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Activation Of Src Kinase Lyn By The Kaposi Sarcoma-Associated Herpesvirus K1 Protein: Implications For Lymphomagenesis, Om Prakash, O Rama Swamy, Xiochang Peng, Zhen-Ya Tang, Li Li, Janet E Larson, J Craig Cohen, Javed Gill, Gist Farr, Suizhao Wang, Felipe Samaniego

Faculty, Staff and Student Publications

The K1 gene of Kaposi sarcoma-associated herpesvirus (KSHV) encodes a transmembrane glycoprotein bearing a functional immunoreceptor tyrosine-based activation motif (ITAM). Previously, we reported that the K1 protein induced plasmablastic lymphomas in K1 transgenic mice, and that these lymphomas showed enhanced Lyn kinase activity. Here, we report that systemic administration of the nuclear factor kappa B (NF-kappaB) inhibitor Bay 11-7085 or an anti-vascular endothelial growth factor (VEGF) antibody significantly reduced K1 lymphoma growth in nude mice. Furthermore, in KVL-1 cells, a cell line derived from a K1 lymphoma, inhibition of Lyn kinase activity by the Src kinase inhibitor PP2 decreased VEGF …

The Cns Role Of Toll-Like Receptor 4 In Innate Neuroimmunity And Painful Neuropathy, Flobert Y. Tanga, Nancy Nutile-Mcmenemy, Joyce A. Deleo

Dartmouth Scholarship

Neuropathic pain remains a prevalent and persistent clinical problem because of our incomplete understanding of its pathogenesis. This study demonstrates for the first time, to our knowledge, a critical role for CNS innate immunity by means of microglial Toll-like receptor 4 (TLR4) in the induction phase of behavioral hypersensitivity in a mouse and rat model of neuropathy. We hypothesized that after L5 nerve transection, CNS neuroimmune activation and subsequent cytokine expression are triggered by the stimulation of microglial membrane-bound TLR4. To test this hypothesis, experiments were undertaken to assess tactile and thermal hypersensitivity in genetically altered (i.e., TLR4 knockout and …

Reduction Of All-Trans Retinal To All-Trans Retinol In The Outer Segments Of Frog And Mouse Rod Photoreceptors, Chunhe Chen, Efthymia Tsina, M. Carter Cornwall, Rosalie K. Crouch, Sukumar Vijayaraghavan, Yiannis Koutalos

MUSC Faculty Journal Articles

The first step in the Visual Cycle, the series of reactions that regenerate the vertebrate visual pigment rhodopsin, is the reduction of all-trans retinal to all-trans retinol, a reaction that requires NADPH. We have used the fluorescence of all-trans retinol to study this reduction in living rod photoreceptors. After the bleaching of rhodopsin, fluorescence (excitation, 360 nm; emission, 457 or 540 nm) appears in frog and wild-type mouse rod outer segments reaching a maximum in 30–60 min at room temperature. With this excitation and emission, the mitochondrial-rich ellipsoid region of the cells shows strong fluorescence as well. Fluorescence measurements at …

Role For Akt3/Protein Kinase Bγ In Attainment Of Normal Brain Size, Rachel M. Easton, Han Cho, Kristin Roovers, Diana W. Shineman

Dartmouth Scholarship

Studies of Drosophila and mammals have revealed the importance of insulin signaling through phosphatidylinositol 3-kinase and the serine/threonine kinase Akt/protein kinase B for the regulation of cell, organ, and organismal growth. In mammals, three highly conserved proteins, Akt1, Akt2, and Akt3, comprise the Akt family, of which the first two are required for normal growth and metabolism, respectively. Here we address the function of Akt3. Like Akt1, Akt3 is not required for the maintenance of normal carbohydrate metabolism but is essential for the attainment of normal organ size. However, in contrast to Akt1^−/− mice, which display a …

Quantitative 1h Magnetic Resonance Spectroscopic Imaging Determines Therapeutic Immunization Efficacy In An Animal Model Of Parkinson's Disease., Michael D. Boska, Travis B. Lewis, Christopher J. Destache, Eric J. Benner, Jay A. Nelson, Mariano Uberti, R. Lee Mosley, Howard Gendelman

