Digital Commons Network^™

Endocarditis And Biofilm-Associated Pili Of Enterococcus Faecalis, Sreedhar R Nallapareddy, Kavindra V Singh, Jouko Sillanpää, Danielle A Garsin, Magnus Höök, Stanley L Erlandsen, Barbara E Murray

Faculty, Staff and Student Publications

Increasing multidrug resistance in Enterococcus faecalis, a nosocomial opportunist and common cause of bacterial endocarditis, emphasizes the need for alternative therapeutic approaches such as immunotherapy or immunoprophylaxis. In an earlier study, we demonstrated the presence of antibodies in E. faecalis endocarditis patient sera to recombinant forms of 9 E. faecalis cell wall-anchored proteins; of these, we have now characterized an in vivo-expressed locus of 3 genes and an associated sortase gene (encoding sortase C; SrtC). Here, using mutation analyses and complementation, we demonstrated that both the ebp (encoding endocarditis and biofilm-associated pili) operon and srtC are important for biofilm production …

Natriuretic Peptides And Nitric Oxide Stimulate Cgmp Synthesis In Different Cellular Compartments, Leslie A Piggott, Kathryn A Hassell, Zuzana Berkova, Andrew P Morris, Michael Silberbach, Thomas C Rich

Faculty, Staff and Student Publications

Cyclic nucleotide-gated (CNG) channels are a family of ion channels activated by the binding of cyclic nucleotides. Endogenous channels have been used to measure cyclic nucleotide signals in photoreceptor outer segments and olfactory cilia for decades. Here we have investigated the subcellular localization of cGMP signals by monitoring CNG channel activity in response to agonists that activate either particulate or soluble guanylyl cyclase. CNG channels were heterologously expressed in either human embryonic kidney (HEK)-293 cells that stably overexpress a particulate guanylyl cyclase (HEK-NPRA cells), or cultured vascular smooth muscle cells (VSMCs). Atrial natriuretic peptide (ANP) was used to activate the …

Accuracy And Self Correction Of Information Received From An Internet Breast Cancer List: Content Analysis, Adol Esquivel, Funda Meric-Bernstam, Elmer V Bernstam

Faculty, Staff and Student Publications

OBJECTIVES: To determine the prevalence of false or misleading statements in messages posted by internet cancer support groups and whether these statements were identified as false or misleading and corrected by other participants in subsequent postings. DESIGN: Analysis of content of postings. SETTING: Internet cancer support group Breast Cancer Mailing List. MAIN OUTCOME MEASURES: Number of false or misleading statements posted from 1 January to 23 April 2005 and whether these were identified and corrected by participants in subsequent postings. RESULTS: 10 of 4600 postings (0.22%) were found to be false or misleading. Of these, seven were identified as false …

Translational Regulation Of Nuclear Gene Cox4 Expression By Mitochondrial Content Of Phosphatidylglycerol And Cardiolipin In Saccharomyces Cerevisiae, Xuefeng Su, William Dowhan

Faculty, Staff and Student Publications

Previous results indicated that translation of four mitochondrion-encoded genes and one nucleus-encoded gene (COX4) is repressed in mutants (pgs1Delta) of Saccharomyces cerevisiae lacking phosphatidylglycerol and cardiolipin. COX4 translation was studied here using a mitochondrially targeted green fluorescence protein (mtGFP) fused to the COX4 promoter and its 5' and 3' untranslated regions (UTRs). Lack of mtGFP expression independent of carbon source and strain background was established to be at the translational level. The translational defect was not due to deficiency of mitochondrial respiratory function but was rather caused directly by the lack of phosphatidylglycerol and cardiolipin in mitochondrial membranes. Reintroduction of …

Application Of Cognitive Engineering Principles To The Redesign Of A Dichotomous Identification Key For Parasitology, Kimberly A. Smith-Akins, Sharon Mclane, Thomas M. Craig, Todd R. Johnson

