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2016

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Articles 1 - 30 of 397

Full-Text Articles in Cell Biology

Cullin-4 Regulates Wingless And Jnk Signaling-Mediated Cell Death In The Drosophila Eye., Meghana Tare, Ankita Sarkar, Shimpi Bedi, Madhuri Kango-Singh, Amit Singh Dec 2016

Cullin-4 Regulates Wingless And Jnk Signaling-Mediated Cell Death In The Drosophila Eye., Meghana Tare, Ankita Sarkar, Shimpi Bedi, Madhuri Kango-Singh, Amit Singh

Biology Faculty Publications

In all multicellular organisms, the fundamental processes of cell proliferation and cell death are crucial for growth regulation during organogenesis. Strict regulation of cell death is important to maintain tissue homeostasis by affecting processes like regulation of cell number, and elimination of unwanted/unfit cells. The developing Drosophila eye is a versatile model to study patterning and growth, where complex signaling pathways regulate growth and cell survival. However, the molecular mechanisms underlying regulation of these processes is not fully understood. In a gain-of-function screen, we found that misexpression of cullin-4 (cul-4), an ubiquitin ligase, can rescue reduced eye mutant phenotypes ...


Phosphorylation Of The Mdm2 Oncoprotein By The C-Abl Tyrosine Kinase Regulates P53 Tumor Suppression And The Radiosensitivity Of Mice, Michael I. Carr, Justine E. Roderick, Hong Zhang, Bruce A. Woda, Michelle A. Kelliher, Stephen N. Jones Dec 2016

Phosphorylation Of The Mdm2 Oncoprotein By The C-Abl Tyrosine Kinase Regulates P53 Tumor Suppression And The Radiosensitivity Of Mice, Michael I. Carr, Justine E. Roderick, Hong Zhang, Bruce A. Woda, Michelle A. Kelliher, Stephen N. Jones

UMass Metabolic Network Publications

The p53 tumor suppressor acts as a guardian of the genome by preventing the propagation of DNA damage-induced breaks and mutations to subsequent generations of cells. We have previously shown that phosphorylation of the Mdm2 oncoprotein at Ser394 by the ATM kinase is required for robust p53 stabilization and activation in cells treated with ionizing radiation, and that loss of Mdm2 Ser394 phosphorylation leads to spontaneous tumorigenesis and radioresistance in Mdm2S394A mice. Previous in vitro data indicate that the c-Abl kinase phosphorylates Mdm2 at the neighboring residue (Tyr393) in response to DNA damage to regulate p53-dependent apoptosis. In this present ...


Wzb117 (2-Fluoro-6-(M-Hydroxybenzoyloxy) Phenyl M-Hydroxybenzoate) Inhibits Glut1-Mediated Sugar Transport By Binding Reversibly At The Exofacial Sugar Binding Site, Ogooluwa A. Ojelabi, Kenneth P. Lloyd, Andrew Simon, Julie K. De Zutter, Anthony Carruthers Dec 2016

Wzb117 (2-Fluoro-6-(M-Hydroxybenzoyloxy) Phenyl M-Hydroxybenzoate) Inhibits Glut1-Mediated Sugar Transport By Binding Reversibly At The Exofacial Sugar Binding Site, Ogooluwa A. Ojelabi, Kenneth P. Lloyd, Andrew Simon, Julie K. De Zutter, Anthony Carruthers

UMass Metabolic Network Publications

WZB117 (2-fluoro-6-(m-hydroxybenzoyloxy) phenyl m-hydroxybenzoate) inhibits passive sugar transport in human erythrocytes and cancer cell lines and, by limiting glycolysis, inhibits tumor growth in mice. This study explores how WZB117 inhibits the erythrocyte sugar transporter glucose transport protein 1 (GLUT1) and examines the transporter isoform specificity of inhibition. WZB117 reversibly and competitively inhibits erythrocyte 3-O-methylglucose (3MG) uptake with Ki(app) = 6 mum but is a noncompetitive inhibitor of sugar exit. Cytochalasin B (CB) is a reversible, noncompetitive inhibitor of 3MG uptake with Ki(app) = 0.3 mum but is a competitive inhibitor of sugar exit indicating that WZB117 and CB ...


