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Medical Sciences

2014

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Articles 31 - 60 of 1429

Full-Text Articles in Medicine and Health Sciences

Sensory Abnormalities In Focal Hand Dystonia And Non-Invasive Brain Stimulation, Angelo Quartarone, Vincenzo Rizzo, Carmen Terranova, Demetrio Milardi, Daniele Bruschetta, Maria Felice Ghilardi, Paolo Girlanda Dec 2014

Sensory Abnormalities In Focal Hand Dystonia And Non-Invasive Brain Stimulation, Angelo Quartarone, Vincenzo Rizzo, Carmen Terranova, Demetrio Milardi, Daniele Bruschetta, Maria Felice Ghilardi, Paolo Girlanda

Publications and Research

It has been proposed that synchronous and convergent afferent input arising from repetitive motor tasks may play an important role in driving the maladaptive cortical plasticity seen in focal hand dystonia (FHD).This hypothesis receives support from several sources. First, it has been reported that in subjects with FHD, paired associative stimulation produces an abnormal increase in corticospinal excitability, which was not confined to stimulated muscles. These findings provide support for the role of excessive plasticity in FHD. Second, the genetic contribution to the dystonias is increasingly recognized indicating that repetitive, stereotyped afferent inputs may lead to late-onset dystonia, such as …


Analysis Of Drug Interactions With Lipoproteins By High Performance Affinity Chromatography, Matthew R. Sobansky Dec 2014

Analysis Of Drug Interactions With Lipoproteins By High Performance Affinity Chromatography, Matthew R. Sobansky

Department of Chemistry: Dissertations, Theses, and Student Research

High density lipoprotein (HDL), low density lipoprotein (LDL), and very low density lipoprotein (VLDL) are lipoproteins previously shown to bind many basic and neutral hydrophobic drugs in serum. These interactions impact the distribution, delivery, metabolism, and excretion of drugs and are important in determining drug activity, pharmacokinetics, and toxicity in the human body. Information about drug-lipoprotein interactions and the strength of these interactions can be useful in determining the distribution of drugs following administration.

The research presented in this dissertation uses high performance affinity chromatography (HPAC) and packed columns to study binding of the drug propranolol to immobilized lipoproteins such …


Regulation Of Crfr1 And 5-Ht2ar By Pdz Domain-Containing Proteins Sap97 And Psd-95, Henry A. Dunn Dec 2014

Regulation Of Crfr1 And 5-Ht2ar By Pdz Domain-Containing Proteins Sap97 And Psd-95, Henry A. Dunn

Electronic Thesis and Dissertation Repository

Previous studies identified a crosstalk mechanism whereby CRFR1 sensitized 5-HT2AR-mediated signaling via interactions with PDZ domain-containing proteins: a mechanism that may underlie stress-induced anxiety and depression. This prompted an investigation into uncovering which PDZ domain-containing proteins could regulate the crosstalk between these two receptors, and how they could be regulated individually. In the current studies, a subset of PDZ domain-containing proteins were identified that may interact with CRFR1 and 5-HT2AR. The focus narrowed to two candidates previously implicated in psychiatric disease: SAP97 and PSD-95. We confirmed SAP97 and PSD-95 as interacting partners of CRFR1 in adult …


A Critical Evaluation Of The Trigger Point Phenomenon, John L. Quintner, Geoffrey M. Bove, Milton L. Cohen Dec 2014

A Critical Evaluation Of The Trigger Point Phenomenon, John L. Quintner, Geoffrey M. Bove, Milton L. Cohen

Biomedical Sciences Faculty Publications

The theory of myofascial pain syndrome (MPS) caused by trigger points (TrPs) seeks to explain the phenomena of muscle pain and tenderness in the absence of evidence for local nociception. Although it lacks external validity, many practitioners have uncritically accepted the diagnosis of MPS and its system of treatment. Furthermore, rheumatologists have implicated TrPs in the pathogenesis of chronic widespread pain (fibromyalgia syndrome). We have critically examined the evidence for the existence of myofascial TrPs as putative pathological entities and for the “vicious cycles that are said to maintain them. We find that both are inventions that have no scientific …


