Medicine and Health Sciences Commons^™

The P2y(12) Antagonists, 2mesamp And Cangrelor, Inhibit Platelet Activation Through P2y(12)/G(I)-Dependent Mechanism, Binggang Xiang, Guoying Zhang, Hongmei Ren, Manjula Sunkara, Andrew J. Morris, T. Kent Gartner, Susan S. Smyth, Zhenyu Li

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: ADP is an important physiological agonist that induces integrin activation and platelet aggregation through its receptors P2Y(1) (Gα(q)-coupled) and P2Y(12) (Gα(i)-coupled). P2Y(12) plays a critical role in platelet activation and thrombosis. Adenosine-based P2Y(12) antagonists, 2-methylthioadenosine 5'-monophosphate triethylammonium salt hydrate (2MeSAMP) and Cangrelor (AR-C69931MX) have been widely used to demonstrate the role of P2Y(12) in platelet function. Cangrelor is being evaluated in clinical trials of thrombotic diseases. However, a recent study reported that both 2MeSAMP and Cangrelor raise intra-platelet cAMP levels and inhibit platelet aggregation through a P2Y(12)-independent mechanism.

METHODOLOGY/PRINCIPAL FINDINGS: The present work, using P2Y(12) deficient mice, sought to …

The Adverse Effects Periodontal Disease Has On Women, Jennifer Long

Honors Theses

The Adverse Effects Periodontal Diseases Has on Women Periodontal diseases are challenging to define given the number and variety of different oral diseases. This review sought to answer the question: How does a periodontal disease impact a woman throughout the life span? Specifically, this document discussed how, because of the cycling hormones and the effects those hormones have on the different bacteria, women's periodontal diseases differ from men's. Diseases of the mouth were first discovered during the Egyptian period and the information and knowledge about the different diseases advanced as time progressed. From here, non-surgical and surgical treatments were discussed …

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 …

Diffuse Traumatic Axonal Injury Within The Visual System: Implications For Visual Pathway Reorganization, Jiaqiong Wang

Theses and Dissertations

Traumatic brain injury is a major health problem with much of its morbidity associated with traumatic axonal injury (TAI). To date, significant insight has been gained into the initiating pathogenesis of TAI. However, the specific anterograde and retrograde sequelae of TAI are poorly understood because the diffuse nature of TAI complicates data analysis. To overcome this limitation, we subjected transgenic mice expressing yellow fluorescent protein (YFP) within the visual system to central fluid percussion injury, and consistently generated diffuse TAI within the optic nerve that could easily be followed in the organized YFP positive fibers. We demonstrated progressive axonal swelling, …

Draft Genome Sequence For Pseudomonas Aeruginosa Strain Pao579, A Mucoid Derivative Of Pao381, T. Ryan Withers, Shannon L. Johnson, Hongwei D. Yu

Biochemistry and Microbiology

Pseudomonas aeruginosa is an opportunistic pathogen that establishes a chronic lung infection in individuals afflicted with cystic fibrosis. Here, we announce the draft genome of P. aeruginosa strain PAO579, an alginate-overproducing derivative of strain PAO381.

Septohippocampal Gabaergic Neurons Mediate The Altered Behaviors Induced By N-Methyl-D-Aspartate Receptor Antagonists., Jingyi Ma, Siew Kian Tai, L Stan Leung

Physiology and Pharmacology Publications

We hypothesize that selective lesion of the septohippocampal GABAergic neurons suppresses the altered behaviors induced by an N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine or MK-801. In addition, we hypothesize that septohippocampal GABAergic neurons generate an atropine-resistant theta rhythm that coexists with an atropine-sensitive theta rhythm in the hippocampus. Infusion of orexin-saporin (ore-SAP) into the medial septal area decreased parvalbumin-immunoreactive (GABAergic) neurons by ~80%, without significantly affecting choline-acetyltransferase-immunoreactive (cholinergic) neurons. The theta rhythm during walking, or the immobility-associated theta induced by pilocarpine, was not different between ore-SAP and sham-lesion rats. Walking theta was, however, more disrupted by atropine sulfate in ore-SAP than …

Artifacts And Noise In Dna Profiling, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.

Dna Technology In Court, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.

