habitat structure provided by corals. Corals are long lived organisms that can live for hundreds of years and as a result growth of many species is very slow. As a result of this, recovery of corals from disease outbreaks is very slow and difficult and therefore the ecosystem is deteriorating rapidly. Due to this increase in disease and its detrimental effect on coral reefs, it has become imperative to study how corals respond to disease outbreaks. The response of the coral to pathogens is believed to be controlled by the innate immune system. However, the immune pathways and components of these pathways used by cnidarians to combat pathogens are still rudimentary. This work showed that C3 and heat shock protein 70 are components of the coral immune system that positively respond to disease occurrence. As disease out breaks become more frequent, the question has arisen as to whether cnidarians have homologs to of the adaptive immune system that allow them to respond more rapidly to subsequent encounters with the same bacterium. In the cnidarian model system Exaiptasia pallida, immune priming occurs up to one month after the initial sub lethal exposure to the pathogen. This transient form of priming could be the result of host energy allocation in place of establishing long term immune priming which could be too energetically costly. Cnidarians may only activate priming during summer months, when ocean temperatures and bacterial load are high. Specificity of immune priming in E. pallida requires further investigation with more bacterial pathogens. In this dissertation, one bacterial strain shows specificity while the other does not. Furthermore, the priming response involves many pathways which include pathogen recognition, inflammation, and activation of NF-κB. The discovery of immune priming in a sea anemone shows that this phenomenon evolved earlier in the tree of life than previously thought. Additionally, identification of priming in E. pallida is suggestive of its presence in corals which would allow for potential vaccinations of vulnerable corals. Advisors/Committee Members: Mauricio Rodriguez-Lanetty, Laurie Richardson, John Makemson, Lidia Kos, Kalai Mathee.

Subjects/Keywords: Exaiptasia pallida; coral; cnidarian; immunology; innate immunity; marine biology; Bacteriology; Environmental Microbiology and Microbial Ecology; Genetics; Genomics; Immunity; Immunology of Infectious Disease; Integrative Biology; Marine Biology; Molecular Genetics; Pathogenic Microbiology; Terrestrial and Aquatic Ecology

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

APA (6^th Edition):

Brown, T. (2017). Phenomenological and Molecular Basis of the Cnidarian Immune System. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/3468 ; 10.25148/etd.FIDC001928 ; FIDC001928

Chicago Manual of Style (16^th Edition):

Brown, Tanya. “Phenomenological and Molecular Basis of the Cnidarian Immune System.” 2017. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/3468 ; 10.25148/etd.FIDC001928 ; FIDC001928.

MLA Handbook (7^th Edition):

Brown, Tanya. “Phenomenological and Molecular Basis of the Cnidarian Immune System.” 2017. Web. 15 Apr 2021.

Vancouver:

Brown T. Phenomenological and Molecular Basis of the Cnidarian Immune System. [Internet] [Doctoral dissertation]. Florida International University; 2017. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/3468 ; 10.25148/etd.FIDC001928 ; FIDC001928.

Council of Science Editors:

Brown T. Phenomenological and Molecular Basis of the Cnidarian Immune System. [Doctoral Dissertation]. Florida International University; 2017. Available from: https://digitalcommons.fiu.edu/etd/3468 ; 10.25148/etd.FIDC001928 ; FIDC001928

Florida International University

13. Benaduce, Ana Paula. UV-Induced Melanoma Mouse Model Dependent on Endothelin 3 Over-Expression.

Degree: PhD, Biology, 2014, Florida International University

URL: https://digitalcommons.fiu.edu/etd/1613 ; 10.25148/etd.FI14110725 ; FI14110725

► Melanoma is one of the most aggressive types of cancer. It originates from the transformation of melanocytes present in the epidermal/dermal junction of the… (more)

▼ Melanoma is one of the most aggressive types of cancer. It originates from the transformation of melanocytes present in the epidermal/dermal junction of the human skin. It is commonly accepted that melanomagenesis is influenced by the interaction of environmental factors, genetic factors, as well as tumor-host interactions. DNA photoproducts induced by UV radiation are, in normal cells, repaired by the nucleotide excision repair (NER) pathway. The prominent role of NER in cancer resistance is well exemplified by patients with Xeroderma Pigmentosum (XP). This disease results from mutations in the components of the NER pathway, such as XPA and XPC proteins. In humans, NER pathway disruption leads to the development of skin cancers, including melanoma. Similar to humans afflicted with XP, Xpa and Xpc deficient mice show high sensibility to UV light, leading to skin cancer development, except melanoma. The Endothelin 3 (Edn3) signaling pathway is essential for proliferation, survival and migration of melanocyte precursor cells. Excessive production of Edn3 leads to the accumulation of large numbers of melanocytes in the mouse skin, where they are not normally found. In humans, Edn3 signaling pathway has also been implicated in melanoma progression and its metastatic potential. The goal of this study was the development of the first UV-induced melanoma mouse model dependent on the over-expression of Edn3 in the skin. The UV-induced melanoma mouse model reported here is distinguishable from all previous published models by two features: melanocytes are not transformed a priori and melanomagenesis arises only upon neonatal UV exposure. In this model, melanomagenesis depends on the presence of Edn3 in the skin. Disruption of the NER pathway due to the lack of Xpa or Xpc proteins was not essential for melanomagenesis; however, it enhanced melanoma penetrance and decreased melanoma latency after one single neonatal erythemal UV dose. Exposure to a second dose of UV at six weeks of age did not change time of appearance or penetrance of melanomas in this mouse model. Thus, a combination of neonatal UV exposure with excessive Edn3 in the tumor microenvironment is sufficient for melanomagenesis in mice; furthermore, NER deficiency exacerbates this process. Advisors/Committee Members: Lidia Kos, James Grichnik, John Makemson, M. Alejandro Barbieri, Richard Bone.

Subjects/Keywords: Melanoma; Ultraviolet Radiation; Endothelin 3; XPA; XPC; Skin Cancer; Basal Cell Carcinoma; Squamous Cell Carcinoma; Cancer Biology

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

APA (6^th Edition):

Benaduce, A. P. (2014). UV-Induced Melanoma Mouse Model Dependent on Endothelin 3 Over-Expression. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/1613 ; 10.25148/etd.FI14110725 ; FI14110725

Chicago Manual of Style (16^th Edition):

Benaduce, Ana Paula. “UV-Induced Melanoma Mouse Model Dependent on Endothelin 3 Over-Expression.” 2014. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/1613 ; 10.25148/etd.FI14110725 ; FI14110725.

MLA Handbook (7^th Edition):

Benaduce, Ana Paula. “UV-Induced Melanoma Mouse Model Dependent on Endothelin 3 Over-Expression.” 2014. Web. 15 Apr 2021.

Vancouver:

Benaduce AP. UV-Induced Melanoma Mouse Model Dependent on Endothelin 3 Over-Expression. [Internet] [Doctoral dissertation]. Florida International University; 2014. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/1613 ; 10.25148/etd.FI14110725 ; FI14110725.

Council of Science Editors:

Benaduce AP. UV-Induced Melanoma Mouse Model Dependent on Endothelin 3 Over-Expression. [Doctoral Dissertation]. Florida International University; 2014. Available from: https://digitalcommons.fiu.edu/etd/1613 ; 10.25148/etd.FI14110725 ; FI14110725

Florida International University

14. Castillo Chabeco, Boris. Redox Regulation of Ras Proteins in Dictyostelium discoideum.

Degree: PhD, Biology, 2015, Florida International University

URL: https://digitalcommons.fiu.edu/etd/1864 ; 10.25148/etd.FI15032137 ; FI15032137

► Reactive oxygen species are a normal consequence of life in an aerobic environment. However when they deviate from the narrow permissible range in cells,… (more)

▼ Reactive oxygen species are a normal consequence of life in an aerobic environment. However when they deviate from the narrow permissible range in cells, oxidative damage can occur. Dictyostelium discoideum is a model organism ideal for the study of cell signaling events such as those affected by oxidative stress. It was previously shown that Ras signaling in Dictyostelium is affected by genetic inactivation of the antioxidant enzyme Superoxide dismutase C (SodC) and in vitro data suggests that the NKCD motif of Ras is the redox target of superoxide. The main objective of this project was to determine the mechanism of superoxide mediated Ras regulation in vivo. To accomplish the main objective, we cloned, and in some cases, mutated different Ras proteins and later determined their activity in wild type and sodC^-cells. RasC and RasD showed normal activation in sodC^- cells, however RasG and RasS displayed high Ras activity. These last two Ras proteins contain the NKC¹¹⁸D motif inside the nucleotide binding region. A mutation of cysteine¹¹⁸ to alanine in RasG rendered the protein less active in sodC^- than the wild type RasG protein and a mutation alanine¹¹⁸ to cysteine in RasD conferred redox sensitivity to this small GTPase. Additionally, the propensity of RasG to be targeted by superoxide was evident when the environment of wild type cells was manipulated to induce the internal generation of superoxide through changes in the extracellular ion levels mainly magnesium. Lack of magnesium ions increased the intracellular level of superoxide and severely hampered directional cell migration. Chemotaxis of cells expressing RasG was negatively impacted by the absence of magnesium ions; however rasG^- cells did not seem to be affected in their ability to perform chemotaxis. The last experiment implies that RasG is an important mediator of cell signaling during oxidative stress, responsible for preventing cells from continuing their developmental program. Our study suggests that the cysteine residue in the NKCD motif is essential for mediating the redox sensitivity of Ras proteins in Dictyostelium and that RasG is an essential mediator of the response to oxidative stress in this organism. Advisors/Committee Members: Lou W. Kim, Lidia Kos, Ophelia Weeks, Fernando Noriega, Xiaotang Wang.