Journal Articles: Radiology

Nigrostriatal degeneration, the pathological hallmark of Parkinson's disease (PD), is mirrored by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication. MPTP-treated animals show the common behavioral, motor, and pathological features of human disease. We demonstrated previously that adoptive transfer of Copaxone (Cop-1) immune cells protected the nigrostriatal dopaminergic pathway in MPTP-intoxicated mice. Herein, we evaluated this protection by quantitative proton magnetic resonance spectroscopic imaging (1H MRSI). 1H MRSI performed in MPTP-treated mice demonstrated that N-acetyl aspartate (NAA) was significantly diminished in the substantia nigra pars compacta (SNpc) and striatum, regions most affected in human disease. When the same regions were coregistered with immunohistochemical stains for …

Dynamic Changes In Mcl-1 Expression Regulate Macrophage Viability Or Commitment To Apoptosis During Bacterial Clearance, Helen M. Marriott, Colin D. Bingle, Robert C. Read, Karen E. Braley, Guido Kroemer, Paul G. Hellewell, Ruth W. Craig, Moira K.B. Whyte, David H. Dockrell

Dartmouth Scholarship

Macrophages are critical effectors of bacterial clearance and must retain viability, despite exposure to toxic bacterial products, until key antimicrobial functions are performed. Subsequently, host-mediated macrophage apoptosis aids resolution of infection. The ability of macrophages to make this transition from resistance to susceptibility to apoptosis is important for effective host innate immune responses. We investigated the role of Mcl-1, an essential regulator of macrophage lifespan, in this switch from viability to apoptosis, using the model of pneumococcal-associated macrophage apoptosis. Upon exposure to pneumococci, macrophages initially upregulate Mcl-1 protein and maintain viability for up to 14 hours. Subsequently, macrophages reduce expression …

Multiple Metabolic Hits Converge On Cd36 As Novel Mediator Of Tubular Epithelial Apoptosis In Diabetic Nephropathy., Katalin Susztak, Emilio Ciccone, Peter Mccue, Kumar Sharma, Erwin P Böttinger

Department of Medicine Faculty Papers

BACKGROUND: Diabetic nephropathy (DNP) is a common complication of type 1 and type 2 diabetes mellitus and the most common cause of kidney failure. While DNP manifests with albuminuria and diabetic glomerulopathy, its progression correlates best with tubular epithelial degeneration (TED) and interstitial fibrosis. However, mechanisms leading to TED in DNP remain poorly understood.

METHODS AND FINDINGS: We found that expression of scavenger receptor CD36 coincided with proximal tubular epithelial cell (PTEC) apoptosis and TED specifically in human DNP. High glucose stimulated cell surface expression of CD36 in PTECs. CD36 expression was necessary and sufficient to mediate PTEC apoptosis induced …

Endothelial-Specific Expression Of Caveolin-1 Impairs Microvascular Permeability And Angiogenesis, Philip M. Bauer, Jun Yu, Yan Chen, Reed Hickey, Pascal N. Bernatchez, Robin Looft-Wilson, Yan Huang, Frank Giordano, Radu V. Stan, William C. Sessa

Dartmouth Scholarship

The functions of caveolae and/or caveolins in intact animals are beginning to be explored. Here, by using endothelial cell-specific transgenesis of the caveolin-1 (Cav-1) gene in mice, we show the critical role of Cav-1 in several postnatal vascular paradigms. First, increasing levels of Cav-1 do not increase caveolae number in the endothelium in vivo. Second, despite a lack of quantitative changes in organelle number, endothelial-specific expression of Cav-1 impairs endothelial nitric oxide synthase activation, endothelial barrier function, and angiogenic responses to exogenous VEGF and tissue ischemia. In addition, VEGF-mediated phosphorylation of Akt and its substrate, endothelial nitric oxide synthase, were …

A Streptococcal Collagen-Like Protein Interacts With The Α 2 Β 1 Integrin And Induces Intracellular Signaling, Joseph O. Humtsoe, Jiyeun K. Kim, Yi Xu, Douglas R. Keene, Magnus Höök, Slawomir Lukomski, Kishore K. Wary

Faculty & Staff Scholarship

No abstract provided.

