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Ghosh S.,Virginia Polytechnic Institute and State University | Elankumaran S.,Center for Molecular Medicine and Infectious Disease | Puri I.K.,Virginia Polytechnic Institute and State University
Cell Proliferation

Objectives: Intercellular cooperation has been hypothesized to enhance cell proliferation during cancer metastasis through autocrine signalling cascades and mathematical models can provide valuable insights into underlying mechanisms of metastatic tumorigenesis. Here, we present a model that incorporates signal-stimulated cell proliferation, and investigate influences of diffusion-driven heterogeneity in signal concentration on proliferation dynamics. Materials and methods: Our model incorporates signal production through both autocrine and paracrine pathways, and signal diffusion and loss for a metastasizing cell population at a host site. We use the signalling pathway of IL-6 for illustration where this signalling species forms an intermediate complex with its receptor IL-6R. This in turn forms a heterodimeric complex with transmembrane protein gp130, ultimately resulting in production of downstream signals. Cell population dynamics are taken to follow a modified logistic equation for which the rate term is dependent on local IL-6 concentration. Results and conclusions: Our spatiotemporal model agrees closely with experimental results. The model is also able to predict two phenomena typical of metastatic tumorigenesis - host tissue preference and long periods of proliferation dormancy. It confirms that diffusivity of the signalling species in a host tissue plays a significant role during the process. Our results show that the proliferation-apoptosis balance is tipped in favour of the former for host sites that have relatively smaller signal diffusivities. © 2011 Blackwell Publishing Ltd. Source

Whichard J.M.,Centers for Disease Control and Prevention | Weigt L.A.,Smithsonian Institution | Borris D.J.,Abbot Point of Care | Li L.L.,Pennsylvania State University | And 8 more authors.

Bacteriophage O1 is a Myoviridae A1 group member used historically for identifying Salmonella. Sequencing revealed a single, linear, 86,155-base-pair genome with 39% average G+C content, 131 open reading frames, and 22 tRNAs. Closest protein homologs occur in Erwinia amylovora phage φEa21-4 and Escherichia coli phage wV8. Proteomic analysis indentified structural proteins: Gp23, Gp36 (major tail protein), Gp49, Gp53, Gp54, Gp55, Gp57, Gp58 (major capsid protein), Gp59, Gp63, Gp64, Gp67, Gp68, Gp69, Gp73, Gp74 and Gp77 (tail fiber). Based on phage-host codon differences, 7 tRNAs could affect translation rate during infection. Introns, holin-lysin cassettes, bacterial toxin homologs and host RNA polymerase-modifying genes were absent. © 2010 by the authors. Source

Hardy C.G.,Naval Medical Center | Larsen C.T.,Center for Molecular Medicine and Infectious Disease | Holladay S.D.,University of Georgia | Johnson M.S.,U.S. Army | Gogal Jr. R.M.,University of Georgia
Avian Biology Research

Ascorbic acid (AA) enhances innate immunity, alters gene expression and functions as a co-factor in specific enzyme reactions. Birds are unique in that they can synthesise ascorbic acid whereas humans and rodents lack this ability. Diagnostic tests that currently exist to measure ascorbic acid levels in birds are time-consuming and expensive. In the present study, a modified and improved reductionbased colorimetric assay was evaluated in turkeys, quail and chickens. The assay was rapid for quantifying ascorbic acid in plasma and tissue samples, and generated values consistent with those obtained using HPLC. Five breeds of heritage turkeys were studied, showing significant plasma AA differences among breeds and, within breeds, by sex. Quail displayed plasma AA levels similar to the corresponding values that were highest in turkeys, which again were significantly greater in males than females. Chicken plasma AA levels were comparable to the turkeys and quail. However, the spleens of chickens had AA levels more than 12-fold higher than plasma, which increased significantly with a 150mg/kg AA feed supplement. These collective results show a broad utility for the modified AA assay, and demonstrate differences in birds by breed, sex and diet. Source

Karpuzoglu E.,Center for Molecular Medicine and Infectious Disease | Karpuzoglu E.,Baskent University | Zouali M.,University Paris Diderot
Clinical Reviews in Allergy and Immunology

Early studies of the immune system disclosed that, generally, females exhibit stronger responses to a variety of antigens than males. Perhaps as a result of this response, women are more prone to developing autoimmune diseases than men. Yet, the precise cellular and molecular mechanisms remain under investigation. Recently, interferon-gamma and the related pro-inflammatory interleukin-12 were found to be under effects of sex steroid hormones, with potential implications in regulating immune cells and autoimmune responses. In B lymphocytes, functional binding sites for estrogen receptors were identified in the promoter of the gene encoding activation-induced deaminase, an enzyme required for somatic hypermutation, and class-switch recombination. The observation that estrogen exerts direct impacts on antibody affinity-maturation provides a potential mechanism that could account for generating pathogenic high-affinity auto-antibodies. Further deciphering the multi-faceted influences of sex hormones on the responsiveness of immune cells could lead to novel therapeutic interventions for autoimmunity management. © 2009 Springer Science+Business Media, LLC. Source

Gogal R.M.,Center for Molecular Medicine and Infectious Disease | Gogal R.M.,University of Georgia | Kerr R.,Center for Molecular Medicine and Infectious Disease | Kerr R.,University of Georgia | And 6 more authors.
Journal of Food Protection

We have previously demonstrated that high pressure processing (HPP) is effective in preventing in vitro replication of murine norovirus strain 1 (MNV-1), a human norovirus surrogate, in a monocyte cell line following extraction from MNV-1-contaminated oysters. In the present study, the efficacy of HPP to prevent in vivo replication within mice fed HPP-treated MNV-1-seeded oyster extracts was evaluated. Oyster homogenate extracts seeded with MNV-1 were given 5-min, 400-MPa (58,016-psi) treatments and orally gavaged into immunodeficient (STAT-1-/-) female mice. Mice orally gavaged with HPP-treated MNV-1 showed significant (P # 0.05) weight loss leading to enhanced morbidity, whereas those given 100 and 200 PFU of HPP-treated MNV-1 were comparable to uninfected controls. MNV-1 was detected, via real-time PCR, within the liver, spleen, and brain of all mice fed non-HPP-treated homogenate but was not detected in the tissues of mice fed HPP-treated homogenates or in uninfected control mice. Hepatocellular necrosis and lymphoid depletion in the spleen were observed in non-HPP-treated MNV-1 mice only. These results clearly show that HPP prevents MNV-1 infection in vivo and validates that viral inactivation by HPP in vitro is essentially equivalent to that in vivo. Further, the data suggest that HPP may be an effective food processing intervention fornorovirus- contaminated shellfish and thus may decrease risk to both immunocompromised and immunocompetent individuals who consume shellfish. Source

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