Subjects/Keywords: Ras; RasG; protein; sodC-; redox; ROS; Dictyostelium; superoxide; NKCD; magnesium; Biochemistry; Biology; Cell Biology; Molecular Biology

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

APA (6^th Edition):

Castillo Chabeco, B. (2015). Redox Regulation of Ras Proteins in Dictyostelium discoideum. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/1864 ; 10.25148/etd.FI15032137 ; FI15032137

Chicago Manual of Style (16^th Edition):

Castillo Chabeco, Boris. “Redox Regulation of Ras Proteins in Dictyostelium discoideum.” 2015. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/1864 ; 10.25148/etd.FI15032137 ; FI15032137.

MLA Handbook (7^th Edition):

Castillo Chabeco, Boris. “Redox Regulation of Ras Proteins in Dictyostelium discoideum.” 2015. Web. 15 Apr 2021.

Vancouver:

Castillo Chabeco B. Redox Regulation of Ras Proteins in Dictyostelium discoideum. [Internet] [Doctoral dissertation]. Florida International University; 2015. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/1864 ; 10.25148/etd.FI15032137 ; FI15032137.

Council of Science Editors:

Castillo Chabeco B. Redox Regulation of Ras Proteins in Dictyostelium discoideum. [Doctoral Dissertation]. Florida International University; 2015. Available from: https://digitalcommons.fiu.edu/etd/1864 ; 10.25148/etd.FI15032137 ; FI15032137

Florida International University

15. Porther, Nicole. Intracellular Signaling and Trafficking in Cancer: Role of Rab5-GTPase in Migration and Invasion of Breast Cells.

Degree: PhD, Biology, 2015, Florida International University

URL: https://digitalcommons.fiu.edu/etd/1939 ; 10.25148/etd.FI15050202 ; FI15050202

► Metastasis is characterized pathologically by uncontrolled cell invasion, proliferation, migration and angiogenesis. Steroid hormones, such as estrogen, and growth factors, which include insulin growth… (more)

▼ Metastasis is characterized pathologically by uncontrolled cell invasion, proliferation, migration and angiogenesis. Steroid hormones, such as estrogen, and growth factors, which include insulin growth factor I/II (IGF-1/IGF-2) therapy has been associated with most if not all of the features of metastasis. It has been determined that IGF-1 increases cell survival of cancer cells and potentiate the effect of E2 and other ligand growth factors on breast cancer cells. However not much information is available that comprehensively expounds on the roles of insulin growth factor receptor (IGFR) and Rab GTPases may play in breast cancer. The latter, Rab GTPases, are small signaling molecules and critical in the regulation of many cellular processes including cell migration, growth via the endocytic pathway. This research involves the role of Rab GTPases, specifically Rab5 and its guanine exchange factors (GEFs), in the promotion of cancer cell migration and invasion. Two important questions abound: Are IGFR stimulation and downstream effect involved the endocytic pathway in carcinogenesis? What role does Rab5 play in cell migration and invasion of cancer cells? The hypothesis is that growth factor signaling is dependent on Rab5 activity in mediating the aggressiveness of cancer cells. The goal is to demonstrate that IGF-1 signaling is dependent on Rab5 function in breast cancer progression. Here, the results thus far, have shown that while activation of Rab5 may mediate increased cell proliferation, migration and invasion in breast cancer cells, the Rab5 GEF, RIN1 interacts with the IGFR thereby facilitating migration and invasion activities in breast cells. Furthermore, endocytosis of the IGFR in breast cancer cells seems to be caveolin dependent as the data has shown. This taken together, the data shows that IGF-1 signaling in breast cancer cells relies on IGF-1R phosphorylation, caveolae internalization and sequestration to the early endosome RIN1 function and Rab5 activation. Advisors/Committee Members: Manuel Barbieri, Marianna Baum, Lidia Kos, Ophelia Weeks, Fernando Noriega.

Subjects/Keywords: migration; invasion; Rab GTPases; endocytosis; receptor trafficking; IGFR; caveolin; Cancer Biology; Cell Biology; Laboratory and Basic Science Research

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

APA (6^th Edition):

Porther, N. (2015). Intracellular Signaling and Trafficking in Cancer: Role of Rab5-GTPase in Migration and Invasion of Breast Cells. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/1939 ; 10.25148/etd.FI15050202 ; FI15050202

Chicago Manual of Style (16^th Edition):

Porther, Nicole. “Intracellular Signaling and Trafficking in Cancer: Role of Rab5-GTPase in Migration and Invasion of Breast Cells.” 2015. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/1939 ; 10.25148/etd.FI15050202 ; FI15050202.

MLA Handbook (7^th Edition):

Porther, Nicole. “Intracellular Signaling and Trafficking in Cancer: Role of Rab5-GTPase in Migration and Invasion of Breast Cells.” 2015. Web. 15 Apr 2021.

Vancouver:

Porther N. Intracellular Signaling and Trafficking in Cancer: Role of Rab5-GTPase in Migration and Invasion of Breast Cells. [Internet] [Doctoral dissertation]. Florida International University; 2015. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/1939 ; 10.25148/etd.FI15050202 ; FI15050202.

Council of Science Editors:

Porther N. Intracellular Signaling and Trafficking in Cancer: Role of Rab5-GTPase in Migration and Invasion of Breast Cells. [Doctoral Dissertation]. Florida International University; 2015. Available from: https://digitalcommons.fiu.edu/etd/1939 ; 10.25148/etd.FI15050202 ; FI15050202

Florida International University

16. Rath, Sasmita. Regulation of Bone Marrow Stem Cells through Oscillatory Shear Stresses - A Heart Valve Tissue Engineering Perspective.

Degree: PhD, Biomedical Engineering, 2015, Florida International University

URL: https://digitalcommons.fiu.edu/etd/1824 ; 10.25148/etd.FI15050204 ; FI15050204

► Heart valve disease occurs in adults as well as in pediatric population due to age-related changes, rheumatic fever, infection or congenital condition. Current treatment… (more)

Subjects/Keywords: Tissue Engineering; Stem Cell; Heart Valve; Biomedical Engineering and Bioengineering

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APA (6^th Edition):

Rath, S. (2015). Regulation of Bone Marrow Stem Cells through Oscillatory Shear Stresses - A Heart Valve Tissue Engineering Perspective. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/1824 ; 10.25148/etd.FI15050204 ; FI15050204

Chicago Manual of Style (16^th Edition):

Rath, Sasmita. “Regulation of Bone Marrow Stem Cells through Oscillatory Shear Stresses - A Heart Valve Tissue Engineering Perspective.” 2015. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/1824 ; 10.25148/etd.FI15050204 ; FI15050204.

MLA Handbook (7^th Edition):

Rath, Sasmita. “Regulation of Bone Marrow Stem Cells through Oscillatory Shear Stresses - A Heart Valve Tissue Engineering Perspective.” 2015. Web. 15 Apr 2021.

Vancouver:

Rath S. Regulation of Bone Marrow Stem Cells through Oscillatory Shear Stresses - A Heart Valve Tissue Engineering Perspective. [Internet] [Doctoral dissertation]. Florida International University; 2015. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/1824 ; 10.25148/etd.FI15050204 ; FI15050204.

