Medicine and Health Sciences Commons^™

(R)-Β-Lysine Modified Elongation Factor P Functions In Translation Elongation, Tammy J. Bullwinkle, S. Betty Zou, Andrei Rajkovic, Steven J. Hersch, Sara Elgamal, Nathaniel Robinson, David Smil, Yuri Bolshan, William Wiley Navarre, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Post-translational modification of bacterial elongation factor P (EF-P) with (R)-β-lysine at a conserved lysine residue activates the protein in vivo and increases puromycin reactivity of the ribosome in vitro. The additional hydroxylation of EF-P at the same lysine residue by the YfcM protein has also recently been described. The roles of modified and unmodified EF-P during different steps in translation, and how this correlates to its physiological role in the cell, have recently been linked to the synthesis of polyproline stretches in proteins. Polysome analysis indicated that EF-P functions in translation elongation, rather than initiation as proposed previously. This was …

Piscine Myocarditis Virus (Pmcv) In Wild Atlantic Salmon Salmo Salar, Torstein Tengs Dr.

Dr. Torstein Tengs

Cardiomyopathy syndrome (CMS) is a severe cardiac disease of sea-farmed Atlantic salmon Salmo salar L., but CMS-like lesions have also been found in wild Atlantic salmon. In 2010 a double-stranded RNA virus of the Totiviridae family, provisionally named piscine myocarditis virus (PMCV), was described as the causative agent of CMS. In the present paper we report the first detection of PMCV in wild Atlantic salmon. The study is based on screening of 797 wild Atlantic salmon by real-time RT-PCR. The samples were collected from 35 different rivers along the coast of Norway, and all individuals included in the study were …

An Assessment Of The Effects Of Desertification In Yobe State, Nigeria, Jibril Musa Phd

Confluence Journal Environmental Studies (CJES), Kogi State University, Nigeria

Desertification is one of the most serious environmental and socio-economic problems of our time. Desertification describes circumstances of land degradation in arid, semi-arid and dry sub-humid regions resulting from the climatic variation and human activities. The fundamental goal of this thesis was to assess the effects of desertification in Yobe State, Nigeria. The present threat of desertification in the sahel has reached an alarming stage where crops cultivation and animal rearing/grazing are no more productive, soil has lost its nutrient/fertility, various infrastructure had given way because of windstorm from the neighbouring Niger Republic and sand dunes had taken over. The …

Human Calmodulin Methyltransferase: Expression, Activity On Calmodulin, And Hsp90 Dependence, Sophia Magen, Roberta Magnani, Sitvanit Haziza, Eli Hershkovitz, Robert Houtz, Franca Cambi, Ruti Parvari

Horticulture Faculty Publications

Deletion of the first exon of calmodulin-lysine N-methyltransferase (CaM KMT, previously C2orf34) has been reported in two multigene deletion syndromes, but additional studies on the gene have not been reported. Here we show that in the cells from 2p21 deletion patients the loss of CaM KMT expression results in accumulation of hypomethylated calmodulin compared to normal controls, suggesting that CaM KMT is essential for calmodulin methylation and there are no compensatory mechanisms for CaM methylation in humans. We have further studied the expression of this gene at the transcript and protein levels. We have identified 2 additional …

Tuning Of Alternative Splicing - Switch From Proto-Oncogene To Tumor Suppressor, Aleksandra Shchelkunova, Boris Ermolinsky, Meghan Boyle, Ivan Mendez, Michael Lehker, Karen S. Martirosyan, Alexander V. Kazanksy

Health & Biomedical Sciences Faculty Publications and Presentations

STAT5B, a specific member of the STAT family, is intimately associated with prostate tumor progression. While the full form of STAT5B is thought to promote tumor progression, a naturally occurring truncated isoform acts as a tumor suppressor. We previously demonstrated that truncated STAT5 is generated by insertion of an alternatively spliced exon and results in the introduction of an early termination codon. Present approaches targeting STAT proteins based on inhibition of functional domains of STAT's, such as DNA-binding, cooperative binding (protein-protein interaction), dimerization and phosphorylation will halt the action of the entire gene, both the proto-oncogenic and tumor suppressor functions …

