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Full-Text Articles in Cell Biology

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 ...


Intestinal Adaptation To Repeated Exposure Of Flavonoid-Rich Foods: In Vitro And Clinical Data, Bejamin W. Redan Aug 2016

Intestinal Adaptation To Repeated Exposure Of Flavonoid-Rich Foods: In Vitro And Clinical Data, Bejamin W. Redan

Open Access Dissertations

Interest in application of flavonoids for chronic disease prevention has grown significantly, but the low oral bioavailability of these compounds from acute doses is commonly highlighted as a limitation when considering their biological significance. Still, the impact of broad dietary patterns such as repeated exposure on flavonoid’s absorption, metabolism, and eventual efficacy is critical to consider since evidence suggests that their bioavailability may be enhanced with repeated exposure. To fill this gap in knowledge, this dissertation will focus on three major areas including characterization of flavonoid metabolites, in addition to use of in vitro models and clinical work to ...


Intestinal Cytoplasmic Lipid Droplets, Associated Proteins, And The Regulation Of Dietary Fat Absorption, Theresa M. D'Aquila Aug 2016

Intestinal Cytoplasmic Lipid Droplets, Associated Proteins, And The Regulation Of Dietary Fat Absorption, Theresa M. D'Aquila

Open Access Dissertations

Dietary fat provides essential nutrients, contributes to energy balance, and regulates blood lipid concentrations. These functions are important to health, but can also become dysregulated and contribute to diseases such as obesity, diabetes, and cardiovascular disease. The small intestine absorbs dietary fat through an efficient multi step process of digestion, uptake, metabolism, and secretion or storage. When dietary fat is taken up by the absorptive cells of the small intestine, enterocytes, it can be secreted into circulation where it contributes to blood lipid levels or temporarily stored in cytoplasmic lipid droplets (CLDs). The objective of this dissertation is to investigate ...


Axonal Transport And Life Cycle Of Mitochondria In Parkinson's Disease Model, Hyun Sung Apr 2016

Axonal Transport And Life Cycle Of Mitochondria In Parkinson's Disease Model, Hyun Sung

Open Access Dissertations

In neurons, normal distribution and selective removal of mitochondria are essential for preserving compartmentalized cellular function. Parkin, an E3 ubiquitin ligase associated with familial Parkinson’s disease, has been implicated in mitochondrial dynamics and removal. However, it is not clear how Parkin plays a role in mitochondrial turnover in vivo, and whether the mature neurons possess a compartmentalized Parkin-dependent mitochondrial life cycle. Using the live Drosophila nervous system, here, I investigate the involvement of Parkin in mitochondrial dynamics; organelle distribution, morphology and removal. Parkin deficient animals displayed less number of axonal mitochondria without disturbing organelle motility behaviors, morphology and metabolic ...


Analysis Of Chd Remodelers During Development: A Tale In Two Organisms, Brett Bishop Apr 2015

Analysis Of Chd Remodelers During Development: A Tale In Two Organisms, Brett Bishop

Open Access Dissertations

The correct development of different organisms requires the precise timing of genes important for development transitions. Organisms have recruited ATP-dependent chromatin remodelers to ensure the correct timing of gene expression during developmental transitions. Here I show how different CHD ATP-dependent chromatin remodelers regulate developmental transitions of different organisms. I show that PICKLE not only promotes H3K27me3 during development to repress developmental genes but also is targeted to these genes. The association of PICKLE to these genes suggests that both repression and H3K27me3 levels is a direct action of PICKLE on these loci. Using zebrafish as a model system, I show ...


Mach: A Model For Explaining Molecular And Cellular Mechanisms, Caleb M. Trujillo Jan 2015

Mach: A Model For Explaining Molecular And Cellular Mechanisms, Caleb M. Trujillo

Open Access Dissertations

Biologists use mechanistic explanations to understand behaviors of the immense complexity of molecular and cellular systems. In undergraduate biology courses, students are expected to explain molecular and cellular mechanisms, but teaching this skill presents many challenges due to the highly abstract, intangible nature of the cellular world, the influence of everyday language, and the tendency of students to overestimate how much they can explain. Therefore, across three studies this dissertation addresses these obstacles to teach undergraduate biology students to explain molecular and cellular mechanisms. ^ The first step was to model how biology experts explain molecular and cellular mechanisms, and to ...


