Medicine and Health Sciences Commons^™

Synchronization Of Pancreatic Islet Oscillations By Intrapancreatic Ganglia: A Modeling Study, B. Fendler, M. Zhang, L. Satin, R. Bertram

Pharmacology and Toxicology Publications

Abstract

Plasma insulin measurements from mice, rats, dogs, and humans indicate that insulin levels are oscillatory, reflecting pulsatile insulin secretion from individual islets. An unanswered question, however, is how the activity of a population of islets is coordinated to yield coherent oscillations in plasma insulin. Here, using mathematical modeling, we investigate the feasibility of a potential islet synchronization mechanism, cholinergic signaling. This hypothesis is based on well-established experimental evidence demonstrating intrapancreatic parasympathetic (cholinergic) ganglia and recent in vitro evidence that a brief application of a muscarinic agonist can transiently synchronize islets. We demonstrate using mathematical modeling that periodic pulses of …

In Silico Whole Genome Association Scan For Murine Prepulse Inhibition, Bradley Todd Webb, Joseph L. Mcclay, Cristina Vargas-Irwin, Timothy P. York, Edwin J. C. G. Van Den Oord

Biomarker Research and Personalized Medicine Publications

Background

The complex trait of prepulse inhibition (PPI) is a sensory gating measure related to schizophrenia and can be measured in mice. Large-scale public repositories of inbred mouse strain genotypes and phenotypes such as PPI can be used to detect Quantitative Trait Loci (QTLs) in silico. However, the method has been criticized for issues including insufficient number of strains, not controlling for false discoveries, the complex haplotype structure of inbred mice, and failing to account for genotypic and phenotypic subgroups.

Methodology/Principal Findings

We have implemented a method that addresses these issues by incorporating phylogenetic analyses, multilevel regression with mixed …

New Genomic Structure For Prostate Cancer Specific Gene Pca3 Within Bmcc1: Implications For Prostate Cancer Detection And Progression, Raymond A. Clarke, Zhongming Zhao, An-Yuan Guo, Kathrein Roper, Linda Teng, Zhi-Ming Fang, Hema Samaratunga, Martin F. Lavin, Robert A. Gardiner

Psychiatry Publications

Background

The prostate cancer antigen 3 (PCA3/DD3) gene is a highly specific biomarker upregulated in prostate cancer (PCa). In order to understand the importance of PCA3 in PCa we investigated the organization and evolution of the PCA3 gene locus.

Methods/Principal Findings

We have employed cDNA synthesis, RTPCR and DNA sequencing to identify 4 new transcription start sites, 4 polyadenylation sites and 2 new differentially spliced exons in an extended form of PCA3. Primers designed from these novel PCA3 exons greatly improve RT-PCR based discrimination between PCa, PCa metastases and BPH specimens. Comparative genomic analyses demonstrated that PCA3 has …

Dental Anatomy Carving Computer-Assisted Instruction Program: An Assessment Of Student Performance And Perceptions, Elizabeth T. Nance, Sharon K. Lanning, John C. Gunsolley

Periodontics Publications

The purpose of this study was to compare the performance of students exposed to two different instructional modalities for dental anatomy wax carving: CAI (computer-assisted instruction) using DVD technology, or traditional laboratory instruction. Students’ self-assessment scores were also compared to faculty scores, and students’ perceptions of their teaching modality were analyzed. Seventy-three first-year dental students (response rate 81 percent) participated in this randomized single blind trial, in which faculty graders were blinded to student group assignment. There were no statistical differences, as determined by the Wilcoxon non-parametric test and a t-test, between the faculty grades on the wax carving from …

Endothelial Cells And Pulmonary Arterial Hypertension: Apoptosis, Proliferation, Interaction And Transdifferentiation, Seiichiro Sakao, Koichiro Tatsumi, Norbert F. Voelkel

VCU Health Publications

Severe pulmonary arterial hypertension, whether idiopathic or secondary, is characterized by structural alterations of microscopically small pulmonary arterioles. The vascular lesions in this group of pulmonary hypertensive diseases show actively proliferating endothelial cells without evidence of apoptosis. In this article, we review pathogenetic concepts of severe pulmonary arterial hypertension and explain the term "complex vascular lesion ", commonly named "plexiform lesion", with endothelial cell dysfunction, i.e., apoptosis, proliferation, interaction with smooth muscle cells and transdifferentiation.

