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Application Of Genetically-Encoded Photoactivatable Crosslinkers To Map Ligand-Binding Sites On G Protein-Coupled Receptors, Amy Grunbeck Jan 2013

Application Of Genetically-Encoded Photoactivatable Crosslinkers To Map Ligand-Binding Sites On G Protein-Coupled Receptors, Amy Grunbeck

Student Theses and Dissertations

G protein-coupled receptors (GPCRs) are dynamic membrane proteins that bind extracellular molecules to transduce biological signals. Although GPCRs represent the largest class of targets for therapeutic agents, ligand-binding sites have been precisely defined for only a small percentage of the receptors in the human genome. A general cellbased photocrosslinking approach was developed to investigate the binding interfaces necessary for the formation of GPCR signaling complexes. Amber codon suppression was extended to facilitate the incorporation of photoactivatable unnatural amino acids, p-benzoyl-L-phenylalanine and p-azido-L-phenylalanine, into engineered GPCRs expressed in mammalian cells in culture. Proof-of-concept studies were carried out in chemokine receptors C-X-C …


Deep Brain Stimulation To Increase Generalized Arousal In Intact Mice And A Mouse Model Of Traumatic Brain Injury, Amy Wells Quinkert Jan 2013

Deep Brain Stimulation To Increase Generalized Arousal In Intact Mice And A Mouse Model Of Traumatic Brain Injury, Amy Wells Quinkert

Student Theses and Dissertations

Deep Brain Stimulation (DBS) is a promising neurosurgical technique that may be useful in promoting emergence to consciousness in minimally conscious state (MCS) patients. In this context, DBS of the central thalamus (CT/DBS) is intended to act as a surrogate input from the ascending arousal systems to support cortical recruitment for cognitive tasks. To test the effectiveness of CT/DBS, intact mice and a mouse model of traumatic brain injury (TBI) have been stimulated under the hypothesis that CT/DBS increases generalized arousal. Two of the three dimensions of the operational definition of generalized arousal are presented here: motor activity and sensory …


Examining The Regulation Of Cell Division By The Spindle Assembly Checkpoint, Maria Maldonado Jan 2013

Examining The Regulation Of Cell Division By The Spindle Assembly Checkpoint, Maria Maldonado

Student Theses and Dissertations

Accurate chromosome segregation during cell division is essential for the maintenance of a cell's genomic stability. The molecular surveillance mechanism called the spindle assembly checkpoint (SAC) inhibits chromosome segregation before all chromosomes are correctly attached (bi-oriented) on the microtubule spindle to prevent segregation errors that may lead to chromosomal instability and cell death. In this thesis, I have developed and used tools to examine the roles of different checkpoint proteins in the mechanism of SAC signaling. In the first part of the thesis, I manipulate the localization of the checkpoint protein Mad1 and show that its constitutive presence at the …


Tuning Of Neuronal Excitation By A Brain Specific Microrna Mir-128: From Targets To Behavior, Chan Lek Tan Jan 2013

Tuning Of Neuronal Excitation By A Brain Specific Microrna Mir-128: From Targets To Behavior, Chan Lek Tan

Student Theses and Dissertations

MicroRNAs constitute a vital new component of our evolving understanding of regulatory mechanisms that shape cellular gene expression. As ubiquitous regulators of protein translation, microRNAs have a unique regulatory function that is only beginning to be fully described. In addition, their role in the control of gene expression in neurons, which underpins neuronal identity and information processing, has not been fully addressed. In this thesis, I present studies that demonstrate a potent yet previously unknown regulation of neuronal intrinsic excitability by the microRNA miR-128. I show using genetic models that endogenous miR-128 plays a powerful role in dampening the excitability …


An Analysis Of Synaptotagmins In Caenorhabditis Elegans, Laura Winzenread Jan 2013