Longitudinal Quantitative Analysis Of Gait And Balance In Friedreich's Ataxia, Jeannie B. Stephenson Dec 2014

Longitudinal Quantitative Analysis Of Gait And Balance In Friedreich's Ataxia, Jeannie B. Stephenson

USF Tampa Graduate Theses and Dissertations

Friedreich's Ataxia (FA) is an autosomal-recessive, neurodegenerative disease characterized by progressive lower extremity muscle weakness and sensory loss, balance deficits, limb and gait ataxia, and dysarthria. FA is considered a sensory ataxia because the dorsal root ganglia and spinal cord dorsal columns are involved early in the disease, whereas the cerebellum is affected later. Balance deficits and gait ataxia are often evaluated clinically and in research using clinical rating scales. Recently, quantitative tools such as the Biodex Balance System SD and the GAITRite Walkway System have become available to objectively assess balance and gait, respectively. However, there are limited studies …


Analysis Of Clock-Regulated Genes In Neurospora Reveals Widespread Posttranscriptional Control Of Metabolic Potential, Jennifer M. M. Hurley, Arko Dasgupta, Jillian M. Emerson, Xiaoying Zhou, Carol S. Ringelberg, Nicole Knabe Dec 2014

Analysis Of Clock-Regulated Genes In Neurospora Reveals Widespread Posttranscriptional Control Of Metabolic Potential, Jennifer M. M. Hurley, Arko Dasgupta, Jillian M. Emerson, Xiaoying Zhou, Carol S. Ringelberg, Nicole Knabe

Dartmouth Scholarship

Neurospora crassa has been for decades a principal model for filamentous fungal genetics and physiology as well as for understanding the mechanism of circadian clocks. Eukaryotic fungal and animal clocks comprise transcription-translation-based feedback loops that control rhythmic transcription of a substantial fraction of these transcriptomes, yielding the changes in protein abundance that mediate circadian regulation of physiology and metabolism: Understanding circadian control of gene expression is key to understanding eukaryotic, including fungal, physiology. Indeed, the isolation of clock-controlled genes (ccgs) was pioneered in Neurospora where circadian output begins with binding of the core circadian transcription factor WCC to a subset …


Syndecan 4 Is Required For Endothelial Alignment In Flow And Atheroprotective Signaling, Nicolas Baeyens, Mary Jo Mulligan-Kehoe, Federico Corti, David D. Simon, Tyler D. Ross, John M. Rhodes, Thomas Z. Wang Dec 2014

Syndecan 4 Is Required For Endothelial Alignment In Flow And Atheroprotective Signaling, Nicolas Baeyens, Mary Jo Mulligan-Kehoe, Federico Corti, David D. Simon, Tyler D. Ross, John M. Rhodes, Thomas Z. Wang

Dartmouth Scholarship

Atherosclerotic plaque localization correlates with regions of disturbed flow in which endothelial cells (ECs) align poorly, whereas sustained laminar flow correlates with cell alignment in the direction of flow and resistance to atherosclerosis. We now report that in hypercholesterolemic mice, deletion of syndecan 4 (S4−/−) drastically increased atherosclerotic plaque burden with the appearance of plaque in normally resistant locations. Strikingly, ECs from the thoracic aortas of S4−/− mice were poorly aligned in the direction of the flow. Depletion of S4 in human umbilical vein endothelial cells (HUVECs) using shRNA also inhibited flow-induced alignment in vitro, which was rescued by re-expression …


E2f4 Regulatory Program Predicts Patient Survival Prognosis In Breast Cancer, Sari S. Khaleel, Erik H. Andrews, Matthew Ung, James Direnzo, Chao Chung Dec 2014

E2f4 Regulatory Program Predicts Patient Survival Prognosis In Breast Cancer, Sari S. Khaleel, Erik H. Andrews, Matthew Ung, James Direnzo, Chao Chung

