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Full-Text Articles in Medicine and Health Sciences

Genetic And Physiological Contribution Of Adrenergic Cells In Heart Development, Kingsley Osuala Jan 2011

Genetic And Physiological Contribution Of Adrenergic Cells In Heart Development, Kingsley Osuala

Electronic Theses and Dissertations

The adrenergic hormones norepinephrine (NE) and epinephrine (EPI) are essential for cardiovascular development as embryos lacking NE/EPI begin to die abruptly between embryonic days 10.5 and 11.5 due to apparent cardiac failure. The objective of this research aims to elucidate the mechanism of the embryonic fatality observed in the NE/EPI deficient mouse model. Here we utilized the dopamine β- hydroxylase knockout (Dbh-/-) mouse model, which lacks the gene and subsequent enzyme necessary for the conversion of dopamine to norepinephrine. Embryonic mouse hearts were extracted from Dbh+/+ (control) and Dbh-/- (experimental model) mice for mRNA transcript expression profiling. These studies were …


Glial Differentiation Of Human Umbilical Stem Cells In 2d And 3d Environments, Hedvika Davis Jan 2011

Glial Differentiation Of Human Umbilical Stem Cells In 2d And 3d Environments, Hedvika Davis

Electronic Theses and Dissertations

During differentiation stem cells are exposed to a range of microenvironmental chemical and physical cues. In this study, human multipotent progenitor cells (hMLPCs) were differentiated from umbilical cord into oligodendrocytes and astrocytes. Chemical cues were represented by a novel defined differentiation medium containing the neurotransmitter norepinephrine (NE). In traditional 2 dimensional (2D) conditions, the hMLPCs differentiated into oligodendrocyte precursors, but did not progress further. However, in a constructed 3 dimensional (3D) environment, the hMLPCs differentiated into committed oligodendrocytes that expressed MBP. When co-cultured with rat embryonic hippocampal neurons (EHNs), hMLPCs developed in astrocytes or oligodendrocytes, based on presence of growth …


Role Of Membrane Lipids In Modulating Protein Structure & Function, Ray Supriyo Jan 2011

Role Of Membrane Lipids In Modulating Protein Structure & Function, Ray Supriyo

Electronic Theses and Dissertations

A-B family of toxins consists of plant toxins such as ricin and bacterial toxins such as cholera. The A subunit is the enzymatic domain and the B subunit is the receptor binding domain. Commonly, these toxins bind to the target cell plasma membrane receptors through their B subunit followed by endocytosis and a transport to the endoplasmic reticulum (ER). Inside the ER, the A subunit dissociates from the rest of the toxin, unfolds and triggers the ER quality control mechanism of ER-associated degradation (ERAD). Most ERAD substrates are purged out of the ER into the cytosol for proteasomal degradation. However, …


Translocation Of The Cholera Toxin A1 Subunit From The Endoplasmic Reticulum To The Cytosol, Michael Prentice Taylor Jan 2011

Translocation Of The Cholera Toxin A1 Subunit From The Endoplasmic Reticulum To The Cytosol, Michael Prentice Taylor

Electronic Theses and Dissertations

AB-type protein toxins such as cholera toxin (CT) consist of a catalytic A subunit and a cell-binding B subunit. CT proceeds through the secretory pathway in reverse, termed retrograde trafficking, and is delivered to the endoplasmic reticulum (ER). In order for the catalytic A1 subunit to become active it must separate from the rest of the holotoxin, and this dissociation event occurs in the ER lumen. CTA1 assumes an unfolded conformation upon dissociation from the holotoxin and is recognized by ERassociated degradation (ERAD), a quality control system that recognizes and exports misfolded proteins to the cytosol for degradation by the …


Distinct Domains Of Bax Are Involved In Mitochondrial Bioenergetics And Apoptosis, Ge Zhang Jan 2011

Distinct Domains Of Bax Are Involved In Mitochondrial Bioenergetics And Apoptosis, Ge Zhang

Electronic Theses and Dissertations

Apoptosis is essential for cellular homeostasis and is also a pathologic feature of various diseases. The balance between Bcl-2 family proteins determines whether a cell will live or die. Bax, a member of the BCL-2 family proteins, is a pro-apoptotic protein that exists in both a soluble, cytoplasmic form and a membrane-bound form. Upon apoptotic stimuli, Bax undergoes a conformational change and translocates to the mitochondria, initiating apoptotic events. However, little is known about whether Bax is involved in the regulation of mitochondrial function under non-apoptotic conditions, and how Bax binds to mitochondria to exert its activity. Here, we investigate …