Council of Science Editors:

Rath S. Regulation of Bone Marrow Stem Cells through Oscillatory Shear Stresses - A Heart Valve Tissue Engineering Perspective. [Doctoral Dissertation]. Florida International University; 2015. Available from: https://digitalcommons.fiu.edu/etd/1824 ; 10.25148/etd.FI15050204 ; FI15050204

Florida International University

17. Tiburcio de Freitas, Juliano. The Immunosuppressive Role of Edn3/Ednrb Signaling in the Melanoma Microenvironment.

Degree: PhD, Biology, 2019, Florida International University

URL: https://digitalcommons.fiu.edu/etd/4029 ; 10.25148/etd.FIDC007654 ; FIDC007654

► Endothelins are cytokines ubiquitously expressed in the microenvironment of several tumors. In melanoma is not clear whether stromal cells respond to the endothelin present… (more)

▼ Endothelins are cytokines ubiquitously expressed in the microenvironment of several tumors. In melanoma is not clear whether stromal cells respond to the endothelin present in the microenvironment. To address this question, I generated tumors derived from different murine melanoma cell lines (B16F10, YUMM1.7, YUMMER1.7) in a transgenic mouse that overexpresses endothelin 3 (Edn3) by keratinocytes in the skin (K5-Edn3). Tumors from all the cell lines grew larger and were more aggressive when Edn3 was overexpressed in the skin. In tumors derived from YUMM1.7-GFP cells, very few tumorigenic cells expressed the Edn3 receptor, Endothelin receptor b (Ednrb) suggesting an environmental role for endothelin signaling in melanoma microenvironment. The present study showed for the first time that Ednrb is expressed in several cell populations inside melanoma microenvironment. The clinical relevance of the finding was validated using publicly available RNA-seq data from melanoma patients. Regulatory T cells (Tregs) was the only population that was numerically different when K5-Edn3 tumors were compared to wild-type tumors suggesting that Edn3 promotes Treg enrichment in melanoma microenvironment. The present study supports the notion that endothelin promotes the formation of an immunosuppressive milieu in melanoma facilitating escape from tumor immunity. Endothelin was required for immune escape of highly immunogenic melanoma cells YUMMER1.7. The immunosuppressive features of Tregs were enhanced in presence of Edn3. The master regulator of Tregs’ suppressive functions, FOXP3, was remarkably upregulated in K5-Edn3 tumors as well as immunosuppressive cytokines TGF-β and IL-10. Overexpression of Edn3 in the tumor microenvironment prevented the expansion of CTLs possibly via GZB-mediated cytolysis. Expression of chemokines and inflammatory cytokines were downregulated in K5-Edn3 tumors. Cytokines that elicit anti-tumor immunity, exhibited reduced levels in K5-Edn3 tumors. The YUMM1.7-GFP tumors exposed to high levels of Edn3 were sensitive to immune checkpoint inhibitor (anti-CTLA-4) as well as to Ednrb blockage (BQ-788). The response to BQ-788 was more pronounced suggesting that EDNRB targeting might be an alternative therapeutic strategy for melanoma patients that are under immunotherapy regimen. In conclusion, the present study indicates that Edn3/Ednrb signaling has an important role in the melanoma microenvironment where it mediates immunosuppression resulting in escape from tumor immunity. Advisors/Committee Members: Lidia Kos, Lou Kim, Mauricio Rodriguez-Lanetty, Anthony McGoron, Marta Torroella.

Subjects/Keywords: Melanoma; Tumor Microenvironment; Endothelin; Regulatory T cell; Cancer Biology; Immune System Diseases; Immunity

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APA (6^th Edition):

Tiburcio de Freitas, J. (2019). The Immunosuppressive Role of Edn3/Ednrb Signaling in the Melanoma Microenvironment. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/4029 ; 10.25148/etd.FIDC007654 ; FIDC007654

Chicago Manual of Style (16^th Edition):

Tiburcio de Freitas, Juliano. “The Immunosuppressive Role of Edn3/Ednrb Signaling in the Melanoma Microenvironment.” 2019. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/4029 ; 10.25148/etd.FIDC007654 ; FIDC007654.

MLA Handbook (7^th Edition):

Tiburcio de Freitas, Juliano. “The Immunosuppressive Role of Edn3/Ednrb Signaling in the Melanoma Microenvironment.” 2019. Web. 15 Apr 2021.

Vancouver:

Tiburcio de Freitas J. The Immunosuppressive Role of Edn3/Ednrb Signaling in the Melanoma Microenvironment. [Internet] [Doctoral dissertation]. Florida International University; 2019. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/4029 ; 10.25148/etd.FIDC007654 ; FIDC007654.

Council of Science Editors:

Tiburcio de Freitas J. The Immunosuppressive Role of Edn3/Ednrb Signaling in the Melanoma Microenvironment. [Doctoral Dissertation]. Florida International University; 2019. Available from: https://digitalcommons.fiu.edu/etd/4029 ; 10.25148/etd.FIDC007654 ; FIDC007654

Florida International University

18. Nagaraja, Sridevi. Theoretical Investigations of Communication in the Microcirculation: Conducted Responses, Myoendothelial Projections and Endothelium Derived Hyperpolarizing Factor.

Degree: PhD, Biomedical Engineering, 2011, Florida International University

URL: https://digitalcommons.fiu.edu/etd/520 ; 10.25148/etd.FI11120802 ; FI11120802

► The contractile state of microcirculatory vessels is a major determinant of the blood pressure of the whole systemic circulation. Continuous bi-directional communication exists between… (more)

▼ The contractile state of microcirculatory vessels is a major determinant of the blood pressure of the whole systemic circulation. Continuous bi-directional communication exists between the endothelial cells (ECs) and smooth muscle cells (SMCs) that regulates calcium (Ca²⁺) dynamics in these cells. This study presents theoretical approaches to understand some of the important and currently unresolved microcirculatory phenomena. Agonist induced events at local sites have been shown to spread long distances in the microcirculation. We have developed a multicellular computational model by integrating detailed single EC and SMC models with gap junction and nitric oxide (NO) coupling to understand the mechanisms behind this effect. Simulations suggest that spreading vasodilation mainly occurs through Ca²⁺ independent passive conduction of hyperpolarization in RMAs. Model predicts a superior role for intercellular diffusion of inositol (1,4,5)-trisphosphate (IP₃) than Ca²⁺in modulating the spreading response. Endothelial derived signals are initiated even during vasoconstriction of stimulated SMCs by the movement of Ca²⁺ and/or IP₃ into the EC which provide hyperpolarizing feedback to SMCs to counter the ongoing constriction. Myoendothelial projections (MPs) present in the ECs have been recently proposed to play a role in myoendothelial feedback. We have developed two models using compartmental and 2D finite element methods to examine the role of these MPs by adding a sub compartment in the EC to simulate MP with localization of intermediate conductance calcium activated potassium channels (IK_Ca) and IP₃ receptors (IP₃R). Both models predicted IP₃ mediated high Ca²⁺ gradients in the MP after SMC stimulation with limited global spread. This Ca²⁺ transient generated a hyperpolarizing feedback of ~ 2-3mV. Endothelium derived hyperpolarizing factor (EDHF) is the dominant form of endothelial control of SMC constriction in the microcirculation. A number of factors have been proposed for the role of EDHF but no single pathway is agreed upon. We have examined the potential of myoendothelial gap junctions (MEGJs) and potassium (K⁺) accumulation as EDHF using two models (compartmental and 2D finite element). An extra compartment is added in SMC to simulate micro domains (MD) which have NaK_α2 isoform sodium potassium pumps. Simulations predict that MEGJ coupling is much stronger in producing EDHF than alone K⁺ accumulation. On the contrary, K⁺ accumulation can alter other important parameters (EC V_m, IK_Ca current) and inhibit its own release as well as EDHF conduction via MEGJs. The models developed in this study are essential building blocks for future models and provide important insights to the current understanding of myoendothelial feedback and EDHF. Advisors/Committee Members: Nikolaos Tsoukias, Wei-Chiang Lin, Anuradha Godavarty, Lidia Kos, Yen-Chih Huang.

Subjects/Keywords: intercellular communication; calcium dynamics; myoendothelial feedback; gap junction coupling; potassium accumulation

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APA (6^th Edition):

Nagaraja, S. (2011). Theoretical Investigations of Communication in the Microcirculation: Conducted Responses, Myoendothelial Projections and Endothelium Derived Hyperpolarizing Factor. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/520 ; 10.25148/etd.FI11120802 ; FI11120802

Chicago Manual of Style (16^th Edition):

Nagaraja, Sridevi. “Theoretical Investigations of Communication in the Microcirculation: Conducted Responses, Myoendothelial Projections and Endothelium Derived Hyperpolarizing Factor.” 2011. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/520 ; 10.25148/etd.FI11120802 ; FI11120802.

MLA Handbook (7^th Edition):

Nagaraja, Sridevi. “Theoretical Investigations of Communication in the Microcirculation: Conducted Responses, Myoendothelial Projections and Endothelium Derived Hyperpolarizing Factor.” 2011. Web. 15 Apr 2021.