Dartmouth Scholarship

Genetic and molecular signatures have been incorporated into cancer prognosis prediction and treatment decisions with good success over the past decade. Clinically, these signatures are usually used in early-stage cancers to evaluate whether they require adjuvant therapy following surgical resection. A molecular signature that is prognostic across more clinical contexts would be a useful addition to current signatures. We defined a signature for the ubiquitous tissue factor, E2F4, based on its shared target genes in multiple tissues. These target genes were identified by chromatin immunoprecipitation sequencing (ChIP-seq) experiments using a probabilistic method. We then computationally calculated the regulatory activity score …


Over-Expression Of Copper/Zinc Superoxide Dismutase In The Median Preoptic Nucleus Attenuates Chronic Angiotensin Ii-Induced Hypertension In The Rat., John P. Collister, Mitch Bellrichard, Donna Drebes, David Nahey, Jun Tian, Matthew C. Zimmerman Dec 2014

Over-Expression Of Copper/Zinc Superoxide Dismutase In The Median Preoptic Nucleus Attenuates Chronic Angiotensin Ii-Induced Hypertension In The Rat., John P. Collister, Mitch Bellrichard, Donna Drebes, David Nahey, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

The brain senses circulating levels of angiotensin II (AngII) via circumventricular organs, such as the subfornical organ (SFO), and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO) have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s) involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O2·-) scavenging enzyme, in …


Anatomical, Functional And Metabolic Imaging Of Radiation-Induced Lung Injury Using Hyperpolarized Mri., Giles Santyr, Matthew Fox, Kundan Thind, Elaine Hegarty, Alexei Ouriadov, Michael Jensen, Timothy J Scholl, Jacob Van Dyk, Eugene Wong Dec 2014

Anatomical, Functional And Metabolic Imaging Of Radiation-Induced Lung Injury Using Hyperpolarized Mri., Giles Santyr, Matthew Fox, Kundan Thind, Elaine Hegarty, Alexei Ouriadov, Michael Jensen, Timothy J Scholl, Jacob Van Dyk, Eugene Wong

Medical Biophysics Publications

MRI of hyperpolarized (129)Xe gas and (13)C-enriched substrates (e.g. pyruvate) presents an unprecedented opportunity to map anatomical, functional and metabolic changes associated with lung injury. In particular, inhaled hyperpolarized (129)Xe gas is exquisitely sensitive to changes in alveolar microanatomy and function accompanying lung inflammation through decreases in the apparent diffusion coefficient (ADC) of alveolar gas and increases in the transfer time (T(tr)) of xenon exchange from the gas and into the dissolved phase in the lung. Furthermore, metabolic changes associated with hypoxia arising from lung injury may be reflected by increases in lactate-to-pyruvate signal ratio obtained by magnetic resonance spectroscopic …


Synthesis And Characterization Of Methacrylated Hyaluronan-Based Hydrogels For Tissue Engineering, Keegan Bradley Compton Dec 2014

Synthesis And Characterization Of Methacrylated Hyaluronan-Based Hydrogels For Tissue Engineering, Keegan Bradley Compton

Theses and Dissertations (ETD)

Polymers have revolutionized the field of tissue engineering due to the countless possibilities of scaffolds that can be constructed from such a material. Through conjugation of other functional groups onto a polymer backbone, the mechanical properties of polymers can be controlled and has the ability to span a wide range of strengths, allowing for application in multiple tissue environments. One such polymer, hyaluronic acid (HA), is a natural polysaccharide found most abundantly in the extracellular matrix (ECM) of connective tissues with structural, lubricating, and wound healing functions in the human body; for this reason, HA has great potential for utilization …


Mapping The Spatial And Temporal Dynamics Of Sensorimotor Integration During The Perception And Performance Of Wallowing, Megan E. Cuellar Dec 2014

Mapping The Spatial And Temporal Dynamics Of Sensorimotor Integration During The Perception And Performance Of Wallowing, Megan E. Cuellar

Theses and Dissertations (ETD)

