Digital Commons Network^™

Acute Hypersensitivity Of Pluripotent Testicular Cancer-Derived Embryonal Carcinoma To Low-Dose 5-Aza Deoxycytidine Is Associated With Global Dna Damage-Associated P53 Activation, Anti-Pluripotency And Dna Demethylation, Bijesh K. Biswal, Maroun J. Beyrouthy, Mary P. Hever-Jardine, David Armstrong, Craig R. Tomlinson, Brock C. Christensen, Carmen J. Marsit, Michael J. Spinella

Dartmouth Scholarship

Human embryonal carcinoma (EC) cells are the stem cells of nonseminoma testicular germ cells tumors (TGCTs) and share remarkable similarities to human embryonic stem (ES) cells. In prior work we found that EC cells are hypersensitive to low nanomolar doses of 5-aza deoxycytidine (5-aza) and that this hypersensitivity partially depended on unusually high levels of the DNA methyltransferase, DNMT3B. We show here that low-dose 5-aza treatment results in DNA damage and induction of p53 in NT2/D1 cells. In addition, low-dose 5-aza results in global and gene specific promoter DNA hypomethylation. Low- dose 5-aza induces a p53 transcriptional signature distinct from …

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 …

The Role Of Dairy Products And Milk In Adolescent Obesity: Evidence From Hong Kong’S ‘‘Children Of 1997’’ Birth Cohort, Shi Lin Lin, Marie Tarrant, Lai Ling Hui, Man Ki Kwok, Tai Hing Lam, Gabriel M. Leung, Mary Schooling

Publications and Research

Background
Observational studies, mainly from Western populations, suggest dairy consumption is inversely associated with adiposity. However, in these populations the intake range is limited and both diet and obesity may share social patterning. Evidence from non-Western developed settings with different social patterning, is valuable in distinguishing whether observed associations are biologically mediated or socially confounded.

Objective
To examine the associations of milk or other dairy product consumption with adolescent obesity.

Methods
We used multivariable linear regression models to examine the associations of milk or other dairy product consumption, obtained from a food frequency questionnaire, at 11 years with body mass …

Association Of Genetic Variation, Gene Expression, And Protein Abundance Within The Natriuretic Peptide Pathway, Bipin Sunkara

Honors College Theses

Background: The natriuretic peptide (NP) system is a critical physiologic pathway in heart failure, but there is marked individual variability in its functioning which may be genetic in origin. We investigated how genetic variations in NP pathway genes correlate with gene expression and protein abundance.

Methods: DNA, RNA, and tissue from human kidney (n=77) were obtained. Kidney was chosen as target tissue because each of the four candidate genes and proteins (natriuretic peptide receptor 1 (NPR1), NPR2, NPR3 and membrane metallo-endopeptidase (MME)) are expressed there. DNA samples were genotyped for 120 single nucleotide polymorphisms (SNP) in these four genes using …

Multiple Regulatory Mechanisms Control B-1 B Cell Activation, Vishal Sindhava, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

B-1 cells constitute a unique subset of B cells identified in several species including mice and humans. B-1 cells are further subdivided into B-1a and B-1b subsets as the former but not the later express CD5.The B-1a subset contributes to innate type of immune responses while the B-1b B cell subset contributes to adaptive responses. B-1 cell responses to B cell receptor (BCR) as well as Toll-like receptor (TLR) ligation are tightly regulated due to the cross-reactivity of antigen specific receptors on B-1 cells to self-antigens. B-1 cells are elevated in several autoimmune diseases. CD5 plays a major role in …

Luteolin Inhibits Human Prostate Tumor Growth By Suppressing Vascular Endothelial Growth Factor Receptor 2-Mediated Angiogenesis, Poyil Pratheeshkumar, Young-Ok Son, Amit Budhraja, Xin Wang, Songze Ding, Lei Wang, Andrew Hitron, Jeong-Chae Lee, Donghern Kim, Sasidharan Padmaja Divya, Gang Chen, Zhuo Zhang, Jia Luo, Xianglin Shi

Toxicology and Cancer Biology Faculty Publications

Angiogenesis, the formation of new blood vessels from pre-existing vascular beds, is essential for tumor growth, invasion, and metastasis. Luteolin is a common dietary flavonoid found in fruits and vegetables. We studied the antiangiogenic activity of luteolin using in vitro, ex vivo, and in vivo models. In vitro studies using rat aortic ring assay showed that luteolin at non-toxic concentrations significantly inhibited microvessel sprouting and proliferation, migration, invasion and tube formation of endothelial cells, which are key events in the process of angiogenesis. Luteolin also inhibited ex vivo angiogenesis as revealed by chicken egg chorioallantoic membrane assay (CAM) …

Degeneration Of Phrenic Motor Neurons Induces Long-Term Diaphragm Deficits Following Mid-Cervical Spinal Contusion In Mice., Charles Nicaise, Rajarshi Putatunda, Tamara J Hala, Kathleen A Regan, David M Frank, Jean-Pierre Brion, Karelle Leroy, Roland Pochet, Megan C Wright, Angelo C Lepore

Department of Neuroscience Faculty Papers

A primary cause of morbidity and mortality following cervical spinal cord injury (SCI) is respiratory compromise, regardless of the level of trauma. In particular, SCI at mid-cervical regions targets degeneration of both descending bulbospinal respiratory axons and cell bodies of phrenic motor neurons, resulting in deficits in the function of the diaphragm, the primary muscle of inspiration. Contusion-type trauma to the cervical spinal cord is one of the most common forms of human SCI; however, few studies have evaluated mid-cervical contusion in animal models or characterized consequent histopathological and functional effects of degeneration of phrenic motor neuron-diaphragm circuitry. We have …

From Linkage To Gwas: A Multifaceted Exploration Of The Genetic Risk For Alcohol Dependence, Amy Adkins

Theses and Dissertations

Family, twin and adoption studies consistently suggest that genetic factors strongly influence the risk for alcohol dependence (AD). Although the literature supports the role of genetics in AD, identification of specific genes contributing to the etiology of AD has proven difficult. These difficulties are due in part to the complex set of risk factors contributing to the development of AD. These risk factors include comorbidities with other clinical diagnoses and behavioral phenotypes (e.g., major depression), physiological differences that contribute to the differences between people in their level of response to ethanol (e.g., initial sensitivity) and finally the large number of …

A Beginning Education In The Anatomy And Function Of The Human Visual Apparatus For Grades 2-4, Evan Andrews

Honors Theses

The human visual apparatus is a remarkable feat of evolution that is nearly a complete mystery to many in the general population. Introducing such a challenging topic is difficult, but, if done in an enjoyable and interactive way to a young audience, the eye can become exciting instead of confusing. The primary objective of this project was to create a short lesson for elementary school students that gave an understanding of the eye's basic anatomy and functions. A fast-paced, interactive format was decided on that included units on the major eye components; color vision and how it can be affected; …

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, …

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.

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.

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 …

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 …