Vancouver:

Nagaraja S. Theoretical Investigations of Communication in the Microcirculation: Conducted Responses, Myoendothelial Projections and Endothelium Derived Hyperpolarizing Factor. [Internet] [Doctoral dissertation]. Florida International University; 2011. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/520 ; 10.25148/etd.FI11120802 ; FI11120802.

Council of Science Editors:

Nagaraja S. Theoretical Investigations of Communication in the Microcirculation: Conducted Responses, Myoendothelial Projections and Endothelium Derived Hyperpolarizing Factor. [Doctoral Dissertation]. Florida International University; 2011. Available from: https://digitalcommons.fiu.edu/etd/520 ; 10.25148/etd.FI11120802 ; FI11120802

Florida International University

19. Rodriguez Silva, Monica. Impact of San-mediated Signaling on Glioblastoma and Neuroblastoma Metabolism.

Degree: PhD, Biomedical Sciences, 2018, Florida International University

URL: https://digitalcommons.fiu.edu/etd/3751 ; 10.25148/etd.FIDC006885 ; FIDC006885

► Glioblastoma (GBM) is the most common and aggressive type of brain cancer, with an average life expectancy of 15 months. The standard of care… (more)

▼ Glioblastoma (GBM) is the most common and aggressive type of brain cancer, with an average life expectancy of 15 months. The standard of care for GBM, surgery accompanied by radiation and chemotherapy (temozolomide-TMZ), has not changed in over 10 years illustrating the need for new and efficacious treatments. Therefore, it is imperative to improve our knowledge of GBM physiology to understand the mechanisms driving recurrence and chemoresistance so that more effective therapeutic options can be developed. Mitochondria-cell communication is key to monitor and maintain both mitochondrial and cellular health, and signaling events on the outer mitochondrial membrane (OMM) have emerged as a crucial signal integration site for cellular responses. Consequently, proteins on the OMM are crucial to determining cellular survival and dictating organelle physiology. Thus, the goal of our current study is to evaluate OMM proteins to determine how alterations in organelle regulation may impact CNS tumor biology. We first measured the concentrations of Bcl-2 family proteins on mitochondria from ten continuous GBM cell lines and correlated the protein levels to IC₅₀values of genotoxic agents TMZ and irinotecan. We found that Bcl-2 levels corresponded to chemoresistance, while increased Bim concentrations promoted chemosensitivity. In contrast to our studies in gynecological cancers, the concentrations of the pro-dysfunction OMM scaffold protein Sab had no impact on chemosensitivity of the GBM cell lines, despite diminished Sab expression in GBM patients. However, we identified a novel truncated variant of Sab in the GBM cell lines. We found that GBM cells expressing only full-length Sab had a slower proliferation rate than those with the variant, which could be attributed to increased glycolysis in GBM cells expressing the Sab variant. To determine if the lack of Sab-mediated apoptosis was consistent across CNS tumors, we analyzed publicly-available patient data and found that Sab expression is down-regulated in neuroblastoma patients, a pediatric malignancy responsible for 12% of childhood cancer deaths. We found that that inhibiting Sab-mediated signaling in human neuroblastoma (SH-SY5Y cells) enhanced oxidative phosphorylation in a pyruvate dehydrogenase-dependent manner, increased BCl-2 levels (pro-survival), decreased Bim concentrations (pro-apoptotic), and promoted chemoresistance. Furthermore, examination of additional neuroblastoma cells derived from CNS tumors revealed that Sab levels correspond to proliferation rate, metabolic phenotype, and chemosensitivity. Our studies demonstrate the importance of OMM signaling in CNS tumor physiology and emphasizes the importance of cellular context to the outcomes of OMM signaling events. Advisors/Committee Members: Jeremy W. Chambers, Ralph DeBerardinis, Lidia Kos, Nazira El-Hage, Helen Tempest.

Subjects/Keywords: Sab; Mitochondria; Metabolism; Glioblastoma; Neuroblastoma; Biochemistry; Cancer Biology; Cell Biology

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APA (6^th Edition):

Rodriguez Silva, M. (2018). Impact of San-mediated Signaling on Glioblastoma and Neuroblastoma Metabolism. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/3751 ; 10.25148/etd.FIDC006885 ; FIDC006885

Chicago Manual of Style (16^th Edition):

Rodriguez Silva, Monica. “Impact of San-mediated Signaling on Glioblastoma and Neuroblastoma Metabolism.” 2018. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/3751 ; 10.25148/etd.FIDC006885 ; FIDC006885.

MLA Handbook (7^th Edition):

Rodriguez Silva, Monica. “Impact of San-mediated Signaling on Glioblastoma and Neuroblastoma Metabolism.” 2018. Web. 15 Apr 2021.

Vancouver:

Rodriguez Silva M. Impact of San-mediated Signaling on Glioblastoma and Neuroblastoma Metabolism. [Internet] [Doctoral dissertation]. Florida International University; 2018. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/3751 ; 10.25148/etd.FIDC006885 ; FIDC006885.

Council of Science Editors:

Rodriguez Silva M. Impact of San-mediated Signaling on Glioblastoma and Neuroblastoma Metabolism. [Doctoral Dissertation]. Florida International University; 2018. Available from: https://digitalcommons.fiu.edu/etd/3751 ; 10.25148/etd.FIDC006885 ; FIDC006885

Florida International University

20. Mustafi, Sushmita. Regulation of Rab5 GTPase activity during Pseudomonas aeruginosa-macrophage interaction.

Degree: PhD, Biology, 2013, Florida International University

URL: https://digitalcommons.fiu.edu/etd/1016 ; 10.25148/etd.FI13121213 ; FI13121213

► Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen. Several antibiotic resistant strains of P. aeruginosa are commonly found as secondary infection in immune-compromised patients leaving… (more)

▼ Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen. Several antibiotic resistant strains of P. aeruginosa are commonly found as secondary infection in immune-compromised patients leaving significant mortality and healthcare cost. Pseudomonas aeruginosa successfully avoids the process of phagocytosis, the first line of host defense, by secreting several toxic effectors. Effectors produced from P. aeruginosa Type III secretion system are critical molecules required to disrupt mammalian cell signaling and holds particular interest to the scientists studying host-pathogen interaction. Exoenzyme S (ExoS) is a bi-functional Type III effector that ADP-ribosylates several intracellular Ras (Rat sarcoma) and Rab (Response to abscisic acid) small GTPases in targeted host cells. The Rab5 protein acts as a rate limiting protein during phagocytosis by switching from a GDP- bound inactive form to a GTP-bound active form. Activation and inactivation of Rab5 protein is regulated by several Rab5-GAPs (GTPase Activating Proteins) and Rab5-GEFs (Rab5-Guanine nucleotide Exchange Factors). Some pathogenic bacteria have shown affinity for Rab proteins during infection and make their way inside the cell. This dissertation demonstrated that Rab5 plays a critical role during early steps of P. aeruginosa invasion in J774-Eclone macrophages. It was found that live, but not heat inactivated, P. aeruginosa inhibited phagocytosis that occurred in conjunction with down-regulation of Rab5 activity. Inactivation of Rab5 was dependent on ExoS ADP-ribosyltransferase activity, and more than one arginine sites in Rab5 are possible targets for ADP-ribosylation modification. However, the expression of Rin1, but not other Rab5GEFs (Rabex-5 and Rap6) reversed this down-regulation of Rab5 in vivo. Further studies revealed that the C-terminus of Rin1 carrying Rin1:Vps9 and Rin1:RA domains are required for optimal Rab5 activation in conjunction with active Ras. These observations demonstrate a novel mechanism of Rab5 targeting to phagosome via Rin1 during the phagocytosis of P. aeruginosa. The second part of this dissertation investigated antimicrobial activities of Dehydroleucodine (DhL), a secondary metabolite from Artemisia douglasiana, against P. aeruginosa growth and virulence. Populations of several P. aeruginosa strains were completely susceptible to DhL at a concentration between 0.48~0.96 mg/ml and treatment at a threshold concentration (0.12 mg/ml) inhibited growth and many virulent activities without damaging the integrity of the cell suggesting anti-Pseudomonas activity of DhL. Advisors/Committee Members: M. Alejandro Barbieri, Lidia Kos, Rita Mukhopadhyay, David Kuhn, Fernando Noriega, John Makemson.

Subjects/Keywords: Pseudomonas aeruginosa; Rab5; Macrophage; host pathogen interaction; Immunology and Infectious Disease; Pathogenic Microbiology

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APA (6^th Edition):

Mustafi, S. (2013). Regulation of Rab5 GTPase activity during Pseudomonas aeruginosa-macrophage interaction. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/1016 ; 10.25148/etd.FI13121213 ; FI13121213

Chicago Manual of Style (16^th Edition):

Mustafi, Sushmita. “Regulation of Rab5 GTPase activity during Pseudomonas aeruginosa-macrophage interaction.” 2013. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/1016 ; 10.25148/etd.FI13121213 ; FI13121213.