Similar to other complex sequences of muscle activity, swallowing relies heavily upon ‘sensorimotor integration.’ It is well known that the premotor cortex and primary sensorimotor cortices provide critical sensorimotor contributions that help control the strength and timing of swallowing muscle effectors. However, the temporal dynamics of sensorimotor integration remains unclear, even when performed normally without neurological compromise. Recent advances in EEG analysis blind source separation techniques via independent component analysis offer a novel and exciting opportunity to measure cortical sensorimotor activity in realtime during swallowing, concurrently with muscle activity during swallow initiation. In the current study, mu components were identified, …


Behavioral Assessment Of Acute Inhibition Of System XC - In Rats, Victoria Lutgen, Jon M. Resch, Krista Qualmann, Nicholas J. Raddatz, Cristina Panhans, Ellen M. Olander, Linghai Kong, Sujean Choi, John R. Mantsch, David A. Baker Dec 2014

Behavioral Assessment Of Acute Inhibition Of System XC - In Rats, Victoria Lutgen, Jon M. Resch, Krista Qualmann, Nicholas J. Raddatz, Cristina Panhans, Ellen M. Olander, Linghai Kong, Sujean Choi, John R. Mantsch, David A. Baker

Biomedical Sciences Faculty Research and Publications

Rationale

Gaps in our understanding of glutamatergic signaling may be key obstacles in accurately modeling complex CNS diseases. System xc - is an example of a poorly understood component of glutamate homeostasis that has the potential to contribute to CNS diseases.

Objectives

This study aims to determine whether system xc - contributes to behaviors used to model features of CNS disease states.

Methods

In situ hybridization was used to map mRNA expression of xCT throughout the brain. Microdialysis in the prefrontal cortex was used to sample extracellular glutamate levels; HPLC was used to measure extracellular glutamate and tissue …


Saturated Free Fatty Acids Induce Cholangiocyte Lipoapoptosis, Sathish Kumar Natarajan, Sally A. Ingham, Ashley M. Mohr, Cody J. Wehrkamp, Anuttoma Ray, Sohini Roy, Sophie C. Cazanave, Mary A. Smith, Justin L. Mott Dec 2014

Saturated Free Fatty Acids Induce Cholangiocyte Lipoapoptosis, Sathish Kumar Natarajan, Sally A. Ingham, Ashley M. Mohr, Cody J. Wehrkamp, Anuttoma Ray, Sohini Roy, Sophie C. Cazanave, Mary A. Smith, Justin L. Mott

Journal Articles: Biochemistry & Molecular Biology

Recent studies have identified a cholestatic variant of nonalcoholic fatty liver disease (NAFLD) with portal inflammation and ductular reaction. Based on reports of biliary damage, as well as increased circulating free fatty acids (FFAs) in NAFLD, we hypothesized the involvement of cholangiocyte lipoapoptosis as a mechanism of cellular injury. Here, we demonstrate that the saturated FFAs palmitate and stearate induced robust and rapid cell death in cholangiocytes. Palmitate and stearate induced cholangiocyte lipoapoptosis in a concentration-dependent manner in multiple cholangiocyte-derived cell lines. The mechanism of lipoapoptosis relied on the activation of caspase 3/7 activity. There was also a significant up-regulation …


Long-Acting Antituberculous Therapeutic Nanoparticles Target Macrophage Endosomes., Benson J. Edagwa, Dongwei Guo, Pavan Puligujja, Han Chen, Joellyn Mcmillan, Xinming Liu, Howard Gendelman, Prabagaran Narayanasamy Dec 2014

Long-Acting Antituberculous Therapeutic Nanoparticles Target Macrophage Endosomes., Benson J. Edagwa, Dongwei Guo, Pavan Puligujja, Han Chen, Joellyn Mcmillan, Xinming Liu, Howard Gendelman, Prabagaran Narayanasamy