Histone Deacetylase 3 Coordinates Heart Development Through Stage-Specific Roles In Cardiac Progenitor Cells, Sara L. Lewandowski Dec 2016

Histone Deacetylase 3 Coordinates Heart Development Through Stage-Specific Roles In Cardiac Progenitor Cells, Sara L. Lewandowski

GSBS Dissertations and Theses

Disruptions in cardiac development cause congenital heart disease, the most prevalent and deadly congenital malformation. Genetic and environmental factors are thought to contribute to these defects, however molecular mechanisms remain largely undefined. Recent work highlighted potential roles of chromatin- modifying enzymes in congenital heart disease pathogenesis. Histone deacetylases, a class of chromatin-modifying enzymes, have developmental importance and recognized roles in the mature heart. This thesis aimed to characterize functions of Hdac3 in cardiac development. We found loss of Hdac3 in the primary heart field causes precocious progenitor cell differentiation, resulting in hypoplastic ventricular walls, ventricular septal defect, and mid- gestational ...


Endothelial-Specific Inhibition Of Nf-Kappab Enhances Functional Haematopoiesis, Michael G. Poulos, Pradeep Ramalingam, Michael C. Gutkin, Maria Kleppe, Michael Ginsberg, Michael J. P. Crowley, Olivier Elemento, Ross L. Levine, Shahin Rafii, Jan Kitajewski, Matthew B. Greenblatt, Jae-Hyuck Shim, Jason M. Butler Dec 2016

Endothelial-Specific Inhibition Of Nf-Kappab Enhances Functional Haematopoiesis, Michael G. Poulos, Pradeep Ramalingam, Michael C. Gutkin, Maria Kleppe, Michael Ginsberg, Michael J. P. Crowley, Olivier Elemento, Ross L. Levine, Shahin Rafii, Jan Kitajewski, Matthew B. Greenblatt, Jae-Hyuck Shim, Jason M. Butler

Open Access Articles

Haematopoietic stem cells (HSCs) reside in distinct niches within the bone marrow (BM) microenvironment, comprised of endothelial cells (ECs) and tightly associated perivascular constituents that regulate haematopoiesis through the expression of paracrine factors. Here we report that the canonical NF-kappaB pathway in the BM vascular niche is a critical signalling axis that regulates HSC function at steady state and following myelosuppressive insult, in which inhibition of EC NF-kappaB promotes improved HSC function and pan-haematopoietic recovery. Mice expressing an endothelial-specific dominant negative IkappaBalpha cassette under the Tie2 promoter display a marked increase in HSC activity and self-renewal, while promoting the accelerated ...


Il-15 Activates The Jak3/Stat3 Signaling Pathway To Mediate Glucose Uptake In Skeletal Muscle Cells, James E. Krolopp, Shantaé M. Thornton, Marcia J. Abbott Dec 2016

Il-15 Activates The Jak3/Stat3 Signaling Pathway To Mediate Glucose Uptake In Skeletal Muscle Cells, James E. Krolopp, Shantaé M. Thornton, Marcia J. Abbott

Health Sciences and Kinesiology Faculty Articles

Myokines are specialized cytokines that are secreted from skeletal muscle (SKM) in response to metabolic stimuli, such as exercise. Interleukin-15 (IL-15) is a myokine with potential to reduce obesity and increase lean mass through induction of metabolic processes. It has been previously shown that IL-15 acts to increase glucose uptake in SKM cells. However, the downstream signals orchestrating the link between IL-15 signaling and glucose uptake have not been fully explored. Here we employed the mouse SKM C2C12 cell line to examine potential downstream targets of IL-15-induced alterations in glucose uptake. Following differentiation, C2C12 cells were treated overnight with 100 ...