Faculty, Staff and Student Publications

Dichotomous identification keys are used throughout biology for identification of plants, insects, and parasites. However, correct use of identification keys can be difficult as they are not usually intended for novice users who may not be familiar with the terminology used or with the morphology of the organism being identified. Therefore, we applied cognitive engineering principles to redesign a parasitology identification key for the Internet. We addressed issues of visual clutter and spatial distance by displaying a single question couplet at a time and by switching to the appropriate next couplet after the user made a choice. Our analysis of …

Construction Of Improved Temperature-Sensitive And Mobilizable Vectors And Their Use For Constructing Mutations In The Adhesin-Encoding Acm Gene Of Poorly Transformable Clinical Enterococcus Faecium Strains, Sreedhar R Nallapareddy, Kavindra V Singh, Barbara E Murray

Faculty, Staff and Student Publications

Inactivation by allelic exchange in clinical isolates of the emerging nosocomial pathogen Enterococcus faecium has been hindered by lack of efficient tools, and, in this study, transformation of clinical isolates was found to be particularly problematic. For this reason, a vector for allelic replacement (pTEX5500ts) was constructed that includes (i) the pWV01-based gram-positive repAts replication region, which is known to confer a high degree of temperature intolerance, (ii) Escherichia coli oriR from pUC18, (iii) two extended multiple-cloning sites located upstream and downstream of one of the marker genes for efficient cloning of flanking regions for double-crossover mutagenesis, (iv) transcriptional terminator …

Cart: An Hrs/Actinin-4/Berp/Myosin V Protein Complex Required For Efficient Receptor Recycling, Qing Yan, Wei Sun, Pekka Kujala, Yasmin Lotfi, Thomas A Vida, Andrew J Bean

Faculty, Staff and Student Publications

Altering the number of surface receptors can rapidly modulate cellular responses to extracellular signals. Some receptors, like the transferrin receptor (TfR), are constitutively internalized and recycled to the plasma membrane. Other receptors, like the epidermal growth factor receptor (EGFR), are internalized after ligand binding and then ultimately degraded in the lysosome. Routing internalized receptors to different destinations suggests that distinct molecular mechanisms may direct their movement. Here, we report that the endosome-associated protein hrs is a subunit of a protein complex containing actinin-4, BERP, and myosin V that is necessary for efficient TfR recycling but not for EGFR degradation. The …

Prime-Boost Vaccination With Plasmid And Adenovirus Gene Vaccines Control Her2/Neu+ Metastatic Breast Cancer In Mice, Xiaoyan Wang, Jian-Ping Wang, Xiao-Mei Rao, Janet E Price, Heshan S Zhou, Lawrence B Lachman

Faculty, Staff and Student Publications

INTRODUCTION: Once metastasis has occurred, the possibility of completely curing breast cancer is unlikely, particularly for the 30 to 40% of cancers overexpressing the gene for HER2/neu. A vaccine targeting p185, the protein product of the HER2/neu gene, could have therapeutic application by controlling the growth and metastasis of highly aggressive HER2/neu+ cells. The purpose of this study was to determine the effectiveness of two gene vaccines targeting HER2/neu in preventive and therapeutic tumor models.

METHODS: The mouse breast cancer cell line A2L2, which expresses the gene for rat HER2/neu and hence p185, was injected into the mammary fat pad …

The Recombinant Adeno-Associated Virus Vector (Raav2)-Mediated Apolipoprotein B Mrna-Specific Hammerhead Ribozyme: A Self-Complementary Aav2 Vector Improves The Gene Expression, Shumei Zhong, Shihua Sun, Ba-Bie Teng

Faculty, Staff and Student Publications

BACKGROUND: In humans, overproduction of apolipoprotein B (apoB) is positively associated with premature coronary artery diseases. To reduce the levels of apoB mRNA, we have designed an apoB mRNA-specific hammerhead ribozyme targeted at nucleotide sequences GUA6679 (RB15) mediated by adenovirus, which efficiently cleaves and decreases apoB mRNA by 80% in mouse liver and attenuates the hyperlipidemic condition. In the current study, we used an adeno-associated virus vector, serotype 2 (AAV2) and a self-complementary AAV2 vector (scAAV2) to demonstrate the effect of long-term tissue-specific gene expression of RB15 on the regulation apoB mRNA in vivo. METHODS: We constructed a hammerhead ribozyme …