MLA Handbook (7^th Edition):

Mustafi, Sushmita. “Regulation of Rab5 GTPase activity during Pseudomonas aeruginosa-macrophage interaction.” 2013. Web. 15 Apr 2021.

Vancouver:

Mustafi S. Regulation of Rab5 GTPase activity during Pseudomonas aeruginosa-macrophage interaction. [Internet] [Doctoral dissertation]. Florida International University; 2013. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/1016 ; 10.25148/etd.FI13121213 ; FI13121213.

Council of Science Editors:

Mustafi S. Regulation of Rab5 GTPase activity during Pseudomonas aeruginosa-macrophage interaction. [Doctoral Dissertation]. Florida International University; 2013. Available from: https://digitalcommons.fiu.edu/etd/1016 ; 10.25148/etd.FI13121213 ; FI13121213

Florida International University

21. Rodriguez, Marbelys. Two Adaptation Mechanisms Regulate Cellular Migration in Dictyostelium discouideum.

Degree: PhD, Biology, 2014, Florida International University

URL: https://digitalcommons.fiu.edu/etd/1144 ; 10.25148/etd.FI14040813 ; FI14040813

► Dictyostelium discoideum is a simple model widely used to study many cellular functions, including differentiation, gene regulation, cellular trafficking and directional migration. Adaptation mechanisms… (more)

▼ Dictyostelium discoideum is a simple model widely used to study many cellular functions, including differentiation, gene regulation, cellular trafficking and directional migration. Adaptation mechanisms are essential in the regulation of these cellular processes. The misregulation of adaptation components often results in persistent activation of signaling pathways and aberrant cellular responses. Studying adaptation mechanisms regulating cellular migration will be crucial in the treatment of many pathological conditions in which motility plays a central role, such as tumor metastasis and acute inflammation. I will describe two adaptation mechanisms regulating directional migration in Dictyostelium cells. The Extracellular signal Regulated Kinase 2 (ERK2) plays an essential role in Dictyostelium cellular migration. ERK2 stimulates intracellular cAMP accumulation in chemotaxing cells. Aberrant ERK2 regulation results in aberrant cAMP levels and defective directional migration. The MAP Phosphatase with Leucine-rich repeats (MPL1) is crucial for ERK2 adaptation. Cells lacking, MPL1 (mpl1^- cells) displayed higher pre-stimulus and persistent post-stimulus ERK2 phosphorylation, defective cAMP production and reduced cellular migration. Reintroduction of a full length Mpl1 into mpl1^- cells restored aggregation, ERK2 regulation, random and directional motility, and cAMP production similar to wild type cells (Wt). These results suggest Mpl1 is essential for proper regulation of ERK2 phosphorylation and optimal motility in Dictyostelium cells. Cellular polarization in Dictyostelium cells in part is regulated by the activation of the AGC-related kinase Protein Kinase Related B1 (PKBR1). The PP2A regulatory subunit, B56, and the Glycogen Synthase Kinase 3 (GSK3) are necessary for PKBR1 adaptation in Dictyostelium cells. Cells lacking B56, psrA^-cells, exhibited high basal and post-stimulus persistent phosphorylation of PKBR1, increased phosphorylation of PKBR1 substrates, and aberrant motility. PKBR1 adaptation is also regulated by the GSK3. When the levels of active GSK3 are reduced in Wt and psrA^- cells, high basal levels of phosphorylated PKBR1 were observed, in a Ras dependent, but B56 independent mechanism. Altogether, PKBR1 adaptation is regulated by at least two independent mechanisms: one by GSK3 and another by PP2A/B56. Advisors/Committee Members: Dr. Lou W. Kim, Dr. Lidia Kos, Dr. Alejandro Barbieri, Dr. Ophelia Weeks, Dr. Xiaotang Wang.

Subjects/Keywords: Motility; Dictyostelium; PKBR1; B56; PP2A; Adaptation; MPL1; ERK2; Biology

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APA (6^th Edition):

Rodriguez, M. (2014). Two Adaptation Mechanisms Regulate Cellular Migration in Dictyostelium discouideum. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/1144 ; 10.25148/etd.FI14040813 ; FI14040813

Chicago Manual of Style (16^th Edition):

Rodriguez, Marbelys. “Two Adaptation Mechanisms Regulate Cellular Migration in Dictyostelium discouideum.” 2014. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/1144 ; 10.25148/etd.FI14040813 ; FI14040813.

MLA Handbook (7^th Edition):

Rodriguez, Marbelys. “Two Adaptation Mechanisms Regulate Cellular Migration in Dictyostelium discouideum.” 2014. Web. 15 Apr 2021.

Vancouver:

Rodriguez M. Two Adaptation Mechanisms Regulate Cellular Migration in Dictyostelium discouideum. [Internet] [Doctoral dissertation]. Florida International University; 2014. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/1144 ; 10.25148/etd.FI14040813 ; FI14040813.

Council of Science Editors:

Rodriguez M. Two Adaptation Mechanisms Regulate Cellular Migration in Dictyostelium discouideum. [Doctoral Dissertation]. Florida International University; 2014. Available from: https://digitalcommons.fiu.edu/etd/1144 ; 10.25148/etd.FI14040813 ; FI14040813

Florida International University

22. Dua, Rupak. Enhanced Anchorage of Tissue-Engineered Cartilage Using an Osteoinductive Approach.

Degree: PhD, Biomedical Engineering, 2014, Florida International University

URL: https://digitalcommons.fiu.edu/etd/1459 ; 10.25148/etd.FI14071120 ; FI14071120

► Articular cartilage injuries occur frequently in the knee joint. Several methods have been implemented clinically, to treat osteochondral defects but none have been able… (more)

Subjects/Keywords: Articular Cartilage; Engineered cartilage; osteochondral defects; Hydrogel; PEGDA; Hydroxyapatiye; nanoparticle; Biomechanics; Integration

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APA (6^th Edition):

Dua, R. (2014). Enhanced Anchorage of Tissue-Engineered Cartilage Using an Osteoinductive Approach. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/1459 ; 10.25148/etd.FI14071120 ; FI14071120

Chicago Manual of Style (16^th Edition):

Dua, Rupak. “Enhanced Anchorage of Tissue-Engineered Cartilage Using an Osteoinductive Approach.” 2014. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/1459 ; 10.25148/etd.FI14071120 ; FI14071120.

MLA Handbook (7^th Edition):

Dua, Rupak. “Enhanced Anchorage of Tissue-Engineered Cartilage Using an Osteoinductive Approach.” 2014. Web. 15 Apr 2021.

Vancouver:

Dua R. Enhanced Anchorage of Tissue-Engineered Cartilage Using an Osteoinductive Approach. [Internet] [Doctoral dissertation]. Florida International University; 2014. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/1459 ; 10.25148/etd.FI14071120 ; FI14071120.

Council of Science Editors:

Dua R. Enhanced Anchorage of Tissue-Engineered Cartilage Using an Osteoinductive Approach. [Doctoral Dissertation]. Florida International University; 2014. Available from: https://digitalcommons.fiu.edu/etd/1459 ; 10.25148/etd.FI14071120 ; FI14071120

Florida International University

23. Saldana Tavares, Amy. The Role of the Transcription Factor Ets1 in Melanocyte Development.

Degree: PhD, Biology, 2014, Florida International University

URL: https://digitalcommons.fiu.edu/etd/1451 ; 10.25148/etd.FI14071121 ; FI14071121

► Melanocytes, pigment-producing cells, derive from the neural crest (NC), a population of pluripotent cells that arise from the dorsal aspect of the neural tube… (more)

Subjects/Keywords: Ets1; Sox10; melanocyte development; genetic interactions; neural crest; mouse

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APA (6^th Edition):

Saldana Tavares, A. (2014). The Role of the Transcription Factor Ets1 in Melanocyte Development. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/1451 ; 10.25148/etd.FI14071121 ; FI14071121

Chicago Manual of Style (16^th Edition):

Saldana Tavares, Amy. “The Role of the Transcription Factor Ets1 in Melanocyte Development.” 2014. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/1451 ; 10.25148/etd.FI14071121 ; FI14071121.

MLA Handbook (7^th Edition):

Saldana Tavares, Amy. “The Role of the Transcription Factor Ets1 in Melanocyte Development.” 2014. Web. 15 Apr 2021.

Vancouver:

Saldana Tavares A. The Role of the Transcription Factor Ets1 in Melanocyte Development. [Internet] [Doctoral dissertation]. Florida International University; 2014. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/1451 ; 10.25148/etd.FI14071121 ; FI14071121.