Sirt1 Regulates Glial Progenitor Proliferation And Regeneration In White Matter After Neonatal Brain Injury., Beata Jablonska, Marcin Gierdalski, Li-Jin Chew, Teresa Hawley, Mackenzie Catron, Arturo Lichauco, Juan Cabrera-Luque, Tracy Yuen, David Rowitch, Vittorio Gallo Dec 2016

Sirt1 Regulates Glial Progenitor Proliferation And Regeneration In White Matter After Neonatal Brain Injury., Beata Jablonska, Marcin Gierdalski, Li-Jin Chew, Teresa Hawley, Mackenzie Catron, Arturo Lichauco, Juan Cabrera-Luque, Tracy Yuen, David Rowitch, Vittorio Gallo

Pediatrics Faculty Publications

Regenerative processes in brain pathologies require the production of distinct neural cell populations from endogenous progenitor cells. We have previously demonstrated that oligodendrocyte progenitor cell (OPC) proliferation is crucial for oligodendrocyte (OL) regeneration in a mouse model of neonatal hypoxia (HX) that reproduces diffuse white matter injury (DWMI) of premature infants. Here we identify the histone deacetylase Sirt1 as a Cdk2 regulator in OPC proliferation and response to HX. HX enhances Sirt1 and Sirt1/Cdk2 complex formation through HIF1α activation. Sirt1 deacetylates retinoblastoma (Rb) in the Rb/E2F1 complex, leading to dissociation of E2F1 and enhanced OPC proliferation. Sirt1 knockdown ...


The Fate Of Icd-1 During Misfolded Protein Induced Apoptosis In Caenorhabditis Elegans, Kyle H. Perez Dec 2016

The Fate Of Icd-1 During Misfolded Protein Induced Apoptosis In Caenorhabditis Elegans, Kyle H. Perez

Senior Honors Projects, 2010-current

Severe misfolded protein stress initiates cellular responses that often result in the death of the affected cell, typically by apoptosis. An essential aspect of apoptosis is caspase-mediated cleavage of proteins that, once cleaved, further propagate death. One heterodimeric structure putatively targeted in this process in the nascent polypeptide-associated complex (NAC), a translational chaperone thought to help prevent misfolded protein stress in the ER. The purpose of this investigation was to determine whether the beta subunit of the NAC in C. elegans (ICD-1) is cleaved during the induction of apoptosis, with the hypothesis that ICD-1 is cleaved during stressed-induced apoptosis to ...


Mechanism Of Action Of Id4 As A Tumor Suppressor, Shravan Kumar Komaragiri Dec 2016

Mechanism Of Action Of Id4 As A Tumor Suppressor, Shravan Kumar Komaragiri

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

Initial studies demonstrated that Inhibitor of DNA binding/differentiation protein 4 (Id4) acts as a tumor suppressor in prostate cancer (PCa). To further confirm and investigate the mechanism by which ID4 acts as a tumor suppressor, herein we concentrated on two different approaches. In the first approach we investigated ID4 role as a tumor suppressor by regulating AKT/PI3K pathway. In the second approach, we examined the role of Id4 in blocking the tumorogenic properties of metastatic PC3 cells. Phosphoinositide 3-kinase/Protein kinase B (PI3/AKT) pathway regulates multiple biological processes leading to cell survival, proliferation and growth in cancerous ...


Id4 And Fkbp52 Interaction Regulates Androgen Receptor Activity: Mechanistic Insight, Jugal Bharat Joshi Dec 2016

Id4 And Fkbp52 Interaction Regulates Androgen Receptor Activity: Mechanistic Insight, Jugal Bharat Joshi

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

The inhibitor of DNA binding protein 4 (ID4) is a dominant negative regulator of basic helix loop helix (bHLH) family of transcription factors.1 Recently, Patel et al., demonstrated that inhibitor of differentiation 4 (ID4) acts as a tumor suppressor and its loss, frequently observed in prostate cancer, promotes castration-resistant prostate cancer (CRPC) through constitutive androgen receptor (AR) activation.2 However, the mechanism by which loss of ID4 promotes constitutively active AR signaling in the CRPC conditions is unknown. The rationale of the present study was to unravel the underlying molecular mechanisms through which loss of ID4 potentiates AR signaling ...