Associated Behavioral, Genetic, And Gene Expression Variation With Alternative Life History Tactics In Salmonid Fishes, Ashley Chin-Baarstad Oct 2014

Associated Behavioral, Genetic, And Gene Expression Variation With Alternative Life History Tactics In Salmonid Fishes, Ashley Chin-Baarstad

Open Access Dissertations

Individual differences in behavior can have potential fitness consequences and often reflect underlying genetic variation. My research focuses on three objectives related to individual level variation: 1) evaluating the innate behavioral variation within and between individuals, families, and progeny of different life-history types across time; 2) testing for differences in gene expression within the brain associated with this behavioral variation; and 3) using genetic polymorphisms to test for associations with ecotype, as well as population structure, in polymorphic populations. First, we evaluated the variation in a suite of ecologically relevant behaviors across time in juvenile progeny produced from crosses within ...


Modulation Of Host Phosphatidylinositol Phosphates By Salmonella Effector Protein Sopb, Heather L. Piscatelli Oct 2014

Modulation Of Host Phosphatidylinositol Phosphates By Salmonella Effector Protein Sopb, Heather L. Piscatelli

Open Access Dissertations

Salmonella spp. are gram negative bacteria capable of infecting a number of eukaryotic hosts. In humans, Salmonella infection can range anywhere from acute gastroenteritis to typhoid fever which can oftentimes be fatal.Salmonella are facultative intracellular pathogens that have acquired the ability to enter non-phagocytic cells such as those lining the intestinal epithelium. Uptake into epithelial cells is mediated by the Salmonellapathogenicity island 1 (SPI1) encoded type III secretion system (T3SS), a needle-like complex composed of over 20 proteins that translocates effector proteins directly into the host cell cytosol. Salmonella possess a second type III secretion system encoded on ...


Intranuclear Strain Measured By Iterative Warping In Cells Under Mechanical And Osmotic Stress, Jonathan T Henderson Oct 2014

Intranuclear Strain Measured By Iterative Warping In Cells Under Mechanical And Osmotic Stress, Jonathan T Henderson

Open Access Dissertations

The nucleus is a membrane bound organelle and regulation center for gene expression in the cell. Mechanical forces transfer to the nucleus directly and indirectly through specific cellular cytoskeletal structures and pathways. There is increasing evidence that the transferred forces to the nucleus orchestrate gene expression activity. Methods to characterize nuclear mechanics typically study isolated cells or cells embedded in 3D gel matrices. Often report only aspect ratio and volume changes, measures that oversimplify the inherent complexity of internal strain patterns. This presents technical challenges to simultaneously observe small scale nuclear mechanics and gene expression levels inside the nuclei of ...


Dj-1 And Atp13a2: Two Proteins Involved In Parkinson’S Disease, Josephat M Asiago Jan 2014

Dj-1 And Atp13a2: Two Proteins Involved In Parkinson’S Disease, Josephat M Asiago

Open Access Dissertations

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, affecting approximately 0.3% of the total U.S. population, and its prevalence increases with age. Two neuropathological hallmarks of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta, a region in the midbrain involved in initiating and sustaining movement, and the presence of cytosolic inclusions called Lewy bodies (LBs) in various brain regions. LBs are enriched with fibrillar forms of the presynaptic protein &agr;-synuclein (aSyn). Two autosomal recessive genes implicated in familial PD are PARK9, encoding the P-type ATPase ATP13A2 ...


Establishing The Role Of The Pancreatic Transcription Factor Mist1 In Xbp1-Mediated Maintenance Of Pancreatic Acinar Cell Homeostasis, David Alan Hess Oct 2013

Establishing The Role Of The Pancreatic Transcription Factor Mist1 In Xbp1-Mediated Maintenance Of Pancreatic Acinar Cell Homeostasis, David Alan Hess

Open Access Dissertations

Pancreatic acinar cells (PACs) continuously produce more protein than any other cell type in the human body. As a result, PACs and other specialized secretory cells have a constant demand placed on their protein synthetic and packaging machinery. When demand for secreted products exceeds the capacity of the cell's basal protein production facilities, dangerous accumulations of misfolded proteins can build up, resulting in a condition known as ER stress. To ameliorate this stress, secretory cells activate a coordinated, three-part compensatory network collectively known as the unfolded protein response (UPR) to both expand the capacity of the ER and directly ...


Measuring And Modeling The Response Characteristics Of The Environmental Phosphate Transducer In Escherichia Coli, Chetan Sood Oct 2013

Measuring And Modeling The Response Characteristics Of The Environmental Phosphate Transducer In Escherichia Coli, Chetan Sood

Open Access Dissertations

The PhoR/PhoB two-component system in Escherichia coli is a biological transducer that senses the limitation of environmental inorganic orthophosphate, the bacteria's preferred source of the essential nutrient phosphate, and transmits that information to the interior of the cell initiating a response that mitigates phosphate starvation. In the first part of this study, we present and apply a fluorescence microscopy technique to measure, in vivo, the dynamic response characteristics of the transducer with single-cell resolution. We report that the transience in the PhoR/PhoB TCS response is consistent with the transducer having a threshold sensitivity to the concentration of ...