Palm Is Expressed In Both Developing And Adult Mouse Lens And Retina., Meryl Castellini, Louise V Wolf, Bharesh K Chauhan, Deni S Galileo, Manfred W Kilimann, Ales Cvekl, Melinda K Duncan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Paralemmin (Palm) is a prenyl-palmitoyl anchored membrane protein that can drive membrane and process formation in neurons. Earlier studies have shown brain preferred Palm expression, although this protein is a major water insoluble protein in chicken lens fiber cells and the Palm gene may be regulated by Pax6. METHODS: The expression profile of Palm protein in the embryonic, newborn and adult mouse eye as well as dissociated retinal neurons was determined by confocal immunofluorescence. The relative mRNA levels of Palm, Palmdelphin (PalmD) and paralemmin2 (Palm2) in the lens and retina were determined by real time rt-PCR. RESULTS: In the …

Cdc42 Regulates Arsenic-Induced Nadph Oxidase Activation And Cell Migration Through Actin Filament Reorganization, Yong Qian, Ke Jian Liu, Yan Chen, Daniel C. Flynn, Vince Castranova, Xianglin Shi

Faculty & Staff Scholarship

No abstract provided.

Global Gene Expression Profiling Of Cells Overexpressing Smc3., Giancarlo Ghiselli, Chang-Gong Liu

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: The Structural Maintenance of Chromosome 3 protein (SMC3) plays an essential role during the sister chromatid separation, is involved in DNA repair and recombination and participates in microtubule-mediated intracellular transport. SMC3 is frequently elevated in human colon carcinoma and overexpression of the protein transforms murine NIH3T3 fibroblasts. In order to gain insight into the mechanism of SMC3-mediated tumorigenesis a gene expression profiling was performed on human 293 cells line stably overexpressing SMC3. RESULTS: Biotinylated complementary RNA (cRNA) was used for hybridization of a cDNAmicroarray chip harboring 18,861 65-mer oligos derived from the published dEST sequences. After filtering, the hybridization …

Mitochondrial Dna Mutations, Apoptosis, And The Misfolded Protein Response., Justin L. Mott, Dekui Zhang, Hans Peter Zassenhaus

Journal Articles: Biochemistry & Molecular Biology

Studies of transgenic mice with accelerated accumulation of mtDNA mutations specifically in the heart lead us to propose that apoptotic signaling and cell death is central to the pathogenesis of mtDNA mutations in aging. It is the cellular response to that apoptotic signaling and the organ?s compensatory response to a loss of cells that specify the phenotype of an accumulation of mtDNA mutations. In the heart, cardiomyocytes induce a vigorous anti-apoptotic, pro-survival response to counteract mitochondrial apoptotic signaling. The heart up-regulates contractility of remaining myocytes in order to maintain cardiac output. We hypothesize that mutant mitochondrial proteins originate apoptotic signaling …

Mechanistic Differences In Rna-Dependent Dna Polymerization And Fidelity Between Murine Leukemia Virus And Hiv-1 Reverse Transcriptases, Mark Skasko, Kellie K. Weiss, Holly M. Reynolds, Varuni Jamburuthugoda, Kwi Lee, Baek Kim

Biology

We compared the mechanistic and kinetic properties of murine leukemia virus (MuLV) and human immunodeficiency virus type 1 (HIV-1) reverse transcriptases (RTs) during RNA-dependent DNA polymerization and mutation synthesis using pre-steady-state kinetic analysis. First, MuLV RT showed 6.5-121.6-fold lower binding affinity (Kd) to deoxynucleotide triphosphate (dNTP) substrates than HIV-1 RT, although the two RTs have similar incorporation rates (kpol). Second, compared with HIV-1 RT, MuLV RT showed dramatic reduction during multiple dNTP incorporations at low dNTP concentrations. Presumably, due to its low dNTP binding affinity, the dNTP binding step becomes rate-limiting in the multiple rounds of the dNTP incorporation by …

Genetic Networks Controlling Retinal Injury, Felix R Vazquez-Chona, Amna N Khan, Chun K Chan, Anthony N Moore, Pramod K Dash, M Rosario Hernandez, Lu Lu, Elissa J Chesler, Kenneth F Manly, Robert W Williams, Eldon E Geisert

Faculty, Staff and Student Publications

PURPOSE: The present study defines genomic loci underlying coordinate changes in gene expression following retinal injury.

METHODS: A group of acute phase genes expressed in diverse nervous system tissues was defined by combining microarray results from injury studies from rat retina, brain, and spinal cord. Genomic loci regulating the brain expression of acute phase genes were identified using a panel of BXD recombinant inbred (RI) mouse strains. Candidate upstream regulators within a locus were defined using single nucleotide polymorphism databases and promoter motif databases.