Regulation Of Alteration/Deficiency In Activation 3 (Ada3) By Acetylation And Its Role In Cell Cycle Regulation And Oncogenesis, Shashank Srivastava Dec 2016

Regulation Of Alteration/Deficiency In Activation 3 (Ada3) By Acetylation And Its Role In Cell Cycle Regulation And Oncogenesis, Shashank Srivastava

Theses & Dissertations

The ADA3 (Alteration/Deficiency in Activation 3) protein is a transcriptional adaptor protein that was initially discovered as a component of several HAT (Histone Acetyltransferase) complexes, the enzyme complex responsible for histone acetylation, which is a prerequisite for transcription. Earlier the studies from Dr. Band’s laboratory and that of others’ have deciphered a crucial role of ADA3 in cell cycle regulation (both through G1/S and G2/M phase transitions) and in maintaining the genomic stability.

While our laboratory investigated the mechanism behind the role of ADA3 in G1/S transition, the same remained unknown for ...


Defining The Role Of Phosphorylation And Dephosphorylation In The Regulation Of Gap Junction Proteins, Hanjun Li Dec 2016

Defining The Role Of Phosphorylation And Dephosphorylation In The Regulation Of Gap Junction Proteins, Hanjun Li

Theses & Dissertations

Gap junctions are intercellular channels that permit the free passage of ions, small metabolites, and signaling molecules between neighboring cells. In the diseased human heart, altered ventricular gap junction organization and connexin expression (i.e., remodeling) are key contributors to rhythm disturbances and contractile dysfunction. Connexin43 (Cx43) is the dominant gap junction protein isoform in the ventricle which is under tight regulation by serine/tyrosine phosphorylation. Phosphorylation and dephosphorylation regulate many aspects of Cx43 function including trafficking, assembly and disassembly, electrical and metabolic coupling at the plaque, as well as to modulate the interaction with other proteins.

Serine phosphorylation has ...


Mitogen And Morphogen Signaling Dysregulation: Pathophysiological Influence In Pancreatic Cancer And Alzheimer’S Disease, Eric Cruz Dec 2016

Mitogen And Morphogen Signaling Dysregulation: Pathophysiological Influence In Pancreatic Cancer And Alzheimer’S Disease, Eric Cruz

Theses & Dissertations

Although the etiology of a particular disease will vary, there are genetic and epigenetic bottlenecks that frequently converge resulting in dysregulation of mitogenic and morphogenetic signaling. This propensity is acutely experienced in malignancy and neurodegenerative disease.

Here, we have first investigated the role of dysregulated signaling in the context of pancreatic cancer (PC). Morphogenetic signaling has been regarded as a pleiotropic pathway with the potential to promote and inhibit metastatic features. Our investigation of bone morphogenetic protein 2 (BMP-2), an archetypical member of the BMP superfamily, has revealed the presence of extracellular, intracellular, and long non-coding RNA products. Our findings ...


Evidence Of A Role For G Protein Signaling Modulator 3 In Cell Division, Drew C. Wallace Dec 2016

Evidence Of A Role For G Protein Signaling Modulator 3 In Cell Division, Drew C. Wallace

Electronic Thesis and Dissertation Repository

Components of G protein-mediated signaling are associated with positioning and orienting the mitotic spindle in the process of cell division. However, a functional role for G protein signaling modulator 3 (GPSM3) in cell division has yet to be defined. The purpose of this study was to investigate a potential role for GPSM3 in cell division. Vascular smooth muscle cells (VSMCs) from Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats, that are known to express GPSM3, were used as a model system. Here I report that GPSM3 mRNA and protein levels varied during different stages of the cell cycle in SHR VSMCs ...