In Vitro Analog Of Classical Conditioning Of Feeding Behavior In Aplysia, Riccardo Mozzachiodi, Hilde A. Lechner, Douglas A. Baxter, John H. Byrne

Faculty, Staff and Student Publications

The feeding behavior of Aplysia californica can be classically conditioned using tactile stimulation of the lips as a conditioned stimulus (CS) and food as an unconditioned stimulus (US). Moreover, several neural correlates of classical conditioning have been identified. The present study extended previous work by developing an in vitro analog of classical conditioning and by investigating pairing-specific changes in neuronal and synaptic properties. The preparation consisted of the isolated cerebral and buccal ganglia. Electrical stimulation of a lip nerve (AT4) and a branch of the esophageal nerve (En2) served as the CS and US, respectively. Three protocols were used: paired, …

Rigorously Assessing Whether The Data Backs The Back School, David T. Vinh, Craig W. Johnson, Cynthia L. Phelps

Faculty, Staff and Student Publications

A rigorous between-subjects methodology employing independent random samples and having broad clinical applicability was designed and implemented to evaluate the effectiveness of back safety and patient transfer training interventions for both hospital nurses and nursing assistants. Effects upon self-efficacy, cognitive, and affective measures are assessed for each of three back safety procedures. The design solves the problem of obtaining randomly assigned independent controls where all experimental subjects must participate in the training interventions.

Randomized Comparisons Among Health Informatics Students Identify Hypertutorial Features As Improving Web-Based Instruction, Craig W. Johnson, Yan Xing, Lan Yang

Faculty, Staff and Student Publications

Hypertutorials optimize five features - presentation, learner control, practice, feedback, and elaborative learning resources. Previous research showed graduate students significantly and overwhelmingly preferred Web-based hypertutorials to conventional "Book-on-the-Web" statistics or research design lessons. The current report shows that the source of hypertutorials' superiority in student evaluations of instruction lies in their hypertutorial features. Randomized comparisons between the two methodologies were conducted in two successive iterations of a graduate level health informatics research design and evaluation course. The two versions contained the same text and graphics, but differed in the presence or absence of hypertutorial features: Elaborative learning resources, practice, feedback, …

An Extended Hierarchical Task Analysis For Error Prediction In Medical Devices, Phillip H. Chung, Jiajie Zhang, Todd R. Johnson, Vimla L. Patel

Faculty, Staff and Student Publications

This paper introduces an extended hierarchical task analysis (HTA) methodology devised to evaluate and compare user interfaces on volumetric infusion pumps. The pumps were studied along the dimensions of overall usability and propensity for generating human error. With HTA as our framework, we analyzed six pumps on a variety of common tasks using Norman’s Action theory. The introduced method of evaluation divides the problem space between the external world of the device interface and the user’s internal cognitive world, allowing for predictions of potential user errors at the human-device level. In this paper, one detailed analysis is provided as an …

A Reduced Model Clarifies The Role Of Feedback Loops And Time Delays In The Drosophila Circadian Oscillator, Paul Smolen, Douglas A. Baxter, John H. Byrne

Faculty, Staff and Student Publications

Although several detailed models of molecular processes essential for circadian oscillations have been developed, their complexity makes intuitive understanding of the oscillation mechanism difficult. The goal of the present study was to reduce a previously developed, detailed model to a minimal representation of the transcriptional regulation essential for circadian rhythmicity in Drosophila. The reduced model contains only two differential equations, each with time delays. A negative feedback loop is included, in which PER protein represses per transcription by binding the dCLOCK transcription factor. A positive feedback loop is also included, in which dCLOCK indirectly enhances its own formation. The model …

Automated Medical Algorithms: Issues For Medical Errors, Kathy A. Johnson, John R. Svirbely, Mg Sriram, Jack W. Smith, Gareth Kantor, Jorge R. Rodriquez

Faculty, Staff and Student Publications

No abstract provided.