RESULTS: The acute phase response of rat retina, brain, and spinal cord was dominated by transcription …

Prime-Boost Vaccination With Plasmid And Adenovirus Gene Vaccines Control Her2/Neu+ Metastatic Breast Cancer In Mice, Xiaoyan Wang, Jian-Ping Wang, Xiao-Mei Rao, Janet E Price, Heshan S Zhou, Lawrence B Lachman

Faculty, Staff and Student Publications

INTRODUCTION: Once metastasis has occurred, the possibility of completely curing breast cancer is unlikely, particularly for the 30 to 40% of cancers overexpressing the gene for HER2/neu. A vaccine targeting p185, the protein product of the HER2/neu gene, could have therapeutic application by controlling the growth and metastasis of highly aggressive HER2/neu+ cells. The purpose of this study was to determine the effectiveness of two gene vaccines targeting HER2/neu in preventive and therapeutic tumor models.

METHODS: The mouse breast cancer cell line A2L2, which expresses the gene for rat HER2/neu and hence p185, was injected into the mammary fat pad …

The Histochemical And Ultrastructural Effects Of Cadmium On Mouse Edl Muscle, Fati̇me Geyi̇koğlu, Aysel Temelli̇, Özgen Vuraler, Hasan Türkez

Turkish Journal of Zoology

The histochemical and ultrastructural effects of cadmium (Cd) on the extensor digitorum longus (EDL) muscles of male mice were investigated. Two doses of Cd (0.1 and 1.0 x 10^{-4} M) were injected into the mice. The animals were killed at the end of 48 h and their EDL muscles excised. Three types of fibers (I, IIA and IIB) were described by the succinic dehydrogenase (SDH) method in the control groups. The mitochondrial and sarcotubular contents of the fibers were different. The histochemical and ultrastructural characteristics of the EDL muscles in mice given Cd did not differ from those of the …

Tsc2 Modulates Actin Cytoskeleton And Focal Adhesion Through Tsc1-Binding Domain And The Rac1 Gtpase, Elena Goncharova, Dmitry Goncharov, Daniel J. Noonan, Vera P Krymskaya

Molecular and Cellular Biochemistry Faculty Publications

Tuberous sclerosis complex (TSC) 1 and TSC2 are thought to be involved in protein translational regulation and cell growth, and loss of their function is a cause of TSC and lymphangioleiomyomatosis (LAM). However, TSC1 also activates Rho and regulates cell adhesion. We found that TSC2 modulates actin dynamics and cell adhesion and the TSC1-binding domain (TSC2-HBD) is essential for this function of TSC2. Expression of TSC2 or TSC2-HBD in TSC2-/- cells promoted Rac1 activation, inhibition of Rho, stress fiber disassembly, and focal adhesion remodeling. The down-regulation of TSC1 with TSC1 siRNA in TSC2-/- cells activated Rac1 and induced loss of …

The Kidney-Specific Wnk1 Isoform Is Induced By Aldosterone And Stimulates Epithelial Sodium Channel-Mediated Na+ Transport, Anikó Naray-Fejes-Toth, Peter M. Snyder, Géza Fejes-Toth

Dartmouth Scholarship

WNK1 belongs to a unique family of Ser/Thr kinases that have been implicated in the control of blood pressure. Intronic deletions in the WNK1 gene result in its overexpression and lead to pseudohypoaldosteronism type II, a disease with salt-sensitive hypertension and hyperkalemia. How overexpression of WNK1 leads to Na⁺ retention and hypertension is not entirely clear. Similarly, there is no information on the hormonal regulation of expression of WNK kinases. There are two main WNK1 transcripts expressed in the kidney: the originally described “long” WNK1 and a shorter transcript that is specifically expressed in the kidney (KS-WNK1). The goal …

Regulatory Role Of Glycogen Synthase Kinase 3 For Transcriptional Activity Of Add1/Srebp1c, Kang Ho Kim, Min Jeong Song, Eung Jae Yoo, Sung Sik Choe, Sang Dai Park, Jae Bum Kim

Faculty, Staff and Student Publications

Adipocyte determination- and differentiation-dependent factor 1 (ADD1) plays important roles in lipid metabolism and insulin-dependent gene expression. Because insulin stimulates carbohydrate and lipid synthesis, it would be important to decipher how the transcriptional activity of ADD1/SREBP1c is regulated in the insulin signaling pathway. In this study, we demonstrated that glycogen synthase kinase (GSK)-3 negatively regulates the transcriptional activity of ADD1/SREBP1c. GSK3 inhibitors enhanced a transcriptional activity of ADD1/SREBP1c and expression of ADD1/SREBP1c target genes including fatty acid synthase (FAS), acetyl-CoA carboxylase 1 (ACC1), and steroyl-CoA desaturase 1 (SCD1) in adipocytes and hepatocytes. In contrast, overexpression of GSK3beta down-regulated the transcriptional …