Journal Articles: Pharmacology & Experimental Neuroscience

Eradication of Mycobacterium tuberculosis (MTB) infection requires daily administration of combinations of rifampin (RIF), isoniazid [isonicotinylhydrazine (INH)], pyrazinamide, and ethambutol, among other drug therapies. To facilitate and optimize MTB therapeutic selections, a mononuclear phagocyte (MP; monocyte, macrophage, and dendritic cell)-targeted drug delivery strategy was developed. Long-acting nanoformulations of RIF and an INH derivative, pentenyl-INH (INHP), were prepared, and their physicochemical properties were evaluated. This included the evaluation of MP particle uptake and retention, cell viability, and antimicrobial efficacy. Drug levels reached 6 μg/10(6) cells in human monocyte-derived macrophages (MDMs) for nanoparticle treatments compared with 0.1 μg/10(6) cells for native drugs. …


Site-Specific Mutation Of The Sensor Kinase Gras In Staphylococcus Aureus Alters The Adaptive Response To Distinct Cationic Antimicrobial Peptides, Ambrose L. Cheung, Arnold S. Bayer, Michael R. Yeaman, Yan Q. Xiong, Alan J. Waring, Guido Memmi, Niles Donegan Dec 2014

Site-Specific Mutation Of The Sensor Kinase Gras In Staphylococcus Aureus Alters The Adaptive Response To Distinct Cationic Antimicrobial Peptides, Ambrose L. Cheung, Arnold S. Bayer, Michael R. Yeaman, Yan Q. Xiong, Alan J. Waring, Guido Memmi, Niles Donegan

Dartmouth Scholarship

The Staphylococcus aureus two-component regulatory system, GraRS, is involved in resistance to killing by distinct host defense cationic antimicrobial peptides (HD-CAPs). It is believed to regulate downstream target genes such as mprF and dltABCD to modify the S. aureus surface charge. However, the detailed mechanism(s) by which the histidine kinase, GraS, senses specific HD-CAPs is not well defined. Here, we studied a well-characterized clinical methicillin-resistant S. aureus (MRSA) strain (MW2), its isogenic graS deletion mutant (ΔgraS strain), a nonameric extracellular loop mutant (ΔEL strain), and four residue-specific ΔEL mutants (D37A, P39A, P39S, and D35G D37G D41G strains). The ΔgraS and …


The Mirnaome Of Opisthorchis Viverrini Induced Intrahepatic Cholangiocarcinoma, Jin Peng, Yanjun Feng, Gabriel Rinaldi, Ponlapat Yonglitthipagon, Samantha Easley, Therawach Laha, Chawalit Pairojkul, Vajarabhongsa Bhudhisawasdi, Banchob Sripa, Paul J. Brindley, Jason P. Mulvenna, Jeffrey M. Bethony, Jordan L. Plieskatt Dec 2014

The Mirnaome Of Opisthorchis Viverrini Induced Intrahepatic Cholangiocarcinoma, Jin Peng, Yanjun Feng, Gabriel Rinaldi, Ponlapat Yonglitthipagon, Samantha Easley, Therawach Laha, Chawalit Pairojkul, Vajarabhongsa Bhudhisawasdi, Banchob Sripa, Paul J. Brindley, Jason P. Mulvenna, Jeffrey M. Bethony, Jordan L. Plieskatt

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer, arising in the biliary ducts that extend into the liver. The highest incidence of ICC occurs in Southeast Asia, particularly in the Mekong River Basin countries of Thailand, Laos, Cambodia, and Vietnam, where it is strongly associated with chronic infection by the food-borne liver fluke Opisthorchis viverrini (OV), one of only three eukaryote pathogens considered Group one carcinogens. Intrahepatic cholangiocarcinoma is usually diagnosed at an advanced stage, with a poor prognosis and survival often less than 24 months. Hence, biomarkers that enable the early detection of ICC would be desirable and have a …


Profiling Mirnas In Nasopharyngeal Carcinoma Ffpe Tissue By Microarray And Next Generation Sequencing, Jin Peng, Yanjun Feng, Gabriel Rinaldi, Paul H. Levine, Samantha Easley, Elizabeth Martinez, Salman Hashmi, Nader Sadeghi, Paul J. Brindley, Jason P. Mulvenna, Jeffrey M. Bethony, Jordan L. Plieskatt Dec 2014