Council of Science Editors:

Saldana Tavares A. The Role of the Transcription Factor Ets1 in Melanocyte Development. [Doctoral Dissertation]. Florida International University; 2014. Available from: https://digitalcommons.fiu.edu/etd/1451 ; 10.25148/etd.FI14071121 ; FI14071121

Florida International University

24. Beaver, Jill M. Trinucleotide Repeat Instability is Modulated by DNA Base Lesions and DNA Base Excision Repair.

Degree: PhD, Biochemistry, 2016, Florida International University

URL: https://digitalcommons.fiu.edu/etd/3056 ; 10.25148/etd.FIDC001178 ; FIDC001178

► Trinucleotide repeat (TNR) expansions are the cause of over 40 human neurodegenerative diseases, and are linked to DNA damage and base excision repair (BER).… (more)

▼ Trinucleotide repeat (TNR) expansions are the cause of over 40 human neurodegenerative diseases, and are linked to DNA damage and base excision repair (BER). We explored the role of DNA damage and BER in modulating TNR instability through analysis of DNA structures, BER protein activities, and reconstitution of repair using human BER proteins and synthesized DNA containing various types of damage. We show that DNA damage and BER can modulate TNR expansions by promoting removal of a TNR hairpin through coordinated activities of BER proteins and cofactors. We found that during repair in a TNR hairpin, coordination between the 5’-flap endonuclease activity of flap endonuclease 1 (FEN1), 3’-5’ exonuclease activity of AP endonuclease 1 (APE1), and activity of DNA ligase I (LIG I) can resolve the double-flap structure produced during BER in the hairpin loop. The resolution of the double-flap structure resulted in hairpin removal and prevention or attenuation of TNR expansions and provides the first evidence that coordination among BER proteins can remove a TNR hairpin. We further explored the role of BER cofactors in modulating TNR instability and found that the repair cofactor proliferating cell nuclear antigen (PCNA) facilitates genomic stability by promoting removal of a TNR hairpin. Hairpin removal was accomplished by altering dynamic TNR structures to allow more efficient FEN1 cleavage and DNA polymerase β (pol β) synthesis and stimulating the activity of LIG I. This study provides the first evidence that a DNA repair cofactor plays an important role in modulating TNR instability. Finally, we explored the effects of sugar modifications in abasic sites on activities of BER proteins and BER efficiency during repair in a TNR tract. We found that an oxidized sugar inhibits the activities of BER enzymes, interrupting their coordination and preventing efficient repair. Inefficient repair results in accumulation of repair intermediates with DNA breaks, contributing to genomic instability. Our results indicate that DNA base lesions and BER play a crucial role in modulating TNR instability. The research presented herein provides a molecular basis for further developing BER as a target for prevention and treatment of neurodegenerative diseases caused by TNR expansion. Advisors/Committee Members: Yuan Liu, Lidia Kos, Watson Lees, Yuk-Ching Tse-Dinh, Xiaotang Wang.

Subjects/Keywords: DNA repair; trinucleotide repeats; DNA damage; trinucleotide repeat instability; DNA base excision repair; Biochemistry

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APA (6^th Edition):

Beaver, J. M. (2016). Trinucleotide Repeat Instability is Modulated by DNA Base Lesions and DNA Base Excision Repair. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/3056 ; 10.25148/etd.FIDC001178 ; FIDC001178

Chicago Manual of Style (16^th Edition):

Beaver, Jill M. “Trinucleotide Repeat Instability is Modulated by DNA Base Lesions and DNA Base Excision Repair.” 2016. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/3056 ; 10.25148/etd.FIDC001178 ; FIDC001178.

MLA Handbook (7^th Edition):

Beaver, Jill M. “Trinucleotide Repeat Instability is Modulated by DNA Base Lesions and DNA Base Excision Repair.” 2016. Web. 15 Apr 2021.

Vancouver:

Beaver JM. Trinucleotide Repeat Instability is Modulated by DNA Base Lesions and DNA Base Excision Repair. [Internet] [Doctoral dissertation]. Florida International University; 2016. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/3056 ; 10.25148/etd.FIDC001178 ; FIDC001178.

Council of Science Editors:

Beaver JM. Trinucleotide Repeat Instability is Modulated by DNA Base Lesions and DNA Base Excision Repair. [Doctoral Dissertation]. Florida International University; 2016. Available from: https://digitalcommons.fiu.edu/etd/3056 ; 10.25148/etd.FIDC001178 ; FIDC001178

Florida International University

25. Nyati, Pratik. Characterization of Juvenile Hormone Biosynthetic Enzymes in the Mosquito, Aedes aegypti.

Degree: PhD, Biology, 2014, Florida International University

URL: https://digitalcommons.fiu.edu/etd/1688 ; 10.25148/etd.FI14110768 ; FI14110768

► The juvenile hormones (JHs) are sesquiterpenoid compounds that play a central role in insect reproduction, development and behavior. They are synthesized and secreted by… (more)

▼ The juvenile hormones (JHs) are sesquiterpenoid compounds that play a central role in insect reproduction, development and behavior. They are synthesized and secreted by a pair of small endocrine glands, the corpora allata (CA), which are intimately connected to the brain. The enzymes involved in the biosynthesis of JH are attractive targets for the control of mosquito populations. This dissertation is a comprehensive functional study of five Aedes aegypti CA enzymes, HMG-CoA synthase (AaHMGS), mevalonate kinase (AaMK), phosphomevalonate kinase (AaPMK), farnesyl diphosphate synthase (AaFPPS) and farnesyl pyrophosphate phosphatase (AaFPPase). The enzyme AaHMGS catalyzes the condensation of acetoacetyl-CoA and acetyl-CoA to produce HMG-CoA. The enzyme does not require any co-factor, although its activity is enhanced by addition of Mg²⁺. The enzyme AaMK is a class I mevalonate kinase that catalyzes the ATP-dependent phosphorylation of mevalonic acid to form mevalonate 5-phosphate. Activity of AaMK is inhibited by isoprenoids. The enzyme AaPMK catalyzes the cation-dependent reversible reaction of phosphomevalonate and ATP to form diphosphate mevalonate and ADP. The enzyme AaFPPS catalyzes the condensation of isopentenyl diphosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) to form geranyl diphosphate (GPP) and farnesyl pyrophosphate (FPP). The enzyme AaFPPS shows an unusual product regulation mechanism, with chain length final product of 10 or 15 C depending on the metal cofactor present. The enzymes AaFPPase-1 and AaFPPase-2 efficiently hydrolyze FPP into farnesol, although RNAi experiments demonstrate that only AaFPPase-1 is involved in the catalysis of FPP into FOL in the CA of A. aegypti. This dissertation also explored the inhibition of the activity of some of the JH biosynthesis enzymes as tools for insect control. We described the effect of N-acetyl-S-geranylgeranyl-L-cysteine as a potent inhibitor of AaFPPase 1 and AaFPPase-2. In addition, inhibitors of AaMK and AaHMGS were also investigated using purified recombinant proteins. The present study provides an important contribution to the characterization of recombinant proteins, the analysis of enzyme kinetics and inhibition constants, as well as the understanding of the importance of these five enzymes in the control of JH biosynthesis rates. Advisors/Committee Members: Fernando G. Noriega, Alejandro Barbieri, Lidia Kos, Lou W. Kim, Kalai Mathee.

Subjects/Keywords: Mosquito; Aedes aegypti; juvenile hormone; corpora allata; farnesyl phosphatase; mevalonate kinase; farnesyl diphosphate synthase; Biochemistry, Biophysics, and Structural Biology; Biology; Entomology

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APA (6^th Edition):

Nyati, P. (2014). Characterization of Juvenile Hormone Biosynthetic Enzymes in the Mosquito, Aedes aegypti. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/1688 ; 10.25148/etd.FI14110768 ; FI14110768

Chicago Manual of Style (16^th Edition):

Nyati, Pratik. “Characterization of Juvenile Hormone Biosynthetic Enzymes in the Mosquito, Aedes aegypti.” 2014. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/1688 ; 10.25148/etd.FI14110768 ; FI14110768.

MLA Handbook (7^th Edition):

Nyati, Pratik. “Characterization of Juvenile Hormone Biosynthetic Enzymes in the Mosquito, Aedes aegypti.” 2014. Web. 15 Apr 2021.

Vancouver:

Nyati P. Characterization of Juvenile Hormone Biosynthetic Enzymes in the Mosquito, Aedes aegypti. [Internet] [Doctoral dissertation]. Florida International University; 2014. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/1688 ; 10.25148/etd.FI14110768 ; FI14110768.