An Analysis Of Synaptotagmins In Caenorhabditis Elegans, Laura Winzenread

Student Theses and Dissertations

Neurotransmission involves the release of neurotransmitters from a presynapticneuron, followed by the reuptake of the protein components of the synaptic vesicle. The basic steps of synaptic vesicle exocytosis and endocytosis have been elucidated, and a number of components of the neurotransmission machinery have been identified. The exact function of each component, however, has been difficult to ascertain as many components act in multiple steps of neurotransmission. In my thesis, I describe the identification of a mutation in the snt-1 gene, which encodes a member of the synaptotagmin family in Caenorhabditis elegans. Synaptotagmins are best known as the calcium-sensing proteins for …


Studies Of G Protein-Coupled Receptor Stability And Dimerization Using Novel Fluorescence And Crosslinking Approaches, Adam Knepp Jan 2013

Studies Of G Protein-Coupled Receptor Stability And Dimerization Using Novel Fluorescence And Crosslinking Approaches, Adam Knepp

Student Theses and Dissertations

G protein-coupled receptors (GPCRs) comprise a large family of related seventransmembrane- helical membrane proteins that bind to specific extracellular ligands, such as hormones or neuromodulators. The active receptor-ligand complex then engages with a heterotrimeric G protein on the cytoplasmic surface of the plasma membrane to facilitate a change in the concentration of an intracellular second messenger, such as cAMP. A number of non-canonical signaling pathways, such as β-arrestin-mediated signaling, also exist for many, if not all, GPCRs. Receptor signaling is attenuated by phosphorylation and receptor internalization. Recent advances in structural studies of GPCRs have revealed high-resolution structures of both inactive …


Frequency Selectivity Of Synaptic Exocytosis In Hair Cells Of The Bullfrog's Amphibian Papilla, Suchit H. Patel Jan 2013

Frequency Selectivity Of Synaptic Exocytosis In Hair Cells Of The Bullfrog's Amphibian Papilla, Suchit H. Patel

Student Theses and Dissertations

Auditory organs act as spectral analyzers by decomposing acoustic stimuli into their frequency constituents. Individual auditory afferent neurons of the VIIIth cranial nerve respond best to a particular frequency of stimulation, and are thus frequency-tuned. Much of the tuning in the inner ears of mammals is ascribed to the frequency dependence of the traveling waves on the basilar membrane, the flexible structure that houses hair cells, the auditory receptors. However, in non-mammalian vertebrates, the basilar membrane does not conduct a traveling wave. In some animals, the membrane is absent entirely. Yet auditory fibers from these animals display comparable sharpness of …


Cannabinoid Cb1r Receptor Mediates Metabolic Syndrome In Models Of Circadian And Glucocorticoid Dysregulation, Nicole Bowles Jan 2013

Cannabinoid Cb1r Receptor Mediates Metabolic Syndrome In Models Of Circadian And Glucocorticoid Dysregulation, Nicole Bowles

Student Theses and Dissertations

The most recent projections in the growing obesity rates across the nation show an increase to 60% by the year 2030. These growing rates of obesity are paralleled by an increased rates of depressive conditions, anxiety, and sleep loss, often with environmental factors at the root of the cause. Stress and the stress response is a dynamic system that reflects one's ability to cope with events, behaviorally or physiologically, as stressors occur over a lifetime. While many key players mediate the effects of stress exposure on disease outcomes including the sympathetic nervous system, parasympathetic, inflammatory cytokines and metabolic hormones, this …


Analysis Of Small Molecule Inhibitors Aimed At Bacterial Virulence, Paul Daniel Dossa Jan 2013

Analysis Of Small Molecule Inhibitors Aimed At Bacterial Virulence, Paul Daniel Dossa

