Digital Commons Network^™

Associatioin Of Plasma Aβ Peptides With Blood Pressure In The Elderly, Jean-Charles Lambert, Jean Dallongeville, Kathryn A. Ellis, Susanna Schraen-Maschke, James Lui, Simon Laws, Julie Dumont, Florence Richard, Dominque Cottel, Claudine Berr, David Ames, Colin L. Masters, Christopher C. Rowe, Cassandra Szoeke, Christophe Tzourio, Jean-Francois Dartigues, Luc Buee, Ralph Martins, Philippe Amouyel

Research outputs 2011

Background Aß peptides are often considered as catabolic by-products of the amyloid ß protein precursor (APP), with unknown physiological functions. However, several biological properties have been tentatively attributed to these peptides, including a role in vasomotion. We assess whether plasma Aß peptide levels might be associated with systolic and diastolic blood pressure values (SBP and DBP, respectively). Methodology/Principal Findings Plasma Aß1-40 and Aß1-42 levels were measured using an xMAP-based assay in 1,972 individuals (none of whom were taking antihypertensive drugs) from 3 independent studies: the French population-based 3C and MONA-LISA (Lille) studies (n = 627 and n = 769, respectively) …

Microbial Community Analysis Of Lake Chillisquaque, A Small Water System In Central Pennsylvania, Allison Mayhew

Honors Theses

Cyanobacteria are photosynthetic organisms that require the absorption of light for the completion of photosynthesis. Cyanobacteria can use a variety of wavelengths of light within thevisible light spectrum in order to harvest energy for this process. Many species of cyanobacteria have light-harvesting proteins that specialize in the absorption of a small range of wavelengths oflight along the visual light spectrum; others can undergo complementary chromatic adaptation and alter these light-harvesting proteins in order to absorb the wavelengths of light that are mostavailable in a given environment. This variation in light-harvesting phenotype across cyanobacteria leads to the utilization of environmental niches …

The Cardiac Atlas Project--An Imaging Database For Computational Modeling And Statistical Atlases Of The Heart, Carissa G. Fonseca, Michael Backhaus, David A. Bluemke, Randall D. Britten, Jae Do Chung, Brett R. Cowan, Alan H. Kadish

Office of the President Publications and Research

MOTIVATION: Integrative mathematical and statistical models of cardiac anatomy and physiology can play a vital role in understanding cardiac disease phenotype and planning therapeutic strategies. However, the accuracy and predictive power of such models is dependent upon the breadth and depth of noninvasive imaging datasets. The Cardiac Atlas Project (CAP) has established a large-scale database of cardiac imaging examinations and associated clinical data in order to develop a shareable, web-accessible, structural and functional atlas of the normal and pathological heart for clinical, research and educational purposes. A goal of CAP is to facilitate collaborative statistical analysis of regional heart shape …

Defining The Phenotypes Of Sickle Cell Disease., Samir K. Ballas

Department of Medicine Faculty Papers

The sickle cell gene is pleiotropic in nature. Although it is a single gene mutation, it has multiple phenotypic expressions that constitute the complications of sickle cell disease. The frequency and severity of these complications vary considerably both latitudinally in patients and longitudinally in the same patient over time. Thus, complications that occur in childhood may disappear, persist or get worse with age. Dactylitis and stroke, for example, occur mostly in childhood, whereas leg ulcers and renal failure typically occur in adults. It is essential that the phenotypic manifestations of sickle cell disease be defined accurately so that communication among …

Update On Pain Management In Sickle Cell Disease., Samir K Ballas

Department of Medicine Faculty Papers

Acute pain is the hallmark of sickle cell disease and is the most common cause of hospital admissions. Tissue damage due to vaso-occlusion releases numerous inflammatory mediators that initiate the transmission of painful stimuli that culminate in the perception of pain. The acute sickle cell painful crisis evolves along four phases. Each phase is coupled with changes in certain markers of the disease. Hospital readmission occurs within 1 week in about 16% of discharged patients and within 1 month in about 50% of discharged patients. Failure to treat acute pain aggressively may lead to chronic pain syndrome which, in turn, …

