Digital Commons Network^™

Development Of Auditory Event-Related Potentials In Young Children And Relations To Word-Level Reading Abilities At Age 8 Years, Kimberly Espy, Dennis L. Molfese, Victoria J. Molfese, Arlene Modglin

Developmental Cognitive Neuroscience Laboratory: Faculty Publications

A relationship between brain responses at birth and later emerging language and reading skills have been shown, but questions remain whether changes in brain responses after birth continue to predict the mastery of language-related skills such as reading development. To determine whether developmental changes in the brain-based perceptual skills are systematically related to differences in word-level reading proficiency at age 8 years, brain event-related potentials (ERPs) to speech and nonspeech stimuli were recorded annually at the ages of 1 through 8 years in a sample of 109 typically developing children. Two measures of word-level reading (one that requires decoding of …

Multiple Roles Of Mucins In Pancreatic Cancer, A Lethal And Challenging Malignancy., N. Moniaux, M. Andrianifahanana, R. E. Brand, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Mucins are members of an expanding family of large multifunctional glycoproteins. Pancreatic mucins have important biological functions, including the protection, lubrication, and moisturisation of the surfaces of epithelial tissues lining ductal structures within the pancreas. Several lines of evidence support the notion that deregulated mucin production is a hallmark of inflammatory and neoplastic disorders of the pancreas. Herein, we discuss the factors that contribute to the lethality of pancreatic cancer as well as the key role played by mucins, particularly MUC1 and MUC4, in the development and progression of the disease. Aspects pertaining to the aberrant expression and glycosylation of …

Evaluating Forensic Dna Evidence, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.

Forensic Dna Evidence: Collection, Mixtures, And Degradation, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.

Inhibition Of Glucocorticoid-Induced Apoptosis By Targeting Splice Variants Of Bim Mrna With Small Interfering Rna And Short Hairpin Rna., Marc T. Abrams, Noreen M. Robertson, Kyonggeun Yoon, Eric Wickstrom

Department of Biochemistry and Molecular Biology Faculty Papers

Glucocorticoids (GCs) induce apoptosis in lymphocytes and are effective agents for the treatment of leukemia. The activated glucocorticoid receptor (GR) initiates a transcriptional program leading to caspase activation and cell death, but the critical signaling intermediates in GC-induced apoptosis remain largely undefined. We have observed that GC induction of the three major protein products of the Bcl-2 relative Bim (BimEL, BimS and BimL) correlates with GC sensitivity in a panel of human pre-B acute lymphoblastic leukemia (ALL) cell lines. To test the hypothesis that Bim facilitates GC-induced apoptosis, we reduced BIM mRNA levels and Bim protein levels by RNA interference …

Myelin Proteolipid Protein-Specific Cd4+ Cd25+ Regulatory Cells Mediate Genetic Resistance To Experimental Autoimmune Encephalomyelitis, Jay Reddy, Zsolt Illés, Xingmin Zhang, Jeffrey Encinas, Jason Pyrdol, Lindsay Nicholson, Raymond A. Sobel, Kai W. Wucherpfennig, Vijay K. Kuchroo, James P. Allison

Jay Reddy Publications

SJL mice are highly susceptible to experimental autoimmune encephalomyelitis (EAE) induced with myelin proteolipid protein (PLP) peptide 139–151, whereas H-2 congenic B10.S mice are resistant. Immunodominance and susceptibility to EAE are associated with a high precursor frequency of PLP 139–151-specific T cells in the naive repertoire of SJL mice. To understand the mechanism of EAE resistance in B10.S mice, we determined the precursor frequency of PLP 139–151-reactive T cells in both strains by using IA^s/PLP 139–151 tetramers. SJL and B10.S mice had similar frequencies of tetramer-reactive T cells in the naive peripheral repertoire. However, in SJL mice, the …

T-Cell Responses To The M3 Immune Evasion Protein Of Murid Gammaherpesvirus 68 Are Partially Protective And Induced With Lytic Antigen Kinetics, Joshua J. Obar, Douglas C. Donovan, Sarah G. Crist, Ondine Silvia, James P. Stewart, Edward J. Usherwood