The Origin Of Human White, Brown, And Brite/Beige Adipocytes, So Yun Min Dec 2016

The Origin Of Human White, Brown, And Brite/Beige Adipocytes, So Yun Min

GSBS Dissertations and Theses

During embryonic development, adipocytes emerge from microvasculature. Lineage-­‐tracing studies in mice have shown that adipocyte progenitors reside in the adipose tissue capillaries. However, the direct evidence of an association between adipocyte progenitors and vasculature in humans is lacking. A specific class of adipocytes (brown and beige/brite) expresses the uncoupling protein 1 (UCP1), which consumes glucose and fatty acids to generate heat. The abundance of UCP1- containing adipocytes correlates with a lean metabolically healthy phenotype in human. However, a causal relationship between the presence of these cells and metabolic benefits in human is not clear.

In this thesis, I ...


The Association Between Oxidative Stress, Cellular Differentiation And Galectins In Human Promyelocytic Leukemia Cells (Hl-60), James R. Vinnai Dec 2016

The Association Between Oxidative Stress, Cellular Differentiation And Galectins In Human Promyelocytic Leukemia Cells (Hl-60), James R. Vinnai

Electronic Thesis and Dissertation Repository

Galectins are a group of β-galactoside-binding proteins involved in different cellular processes including stress responses and differentiation. The role and expression of galectins under oxidative stress and during neutrophilic differentiation was examined in HL-60 cells. Galectin gene (LGALS), and galectin protein expression were determined using RT-qPCR and immunoblotting, respectively. Neutrophilic differentiation was measured via a spectrofluorometric assay. DNA methylation and JNK signaling were investigated as galectin regulatory mechanisms. Menadione-induced oxidative stress, DMSO-induced differentiation, DNA hypomethylation and JNK signaling all promoted similar galectin expression profiles. Antioxidant N-acetylcysteine attenuated the menadione-induced galectin expression but only partially attenuated DMSO-induced galectin expression. Galectin inhibitory ...


Developing A Cr281 Peptide Specific T Lymphocyte Immune Response To Target Pancreatic Cancer Cck2i4sv Receptor, Taylor Hook Dec 2016

Developing A Cr281 Peptide Specific T Lymphocyte Immune Response To Target Pancreatic Cancer Cck2i4sv Receptor, Taylor Hook

Honors Projects and Presentations: Undergraduate

Pancreatic cancer is a debilitating disease with a poor survival rate. There are no effective treatments for pancreatic cancer necessitating research to find new targets for treatment. The basis of this research is to determine whether a novel target located inside of pancreatic cancer cells can be utilized to control or eradicate pancreatic tumors by T cell-based immunity. Gastrin and Cholecystokinin (CCK) are hormones that regulate activity of the gastrointestinal tract.Each can signal via CCK-BR, which normally acts as an on/off switch for pancreatic cells to secrete enzymes and bicarbonate. An altered form of the CCK-B receptor, CCK2i4sv ...


Cd4+ T Cell Regulation Of Immune Responses To The Simian Virus 40 Large Tumor Antigen Is Complex And Involves Multiple Layers Of Coordination Dependent On Immune Conditions, Arielle Raugh, Lawrence Mylin Dec 2016

Cd4+ T Cell Regulation Of Immune Responses To The Simian Virus 40 Large Tumor Antigen Is Complex And Involves Multiple Layers Of Coordination Dependent On Immune Conditions, Arielle Raugh, Lawrence Mylin

Honors Projects and Presentations: Undergraduate

Cytotoxic (CD8+) and Helper (CD4+) T lymphocytes play an important role in the immune detection and destruction of tumors. The induction of Cytotoxic T cell responses by multiple CD8 epitopes located within the Simian Virus 40 Large Tumor Antigen (SV40 T ag) oncoprotein has been well characterized, and we have begun to characterize the role(s) of CD4+ Helper T cells in controlling cellular immune responses to the SV40 T ag. The goal of this study was to characterize the cytokines produced by activated SV40T ag-specific Helper T cells in order to identify subset(s) of Helper T cells that ...


