Medicine and Health Sciences Commons^™

Naloxone's Pentapeptide Binding Site On Filamin A Blocks Mu Opioid Receptor–Gs Coupling And Creb Activation Of Acute Morphine, Hoau-Yan Wang, Lindsay H. Burns

Publications and Research

Chronic morphine causes the mu opioid receptor (MOR) to switch its coupling from Gi/o to Gs, resulting in excitatory signaling via both Gαs and its Gβγ dimer. Ultra-low-dose naloxone (NLX) prevents this switch and attenuates opioid tolerance and dependence. This protective effect is mediated via a high-affinity interaction of NLX to a pentapeptide region in c-terminal filamin A (FLNA), a scaffolding protein interacting with MOR. In organotypic striatal slice cultures, we now show that acute morphine induces a dose-dependent Go-to-Gs coupling switch at 5 and 15 min that resolves by 1 hr. The acute Gs coupling induced by 100 µM …

Corr4a And Vrt325 Do Not Reduce The Inflammatory Response To P. Aeruginosa In Human Cystic Fibrosis Airway Epithelial Cells, Laleh Talebian, Bonita Coutermarsh, Jacqueline Y. Channon, Bruce A. Stanton

Dartmouth Scholarship

P. aeruginosa chronically colonizes the lung in CF patients and elicits a proinflammatory response. Excessive secretion of IL-6 and IL-8 by CF airway cells in response to P. aeruginosa infection in the CF airway is though to contribute to lung injury. Accordingly, the goal of this study was to test the hypothesis that Corr4a and VRT325, investigational compounds that increase ΔF508-CFTR mediated Cl⁻ secretion in human CF airway cells, reduce the pro-inflammatory response to P. aeruginosa.

Scientific Components Of Dna Evidence: Molecular Biology And Population Genetics, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.

Hepatitis B Virus Subgenotypes D1 And D3 Are Prevalent In Pakistan, Anwar Ali Siddiqui, Saeeda Baig, Runu Chakravarty Runu Chakravarty, Tariq Moatter

Department of Biological & Biomedical Sciences

Background:

As the hepatitis B genotyping is important for assessing its clinical implications and geographical distribution, the sub-genotypes have been found useful for determination of specific genomic markers related to hepatocarcinogenesis. In Pakistan, there is no reported data on molecular evolutionary analysis of HBV. A study was, therefore, much needed to evaluate the spectra of mutations present in the strains prevalent here.

Findings:

To confirm specificity of PCR typing, phylogenetic analysis of the pre-S1 region and the divergence was studied through 13 sequences of 362 bp (accession number EF432765 – EF432777). A total of 315 serum samples, selected from HBsAg …

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 …

Effect Of Growth Hormone On Hippocampal Synaptic Function During Sleep Deprivation, Eun Young Kim

Theses, Dissertations and Capstones

Long term potentiation (LTP) in the hippocampus is considered a cellular basis of learning memory. Sleep deprivation, especially rapid eye movement (REM) sleep deprivation, impairs learning and memory as well as LTP. Since most of the previous LTP studies were conducted in the in vitro condition, the full consequences of sleep deprivation (SD) in the living animal are yet to be found. Thus, I tested hippocampal LTP in living animals after 5 days of REM sleep deprivation to determine the effect of SD in vivo. SD also disrupts growth hormone (GH) release. Recent evidence indicates that GH regulates cognitive and …

Loss Of Ski Expression In Testicular Cancer Leads To An Enhanced Invasive Phenotype Through Both Bmp-Dependent And Bmp-Independent Pathways, Amy N. Nash

Theses, Dissertations and Capstones

The proto-oncogene SKI is a transcription factor and a co-repressor of the TGFβ superfamily, including TGF

