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2016

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Articles 1 - 30 of 237

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. Previously, …


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 in culture …


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, 2010-2019

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 …


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. …


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 …


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. …


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 long been …


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 G2 …


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

Dartmouth 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 their …


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 …


Microtubule Actin Cross-Linking Factor 1, A Novel Target In Glioblastoma, Najlaa Afghani, Toral Mehta, Jialiang Wang, Nan Tang, Omar Skalli, Quincy A. Quick Dec 2016

Microtubule Actin Cross-Linking Factor 1, A Novel Target In Glioblastoma, Najlaa Afghani, Toral Mehta, Jialiang Wang, Nan Tang, Omar Skalli, Quincy A. Quick

Biology Faculty Research

Genetic heterogeneity is recognized as a major contributing factor of glioblastoma resistance to clinical treatment modalities and consequently low overall survival rates. This genetic diversity results in variations in protein expression, both intratumorally and between individual glioblastoma patients. In this regard, the spectraplakin protein, microtubule actin cross-linking factor 1 (MACF1), was examined in glioblastoma. An expression analysis of MACF1 in various types of brain tumor tissue revealed that MACF1 was predominately present in grade III-IV astroctyomas and grade IV glioblastoma, but not in normal brain tissue, normal human astrocytes and lower grade brain tumors. Subsequent genetic inhibition experiments showed that …


Hnrnpa2 Is A Novel Histone Acetyltransferase That Mediates Mitochondrial Stress-Induced Nuclear Gene Expression, Manti Guha, Satish Srinivasan, Kip Guja, Edison Mejia, Miguel Garcia-Diaz, F. Brad Johnson, Gordon Ruthel, Brett A. Kaufman, Eric F. Rappaport, M. Rebecca Glineburg, Ji-Kang Fang, Andres J. Klein-Szanto, Hiroshi Nakagawa, Jeelan Basha, Tapas Kundu, Narayan G. Avadhani Dec 2016

Hnrnpa2 Is A Novel Histone Acetyltransferase That Mediates Mitochondrial Stress-Induced Nuclear Gene Expression, Manti Guha, Satish Srinivasan, Kip Guja, Edison Mejia, Miguel Garcia-Diaz, F. Brad Johnson, Gordon Ruthel, Brett A. Kaufman, Eric F. Rappaport, M. Rebecca Glineburg, Ji-Kang Fang, Andres J. Klein-Szanto, Hiroshi Nakagawa, Jeelan Basha, Tapas Kundu, Narayan G. Avadhani

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Reduced mitochondrial DNA copy number, mitochondrial DNA mutations or disruption of electron transfer chain complexes induce mitochondria-to-nucleus retrograde signaling, which induces global change in nuclear gene expression ultimately contributing to various human pathologies including cancer. Recent studies suggest that these mitochondrial changes cause transcriptional reprogramming of nuclear genes although the mechanism of this cross talk remains unclear. Here, we provide evidence that mitochondria-to-nucleus retrograde signaling regulates chromatin acetylation and alters nuclear gene expression through the heterogeneous ribonucleoprotein A2 (hnRNAP2). These processes are reversed when mitochondrial DNA content is restored to near normal cell levels. We show that the mitochondrial stress-induced …


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 …


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

Dissertations & 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 …


Analysis Of Rna Expression Of Normal And Cancer Tissues Reveals High Correlation Of Cop9 Gene Expression With Respiratory Chain Complex Components, Christina A. Wicker, Tadahide Izumi Dec 2016

Analysis Of Rna Expression Of Normal And Cancer Tissues Reveals High Correlation Of Cop9 Gene Expression With Respiratory Chain Complex Components, Christina A. Wicker, Tadahide Izumi

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: The COP9 signalosome, composed of eight subunits, is implicated in cancer genetics with its deneddylase activity to modulate cellular concentration of oncogenic proteins such as IkB and TGFβ. However, its function in the normal cell physiology remains elusive. Primarily focusing on gene expression data of the normal tissues of the head and neck, the cancer genome atlas (TCGA) database was used to identify groups of genes that were expressed synergistically with the COP9 genes, particularly with the COPS5 (CSN5), which possesses the catalytic activity of COP9.