Dartmouth Scholarship

DNA vaccination with the M3 gene, encoding an immune evasion molecule expressed during both the acute lytic and persistent phases of murid gammaherpesvirus 68 infection, yielded a significantly lower titer of virus in the lung than controls. The protection seen was dependent on T cells, and we mapped an epitope recognized by CD8 T cells. The immune response to this epitope follows the same kinetics as lytic cycle antigens, despite the fact that this gene is expressed in both lytic and persistent stages of infection. This has important implications for our understanding of T-cell responses to putative latency-associated gammaherpesvirus proteins …

Multiple Mechanisms Regulate Numa Dynamics At Spindle Poles, Olga Kisurina-Evgenieva, Gary Mack, Quansheng Du, Ian Macara, Alexey Khodjakov, Duane A. Compton

Dartmouth Scholarship

The large coiled-coil protein NuMA plays an essential role in organizing microtubule minus ends at spindle poles in vertebrate cells. Here, we use both in vivo and in vitro methods to examine NuMA dynamics at mitotic spindle poles. Using fluorescence recovery after photobleaching, we show that an exogenously expressed green-fluorescent-protein/NuMA fusion undergoes continuous exchange between soluble and spindle-associated pools in living cells. These dynamics require cellular energy and display an average half-time for fluorescence recovery of approximately 3 minutes. To explore how NuMA dynamics at spindle poles is regulated, we exploited the association of NuMA with microtubule asters formed in …

Il-2 Receptor Signaling Regulates Ets1 Translation In Human Natural Killer Cells, Eric M. Grund

MUSC Theses and Dissertations

Natural Killer (NK) cells are critical for protection from cancer and infectious disease. The hypothesis that there is a molecular link between IL-2 receptor signaling and Ets1 was investigated. This hypothesis was based on the correlation between an NK-deficient phenotype generated by gene targeting of the Ets1 transcription factor, IL-2 receptor, IL-2 and IL-15, indicating that each of these proteins is required for the proper development and function of NK cells. The findings presented show that both IL-2 and IL-15 induce a post-transcriptional regulation of Ets1 in NK cells. Pharmacological and transient transfection analyses, using a method developed within to …

Waccnes Containing Bovine Herpe Svirus 1 Attenuated By Mutation In Latency-Related Gene, Clinton J. Jones

School of Veterinary and Biomedical Sciences: Faculty Publications

Vaccines for pathogenic Strains of bovine herpesvirus 1 (BHV-1) which are based on attenuated BHV-1 having a mutation in the latency-related gene are provided. Live, attenuated vaccines are also provided which express anti gens from other viral or bacterial pathogens and thus form the basis of a variety of vaccines.

Heme Oxygenase-2 Gene Deletion Attenuates Oxidative Stress In Neurons Exposed To Extracellular Hemin., Raymond F Regan, Jing Chen, Luna Benvenisti-Zarom

Department of Emergency Medicine Faculty Papers

BACKGROUND: Hemin, the oxidized form of heme, accumulates in intracranial hematomas and is a potent oxidant. Growing evidence suggests that it contributes to delayed injury to surrounding tissue, and that this process is affected by the heme oxygenase enzymes. In a prior study, heme oxygenase-2 gene deletion increased the vulnerability of cultured cortical astrocytes to hemin. The present study tested the effect of HO-2 gene deletion on protein oxidation, reactive oxygen species formation, and cell viability after mixed cortical neuron/astrocyte cultures were incubated with neurotoxic concentrations of hemin. RESULTS: Continuous exposure of wild-type cultures to 1-10 microM hemin for 14 …

Amyloid Directly Inhibits Human Alpha4beta2-Nicotinic Acetylcholine Receptors Heterologously Expressed In Human Sh-Ep1 Cells, J. Wu, Y-P Kuo, L. Xu, J. B. Eaton, L. Zhao, J. Wu, R. J. Lukas

Osteopathic Medicine, Jerry M. Wallace School of

No abstract provided.

