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3d Mapping Of The Spry2 Domain Of Ryanodine Receptor 1 By Single-Particle Cryo-Em, Alex Peralvaerz-Marin, Hanshen Tae, Phillip G. Board, Marco G. Casarotto, Angela F. Dulhunty, Montserrat Samsó

Physiology and Biophysics Publications and Presentations

The type 1 skeletal muscle ryanodine receptor (RyR1) is principally responsible for Ca2+release from the sarcoplasmic reticulum and for the subsequent muscle contraction. The RyR1 contains three SPRY domains. SPRY domains are generally known to mediate protein-protein interactions, however the location of the three SPRY domains in the 3D structure of the RyR1 is not known. Combining immunolabeling and single-particle cryo-electron microscopy we have mapped the SPRY2 domain (S1085-V1208) in the 3D structure of RyR1 using three different antibodies against the SPRY2 domain. Two obstacles for the image processing procedure; limited amount of data and signal dilution introduced by the …

State-Dependent Camp Binding To Functioning Hcn Channels Studied By Patch-Clamp Fluorometry, Shengjun Wu, Zhanna V. Vysotskaya, Xinping Xu, Changan Xie, Qinglian Liu, Lei Zhou

Physiology and Biophysics Publications and Presentations

Abstract

One major goal of ion channel research is to delineate the molecular events from the detection of the stimuli to the movement of channel gates. For ligand-gated channels, it is challenging to separate ligand binding from channel gating. Here we studied the cyclic adenosine monophosphate (cAMP)-dependent gating in hyperpolarization-activated cAMP-regulated (HCN) channel by simultaneously recording channel opening and ligand binding, using the patch-clamp fluorometry technique with a unique fluorescent cAMP analog that fluoresces strongly in the hydrophobic binding pocket and exerts regulatory effects on HCN channels similar to those imposed by cAMP. Corresponding to voltage-dependent channel activation, we observed …

Pedagogies Of Race: The Politics Of Whiteness In An African American Studies Course, Regina V. Jones

Ethnic Studies Review

This paper evaluates students' arguments for a color-blind society to avoid discussions related to the continued existence of racism in USA culture. Relatedly, this writer finds that as an black woman her status as facilitator in the classroom is directly challenged, on occasion, and that race and gender play a primary role in students' perception of classroom material and how she is perceived. Classroom discussions related to historical texts reveal that structures of domination have slanted perception of black and white people in U.S. culture. Finally, a key to open dialogue about race and racism, primarily for white students, is …

"We Are Joined Together Temporarily" The Tragic Mulatto, Fusion Monster In Lee Frost's The Thing With Two Heads, Justin Ponder

Ethnic Studies Review

In Lee Frost's 1972 film The Thing with Two Heads, a white bigot unknowingly has his head surgically grafted onto the body of a black man. From that moment on, these two personalities compete for control of their shared body with ridiculous results. Somewhere between horror and comedy, this Blaxploitation film occupies a strange place in interracial discourse. Throughout American literature, the subgenre of tragic mulatto fiction has critiqued segregation by focusing on the melodramatic lives of those divided by the color line. Most tragic mulatto scholarship has analyzed overtly political novels written by African American writers from the Reconstruction …

Ethnic Studies Review

Ethnic Studies Review

No abstract provided.

Characterization Of The Expression Of Bdnf And Cgrp And Their Regulatory Pathways In Dorsal Root Ganglion During Cystitis., Sharon Yu

Theses and Dissertations

Interstitial cystitis is a chronic debilitating disease that causes pain and increased frequency of micturition, amongst other symptoms, without any identifiable cause. This disease affects a large number of the population, yet the etiology is still unknown. The present study aimed to characterize BDNF and CGRP—two neuropeptides that have both been proven to play an important role in the transmission of pain as well as in hypersensitivity. The signaling pathways regulating the expression of the two neuropeptides were also examined. Results revealed that BDNF protein expression levels increased in both L1 and L6 DRG following 48 hours post CYP-induced cystitis. …

Systematic Study Of Gene Functions For Morphological Chain Formation In Streptococcus Sanguinis, Karra Evans