Detecting Structure In Glass Patterns: An Interocular Transfer Study, Dawn Vreven, Jarrod Berge

Dawn L Vreven

Glass patterns are visual stimuli used here to study how local orientation signals are spatially integrated into global pattern perception. We measured a form aftereffect from adaptation to both static and dynamic Glass patterns and calculated the amount of interocular transfer to determine the binocularity of the detectors responsible for the perception of global structure. Both static and dynamic adaptation produced significant form aftereffects and showed a very high degree of interocular transfer, suggesting that Glass-pattern perception involves cortical processing beyond primary visual cortex. Surprisingly, dynamic adaptation produced significantly greater interocular transfer than static adaptation. Our results suggest a functional …

Using Remote Sensing Data To Improve Rice Production In Kutigi, Niger State, Nigeria, Jibril Musa Phd, M B. Yunusa

Confluence Journal Environmental Studies (CJES), Kogi State University, Nigeria

This research work looked in the used of Remote Sensing to improve Agricultural production in Kutigi, Niger State. The aim of the study is to use remote sensing to improve rice farming activities in Kutigi, Niger State. It is very important to identify such methods to improve Agricultural production because experts are always interested in new researches and findings to better the standard of living in any environment. In view of this, Remotely-sensed data could be used or employed to elevate most of these agricultural problems in Kutigi through the following objectives: Using Landsat imagery to assess the present landuse …

Persistence Of Episomal Hiv-1 Infection Intermediates In Patients On Highly Active Anti-Retroviral Therapy, Mark Sharkey, Ian Teo, Thomas Greenough, Natalia Sharova, Katherine Luzuriaga, John Sullivan, R. Bucy, Leondios Kostrikis, Ashley Haase, Claire Veryard, Raul Davaro, Sarah Cheeseman, Jennifer Daly, Carol Bova, Richard Ellison, Brian Mady, Kwan Lai, Graeme Moyle, Mark Nelson, Brian Gazzard, Sunil Shaunak, Mario Stevenson

Associate Professor Mark Nelson

Treatment of HIV-1-infected individuals with a combination of anti-retroviral agents results in sustained suppression of HIV-1 replication, as evidenced by a reduction in plasma viral RNA to levels below the limit of detection of available assays. However, even in patients whose plasma viral RNA levels have been suppressed to below detectable levels for up to 30 months, replication-competent virus can routinely be recovered from patient peripheral blood mononuclear cells and from semen. A reservoir of latently infected cells established early in infection may be involved in the maintenance of viral persistence despite highly active anti-retroviral therapy. However, whether virus replication …

Autonomic And Behavioral Reactivity To An Acute Laboratory Stressor, Jeremy C. Peres

University of New Orleans Theses and Dissertations

Stress has been widely shown to directly influence people’s emotional and behavioral processing as well as their underlying biological systems. This project examined physiological and behavioral responses as indicators of stress and coping in the context of a psychosocial stressor in a controlled laboratory setting. We examined the association between indicators of behavioral coping and underlying physiological reactivity within participants while experiencing stress. Participants included 68 emerging adults. Physiological measures include autonomic biomarkers (e.g., heart-rate, skin conductance) at rest and during the stressor while behavioral indicators that were coded include acute verbal and non-verbal actions exhibited by participants during the …

أمراض الأطفال المزمنة, Suad Fahad Alferaih

Dr. Suad Fahad AlFuraih

No abstract provided.

