Medical Sciences Commons^™

The Effect Of Nonassociative Learning On Oxidative Stress In Caenorhabditis Elegans: A Potential Application For Alzheimer’S Disease Research, Gillian Patton

Journal of the South Carolina Academy of Science

Alzheimer’s disease results in learning and memory deficits due to toxic changes in the brain caused by amyloid-β plaques and oxidative stress. Oxidative stress is caused by the overproduction of free radicals, which are uncharged molecules containing an unpaired valence electron. Nonassociative learning is a type of cognitive processing that only uses one stimulus instead of two related stimuli. Cognitive processing promotes neural growth and learning, while Alzheimer’s inhibits it. The purpose of this study was to test how nonassociative learning impacts oxidative stress and thus, if it might be considered as a potential treatment option for Alzheimer ...

The Effect Of Flavonoid Galangin On The Cell Viability And Toxicity Of Mcf-7 Human Breast Cancer Cells Exposed To Polycyclic Aromatic Hydrocarbons (Pahs), Abhimanyu Sailesh

Journal of the South Carolina Academy of Science

Polycyclic aromatic hydrocarbons (PAHs) are chemical compounds ubiquitous in the environment; many of which are known human and animal carcinogen. The purpose of this study was to investigate MCF-7 epithelial breast cancer cells’ viability and toxicity following a short-term in vitro exposure to a cocktail of PAHs and benzo[a]pyrene (B[a]P) separately in the presence and absence of varying concentrations of flavonoid galangin. It was predicted that presence of galangin will completely or partially block the damaging effects of PAHs. It was hypothesized that exposing the cells to 7 µM cocktail of PAHs or 10 µM B ...

Epha4b Expression In The Craniofacial Development Of African Cichlid Fishes, Chelse Vanatter

Journal of the South Carolina Academy of Science

Epha4b gene expression may contribute to variances in facial formation including functional differences such as nose shape and clinical conditions such as cleft palate. During craniofacial development, neural crest cells migrate to the pharyngeal arches then differentiate to form bone, muscle, and cartilage cells. The Eph/ephrin signaling pathway guides the streams of migrating neural crest cells into the pharyngeal arches; epha4b, a gene encoding an Eph receptor, contributes to this signaling pathway. To determine how epha4b expression differs between species at different developmental stages, in situ hybridization, a process that stains areas of gene expression, was performed. African cichlid ...

The Effects Of Oxidative Stress On Inducing Senescence In Human Fibroblasts, Shivani Chowdhary

Journal of the South Carolina Academy of Science

Oxidative stress, specifically from hydrogen peroxide exposure, was performed to determine if it induced senescence in cell lines such as Hela cells and primary human fibroblasts. The purpose of this experiment was to find the optimal stage, concentration, and time of exposure to induce the greatest number of senescent cells. After dividing cultures of both the Hela and human fibroblasts cells in order to reduce confluency, the cells were placed in a six well plate and exposed to hydrogen peroxide for two hours at various concentrations. The plates were checked at twenty-four-hour intervals, and then fixed with senescence associated beta-galactosidase ...

The Effect Of Acetaminophen (Analgesic) And Diphenhydramine (Antihistamine) On Nociception Response Of Caenorhabditis Elegans, Heart Rate Of Eisenia Fetida, And Mortality Of Both E. Fetida And C. Elegans, Vamsi Gorrepati

Journal of the South Carolina Academy of Science

Pharmaceutical pollution continues to increase each year but its adverse effects on the environment are still largely unknown. Pharmaceuticals can enter the terrestrial ecosystem when animal manure and sewage sludge are applied to land as a fertilizer or when irrigated with contaminated water. To understand the extent to which common drugs impact the ecosystem, two commonly polluting pharmaceuticals, acetaminophen and diphenhydramine, which have been found in many cities such as Chicago, Dallas, and most notably The Great Lakes, were studied. Various concentrations were tested on E. fetida and C. elegans. Indicators such as heart rate were observed for E. fetida ...

