U.S. Navy, Naval Sea Systems Command

U.S. Navy, Naval Sea Systems Command and Program Executive Office SHIPS, PMS 500 DD X Program

U.S. Navy, Naval Sea Systems Command

A mixture of shipbuilding, architecture, and art went into producing the wooden decorative work aboard ships of all nations from around the late 1500s until the advent of steam and the steel ship in the late 19th century. The leading humanists and artists in each country were called upon to draw up the iconographic plan for a ship??s ornamentation and to ensure that the work was done according to the ruler??s instructions. By looking through previous research, admiralty records, archaeological examples, and contemporary ship models, the progression of this maritime art form can be followed.

The SH2 domain-containing inositol 5’-phosphatase, SHIP, negatively regulates hematopoietic cell functions and is critical for maintaining immune homeostasis. However, whether SHIP plays a role in controlling bacterial infections in vivo remained unknown. Salmonella enterica causes human salmonellosis, a disease that ranges in severity from mild gastroenteritis to severe systemic illness, resulting in significant morbidity and mortality worldwide. The focus of this work was to determine the role of SHIP in a murine model of systemic Salmonellosis. Susceptibility of ship⁺/⁺and ship⁻/⁻ mice to S. enterica serovar Typhimurium infection was compared. ship⁻/⁻ mice displayed an increased susceptibility to both oral and intraperitoneal S. Typhimurium infection and had significantly higher bacterial loads in intestinal and systemic sites than ship⁺/⁺mice, indicating a role for SHIP in the gut and systemic pathogenesis of S. Typhimurium in vivo. Blood cytokine levels showed that infected ship⁻/⁻ mice produce lower levels of Th1 polarizing cytokines compared to ship⁺/⁺ animals, and analysis of supernatants taken from M2 bone marrow derived macrophages correlated with this data. M2 macrophages were the predominant population in vivo during both oral and intraperitoneal infections. Because M2 macrophages are poor defenders against bacterial infection, these data suggest that M2 macrophage skewing in ship⁻/⁻ mice contributes to ineffective clearance of Salmonella. The role of SHIP in the gut during enteric infections was also explored. ship⁻/⁻ mice were not susceptible to Citrobacter rodentium infection, yet developed severe inflammation of the ileum upon infection with this bacterium, with Salmonella, or when challenged orally with LPS. Increased collagen deposition was also observed at early time points post-infection, suggesting that ship⁻/⁻ mice may be used to study the development of inflammatory bowel diseases characterized by fibrosis, such as Crohn's. Because SHIP is such a critical negative regulator in both innate and adaptive immune cells, it has the potential to significantly alter the outcome of infections. This work highlights the fact that SHIP is important in vivo during Salmonellosis and opens new avenues to explore targeting SHIP in therapies for both systemic infections as well as inflammatory bowel diseases.

The SH2 domain-containing inositol 5’-phosphatase, SHIP, negatively regulates hematopoietic cell functions and is critical for maintaining immune homeostasis. However, whether SHIP plays a role in controlling bacterial infections in vivo remained unknown. Salmonella enterica causes human salmonellosis, a disease that ranges in severity from mild gastroenteritis to severe systemic illness, resulting in significant morbidity and mortality worldwide. The focus of this work was to determine the role of SHIP in a murine model of systemic Salmonellosis. Susceptibility of ship⁺/⁺and ship⁻/⁻ mice to S. enterica serovar Typhimurium infection was compared. ship⁻/⁻ mice displayed an increased susceptibility to both oral and intraperitoneal S. Typhimurium infection and had significantly higher bacterial loads in intestinal and systemic sites than ship⁺/⁺mice, indicating a role for SHIP in the gut and systemic pathogenesis of S. Typhimurium in vivo. Blood cytokine levels showed that infected ship⁻/⁻ mice produce lower levels of Th1 polarizing cytokines compared to ship⁺/⁺ animals, and analysis of supernatants taken from M2 bone marrow derived macrophages correlated with this data. M2 macrophages were the predominant population in vivo during both oral and intraperitoneal infections. Because M2 macrophages are poor defenders against bacterial infection, these data suggest that M2 macrophage skewing in ship⁻/⁻ mice contributes to ineffective clearance of Salmonella. The role of SHIP in the gut during enteric infections was also explored. ship⁻/⁻ mice were not susceptible to Citrobacter rodentium infection, yet developed severe inflammation of the ileum upon infection with this bacterium, with Salmonella, or when challenged orally with LPS. Increased collagen deposition was also observed at early time points post-infection, suggesting that ship⁻/⁻ mice may be used to study the development of inflammatory bowel diseases characterized by fibrosis, such as Crohn's. Because SHIP is such a critical negative regulator in both innate and adaptive immune cells, it has the potential to significantly alter the outcome of infections. This work highlights the fact that SHIP is important in vivo during Salmonellosis and opens new avenues to explore targeting SHIP in therapies for both systemic infections as well as inflammatory bowel diseases.

Thesis (doctoral)--Georg-August-Universität zu Göttingen.

Thesis (Ph. D.)--University of Pennsylvania, 1928. / Bibliography: p. [111]-116.

Report (M.S.)--Virginia Polytechnic Institute and State University, 1994. / Abstract. Includes bibliographical references (leaves 55-56). Also available via the Internet.

The SH2 domain-containing inositol 5’-phosphatase, SHIP, negatively regulates hematopoietic cell functions and is critical for maintaining immune homeostasis. However, whether SHIP plays a role in controlling bacterial infections in vivo remained unknown. Salmonella enterica causes human salmonellosis, a disease that ranges in severity from mild gastroenteritis to severe systemic illness, resulting in significant morbidity and mortality worldwide. The focus of this work was to determine the role of SHIP in a murine model of systemic Salmonellosis. Susceptibility of ship⁺/⁺and ship⁻/⁻ mice to S. enterica serovar Typhimurium infection was compared. ship⁻/⁻ mice displayed an increased susceptibility to both oral and intraperitoneal S. Typhimurium infection and had significantly higher bacterial loads in intestinal and systemic sites than ship⁺/⁺mice, indicating a role for SHIP in the gut and systemic pathogenesis of S. Typhimurium in vivo. Blood cytokine levels showed that infected ship⁻/⁻ mice produce lower levels of Th1 polarizing cytokines compared to ship⁺/⁺ animals, and analysis of supernatants taken from M2 bone marrow derived macrophages correlated with this data. M2 macrophages were the predominant population in vivo during both oral and intraperitoneal infections. Because M2 macrophages are poor defenders against bacterial infection, these data suggest that M2 macrophage skewing in ship⁻/⁻ mice contributes to ineffective clearance of Salmonella. The role of SHIP in the gut during enteric infections was also explored. ship⁻/⁻ mice were not susceptible to Citrobacter rodentium infection, yet developed severe inflammation of the ileum upon infection with this bacterium, with Salmonella, or when challenged orally with LPS. Increased collagen deposition was also observed at early time points post-infection, suggesting that ship⁻/⁻ mice may be used to study the development of inflammatory bowel diseases characterized by fibrosis, such as Crohn's. Because SHIP is such a critical negative regulator in both innate and adaptive immune cells, it has the potential to significantly alter the outcome of infections. This work highlights the fact that SHIP is important in vivo during Salmonellosis and opens new avenues to explore targeting SHIP in therapies for both systemic infections as well as inflammatory bowel diseases. / Science, Faculty of / Microbiology and Immunology, Department of / Graduate