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      1. Author :
        Schwan, William R; Lehmann, Lynn; McCormick, James
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2006
      5. Publication :
        Infection and immunity
      6. Products :
      7. Volume :
        74
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Amino Acid Transport Systems, Neutral; Animals; Bacterial Proteins; Bioware; Blotting, Northern; Disease Models, Animal; Gene Expression Regulation, Bacterial; Humans; Lac Operon; Mice; Osmolar Concentration; Proline; pXen-5; Recombinant Fusion Proteins; Staphylococcal Infections; Staphylococcus aureus; Symporters; Transcriptional Activation
      12. Abstract :
        Staphylococcus aureus can grow virtually anywhere in the human body but needs to import proline through low- and high-affinity proline transporters to survive. This study examined the regulation of the S. aureus putP gene, which encodes a high-affinity proline permease. putP::lacZ and putP::lux transcriptional fusions were constructed and integrated into the genomes of several S. aureus strains. Enzyme activity was measured after growth in media with various osmolyte concentrations. As osmolarity rose, putP expression increased, with a plateau at 2 M for NaCl in strain LL3-1. Proline concentrations as low as 17.4 muM activated expression of the putP gene. The putP::lux fusion was also integrated into the genomes of S. aureus strains that were either SigB inactive (LL3-1, 8325-4, and SH1003) or SigB active (Newman and SH1000). SigB inactive strains showed increased putP gene expression as NaCl concentrations rose, whereas SigB active strains displayed a dramatic decrease in putP expression, suggesting that the alternative sigma factor B plays a negative role in putP regulation. Mice inoculated with S. aureus strains containing the putP::lux fusion exhibited up to a 715-fold increase in putP expression, although levels in the various murine organs differed. Moreover, urine from human patients infected with S. aureus showed elevated putP levels by use of a PCR procedure, whereas blood and some abscess material had no significant increase. Thus, putP is transcriptionally activated by a low-proline and high osmotic environment both in growth media and in murine or human clinical specimens.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/16368996
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9023
      1. Author :
        N/A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        PloS one
      6. Products :
      7. Volume :
        2
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Adhesins, Bacterial; Animals; Antigens, CD46; Bacteremia; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Translocation; Bioware; Blood-Brain Barrier; Central Nervous System; Disease Progression; Female; Luminescent Measurements; Luminescent Proteins; Male; Meningitis, Meningococcal; Meningococcal Infections; Mice; Mice, Transgenic; Nasal Cavity; pXen-13; Recombinant Fusion Proteins; Respiratory System; Sepsis; Thyroid Gland
      12. Abstract :
        Neisseria meningitidis is a human pathogen that causes septicemia and meningitis with high mortality. The disease progression is rapid and much remains unknown about the disease process. The understanding of disease development is crucial for development of novel therapeutic strategies and vaccines against meningococcal disease. The use of bioluminescent imaging combined with a mouse disease model allowed us to investigate the progression of meningococcal sepsis over time. Injection of bacteria in blood demonstrated waves of bacterial clearance and growth, which selected for Opa-expressing bacteria, indicating the importance of this bacterial protein. Further, N. meningitidis accumulated in the thyroid gland, while thyroid hormone T4 levels decreased. Bacteria reached the mucosal surfaces of the upper respiratory tract, which required expression of the meningococcal PilC1 adhesin. Surprisingly, PilC1 was dispensable for meningococcal growth in blood and for crossing of the blood-brain barrier, indicating that the major role of PilC1 is to interact with mucosal surfaces. This in vivo study reveals disease dynamics and organ targeting during meningococcal disease and presents a potent tool for further investigations of meningococcal pathogenesis and vaccines in vivo. This might lead to development of new strategies to improve the outcome of meningococcal disease in human patients.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/17311106
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9032
      1. Author :
        Woelfle, Mark A; Xu, Yao; Qin, Ximing; Johnson, Carl Hirschie
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        Proceedings of the National Academy of Sciences of the United States of America
      6. Products :
      7. Volume :
        104
      8. Issue :
        47
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Bioware; Circadian Rhythm; Cyanobacteria; DNA, Bacterial; DNA, Superhelical; Gene Expression Regulation, Bacterial; Light; Plasmids; Promoter Regions, Genetic; pXen-13; Transcription, Genetic
      12. Abstract :