Dna Structure Modulates The Oligomerization Properties Of The Aav Initiator Protein Rep68, Jorge Mansilla-Soto, Miran Yoon-Robarts, William J. Rice, Shailee Arya, Carlos R. Escalante, R. Michael Linden

Physiology and Biophysics Publications

Rep68 is a multifunctional protein of the adeno-associated virus (AAV), a parvovirus that is mostly known for its promise as a gene therapy vector. In addition to its role as initiator in viral DNA replication, Rep68 is essential for site-specific integration of the AAV genome into human chromosome 19. Rep68 is a member of the superfamily 3 (SF3) helicases, along with the well-studied initiator proteins simian virus 40 large T antigen (SV40-LTag) and bovine papillomavirus (BPV) E1. Structurally, SF3 helicases share two domains, a DNA origin interaction domain (OID) and an AAA+ motor domain. The AAA+ motor domain is also …

Peginterferon Alfa-2b Or Alfa-2a With Ribavirin For Treatment Of Hepatitis C Infection, John G. Mchutchison, Eric J. Lawitz, Mitchell L. Shiffman, Andrew J. Muir, Greg W. Galler, Jonathan Mccone, Lisa M. Nyberg, William M. Lee, Reem H. Ghalib, Eugene R. Schiff, Joseph S. Galati M.D., Bruce R. Bacon, Mitchell N. Davis, Pabak Mukhopadhyay, Kenneth Koury, Stephanie Noviello, Lisa D. Pedicone, Clifford A. Bass, Janice K. Albrecht, Mark S. Sulkowski

Internal Medicine Publications

Background

Treatment guidelines recommend the use of peginterferon alfa-2b or peginterferon alfa-2a in combination with ribavirin for chronic hepatitis C virus (HCV) infection. However, these regimens have not been adequately compared.

Methods

At 118 sites, patients who had HCV genotype 1 infection and who had not previously been treated were randomly assigned to undergo 48 weeks of treatment with one of three regimens: peginterferon alfa-2b at a standard dose of 1.5 μg per kilogram of body weight per week or a low dose of 1.0 μg per kilogram per week, plus ribavirin at a dose of 800 to 1400 mg …

The Importance Of Saccular Function To Motor Development In Children With Hearing Impairments, Mary S. Shall

Physical Therapy Publications

Children with hearing deficits frequently have delayed motor development. The purpose of this study was to evaluate saccular function in children with hearing impairments using the Vestibular Evoked Myogenic Potential (VEMP). The impact of the saccular hypofunction on the timely maturation of normal balance strategies was examined using the Movement Assessment Battery for Children (Movement ABC). Thirty-three children with bilateral severe/profound hearing impairment between 4 and 7 years of age were recruited from a three-state area. Approximately half of the sample had one or bilateral cochlear implants, one used bilateral hearing aids, and the rest used no amplification. Parents reported …

Rcmat: A Regularized Covariance Matrix Approach To Testing Gene Sets, Phillip D. Yates, Mark A. Reimers

Biostatistics Publications

Background Gene sets are widely used to interpret genome-scale data. Analysis techniques that make better use of the correlation structure of microarray data while addressing practical "n

Results We evaluated our testing procedure using both simulated data and a widely analyzed diabetes data set. We compared our approach to another popular multivariate test for both sets of data. Our results suggest an increase in power for detecting gene set differences can be obtained using our approach relative to the popular multivariate test with no increase in the false positive rate.