Association Of Ubqln1 Mutation With Brown-Vialetto-Van Laere Syndrome But Not Typical Als, Paloma Gonzalez-Perez, Yubing Lu, Ru-Ju Chian, Peter Sapp, Rudolph Tanzi, Lars Bertram, Diane Mckenna-Yasek, Fen-Biao Gao, Robert Brown

Dr Robert Brown

Genetic variants in UBQLN1 gene have been linked to neurodegeneration and mutations in UBQLN2 have recently been identified as a rare cause of amyotrophic lateral sclerosis (ALS). OBJECTIVE: To test if genetic variants in UBQLN1 are involved in ALS. METHODS: 102 and 94 unrelated patients with familial and sporadic forms of ALS were screened for UBQLN1 gene mutations. Single nucleotide variants were further screened in a larger set of sporadic ALS (SALS) patients and unrelated control subjects using high-throughput Taqman genotyping; variants were further assessed for novelty using the 1000Genomes and NHLBI databases. In vitro studies tested the effect of …

Dsarm/Sarm1 Is Required For Activation Of An Injury-Induced Axon Death Pathway, Jeannette Osterloh, Jing Yang, Timothy Rooney, A. Fox, Robert Adalbert, Eric Powell, Amy Sheehan, Michelle Avery, Rachel Hackett, Mary Logan, Jennifer Macdonald, Jennifer Ziegenfuss, Stefan Milde, Ying-Ju Hou, Carl Nathan, Aihao Ding, Robert Brown, Laura Comforti, Michael Coleman, Marc Tessier-Lavigne, Stephan Zuchner, Marc Freeman

Dr Robert Brown

Axonal and synaptic degeneration is a hallmark of peripheral neuropathy, brain injury, and neurodegenerative disease. Axonal degeneration has been proposed to be mediated by an active autodestruction program, akin to apoptotic cell death; however, loss-of-function mutations capable of potently blocking axon self-destruction have not been described. Here, we show that loss of the Drosophila Toll receptor adaptor dSarm (sterile alpha/Armadillo/Toll-Interleukin receptor homology domain protein) cell-autonomously suppresses Wallerian degeneration for weeks after axotomy. Severed mouse Sarm1 null axons exhibit remarkable long-term survival both in vivo and in vitro, indicating that Sarm1 prodegenerative signaling is conserved in mammals. Our results provide direct …

Genetic Determinants Of Cerebral Edema In Severe Traumatic Brain Injury: A Pilot Study Of The Role Of Cacna1 And Aqp4 Gene Mutations, Raphael A. Carandang, Susanne Muehlschlegel, Wiley R. Hall, Cynthia Ouillette, Robert H. Brown Jr.

Dr Robert Brown

Cerebral edema is the one of the most significant predictors of poor outcome after traumatic brain injury. It is still unclear what the pathophysiological and cellular mechanisms and predictors of post-traumatic edema are. The exponential growth in genetic information has opened an avenue for investigation in traumatic brain injury and implicated specific genes in the pathophysiology of post-traumatic injury edema. Two examples are the Aquaporin-4 and CACNA1 genes, which respectively encode water and calcium channels. The Aquaporin-4 gene on chromosome 18q11.2-12.1 encodes the Aquaporin-4 protein (AQP4) water channel. AQP4 is one of the bidirectional high capacity water channels that is …

Targeted Mutation Of Mouse Skeletal Muscle Sodium Channel Produces Myotonia And Potassium-Sensitive Weakness, Lawrence Hayward, Joanna Kim, Ming-Yang Lee, Hongru Zhou, Ji Kim, Kumudini Misra, Mohammad Salajegheh, Fen-Fen Wu, Shinji Matsuda, Valerie Reid, Didier Cros, Eric Hoffman, Jean-Marc Renaud, Stephen Cannon, Robert Brown

Dr Robert Brown

Hyperkalemic periodic paralysis (HyperKPP) produces myotonia and attacks of muscle weakness triggered by rest after exercise or by K+ ingestion. We introduced a missense substitution corresponding to a human familial HyperKPP mutation (Met1592Val) into the mouse gene encoding the skeletal muscle voltage-gated Na+ channel NaV1.4. Mice heterozygous for this mutation exhibited prominent myotonia at rest and muscle fiber-type switching to a more oxidative phenotype compared with controls. Isolated mutant extensor digitorum longus muscles were abnormally sensitive to the Na+/K+ pump inhibitor ouabain and exhibited age-dependent changes, including delayed relaxation and altered generation of tetanic force. Moreover, rapid and sustained weakness …