The Role Of Ykl-40 In The Progression Of Glioblastoma, Ralph Anthony Francescone Sep 2013

The Role Of Ykl-40 In The Progression Of Glioblastoma, Ralph Anthony Francescone

Open Access Dissertations

Glioblastoma Multiforme (GBM) is the most common brain cancer and one of the most fatal forms of cancer overall. The average survival time is 10-14 months, and less than 10% of patients survive more than 5 years after diagnosis. It is characterized by extreme vasculature, chemo/radioresistance, and invasiveness into the normal brain. The current standard of care, which includes surgical removal of tumor, radiation, and the chemotherapeutic agent temozolomide, initially stunt tumor growth. Nevertheless, the tumor invariably rebounds and the patient succumbs to the disease. Therefore, there is an urgent need to develop new therapies for this devastating disease ...


Effects Of Phytochemicals From Rhodiola Crenulata On Highly Invasive Breast Cancer Cell Lines And Embryonic Models Of Migration, Adaris Rodriguez-Cortes Sep 2013

Effects Of Phytochemicals From Rhodiola Crenulata On Highly Invasive Breast Cancer Cell Lines And Embryonic Models Of Migration, Adaris Rodriguez-Cortes

Open Access Dissertations

The root of the Tibetan plant Rhodiola crenulata is part of eastern traditional medicine. Studies have suggested that members of the Rhodiola genus display anticancer properties. In this study we examine the effect of R. crenulata in a cellular model of invasive breast cancer, this disease being the second cause of cancer death among women in the US. Deregulation of the Wnt/β-catenin pathway has been frequently observed in breast cancers and appears to have a key role in the transformation of benign cells to a malignant form. Although mutations of the Wnt growth factor are rarely observed in cancer ...


Identification And Functional Characterization Of The Zebrafish Gene Quetschkommode (Que), Timo Friedrich Sep 2012

Identification And Functional Characterization Of The Zebrafish Gene Quetschkommode (Que), Timo Friedrich

Open Access Dissertations

Locomotion in vertebrates depends on proper formation and maintenance of neuronal networks in the hind-brain and spinal cord. Malformation or loss of factors required for proper maintenance of these networks can lead to severe neurodegenerative diseases limiting or preventing locomotion. A powerful tool to investigate the genetic and cellular requirements for development and/or maintenance of these networks is a collection of zebrafish mutants with defects in motility. The zebrafish mutant quetschkommode (que) harbors a previously unknown gene defect leading to abnormal locomotor behavior. Here I show that the que mutants display a seizure-like behavior starting around four days post ...


Target Recognition And Competitive Synaptogenesis In The Drosophila Giant Fiber System, Jason Joseph Hill May 2012

Target Recognition And Competitive Synaptogenesis In The Drosophila Giant Fiber System, Jason Joseph Hill

Open Access Dissertations

The development of complex neural networks relies on a careful balance of environmental cues to guide and shape both ends of the eventual connection. However, the correct wiring of circuits whose components share molecular profiles depends on a more elaborate phenomenon, competition. Despite being highly studied, there is still a lack of understanding as to the mechanism that allows molecularly identical cells to form exclusive connections with their targets. To address this complex question, we turned to a simple circuit within the genetically tractable fly. Responsible for the escape reflex, the Giant Fiber System is comprised of bilaterally symmetrical axons ...


Components Of A Protein Machine: Allosteric Domain Assembly And A Disordered C-Terminus Enable The Chaperone Functions Of Hsp70, Robert G. Smock Sep 2011

Components Of A Protein Machine: Allosteric Domain Assembly And A Disordered C-Terminus Enable The Chaperone Functions Of Hsp70, Robert G. Smock

Open Access Dissertations

Hsp70 molecular chaperones protect proteins from aggregation, assist in their native structure formation, and regulate stress responses in the cell. A mechanistic understanding of Hsp70 function will be necessary to explain its physiological roles and guide the therapeutic modulation of various disease states. To this end, several fundamental features of the Hsp70 structure-function relationship are investigated. The central component of Hsp70 chaperone function is its capacity for allosteric signaling between structural domains and tunable binding of misfolded protein substrates. In order to identify a cooperative network of sites that mediates interdomain allostery within Hsp70, a mutational correlation analysis is performed ...