A “Diagnosis Method" For The Analysis Of Epidemiological Studies. A Reevaluation Of Pan, Et Al. Arch Intern Med 2012, 172:555., Richard D. Feinman, Eugene J. Fine

Journal of Evolution and Health

The medical literature has been subject to extensive criticism for a lack of accuracy and reproducibility. A major cause, in our view, is misleading or inappropriate presentation and interpretation of statistical results. Emphasis on percentages or relative values (odds ratios, relative risk, and hazard ratio) always reduces and often obscures information. We suggest a more direct method using the 2 x 2 matrix commonly employed in diagnosis testing. We demonstrate the “diagnosis method,” by evaluating a previously published paper (Pan A, et al.: Arch Intern Med 2012, 172:555-563). on the risk of red meat for disease, focussing on cancer ...

Principles For Enhancing Virus Capsid Capacity And Stability From A Thermophilic Virus Capsid Structure, Nicholas P. Stone, Gabriel Demo, Emily Agnello, Brian A. Kelch

University of Massachusetts Medical School Faculty Publications

The capsids of double-stranded DNA viruses protect the viral genome from the harsh extracellular environment, while maintaining stability against the high internal pressure of packaged DNA. To elucidate how capsids maintain stability in an extreme environment, we used cryoelectron microscopy to determine the capsid structure of the thermostable phage P74-26. We find the P74-26 capsid exhibits an overall architecture that is very similar to those of other tailed bacteriophages, allowing us to directly compare structures to derive the structural basis for enhanced stability. Our structure reveals lasso-like interactions that appear to function like catch bonds. This architecture allows the capsid ...

Debrowser: Interactive Differential Expression Analysis And Visualization Tool For Count Data, Alper Kucukural, Onur Yukselen, Deniz M. Ozata, Melissa J. Moore, Manuel Garber

Program in Bioinformatics and Integrative Biology Publications and Presentations

BACKGROUND: Sequencing data has become a standard measure of diverse cellular activities. For example, gene expression is accurately measured by RNA sequencing (RNA-Seq) libraries, protein-DNA interactions are captured by chromatin immunoprecipitation sequencing (ChIP-Seq), protein-RNA interactions by crosslinking immunoprecipitation sequencing (CLIP-Seq) or RNA immunoprecipitation (RIP-Seq) sequencing, DNA accessibility by assay for transposase-accessible chromatin (ATAC-Seq), DNase or MNase sequencing libraries. The processing of these sequencing techniques involves library-specific approaches. However, in all cases, once the sequencing libraries are processed, the result is a count table specifying the estimated number of reads originating from each genomic locus. Differential analysis to determine which loci ...

Quantitative Clinical And Autoimmune Assessments In Stiff Person Syndrome: Evidence For A Progressive Disorder., Goran Rakocevic, Harry Alexopoulos, Marinos C. Dalakas

Department of Neurology Faculty Papers

BACKGROUND: Stiff Person Syndrome (SPS) is an under-diagnosed disorder that affects mobility and the quality of life of affected patients. The aim of the study is to describe the natural history of SPS, the extent of accumulated disability and the associated clinical and immunological features in patients followed for up to 8 years in a single center.

METHODS: Our collective cohort included 57 SPS patients. Additionally, 32 of these patients were examined every 6 months for a two-year period in a longitudinal study protocol, to assess disease progression using quantitative measures of stiffness and heightened sensitivity.

RESULTS: The most frequent ...

Table Of Contents

Journal of the South Carolina Academy of Science

No abstract provided.

Analytical Validation Of A Prognostic Prostate Cancer Gene Expression Assay Using Formalin Fixed Paraffin Embedded Tissue., Paul W. Medlow, Christopher J. Steele, Andrena M. Mccavigan, Wesley Reardon, Christopher M. Brown, Shauna M. Lambe, Felipe Aa Ishiy, Steven M. Walker, Gemma E. Logan, Olaide Y. Raji, Viktor Berge, Betina Katz, Elaine W. Kay, Katherine M. Sheehan, Ronald W. Watson, Denis P. Harkin, Richard D. Kennedy, Laura A. Knight

Pathology Articles

BACKGROUND: There is a clear need for assays that can predict the risk of metastatic prostate cancer following curative procedures. Importantly these assays must be analytically robust in order to provide quality data for important clinical decisions. DNA microarray based gene expression assays measure several analytes simultaneously and can present specific challenges to analytical validation. This study describes the analytical validation of one such assay designed to predict metastatic recurrence in prostate cancer using primary formalin fixed paraffin embedded tumour material.

METHODS: Accuracy was evaluated with a method comparison study between the assay development platform (Prostate Disease Specific Array) and ...