Decreased Metallation And Activity In Subsets Of Mutant Superoxide Dismutases Associated With Familial Amyotrophic Lateral Sclerosis, Lawrence Hayward, Jorge Rodriguez, Ji Kim, Ashutosh Tiwari, Joy Goto, Diane Cabelli, Joan Valentine, Robert Brown

Dr Robert Brown

Over 90 different mutations in the gene encoding copper/zinc superoxide dismutase (SOD1) cause approximately 2% of amyotrophic lateral sclerosis (ALS) cases by an unknown mechanism. We engineered 14 different human ALS-related SOD1 mutants and obtained high yields of biologically metallated proteins from an Sf21 insect cell expression system. Both the wild type and mutant "as isolated" SOD1 variants were deficient in copper and were heterogeneous by native gel electrophoresis. By contrast, although three mutant SOD1s with substitutions near the metal binding sites (H46R, G85R, and D124V) were severely deficient in both copper and zinc ions, zinc deficiency was not a …

Homologous Recombination Mediates Functional Recovery Of Dysferlin Deficiency Following Aav5 Gene Transfer, William E. Grose, K. Reed Clark, Danielle Griffin, Vinod Malik, Kimberly M. Shontz, Chrystal L. Montgomery, Sarah Lewis, Robert H. Brown Jr., Paul M. L. Janssen, Jerry R. Mendell, Louise R. Rodino-Klapac

Dr Robert Brown

The dysferlinopathies comprise a group of untreatable muscle disorders including limb girdle muscular dystrophy type 2B, Miyoshi myopathy, distal anterior compartment syndrome, and rigid spine syndrome. As with other forms of muscular dystrophy, adeno-associated virus (AAV) gene transfer is a particularly auspicious treatment strategy, however the size of the DYSF cDNA (6.5 kb) negates packaging into traditional AAV serotypes known to express well in muscle (i.e. rAAV1, 2, 6, 8, 9). Potential advantages of a full cDNA versus a mini-gene include: maintaining structural-functional protein domains, evading protein misfolding, and avoiding novel epitopes that could be immunogenic. AAV5 has demonstrated unique …

Geant4 Physics Processes For Microdosimetry Simulation: Design Foundation And Implementation Of The First Set Of Models, S. Chauvie, Z. Francis, S. Guatelli, S. Incerti, B. Mascialino, P. Moretto, P. Nieminen, Maria Pia

Susanna Guatelli

New physical processes specific for microdosimetry simulation are under development in the Geant4 Low Energy Electromagnetic package. The first set of models implemented for this purpose cover the interactions of electrons, protons and light ions in liquid water; they address a physics domain relevant to the simulation of radiation effects in biological systems, where water represents an important component. The design developed for effectively handling particle interactions down to a low energy scale and the physics models implemented in the first public release of the software are described.

Nutrition Status Of Primary Care Patients With Depression And Anxiety, Adrienne K. Forsyth, Peter G. Williams, Frank P. Deane

Frank Deane

The objective of this study was to evaluate the nutrition status of people referred to a nutrition and physical activity program for the management of mental health in a general practice.

Predicting Dropout In The First 3 Months Of 12-Step Residential Drug And Alcohol Treatment In An Australian Sample, Frank P. Deane, David J. Wootton, Ching-I Hsu, Peter J. Kelly

Frank Deane

Objective: Premature termination from treatment is a major factor associated with poorer drug and alcohol treatment outcomes. The present study investigated client-related baseline predictors of dropout at 3 months from a faith-based 12-step residential drug treatment program. Method: Data were collected over a period of 14 months from eight residential drug and alcohol treatment programs run by The Australian Salvation Army. The final sample consisted of 618 participants, including 524 men (84.8%) and 94 women (15.2%). Predictor variables of interest were age, gender, primary drug of concern, criminal involvement, psychological distress, drug cravings, self-efficacy to abstain, spirituality, forgiveness of self …