Theses and Dissertations

Streptococcus sanguinis is a gram-positive facultative anaerobe that is indigenous to the oral cavity and a primary colonizer of the oral cavity. It serves as a tether for the attachment of several oral bacteria that colonize the tooth surface, form dental plaque, and cause periodontal disease. Previous experiments with streptococcal strains have suggested that cellular chain morphology of streptococci may influence the competitiveness, susceptibility to phagocytosis, acidurance, and aggregation of the bacterium. The purpose of this study was to systematically determine gene functions that contribute to cellular chain length morphology in the SK36 strain of S. sanguinis. Gene functions for …

Visual Arts And Literacy: The Potential Of Interdisciplinary Coalitions For Social Justice, Melanie L. Buffington, William Muth

Journal of Social Theory in Art Education

In this article, we explore the possibilities of creating a coalition of the visual arts with literacy to work toward meaningful integrated learning experiences with a social justice agenda. We discuss the benefits of integrated curriculum and its potential to support learning at many levels. Following that, we introduce the Hope House mural project as an example of an integrated visual arts and literacy program. Through this project, children and their incarcerated fathers grapple with significant issues in their lives and to build a bond while doing so. We argue that this coalition results in learning that is inseparably tied …

Phosphodiesterase-5 Inhibition: A Novel Strategy To Improve Stem Cell Therapy In The Heart, Nicholas Hoke

Theses and Dissertations

Several studies have shown cellular replacement therapy as a treatment strategy of myocardial infarction but results have been limited. Therefore, enhancing the therapeutic potential of stem cells injected into ischemic microenvironments by novel preconditioning (PC) techniques is critical for improving cellular therapy. Recent studies have shown that inhibition of phosphodiesterase-5 (PDE-5) is a powerful strategy to precondition the heart and cardiomyocytes against ischemia/reperfusion injury. We therefore tested the hypothesis that inhibition of PDE-5 with sildenafil (Viagra®) or selective knockdown with a silencing vector in adipose derived stem cells (ASCs) would improve their survival after ischemia/reoxygenation in vitro and enhance cardiac …

Rate-Limiting Step Of Cone Phototransduction Recovery And Oguchi Disease Mechanisms, Frank Chen

Theses and Dissertations

ABSTRACT RATE-LIMITING STEP OF CONE PHOTOTRANSDUCTION RECOVERY AND OGUCHI DISEASE MECHANISMS By Frank Sungping Chen Advisor: Ching-Kang Jason Chen, Ph.D. Retinal photoreceptors provide the first gateway in which light information from the environment is transformed into neuronal signals. The cone and rod photoreceptors are responsible for day and night vision, respectively. Understanding rod and cone phototransduction is to figure out how these cells differ in their temporal and spatial sensitivities to allow perception of a broad dynamic range of stimuli. Phototransduction is mediated through a Gprotein signaling cascade. Light absorption by visual pigment triggers the isomerization of 11- cis-retinal covalently …

The Characterization Of Pg0228 In Porphyromonas Gingivalis W83, Courtney Schlenker

Theses and Dissertations

Periodontitis affects 10 to 15 percent of most adult populations and can contribute to numerous systemic diseases. Porphyromonas gingivalis, a gram-negative anaerobic bacterium, is a recognized prime causative agent in periodontitis. Studies have shown a number of small non-coding RNAs (sRNAs) have been related to bacterial virulence. Many of these sRNAs require the facilitation of the bacterial Sm-like protein, Hfq, for optimum function. Hfq is a RNA chaperone involved in RNA stability, sRNA function, and polyadenylation. Mutants lacking in Hfq often show pleiotropic phenotypes, although the extent and severity of hfq null phenotypes is often species-specific. Hfq has been encoded …

Acquired Cytogenetic Changes In Adult Twins Discordant For A History Of Childhood Sexual Abuse, Jenni Brumelle

Theses and Dissertations

The primary study aim was to evaluate the latent biological effect of childhood sexual abuse (CSA) on adults by quantifying acquired cytogenetic changes and cortisol levels in identical twins who were discordant (N=22) or concordant (N=2) for a history of CSA. Although the difference scores for cortisol values between discordant identical co-twins were not significantly different from zero, a trend was observed for the twins exposed to intercourse, the most severe form of CSA, to have a blunted cortisol awakening response. Acquired cytogenetic changes were assessed by scoring telomere lengths and somatic cell abnormality frequencies via a cytokinesis-block micronucleus (MN) …

Hiv Protease Inhibitors Trigger Lipid Metabolism Dysregulation Through Endoplasmic Reticulum Stress And Autophagy, Beth Shoshana Zha