Student Theses and Dissertations

The emergence of antibiotic-resistant bacterial pathogens and the discovery of new bacterial pathogens have motivated the development of novel antibacterials. One recently proposed strategy is to target pathogenic bacteria specifically by inhibiting virulence mechanisms as opposed to killing bacteria indiscriminately, which includes commensal strains. Due to the increased appreciation for the role commensal bacteria play in the immune response and the importance for maintaining a healthy microbiota, specifically targeting pathogenic bacteria is a desirable goal to attain. Genetic and biochemical studies have highlighted type III secretion systems (T3SSs) as essential components for infection of host cells by Gram-negative bacterial pathogens. …


Rna Dynamics In T Cell Activation, Emily Conn Gantman Jan 2013

Rna Dynamics In T Cell Activation, Emily Conn Gantman

Student Theses and Dissertations

Eukaryotic cells employ multiple posttranscriptional mechanisms to fine tune gene expression programs in response to external signals. Regulation of messenger RNA and microRNA by RNA-binding proteins is critical to the control of this process. Hence, disruptions of RNA regulatory processes result in neurologic diseases, cancer, and immunologic disorders among other complications. Posttranscriptional control of RNA is particularly important for precise cytokine expression in T cells during adaptive immune responses. We have studied human lymphocyte activation as a model for correlating changes in RNA regulation with dynamic cellular state changes and stress responses. We hypothesize that RNA-binding proteins such as Argonaute …


Mechanism Of Translational Control By The Fragile X Mental Retardation Protein And Creation Of The Fmrp Ctag Mouse, Sarah Van Driesche Jan 2013

Mechanism Of Translational Control By The Fragile X Mental Retardation Protein And Creation Of The Fmrp Ctag Mouse, Sarah Van Driesche

Student Theses and Dissertations

The Fragile X Mental Retardation Protein (FMRP) is a neuronal RNA-binding protein that is predominantly associated with polyribosomes. Loss of FMRP results in Fragile X Syndrome, characterized by mental retardation, autism and epilepsy. FMRP was recently found to be associated with a specific set of mRNAs with key roles in neuronal function and to physically interact with targeted mRNAs along their entire coding sequences (Darnell 2011). Here, we find that FMRP inhibits translation on these target transcripts by stalling ribosomes, both in vivo and in rabbit reticulocyte lysate programmed with endogenous brain polyribosomes. In these systems, loss of FMRP function …


Communication Of Emotion In Music, Jesse Paul Huhnerkoch Jan 2013

Communication Of Emotion In Music, Jesse Paul Huhnerkoch

All Graduate Theses, Dissertations, and Other Capstone Projects

The communication of emotion in music has been shown to be dependent on musical structure and emotional prompting with lyrical messages. This study seeks a new approach to researching the communication of emotion in music by creating musical samples that are based upon the sound wave frequency parameters of emotive speaking. An electronic survey containing six different emotive musical samples was conducted to gather listener interpretations of the intended emotional quality. Further research is needed to properly distinguish the parameters of emotive frequencies in order to provide for exposure of the functionalities of this phenomenon.


Medicine@Yale August 2013 Volume 9, Issue 3, Yale School Of Medicine Office Of Communications Jan 2013

Medicine@Yale August 2013 Volume 9, Issue 3, Yale School Of Medicine Office Of Communications

Medicine@Yale - development newsletter

Medicine@Yale : advancing biomedical science, education and health care was a print and online newsletter which published news about academics, research and philanthropy for alumni, donors, faculty, students and the general public. It was initially published 6 times a year and then changed to a quarterly schedule. The first issue came out June/Jul. 2005. The final issue was published in May/June 2022, vol. 17, issue 1. Published by Yale School of Medicine, Office of Communications.


Counseling Families In Poverty: Moving From Paralyzing To Revitalizing, Blaire Cholewa, Sondra Smith-Adcock Jan 2013

Counseling Families In Poverty: Moving From Paralyzing To Revitalizing, Blaire Cholewa, Sondra Smith-Adcock

Michigan Journal of Counseling: Research, Theory and Practice

Counseling families in poverty can be a daunting process if one only focuses on what is lacking. Taking such a deficit approach is limiting not only to the counselor but also can serve to disempower the clients. This paper presents a strengths-based approach for counseling families living in poverty that emphasizes relational processes and the excavation of resources and resilience. More specifically, recommendations are presented that recognize the contextual factors of families living in poverty and that stress the therapeutic relationship, counselor self-reflection, an unassuming professional stance, and taking on of an advocacy role.