RESULTS: Expressions of seven of the COP9 genes (COPS2, COPS3, COPS4, COPS5, COPS6, …


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 …


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

Dissertations & 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 induce …


Punctuated Evolution Within A Eurythermic Genus (Mesenchytraeus) Of Segmented Worms: Genetic Modification Of The Glacier Ice Worm F1f0 Atp Synthase, Shirley A. Lang Dec 2016

Punctuated Evolution Within A Eurythermic Genus (Mesenchytraeus) Of Segmented Worms: Genetic Modification Of The Glacier Ice Worm F1f0 Atp Synthase, Shirley A. Lang

Graduate School of Biomedical Sciences Theses and Dissertations

Segmented worms (Annelida) are among the most successful animal inhabitants of extreme environments worldwide. An unusual group of Mesenchytraeus worms endemic to the Pacific Northwest of North America occupy geographically proximal ecozones ranging from low elevation temperate rainforests to high altitude glaciers. Along this altitudinal transect, Mesenchytraeus representatives from disparate habitat types were collected and subjected to deep mitochondrial and nuclear phylogenetic analyses. Evidence presented here employing modern bioinformatic analyses (i.e., maximum likelihood, Bayesian inference, multi-species coalescent) supports a Mesenchytraeus “explosion” in the upper Miocene (5-10 million years ago) that gave rise to ice, snow and terrestrial worms, derived from …


Engineered Human Acidic Fibroblast Growth Factor (Fgf1) With An Enhanced Thermal And Proteolytic Stability, Duaa Abdullah Almansaf Dec 2016

Engineered Human Acidic Fibroblast Growth Factor (Fgf1) With An Enhanced Thermal And Proteolytic Stability, Duaa Abdullah Almansaf

Graduate Theses and Dissertations

Fibroblast growth factor receptor (FGFR) is made up of three significant domains. The most important domain is the intracellular domain where the dimerization and autophosphorylation occur. Fibroblast growth factor (FGF) interacts with specific FGFR to regulate many cellular processes during the embryonic stage. Furthermore, FGF is significant for adults because FGF plays an important role in regulating cellular differentiation as well as wound healing. The cellular regulating processes are initiated through binding FGF to heparin followed by binding FGF/heparin to FGFR to form FGF/heparin/FGFR complex. Thus, FGFR is dimerized and autophosphorylated. The phosphorylation of FGFR triggers downstream signaling pathways, which …


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 …


Exploring The Production Of Extracellular Matrix By Astrocytes In Response To Mimetic Traumatic Brain Injury, Addison Walker Dec 2016

Exploring The Production Of Extracellular Matrix By Astrocytes In Response To Mimetic Traumatic Brain Injury, Addison Walker

Graduate Theses and Dissertations

Following injury to the central nervous system, extracellular modulations are apparent at

the site of injury, often resulting in a glial scar. Astrocytes are mechanosensitive cells, which can create a neuroinhibitory extracellular environment in response to injury. The aim for this research was to gain a fundamental understanding of the affects a diffuse traumatic brain injury has on the astrocyte extracellular environment after injury. To accomplish this, a bioreactor culturing astrocytes in 3D constructs delivered 150G decelerations with 20% biaxial strain to mimic a traumatic brain injury. Experiments were designed to compare the potential effects of media type, number of …


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

Dissertations & 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 …


Effect Of Oxygen-Limiting Tidal Conditions On Muscle Metabolism And Structure In The Giant Acorn Barnacle, Balanus Nubilus, Katie O. Grady Dec 2016

Effect Of Oxygen-Limiting Tidal Conditions On Muscle Metabolism And Structure In The Giant Acorn Barnacle, Balanus Nubilus, Katie O. Grady

Master's Theses

Crustacean muscle fibers are some of the largest cells in the animal kingdom, with fiber diameters in the giant acorn barnacle (Balanus nubilus) exceeding 3 mm. Sessile animals with extreme muscle sizes and that live in the hypoxia-inducing intertidal zone – like B. nubilus – represent ideal models for probing the effects of oxygen limitation on muscle cells. We investigated changes in metabolism and structure of B. nubilus muscle in response to: normoxic immersion, anoxic immersion, or air emersion, for acute (6h) or chronic (6h exposures twice daily for 2wks) time periods. Following exposure, we immediately measured hemolymph …