Prevalence Of Smoking And Other Health Risk Factors In People Attending Residential Substance Abuse Treatment, Peter J. Kelly, Amanda L. Baker, Frank P. Deane, Frances Kay-Lambkin, Billie Bonevski, Jenna Tregarthen

Frank Deane

Introduction and Aims. People attending substance abuse treatment have an elevated risk of developing cardiovascular disease (CVD) and cancer. Consequently, there have been increasing calls for substance abuse treatment services to address smoking.The current study examined smoking behaviours of people attending residential substance abuse treatment. Additionally, the study examined rates of other potentially modifiable health risk factors for the development of CVD and cancer. Design and Methods. A cross-sectional survey was completed by participants attending Australian Salvation Army residential substance abuse treatment services (n = 228). Rates of smoking, exercise, dietary fat intake, body mass index and depression were identified …

A Comparison Of Treatment Outcomes For Individuals With Substance Use Disorder Alone And Individuals With Probable Dual Diagnosis, Elizabeth K. Cridland, Frank P. Deane, Ching-I Hsu, Peter J. Kelly

Frank Deane

The co-occurrence of substance use and mental health problems, often referred to as dual diagnosis (DD), is increasingly recognised as commonplace within substance abuse treatment programs. Two-hundred and thirty-four individuals from 9 Australian Salvation Army drug and alcohol rehabilitation programs completed a 3-month post-discharge telephone follow-up. Using a cut-off score from the Psychiatric Subscale of the Addiction Severity Index (5th ed.), 66.7% were classified as likely to have DD and 33.3% as substance use disorder only (SUD). Both groups reported comparable and decreased substance use levels at follow-up, yet DD individuals perceived less improvement in substance use problems. Comparable improvements …

Molecular Characterization Of A Tetraspanin From The Human Liver Fluke, Opisthorchis Viverrini, Supawadee Piratae, Smarn Tesana, Malcolm K. Jones, Paul J. Brindley, Alex Loukas, Erica Lovas, Veerachai Eursitthichai, Banchob Sripa, Sirikanda Thanasuwan, Thewarach Laha

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

The human liver fluke, Opisthorchis viverrini, is designated as a group 1 carcinogen, and is the major risk factor for cholangiocarcinoma in endemic countries throughout Southeast Asia. Proteins in the excretory-secretory products and tegumental surface membranes of the fluke have been proposed to play pivotal roles in parasite survival in the host, and subsequent pathogenesis. These macromolecules are therefore valid targets for the development of vaccines and new drugs to control the infection. Tetraspanins (TSP) are prominent components of the tegument of blood flukes where they are essential for tegument formation, are directly exposed to the immune system, …

Involvement Of Interleukin-33/St2 In Myocardial Dysfunction In Murine Model Of Sepsis, Yoonmi Choe

Electronic Thesis and Dissertation Repository

The disruption of myocardial extracellular matrix (ECM) has been implicated in myocardial dysfunction during sepsis. However, the underlying mechanism(s) are not clear. Interleukin-33 (IL-33) is a cytokine which regulates collagen synthesis in various cardiac pathologies. The purpose of the present study is to test whether IL-33 contributes to sepsis-induced myocardial dysfunction through regulation of matrix metalloproteinase-9 (MMP-9). The in vivo, feces-induced peritonitis (FIP) in mice and in vitro lipopolysaccharide (LPS) treatments to isolated cardiomyocytes were used. In FIP mice, myocardial IL-33 and MMP-9 expression were increased and myocardial contractility was decreased. Myocardial function in FIP mice was improved when treated …