Binding Between The Niemann–Pick C1 Protein And A Photoactivatable Cholesterol Analog Requires A Functional Sterol-Sensing Domain, Nobutaka Ohgami, Dennis C. Ko, Matthew Thomas, Matthew P. Scott, Catherine C. Y. Chang, Ta-Yuan Chang

Dartmouth Scholarship

Niemann-Pick type C (NPC) 1 protein plays important roles in moving cholesterol and other lipids out of late endosomes by means of vesicular trafficking, but it is not known whether NPC1 directly interacts with cholesterol. We performed photoaffinity labeling of intact cells expressing fluorescent protein (FP)-tagged NPC1 by using [(3)H]7,7-azocholestanol ([(3)H]AC). After immunoprecipitation, (3)H-labeled NPC1-GFP appeared as a single band. Including excess unlabeled sterol to the labeling reaction significantly diminished the labeling. Altering the NPC1 sterol-sensing domain (SSD) with loss-of-function mutations (P692S and Y635C) severely reduced the extent of labeling. To further demonstrate the specificity of labeling, we show that …

Durable Cytotoxic Immune Responses Against Gp120 Elicited By Recombinant Sv40 Vectors Encoding Hiv-1 Gp120 +/- Il-15., Hayley J Mckee, Patricia Y T'Sao, Maria Vera, Puri Fortes, David S Strayer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: A vaccine that elicits durable, powerful anti-HIV immunity remains an elusive goal. In these studies we tested whether multiple treatments with viral vector-delivered HIV envelope antigen (gp120), with and without IL-15, could help to approach that goal. For this purpose, we used recombinant Tag-deleted SV40-derived vectors (rSV40s), since they do not elicit neutralizing antibody responses, and so can be given multiply without loss of transduction efficiency. METHODS: SV(gp120) carried the coding sequences for HIV-1NL4-3 Env, and SV(mIL-15) carried the cDNA for mouse IL-15. Singly, and in combination, these two vectors were given monthly to BALB/cJ mice. Cytotoxic immunity and …

Nongenomic Effects Of Estrogens On Epithelial Chloride Secretion., Sabyasachi Moulik

Electronic Theses and Dissertations

The human colonic cell line T84, a model for studying epithelial chloride secretion and cystic fibrosis chloride channel (CFTR) function, was used to investigate the regulatory role of estrogens in transepithelial ion transport. Estrogens and other steroid hormones do not stimulate chloride secretion by themselves. However, 17 β-estradiol (17β-E2) rapidly (within seconds to minutes) potentiates carbachol- and thapsigargin-stimulated chloride secretion measured as short circuit current in voltage-clamped T84 monolayer cultures. The cholinergic agonist carbachol and the SR Ca²⁺ ATPase inhibitor thapsigargin stimulate chloride secretion by elevating intracellular calcium. 17α-estradiol, a stereoisomer that does not activate nuclear estrogen receptors, is …

Modified Amino Acid Copolymers Suppress Myelin Basic Protein 85–99-Induced Encephalomyelitis In Humanized Mice Through Different Effects On T Cells, Zsolt Illés, Joel N.H. Stern, Jay Reddy, Hanspeter Waldner, Marcin P. Mycko, Celia F. Brosnan, Stephan Ellmerich, Daniel M. Altmann, Laura Santambrogio, Jack L. Strominger, Vijay K. Kuchroo

Jay Reddy Publications

A humanized mouse bearing the HLA-DR2 (DRA/DRB1*1501) pro- tein associated with multiple sclerosis (MS) and the myelin basic protein (MBP) 85–99-specific HLA-DR2-restricted T cell receptor from an MS patient has been used to examine the effectiveness of modified amino acid copolymers poly(F,Y,A,K)n and poly- (V,W,A,K)n in therapy of MBP 85–99-induced experimental auto-immune encephalomyelitis (EAE) in comparison to Copolymer 1 [Copaxone, poly(Y,E,A,K)n]. The copolymers were designed to optimize binding to HLA-DR2. Vaccination, prevention, and treatment of MBP-induced EAE in the humanized mice with copolymers FYAK and VWAK ameliorated EAE more effectively than Copolymer 1, reduced the number of pathological lesions, and …

