1000 resultados para XA.418035s(Illinois)
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n.s. v. 22
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OBJECTIVE: Blood-sucking arthropods' salivary glands contain a remarkable diversity of antihemostatics. The aim of the present study was to identify the unique salivary anticoagulant of the sand fly Lutzomyia longipalpis, which remained elusive for decades. METHODS AND RESULTS: Several L. longipalpis salivary proteins were expressed in human embryonic kidney 293 cells and screened for inhibition of blood coagulation. A novel 32.4-kDa molecule, named Lufaxin, was identified as a slow, tight, noncompetitive, and reversible inhibitor of factor Xa (FXa). Notably, Lufaxin's primary sequence does not share similarity to any physiological or salivary inhibitors of coagulation reported to date. Lufaxin is specific for FXa and does not interact with FX, Dansyl-Glu-Gly-Arg-FXa, or 15 other enzymes. In addition, Lufaxin blocks prothrombinase and increases both prothrombin time and activated partial thromboplastin time. Surface plasmon resonance experiments revealed that FXa binds Lufaxin with an equilibrium constant ≈3 nM, and isothermal titration calorimetry determined a stoichiometry of 1:1. Lufaxin also prevents protease-activated receptor 2 activation by FXa in the MDA-MB-231 cell line and abrogates edema formation triggered by injection of FXa in the paw of mice. Moreover, Lufaxin prevents FeCl(3)-induced carotid artery thrombus formation and prolongs activated partial thromboplastin time ex vivo, implying that it works as an anticoagulant in vivo. Finally, salivary gland of sand flies was found to inhibit FXa and to interact with the enzyme. CONCLUSIONS: Lufaxin belongs to a novel family of slow-tight FXa inhibitors, which display antithrombotic and anti-inflammatory activities. It is a useful tool to understand FXa structural features and its role in prohemostatic and proinflammatory events.
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Vertebral lesions have been the main evidence for infection by the Mycobacterium tuberculosis complex (MTC) in paleopathology. Skeletal involvement is expected in a small percentage of infected individuals. Recently, several authors report a correlation between rib lesions and tuberculosis (TB) complex infection. This study tests the hypothesis that rib lesions can serve as a useful marker for MTC infection within the Mississippian Schild skeletal collection from West-Central Illinois. Ribs from 221 adults and juveniles were examined, and affected individuals were tested for TB complex infection. DNA from rib samples of affected individuals was amplified with primers targeting the IS6110 insertion element, which is common to all members of the TB complex. Although it cannot allow discrimination between different species of TB, IS6110 is present in many copies within their genomes, and its presence is thus an indication of MTC infection. The results support the use of rib lesions as a marker for TB infection. Additionally, we demonstrate that MTC DNA can be recovered from ribs that lack lesions in individuals who have lesions of other bones. We recommend that an examination of ribs be incorporated into investigations for TB.
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Newsletter updating the corridor study of the Mississippi Bridge project for the states of Iowa and Illinois.
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Newsletter updating the corridor study of the Mississippi Bridge project for the states of Iowa and Illinois.
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Newsletter updating the corridor study of the Mississippi Bridge project for the states of Iowa and Illinois.
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Newsletter updating the corridor study of the Mississippi Bridge project for the states of Iowa and Illinois.
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Newsletter updating the corridor study of the Mississippi Bridge project for the states of Iowa and Illinois.
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Newsletter updating the corridor study of the Mississippi Bridge project for the states of Iowa and Illinois.
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Newsletter updating the corridor study of the Mississippi Bridge project for the states of Iowa and Illinois.
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Thrombin is involved in mediating neuronal death in cerebral ischemia. We investigated its so far unknown mode of activation in ischemic neural tissue. We used an in vitro approach to distinguish the role of circulating coagulation factors from endogenous cerebral mechanisms. We modeled ischemic stroke by subjecting rat organotypic hippocampal slice cultures to 30-min oxygen (5%) and glucose (1 mmol/L) deprivation (OGD). Perinuclear activated factor X (FXa) immunoreactivity was observed in CA1 neurons after OGD. Selective FXa inhibition by fondaparinux during and after OGD significantly reduced neuronal death in the CA1 after 48 h. Thrombin enzyme activity was increased in the medium 24 h after OGD and this increase was prevented by fondaparinux suggesting that FXa catalyzes the conversion of prothrombin to thrombin in neural tissue after ischemia in vitro. Treatment with SCH79797, a selective antagonist of the thrombin receptor protease-activated receptor-1 (PAR-1), significantly decreased neuronal cell death indicating that thrombin signals ischemic damage via PAR-1. The c-Jun N-terminal kinase (JNK) pathway plays an important role in excitotoxicity and cerebral ischemia and we observed activation of the JNK substrate, c-Jun in our model. Both the FXa inhibitor, fondaparinux and the PAR-1 antagonist SCH79797, decreased the level of phospho-c-Jun Ser73. These results indicate that FXa activates thrombin in cerebral ischemia, which leads via PAR-1 to the activation of the JNK pathway resulting in neuronal death.
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The I-74 Aesthetic Design Guideline (ADG) document has two primary goals: To establish and identify an overall design theme To prioritize enhancement opportunities within the framework of corridor elements The recommendations of this report have been developed based on an “unconstrained” framework for future corridor–wide enhancements. Future funding availability, along with the recommendations of this report, will guide the final design process. ADG Future Uses: This document is intended to be used as a reference to future processes in the following ways: Guidance for I-74 final design teams Reference document for future local community redevelopment initiatives Inspiration for identification and development of other I-74 corridor aesthetic enhancement opportunities Process: As illustrated in Figure 1.3, the overall process for corridor aesthetics began traditionally with inventory and identification of potential aesthetic applications. The ADG does not document all the reports and presentations related to these early design stages, but has incorporated these efforts into the design theme, guiding principles and prioritized enhancements shown on the following pages of this report. The I-74 final design phase will incorporate these recommendations into the project. The consultant design team and representatives of the DOTs have worked with the CAAT members to facilitate community input and have helped develop recommendations for improving I-74 corridor aesthetics. CAAT recommendations have been advanced to the I-74 Advisory Committee for review and endorsement. Both DOTs have reviewed the CAAT recommendations and have endorsed the contents of this report. Figure 1.4 illustrates the status of corridor aesthetic design development. As of the date of this report, aesthetic design is approximately 50% complete. Future detailed design, cost evaluation, feasibility and prioritizations all need to occur for this process to be successfully completed.
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The I-74 Iowa-Illinois Corridor Study has been progressing since the last newsletter and the Public Information Meetings in July of 2002, and the Advisory Committee has been involved in every step. Our goal has been and continues to be ensuring that community priorities and goals are reflected in the I-74 project, and that local concerns are considered.
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The I-74 Iowa-Illinois Corridor Study has been progressing since the last newsletter and the Public Information Meetings in July of 2002, and the Advisory Committee has been involved in every step. Our goal has been and continues to be ensuring that community priorities and goals are reflected in the I-74 project, and that local concerns are considered.