Profiling Mirnas In Nasopharyngeal Carcinoma Ffpe Tissue By Microarray And Next Generation Sequencing, Jin Peng, Yanjun Feng, Gabriel Rinaldi, Paul H. Levine, Samantha Easley, Elizabeth Martinez, Salman Hashmi, Nader Sadeghi, Paul J. Brindley, Jason P. Mulvenna, Jeffrey M. Bethony, Jordan L. Plieskatt

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Nasopharyngeal carcinoma (NPC) is a non-lymphomatous, squamous-cell carcinoma that occurs in the epithelial lining of the nasopharynx. Nasopharyngeal carcinoma has a geographically well-defined distribution worldwide, with the highest prevalence in China, Southeast Asia, and Northern Africa. Symptoms of nascent NPC may be unapparent or trivial, with diagnosis based on the histopathology of biopsied tissue following endoscopy of the nasopharynx. The tumor node metastasis (TNM) staging system is the benchmark for the prognosis of NPC and guides treatment strategy. However, there is a consensus that the TNM system is not sufficiently specific for the prognosis of NPC, as it does not …


Effects Of Fatty Acid Structure On Endothelial Cell Expression Of Connexin43, Albert E. Sowers Iii Dec 2014

Effects Of Fatty Acid Structure On Endothelial Cell Expression Of Connexin43, Albert E. Sowers Iii

Masters Theses

The epidemic of obesity-related metabolic and cardiovascular diseases is linked to elevated fatty acids (FA). Epidemiological data argue that trans FA contribute to the development and progression of these disease processes. Previous work suggests the similarity in structure between saturated and trans FA may stimulate inflammation through trans FA interactions with toll-like receptor 4 (TLR4). To evaluate the impact of trans FA on cardiovascular health, the response of endothelial cells to trans FA was evaluated. Specifically, responses to the 18-carbon trans FA elaidic acid (EA) were compared to the same length cis FA oleic acid (OA). Endothelial cells were exposed …


Glutaredoxin 2 (Grx2) Gene Deletion Induces Early Onset Of Age-Dependent Cataracts In Mice, Hongli Wu, Yibo Yu, Larry David, Ye-Shih Ho, Marjorie . F. Lou Dec 2014

Glutaredoxin 2 (Grx2) Gene Deletion Induces Early Onset Of Age-Dependent Cataracts In Mice, Hongli Wu, Yibo Yu, Larry David, Ye-Shih Ho, Marjorie . F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Glutaredoxin 2 (Grx2) is an isozyme of glutaredoxin1 (thioltransferase) present in the mitochondria and nucleus with disulfide reductase and peroxidase activities, and it controls thiol/ disulfide balance in cells. In this study, we investigated whether Grx2 gene deletion could induce faster age-related cataract formation and elucidated the biochemical changes effected by Grx2 gene deletion that may contribute to lens opacity. Slit lamp was used to examine the lenses in Grx2 knock-out (KO) mice and age-matched wild-type (WT) mice ages 1 to 16 months. In the Grx2 null mice, the lens nuclear opacity began at 5 months, 3 months sooner than …


The Nutrient Intake Of Homeless Women Of Grand Rapids, Michigan, Emily D. Popma-Metsaars Dec 2014

The Nutrient Intake Of Homeless Women Of Grand Rapids, Michigan, Emily D. Popma-Metsaars

Masters Theses

Background Homeless individuals comprise about 1% of the American population with 1/3 of this particular population being women. And despite the potential for hunger, the homeless population has a similar prevalence of overweight/obese as other Americans. The Heartside neighborhood of Grand Rapids is a very low-income area of the city, inhabited by the poor and homeless. The Food Access in Michigan Project is studying the relationship between food insecurity and food environments in Michigan.

