Life Sciences Commons^™

The Allantois And Chorion, When Isolated Before Circulation Or Chorio-Allantoic Fusion, Have Hematopoietic Potential, Brandon M. Zeigler, Daisuke Sugiyama, Michael Chen, Yalin Guo, K. M. Downs, N. A. Speck

Dartmouth Scholarship

The chorio-allantoic placenta forms through the fusion of the allantois (progenitor tissue of the umbilical cord), with the chorionic plate. The murine placenta contains high levels of hematopoietic stem cells, and is therefore a stem cell niche. However, it is not known whether the placenta is a site of hematopoietic cell emergence, or whether hematopoietic cells originate from other sites in the conceptus and then colonize the placenta. Here, we show that the allantois and chorion, isolated prior to the establishment of circulation, have the potential to give rise to myeloid and definitive erythroid cells following explant culture. We further …

The Role Of Mapks In B Cell Receptor-Induced Down-Regulation Of Egr-1 In Immature B Lymphoma Cells, Jiyuan Ke, Murali Gururajan, Anupam Kumar, Alan Simmons, Lilia Turcios, Ralph Lakshman Chelvarajan, David M. Cohen, David L. Wiest, John G. Monroe, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Cross-linking of the B cell receptor (BCR) on the immature B lymphoma cell line BKS-2 induces growth inhibition and apoptosis accompanied by rapid down-regulation of the immediate-early gene egr-1. In these lymphoma cells, egr-1 is expressed constitutively and has a prosurvival role, as Egr-1-specific antisense oligonucleotides or expression of a dominant-negative inhibitor of Egr-1 also prevented the growth of BKS-2 cells. Moreover, enhancement of Egr-1 protein with phorbol 12-myristate 13-acetate or an egr-1 expression vector rescued BKS-2 cells from BCR signal-induced growth inhibition. Nuclear run-on and mRNA stability assays indicated that BCR-derived signals act at the transcriptional level to …

Cd80 And Cd86 Control Antiviral Cd8+ T-Cell Function And Immune Surveillance Of Murine Gammaherpesvirus 68, Shinichiro Fuse, Joshua J. Obar, Sarah Bellfy, Erica K. Leung, Weijun Zhang, Edward J. Usherwood

Dartmouth Scholarship

The interactions between CD80 and CD86 on antigen-presenting cells and CD28 on T cells serve as an important costimulatory signal in the activation of T cells. Although the simplistic two-signal hypothesis has been challenged in recent years by the identification of different costimulators, this classical pathway has been shown to significantly impact antiviral humoral and cellular immune responses. How the CD80/CD86-CD28 pathway affects the control of chronic or latent infections has been less well characterized. In this study, we investigated its role in antiviral immune responses against murine gammaherpesvirus 68 (MHV-68) and immune surveillance using CD80/CD86^−/− mice. In the …

Gammaherpesvirus Persistence Alters Key Cd8 T-Cell Memory Characteristics And Enhances Antiviral Protection, Joshua J. Obar, Shinichiro Fuse, Erica K. Leung, Sarah C. Bellfy, Edward J. Usherwood

Dartmouth Scholarship

In herpesvirus infections, the virus persists for life but is contained through T-cell-mediated immune surveillance. How this immune surveillance operates is poorly understood. Recent studies of other persistent infections have indicated that virus persistence is associated with functional deficits in the CD8(+) T-cell response. To test whether this is the case in a herpesvirus infection, we used a mutant murine gammaherpesvirus that is defective in its ability to persist in the host. By comparing the immune response to this virus with a revertant virus that can persist, we were able to dissect the changes in the antiviral CD8(+) T-cell response …

Gene Order Data From A Model Amphibian (Ambystoma): New Perspectives On Vertebrate Genome Structure And Evolution, Jeramiah J. Smith, S. Randal Voss

Biology Faculty Publications

BACKGROUND: Because amphibians arise from a branch of the vertebrate evolutionary tree that is juxtaposed between fishes and amniotes, they provide important comparative perspective for reconstructing character changes that have occurred during vertebrate evolution. Here, we report the first comparative study of vertebrate genome structure that includes a representative amphibian. We used 491 transcribed sequences from a salamander (Ambystoma) genetic map and whole genome assemblies for human, mouse, rat, dog, chicken, zebrafish, and the freshwater pufferfish Tetraodon nigroviridis to compare gene orders and rearrangement rates.