Conclusion Our regularized covariance matrix multivariate approach to gene set …

Chaotic Signatures Of Heart Rate Variability And Its Power Spectrum In Health, Aging And Heart Failure, Guo-Qiang Wu, Natalia M. Arzeno, Lin-Lin Shen, Da-Kan Tang, Da-An Zheng, Nai-Qing Zhao, Dwain L. Eckberg, Chi-Sang Poon

VCU Health Publications

A paradox regarding the classic power spectral analysis of heart rate variability (HRV) is whether the characteristic high- (HF) and low-frequency (LF) spectral peaks represent stochastic or chaotic phenomena. Resolution of this fundamental issue is key to unraveling the mechanisms of HRV, which is critical to its proper use as a noninvasive marker for cardiac mortality risk assessment and stratification in congestive heart failure (CHF) and other cardiac dysfunctions. However, conventional techniques of nonlinear time series analysis generally lack sufficient sensitivity, specificity and robustness to discriminate chaos from random noise, much less quantify the chaos level. Here, we apply a …

Blanche Dubois Geriatrics, Edward F. Ansello

Director's Editorials from Age in Action

While the numbers of older adults are growing and the leading edge of the Baby Boom is in its 60s, aging-related education, service, and practice are far from burgeoning. We look forward to continuing Virginia's Geriatric Training and Education program, which produces geriatrically or gerontologically trained physicians, nurses, pharmacists, therapists, recreators, and social workers.

My Passage To India, Edward F. Ansello

Director's Editorials from Age in Action

Different cultures select different "colors" from the curriculum palette in painting the experience of aging as they see it. Aging is a construct, experienced amid and influenced by the norms, limitations, expectations, and horizons around us.

Sold A Bill Of Goods, Edward F. Ansello

Director's Editorials from Age in Action

With regard to Boomers, elders, and all of us growing older, we have been sold a bill of goods in America. Rather than independence, assisted autonomy is a means to empowerment and inclusion. Additionally, as we grow older, we grow less like our age mates, and dissimilarity and heterogeneity increases.

Awaken The Sleeping Giant, Edward F. Ansello

Director's Editorials from Age in Action

In order to maintain our commitment to quality, we in the Aging Network need to invest in the future despite the monetary problems of the present. In Virginia, older Virginians are a remarkable resource for our future.

Virginia's Money Follows The Person Demonstration, Jason A. Rachel, Karen Lawson

Case Studies from Age in Action

Educational Objectives

1. Describe Virginia's Money Follows the Person Demonstration project, including the new services available to individuals through Virginia's Medicaid-funded home and community-based waiver program.

2. Explain how Virginia's Money Follows the Person Demonstration project, being administered by the Virginia Department of Medical Assistance Services (DMAS), would assist an individual in transitioning from a long-term care facility to the community.

3. Illustrate how someone might experience the MFP processes from pre-transition through post-transition.

The Older Inmate, Tara Livengood

Case Studies from Age in Action

Educational Objectives

1. Present a general overview of elderly inmates, including statistics, characteristics, crimes, mental and medical illnesses, and disabilities.

2. Describe Virginia’s only geriatric correctional facility.

3. Explain the practice of release planning, focusing especially on geriatric release.

Sleep And Sleep Disorders In Later Life, Robert D. Vorona

Case Studies from Age in Action

Educational Objectives

1. Describe basic changes in sleep that occur as we age.

2. Review several important sleep disorders common in later life

3. Discuss treatment modalities for these sleep disorders and potential benefits of therapy.

Activity Engagement For Persons With Dementia, Barbara Braddock, Ellen Phipps

Case Studies from Age in Action

Educational Objectives

1. Describe a successful approach to activity engagement for persons with dementia.

2. Review three cognitive interventions useful for activity engagement for persons with dementia.

3. Discuss applications of this approach using university students in home visits.

Apoptotic Engulfment Pathway And Schizophrenia, Xiangning Chen, Cuie Sun, Qi Chen, F. Anthony O'Neill, Dermot Walsh, Ayman H. Fanous, Kodavali V. Chowdari, Vishwajit L. Nimgaonkar, Adrian Scott, Sibylle G. Schwab, Dieter B. Wildenauer, Ronglin Che, Wei Tang, Yongyong Shi, Lin He, Xiong-Jian Luo, Bing Su, Todd L. Edwards, Zhongming Zhao, Kenneth S. Kendler

Human and Molecular Genetics Publications

Background

Apoptosis has been speculated to be involved in schizophrenia. In a previously study, we reported the association of the MEGF10 gene with the disease. In this study, we followed the apoptotic engulfment pathway involving the MEGF10, GULP1, ABCA1 and ABCA7 genes and tested their association with the disease.