Finding A Cure: Incentivizing Partnerships Between Disease Advocacy Groups And Academic Commercial Researchers , Anne M. Readel Jan 2013

Finding A Cure: Incentivizing Partnerships Between Disease Advocacy Groups And Academic Commercial Researchers , Anne M. Readel

Journal of Law and Health

Collaborations between for-profit drug companies and not-for-profit disease advocacy groups have risen in recent years in an effort to find cures for orphan diseases. These unique and beneficial collaborations are a result of disease advocacy groups assuming a more active role in drug development through the use of “venture philanthropy,” which employs concepts and techniques from venture capitalism and applies them to achieving philanthropic goals. While these collaborations have found remarkable success, such as the discovery of the first known cure for cystic fibrosis in 2012, venture philanthropy for drug discovery presents numerous legal and social challenges. This Article examines …


Do You Know Where Your Dna Is? The Need For Dna Legislation In Ohio, Elizabeth Collins Jan 2013

Do You Know Where Your Dna Is? The Need For Dna Legislation In Ohio, Elizabeth Collins

Journal of Law and Health

This Note examines the several privacy and safety issues stemming from DNA theft. Part II discusses constitutional and common law regarding the abandonment of property, particularly under the Fourth Amendment, and explains how the Fourth Amendment does not protect individuals from DNA theft. Part III details the many consequences resulting from DNA theft. These risks, among countless others, include employment and insurance discrimination, family turmoil caused by paternity testing which is often inaccurate and conducted without consent, genetic stalking, security risks, and the unauthorized publication of personal medical information and ancestral information. Part IV examines DNA theft legislation adopted by …


The Law And Politics Of Unjust Enrichment, Dan Priel Jan 2013

The Law And Politics Of Unjust Enrichment, Dan Priel

Comparative Research in Law & Political Economy

One of the marked differences between American private law and the private law of the rest of the common law world is the relative lack of interest in restitution in the former compared with the enthusiasm for the subject in the latter. It has recently been suggested that this difference has to do with the impact of legal realism on American law. It was realism’s disdain for doctrinal analysis, it is said, which explains why American scholars did not find the largely doctrinally-driven work on restitution very interesting. In this essay I reject this argument as it fails to explain …


Fruitful Diversity: Revisiting The Enforceability Of Gestational Carriage Contracts, Susan G. Drummond Jan 2013

Fruitful Diversity: Revisiting The Enforceability Of Gestational Carriage Contracts, Susan G. Drummond

Comparative Research in Law & Political Economy

While the federal Assisted Human Reproduction Act was eviscerated by the Supreme Court challenge from Quebec to its constitutional integrity, the room allotted to the provinces to regulate aspects of assisted regulation remains to a large extent unoccupied. This is particularly evident in the domain of parentage law where a significant number of provinces have either thin statutory regulation or none at all, leaving dated common law principles to resolve disputes around parentage. Given that these common law principles were crafted in an era when assisted reproduction and the fracturing of biological, genetic, and intentional motherhood was inconceivable, the legislative …