RESULTS: Ambystoma has experienced a rate of genome rearrangement that is substantially lower than mammalian …

A Pdz-Binding Motif As A Critical Determinant Of Rho Guanine Exchange Factor Function And Cell Phenotype, Miaoliang Liu, Arie Horowitz

Dartmouth Scholarship

We identified a Rho guanine exchange factor (GEF) expressed as two splice variants, which differ only in either having or lacking a Postsynaptic density 95, Disk large, Zona occludens-1 (PDZ) motif. The PDZ adaptor protein synectin bound the longer splice variant, Syx1, which was targeted to the plasma membrane in a synectin-dependent manner. The shorter variant, Syx2, was diffusely distributed in the cytoplasm. Fluorescence resonance energy transfer (FRET) imaging revealed similar differences between the spatial patterns of active RhoA in Syx1 versus Syx2-expressing cells. Expression of Syx1 augmented endothelial cell (EC) migration and tube formation, whereas Syx2 expression did not. …

H2-M3-Restricted Cd8+ T Cells Are Not Required For Mhc Class Ib-Restricted Immunity Against Listeria Monocytogenes, Sarah E. F. D'Orazio, Christine A. Shaw, Michael N. Starnbach

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Studies using major histocompatibility complex (MHC)-Ia–deficient mice have shown that MHC-Ib–restricted CD8⁺ T cells can clear infections caused by intracellular pathogens such as Listeria monocytogenes. M3-restricted CD8⁺ T cells, which recognize short hydrophobic N-formylated peptides, appear to comprise a substantial portion of the MHC-Ib–restricted T cell response in the mouse model of L. monocytogenes infection. In this study, we isolated formyltransferase (fmt) mutant strains of L. monocytogenes that lacked the ability to add formyl groups to nascent polypeptides. These fmt mutant Listeria strains did not produce antigens that could be recognized by M3-restricted T …

Type 3 Deiodinase Is Critical For The Maturation And Function Of The Thyroid Axis, Arturo Hernandez, M. Elena Martinez, Steven Flering, Valerie Anne Galton, Donald St. German

Dartmouth Scholarship

Developmental exposure to appropriate levels of thyroid hormones (THs) in a timely manner is critical to normal development in vertebrates. Among the factors potentially affecting perinatal exposure of tissues to THs is type 3 deiodinase (D3). This enzyme degrades THs and is highly expressed in the pregnant uterus, placenta, and fetal and neonatal tissues. To determine the physiological role of D3, we have generated a mouse D3 knockout model (D3KO) by a targeted inactivating mutation of the Dio3 gene in mouse ES cells. Early in life, D3KO mice exhibit delayed 3,5,3′-triiodothyronine (T3) clearance, a markedly elevated serum T3 level, and …

Comparison Of Feed Energy Costs Of Maintenance, Lean Deposition, And Fat Deposition In Three Lines Of Mice Selected For Heat Loss, D. L. Eggert, Merlyn K. Nielsen

Department of Animal Science: Faculty Publications

Three replications of mouse selection populations for high heat loss (MH), low heat loss (ML), and a nonselected control (MC) were used to estimate the feed energy costs of maintenance and gain and to test whether selection had changed these costs. At 21 and 49 d of age, mice were weighed and subjected to dual x-ray densitometry measurement for prediction of body composition. At 21 d, mice were randomly assigned to an ad libitum, an 80% of ad libitum, or a 60% of ad libitum feeding group for 28-d collection of individual feed intake. Data were analyzed using 3 approaches. …

Gene Expression And Discovery During Lens Regeneration In Mouse: Regulation Of Epithelial To Mesenchymal Transition And Lens Differentiation, Mario Medvedovic, Craig R. Tomlinson, Mindy Kay Call, Matthew Grogg, Panagiotis A. Tsonis

Biology Faculty Publications

Purpose: It has been shown that after extracapsular lens removal by anterior capsulotomy in the mouse, the lens can be regenerated. However, as the capsular bag is filled with fibers, epithelial to mesenchymal transition (EMT), an event which is common after cataract surgery as well, takes place during early stages. This study, using a unique mouse model, was undertaken to identify novel regulators and networks in order to more clearly understand secondary cataracts at the molecular level.

Evaluation Of Immunomodulators, Interferons And Known In Vitro Sars-Cov Inhibitors For Inhibition Of Sars-Cov Replication In Balb/C Mice, Dale L. Barnard, C. W. Day, K. Bailey, M. Heiner, R. Montgomery, L. Lauridsen, P. K-S. Chan, R. W. Sidwell

Animal, Dairy, and Veterinary Science Faculty Publications

Compounds approved for therapeutic use and in vitro inhibitors of severe acute respiratory syndrome coronavirus (SARS-CoV) were evaluated for inhibition in the mouse SARS-CoV replication model. A hybrid interferon, interferon alpha (IFN-alpha) B/D, and a mismatched double-stranded (ds) RNA interferon (IFN) inducer, Ampligen® (poly I:poly C124), were the only compounds that potently inhibited virus titres in the lungs of infected mice as assessed by CPE titration assays. When mice were dosed intraperitoneally (i.p.) with IFN-alpha B/D once daily for 3 days beginning 4 h after virus exposure, SARS-CoV replication in the lungs of infected mice was reduced by 1 log10 …