Physiology And Biochemistry Of Lead Accumulation In Sesbania Drummondii, Adam Ruley

Masters Theses & Specialist Projects

This thesis presents the results of three different studies conducted to elucidate the physiology and biochemistry of lead tolerance of Sesbania drummondii. These studies were conducted to determine: 1) the presence of an antioxidant mechanism in S. drummondii to counteract oxidative stress resulting from Pb exposure, 2) the extent of Pb tolerance of S. drummondii seedlings grown in the presence of Pb and synthetic chelators in soil and 3) the expression of antioxidant enzymes in S. drummondii seedlings exposed to Pb and synthetic chelators in aqueous media. In the first study, Sesbania drummondii plants were grown in soil containing 0-10 …

Cloning And Sequencing Of Bovine Na+/K= Atpase Α-1 Sub-Unit, Srikanth Aakula

Masters Theses & Specialist Projects

The major focus of this project was cloning and sequencing the α-1 sub-unit of Na+/K+-ATase gene in bovine corneal endothelium. The Na+/K+-ATase, also called the Na+ pump, is a crucial transmembrane protein. By transporting water and ions from and through the cornea into the aqueous humor, it is responsible for maintenance of structural integrity, corneal hydration and thereby transparency of the cornea. The Na+ pump is characterized by a complex molecular heterogeneity that results from differential association of multiple isoforms of both a (the catalytic) and [3 (glycoprotein) sub-units. In the corneal endothelium, α-1 α-2, β-l and β-2 sub-units are …

Cloning And Functional Analysis Of The Putative Tetracycline Resistance Gene Hp1165 In Helicobacter Pylori, Yuhuan Li

All-Inclusive List of Electronic Theses and Dissertations

Tetracycline has been used in combination with other antibiotics in treatment of Helicobacter pylori infection. However, tetracycline resistance has developed in clinical isolates of H. pylori, rendering treatment failure. Mutations in the 16S rRNA gene have been reported to mediate tetracycline resistance in some patient isolates. Nevertheless, the diversity of tetracycline resistance cases suggests multiple genes are involved. HPl 165, a putative tetracycline resistance gene in the genome of H. pylori 26695, displays 49.8% identity to the tetracycline efflux gene tetA (P) from Clostridium perfringens. To determine the function of the HPl 165 gene and gain a better understanding of …

Hsp27 Anti-Sense Oligonucleotides Sensitize The Microtubular Cytoskeleton Of Chinese Hamster Ovary Cells Grown At Low Ph To 42 Degrees C-Induced Reorganization, Michael T. Hargis, C. W. Storck, Eric Wickstrom, Leonid A. Yakubov, Dennis B. Leeper, Ronald A. Coss

Department of Biochemistry and Molecular Biology Faculty Papers

Chinese hamster ovary (CHO) cells maintained in vitro at pH 6.7 were used to model cells in the acidic environment of tumours. CHO cells grown at pH 6.7 develop thermotolerance during 42 degrees C heating at pH 6.7 and their cytoskeletal systems are resistant to 42 degrees C-induced perinuclear collapse. Hsp27 levels are elevated in cells grown at pH 6.7 and are further induced during 42 degrees C heating, while Hsp70 levels remain low or undetectable, suggesting that Hsp27 is responsible for some of the novel characteristics of these cells. An anti-sense oligonucleotide strategy was used to test the importance …

Biochemical Enrichment And Biophysical Characterization Of A Taste Receptor For L-Arginine From The Catfish, Ictalurus Puntatus., William Grosvenor, Yuri Kaulin, Andrew I Spielman, Douglas L Bayley, D Lynn Kalinoski, John H Teeter, Joseph G Brand