β and BMP. However, additional data suggests that SKI may function as a tumor suppressor in some cell types. The TGFβ superfamily has been implicated in cancer progression and germ cell migration. Testicular cancer afflicts men during their peak reproductive years and is the most common cancer among men of this age group. Cisplatin-based chemotherapy is the standard treatment for testicular cancer. This treatment can lead to undesirable side effects, including infertility. We have shown that SKI expression is decreased in testicular germ cell …

Effects Of Microgravity On Cancer Stem Cells Cultured In A Nasa Developed Bioreactor: Chemotherapeutic Implications., Sarah Elizabeth Daron Kelly

Theses, Dissertations and Capstones

The purpose of this study was to investigate the effects of simulated microgravity on cancer cell growth. Simulated microgravity is a condition in which cells are in constant free-fall and in which they are able to grow suspended without the shear and stress. Microgravity allows for important insights into the cellular mechanism and may be key in understanding why some cells thrive in this condition and others go into apoptosis. Cancer stem cells (CSCs) are considered a subset of the bulk tumor responsible for initiating and maintaining cancer. SAOS-2 is a human bone cancer cell line which consists of a …

Deferasirox Decreases Age-Associated Iron Accumulation In The Aging F344bn Rat Heart, Ravi K. Arvapalli

Theses, Dissertations and Capstones

It is thought that aging in rats and humans is associated with increases in iron accumulation and these increases in iron may be associated with increased cellular apoptosis. Here we examine the relationship between cardiac iron levels and cardiomyocyte apoptosis in aged F344BN rats which were treated with an oral iron chelator (Deferasirox; 100mg/kg body. weight/day) for 6 months. Compared with 6- month controls, the levels of cardiac iron, cardiac apoptosis, FLC and DMT-1 were higher in 33-month hearts. Deferasirox treatment for six months decreased cardiac iron and this was associated with decreases in the number of apoptotic cardiac myocytes. …

Fusion, 2009, George Washington University, William H. Beaumont Medical Research Honor Society

Fusion

No abstract provided.

Interactions Of Alkali Cations With Glutamate Transporters, David C. Holley, Michael P. Kavanaugh

Biomedical and Pharmaceutical Sciences Faculty Publications

The transport of glutamate is coupled to the co-transport of three Na+ ions and the countertransport of one K+ ion. In addition to this carrier-type exchange behaviour, glutamate transporters also behave as chloride channels. The chloride channel activity is strongly influenced by the cations that are involved in coupled flux, making glutamate transporters representative of the ambiguous interface between carriers and channels. In this paper, we review the interaction of alkali cations with glutamate transporters in terms of these diverse functions. We also present a model derived from electrostatic mapping of the predicted cation-binding sites in the X-ray crystal structure …

Nerve, Muscle, Blood, Toil, Tears, And Sweat: England’S Pioneering Biophysicist, Soldier, And Statesman, Arshad Khan

Selected Works Temporary Series

No abstract provided.

Group Feeding For The Lactating Cow, Anthony Joseph Martin

Dairy Science

Feeding individualized rations for lactating dairy cattle in the commercial herd based on dietary needs is a popular issue. This has been a debating topic since evolution of the Total Mixed Ration (TMR). Since dairymen were able to mix grain in a feed wagon and mix a specific dietary ration to meet the demand for an organized group, there has been an issue in which protocol cow pen grouping should take. Dairymen have always feed cattle based on if lactating or late in their gestation, nonlactating. With the evolution of the TMR dairymen are then allowed to go into more …

Saving Lives And Changing Family Histories: Appropriate Counseling Of Pregnant Women And Men And Women Of Reproductive Age, Concerning The Risk Of Radiation Exposures During And Before Pregnancy, Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

Apd2: The Updated Antimicrobial Peptide Database And Its Application In Peptide Design., Guangshun Wang, Xia Li, Zhe Wang