Tdp-43 Potentiates Alpha-Synuclein Toxicity To Dopaminergic Neurons In Transgenic Mice., Tian Tian, Cao Huang, Jianbin Tong, Ming Yang, Hongxia Zhou, Xugang Xia

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

TDP-43 and α-synuclein are two disease proteins involved in a wide range of neurodegenerative diseases. While TDP-43 proteinopathy is considered a pathologic hallmark of sporadic amyotrophic lateral sclerosis and frontotemporal lobe degeneration, α-synuclein is a major component of Lewy body characteristic of Parkinson's disease. Intriguingly, TDP-43 proteinopathy also coexists with Lewy body and with synucleinopathy in certain disease conditions. Here we reported the effects of TDP-43 on α-synuclein neurotoxicity in transgenic mice. Overexpression of mutant TDP-43 (M337V substitution) in mice caused early death in transgenic founders, but overexpression of normal TDP-43 only induced a moderate loss of cortical neurons in …

Protein Modification By Arginylation, Hideko Kaji, Akira Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

The modification of protein by arginine catalyzed by arginyltransferases (ATE1) described by the Kashina group in this issue shows that arginylation of protein occurs widely in biology and is being recognized as a key regulatory reaction such as phosphorylation of proteins (Wang et al., 2011).

The Effect Of High Dose Total Body Irradiation On Acth, Corticosterone, And Catecholamines In The Rat, Eric P. Cohen, Eric D. Bruder, William E. Cullinan, Dana R. Ziegler, Hershel Raff

Biomedical Sciences Faculty Research and Publications

Total body irradiation (TBI) or partial body irradiation is a distinct risk of accidental, wartime, or terrorist events. Total body irradiation is also used as conditioning therapy before hematopoietic stem cell transplantation. This therapy can result in injury to multiple tissues and might result in death as a result of multiorgan failure. The hypothalamic–pituitary–adrenal (HPA) axis could play a causative role in those injuries, in addition to being activated under conditions of stress. In a rat model of TBI, we have established that radiation nephropathy is a significant lethal complication, which is caused by hypertension and uremia. The current study …

Differential Effects Of Isoflurane And Propofol Anesthesia On Neurogenesis In Young And Aged Rats, Diana Marcela Erasso

USF Tampa Graduate Theses and Dissertations

Worldwide, millions of young and elderly patients receive procedures that could not be performed without the use of anesthetics. Unfortunately, emerging animal and human data suggest an association between exposure to general anesthesia and impairment of cognitive function in pediatric and geriatric patients. Recent laboratory data have shown that general anesthetics are potentially damaging to the developing and aging brain. However, the mechanism by which this happens is still unknown. General anesthetics affect learning and memory, a brain function involving neural plasticity. An important form of neural plasticity receiving attention is postnatal neurogenesis. This process is highly regulated and involved …

The Role Of Hiv-1 Proteins In Alzheimer's Disease Pathology, Brian Nelson Giunta

USF Tampa Graduate Theses and Dissertations

Prevalence of HIV-associated cognitive impairment is rising, the worst form of which is HIV-associated dementia (HAD). The disease is fuiled by a chronic innate type pro-inflammatory response in the brain which is highly dependent upon the activation of microglia. We first created an in vitro model of HAD composed of cultured microglial cells synergistically activated by the addition of IFN-gamma and the HIV-1 coat glycoprotein, gp120. This activation, as measured by TNF-alpha and NO release, is synergistically attenuated through the alpha7nAChR and p44/42 MAPK system by pretreatment with nicotine, and the cholinesterase inhibitor, galantamine. As these medications have been FDA …

Current Review Of In Nivo Gbm Rodent Models: Emphasis On The Cns-1 Tumour Model, Valerie L. Jacobs, Pablo A. Valdes, William F. Hickey, Joyce A. De Leo

Dartmouth Scholarship

GBM (glioblastoma multiforme) is a highly aggressive brain tumour with very poor prognosis despite multi-modalities of treatment. Furthermore, recent failure of targeted therapy for these tumours highlights the need of appropriate rodent models for preclinical studies. In this review, we highlight the most commonly used rodent models (U251, U86, GL261, C6, 9L and CNS-1) with a focus on the pathological and genetic similarities to the human disease. We end with a comprehensive review of the CNS-1 rodent model.