Toll-Like Receptor-4 Disruption Suppresses Adipose Tissue Remodeling And Increases Survival In Cancer Cachexia Syndrome, Felipe Henriques, Magno A. Lopes, Felipe O. Franco, Pamela Knobl, Kaltinaitis B. Santos, Luana L. Bueno, Victor A. Correa, Alexander H. Bedard, Adilson L. Guilherme, Alexander Birbrair, Sidney B. Peres, Stephen R. Farmer, Miguel L. Batista Jr.

Open Access Articles

Cancer-induced cachexia, characterized by systemic inflammation, body weight loss, adipose tissue (AT) remodeling and muscle wasting, is a malignant metabolic syndrome with undefined etiology. Here, we show that both genetic ablation and pharmacological inhibition of TLR4 were able to attenuate the main clinical markers of cachexia in mice bearing Lewis lung carcinoma (LLC). AT remodelling was not found in LLC tumor-bearing (TB) TLR4(-/-) mice due to reduced macrophage infiltration and adipocyte atrophy. TLR4(-/-) mice were also resistant to cold-induced browning of subcutaneous AT (scAT). Importantly, pharmacological inhibition of TLR4 (Atorvastatin) reproduced the main protective effect against AT remodeling found in ...

The Trim-Nhl Protein Nhl-2 Is A Co-Factor In The Nuclear And Somatic Rnai Pathways In C. Elegans, Gregory M. Davis, Shikui Tu, Jacqueline A. Wilce, Julie M. Claycomb, Zhiping Weng, Peter R. Boag

Program in Bioinformatics and Integrative Biology Publications and Presentations

Proper regulation of germline gene expression is essential for fertility and maintaining species integrity. In the C. elegans germline, a diverse repertoire of regulatory pathways promote the expression of endogenous germline genes and limit the expression of deleterious transcripts to maintain genome homeostasis. Here we show that the conserved TRIM-NHL protein, NHL-2, plays an essential role in the C. elegans germline, modulating germline chromatin and meiotic chromosome organization. We uncover a role for NHL-2 as a co-factor in both positively (CSR-1) and negatively (HRDE-1) acting germline 22G-small RNA pathways and the somatic nuclear RNAi pathway. Furthermore, we demonstrate that NHL-2 ...

An Evaluation Of The Impact Of Medication On Behavioral Intervention Effectiveness For Adults With Traumatic Brain Injury, Sulay Martinez

Capstone Projects

A systematic search of the literature was conducted to identify articles implementing both pharmacological and behavioral interventions with subjects with traumatic brain injury (TBI). Limitations of pharmacological interventions were evaluated and compared to the implications for behavioral interventions for adults with TBI. Results of this study indicate further research is necessary to adequately evaluate the effects of medication on behavioral intervention effectiveness for adults with TBI.

Trypanosoma Brucei Prmt1 Is A Nucleic Acid Binding Protein With A Role In Energy Metabolism And The Starvation Stress Response., Lucie Kafková, Chengjian Tu, Kyle L. Pazzo, Kyle P. Smith, Erik W. Debler, Kimberly S. Paul, Jun Qu, Laurie K. Read

Department of Biochemistry and Molecular Biology Faculty Papers

In Trypanosoma brucei and related kinetoplastid parasites, transcription of protein coding genes is largely unregulated. Rather, mRNA binding proteins, which impact processes such as transcript stability and translation efficiency, are the predominant regulators of gene expression. Arginine methylation is a posttranslational modification that preferentially targets RNA binding proteins and is, therefore, likely to have a substantial impact on T. brucei biology. The data presented here demonstrate that cells depleted of T. brucei PRMT1 (TbPRMT1), a major type I protein arginine methyltransferase, exhibit decreased virulence in an animal model. To understand the basis of this phenotype, quantitative global proteomics was employed ...

Resistance From Afar: Distal Mutation V36m Allosterically Modulates The Active Site To Accentuate Drug Resistance In Hcv Ns3/4a Protease, Aysegul Ozen, Kuan-Hung Lin, Keith P. Romano, Davide Tavella, Alicia Newton, Christos J. Petropoulos, Wei Huang, Cihan Aydin, Celia A. Schiffer

University of Massachusetts Medical School Faculty Publications

Hepatitis C virus rapidly evolves, conferring resistance to direct acting antivirals. While resistance via active site mutations in the viral NS3/4A protease has been well characterized, the mechanism for resistance of non-active site mutations is unclear. R155K and V36M often co-evolve and while R155K alters the electrostatic network at the binding site, V36M is more than 13 Angstrom away. In this study the mechanism by which V36M confers resistance, in the context of R155K, is elucidated with drug susceptibility assays, crystal structures, and molecular dynamics (MD) simulations for three protease inhibitors: telaprevir, boceprevir and danoprevir. The R155K and R155K ...