Council of Science Editors:

Nyati P. Characterization of Juvenile Hormone Biosynthetic Enzymes in the Mosquito, Aedes aegypti. [Doctoral Dissertation]. Florida International University; 2014. Available from: https://digitalcommons.fiu.edu/etd/1688 ; 10.25148/etd.FI14110768 ; FI14110768

Florida International University

26. Chin, Nikeisha L. The Role of Endothelin 3 in Melanoma Progression and Metastasis.

Degree: PhD, Biology, 2015, Florida International University

URL: https://digitalcommons.fiu.edu/etd/2286 ; 10.25148/etd.FIDC000185 ; FIDC000185

► Endothelin receptor b (Ednrb) and its ligand Endothelin 3 (Edn3) have been implicated in melanoma. Several studies have shown an upregulation of EDNRB and… (more)

Subjects/Keywords: Melanoma; Endothelin 3; Endothelin receptor B; metastasis; Biology; Cancer Biology; Cell Biology

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APA (6^th Edition):

Chin, N. L. (2015). The Role of Endothelin 3 in Melanoma Progression and Metastasis. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/2286 ; 10.25148/etd.FIDC000185 ; FIDC000185

Chicago Manual of Style (16^th Edition):

Chin, Nikeisha L. “The Role of Endothelin 3 in Melanoma Progression and Metastasis.” 2015. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/2286 ; 10.25148/etd.FIDC000185 ; FIDC000185.

MLA Handbook (7^th Edition):

Chin, Nikeisha L. “The Role of Endothelin 3 in Melanoma Progression and Metastasis.” 2015. Web. 15 Apr 2021.

Vancouver:

Chin NL. The Role of Endothelin 3 in Melanoma Progression and Metastasis. [Internet] [Doctoral dissertation]. Florida International University; 2015. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/2286 ; 10.25148/etd.FIDC000185 ; FIDC000185.

Council of Science Editors:

Chin NL. The Role of Endothelin 3 in Melanoma Progression and Metastasis. [Doctoral Dissertation]. Florida International University; 2015. Available from: https://digitalcommons.fiu.edu/etd/2286 ; 10.25148/etd.FIDC000185 ; FIDC000185

27. Areiza, Maria. Regulation of Juvenile Hormone Synthesis by 20-Hydroxyecdysone in the Yellow-fever Mosquito, Aedes aegypti.

Degree: PhD, Biology, 2018, Florida International University

URL: https://digitalcommons.fiu.edu/etd/3804 ; 10.25148/etd.FIDC006829 ; FIDC006829

► In Aedes aegypti, development and reproduction are regulated by juvenile hormone III (JH). This master regulatory hormone is synthesized by the corpora allata (CA),… (more)

▼ In Aedes aegypti, development and reproduction are regulated by juvenile hormone III (JH). This master regulatory hormone is synthesized by the corpora allata (CA), a pair of endocrine glands with neural connections to the brain. JH titers are largely determined by the rate of biosynthetic activity of the CA and are regulated by inhibitory and stimulatory factors. Like JH, the ecdysteroid 20-hydroxyecdysone (20E) is a key hormonal regulator and has been proposed as an allatoregulator in other insects. However, its part in the regulation of JH biosynthesis of mosquitoes was unknown. The specific aims of this dissertation were to (1) evaluate if 20E plays a role in the activation of the late pupal CA and (2) evaluate if 20E plays a role in the reactivation of JH synthesis in blood-fed females. To this end, we evaluated if 20E could prematurely activate JH biosynthesis in the CA of an early pupa (24h prior to eclosion or -24h). Remarkably, in vitro stimulation with 20E at -24h initiated JH synthesis at a time when transcript levels for most JH biosynthetic enzymes are low. Moreover, the application of 20E correlated with an increase in the enzymatic activity of juvenile hormone acid methyltransferase (JHAMT), a critical enzyme of the biosynthetic pathway. Additionally, separation of the CA from the brain increased JH synthesis. Together, these results indicate that 20E acts as a developmental mediator of CA maturation which overrides an inhibitory effect of the brain. In our previous aim we demonstrated that 20E mediates activation of the pupal CA which ensures the development of ovarian follicles of the newly emerged female. For mosquitoes, a blood-meal is required to complete vitellogenesis and results in suppression of CA activity. However, the CA must be reactivated to initiate the second gonotrophic cycle. Our findings show that in vitro stimulation with 20E at 24h post blood feeding reactivates the gland. Again, stimulation with the ecdysteroid resulted in increased activity of another key enzyme, farnesal dehydrogenase (FALDH). These results suggest a stimulatory role of 20E on the biosynthetic activity of the CA in the blood fed female. Advisors/Committee Members: Dr. Fernando G. Noriega, Dr. Lidia Kos, Dr. Matthew DeGennaro, Dr. Kalai Mathee, Dr. Marten J. Edwards.

Subjects/Keywords: 20-Hydroxyecdysone; 20E; Juvenile hormone; JH; Biology; Cellular and Molecular Physiology; Endocrinology; Molecular Biology

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APA (6^th Edition):

Areiza, M. (2018). Regulation of Juvenile Hormone Synthesis by 20-Hydroxyecdysone in the Yellow-fever Mosquito, Aedes aegypti. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/3804 ; 10.25148/etd.FIDC006829 ; FIDC006829

Chicago Manual of Style (16^th Edition):

Areiza, Maria. “Regulation of Juvenile Hormone Synthesis by 20-Hydroxyecdysone in the Yellow-fever Mosquito, Aedes aegypti.” 2018. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/3804 ; 10.25148/etd.FIDC006829 ; FIDC006829.

MLA Handbook (7^th Edition):

Areiza, Maria. “Regulation of Juvenile Hormone Synthesis by 20-Hydroxyecdysone in the Yellow-fever Mosquito, Aedes aegypti.” 2018. Web. 15 Apr 2021.

Vancouver:

Areiza M. Regulation of Juvenile Hormone Synthesis by 20-Hydroxyecdysone in the Yellow-fever Mosquito, Aedes aegypti. [Internet] [Doctoral dissertation]. Florida International University; 2018. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/3804 ; 10.25148/etd.FIDC006829 ; FIDC006829.

Council of Science Editors:

Areiza M. Regulation of Juvenile Hormone Synthesis by 20-Hydroxyecdysone in the Yellow-fever Mosquito, Aedes aegypti. [Doctoral Dissertation]. Florida International University; 2018. Available from: https://digitalcommons.fiu.edu/etd/3804 ; 10.25148/etd.FIDC006829 ; FIDC006829

Florida International University

28. Sharief, Mujataba Rahiman. Regulation of Particle Uptake by PP2A/B56 and LKB1 in Dictyostelium Discoideum.

Degree: PhD, Biochemistry, 2016, Florida International University

URL: https://digitalcommons.fiu.edu/etd/2539 ; 10.25148/etd.FIDC000781 ; FIDC000781

► Dictyostelium discoideum is a soil dwelling amoeba which has been widely used as a model organism to study cellular processes such as signal transduction,… (more)

▼ Dictyostelium discoideum is a soil dwelling amoeba which has been widely used as a model organism to study cellular processes such as signal transduction, chemotaxis, endocytosis and exocytosis. The process of phagocytosis in Dicytostelium is largely comparable to that of neutrophils and macrophages in the mammalian system. Neutrophils and macrophages are cells of the innate immune system and they engulf infectious bacteria through phagocytosis. Dictyostelium cells uptake yeast and bacteria for their nutrition through phagocytosis, which is an actin dependent mechanism and is a target of multiple signaling inputs. Recent studies have uncovered different proteins involved in the signaling of particle and further studies are required to decipher the intricate mechanism leading to the F-actin rearrangement. Two of the proteins have previously known to be involved in the pathways regulating the F- actin rearrangement name PP2A phosphatase and LKB1 kinase The main objective of this project was to determine how these proteins are affecting the two actin driven particle uptake processes, phagocytosis and fluid uptake. We showed that ablation of PsrA gene which codes the regulatory subunit of PP2A resulted in a defective phagocytosis, whereas the fluid uptake was normal. We also showed for the first time that there was an increase in the phosphorylation of some of the PKB substrate proteins in wild type cell. Cells lacking PsrA gene displayed an aberrant phosphorylation of PKB substrate protein when compared to the wild type cells further confirming the involvement of PKB substrate in phagocytosis. Further, we looked at the effects of LKB1 kinase on phagocytosis by using a LKB1 knockdown construct introduced into wild type cells. The knock down of LKB1 resulted in a higher rate of phagocytosis while introduction of a LKB1 over expressing construct severally decreased the rate of phagocytosis indicating an inhibitory effect of LKB1. Furthermore there was an increase in the PKB substrate protein but a different pattern compared to the psrA^-cells. We also carried out adhesion assays on LKB1 knockdown cells and the results showed a higher substrate adhesion as compared to the wild type cells, while psrA^-cells had no adhesion defect. Advisors/Committee Members: Dr. Lou W. Kim, Dr. Lidia Kos, Dr. Xiaotang Wang, Dr. Yukching Tse-Dinh, Dr. Mauricio Rodriguez-Lannetty.