        The cyanobacterium Synechococcus elongatus expresses robust circadian (daily) rhythms under the control of the KaiABC-based core clockwork. Unlike eukaryotic circadian systems characterized thus far, the cyanobacterial clockwork modulates gene expression patterns globally and specific clock gene promoters are not necessary in mediating the circadian feedback loop. The oscilloid model postulates that global rhythms of transcription are based on rhythmic changes in the status of the cyanobacterial chromosome that are ultimately controlled by the KaiABC oscillator. By using a nonessential, cryptic plasmid (pANS) as a reporter of the superhelical state of DNA in cyanobacteria, we show that the supercoiling status of this plasmid changes in a circadian manner in vivo. The rhythm of topological change in the plasmid is conditional; this change is rhythmic in constant light and in light/dark cycles, but not in constant darkness. In further support of the oscilloid model, cyanobacterial promoters that are removed from their native chromosomal locations and placed on a plasmid preserve their circadian expression patterns.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/18000054
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9031
      1. Author :
        Xu, Xiulan; Miller, Sally A; Baysal-Gurel, Fulya; Gartemann, Karl-Heinz; Eichenlaub, Rudolf; Rajashekara, Gireesh
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Applied and environmental microbiology
      6. Products :
      7. Volume :
        76
      8. Issue :
        12
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Actinomycetales; Bioware; Genes, Reporter; Genetic Engineering; Luminescent Proteins; Lycopersicon esculentum; Mirabilis; Plant Diseases; pXen-13; Recombinant Proteins; Seeds; Staining and Labeling
      12. Abstract :
        Clavibacter michiganensis subsp. michiganensis is a Gram-positive bacterium that causes wilting and cankers, leading to severe economic losses in commercial tomato production worldwide. The disease is transmitted from infected seeds to seedlings and mechanically from plant to plant during seedling production, grafting, pruning, and harvesting. Because of the lack of tools for genetic manipulation, very little is known regarding the mechanisms of seed and seedling infection and movement of C. michiganensis subsp. michiganensis in grafted plants, two focal points for application of bacterial canker control measures in tomato. To facilitate studies on the C. michiganensis subsp. michiganensis movement in tomato seed and grafted plants, we isolated a bioluminescent C. michiganensis subsp. michiganensis strain using the modified Tn1409 containing a promoterless lux reporter. A total of 19 bioluminescent C. michiganensis subsp. michiganensis mutants were obtained. All mutants tested induced a hypersensitive response in Mirabilis jalapa and caused wilting of tomato plants. Real-time colonization studies of germinating seeds using a virulent, stable, constitutively bioluminescent strain, BL-Cmm17, showed that C. michiganensis subsp. michiganensis aggregated on hypocotyls and cotyledons at an early stage of germination. In grafted seedlings in which either the rootstock or scion was exposed to BL-Cmm17 via a contaminated grafting knife, bacteria were translocated in both directions from the graft union at higher inoculum doses. These results emphasize the use of bioluminescent C. michiganensis subsp. michiganensis to help better elucidate the C. michiganensis subsp. michiganensis-tomato plant interactions. Further, we demonstrated the broader applicability of this tool by successful transformation of C. michiganensis subsp. nebraskensis with Tn1409::lux. Thus, our approach would be highly useful to understand the pathogenesis of diseases caused by other subspecies of the agriculturally important C. michiganensis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20400561
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9028
      1. Author :
        Kim, J. B.; Urban, K.; Cochran, E.; Lee, S.; Ang, A.; Rice, B.; Bata, A.; Campbell, K.; Coffee, R.; Gorodinsky, A.; Lu, Z.; Zhou, H.; Kishimoto, T. K.; Lassota, P.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        PLoS One
      6. Products :
      7. Volume :
        5
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xenogen, VIS, 4T1-luc2, Animals; Cell Line, Tumor; Diagnostic Imaging/*methods; Female; Genetic Vectors/genetics; Lentivirus/genetics; Luciferases/genetics/*metabolism; Luminescent Measurements/instrumentation/*methods; Lung Neoplasms/diagnosis/metabolism/secondary; Mammary Neoplasms, Experimental/diagnosis/genetics/*metabolism; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Neoplasms/genetics/metabolism/pathology; Sensitivity and Specificity; Time Factors; Transfection; Tumor Burden
      12. Abstract :
        Early detection of tumors can significantly improve the outcome of tumor treatment. One of the most frequently asked questions in cancer imaging is how many cells can be detected non-invasively in a live animal. Although many factors limit such detection, increasing the light emission from cells is one of the most effective ways of overcoming these limitations. Here, we describe development and utilization of a lentiviral vector containing enhanced firefly luciferase (luc2) gene. The resulting single cell clones of the mouse mammary gland tumor (4T1-luc2) showed stable light emission in the range of 10,000 photons/sec/cell. In some cases individual 4T1-luc2 cells inserted under the skin of a nu/nu mouse could be detected non-invasively using a cooled CCD camera in some cases. In addition, we showed that only few cells are needed to develop tumors in these mice and tumor progression can be monitored right after the cells are implanted. Significantly higher luciferase activity in these cells allowed us to detect micrometastases in both, syngeneic Balb/c and nu/nu mice.