Rapamycin Increases Length And Mechanosensory Function Of Primary Cilia In Renal Eptihelial And Vascular Endothelial Cells, Rinzhin T. Sherpa, Kimberly F. Atkinson, Viviana P. Ferreira, Surya M. Nauli Dec 2016

Rapamycin Increases Length And Mechanosensory Function Of Primary Cilia In Renal Eptihelial And Vascular Endothelial Cells, Rinzhin T. Sherpa, Kimberly F. Atkinson, Viviana P. Ferreira, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia arebiophysically-sensitive organelles responsible for sensing fluid-flow and transducing this stimulus into intracellular responses. Previous studies have shown that the primary cilia mediate flow-induced calcium influx, and sensitivity of cilia function to flow is correlated to cilia length. Cells with abnormal cilia length or function can lead to a host of diseases that are collectively termed as ciliopathies. Rapamycin, a potent inhibitor of mTOR (mammalian target of rapamycin), has been demonstrated to be a potential pharmacological agent against the aberrant mTOR signaling seen in ciliopathies such as polycystic kidney disease (PKD) and tuberous sclerosis complex (TSC). Here we look …


Influence Of Ph And Acidic Side Chain Charges On The Behavior Of Designed Model Peptides In Lipid Bilayer Membranes, Venkatesan Rajagopalan Dec 2016

Influence Of Ph And Acidic Side Chain Charges On The Behavior Of Designed Model Peptides In Lipid Bilayer Membranes, Venkatesan Rajagopalan

Graduate Theses and Dissertations

The molecular properties of transmembrane proteins and their interactions with lipids regulate biological function. Of particular interest are interfacial aromatic residues and charged residues in the core helix whose functions range from stabilizing the native structure to regulating ion channels. This dissertation addresses the pH dependence and influence of potentially negatively charged tyrosine, glutamic acid or aspartic acid side chains. We have employed GWALP23 (acetyl-GGALW5LALALALALALALW19LAGA-amide) as favorable host peptide framework. We have substituted W5 with Tyr (Y5GWALP23) and Leu residues with Glu (L12E, L14E or L16E) or Asp (L14D or L16D), and have incorporated specific 2H-labeled alanine residues within the …


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 …


Dopamine Effects Of Stimulant And Non-Stimulant Drugs Used In The Treatment Of Attention Deficit Hyperactivity Disorder, Preeti Chalwadi Nov 2016

Dopamine Effects Of Stimulant And Non-Stimulant Drugs Used In The Treatment Of Attention Deficit Hyperactivity Disorder, Preeti Chalwadi

Theses and Dissertations

Attention deficit hyperactivity disorder (ADHD) is thought to be associated with dysfunction of ascending catecholamine neuronal systems, particularly dopamine (DA) and norepinephrine (NE). Dysfunction of these catecholamine neurons innervating the prefrontal cortex is hypothesized to underlie impaired executive functions. Dysfunction of the DA neurons innervating the striatum is additionally hypothesized to underlie deficits in motivation and reinforcement learning. However, mechanisms of action of therapeutic drugs used for treating ADHD have mainly focused on catecholamines in the prefrontal cortex and have not adequately addressed the role played by DA signaling in the striatum. Stimulants such as Adderall® and Ritalin® are chemically …


Mxa Is A Novel Regulator Of Endosome-Associated Transcriptional Signaling By Bone Morphogenetic Proteins 4 And 9 (Bmp4 And Bmp9), Huijuan Yuan, Pravin B. Sehgal Nov 2016

Mxa Is A Novel Regulator Of Endosome-Associated Transcriptional Signaling By Bone Morphogenetic Proteins 4 And 9 (Bmp4 And Bmp9), Huijuan Yuan, Pravin B. Sehgal

NYMC Faculty Publications

There is confusion about the role that IFN-α plays in the pathogenesis of pulmonary arterial hypertension (PAH) with different investigators reporting a causative or a protective role. There is now clear evidence in PAH pathogenesis for the involvement of BMP4 and BMP9 signaling, and its disruption by mutations in BMPR2. In the present study, we investigated MxA, an IFN-α-inducible cytoplasmic dynamin-family GTPase for effects on BMP4/9 signaling, including in the presence of PAH-disease-associated mutants of BMPR2. In human pulmonary arterial endothelial cells (HPAECs), IFN-α-induced endogenous as well as exogenously expressed MxA was associated with endosomes that aligned alongside microtubules and …