Subjects/Keywords: PP2A/B56; LKB1; Phagocytosis; Macropinocytosis; Biochemistry; Cell Biology; Molecular Biology

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APA (6^th Edition):

Sharief, M. R. (2016). Regulation of Particle Uptake by PP2A/B56 and LKB1 in Dictyostelium Discoideum. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/2539 ; 10.25148/etd.FIDC000781 ; FIDC000781

Chicago Manual of Style (16^th Edition):

Sharief, Mujataba Rahiman. “Regulation of Particle Uptake by PP2A/B56 and LKB1 in Dictyostelium Discoideum.” 2016. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/2539 ; 10.25148/etd.FIDC000781 ; FIDC000781.

MLA Handbook (7^th Edition):

Sharief, Mujataba Rahiman. “Regulation of Particle Uptake by PP2A/B56 and LKB1 in Dictyostelium Discoideum.” 2016. Web. 15 Apr 2021.

Vancouver:

Sharief MR. Regulation of Particle Uptake by PP2A/B56 and LKB1 in Dictyostelium Discoideum. [Internet] [Doctoral dissertation]. Florida International University; 2016. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/2539 ; 10.25148/etd.FIDC000781 ; FIDC000781.

Council of Science Editors:

Sharief MR. Regulation of Particle Uptake by PP2A/B56 and LKB1 in Dictyostelium Discoideum. [Doctoral Dissertation]. Florida International University; 2016. Available from: https://digitalcommons.fiu.edu/etd/2539 ; 10.25148/etd.FIDC000781 ; FIDC000781

29. Areiza, Maria. Ecdysis Triggering Hormone and its Role in Juvenile Hormone Synthesis in the Yellow-fever Mosquito, Aedes aegypti.

Degree: MS, Biology, 2014, Florida International University

URL: https://digitalcommons.fiu.edu/etd/1147 ; 10.25148/etd.FI14040812 ; FI14040812

► Ecdysis triggering hormone (ETH) is a neuropeptide known for its role in the orchestration of ecdysis. However, its role in the regulation of Juvenile… (more)

Subjects/Keywords: Juvenile Hormone; corpora allata; Regulation; Aedes aegypti; Mosquito; Ecdysis Triggering Hormone; Biology; Cellular and Molecular Physiology; Comparative and Evolutionary Physiology; Molecular Biology

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APA (6^th Edition):

Areiza, M. (2014). Ecdysis Triggering Hormone and its Role in Juvenile Hormone Synthesis in the Yellow-fever Mosquito, Aedes aegypti. (Thesis). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/1147 ; 10.25148/etd.FI14040812 ; FI14040812

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

Chicago Manual of Style (16^th Edition):

Areiza, Maria. “Ecdysis Triggering Hormone and its Role in Juvenile Hormone Synthesis in the Yellow-fever Mosquito, Aedes aegypti.” 2014. Thesis, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/1147 ; 10.25148/etd.FI14040812 ; FI14040812.

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

MLA Handbook (7^th Edition):

Areiza, Maria. “Ecdysis Triggering Hormone and its Role in Juvenile Hormone Synthesis in the Yellow-fever Mosquito, Aedes aegypti.” 2014. Web. 15 Apr 2021.

Vancouver:

Areiza M. Ecdysis Triggering Hormone and its Role in Juvenile Hormone Synthesis in the Yellow-fever Mosquito, Aedes aegypti. [Internet] [Thesis]. Florida International University; 2014. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/1147 ; 10.25148/etd.FI14040812 ; FI14040812.

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

Council of Science Editors:

Areiza M. Ecdysis Triggering Hormone and its Role in Juvenile Hormone Synthesis in the Yellow-fever Mosquito, Aedes aegypti. [Thesis]. Florida International University; 2014. Available from: https://digitalcommons.fiu.edu/etd/1147 ; 10.25148/etd.FI14040812 ; FI14040812

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

30. clifton, Mark E. The Endocrine Basis for Reproductive Life-history Trade-offs during the Previtellogenic Resting Stage in the Yellow Fever Mosquito, Aedes aegypti.

Degree: PhD, Biology, 2012, Florida International University

URL: https://digitalcommons.fiu.edu/etd/721 ; 10.25148/etd.FI12110706 ; FI12110706

► Juvenile hormone (JH) is the central hormonal regulator of life-history trade-offs in many insects. In Aedes aegypti, JH regulates reproductive development after emergence. Little… (more)

▼ Juvenile hormone (JH) is the central hormonal regulator of life-history trade-offs in many insects. In Aedes aegypti, JH regulates reproductive development after emergence. Little is known about JH’s physiological functions after reproductive development is complete or JH’s role in mediating life-history trade-offs. By examining the effect of hormones, nutrition, and mating on ovarian physiology during the previtellogenic resting stage, critical roles were determined for these factors in mediating life-history trade-offs and reproductive output. The extent of follicular resorption during the previtellogenic resting stage is dependent on nutritional quality. Feeding females a low quality diet during the resting stage causes the rate of follicular resorption to increase and reproductive output to decrease. Conversely, feeding females a high quality diet causes resorption to remain low. The extent of resorption can be increased by separating the ovaries from a source of JH or decreased by exogenous application of methoprene. Active caspases were localized to resorbing follicles indicating that an apoptosis-like mechanism participates in follicular resorption. Accumulations of neutral lipids and the accumulation of mRNA’s integral to endocytosis and oocyte development such as the vitellogenin receptor (AaVgR), lipophorin receptor (AaLpRov), heavy-chain clathrin (AaCHC), and ribosomal protein L32 (rpL32) were also examined under various nutritional and hormonal conditions. The abundance of mRNA's and neutral lipid content increased within the previtellogenic ovary as mosquitoes were offered increasing sucrose concentrations or were treated with methoprene. These same nutritional and hormonal manipulations altered the extent of resorption after a blood meal indicating that the fate of follicles and overall fecundity depends, in part, on nutritional and hormonal status during the previtellogenic resting stage. Mating female mosquitoes also altered follicle quality and resorption similarly to nutrition or hormonal application and demonstrates that male accessory gland substances such as JH III passed to the female during copulation have a strong effect on ovarian physiology during the previtellogenic resting stage and can influence reproductive output. Taken together these results demonstrate that the previtellogenic resting stage is not an inactive period but is instead a period marked by extensive life-history and fitness trade-offs in response to nutrition, hormones and mating stimuli. Advisors/Committee Members: Fernando Noriega, Lidia Kos, Lou Kim, Fenfei Leng, Alejandro Barbieri.

Subjects/Keywords: Mosquito; oosorption; oogenesis; juvenile hormone; mating; Aedes aegypti

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APA (6^th Edition):

clifton, M. E. (2012). The Endocrine Basis for Reproductive Life-history Trade-offs during the Previtellogenic Resting Stage in the Yellow Fever Mosquito, Aedes aegypti. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/721 ; 10.25148/etd.FI12110706 ; FI12110706

Chicago Manual of Style (16^th Edition):

clifton, Mark E. “The Endocrine Basis for Reproductive Life-history Trade-offs during the Previtellogenic Resting Stage in the Yellow Fever Mosquito, Aedes aegypti.” 2012. Doctoral Dissertation, Florida International University. Accessed April 15, 2021. https://digitalcommons.fiu.edu/etd/721 ; 10.25148/etd.FI12110706 ; FI12110706.

MLA Handbook (7^th Edition):

clifton, Mark E. “The Endocrine Basis for Reproductive Life-history Trade-offs during the Previtellogenic Resting Stage in the Yellow Fever Mosquito, Aedes aegypti.” 2012. Web. 15 Apr 2021.

Vancouver:

clifton ME. The Endocrine Basis for Reproductive Life-history Trade-offs during the Previtellogenic Resting Stage in the Yellow Fever Mosquito, Aedes aegypti. [Internet] [Doctoral dissertation]. Florida International University; 2012. [cited 2021 Apr 15]. Available from: https://digitalcommons.fiu.edu/etd/721 ; 10.25148/etd.FI12110706 ; FI12110706.

Council of Science Editors:

clifton ME. The Endocrine Basis for Reproductive Life-history Trade-offs during the Previtellogenic Resting Stage in the Yellow Fever Mosquito, Aedes aegypti. [Doctoral Dissertation]. Florida International University; 2012. Available from: https://digitalcommons.fiu.edu/etd/721 ; 10.25148/etd.FI12110706 ; FI12110706

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Open Access Theses and Dissertations