The Effects Of Pre-Exercise Carbohydrate Supplementation On Resistance Training Performance During An Acute Resistance Training Session, Kelly Raposo

USF Tampa Graduate Theses and Dissertations

It appears that "carbohydrate loading" may enhance the performance of resistance training, but studies on CHO supplementation prior to a resistance-training bout are limited and have resulted in conflicting findings. PURPOSE: To investigate the effects of pre-exercise CHO supplementation on high-intensity (>75% 1RM) resistance training performance for resistance-trained women during an acute bout of resistance exercise. METHODS: Thirteen resistance trained female participants (21.9 ± 4.8 yrs; 64.5 ± 3.0 in; 137.0 ± 14.8 lbs) came to the Exercise and Performance Nutrition Laboratory on three separate occasions; the day of the Familiarization Trial (FT) and the two Exercise Testing sessions …

Repeated Binge Pattern Ethanol Administration During Adolescence Or Adulthood: Long-Term Changes In Voluntary Ethanol Intake And Mesolimbic Dopamine Functionality In Male Rats, Antoniette Michelle Maldonado-Devincci

USF Tampa Graduate Theses and Dissertations

Binge alcohol consumption is a rising concern in the United States, especially among adolescents as during this developmental period alcohol use is usually initiated and has been shown to cause detrimental effects on brain structure and function. These findings have been established through the use of binge models in animals, where animals are repeatedly administered high doses of ethanol typically over a period of three or four days. While such work has examined the effects of a four-day and repeated three-day binge, there has been almost no work conducted aimed at investigating the long-term behavioral and neurochemical and/or functional consequences …

Is Chronic Use Of Bacopa Monnieri An Effective Treatment To Improve Memory Performance In Healthy And Aging Adults?, Brian M. Kairalla

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of the systematic review is to determine whether or not chronic use of Bacopa monnieri is an effective treatment to improve memory performance in healthy and aging adults.

Effects Of Managed Care On The Health And Health-Care Of The Non-Elderly With Diabetes, Meihua Lu

Wayne State University Dissertations

This dissertation attempts to examine the quality effect of managed care plans (as compared with traditional fee-for-service plans, or FFS) on the health outcome and health care use of patients with diabetes. As the number of diabetics is growing rapidly with many of them are relying on managed care plans, knowing better the effects of different plans on health status and health care utilization is of great interest and significance to consumers, employers, and policymakers, especially at a time that universal health care is under being implemented.

Using up-to-date data from MEPS, a nationally representative survey, I compared 484 HMO …

Frazzled And Abelson Interact To Regulate The Actin Cytoskeleton In Drosophila, Bridget Elsa Varughese

Wayne State University Dissertations

Guidance receptors such as Frazzled affect cell shape and motility by directly or indirectly modulating the cytoskeleton. Fra is particularly needed for the formation of the posterior commissures in a developing Drosophila embryo. The cytoplasmic tyrosine kinase, Abelson Kinase (Abl) enhances the loss of commissures observed in fra mutant. Abl physically interacts with Frazzled to help guide commissural axons across the midline. Furthermore, the loss of commissural axons is only seen when the actin dynamics are perturbed. Abl is also known to regulate actin-dependent processes underlying formation of filopodia, microspikes and membrane ruffles. So, we established a Drosophila S2 cell …

Mechanisms Of Translation Arrest Following Focal Brain Ischemia, Monique K. Lewis