Journal Articles: Pathology and Microbiology

The antimicrobial peptide database (APD, http://aps.unmc.edu/AP/main.php) has been updated and expanded. It now hosts 1228 entries with 65 anticancer, 76 antiviral (53 anti-HIV), 327 antifungal and 944 antibacterial peptides. The second version of our database (APD2) allows users to search peptide families (e.g. bacteriocins, cyclotides, or defensins), peptide sources (e.g. fish, frogs or chicken), post-translationally modified peptides (e.g. amidation, oxidation, lipidation, glycosylation or d-amino acids), and peptide binding targets (e.g. membranes, proteins, DNA/RNA, LPS or sugars). Statistical analyses reveal that the frequently used amino acid residues (>10%) are Ala and Gly in bacterial peptides, Cys and Gly in plant …

Epithelial Cell Gene Expression Induced By Intracellular Staphylococcus Aureus., Xianglu Li, William G. Fusco, Keun S. Seo, Kenneth W. Bayles, Erin E. Mosley, Mark A. Mcguire, Gregory A. Bohach

Journal Articles: Pathology and Microbiology

HEp-2 cell monolayers were cocultured with intracellular Staphylococcus aureus, and changes in gene expression were profiled using DNA microarrays. Intracellular S. aureus affected genes involved in cellular stress responses, signal transduction, inflammation, apoptosis, fibrosis, and cholesterol biosynthesis. Transcription of stress response and signal transduction-related genes including atf3, sgk, map2k1, map2k3, arhb, and arhe was increased. In addition, elevated transcription of proinflammatory genes was observed for tnfa, il1b, il6, il8, cxcl1, ccl20, cox2, and pai1. Genes involved in proapoptosis and fibrosis were also affected at transcriptional level by intracellular S. aureus. Notably, intracellular S. aureus induced strong transcriptional down-regulation of several …

Viewing Preschool Disruptive Behavior Disorders And Attention-Deficit/Hyperactivity Disorder Through A Developmental Lens: What We Know And What We Need To Know, Anil Chacko, Lauren Wakschlag, Carri Hill, Barbara Danis, Kimberly A. Espy

Developmental Cognitive Neuroscience Laboratory: Faculty Publications

Although DSM-defined DBDs and ADHD manifest during early childhood in meaning¬ful ways, the emphasis of extending the DBD and ADHD nosology, which is based on studies of older youth, to younger children potentially limits the utility of these symptoms. Given that it is clear that DBDs and ADHD often emerge during early childhood and that early intervention is most efficacious, developing a more refined understanding of the clinical phenomenology of behavior disorders in early childhood is a critical next step. We contend that an approach that emphasizes the developmental specification of symptoms has the potential to address several long-standing issues …

Efficacy Of Deferasirox In Preventing Complications Of Iron Overload In The Iron Overloaded Gerbil, Rabaa M. Al-Rousan

Theses, Dissertations and Capstones

Iron overload is a significant, world-wide problem that results in several chronic diseases including cardiovascular, hepatic and pancreatic complications.The newly developed, orally effective, iron chelating agent deferasirox is thought to offer tremendous promise as an alternative to deferoxamine. However, the efficacy and safety profile of deferasirox is not yet clear. In the present study, the efficacy of deferasirox in removing iron from target tissues has been examined using the gerbil model of iron overload. Deferasirox administration resulted in a significant reduction of iron from cardiac and hepatic tissue. In addition deferasirox reduced iron induced increase in cardiac and hepatic oxidative …

Urinary Levoglucosan As A Biomarker Of Wood Smoke Exposure: Observations In A Mouse Model And In Children, Christopher T. Migliaccio, M. A. Bergauff, Christopher P. Palmer, Forrest Jessop, Curtis W. Noonan, Tony Ward

Biomedical and Pharmaceutical Sciences Faculty Publications

BACKGROUND: Biomass smoke is an important source of particulate matter (PM), and much remains to be discovered with respect to the human health effects associated with this specific PM source. Exposure to biomass smoke can occur in one of two main categories: short-term exposures consist of periodic, seasonal exposures typified by communities near forest fires or intentional agricultural burning, and long-term exposures are chronic and typified by the use of biomass materials for cooking or heating. Levoglucosan (LG), a sugar anhydride released by combustion of cellulose-containing materials, is an attractive candidate as a biomarker of wood smoke exposure. OBJECTIVES: In …