The Role Of The Suprmam1 Locus In Responses To Ionizing Radiation And Susceptibility To Mammary Tumors, Nicholas B. Griner May 2011

The Role Of The Suprmam1 Locus In Responses To Ionizing Radiation And Susceptibility To Mammary Tumors, Nicholas B. Griner

Open Access Dissertations

Loss of p53 function can lead to a variety of cancers, including breast cancer. Mice heterozygous for the p53 gene (designated Trp53+/-) develop spontaneous mammary tumors, but this depends on the strain background and has been linked to a locus on chromosome 7 (designated SuprMam1). Mammary tumors are common in BALB/c-Trp53+/-females, but are rare in C57BL/6-Trp53+/- mice. Prevalence of genomic instability appears to contribute to the phenotype as loss of heterozygosity (LOH) is significantly more common among tumors arising in BALB/c-Trp53+/- mice compared to C57BL/6J-Trp53+/- mice. This increased LOH in BALB/c-Trp53+/- tumors was shown ...


Xenopus Adam13 And Adam19 Are Important For Proper Convergence And Extension Of The Notochord, Russell David Neuner Feb 2011

Xenopus Adam13 And Adam19 Are Important For Proper Convergence And Extension Of The Notochord, Russell David Neuner

Open Access Dissertations

Gastrulation is a fundamental process that reorganizes the primary germ layers to shape the internal and external features of an early embryo. Morphogenetic movements underlying this process can be classified into a variety of different types of cellular movements. I will focus on investigating in this thesis two types of cell movements in the dorsal mesoderm; mediolateral cell intercalation and convergence and extension. During gastrulation, mesoderm cells send protrusions to gain traction on neighboring cells and the surrounding extracellular matrix; a process called mediolateral cell intercalation. Mesoderm cells use this type of cell movement to converge and extend the dorsal ...


From Mouse Mammary Tumor Model To New Therapeutic Method ---Mammary Tumor Development In Balb/C-Trp53+/- Mice And Magnetic Nanoparticle Induced Heating For Cancer Treatment, Haoheng Yan May 2010

From Mouse Mammary Tumor Model To New Therapeutic Method ---Mammary Tumor Development In Balb/C-Trp53+/- Mice And Magnetic Nanoparticle Induced Heating For Cancer Treatment, Haoheng Yan

Open Access Dissertations

PATHWAYS CONTRIBUTING TO DEVELOPMENT OF SPONTANEOUS MAMMARY TUMORS IN BALB/c-Trp53+/- MICE Mutation and loss of p53 function are common features among human breast cancers. We use BALB/c-Trp53+/- mice as a model to examine the sequence of events leading to mammary tumors. Mammary epithelium proliferation rates were similar in both BALB/c-Trp53+/- mice and wild type controls. Among the 28 mammary tumors collected from BALB/c-Trp53+/- mice, loss of heterozygosity for Trp53 was detected in more than 90% of invasive mammary tumors. Transplantation of Trp53+/- ductal hyperplasias indicated an association between loss of the wild type allele of Trp53 ...


Notch 1 Mediated Inhibition Of Nur77-Induced Apoptosis: Implications For T-Cell Leukemia, Jonathan George Rud May 2010

Notch 1 Mediated Inhibition Of Nur77-Induced Apoptosis: Implications For T-Cell Leukemia, Jonathan George Rud

Open Access Dissertations

It is widely accepted that activating mutations of genes encoding the Notch family of transmembrane receptors, specifically Notch1, are associated with oncogenic transformation. Previous data from our lab has shown that an active form of Notch1 (NICD) provides protection against apoptosis in D011.10 T cells; and that this effect may be attributed to NICD binding the pro-apoptotic protein Nur77. Nur77 is an immediate early gene that is upregulated during both negative selection of thymocytes and activation-induced apoptosis in D011.10 T cells. Nur77 upregulation is tightly regulated and requires MEF2D, NFAT, and the transcriptional co-activator, p300, to effectively respond ...


The Role Of Runx1 N-Terminal Splice Isoforms In Hematopoietic Development, Emmett E. Hedblom Feb 2010

The Role Of Runx1 N-Terminal Splice Isoforms In Hematopoietic Development, Emmett E. Hedblom

Open Access Dissertations

Runx1/AML1 transcription factor expression in hematopoietic cell lineages is differentially regulated via usage of two distinct promoters. The 5' UTR and a 19 amino acid encoding sequence transcribed from the distal promoter is inserted via alternative splicing into the 5' end of the mRNA transcript, replacing the 5' UTR and a 5 amino acid encoding sequence usually transcribed from the proximal promoter. Expression of proximal Runx1 in 32Dcl.3 cells delays G-CSF induced neutrophil terminal differentiation by increasing viability compared to distal Runx1. We utilized Runx1 Nterminal deletion and point mutants of three evolutionarily conserved residues to describe dual ...