Biophysical And Functional Characterization Of Rhesus Macaque Igg Subclasses, Austin W. Boesch, Nana Yaw Osei-Owusu, Andrew R. Crowley, Thach H. Chu, Ying Chan, Joshua Weiner, Pranay Bharadwaj, Rufus Hards, Mark Adamo, Scott Gerber, Sarah Cocklin, Joern Schmitz, Adam Miles, Joshua Eckman, Aaron J. Belli, Keith Reimann, Margaret E. Ackerman Dec 2016

Biophysical And Functional Characterization Of Rhesus Macaque Igg Subclasses, Austin W. Boesch, Nana Yaw Osei-Owusu, Andrew R. Crowley, Thach H. Chu, Ying Chan, Joshua Weiner, Pranay Bharadwaj, Rufus Hards, Mark Adamo, Scott Gerber, Sarah Cocklin, Joern Schmitz, Adam Miles, Joshua Eckman, Aaron J. Belli, Keith Reimann, Margaret E. Ackerman

Open Dartmouth: Faculty Open Access Scholarship

Antibodies raised in Indian rhesus macaques [Macaca mulatta (MM)] in many preclinical vaccine studies are often evaluated in vitro for titer, antigen-recognition breadth, neu- tralization potency, and/or effector function, and in vivo for potential associations with protection. However, despite reliance on this key animal model in translation of promising candidate vaccines for evaluation in first in man studies, little is known about the proper- ties of MM immunoglobulin G (IgG) subclasses and how they may compare to human IgG subclasses. Here, we evaluate the binding of MM IgG1, IgG2, IgG3, and IgG4 to human Fc gamma receptors (FcγR) and ...


Insights Into The Role Of Connexin26 And Connexin30 In Skin Health, Syndromic Disease, And Cutaneous Wound Healing, Eric R. Press Dec 2016

Insights Into The Role Of Connexin26 And Connexin30 In Skin Health, Syndromic Disease, And Cutaneous Wound Healing, Eric R. Press

Electronic Thesis and Dissertation Repository

Connexin26 (Cx26) and Cx30 facilitate gap junctional intercellular communication (GJIC) in the epidermis and are linked to several syndromic skin diseases. We investigated 5 disease- linked Cx26 mutants and demonstrated that the severity and extent of disease can be predicted from the gain- or loss-of function properties of each mutant, as well as the ability to induce cell death. We also used transgenic mice expressing S17F Cx26 (linked to keratitis-ichthyosis- deafness syndrome) or A88V Cx30 (linked to Clouston Syndrome) to investigate the pathophysiology these skin diseases. We demonstrated that S17F Cx26, but not A88V Cx30, promotes palmoplantar keratoderma by disrupting ...


Investigating The Synergistic Effects Of Combined Modified Alginates On Macrophage Phenotype, Hannah C. Bygd, Kaitlin M. Bratlie Dec 2016

Investigating The Synergistic Effects Of Combined Modified Alginates On Macrophage Phenotype, Hannah C. Bygd, Kaitlin M. Bratlie

Materials Science and Engineering Publications

Understanding macrophage responses to biomaterials is crucial to the success of implanted medical devices, tissue engineering scaffolds, and drug delivery vehicles. Cellular responses to materials may depend synergistically on multiple surface chemistries, due to the polyvalent nature of cell–ligand interactions. Previous work in our lab found that different surface functionalities of chemically modified alginate could sway macrophage phenotype toward either the pro-inflammatory or pro-angiogenic phenotype. Using these findings, this research aims to understand the relationship between combined material surface chemistries and macrophage phenotype. Tumor necrosis factor-α (TNF-α) secretion, nitrite production, and arginase activity were measured and used to determine ...


Netrin-3 Peptide (C-19) Is A Chemorepellent And A Growth Inhibitor In Tetrahymena Thermophila, Matthew S. Merical, Kenneth W. Ward, Lois Parks, Heather G. Kuruvilla Dec 2016

Netrin-3 Peptide (C-19) Is A Chemorepellent And A Growth Inhibitor In Tetrahymena Thermophila, Matthew S. Merical, Kenneth W. Ward, Lois Parks, Heather G. Kuruvilla

Science and Mathematics Faculty Presentations

The netrins are a family of signaling proteins expressed throughout the animal kingdom. Netrins play important roles in developmental processes such as axonal guidance and angiogenesis. Netrin-1, for example, can act as either a chemoattractant or a chemorepellent for axonal growth cones depending upon the concentration of the protein as well as the cell type. Netrin-1 acts as a growth factor in some cell types and is expressed by some tumor cells. Netrin-3 appears to share some signaling apparatus with netrin-1, but is less widely expressed, and its physiological roles are much less understood.