Objectives The purpose of this study was to determine the characteristics of the diet of homeless women in Heartside. This study examined the level of food …


Arsenic Targets Neural Plate Border Specifier Cells In P19 Cells, Christopher Mccoy Dec 2014

Arsenic Targets Neural Plate Border Specifier Cells In P19 Cells, Christopher Mccoy

All Theses

Epidemiological studies have shown that arsenic exposure during early embryogenesis can cause reduced weight gain and neurological deficits later on in life. In addition, in vitro and in vivo studies have indicated that arsenic suppresses neurogenesis and myogenesis. The exact mechanism of how arsenic causes these undesired developmental outcomes is poorly understood, however both skeletal muscle and sensory neuron development require the Wnt/β-catenin signaling pathway to initiate the specific differentiation of precursor cells. We were interested in determining the target cell population of arsenic and its metabolites. Arsenic's metabolites were of interest because they have been shown to be more …


Mrp4-Dependent Regulation Of Fibroblast Migration, Chandrima Sinha Dec 2014

Mrp4-Dependent Regulation Of Fibroblast Migration, Chandrima Sinha

Theses and Dissertations (ETD)

Roles of cyclic nucleotides and cyclic nucleotide-dependent signaling molecules in regulating several signaling pathways including cell migration have long been known. However, the new and revolutionary concept is that it is not just the absence or presence of cyclic nucleotides, but a highly coordinated balance between these molecules regulates cell migration. Multi-drug resistance protein 4 (MRP4), is a member of the large family of ATP binding cassette (ABC) transporter proteins, that localizes to the plasma membrane and functions as a nucleotide efflux transporter and thus plays a pivotal role in the regulation of intracellular cyclic nucleotide dynamics. In our study …


Vitamin D And White Matter Abnormalities In Older Adults: A Cross-Sectional Neuroimaging Study., C Annweiler, T Annweiler, R Bartha, F R Herrmann, R Camicioli, O Beauchet Dec 2014

Vitamin D And White Matter Abnormalities In Older Adults: A Cross-Sectional Neuroimaging Study., C Annweiler, T Annweiler, R Bartha, F R Herrmann, R Camicioli, O Beauchet

Medical Biophysics Publications

BACKGROUND AND PURPOSE: Morphological brain changes related to hypovitaminosis D have been poorly studied. In particular, the age-related decrease in vitamin D concentrations may explain the onset of white matter abnormalities (WMA) in older adults. Our objectives were (i) to investigate whether there was an association between serum 25-hydroxyvitamin D (25OHD) concentration and the grade of WMA in older adults and (ii) to determine whether the location of WMA was associated with 25OHD concentration.

METHODS: One hundred and thirty-three Caucasian older community-dwellers with no clinical hydrocephalus (mean 71.6 ± 5.6 years; 43.6% female) received a blood test and a magnetic …


Nprl2/Tusc4 Functions As A Tumor Suppressor By Regulating Brca1’S Stability Via The E3 Ubiquitination Pathway, Yang Peng Dec 2014

Nprl2/Tusc4 Functions As A Tumor Suppressor By Regulating Brca1’S Stability Via The E3 Ubiquitination Pathway, Yang Peng

Dissertations & Theses (Open Access)

Expression of the tumor suppressor protein BRCA1 is frequently lost in breast cancer patients, and the loss of its expression is associated with disruption of various critical functions in cells and cancer development. In the present study, we demonstrate through microarray analysis that cells with tumor suppressor candidate 4 (NPRL2/TUSC4) knockdown show critical changes to cell cycle, cell death pathways and a global impact on cancer development. More importantly, we observed a clear cluster pattern of NPRL2/TUSC4-knockdown gene profiles with established homologous recombination (HR) repair defect signature. Additionally, NPRL2/TUSC4 protein physically interacts with the E3 ligase HERC2 and prevents ubiquitin …


The Crebh In Hepatic Lipid And Lipoprotein Metabolism: Implication For The Pathogenesis Of Hyperlipidemia And Metainflammation, Miaoyun Zhao Dec 2014

The Crebh In Hepatic Lipid And Lipoprotein Metabolism: Implication For The Pathogenesis Of Hyperlipidemia And Metainflammation, Miaoyun Zhao

Department of Nutrition and Health Sciences: Dissertations, Theses, and Student Research