Gender Differences And Factors Affecting Brand Loyalty, Olivia Rajska Jan 2013

Gender Differences And Factors Affecting Brand Loyalty, Olivia Rajska

Honors Capstones

Little is known about apparel brand loyalty regarding satisfaction of clothing purchase. This study was developed to examine whether brand satisfaction and brand reputation influence brand loyalty. Another objective of this study was to compare clothing satisfaction of a loyal brand between males and females. Following a focus group interview, a survey questionnaire was developed. A total of 106 participants consisting of 46 males and 58 females completed the survey questionnaire. Results of Pearson Correlations showed brand loyalty was positively related to brand satisfaction (r = .37, p <.001) and brand reputation (r = .33, p <.001). A strong positive correlation (r = .51, p <.001) was found between brand satisfaction and brand reputation. Independent sample t-tests indicated significant differences between males and females in trend (Mf = 4.46, Mm=3.98), promotion(MF = 3.60, Mm=2.90), return policies (Mf = 3.98, Mm=3.20)., display (Mf = 4.08, Mm=3.02), fitting rooms(MF = 3.64, Mm=2.68), store environment (Mf = 4.21, Mm=3.54), sales associates (Mp = 4.02, Mm=3.39) and overall experience (Mf = 3.15, Mm=2.63) on a 5-point scale. This study had implications for apparel retailers and marketers and they could develop brand loyalty for male and female customers. In order to develop customer loyalty, apparel brand should focus on trendy apparel, sales and promotions, return policies, displays, fitting rooms, merchandise layout, sales associates and an overall good store experience.


Characterization And Distribution Of Novel Non-Ltr Retroelements Driving High Telomere Rflp Diversity In Clonal Lines Of Magnaporthe Oryzae, John H. Starnes Jan 2013

Characterization And Distribution Of Novel Non-Ltr Retroelements Driving High Telomere Rflp Diversity In Clonal Lines Of Magnaporthe Oryzae, John H. Starnes

Theses and Dissertations--Plant Pathology

The filamentous ascomycete fungus Magnaporthe oryzae is a pathogen of over 50 genera of grasses. Two important diseases it can cause are gray leaf spot in Lolium perenne (perennial ryegrass) and blast in Oryza sativa (rice). The telomeres of M. oryzae isolates causing gray leaf spot are highly variable, and can spontaneously change during fungal culture. In this dissertation, it is shown that a rice-infecting isolate is much more stable at the telomeres than an isolate from gray leaf spot. To determine the molecular basis of telomere instability several gray leaf spot isolates telomeres were cloned, which revealed two non-LTR …


2013 Commencement Program, Morehead State University. Registrar's Office. Jan 2013

2013 Commencement Program, Morehead State University. Registrar's Office.

Morehead State Commencement Programs

2013 commencement programs of Morehead State University.


Phenytoin Reduces 5-Ala Mediated Fluorescence In Glioblastoma Cells , Christopher Steele, Johnathan Lawrence, Richard A. Rovin, Robert J. Winn Jan 2013

Phenytoin Reduces 5-Ala Mediated Fluorescence In Glioblastoma Cells , Christopher Steele, Johnathan Lawrence, Richard A. Rovin, Robert J. Winn

Journal Articles

Glioblastoma multiforme (GBM) is a devastating form of cancer, and essentially all GBM tumors recur causing fatality. A new surgical technique, fluorescence-guided resection of GBM using 5-aminolevulinic acid (5-ala), improves the extent of resection and positively impacts the length and quality of patient survival. The fluorescence achieved in neoplastic tissue depends directly on the accumulation of porphyrins derived from the metabolism of the 5-ala prodrug within the cancer cell. However, 5-ala induced fluorescence has been reported to be inconsistent. In an effort to determine the cause of the inconsistent fluorescence, the authors investigated the effect of medications commonly prescribed to …


"Going To Pieces" Over Lgbt Health Disparities: How An Amended Affordable Care Act Could Cure The Discrimination That Ails The Lgbt Community, Travis F. Chance Jan 2013

"Going To Pieces" Over Lgbt Health Disparities: How An Amended Affordable Care Act Could Cure The Discrimination That Ails The Lgbt Community, Travis F. Chance

Journal of Health Care Law and Policy

No abstract provided.


Astrue V. Capato: Forcing A Shoe That Doesn't Fit, Courtney Hannon Jan 2013

Astrue V. Capato: Forcing A Shoe That Doesn't Fit, Courtney Hannon

Journal of Health Care Law and Policy

No abstract provided.