Scopolamine-Induced Dry Eye Model In Female Rats, Ryan Alderson

Masters Theses

The objective of this study will be to establish, validate, and characterize a dry eye model in female rats induced by continuous systemic administration of scopolamine via Alzet® osmotic pumps for 28 days. This study will use female rats as a model for dry eye and will be implanted with osmotic pumps that will continuously distribute scopolamine or saline systemically over 28 days. Scopolamine will be used to induce the dry eye condition and saline will be used as a negative control. The clinical signs of dry eye will be evaluated by tear volume measurements with sterilized phenol-red thread (FCI …

Changes In Serum Interleukin-33 Concentration Before And After Treatment With Pegylated Interferon Alfa-2a Plus Ribavirin In Patients With Chronic Hepatitis C Genotype 1b Infection., Bruno Cacopardo, Marilia Rita Pinzone, Filippo Palermo, Giuseppe Nunnari

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: IL-33 is a novel member of the IL-1 family, which has been shown to play an important role in T helper 2 (Th2)-associated immune responses. Recent studies have suggested a possible role for IL-33 in the pathogenesis of liver damage during acute and chronic hepatitis; furthermore, IL-33 may be involved in the development and progression of liver fibrosis.

OBJECTIVES: To evaluate serum IL-33 levels in a group of patients with chronic hepatitis C (CHC) genotype 1b at enrolment and after a course of pegylated (PEG)-IFN plus ribavirin.

PATIENTS AND METHODS: 60 patients with chronic hepatitis C (CHC) and 65 …

Statistical Weights Of Single Source Dna Profiles, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.

Generating Forensic Dna Profiles, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.

What Can Go Wrong With Dna Profiling, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.

Observer Effects In Dna Profiling, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.

Statistical Weights Of Mixed Dna Profiles, Dan E. Krane

Biological Sciences Faculty Publications

Presentation recording from December 2012 can be found at http://youtu.be/daRBTopFA1A.

Part of the Forensic DNA Profiling Video Series.

Implications Of Database Searches For Dna Profiling Statistics, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.

Metabotropic Glutamate Receptor 5 In The Medial Prefrontal Cortex: Role In Cocaine Sensitization And Addiction, Kristin Marie Timmer

Theses and Dissertations (ETD)

Cocaine sensitization is associated with cocaine-induced hyperexcitability of pyramidal projection neurons within the medial prefrontal cortex (mPFC). Such hyperexcitability presumably results in increased glutamatergic input to reward-affiliated brain regions such as the ventral tegemental area (VTA) and nucleus accumbens (NAc), consequently facilitating drugseeking behavior. Metabotropic glutamate receptor 5 (mGluR5) has been implicated in cocaine addiction and demonstrated to increase neuronal excitability, therefore, the aim of the present study was to investigate the effect of intra-mPFC mGluR5 manipulation on behavioral and neurochemical sensitization and drug-seeking. Bilateral cannulae were implanted into the mPFC of male Sprague-Dawley rats and mGluR5 antagonist MTEP (15 …

Characterization Of Beryllium As A Novel Agent To Study Cell Cycle Arrest And Cellular Senescence, Priyatham Gorjala

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cancer cells evade senescence, apoptosis, and other constraints on proliferation, often via mutation of the p53 tumor suppressor gene (TP53). Normal human lung fibroblasts have been shown to enter premature senescence upon exposure to beryllium. In these cells, BeSO₄ stabilizes p53 protein, increases p21 gene expression, induces senescence-associated β-galactosidase activity and causes cell proliferation arrest. In the present study, we have investigated whether BeSO₄ is able to induce similar effects in cancer cells that have wildtype p53. We have demonstrated that beryllium salt at low concentration can induce molecular changes in the p53 signaling pathway leading to cell …

Credentialing Success In Respiratory Therapy Education: Revisiting Bourdieu's Concepts Of Field And Capital, Karen Lightbody Shaw

UNLV Theses, Dissertations, Professional Papers, and Capstones

The field of Respiratory Therapy (RT) is expected to experience a workforce shortfall over the next decade. The numbers of both program applicants and graduates have declined in recent years, necessitating strategies to improve board exam pass rates for future graduates. In response to the pending employment crisis, the Commission on Accreditation for Respiratory Care has published Programmatic Outcomes Data detailing individual program statistics. A theoretical framework adapted from Pierre Bourdieu's Concepts of Field and Capital was proposed to explain a possible re-stratification of RT programs. It states, in part, that a modification of position-takings within the RT educational field …