Theses and Dissertations

HIV protease inhibitors (PI) are core components of Highly Active Antiretroviral Therapy (HAART). HIV PIs are extremely effective at suppressing viral load, but have been linked to lipodystrophy and dyslipidemia, which are major risk factors for cardiovascular disease. Recent studies indicate that activation of endoplasmic reticulum (ER) stress is an important cellular mechanism underlying HIV PI-induced dysregulation of lipid metabolism. However, the exact role of ER stress in HIV PI-associated lipodystrophy and dyslipidemia remains to be identified. Hepatocytes and adipocytes are important players in regulating lipid metabolism and the inflammatory state. Dysfunction of these two cell types is closely linked …

Synthesis, Screening And Cocrystallization Of Adenosine Based Inhibitors With Methyltransferases, Ermc' And Ksga, Matthew Baker

Theses and Dissertations

Antibiotic resistance threatens to throw mankind back into an era when infectious disease was the predominant cause of death. In an effort to mitigate this danger, we targeted ErmC’ and KsgA. Both methylate N6-adenosine of ribosomal RNA, though each serve different roles in their bacterial host. ErmC’ dimethylates A2058 on 23S rRNA, conferring resistance to MLSB antibiotics (macrolides, lincosamides, streptogramin B). KsgA aids in ribosome assembly, binding inactive 30S until dimethylating A1518/A1519 of 16S rRNA. Like most methyltransferases, ErmC’ and KsgA use cofactor S-adenosylmethionine (SAM) as their methyl source, which binds adjacent to their specific adenosine substrate. ErmC’ inhibitors could …

Biobehavioral Relationships And Health Related Quality Of Life In Persons With End Stage Renal Disease On Hemodialysis, Avis Allen

Theses and Dissertations

The study of immune status and biobehavioral measures is limited in professional nursing. The purpose of the pre-pilot study was to describe levels of cytokines prior to, during, and after dialysis, examine changes in cytokine levels from immediate pre-dialysis to immediate post-dialysis, and to compare cytokine patterns prior to and after dialysis. A within subject descriptive study was conducted as part of a larger pilot study to describe levels of cytokines prior to, during, and after dialysis, examine changes in cytokine levels from immediate pre-dialysis to immediate post-dialysis, and to compare cytokine patterns prior to and after dialysis. Serum cytokine …

Morphometric And Genetic Variation Among Populations Of The Southern Short-Tailed Shrew, Blarina Carolinensis, Located Along The Coastal Plain Of Virginia, Devon Kersten

Theses and Dissertations

The distribution of short-tailed shrews, Blarina carolinensis and B. brevicauda, demonstrates contiguous allopatry in peninsular situations in the Coastal Plain of Virginia, and in other areas. The distribution of these two species is unusual in that they do not exhibit syntopy except within a narrow corridor along the borders of their ranges. Interestingly, along the Coastal Plain of Virginia, B. carolinensis is generally found only at the distal ends of the peninsular areas, existing as local populations that appear to be isolated from each other and from the primary population that exists in south-central Virginia. It is thought that the …

Virginia Dental Journal (Vol. 88, No. 2, 2011)

Virginia Dental Journal

No abstract provided.

Virginia Dental Journal (Vol. 88, No. 4, 2011)

Virginia Dental Journal

No abstract provided.

African American Males Diagnosed With Schizophrenia: A Phenomenological Study, Lorraine Anderson

Theses and Dissertations

Abstract Little is known about how African American men with schizophrenia experience their every day existence. Through applying interpretive phenomenology and using a methodological structure designed by van Manen (1990, 1997), this research aimed to enrich the understanding of living with schizophrenia for these African American males. In this study, five men ranging in age from 21 to 57 described their lives within the context of existing with the diagnosis of schizophrenia. The lived experiences across the interviews revealed four overarching themes: They know that they are mentally ill; they make a special effort to test reality; they assert their …