Tetrahymena thermophila are free-living, eukaryotic, ciliated ...


Pgc-1alpha Dictates Endothelial Function Through Regulation Of Enos Expression, Siobhan M. Craige, Swenja Kroller-Schon, Chunying Li, Shashi Kant, Shenghe Cai, Kai Chen, Mayur M. Contractor, Yongmei Pei, Eberhard Schulz, John F. Keaney Jr. Dec 2016

Pgc-1alpha Dictates Endothelial Function Through Regulation Of Enos Expression, Siobhan M. Craige, Swenja Kroller-Schon, Chunying Li, Shashi Kant, Shenghe Cai, Kai Chen, Mayur M. Contractor, Yongmei Pei, Eberhard Schulz, John F. Keaney Jr.

UMass Metabolic Network Publications

Endothelial dysfunction is a characteristic of many vascular related diseases such as hypertension. Peroxisome proliferator activated receptor gamma, coactivator 1alpha (PGC-1alpha) is a unique stress sensor that largely acts to promote adaptive responses. Therefore, we sought to define the role of endothelial PGC-1alpha in vascular function using mice with endothelial specific loss of function (PGC-1alpha EC KO) and endothelial specific gain of function (PGC-1alpha EC TG). Here we report that endothelial PGC-1alpha is suppressed in angiotensin-II (ATII)-induced hypertension. Deletion of endothelial PGC-1alpha sensitized mice to endothelial dysfunction and hypertension in response to ATII, whereas PGC-1alpha EC TG mice were ...


Molecular And Functional Analysis Of The Pixb Gene In Xenorhabdus Nematophila, John Lucas Dec 2016

Molecular And Functional Analysis Of The Pixb Gene In Xenorhabdus Nematophila, John Lucas

Theses and Dissertations

Xenorhabdus nematophila and the entomopathogenic nematode Steinernema carpocapsae form a mutualistic relationship facilitating the infection, death and consumption of an insect host. The infective juvenile (IJ) form of S. carpocapsae invades the insect host through natural openings and proceeds to the hemocoel where exposure to hemolymph stimulates the release of X. nematophila from the anterior vesicle. Excreted X. nematophila releases immunosuppressive compounds and insect toxins into the insect hemolymph that facilitates death of the host. As X. nematophila reaches high cell density it secretes exoenzymes that degrade insect tissues and produces antibiotics that reduce microbial competition. S. carpocapsae utilizes the ...


Ultrastructural Changes During Pollen Wall Development And Germination In Arabidopsis Thalaiana, Katrina Olsen Dec 2016

Ultrastructural Changes During Pollen Wall Development And Germination In Arabidopsis Thalaiana, Katrina Olsen

Theses and Dissertations

The Arabidopsis thaliana meiotic mutant 6491 has been identified as displaying temperature sensitive male reduced- fertility. It has been determined that callose wall formation is defective, both in temporal and structural areas. There is irregular rippling in the plasma membrane and aberrant formation of the exine portion of the pollen wall. A developmental study using brightfield, epifluorescence, and transmission electron microscopy of the early stages of wall formation in 6491 has been completed, along with a similar study of Arabidopsis thaliana (L.) heynh, ecotype Wassilewskija (WS). Due to the temperature-sensitive nature of the mutant line, a further study of both ...


Ros Regulation Of Axonal Mitochondrial Transport, Pin-Chao Liao Dec 2016

Ros Regulation Of Axonal Mitochondrial Transport, Pin-Chao Liao

Open Access Dissertations

Mitochondria perform critical functions including aerobic ATP production and calcium (Ca2+) homeostasis, but are also a major source of reactive oxygen species (ROS) production. To maintain cellular function and survival in neurons, mitochondria are transported along axons, and accumulate in regions with high demand for their functions. Oxidative stress and abnormal mitochondrial axonal transport are associated with neurodegenerative disorders. However, we know little about the connection between these two. Using primaryDrosophila neuronal cell culture and the third instar larval nervous system as in vitro and in vivo models, respectively, we studied mitochondrial transport under oxidative stress conditions. In vitro ...