Wayne State University Dissertations

MECHANISMS OF TRANSLATION ARREST FOLLOWING FOCAL BRAIN

ISCHEMIA

by

MONIQUE K. LEWIS

August 2011

Advisor: Dr. Donald DeGracia

Major: Physiology

Degree: Doctor of Philosophy

The loss of blood flow to the brain is termed ischemia and the subsequent resumption of blood flow is termed reperfusion. Brain ischemia and reperfusion (I/R) occurs primarily following resuscitation from cardiac arrest and stroke and presents one of the most significant clinical challenges. At present, there are no clinically effective pharmacologic interventions to halt brain damage following I/R. The major Aim of this dissertation will be to investigate possible mechanisms involved in neuron death following …

Axogial Communication Mediated By Soluble Neuregulin-1 And Bdnf, Zhenzhong Ma

Wayne State University Dissertations

During peripheral nervous system development, successful communication between axons and glial cells including Schwann cells in peripheral nervous system and oligodendrocytes in central nervous system, is required for the proper functions of both neurons and glia. Three types of alternatively-spliced proteins belonging to the neuregulin1 (NRG1) gene family of growth and differentiation factors are essential for Schwann cell survival and peripheral nerve development. While membrane-bound NRG1 forms (type III) has been strongly implicated in the regulation of myelination process at late stage of Schwann cell development, little is known about the role of soluble, heparin-binding forms of NRG1 (type I/II) …

Expression Of Microbial Rhodopsins In Retinal Neurons With Subcellular Targeting Motifs: For The Study Of The Structure/Function Of Aii Amacrine Cells And For Vision Restoration, Chaowen Wu

Wayne State University Dissertations

Protein-targeting motifs serve as addresses for subcellular protein localization. This feature of targeting-motifs was used to study the retina. The first part of the dissertation reports in the axonless spiking AII amacrine cell of the mammalian retina a dendritic process sharing organizational and functional similarities with the axon initial segment, the typical site of action potential initiation. This process was revealed through viral-mediated expression of channelrhodopsin-2-GFP (ChR2-GFP) with the AIS-targeting motif of sodium channels (NavII-III) and was shown to be the site of spike initiation. The second part of the dissertation aimed to improve microbial rhodopsin-mediated gene therapy for vision …

Mechanisms Of Persistent Translation Arrest Following Global Brain Ischemia And Reperfusion, Jill Theresa Jamison

Wayne State University Dissertations

ABSTRACT

MECHANISMS OF PERSISTENT TRANSLATION ARREST FOLLOWING GLOBAL BRAIN ISCHEMIA and REPERFUSION

by

JILL T. JAMISON

December 2011

Advisor: Donald J. DeGracia, Ph.D.

Major: Physiology

Degree: Doctor of Philosophy

The information presented here studies the mechanisms that underlie persistent translation arrest (TA) following global brain ischemia and reperfusion (I/R). To summarize the main findings I have discovered a new mechanism for prolonged post-ischemic TA that correlated exactly with in vivo translation rates and correlated precisely with cell outcome. Through the extensive colocalization studies, my results indicate that the mRNA granules are ribonomic structures involved with mRNA regulation. This finding is …

Processing Random Signals In Neuroscience, Electrical Engineering And Operations Research, Kalyan Raman

Wayne State University Dissertations

The topic of this dissertation is the study of noise in electrical engineering, neuroscience, biomedical engineering, and operations research through mathematical models that describe, explain, predict and control dynamic phenomena. Noise is modeled through Brownian Motion and the research problems are mathematically addressed by different versions of a generalized Langevin equation. Our mathematical models utilize stochastic differential equations (SDEs) and stochastic optimal control, both of which were born in the soil of electrical engineering. Central to this dissertation is a brain-physics based model of cerebrospinal fluid (CSF) dynamics, whose structure is fundamentally determined by an electrical circuit analogy. Our general …

Cellular Inhibitor Of Apoptosis 1 (Ciap-1) Degradation By Caspase 8 During Tnf-Related Apoptosis-Inducing Ligand (Trail)-Induced Apoptosis., Maria Eugenia Guicciardi, Justin L. Mott, Steven F. Bronk, Satoshi Kurita, Christian D. Fingas, Gregory J. Gores