Characterization Of The Chicken Inward Rectifier K+ Channel Irk1/Kir2.1 Gene., Hideki Mutai, Lawrence C Kenyon, Emily Locke, Nami Kikuchi, John Carl Oberholtzer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Inward rectifier potassium channels (IRK) contribute to the normal function of skeletal and cardiac muscle cells. The chick inward rectifier K+ channel cIRK1/Kir2.1 is expressed in skeletal muscle, heart, brain, but not in liver; a distribution similar but not identical to that of mouse Kir2.1. We set out to explore regulatory domains of the cIRK1 promoter that enhance or inhibit expression of the gene in different cell types. RESULTS: We cloned and characterized the 5'-flanking region of cIRK1. cIRK1 contains two exons with splice sites in the 5'-untranslated region, a structure similar to mouse and human orthologs. cIRK1 has …

Rgs14 Is A Mitotic Spindle Protein Essential From The First Division Of The Mammalian Zygote., Luke Martin-Mccaffrey, Francis S Willard, Antonio J Oliveira-Dos-Santos, David R C Natale, Bryan E Snow, Randall J Kimple, Agnieszka Pajak, Andrew J Watson, Lina Dagnino, Josef M Penninger, David P Siderovski, Sudhir J A D'Souza

Obstetrics & Gynaecology Publications

Heterotrimeric G protein alpha subunits, RGS proteins, and GoLoco motif proteins have been recently implicated in the control of mitotic spindle dynamics in C. elegans and D. melanogaster. Here we show that "regulator of G protein signaling-14" (RGS14) is expressed by the mouse embryonic genome immediately prior to the first mitosis, where it colocalizes with the anastral mitotic apparatus of the mouse zygote. Loss of Rgs14 expression in the mouse zygote results in cytofragmentation and failure to progress to the 2-cell stage. RGS14 is found in all tissues and segregates to the nucleus in interphase and to the mitotic spindle …

A Subset Of Liver Nk T Cells Is Activated During Leishmania Donovani Infection By Cd1d-Bound Lipophosphoglycan, Joseph L. Amprey, Jin S. Im, Salvatore J. Turco, Henry W. Murray, Petr A. Illarionov, Gurdyal S. Besra, Steven A. Porcelli, Gerald F. Späth

Molecular and Cellular Biochemistry Faculty Publications

Natural killer (NK) T cells are activated by synthetic or self-glycolipids and implicated in innate host resistance to a range of viral, bacterial, and protozoan pathogens. Despite the immunogenicity of microbial lipoglycans and their promiscuous binding to CD1d, no pathogen-derived glycolipid antigen presented by this pathway has been identified to date. In the current work, we show increased susceptibility of NK T cell–deficient CD1d^−/− mice to Leishmania donovani infection and Leishmania-induced CD1d-dependent activation of NK T cells in wild-type animals. The elicited response was Th1 polarized, occurred as early as 2 h after infection, and was independent from …

A Vibrio Cholerae Classical Tcpa Amino Acid Sequence Induces Protective Antibody That Binds An Area Hypothesized To Be Important For Toxin-Coregulated Pilus Structure, Ronald K. Taylor, Thomas J. Kirn, Michael D. Meeks, Terri K. Wade, William F. Wade

Dartmouth Scholarship

Vibrio cholerae is a gram-negative bacterium that has been associated with cholera pandemics since the early 1800s. Whole-cell, killed, and live-attenuated oral cholera vaccines are in use. We and others have focused on the development of a subunit cholera vaccine that features standardized epitopes from various V. cholerae macromolecules that are known to induce protective antibody responses. TcpA protein is assembled into toxin-coregulated pilus (TCP), a type IVb pilus required for V. cholerae colonization, and thus is a strong candidate for a cholera subunit vaccine. Polypeptides (24 to 26 amino acids) in TcpA that can induce protective antibody responses have …

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 …

Combined Adipocyte-Macrophage Fatty Acid-Binding Protein Deficiency Improves Metabolism, Atherosclerosis, And Survival In Apolipoprotein E-Deficient Mice., Jeffrey Boord, Kazuhisa Maeda, Liza Makowski, Vladimir R Babaev, Sergio Fazio, Macrae F Linton, Gökhan S Hotamisligil

Hospital Medicine

BACKGROUND: The adipocyte fatty acid-binding protein (FABP) aP2 is expressed by adipocytes and macrophages and modulates insulin resistance, glucose and lipid metabolism, and atherosclerosis. Insulin sensitivity is improved in obese but not in lean aP2-deficient mice. A second fatty acid-binding protein, mal1, also is expressed in adipocytes and macrophages, and mal1 deficiency produces similar effects on insulin resistance. We tested the hypothesis that combined aP2 and mal1 deficiency would produce synergistic effects on metabolism and reduce atherosclerosis in apolipoprotein E-deficient (apoE-/-) mice.