Light-Induced Fos Expression In Intrinsically Photosensitive Retinal Ganglion Cells In Melanopsin Knockout (Opn4-/-) Mice, Gary E. Pickard, Scott B. Baver, Malcolm D. Ogilvie, Patricia J. Sollars

School of Veterinary and Biomedical Sciences: Faculty Publications

Retinal ganglion cells that express the photopigment melanopsin are intrinsically photosensitive (ipRGCs) and exhibit robust synaptically driven ON-responses to light, yet they will continue to depolarize in response to light when all synaptic input from rod and cone photoreceptors is removed. The light-evoked increase in firing of classical ganglion cells is determined by synaptic input from ON-bipolar cells in the proximal sublamina of the inner plexiform layer. OFF-bipolar cells synapse with ganglion cell dendrites in the distal sublamina of the inner plexiform layer. Of the several types of ipRGC that have been described, M1 ipRGCs send dendrites exclusively into the …

A Dissociation Between Perception And Action In The Material‐Weight Illusion, Gavin Buckingham, Jonathan S. Cant, Kai-Ling C. Kao, Melvyn A. Goodale

Psychology Presentations

We examined what forces are applied to objects that elicit this illusion when they are lifted.We predicted that:

(1) Forces on early trials will scale to each participant’s expectations of how much a particular block will weigh ‐ excessive force will be applied to the metal block and insufficient force applied to the polystyrene block.

(2) Forces on later trials will scale to the real weight of each block ‐ identical levels of force applied to all the blocks.

(3) MWI will persist throughout ‐ polystyrene block will feel the heaviest, metal block will feel the lightest.

Grasping And Lifting Different Materials, Gavin Buckingham, Jonathan S. Cant, Melvyn A. Goodale

Psychology Presentations

The material from which an object is made can determine how heavy it feels (Seashore, 1899). Interestingly, a metal block that has been adjusted to have the same size and mass as a polystyrene block will feel lighter than the polystyrene block. We recently showed that participants experiencing this material-weight illusion’ (MWI) do not apply forces that match their perceptual experience of heaviness ‐ just like in the size‐weight illusion ( Flanagan & Beltzner, 2000).

Our previous study showed that forces on early trials were scaled to each participant’s expectations of how much a particular block should weigh ‐ excessive …

Identification Of Wnt/Β-Catenin Signaling Pathway Components In Human Cumulus Cells, Hong-Xing Wang, Francis R. Tekpetey, Gerald M. Kidder

Physiology and Pharmacology Publications

Signaling via the conserved WNT/β-CATENIN pathway controls diverse developmental processes. To explore its potential role in the ovary, we investigated the expression of WNTs, frizzled (FZD) receptors and other pathway components in human cumulus cells obtained from oocytes collected for in vitro fertilization. Proteins were detected in cultured cells using immunofluorescence microscopy. Protein–protein interactions were analyzed by means of immunoprecipitation. WNT2, FZD2, FZD3 and FZD9 were identified but WNT1, WNT4 and FZD4 were not detected. WNT2 is co-expressed with FZD2, FZD3 and FZD9. Co-immunoprecipitation using WNT2 antibody demonstrated that WNT2 interacts with both FZD3 and FZD9, but only FZD9 antibody …

Adaptive Radiation Therapy For Localized Mesothelioma With Mediastinal Metastasis Using Helical Tomotherapy., James Renaud, Slav Yartsev, A Rashid Dar, Jacob Van Dyk