Journal Articles: Biochemistry & Molecular Biology

TNF-related apoptosis-inducing ligand (TRAIL) is a potential chemotherapeutic agent with high selectivity for malignant cells. Many tumors, however, are resistant to TRAIL cytotoxicity. Although cellular inhibitors of apoptosis 1 and 2 (cIAP-1 and -2) are often over-expressed in cancers, their role in mediating TRAIL resistance remains unclear. Here, we demonstrate that TRAIL-induced apoptosis of liver cancer cells is associated with degradation of cIAP-1 and X-linked IAP (XIAP), whereas cIAP-2 remains unchanged. Lower concentrations of TRAIL causing minimal or no apoptosis do not alter cIAP-1 or XIAP protein levels. Silencing of cIAP-1 expression, but not XIAP or cIAP-2, as well as …

Getting To Know You: Key Clinical Concepts In Relationship-Based Interventions And Neurobehavioral Observations With Young Infants, Yvette Blanchard

All PTHMS Faculty Publications

The newborn infant is a social organism, pre-disposed to interact with his caregiver and able to elicit the kind of caregiving necessary for successful adaptation. The earliest developmental task of the newborn is to organize behavior to be able to play an active role in influencing the caregiving environment and eliciting the kind of support needed for development. This task is accomplished through the attainment of self-regulation or balanced neurobehavioral functioning of the infant's autonomic, motor, state, and responsivity behavioral dimensions as described by Als.

Human Chondrosarcoma Cells Acquire An Epithelial-Like Gene Expression Pattern Via An Epigenetic Switch: Evidence For Mesenchymal-Epithelial Transition During Sarcomagenesis., Matthew P. Fitzgerald, Francoise Gourronc, Melissa L.T. Teoh, Matthew J. Provenzano, Adam J. Case, James A. Martin, Frederick E. Domann

Journal Articles: Cellular & Integrative Physiology

Chondrocytes are mesenchymally derived cells that reportedly acquire some epithelial characteristics; however, whether this is a progression through a mesenchymal to epithelial transition (MET) during chondrosarcoma development is still a matter of investigation. We observed that chondrosarcoma cells acquired the expression of four epithelial markers, E-cadherin,desmocollin 3, maspin, and 14-3-3σ, all of which are governed epigenetically through cytosine methylation. Indeed, loss of cytosine methylation was tightly associated with acquired expression of both maspin and 14-3-3σ in chondrosarcomas. In contrast, chondrocyte cells were negative for maspin and 14-3-3σ and displayed nearly complete DNA methylation. Robust activation of these genes was also …

Computational Analyses Of The Uptake And Distribution Of Carbon Monoxide (Co) In Human Subjects, Kinnera Chada

University of Kentucky Doctoral Dissertations

Carbon monoxide (CO) is an odorless, colorless, tasteless gas that binds to hemoglobin with high affinity. This property underlies the use of low doses of CO to determine hemoglobin mass (M_Hb) in the fields of clinical and sports medicine. However, hemoglobin bound to CO is unable to transport oxygen and exposure to high CO concentrations is a significant environmental and occupational health concern. These contrasting aspects of CO—clinically useful in low doses but potentially lethal in higher doses—mandates a need for a quantitative understanding of the temporal profiles of the uptake and distribution of CO …

Rit Gtpase Signaling Mediates Oxidative Stress Resistance And Survival Of Adult Newborn Neurons After Traumatic Brain Injury, Weikang Cai

Theses and Dissertations--Molecular and Cellular Biochemistry

The small GTPases function as molecular switches to control diverse signaling cascades. The mammalian Rit and Rin, along with Drosophila Ric, comprise an evolutionarily conserved subfamily of the Ras-related GTPases. Previous studies using cultured cell models suggested that Rit was involved in the control of cell proliferation, transformation, neuronal differentiation, morphogenesis, and cell survival, but the principal physiological function of Rit remained uncharacterized.