Genetically Modified Es Cells Enhance Cardiac Repair And Regeneration In The Infarcted Heart, Carley E. Glass Jan 2011

Genetically Modified Es Cells Enhance Cardiac Repair And Regeneration In The Infarcted Heart, Carley E. Glass

Electronic Theses and Dissertations

Transplanted embryonic stem (ES) cells following myocardial infarction (MI) contribute to limited cardiac repair and regeneration with improved function. Therefore novel strategies are still needed to enhance the efficacy by which ES cells differentiate into cardiac cell types and inhibit adverse remodeling in the infarcted myocardium. Our studies evaluate whether genetic manipulation of transplanted ES cells employing miR- 1, a pro-cardiac microRNA, and TIMP-1, an anti-apoptotic and anti-fibrotic protein, will enhance cardiac myocyte differentiation, inhibit native cardiac apoptosis, and reduce fibrosis in the infarcted myocardium. Furthermore, we assess levels of associated pro- (caspase-3, PTEN) and anti-(Akt) apoptotic proteins as well …


Avian Cerebellum Specialization In Relation To Acrobatic Courtship Displays In Manakins (Pipridae), Steven Ray Wilkening Jan 2011

Avian Cerebellum Specialization In Relation To Acrobatic Courtship Displays In Manakins (Pipridae), Steven Ray Wilkening

Electronic Theses and Dissertations

The courtship displays of male manakins (Pipridae) involve an array of acrobatic and postural elements. Previously it was found that species with elaborate displays exhibit specializations in motor planning and coordination areas of the brain. Several studies have suggested a relationship between cerebellum (Cb) morphology and distinct motor-related functions for the anterior Cb (somatosensory, flying, hopping/walking), posterior Cb (vision, audition, flying, hopping/walking), and vestibular Cb (flying, hopping/walking, vestibular). The anterior, posterior and vestibular Cb as well as basic morphological features of the Cb were measured and tested for a relationship with courtship display complexity in manakins. I compared Cb morphology …


Stem Cell Biology And Strategies For Therapeutic Development In Degenerative Diseases And Cancer, Angel A. Alvarez Jan 2011

Stem Cell Biology And Strategies For Therapeutic Development In Degenerative Diseases And Cancer, Angel A. Alvarez

Electronic Theses and Dissertations

Stem cell biology is an exciting field that will lead to significant advancements in science and medicine. We hypothesize that inducing the expression of stem cell genes, using the embryonic stem cell gene nanog, will reprogram cells and dedifferentiate human mesenchymal stem cells into pluripotent stem cells capable of neural differentiation. The aims of initial studies are as follows: Aim 1: Demonstrate that forced expression of the embryonic stem cell gene nanog induces changes in human mesenchymal stem cells to an embryonic stem cell-like phenotype. Aim 2: Demonstrate that induced expression of nanog up-regulates the expression of multiple embryonic stem …


Hybrid Adult Neuron Culture Systems For Use In Pharmacological Testing, Darin Keay Edwards Jan 2011

Hybrid Adult Neuron Culture Systems For Use In Pharmacological Testing, Darin Keay Edwards

Electronic Theses and Dissertations

Neuronal culture systems have many applications, such as basic research into neuronal structure, function, and connectivity as well as research into diseases, conditions, and injuries affecting the brain and its components. In vitro dissociated neuronal systems have typically been derived from embryonic brain tissue, most commonly from the hippocampus of E18 rats. This practice has been motivated by difficulties in supporting regeneration, functional recovery and long-term survival of adult neurons in vitro. The overall focus of this dissertation research was to develop a dissociated neuronal culture system from human and animal adult brain tissue, one more functionally and developmentally correlative …


Discovery And Optimization Of Novel Small-Molecular Inhibitors Suppressing Stat3-Dependent Tumor Process, Xiaolei Zhang Jan 2011

Discovery And Optimization Of Novel Small-Molecular Inhibitors Suppressing Stat3-Dependent Tumor Process, Xiaolei Zhang

Electronic Theses and Dissertations

With the critical role of aberrantly active Signal Transducer and Activator of Transcription (Stat) 3 protein in many human cancers, selective small-molecule inhibitors targeting the dimerization event which is required for stat3 activation, would be valuable as therapeutic agents. And the inhibitors will be useful chemical probes to clarify the complex biological functions of Stat3. By computational and structural analyses of the interaction between Stat3 and the lead dimerization disruptor, S3I-201, we have designed a diverse set of analogs. One of the most active analogs, S3I-201.1066 is derived to contain a cyclo-hexyl benzyl moiety on the amide nitrogen, which increases …