METHODS AND RESULTS: Male and female apoE-/- mice null for both aP2 and mal1 (3KO) and apoE-/- controls …

Nf-Kappab And Ap-1 Connection: Mechanism Of Nf-Kappab-Dependent Regulation Of Ap-1 Activity, Shuichi Fujioka, Jiangong Niu, Christian Schmidt, Guido M Sclabas, Bailu Peng, Tadashi Uwagawa, Zhongkui Li, Douglas B Evans, James L Abbruzzese, Paul J Chiao

Faculty, Staff and Student Publications

Nuclear factor kappaB (NF-kappaB) and activator protein 1 (AP-1) transcription factors regulate many important biological and pathological processes. Activation of NF-kappaB is regulated by the inducible phosphorylation of NF-kappaB inhibitor IkappaB by IkappaB kinase. In contrast, Fos, a key component of AP-1, is primarily transcriptionally regulated by serum responsive factors (SRFs) and ternary complex factors (TCFs). Despite these different regulatory mechanisms, there is an intriguing possibility that NF-kappaB and AP-1 may modulate each other, thus expanding the scope of these two rapidly inducible transcription factors. To determine whether NF-kappaB activity is involved in the regulation of fos expression in response …

Cd4+ T Cells In The Pathogenesis Of Murine Ocular Toxoplasmosis, Fangli Lu, Shiguang Huang, Lloyd H. Kasper

Dartmouth Scholarship

The role of CD4⁺ T cells in the pathogenesis of ocular toxoplasmosis was investigated in murine models utilizing inbred C57BL/6 mice deficient either in CD4⁺, CD8⁺, or B cells (μMT). Severe necrosis and inflammation with replicating parasites were observed in the eyes of control mice after primary ocular infection, and near-normal histology with few tachyzoites was observed in the eyes of mice immunized intraperitoneally with the avirulent ts-4 strain followed by intraocular challenge with the RH strain of Toxoplasma gondii. In contrast, mild inflammation without evidence of necrosis associated with increased parasite burdens were …

Esophageal Muscle Physiology And Morphogenesis Require Assembly Of A Collagen Xix-Rich Basement Membrane Zone., Hideaki Sumiyoshi, Niv Mor, Sui Y Lee, Stephen Doty, Scott Henderson, Shizuko Tanaka, Hidekatsu Yoshioka, Satish Rattan, Francesco Ramirez

Department of Medicine Faculty Papers

Collagen XIX is an extremely rare extracellular matrix component that localizes to basement membrane zones and is transiently expressed by differentiating muscle cells. Characterization of mice harboring null and structural mutations of the collagen XIX (Col19a1) gene has revealed the critical contribution of this matrix protein to muscle physiology and differentiation. The phenotype includes smooth muscle motor dysfunction and hypertensive sphincter resulting from impaired swallowing-induced, nitric oxide-dependent relaxation of the sphincteric muscle. Muscle dysfunction was correlated with a disorganized matrix and a normal complement of enteric neurons and interstitial cells of Cajal. Mice without collagen XIX exhibit an additional defect, …

Vegetation Characteristics Associated With Small Mammal Populations In The Las Vegas Wash, Christine Therese Herndon

UNLV Theses, Dissertations, Professional Papers, and Capstones

Percent litter, average litter depth, percent bare ground, vegetation density, vegetation canopy, and distance to an ecotone boundary were measured and compared to small mammal capture locations in the Las Vegas Wash. Neotoma lepida appear to be greatly dependent upon the foliage litter of T. ramosissima. Alternatively, ecotone boundaries appear to be the most important factor affecting Dipodomys merriami distributions. Peromyscus eremicus distributions may be predicted based on vegetation density and increased canopy during shorter, winter torpor periods. Chaetodipus penicillatus were consistently associated with dense, seed-bearing vegetation, although C. penicillatus is extremely opportunistic and vegetation density should not limit their …