New Fusion Transcripts Identified In Normal Karyotype Acute Myeloid Leukemia, Hongxiu Wen, Yongjin Li, Sami N. Malek, Yeong C. Kim, Jia Xu, Pei Xian Chen, Fengxia Xiao, Xin Huang, Xianzheng Zhou, Zhenyu Xuan, Shiva Mankala, Guihua Hou, Janet D. Rowley, Michael Q. Zhang, San Ming Wang

Journal Articles: Genetics, Cell Biology & Anatomy

Genetic aberrations contribute to acute myeloid leukemia (AML). However, half of AML cases do not contain the well-known aberrations detectable mostly by cytogenetic analysis, and these cases are classified as normal karyotype AML. Different outcomes of normal karyotype AML suggest that this subgroup of AML could be genetically heterogeneous. But lack of genetic markers makes it difficult to further study this subgroup of AML. Using paired-end RNAseq method, we performed a transcriptome analysis in 45 AML cases including 29 normal karyotype AML, 8 abnormal karyotype AML and 8 AML without karyotype informaiton. Our study identified 134 fusion transcripts, all of …

N200 And P300 Evoked By Stimuli Straddling Category Boundary In Lexical Context, Ji Young Lee

Theses and Dissertations (ETD)

Background and Objectives: Event-related potentials (ERPs) like N200 and P300 have been reported to reflect the categorical perception of speech. The purpose of the present study is to explore whether these ERP components reflect the influence of lexical context on categorical perception. Findings may provide evidence for bottom-up or top-down processing of speech. Methods: On a seven step series of the /bi/-/pi/ continuum, a two-forced choice labeling test was administered in two conditions: /bi/ context (e.g. bee sting) and /pi/ context (e.g. pea soup). From the labeling results, Stimulus 1which is a prototypical /bi/ was selected for standard stimuli, and …

Hematopoietic Stem Cell Threshold Sensing Controls Regulatory Pathways Facilitating Clinically Relevant Ex Vivo Expansion For Stem Cell Transplantation, Andrew D. Lasiter

Theses and Dissertations (ETD)

The ex vivo expansion of hematopoietic stem cells (HSCs) for transplantation has threefold importance: 1.) First, because of the rarity of stem cells there often isn’t a sufficient supply obtainable from common sources for larger children and adults. 2.) Secondly, patient morbidity and time to hematopoietic reconstitution following myeloablative preconditioning is improved by administering a larger pool of HSCs. 3.) Lastly, gene therapies for hematological diseases still require a robust supply of HSCs to offset varying degrees of inefficiency in vector mediated transfection protocols. These reasons, and others, have been an impetus for many discoveries made within four primary subdivisions …

Mrp4 Is A Crucial Regulator Of Testosterone Biosynthesis, Jessica Ann Morgan

Theses and Dissertations (ETD)

The physiological role of multidrug resistance protein 4 (Mrp4) in the testes is unknown. It was discovered that Mrp4 is expressed primarily in mouse and human Leydig cells; however, there is no current evidence that Mrp4 regulates testosterone biosynthesis. The role of Mrp4 was investigated in Leydig cells where testosterone production is regulated by cAMP, an intracellular second messenger formed when the luteinizing hormone (LH) receptor (Lhr) is activated. As Mrp4 regulates cAMP, we compared testosterone levels in our Mrp4 WT and KO mice. Prepubertal KO mice had significantly reduced testicular testosterone, impaired gametogenesis, and disrupted cAMP homeostasis, resulting in …

The Role Of Bip Nucleotide Exchange Factor Sil1 In Immunoglobulin Biosynthesis, Tyler Sanford

Theses and Dissertations (ETD)

BiP is an essential endoplasmic reticulum resident molecular chaperone of the HSP70 family that binds exposed hydrophobic regions of unfolded proteins. Substrates bound by BiP are protected from dangerous non-specific interaction with other unfolded proteins via their aggregation prone exposed hydrophobic regions, which are normally buried in the native state, and act as BiP binding targets. For these substrates to mature into the native state, BiP must be released. Like all HSP70 family members, cycles of BiP binding and release are nucleotide dependent and facilitated by two genres of cochaperones, HSP40s, and nucleotide exchange factors (NEFs). HSP40s function in stimulating …

Parenteral Nutrition Additive Shortages: The Short-Term, Long-Term And Potential Epigenetic Implications In Premature And Hospitalized Infants., Corrine K. Hanson, Melissa Thoene, Julie Wagner, Dean Collier, Kassandra Lecci, Ann Anderson-Berry