Highly Efficient 5' Capping Of Mitochondrial Rna With Nad+ And Nadh By Yeast And Human Mitochondrial Rna Polymerase, Jeremy G Bird, Urmimala Basu, David Kuster, Aparna Ramachandran, Ewa Grudzien-Nogalska, Atif Towheed, Douglas C. Wallace, Megerditch Kiledjian, Dmitry Temiakov, Smita S. Patel, Richard H. Ebright, Bryce E. Nickels

Department of Biochemistry and Molecular Biology Faculty Papers

Bacterial and eukaryotic nuclear RNA polymerases (RNAPs) cap RNA with the oxidized and reduced forms of the metabolic effector nicotinamide adenine dinucleotide, NAD+ and NADH, using NAD+ and NADH as non-canonical initiating nucleotides for transcription initiation. Here, we show that mitochondrial RNAPs (mtRNAPs) cap RNA with NAD+ and NADH, and do so more efficiently than nuclear RNAPs. Direct quantitation of NAD+- and NADH-capped RNA demonstrates remarkably high levels of capping in vivo: up to ~60% NAD+ and NADH capping of yeast mitochondrial transcripts, and up to ~15% NAD+ capping of human mitochondrial transcripts. The capping efficiency is determined by promoter ...

The Caenorhabditis Elegans Oxidative Stress Response Requires The Nhr-49 Transcription Factor, Queenie Hu, Dayana R. D'Amora, Lesley T. Macneil, Albertha J. M. Walhout, Terrance J. Kubiseski

Open Access Articles

The overproduction of reactive oxygen species (ROS) in cells can lead to the development of diseases associated with aging. We have previously shown that C. elegans BRAP-2 (Brca1 associated binding protein 2) regulates phase II detoxification genes such as gst-4, by increasing SKN-1 activity. Previously, a transcription factor (TF) RNAi screen was conducted to identify potential activators that are required to induce gst-4 expression in brap-2(ok1492) mutants. The lipid metabolism regulator NHR-49/HNF4 was among 18 TFs identified. Here, we show that knockdown of nhr-49 suppresses the activation of gst-4 caused by brap-2 inactivation and that gain-of-function alleles of ...

Conserved Mrna-Granule Component Scd6 Targets Dhh1 To Repress Translation Initiation And Activates Dcp2-Mediated Mrna Decay In Vivo, Quira Zeidan, Feng He, Fan Zhang, Hongen Zhang, Allan Jacobson, Alan G. Hinnebusch

Open Access Articles

Scd6 protein family members are evolutionarily conserved components of translationally silent mRNA granules. Yeast Scd6 interacts with Dcp2 and Dhh1, respectively a subunit and a regulator of the mRNA decapping enzyme, and also associates with translation initiation factor eIF4G to inhibit translation in cell extracts. However, the role of Scd6 in mRNA turnover and translational repression in vivo is unclear. We demonstrate that tethering Scd6 to a GFP reporter mRNA reduces mRNA abundance via Dcp2 and suppresses reporter mRNA translation via Dhh1. Thus, in a dcp2Delta mutant, tethered Scd6 reduces GFP protein expression with little effect on mRNA abundance, whereas ...

Applications Of Ct Perfusion-Based Triaging And Prognostication In Acute Ischemic Stroke, Eric A. Wright

Electronic Thesis and Dissertation Repository

CT Perfusion (CTP) is a minimally invasive imaging technique that aids acute ischemic stroke (AIS) triage and prognostication by determining tissue viability based on hemodynamic parameters. The goals of this research are to determine: 1) CTP thresholds for estimation of infarct and penumbra volume, 2) how CTP scan duration impacts infarct and penumbra volume estimates, and 3) reliability of CTP for predicting functional outcomes following intra-arterial therapy (IAT).

Chapter 2 introduced an experimental study for determining ischemia-time dependent thresholds for brain infarction using multimodal imaging in a porcine stroke model that is easier to implement than previous large animal stroke ...