Redesign And Prototype For The Interface Of A Volumetric Infusion Pump Following The Usability Engineering Lifecycle, Juliana Brixey, John Frenzel, Michael Chalambaga, Todd R. Johnson

Faculty, Staff and Student Publications

No abstract provided.

Evaluating A Medical Error Taxonomy, Juliana Brixey, Todd R. Johnson, Jiajie Zhang

Faculty, Staff and Student Publications

Healthcare has been slow in using human factors principles to reduce medical errors. The Center for Devices and Radiological Health (CDRH) recognizes that a lack of attention to human factors during product development may lead to errors that have the potential for patient injury, or even death. In response to the need for reducing medication errors, the National Coordinating Council for Medication Errors Reporting and Prevention (NCC MERP) released the NCC MERP taxonomy that provides a standard language for reporting medication errors. This project maps the NCC MERP taxonomy of medication error to MedWatch medical errors involving infusion pumps. Of …

Focusing Feedback On Interpersonal Skills: Practice Makes Perfect A Web-Based Tutorial For Standardized Patients, Tamara Owens, Zhong Xie, Peggy Gregg, Cynthia Phelps, Craig W. Johnson

Faculty, Staff and Student Publications

Focusing Feedback on Interpersonal Skills: Practice Makes Perfect is a Web-Based learning environment enabling standardized patients (SPs) to develop, practice and enhance constructive feedback skills. The Web-based training environment for SPs features realistic professional healthcare provider/patient video scenarios, graphics, audio and immediate feedback in a student-centered self-instructional environment. SPs, who are trained to simulate an illness and portray a patient in a realistic and consistent way, subsequently provide feedback from a patient's perspective to students undergoing communication and interpersonal skills training in health science fields like medicine and nursing.

Toward A Cognitive Taxonomy Of Medical Errors, Jiajie Zhang, Vimla L Patel, Todd R Johnson, Edward H Shortliffe

Faculty, Staff and Student Publications

One critical step in addressing and resolving the problems associated with human errors is the development of a cognitive taxonomy of such errors. In the case of errors, such a taxonomy may be developed (1) to categorize all types of errors along cognitive dimensions, (2) to associate each type of error with a specific underlying cognitive mechanism, (3) to explain why, and even predict when and where, a specific error will occur, and (4) to generate intervention strategies for each type of error. Based on Reason's (1992) definition of human errors and Norman's (1986) cognitive theory of human action, we …

Intelligent Support Of Gait Analysis, Kathy A. Johnson, Sheldon R. Simon, Philip J. Smith, Jack W. Smith

Faculty, Staff and Student Publications

No abstract provided.

Population Amalgamation And Genetic Variation: Observations On Artificially Agglomerated Tribal Populations Of Central And South America, R Chakraborty, P E Smouse, J V Neel

Faculty, Staff and Student Publications

The interpretation of data on genetic variation with regard to the relative roles of different evolutionary factors that produce and maintain genetic variation depends critically on our assumptions concerning effective population size and the level of migration between neighboring populations. In humans, recent population growth and movements of specific ethnic groups across wide geographic areas mean that any theory based on assumptions of constant population size and absence of substructure is generally untenable. We examine the effects of population subdivision on the pattern of protein genetic variation in a total sample drawn from an artificial agglomerate of 12 tribal populations …

Parentage Analysis With Genetic Markers In Natural Populations I The Expected Proportion Of Offspring With Unambiguous Paternity, R Chakraborty, T R Meagher, P E Smouse

Faculty, Staff and Student Publications

Recent studies indicate that polymorphic genetic markers are potentially helpful in resolving genealogical relationships among individuals in a natural population. Genetic data provide opportunities for paternity exclusion when genotypic incompatibilities are observed among individuals, and the present investigation examines the resolving power of genetic markers in unambiguous positive determination of paternity. Under the assumption that the mother for each offspring in a population is unambiguously known, an analytical expression for the fraction of males excluded from paternity is derived for the case where males and females may be derived from two different gene pools. This theoretical formulation can also be …

Body Composition And Its Outcomes And Management In Multiple Sclerosis: Narrative Review, H W Van Landuyt, J Boelaert, P Piot, L Verbist

Faculty, Staff and Student Publications

Background: There is emerging interest in obesity and its prevalence, outcomes, and management in people with multiple sclerosis (MS). Body mass index (BMI) is the traditional marker of obesity in MS, whereas body composition, inclusive of specific body tissue compartments (e.g., fat, bone, and muscle), is often overlooked despite its relevance.