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: The channel catfish, Ictalurus punctatus, is invested with a high density of cutaneous taste receptors, particularly on the barbel appendages. Many of these receptors are sensitive to selected amino acids, one of these being a receptor for L-arginine (L-Arg). Previous neurophysiological and biophysical studies suggested that this taste receptor is coupled directly to a cation channel and behaves as a ligand-gated ion channel receptor (LGICR). Earlier studies demonstrated that two lectins, Ricinus communis agglutinin I (RCA-I) and Phaseolus vulgaris Erythroagglutinin (PHA-E), inhibited the binding of L-Arg to its presumed receptor sites, and that PHA-E inhibited the L-Arg-stimulated ion conductance …

Transcriptional Activation Of The Human Prostatic Acid Phosphatase Gene By Nf-Kappab Via A Novel Hexanucleotide-Binding Site., Stanislav Zelivianski, Richard Glowacki, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

Human prostatic acid phosphatase (PAcP) is a prostate epithelium-specific differentiation antigen. Cellular PAcP functions as a neutral protein tyrosine phosphatase and is involved in regulating androgen-promoted prostate cancer cell proliferation. Despite the fact that the promoter of the PAcP gene has been cloned, the transcriptional factors that regulate PAcP expression remain unidentified. This article describes our analyses of the promoter of the PAcP gene. Deletion analyses of the promoter sequence up to -4893 (-4893/+87) revealed that a 577 bp fragment (-1356/-779) represents the unique positive cis-active element in human prostate cancer cells but not in HeLa cervix carcinoma cells. Interestingly, …

Sadb Is Required For The Transition From Reversible To Irreversible Attachment During Biofilm Formation By Pseudomonas Aeruginosa Pa14, Nicky C. Caiazza, George A. O'Toole

Dartmouth Scholarship

Current models of biofilm formation by Pseudomonas aeruginosa propose that (i) planktonic cells become surface associated in a monolayer, (ii) surface-associated cells form microcolonies by clonal growth and/or aggregation, (iii) microcolonies transition to a mature biofilm comprised of exopolysaccharide-encased macrocolonies, and (iv) cells exit the mature biofilm and reenter the planktonic state. Here we report a new class of P. aeruginosa biofilm mutant that defines the transition from reversible to irreversible attachment and is thus required for monolayer formation. The transposon insertion carried by the sadB199 mutant was mapped to open reading frame PA5346 of P. aeruginosa PA14 and encodes …

Activation Of The Phosphatidylinositol 3-Kinase/Akt Pathway Contributes To Survival Of Primary Epithelial Cells Infected With The Periodontal Pathogen Porphyromonas Gingivalis, Özlem Yilmaz, Thomas Jungas, Philippe Verbeke, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

Porphyromonas gingivalis, an important periodontal pathogen, infects primary gingival epithelial cells (GECs). Despite the large number of bacteria that replicate inside the GECs, the host cell remains viable. We demonstrate that P. gingivalis triggers rapid and reversible surface phosphatidylserine exposure through a mechanism requiring caspase activation. However, after 1 day of infection, the bacteria no longer induce phosphatidylserine externalization and instead protect infected cells against apoptosis. Infection exerts its effect at the level of mitochondria, as P. gingivalis also blocks depolarization of the mitochondrial transmembrane potential and cytochrome c release. Interestingly, protein kinase B/Akt is phosphorylated during infection, which can …

Politics Of Embryonic Discourse, Kevin Quinn

Faculty Publications

In our brave new world of stem cells, clones, and parthenotes, how should we talk about early human embryos? In fashioning a response to this very thorny question, Ann Kiessling has a core message. It is: (1)that new science produces "new" conceptuses;(2) that science and scientists have failed to differentiate (with appropriate clarity) these new ex vivo conceptuses from those createdin vivo; (3) that new, more appropriate and scientifically-informed, terms are necessary; and (4) that this new language should transform the public discourse about human embryos. No one would deny that the subtleties of human embryology are neglected in public …

Methods For Increasing Leptin Levels Using Nicotinic Acid Compounds, Elaine L. Jacobson, Myron Jacobson, Hyuntae Kim

Graduate Center for Nutritional Sciences Faculty Patents

The invention relates to the use of nicotinic acid and nicotinic acid esters, such as nicotinic acid alkyl esters, to increase the amount of leptin in a subject. As a result, one can treat conditions, such as conditions characterized by wounds, by administering sufficient amounts of nicotinic acid or nicotinic acid ester to increase leptin levels to alleviating amounts. Various conditions and modes of treatment are disclosed.