Hyperlipidemia is reemerging as an important cardiovascular disease risk factor and other metabolic disorders, such as obesity, insulin resistance and type-2 diabetes. Hepatic de novo lipogenesis is controlled by a family of the b-zip transcription factors, the sterol regulatory element-binding proteins (SREBPs), which targets downstream genes involved in free fatty acids, triglycerides and cholesterol synthesis. Regulation of SREBPs signaling is controlled by a cluster of the ER membrane-bound proteins, the insulin induced gene-1(Insig-1) and gene-2 (Insig-2) and the SCAP protein. The cAMP responsive element binding protein H (CREBH) is a recently identified member of this family. CREBH is selectively and …


The Effect Of Spinal Cord Injury On Vagal Afferents., April N. Herrity Dec 2014

The Effect Of Spinal Cord Injury On Vagal Afferents., April N. Herrity

Electronic Theses and Dissertations

Spinal cord injury (SCI) is a significant public health concern that leaves patients with a multitude of life-long disabilities. Major complications of SCI apart from paralysis, include deficits in bladder and bowel function. Lower urinary tract dysfunction continues to remain a top priority issue affecting quality of life for this population. The majority of visceral organs receive a dual sensory innervation from both spinal nerves as well as the vagus nerve. Following SCI, the vagus nerve is a potential pathway through which information from regions below the level of a spinal injury can travel directly to the brainstem, bypassing the …


Development Of Models For The Study Of The Molecular Mechanisms Of Host Restriction And Adaptation Of Hantaviruses., Ryan Carroll Mcallister 1988- Dec 2014

Development Of Models For The Study Of The Molecular Mechanisms Of Host Restriction And Adaptation Of Hantaviruses., Ryan Carroll Mcallister 1988-

Electronic Theses and Dissertations

Hantaviruses, family Bunyaviridae, are present throughout the globe in a variety of mouse, rat, mole, vole, shrew, or bat species. Hantaviruses persist for the lifetime of the animal reservoir, while causing no signs or symptoms of disease. Only the rodent-borne hantaviruses cause disease in humans. In contrast, a “spillover” infection of a hantavirus into a nonreservoir rodent species results in an asymptomatic acute infection. We and others in the field are interested in understanding the biology of these virus-host interactions and mechanisms that underlie these three very different outcomes. The second chapter of my thesis focused on probing the intrahost …


The Role Of Mcl-1 In The Heart: Gateway From Life To Death, Xi Wang Dec 2014

The Role Of Mcl-1 In The Heart: Gateway From Life To Death, Xi Wang

Theses and Dissertations (ETD)

MCL-1 is an essential BCL-2 family member that promotes the survival of multiple cellular lineages, but its role in cardiac muscle has remained unclear. Here, we have demonstrated that cardiac-specific ablation of Mcl-1 results in a rapidly fatal, dilated cardiomyopathy preceded by loss of myofibrils and cardiac contractility, abnormal mitochondria ultrastructure, defective mitochondrial respiration, and impaired autophagy. Genetic ablation of both pro-apoptotic effectors (Bax and Bak) could largely rescue the lethality and impaired cardiac function induced by Mcl-1 deletion. However, Mcl-1-, Bax-, and Bak-deficient hearts still revealed mitochondrial ultrastructural abnormalities and displayed deficient mitochondrial respiration, and are hypersensitive to chronic …


Measuring The Role Of Inhibition In Auditory Discrimination In Mice, Tazima Nur Dec 2014

Measuring The Role Of Inhibition In Auditory Discrimination In Mice, Tazima Nur

Graduate Theses and Dissertations

Understanding how inhibitory neurons affect sensory information processing in the cerebral cortex is an ongoing goal of both neuroscience and statistical physics research. In this master's thesis research project, an experimental system has been designed and built for studying how auditory dynamic range depends on inhibitory neurons, based on observations of mouse behavior. In this thesis, firstly, the topic of inhibition and information processing has been introduced. Then two papers related to inhibition and dynamic range has been reviewed in detail. One of the papers is an experimental work that analyzes the affect of inhibition on dynamic range. The other …