      13. URL :
        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20186331
      14. Call Number :
        139615
      15. Serial :
        7111
      1. Author :
        Beck, Benjamin H; Kim, Hyung-Gyoon; Kim, Hyunki; Samuel, Sharon; Liu, Zhiyong; Shrestha, Robin; Haines, Hilary; Zinn, Kurt; Lopez, Richard D
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Breast cancer research and treatment
      6. Products :
      7. Volume :
        122
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        4T1-luc2; Adenocarcinoma; Animals; Bioware; Breast Neoplasms; Cell Line, Tumor; Chemotaxis, Leukocyte; Cytotoxicity, Immunologic; Female; Humans; Immunotherapy, Adoptive; Indium Radioisotopes; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Mice, Knockout; Neoplasm Transplantation; Radiopharmaceuticals; Receptors, Antigen, T-Cell, gamma-delta; Spleen; Tissue Distribution; T-Lymphocyte Subsets; Tomography, Emission-Computed, Single-Photon; Transplantation, Heterologous; Transplantation, Isogeneic
      12. Abstract :
        In contrast to antigen-specific alphabeta-T cells (adaptive immune system), gammadelta-T cells can recognize and lyse malignantly transformed cells almost immediately upon encounter in a manner that does not require the recognition of tumor-specific antigens (innate immune system). Given the well-documented capacity of gammadelta-T cells to innately kill a variety of malignant cells, efforts are now actively underway to exploit the antitumor properties of gammadelta-T cells for clinical purposes. Here, we present for the first time preclinical in vivo mouse models of gammadelta-T cell-based immunotherapy directed against breast cancer. These studies were explicitly designed to approximate clinical situations in which adoptively transferred gammadelta-T cells would be employed therapeutically against breast cancer. Using radioisotope-labeled gammadelta-T cells, we first show that adoptively transferred gammadelta-T cells localize to breast tumors in a mouse model (4T1 mammary adenocarcinoma) of human breast cancer. Moreover, by using an antibody directed against the gammadelta-T cell receptor (TCR), we determined that localization of adoptively transferred gammadelta-T cells to tumor is a TCR-dependant process. Additionally, biodistribution studies revealed that adoptively transferred gammadelta-T cells traffic differently in tumor-bearing mice compared to healthy mice with fewer gammadelta-T cells localizing into the spleens of tumor-bearing mice. Finally, in both syngeneic (4T1) and xenogeneic (2Lmp) models of breast cancer, we demonstrate that adoptively transferred gammadelta-T cells are both effective against breast cancer and are otherwise well-tolerated by treated animals. These findings provide a strong preclinical rationale for using ex vivo expanded adoptively transferred gammadelta-T cells as a form of cell-based immunotherapy for the treatment of breast cancer. Additionally, these studies establish that clinically applicable methods for radiolabeling gammadelta-T cells allows for the tracking of adoptively transferred gammadelta-T cells in tumor-bearing hosts.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19763820
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8939
      1. Author :
        Kim, Jae-Beom; Urban, Konnie; Cochran, Edward; Lee, Steve; Ang, Angel; Rice, Bradley; Bata, Adam; Campbell, Kenneth; Coffee, Richard; Gorodinsky, Alex; Lu, Zhan; Zhou, He; Kishimoto, Takashi Kei; Lassota, Peter
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        PloS one
      6. Products :
      7. Volume :
        5
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        4T1-luc2; Animals; Bicuculline; Bioware; Cell Line, Tumor; Diagnostic Imaging; Female; Genetic Vectors; Lentivirus; Luciferases; Luminescent Measurements; Lung Neoplasms; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Neoplasms; Sensitivity and Specificity; Time Factors; Transfection; Tumor Burden
      12. Abstract :
        Early detection of tumors can significantly improve the outcome of tumor treatment. One of the most frequently asked questions in cancer imaging is how many cells can be detected non-invasively in a live animal. Although many factors limit such detection, increasing the light emission from cells is one of the most effective ways of overcoming these limitations. Here, we describe development and utilization of a lentiviral vector containing enhanced firefly luciferase (luc2) gene. The resulting single cell clones of the mouse mammary gland tumor (4T1-luc2) showed stable light emission in the range of 10,000 photons/sec/cell. In some cases individual 4T1-luc2 cells inserted under the skin of a nu/nu mouse could be detected non-invasively using a cooled CCD camera in some cases. In addition, we showed that only few cells are needed to develop tumors in these mice and tumor progression can be monitored right after the cells are implanted. Significantly higher luciferase activity in these cells allowed us to detect micrometastases in both, syngeneic Balb/c and nu/nu mice.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20186331