Journal Articles: Medical Nutrition

Nutrition support practitioners are currently dealing with shortages of parenteral nutrition micronutrients, including multivitamins (MVI), selenium and zinc. A recent survey from the American Society of Enteral and Parenteral Nutrition (ASPEN) indicates that this shortage is having a profound effect on clinical practice. A majority of respondents reported taking some aggressive measures to ration existing supplies. Most premature infants and many infants with congenital anomalies are dependent on parenteral nutrition for the first weeks of life to meet nutritional needs. Because of fragile health and poor reserves, they are uniquely susceptible to this problem. It should be understood that shortages …

Tumour Inflammasome-Derived Il-1b Recruits Neutrophils And Improves Local Recurrence-Free Survival In Ebv-Induced Nasopharyngeal Carcinoma, Lih-Chyang Chen, Li-Jie Wang, Nang-Ming Tsang, David M. Ojcius, Chia-Chen Chen, Chun-Nan Ouyang, Chuen Hsueh, Ying Liang, Kai-Ping Chang, Chiu-Chin Chen, Yu-Sun Chang

All Dugoni School of Dentistry Faculty Articles

Inflammasomes sense infection and cellular damage and are critical for triggering inflammation through IL-1β production. In carcinogenesis, inflammasomes may have contradictory roles through facilitating antitumour immunity and inducing oncogenic factors. Their function in cancer remains poorly characterized. Here we show that the NLRP3, AIM2 and RIG-I inflammasomes are overexpressed in Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), and expression levels correlate with patient survival. In tumour cells, AIM2 and RIG-I are required for IL-1β induction by EBV genomic DNA and EBV-encoded small RNAs, respectively, while NLRP3 responds to extracellular ATP and reactive oxygen species. Irradiation and chemotherapy can further activate AIM2 …

Reversible Inhibition Of Chlamydia Trachomatis Infection In Epithelial Cells Due To Stimulation Of P2x4 Receptors, Matthew A. Pettengill, Camila Marques-Da-Silva, Maria Luisa Avila, Verissa W. Lam, Ikechukwu Ollawa, Ali Abdul-Sater, Robson Coutinho-Silva, Georg Hacker, David M. Ojcius, Suellen D'Arc Dos Santos Oliveira

All Dugoni School of Dentistry Faculty Articles

Bacterial infections of the mucosal epithelium are a major cause of human disease. The prolonged presence of microbial pathogens stimulates inflammation of the local tissues, which leads to changes in the molecular composition of the extracellular milieu. A well-characterized molecule that is released to the extracellular milieu by stressed or infected cells is extracellular ATP and its ecto-enzymatic degradation products, which function as signaling molecules through ligation of purinergic receptors. There has been little information, however, on the effects of the extracellular metabolites on bacterial growth in inflamed tissues. Millimolar concentrations of ATP have been previously shown to inhibit irreversibly …

Anti-Apoptotic Mcl-1 Localizes To The Mitochondrial Matrix And Couples Mitochondrial Fusion To Respiration, Rhonda Perciavalle

Theses and Dissertations (ETD)

MCL-1, an anti-apoptotic BCL-2 family member that is essential for the survival of multiple cell lineages, is also among the most highly amplified genes in cancer. Although MCL-1 is known to oppose cell death, precisely how it functions to promote survival of normal and malignant cells is poorly understood. Here, I report that different forms of MCL-1 reside in distinct mitochondrial locations and exhibit separable functions. On the outer mitochondrial membrane, a MCL-1 isoform acts like other anti-apoptotic BCL-2 molecules to antagonize apoptosis, whereas an amino-terminally truncated isoform of MCL-1 that is imported into the mitochondrial matrix is necessary to …

Glutaredoxin 2 (Grx2) Knockout Increases Sensitivity To Oxidative Stress In Mouse Lens Epithelial Cells, Hongli Wu, Liren Lin, Frank Giblin, Ye-Sheh Ho, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Glutaredoxin belongs to the oxidoreductase family with cytosolic glutaredoxin 1 (Grx1) and mitochondrial gluraredoxin 2 (Grx2) isoforms. Of the two isozymes, the function of Grx2 is not well understood. This paper studied the effect of Grx2 deletion on cellular function using primary lens epithelial cell cultures isolated from Grx2 gene knockout (KO) and wild type (WT) mice. We found that both cell types showed similar growth patterns and morphology, and comparable mitochondrial glutathione pool and complex I activity. Cells with deleted Grx2 did not show affected Grx1 or thioredoxin (Trx) expression but exhibited high sensitivity to oxidative stress. Under treatment …