Objective: This narrative review (a) underscored the use and utility of dual-energy X-ray absorptiometry (DEXA) as an accurate and reliable measure of body composition; (b) thematically analyzed and synthesized the current evidence regarding body composition (using DEXA); and (c) determined gaps to be addressed in future research.

Methods: The …

Detection Of Nonrandom Association Of Alleles From The Distribution Of The Number Of Heterozygous Loci In A Sample, R Chakraborty

Faculty, Staff and Student Publications

The distribution of the number of heterozygous loci in two randomly chosen gametes or in a random diploid zygote provides information regarding the nonrandom association of alleles among different genetic loci. Two alternative statistics may be employed for detection of nonrandom association of genes of different loci when observations are made on these distributions: observed variance of the number of heterozygous loci (s2k) and a goodness-of-fit criterion (X2) to contrast the observed distribution with that expected under the hypothesis of random association of genes. It is shown, by simulation, that s2k is statistically more efficient than X2 to detect a …

Genetics And Epidemiology Of Gallbladder Disease In New World Native Peoples, K M Weiss, R E Ferrell, C L Hanis, P N Styne

Faculty, Staff and Student Publications

Native peoples of the New World, including Amerindians and admixed Latin Americans such as Mexican-Americans, are highly susceptible to diseases of the gallbladder. These include cholesterol cholelithiasis (gallstones) and its complications, as well as cancer of the gallbladder. Although there is clearly some necessary dietary or other environmental risk factor involved, the pattern of disease prevalence is geographically associated with the distribution of genes of aboriginal Amerindian origin, and levels of risk generally correspond to the degree of Amerindian admixture. This pattern differs from that generally associated with Westernization, which suggests a gene-environment interaction, and that within an admixed population …

Genetically Controlled Variation Of “Acid” Beta-Galactosidase Detected In Rattus Norvegicus By Isoelectric Focusing, T C Douglas, K A Kimmel, P E Dawson

Faculty, Staff and Student Publications

Two genetically variant forms of rat "acid" beta-galactosidase were found to differ in isoelectric point and pH dependence, but not in thermostability or sensitivity to inhibition by p-mercuribenzoate (PMB). The results of two backcrosses and an intercross indicated that the isoelectric focusing phenotypes are controlled by two codominant alleles at a single autosomal locus, for which we propose the name Glb-1. No significant linkage between Glb-1 and albino (LG I), brown (LG II), or hooded (LG VI) was observed. Strain-specific differences in total levels of kidney beta-galactosidase were detected, but it is not yet known whether the variation is controlled …

Three Linked Enzyme Loci In Fishes: Implications In The Evolution Of Vertebrate Chromosomes, D C Morizot, D A Wright, M J Siciliano

Faculty, Staff and Student Publications

A three-point linkage group comprised of loci coding for adenosine deaminase (ADA), glucose-6-phosphate dehydrogenase (G6PDH), and 6-phospho-gluconate dehydrogenase (6PGD) is described in fish of the genus Xiphophorus (Poeciliidae). The alleles at loci in this group were shown to assort independently from the alleles at three other loci--isocitrate dehydrogenase 1 and 2, and glyceraldehyde-3-phosphate dehydrogenase 1. Alleles at the latter three loci also assort independently from each other. Data were obtained by observing the segregation of electrophoretically variant alleles in reciprocal backcross hybrids derived from crosses between either X. helleri guentheri or X. h. strigatus and X. maculatus. The linkage component …