Oncology Publications

The purpose of this study was to compare 2 adaptive radiotherapy strategies with helical tomotherapy. A patient having mesothelioma with mediastinal nodes was treated using helical tomotherapy with pretreatment megavoltage CT (MVCT) imaging. Gross tumor volumes (GTVs) were outlined on every MVCT study. Two alternatives for adapting the treatment were investigated: (1) keeping the prescribed dose to the targets while reducing the dose to the OARs and (2) escalating the target dose while maintaining the original level of healthy tissue sparing. Intensity modulated radiotherapy (step-and-shoot IMRT) and 3D conformal radiotherapy (3DCRT) plans for the patient were generated and compared. The …

Growth Mixture Modeling Of Academic Achievement In Children Of Varying Birth Weight Risk, Kimberly A. Espy, Julia Hua Fang, David Charak, Nori Minich, H. Gerry Taylor

Developmental Cognitive Neuroscience Laboratory: Faculty Publications

The extremes of birth weight and preterm birth are known to result in a host of adverse outcomes, yet studies to date largely have used cross-sectional designs and variable-centered methods to understand long-term sequelae. Growth mixture modeling (GMM) that utilizes an integrated person- and variable-centered approach was applied to identify latent classes of achievement from a cohort of school-age children born at varying birth weights. GMM analyses revealed 2 latent achievement classes for calculation, problem-solving, and decoding abilities. The classes differed substantively and persistently in proficiency and in growth trajectories. Birth weight was a robust predictor of class membership for …

Power Of Models In Longitudinal Study: Findings From A Full- Crossed Simulation Design, Hua Fang, Gordon P. Brooks, Maria L. Rizzo, Kimberly A. Espy, Robert S. Barcikowski

Developmental Cognitive Neuroscience Laboratory: Faculty Publications

Because the power properties of traditional repeated measures and hierarchical multivariate linear models have not been clearly determined in the balanced design for longitudinal studies in the literature, the authors present a power comparison study of traditional repeated measures and hierarchical multivariate linear models under 3 variance-covariance structures. The results from a full-crossed simulation design suggest that traditional repeated measures have significantly higher power than do hierarchical multivariate linear models for main effects, but they have significantly lower power for interaction effects in most situations. Significant power differences are also exhibited when power is compared across different covariance structures.

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 …

Nerve, Muscle, Blood, Toil, Tears, And Sweat: England’S Pioneering Biophysicist, Soldier, And Statesman, Khan

Departmental Papers (Biology)

No abstract provided.

Reduced Genomic Potential For Secreted Plant Cell-Wall-Degrading Enzymes In The Ectomycorrhizal Fungus Amanita Bisporigera, Based On The Secretome Of Trichoderma Reesei, Subashini Nagendran, Heather E. Hallen-Adams, Janet M. Paper, Nighat Aslam, Jonathan D. Walton

Heather Hallen-Adams Publications

Based on the analysis of its genome sequence, the ectomycorrhizal (ECM) basidiomycetous fungus Laccaria bicolor was shown to be lacking many of the major classes of secreted enzymes that depolymerize plant cell wall polysaccharides. To test whether this is also a feature of other ECM fungi, we searched a survey genome database of Amanita bisporigera with the proteins found in the secretome of Trichoderma reesei (syn. Hypocrea jecorina), a biochemically well-characterized industrial fungus. Additional proteins were also used as queries to compensate for major groups of cell-wall-degrading enzymes lacking in the secretome of T. reesei and to substantiate conclusions …

Identification And Characterization Of Novel Sir3/Mecp2-Chromatin Interactions, Nicholas L. Adkins

Theses, Dissertations and Capstones

The eukaryotic genome is packaged into chromosomes that are made up of a highly organized and heavily regulated structure called chromatin. The proteins involved in the compaction of DNA into this condensed state are mostly understood at the level of the structure of the nucleosome. The higher order arrangement of chromatin and how it effects gene regulation is only partially understood and characterized. The compaction of nucleosomal arrays into 30-nm and higher structures are partially the responsibility of architectural, or structural, chromatin associated proteins. The following dissertation analyzes the individual chromatin contributions of two well studied architectural proteins, the yeast …