Methodology/Principal Findings

Ten, eleven and five SNPs were genotyped in the GULP1, ABCA1 and ABCA7 genes respectively for the ISHDSF and ICCSS samples. In all 3 genes, we observed nominally significant associations. Rs2004888 at GULP1 was significant in both ISHDSF and ICCSS samples (p = 0.0083 and …

The Servant Leader: A Higher Calling For Dental Professionals, Fred Certosimo

General Practice Publications

The dental profession is guided by normative principles that provide guidance to our leaders and practicing dentists in addressing the needs of patients and the profession, yet there is room for incorporating new ideas that help dental professionals meet their professional obligations. The purpose of this essay is to discuss the concept of “servant leadership,” especially in contrast with “self-serving leaders,” and to suggest that servant leadership is consistent with the high ethical and professional ideals of the dental profession. The servant leader is the antithesis of the self-serving leader, who incessantly seeks more power and acquisition of material possessions. …

Staphylococcus Aureus Immunodominant Surface Antigen B Is A Cell-Surface Associated Nucleic Acid Binding Protein, Nicole M. Mackey-Lawrence, Denise E. Potter, Nuno Cerca, Kimberly K. Jefferson

Microbiology and Immunology Publications

Background

Staphylococcus aureus immunodominant surface antigen B (IsaB) elicits an immune response during septicemia and is generally classified as a virulence factor, but its biological function remains completely undefined. In an attempt to identify staphylococcal RNA-binding proteins, we designed an RNA Affinity Chromatography assay and subsequently isolated IsaB.

Results

Western analysis indicated that IsaB was both secreted and cell-surface associated. Gel Shift analysis confirmed the RNA binding activity but revealed that IsaB bound to any nucleic acid without sequence specificity. IsaB exhibited the highest affinity for double-stranded DNA followed by single-stranded DNA and RNA. Because extracellular DNA has been shown …

Human T Cells Express Cd25 And Foxp3 Upon Activation And Exhibit Effector/Memory Phenotypes Without Any Regulatory/Suppressor Function, Maciej Kmieciak, Madhu Gowda, Laura Graham, Kamar Godder, Harry D. Bear, Francesco M. Marincola, Masoud H. Manjili

Microbiology and Immunology Publications

Background Foxp3 has been suggested to be a standard marker for murine Tregs whereas its role as marker for human Tregs is controversial. While some reports have shown that human Foxp3+ T cells had no regulatory function others have shown their role in the inhibition of T cell proliferation.

Methods T cell activation was performed by means of brayostatin-1/ionomycin (B/I), mixed lymphocyte reaction (MLR), and CD3/CD28 activation. T cell proliferation was performed using BrdU and CFSE staining. Flow cytometry was performed to determine Foxp3 expression, cell proliferation, viabilities and phenotype analyses of T cells.

Results Both CD4+ and CD8+ T …

Diagnosis Of Infections Caused By Pathogenic Free-Living Amoebae, Bruno Da Rocha-Azevedo, Herbert B. Tanowitz, Francine Marciano-Cabral

Microbiology and Immunology Publications

Naegleria fowleri, Acanthamoeba spp., Balamuthia mandrillaris, and Sappinia sp. are pathogenic free-living amoebae. N. fowleri causes Primary Amoebic Meningoencephalitis, a rapidly fatal disease of the central nervous system, whileAcanthamoeba spp. and B. mandrillaris cause chronic granulomatous encephalitis.Acanthamoeba spp. also can cause cutaneous lesions and Amoebic Keratitis, a sight-threatening infection of the cornea that is associated with contact lens use or corneal trauma. Sappinia pedata has been identified as the cause of a nonlethal case of amoebic encephalitis. In view of the potential health consequences due to infection with these amoebae, rapid diagnosis is critical for early treatment. Microscopic examination and …