Kenyon College Alumni Bulletin - Winter 2013 Jan 2013

Kenyon College Alumni Bulletin - Winter 2013

Kenyon College Alumni Bulletin

No abstract provided.


College Of Education Annual Report And Findings, Fiscal Year 2012, College Of Education, Illinois State University Jan 2013

College Of Education Annual Report And Findings, Fiscal Year 2012, College Of Education, Illinois State University

Annual Report and Findings

No abstract provided.


Laboratory Schools Annual Report, 2012-2013, Laboratory Schools, Illinois State University Jan 2013

Laboratory Schools Annual Report, 2012-2013, Laboratory Schools, Illinois State University

Annual Reports – Laboratory Schools

Illinois State University Laboratory Schools annual report


Cam Kk Mediates Mdm2 Activation In Lncap Cells, John M. Schmitt, Philip Graber Jan 2013

Cam Kk Mediates Mdm2 Activation In Lncap Cells, John M. Schmitt, Philip Graber

Faculty Publications - Department of Biological & Molecular Science

Abstract Agonists and hormones that cause an influx of calcium in LNCaP prostate cancer cells activate the calcium/calmodulin-dependent protein kinase (CaM Kinase) pathway and AKT phosphorylation. CaM KK and AKT are essential for promoting LNCaP cell survival. AKT phosphorylation of MDM2 protein may negatively regulate the tumor suppressor protein, p53. CaM KK and AKT have yet to be demonstrated as upstream regulators of MDM2 and p53 in LNCaP cells. Our goals were to examine the ability of carbachol and testosterone to stimulate MDM2 phosphorylation, its association with p53, and whether CaM KK is upstream of MDM2. Stimulation of LNCaP cells …


Akap7 Regulates Cam Kinase Activation In Mcf-7 Cells, John M. Schmitt, Hannah M. Mcfarland, Kimberly Dodge-Kafka Jan 2013

Akap7 Regulates Cam Kinase Activation In Mcf-7 Cells, John M. Schmitt, Hannah M. Mcfarland, Kimberly Dodge-Kafka

Faculty Publications - Department of Biological & Molecular Science

Abstract Estrogen (E2) activates calcium/calmodulin-dependent protein kinases (CaM Kinases) in MCF-7 breast cancer cells. In particular E2 activates a CaM KK, CaM KI, and ERK pathway to promote proliferation. CaM Kinase activation of ERK may be blocked by PKA in certain cell types through direct phosphorylation and inhibition of CaM KK. The ability of PKA to phosphorylate its cellular targets may be dictated by protein kinase A anchoring proteins (AKAPs). Hormones that elevate cAMP and activate PKA may utilize AKAPs to regulate signal transduction. Our goal was to evaluate the role of AKAPs in regulating E2 activation of the CaM …


Estrogen Regulation Of Jun And Fos In Mcf-7 Cells, John M. Schmitt, Renee Geck, Jessica N. Magill Jan 2013

Estrogen Regulation Of Jun And Fos In Mcf-7 Cells, John M. Schmitt, Renee Geck, Jessica N. Magill

Faculty Publications - Department of Biological & Molecular Science

Abstract C-Fos and c-Jun are transcription factors that form the dimer Activator Protein 1 (AP-1) and bind DNA to initiate transcription. C-Fos, c-Jun are targets of the Extracellular Signal-Regulated Kinase (ERK) in multiple cell types, including MCF-7 breast cancer cells. The hormone estrogen (E2) can increase intracellular calcium levels which activates calcium/calmodulin-dependent kinase (CaM Kinase) proteins, which control ERK and gene transcription. Our goal was to evaluate the ability of E2 to activate c-Fos and c-Jun and induce their dimerization, via CaM KK and ERK, in MCF-7 cells. Interestingly, E2 stimulation of MCF-7 cells triggered phosphorylation of c-Jun and c-Fos …