The Recombinant Adeno-Associated Virus Vector (Raav2)-Mediated Apolipoprotein B Mrna-Specific Hammerhead Ribozyme: A Self-Complementary Aav2 Vector Improves The Gene Expression, Shumei Zhong, Shihua Sun, Ba-Bie Teng

Faculty, Staff and Student Publications

BACKGROUND: In humans, overproduction of apolipoprotein B (apoB) is positively associated with premature coronary artery diseases. To reduce the levels of apoB mRNA, we have designed an apoB mRNA-specific hammerhead ribozyme targeted at nucleotide sequences GUA6679 (RB15) mediated by adenovirus, which efficiently cleaves and decreases apoB mRNA by 80% in mouse liver and attenuates the hyperlipidemic condition. In the current study, we used an adeno-associated virus vector, serotype 2 (AAV2) and a self-complementary AAV2 vector (scAAV2) to demonstrate the effect of long-term tissue-specific gene expression of RB15 on the regulation apoB mRNA in vivo. METHODS: We constructed a hammerhead ribozyme …

The Anti-Proliferation Effects Of Lycopene On Breast Cancer Cells, Tixieanna Dissmore

Loma Linda University Electronic Theses, Dissertations & Projects

Background: The incidence and deaths from breast cancer represent the most cause of all cancer deaths among women. Lycopene, the carotenoid in tomatoes has been associated with decreasing risk of prostate, breast, and digestive tract cancers. Various mechanisms of lycopene action have been proposed, including antioxidant activity and pro-differentiation activities. Identifying changes in the expression of proteins modified by lycopene can provide information to study the modulating effects of lycopene carcinogenesis and tumorigenesis development.

Objective: The objective was to study the anti-proliferative effects of lycopene on MCF- 7 human breast cancer cells and to identify changes in protein expression patterns. …

Ionizing Radiation And Endostatin Gene Therapy Against Lung Tumor, Xian Luo

Loma Linda University Electronic Theses, Dissertations & Projects

Although many advances have been made in radiotherapy, tumor radioresistance and normal tissue damage continue to always be important issues for radiation oncologists. Numerous reports have also documented that radiation exposure increases the risk for malignancy and suppresses immune mechanisms. However, increasing evidence has suggested that anti-angiogenic therapy that targets tumor blood supply may alter abnormal tumor vasculature, thus synergizing radiotherapy. The governing hypothesis of the present study was that modification of tumor vasculature by antiangiogenic gene therapy can increase the efficacy of radiotherapy and that radiation can also improve DNA transfection efficiency by increasing expression of the administered gene. …

Endogenous No Regulates Superoxide Production At Low Oxygen Concentrations By Modifying The Redox State Of Cytochrome C Oxidase, Miriam Palacios-Callender, Marisol Quintero, Veronica S. Hollis, Roger J. Springett, Salvador Moncada

Dartmouth Scholarship

We have investigated in whole cells whether, at low oxygen concentrations ([O(2)]), endogenous nitric oxide (NO) modulates the redox state of the mitochondrial electron transport chain (ETC), and whether such an action has any signaling consequences. Using a polarographic-and-spectroscopic-coupled system, we monitored redox changes in the ETC cytochromes b(H), cc(1), and aa(3) during cellular respiration. The rate of O(2) consumption (VO(2)) remained constant until [O(2)] fell below 15 microM, whereas the onset of reduction of cytochromes aa(3), part of the terminal ETC enzyme cytochrome c oxidase, occurred at approximately 50 microM O(2). Incubation of the cells with an inhibitor of …