Novel Role Of Mecp2 In Developing Oligodendrocytes And Myelination, Daniel Moore

Theses and Dissertations

Methyl-CpG-binding protein 2 (MeCP2 is) is an epigenetic regulator that binds to methylated DNA. Initially identified as transcriptional repressor, MeCP2 also binds to different proteins functioning as gene activator. Importantly, MecCP2 gene mutations and changes in MeCP2 levels are associated to several forms of mental retardation and autism-related disorders; including Rett, a neurodevelopmental disorder affecting primarily girls. While brain MeCP2 was considered to be exclusively neuronal, this regulator is also present in glia. We found that oligodendrocytes, the myelinating cells of the central nervous system (CNS), express particularly high MeCP2 levels at a developmental stage that precedes their final maturation. …

Head-Start Juvenile And Adult Resident Eastern Box Turtles (Terrapene Carolina Carolina): Winter Ecology Including Microhabitat Selection, Temperature Tolerance And Philopatry, Amberly Moon

Theses and Dissertations

The Eastern box turtle (Terrapene carolina carolina) is one of the most common reptiles in North America, but is soon to be threatened due to increased urbanization, disease, and the pet and food trades. In order to assist resource managers in choosing suitable sites for relocation studies, more information on the winter ecology of this species is necessary. We examined the temperature tolerance, microhabitat and degree of philopatry to hibernacula for juvenile and adult E. box turtles for two consecutive winters in Charles City Co, VA. The turtles were tracked via radio telemetry to record point locations during the active …

Determining Impediments To Gene Flow In A Natural Population Of Cornus Florida L. Cornaceae, Using Integrative Landscape Genetic Techniques, Crystal Meadows

Theses and Dissertations

This study examined the impact intervening environment has on gene flow in the insect pollinated understory tree, Cornus florida L., by combining GIS and landscape genetic techniques (Least Cost Path Analysis, Circuit Theory, and Conditional Genetic Distance). Traditional population genetic analysis indicated pair-wise relatedness was significantly correlated to distance (Pearson; r = -0.312, P < 0.001) suggesting a spatial component to offspring relatedness. Dispersal throughout the study site was non-random, exhibiting a high degree of pollen pool structure due to restricted gene flow (Two-Generation Analysis; Φft = 0.161, P = 0.001). Forest structure was quantified in GIS layers representing coniferous canopies, mixed hardwood canopies, C. florida canopies, open understory (roads), and open understory/canopy due to tree removal. Of these layers, landscape isolation for the roads layer provided the best-fit model for describing genetic differentiation among sampled pollen pools (Mantel; r = 0.542, P = 0.001). These data also suggest that improved biological inferences can be gained by examining a range of landscape isolation models.

Biochemical Evaluation Of Lignin-Like Molecules, Jay Thakkar

Theses and Dissertations

Current anticoagulants carry a serious risk of bleeding complications. In addition, narrow therapeutic index, drug interactions, immunological reactions, toxicity and high cost to benefit ratio limits the effective use of these drugs in patients with thrombotic conditions.Heparin is the most widely used anticoagulant. We hypothesized that one of the major drawback of heparins, its non-specific interaction with the plasma proteins arises as a result of negative charges. To reduce these non-specific interactions, our laboratory designed sulfated low molecular weight lignin (LMWL) like biomacromolecules, which were found to be direct inhibitors of thrombin and factor Xa, acting through a unique exosite-2 …

The Synthesis, Characterization, And Upconverting Properties Of Erbium Doped; Ytterbium, Erbium Co-Doped Yttrium Oxysulfide Phosphors Under 808, 980, And 1560 Nm Excitation, James Wilkins

Theses and Dissertations

Bulk yttrium oxysulfide phosphors were prepared using the polysulfide flux method. The morphology and structure was characterized using transmission electron microscopy and x-ray powdered diffraction. Visible emissions occurring near 530 and 550 nm and 660 - 670 nm consistent with the 2H11/2, 4S3/2 → 4I15/2 and 4F9/2 → 4I15/2 transitions, respectively, were observed under 808, 980, and 1560 nm excitation. The upconverting mechanisms excited at 808, 980, and 1560 nm have been investigated in detail. The power dependent behavior of the upconverted emission intensities for singly doped erbium phosphors excited at 808 and 980 nm indicated a two-photon excitation process. …

“Clicked” Bivalent Multifunctional Ligands In Alzheimer’S Disease., Ronak Gandhi

Theses and Dissertations

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by beta-amyloid (Aβ) aggregation/oligomerization, biometal dyshomeostasis, oxidative stress, and neuroinflammation. The multifactorial nature of AD may indicate the therapeutic potential of multifunctional ligands that tackle various risk factors simultaneously as effective AD-modifying agents. This notion is further supported by the fact that while numerous AD-modifying agents targeting one single risk factor have been developed and a number of them entered clinical trials, none of them has been successfully approved by the FDA. Furthermore, neuronal cell membrane/lipid rafts (CM/LR) have been demonstrated to associate with all the indicated risk factors, indicating that this …

