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  • 1
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 110, No. 48 ( 2013-11-26), p. 19615-19620
    Abstract: Rickettsiae are responsible for some of the most devastating human infections. A high infectivity and severe illness after inhalation make some rickettsiae bioterrorism threats. We report that deletion of the exchange protein directly activated by cAMP (Epac) gene, Epac1 , in mice protects them from an ordinarily lethal dose of rickettsiae. Inhibition of Epac1 suppresses bacterial adhesion and invasion. Most importantly, pharmacological inhibition of Epac1 in vivo using an Epac-specific small-molecule inhibitor, ESI-09, completely recapitulates the Epac1 knockout phenotype. ESI-09 treatment dramatically decreases the morbidity and mortality associated with fatal spotted fever rickettsiosis. Our results demonstrate that Epac1-mediated signaling represents a mechanism for host–pathogen interactions and that Epac1 is a potential target for the prevention and treatment of fatal rickettsioses.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2013
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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  • 2
    Online Resource
    Online Resource
    Wiley ; 2008
    In:  Annals of the New York Academy of Sciences Vol. 1140, No. 1 ( 2008-10), p. 184-189
    In: Annals of the New York Academy of Sciences, Wiley, Vol. 1140, No. 1 ( 2008-10), p. 184-189
    Abstract: Anembryonic pregnancy (AP; blighted ovum is the clinical term) is a common presentation of first‐trimester abortion in China and affected women usually miscarry at 8–13 weeks. The association of plasma lead and the risk of AP in women from Shanxi Province, China, was examined. A case–control study was conducted, and plasma concentrations of lead were measured in blood obtained from women ( n = 40) with AP and controls ( n = 40) of normal pregnancy at their prenatal examination. AP was diagnosed by ultrasound scanning. The controls were identified and qualified by following up until a normal neonate was born. The mean concentration of lead in patients (53 μg/L, 95%CI: 4.3–6.3 μg/L) was slightly greater than the normal reference (50 μg/L, P 〈 0.01). The mean concentration of lead was higher in patients than in controls (53 versus 45 μg/L, P = 0.03). The lead concentration may be associated with the risk of AP, and should be paid more attention. Lead concentration that is slightly more than the standard limit may increase the risk of AP, but there may also be some other factors assisting lead to cause the occurrence of AP. Additional studies will be needed to confirm the findings and to find which factors were associated with the risk of AP when plasma lead is present.
    Type of Medium: Online Resource
    ISSN: 0077-8923 , 1749-6632
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2008
    detail.hit.zdb_id: 2834079-6
    detail.hit.zdb_id: 211003-9
    detail.hit.zdb_id: 2071584-5
    SSG: 11
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  • 3
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2007
    In:  Proceedings of the National Academy of Sciences Vol. 104, No. 37 ( 2007-09-11), p. 14553-14558
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 104, No. 37 ( 2007-09-11), p. 14553-14558
    Abstract: Cells respond to mechanical forces whether applied externally or generated internally via the cytoskeleton. To study the cellular response to forces separately, we applied external forces to cells via microfabricated magnetic posts containing cobalt nanowires interspersed among an array of elastomeric posts, which acted as independent sensors to cellular traction forces. A magnetic field induced torque in the nanowires, which deflected the magnetic posts and imparted force to individual adhesions of cells attached to the array. Using this system, we examined the cellular reaction to applied forces and found that applying a step force led to an increase in local focal adhesion size at the site of application but not at nearby nonmagnetic posts. Focal adhesion recruitment was enhanced further when cells were subjected to multiple force actuations within the same time interval. Recording the traction forces in response to such force stimulation revealed two responses: a sudden loss in contractility that occurred within the first minute of stimulation or a gradual decay in contractility over several minutes. For both types of responses, the subcellular distribution of loss in traction forces was not confined to locations near the actuated micropost, nor uniformly across the whole cell, but instead occurred at discrete locations along the cell periphery. Together, these data reveal an important dynamic biological relationship between external and internal forces and demonstrate the utility of this microfabricated system to explore this interaction.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2007
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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