Selection Of Trna Charging Quality Control Mechanisms That Increase Mistranslation Of The Genetic Code, Srujana S. Yadavalli, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Mistranslation can follow two events during protein synthesis: production of non-cognate amino acid:transfer RNA (tRNA) pairs by aminoacyl-tRNA synthetases (aaRSs) and inaccurate selection of aminoacyl-tRNAs by the ribosome. Many aaRSs actively edit non-cognate amino acids, but editing mechanisms are not evolutionarily conserved, and their physiological significance remains unclear. To address the connection between aaRSs and mistranslation, the evolutionary divergence of tyrosine editing by phenylalanyl-tRNA synthetase (PheRS) was used as a model. Certain PheRSs are naturally error prone, most notably a Mycoplasma example that displayed a low level of specificity consistent with elevated mistranslation of the proteome. Mycoplasma PheRS was found …

Microrna Mir-155 Affects Antiviral Effector And Effector Memory Cd8 T Cell Differentiation, Ching-Yi Tsai, S. Rameeza Allie, Weijun Zhang, Edward J. Usherwood

Dartmouth Scholarship

MicroRNAs are key regulators of the immune response, but their role in CD8 T cell differentiation in vivo is not known. We show that miR-155 is important in both effector and memory antiviral CD8 T cell responses. Without miR-155, there was a weaker effector response and a skewing toward memory precursor cells. At the memory stage, miR-155-deficient CD8 T cells preferentially differentiated into central memory cells and were capable of mounting a potent secondary response.

Myeloid-Derived Suppressor Cells In Murine Retrovirus-Induced Aids Inhibit T- And B-Cell Responses In Vitro That Are Used To Define The Immunodeficiency, Kathy A. Green, W. James Cook, William R. Green

Dartmouth Scholarship

Myeloid-derived suppressor cells (MDSCs) have been characterized in several disease settings, especially in many tumor systems. Compared to their involvement in tumor microenvironments, however, MDSCs have been less well studied in their responses to infectious disease processes, in particular to retroviruses that induce immunodeficiency. Here, we demonstrate for the first time the development of a highly immunosuppressive MDSC population that is dependent on infection by the LP-BM5 retrovirus, which causes murine acquired immunodeficiency. These MDSCs express a cell surface marker signature (CD11b Gr-1 Ly6C ) characteristic of monocyte-type MDSCs. Such MDSCs profoundly inhibit immune responsiveness by a cell dose- and …

Updating The Dietadvice Website With New Australian Food Composition Data, Yasmine Probst, Holley-Anne Jones, Shannon Lin, S. Burden, David G. Steel, Linda C. Tapsell

Professor David Steel

DietAdvice is an Australian self-administered dietary assessment website initially developed in 2003- 2005. The website allows patients to enter their dietary information and dieticians to remotely access and interpret the data. DietAdvice is presently being updated with new Australian food composition data. This study aims to describe the update process for moving from 1995 to 2006 food composition data. The database for the website was developed using grouped food data from the NUTTAB 1995 database. All food groups were cross-matched with the food from the NUTTAB 2006 database using the food ID codes. Rules were applied to determine the suitability …

The Impact Of Complex Survey Design On Prevalence Estimates Of Intakes Of Food Groups In The Australian National Children's Nutrition And Physical Activity Survey, Sandy Burden, Yasmine Probst, David G. Steel, Linda C. Tapsell

Professor David Steel

No abstract provided.

Video-Recorded Usability Testing Of A Web-Based Self-Administered Dietary Assessment, Yasmine Probst, David Steel, Linda Tapsell

Professor David Steel

No abstract provided.

Us Patent #8,326,389 - A System For In Vivo Biosensing Based On The Optical Response, Arthur Epstein, Louis R. Nemzer

Louis R Nemzer

A system for continuous in vivo biosensing of specific analyte molecule concentrations based on the dynamic optical properties of electronic polymers is disclosed. The biosensor system includes at least one implant member subcutaneously exposed to the interstitial fluid of the subject, and a reader member at least temporarily positioned over the implant member to probe it with light of specific wavelengths through the skin. The system has many potential applications, including the real-time monitoring of blood glucose levels in diabetics as a method to supplement or replace conventional capillary blood testing.