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8938
      1. Author :
        Kosaka, Nobuyoshi; Iguchi, Haruhisa; Yoshioka, Yusuke; Takeshita, Fumitaka; Matsuki, Yasushi; Ochiya, Takahiro
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        The Journal of biological chemistry
      6. Products :
      7. Volume :
        285
      8. Issue :
        23
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Aniline Compounds; Animals; Benzylidene Compounds; Biological Transport; Bioware; Cercopithecus aethiops; COS Cells; Culture Media, Conditioned; Exosomes; Gene Silencing; Humans; MicroRNAs; Neoplasms; PC-3M-luc; RNA Interference; RNA, Small Interfering; Sphingomyelin Phosphodiesterase; Tumor Markers, Biological
      12. Abstract :
        The existence of circulating microRNAs (miRNAs) in the blood of cancer patients has raised the possibility that miRNAs may serve as a novel diagnostic marker. However, the secretory mechanism and biological function of extracellular miRNAs remain unclear. Here, we show that miRNAs are released through a ceramide-dependent secretory machinery and that the secretory miRNAs are transferable and functional in the recipient cells. Ceramide, whose biosynthesis is regulated by neutral sphingomyelinase 2 (nSMase2), triggers secretion of small membrane vesicles called exosomes. The decreased activity of nSMase2 with a chemical inhibitor, GW4869, and a specific small interfering RNA resulted in the reduced secretion of miRNAs. Complementarily, overexpression of nSMase2 increased extracellular amounts of miRNAs. We also revealed that the endosomal sorting complex required for transport system is unnecessary for the release of miRNAs. Furthermore, a tumor-suppressive miRNA secreted via this pathway was transported between cells and exerted gene silencing in the recipient cells, thereby leading to cell growth inhibition. Our findings shed a ray of light on the physiological relevance of secretory miRNAs.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20353945
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8946
      1. Author :
        N/A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Clinical & experimental metastasis
      6. Products :
      7. Volume :
        26
      8. Issue :
        7
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        4T1-luc2; Animals; Bioware; Cell Line, Tumor; Disease Models, Animal; DNA-Binding Proteins; Female; Flow Cytometry; Killer Cells, Natural; Lung Neoplasms; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Mice, Knockout; Mice, SCID; Neoplasm Metastasis; Rats
      12. Abstract :
        The occurrence of metastases is a critical determinant of the prognosis for breast cancer patients. Effective treatment of breast cancer metastases is hampered by a poor understanding of the mechanisms involved in the formation of these secondary tumor deposits. To study the processes of metastasis, valid in vivo tumor metastasis models are required. Here, we show that increased expression of the EGF receptor in the MTLn3 rat mammary tumor cell-line is essential for efficient lung metastasis formation in the Rag mouse model. EGFR expression resulted in delayed orthotopic tumor growth but at the same time strongly enhanced intravasation and lung metastasis. Previously, we demonstrated the critical role of NK cells in a lung metastasis model using MTLn3 cells in syngenic F344 rats. However, this model is incompatible with human EGFR. Using the highly metastatic EGFR-overexpressing MTLn3 cell-line, we report that only Rag2(-/-)gammac(-/-) mice, which lack NK cells, allow efficient lung metastasis from primary tumors in the mammary gland. In contrast, in nude and SCID mice, the remaining innate immune cells reduce MTLn3 lung metastasis formation. Furthermore, we confirm this finding with the orthotopic transplantation of the 4T1 mouse mammary tumor cell-line. Thus, we have established an improved in vivo model using a Rag2(-/-) gammac(-/-) mouse strain together with MTLn3 cells that have increased levels of the EGF receptor, which enables us to study EGFR-dependent tumor cell autonomous mechanisms underlying lung metastasis formation. This improved model can be used for drug target validation and development of new therapeutic strategies against breast cancer metastasis formation.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19466569
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8940