New Insights In The Tssk Family: Studies In The Activity And Function Of The Testis Specific Serine Kinases, Julian Sosnik Feb 2010

New Insights In The Tssk Family: Studies In The Activity And Function Of The Testis Specific Serine Kinases, Julian Sosnik

Open Access Dissertations

The Testis Specific Serine Kinase (Tssk) family of proteins is a large group of kinases that present high level of conservation within paralogs, as well as within species. In addition, in all reported cases as well as in the analysis of expressed sequence tags available in databases, this family of proteins presents a very strict pattern of either testicular or male-gonadal expression. This high level of conservation prompted the postulate that these kinases ought to be important for either testicular function or fertilization. In this work we attempt a biochemical characterization of one family member (Tssk6) in the mouse. We ...


Beyond Cell Adhesion: Exploring The Role Of Cadherin-11 Extracellular Processing By Adam Metalloproteases In Cranial Neural Crest Migration, Catherine D. Mccusker Feb 2010

Beyond Cell Adhesion: Exploring The Role Of Cadherin-11 Extracellular Processing By Adam Metalloproteases In Cranial Neural Crest Migration, Catherine D. Mccusker

Open Access Dissertations

The migration of the cranial neural crest is an essential part of cranio-facial development in every vertebrate embryo. The cranial neural crest (CNC) is a transient population of cells that forms the lateral border of the anterior neural plate. In the tailbud stage Xenopus embryo, the neural crest cells delaminate from the neural tube, and undergo a large-scale migration from the dorsal to ventral region of the embryo. The CNC travels along distinct pathways, and populates specific regions of the embryos face. Once the CNC ceases migrating, it differentiates into a variety of tissues that are essential for cranio-facial structure ...


Modulation Of Macrophage Responses To Borrelia Burgdorferi In Acute Murine Lyme Carditis, Chris Martin Olson May 2009

Modulation Of Macrophage Responses To Borrelia Burgdorferi In Acute Murine Lyme Carditis, Chris Martin Olson

Open Access Dissertations

The Lyme disease spirochete Borrelia burgdorferi is the only known human pathogen that directly activates invariant natural killer T (iNKT) cells. The number and activation kinetics of iNKT cells vary greatly among different strains of mice. Here, we report the role of the iNKT cell response in the pathogenesis of Lyme disease using C57BL/6 (B6) mice, a strain with optimal iNKT cell activation that is resistant to the development of spirochetal-induced inflammation. During experimental infection of B6 mice with B. burgdorferi , iNKT cells localize to the inflamed heart where they are activated by CD1d-expressing macrophages. Activation of iNKT cells ...


The Conformational Gymnastics Of The Escherichia Coli Seca Molecular Machine And Its Interactions With Signal Sequences, Jenny Lynn Maki May 2009

The Conformational Gymnastics Of The Escherichia Coli Seca Molecular Machine And Its Interactions With Signal Sequences, Jenny Lynn Maki

Open Access Dissertations

Protein secretion is a selective and regulated process that is essential in all organisms. In bacteria the preprotein translocase SecA, either free in the cytosol or associated with the SecYEG translocon, recognizes and binds most post-translational secretory proteins containing an N-terminal signal sequence. In Gram-negative bacteria, the molecular chaperone SecB binds many of the preproteins to keep them in a translocation-competent state. Subsequently, SecB delivers the preproteins to the translocon-associated SecA, which binds the signal sequence and also interacts with mature regions of the preprotein. After the preprotein/SecA/SecYEG complex has formed, the energy derived from ATP hydrolysis by ...


Delayed Anesthetic Preconditioning And Metallothioneins I+Ii: Novel Mediators Of Anesthetic-Induced Protection, Scott David Edmands May 2009

Delayed Anesthetic Preconditioning And Metallothioneins I+Ii: Novel Mediators Of Anesthetic-Induced Protection, Scott David Edmands

Open Access Dissertations

Ischemic injury is a common and debilitating outcome of natural illness and as a complication of commonly performed medical procedures. Whereas naturally occurring ischemic insults are often the result of unpredictable events, such as in the case of stroke or heart attack, the risk of operative and perioperative ischemia is somewhat better characterized in the clinical setting. Given the prevalence and severity of outcomes in ischemic injury, there is significant interest in developing better pharmacological and procedural approaches to improve patient outcomes. One approach that has shown significant promise in the laboratory setting, particularly in the context of planned medical ...