Investigating The Effects Of Ph On Alphaviral E3-E2 Glycoprotein Association, Organization, And Cellular Tropism, Jason Michael Sequra Dec 2016

Investigating The Effects Of Ph On Alphaviral E3-E2 Glycoprotein Association, Organization, And Cellular Tropism, Jason Michael Sequra

Open Access Dissertations

In alphaviruses the role of E3 is required in protecting the fusion peptide region of E1 during intracellular transport. Throughout viral processing, the association of E2 and E3 is required for the successful trafficking and incorporation of E1 into the mature virion. This E3-E2 association has been observed to extend to mature virions in the solved structure for the envelope of Semliki Forest virus (SFV) and supported by the solved structure for the entire Venezuelan equine encephalitis virion (VEEV) with exclusive contacts being made between E3-E2. Immunization with monoclonal antibodies against VEEV E3 provided protection for mice challenged by lethal ...


Microenvironment-Induced Pten Loss By Exosomal Microrna Primes Brain Metastasis Outgrowth, Lin Zhang Dec 2016

Microenvironment-Induced Pten Loss By Exosomal Microrna Primes Brain Metastasis Outgrowth, Lin Zhang

UT GSBS Dissertations and Theses (Open Access)

Development of life-threatening cancer metastases at distant organs requires disseminated tumor cells’ adaptation to and co-evolution with the drastically different microenvironments of metastatic sites. Cancer cells of common origin manifest distinct gene expression patterns after metastasizing to different organs. Clearly, the dynamic interplay between metastatic tumor cells and extrinsic signals at individual metastatic organ sites critically impacts the subsequent metastatic outgrowth. Yet, it is unclear when and how disseminated tumor cells acquire the essential traits from the microenvironment of metastatic organs that prime their subsequent outgrowth. Here we show that primary tumor cells with normal expression of PTEN, an important ...


Characterization Of Vesicular Monoamine Transporter 2 And Its Role In Parkinson's Disease Pathogenesis Using Drosophila, Antonio Joel Tito Jr., Sheng Zhang Dec 2016

Characterization Of Vesicular Monoamine Transporter 2 And Its Role In Parkinson's Disease Pathogenesis Using Drosophila, Antonio Joel Tito Jr., Sheng Zhang

UT GSBS Dissertations and Theses (Open Access)

Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by the selective loss of the dopaminergic neurons in the Substantia nigra pars compacta region of the brain. PD is also the most common neurodegenerative disorder and the second most common movement disorder. PD patients exhibit the cardinal symptoms, including tremor of the extremities, rigidity, slowness of movement, and postural instability, after 70-80% of DA neurons degenerate. It is, therefore, imperative to elucidate the underlying mechanisms involved in the selective degeneration of DA neurons. Although increasing numbers of PD genes have been identified, why these largely widely expressed genes ...


Using Mouse Models To Define How The P53 R72p Polymorphism Impacts The Adverse Effects Of Doxorubicin And Ionizing Radiation, Emily Dominguez Dec 2016

Using Mouse Models To Define How The P53 R72p Polymorphism Impacts The Adverse Effects Of Doxorubicin And Ionizing Radiation, Emily Dominguez

UT GSBS Dissertations and Theses (Open Access)

The single nucleotide polymorphism (SNP) at codon 72 of the tumor suppressor gene p53 codes for either an arginine (R) or proline (P) (p53 R72P). This SNP may impact how cells respond to genotoxic insult. Studies in cell culture and in tissues from mouse models of the SNP indicate that, in response to gentoxic treatment, the two variants may differentially induce apoptosis and expression of p53 target genes. In epidemiological studies, the P variant is associated with decreased cancer survival and increased risk of side-effects from genotoxic cancer treatment. Genotoxic therapy is still the mainstay of cancer treatment, and doxorubicin ...