To address this outstanding question, we employed a genetic approach, engineering a Rit knockout mouse. Using this animal model, we demonstrate a central role of Rit in governing cell survival in a p38-dependent fashion. Primary mouse embryonic …

Mitochondrial Genome Sequence Analysis: A Custom Bioinformatics Pipeline Substantially Improves Affymetrix Mitochip V2.0 Call Rate And Accuracy., Hongbo M Xie, Juan C Perin, Theodore G Schurr, Matthew C Dulik, Sergey I Zhadanov, Joseph A Baur, Michael P King, Emily Place, Colleen Clarke, Michael Grauer, Jonathan Schug, Avni Santani, Anthony Albano, Cecilia Kim, Vincent Procaccio, Hakon Hakonarson, Xiaowu Gai, Marni J Falk

Department of Biochemistry and Molecular Biology Faculty Papers

BACKGROUND: Mitochondrial genome sequence analysis is critical to the diagnostic evaluation of mitochondrial disease. Existing methodologies differ widely in throughput, complexity, cost efficiency, and sensitivity of heteroplasmy detection. Affymetrix MitoChip v2.0, which uses a sequencing-by-genotyping technology, allows potentially accurate and high-throughput sequencing of the entire human mitochondrial genome to be completed in a cost-effective fashion. However, the relatively low call rate achieved using existing software tools has limited the wide adoption of this platform for either clinical or research applications. Here, we report the design and development of a custom bioinformatics software pipeline that achieves a much improved call rate …

Suggested Improvements For The Allergenicity Assessment Of Genetically Modified Plants Used In Foods, Richard E. Goodman

Department of Food Science and Technology: Faculty Publications

Genetically modified (GM) plants are increasingly used for food production and industrial applications. As the global population has surpassed 7 billion and per capita consumption rises, food production is challenged by loss of arable land, changing weather patterns, and evolving plant pests and disease. Previous gains in quantity and quality relied on natural or artificial breeding, random mutagenesis, increased pesticide and fertilizer use, and improved farming techniques, all without a formal safety evaluation. However, the direct introduction of novel genes raised questions regarding safety that are being addressed by an evaluation process that considers potential increases in the allergenicity, toxicity, …

Robust Rnai-Based Resistance To Mixed Infection Of Three Viruses In Soybean Plants Expressing Separate Short Hairpins From A Single Transgene, Xiuchun Zhang, Shirley Sato, Xiaohong Ye, Anne E. Dorrance, Thomas Jack Morris, Thomas E. Clemente, Feng Qu

Nebraska Center for Virology: Faculty Publications

Transgenic plants expressing double-stranded RNA (dsRNA) of virus

origin have been previously shown to confer resistance to virus infections

through the highly conserved RNA-targeting process termed RNA silencing

or RNA interference (RNAi). In this study we applied this strategy to

soybean plants and achieved robust resistance to multiple viruses with a

single dsRNA-expressing transgene. Unlike previous reports that relied

on the expression of one long inverted repeat (IR) combining sequences

of several viruses, our improved strategy utilized a transgene designed to

express several shorter IRs. Each of these short IRs contains highly conserved

sequences of one virus, forming dsRNA of …

Kaposi Sarcoma-Associated Herpesvirus Degrades Cellular Toll-Interleukin-1 Receptor Domain-Containing Adaptor-Inducing Β-Interferon (Trif), Humera Ahmad, Rachel Gubbels, Florencia Meyer, Thomas Waterbury, Rongtuan Lin, Luwen Zhang

Nebraska Center for Virology: Faculty Publications

Kaposi sarcoma-associated herpesvirus (KSHV) is a human ƴ - herpesvirus associated with several human malignancies. The replication and transcription activator (RTA) is necessary and sufficient for the switch from KSHV latency to lytic replication. Toll-interleukin-1 receptor (TIR) domain-containing adaptorinducing β-interferon (TRIF, also called TIR-domain-containing adaptor molecule-1 (TICAM-1)) is a signaling adaptor molecule that is critically involved in the Toll-like receptor 3 (TLR-3) and TLR-4 signaling pathways for type I interferon (IFN) production, a key component of innate immunity against microbial infection. In this report, we find a new mechanism by which RTA blocks innate immunity by targeting cellular TRIF. RTA …