A Study On The Biochemical And Cellular Effects Of Enviormental Tobacco Smoke On Adult And Developing Rat Brain Biochemistry, Brian Fuller

Theses and Dissertations

Exposure to environmental tobacco smoke (ETS) has been recognized as a significant health risk for adults and children. In adults, ETS exposure has been linked to increased incidences of cardiovascular disease and dementia. In children, exposure has been linked to behavioral and cognitive deficits. Studies on the effects of ETS in the brain have been largely epidemiological, and have lacked a defined explanation of the molecular/biochemical effects of ETS. The present dissertation aims to test whether ETS exposure leads to altered biochemistry in the adult and developing mammalian brain. A rat ETS exposure model was employed to investigate changes at …

Renal Epithelial Sodium Channel (Enac) Regulation Of Pregnancy Mediated Hemodynamic Adaptations: Mechanistic Insights, Crystal West

Theses and Dissertations

Pregnancy-mediated sodium (Na) retention is required to provide an increase in plasma volume for the growing fetus. The mechanisms responsible for this Na retention are not clear. In the first study, we generated a renal tubule protein profile indicating α ENaC as the only sodium transport protein upregulated in mid and late pregnancy. To determine the in vivo activity of ENaC we conducted in vivo studies in late pregnant rats (day 18-20) and virgin rats to measure the natriuretic response to ENaC blockade (with benzamil). The in vivo activity of ENaC (UNaV post benzamil - UNaV post vehicle) was markedly …

Approaches For Enhancing Therapeutic Efficacy Of A Novel Il-10 Gene Family Member: Mda-7/Il-24, Belal Azab

Theses and Dissertations

Melanoma differentiation associated gene-7 (mda-7) was discovered in the Fisher laboratory by subtraction hybridization of temporally spaced subtracted cDNA libraries prepared from terminally differentiated human melanoma cells treated with human fibroblast interferon (IFN-β) and the protein kinase C activator mezerein (MEZ), an approach called ‘differentiation induction subtraction hybridization’ (DISH). mda-7 is located in human chromosome 1q32–33 and based on sequence homology, chromosomal localization, and its functional properties, the mda-7 gene is now classified as a member of the IL-10 family of cytokines and named IL-24. The mda-7/IL-24 cDNA encodes a protein of 206-amino acids with a predicted size of ~24-kDa, …

Cyclic-Di-Gmp Signaling In The Borrelia Spirochetes, John Freedman

Theses and Dissertations

Lyme disease is the most common tick-borne disease in North America, with approximately 35,000 cases reported to the Centers for Disease Control in 2008. The genome of its causative agent, Borrelia burgdorferi, encodes for a set of genes involved in the metabolism and regulatory activities of the second messenger nucleotide, cyclic-di-GMP (c-di-GMP). Rrp1 is a response regulatory-diguanylate cyclase, and its regulatory capability is likely mediated via production of c-di-GMP, as it lacks a DNA-binding domain. One known class of c-di-GMP effector/binding proteins are those that harbor a PIlZ domain. The genome of B. burgdorferi strain 5A4 encodes for one chromosomally-carried …

Functional Consequences Of Cytosine Methylation In Mitochondrial Dna Catalyzed By Dna Methyltransferase 1, Lisa Shock

Theses and Dissertations

Cytosine methylation of mitochondrial DNA (mtDNA) was first described several decades ago, but neither the mechanism generating this modification nor its functional significance was known. Because mitochondrial dysfunction is a hallmark characteristic of numerous human diseases, including neurological and cardiovascular disease, aging and cancer, this dissertation addressed whether epigenetic modification of mtDNA regulates mitochondrial function. We show that mtDNA contains not only 5-methylcytosine (5mC), but also 5-hydroxymethylcytosine (5hmC), suggesting that previous reports likely underestimated the degree of epigenetic modification within the mitochondrial genome. We questioned how these modifications were generated by looking for mitochondrial isoforms of the nuclear-encoded DNA methyltransferases. …