30 research outputs found

    Initial properdin binding contributes to alternative pathway activation at the surface of viable and necrotic cells

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    Properdin, the only known positive regulator of the complement system, stabilizes the C3 convertase, thereby increasing its half-life. In contrast to most other complement factors, properdin is mainly produced extrahepatically by myeloid cells. Recent data suggest a role for properdin as a pattern recognition molecule. Here, we confirmed previous findings of properdin binding to different necrotic cells including Jurkat T cells. Binding can occur independent of C3, as demonstrated by HAP-1 C3 KO cells, excluding a role for endogenous C3. In view of the cellular source of properdin, interaction with myeloid cells was examined. Properdin bound to the surface of viable monocyte-derived pro- and anti-inflammatory macrophages, but not to DCs. Binding was demonstrated for purified properdin as well as fractionated P2, P3, and P4 properdin oligomers. Binding contributed to local complement activation as determined by C3 and C5b-9 deposition on the cell surfaces and seems a prerequisite for alternative pathway activation. Interaction of properdin with cell surfaces could be inhibited with the tick protein Salp20 and by different polysaccharides, depending on sulfation and chain length. These data identify properdin as a factor interacting with different cell surfaces, being either dead or alive, contributing to the local stimulation of complement activation.</p

    Establishing human leukemia xenograft mouse models by implanting human bone marrow-like scaffold-based niches

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    To begin to understand the mechanisms that regulate self-renewal, differentiation, and transformation of human hematopoietic stem cells or to evaluate the efficacy of novel treatment modalities, stem cells need to be studied in their own species-specific microenvironment. By implanting ceramic scaffolds coated with human mesenchymal stromal cells into immune-deficient mice, we were able to mimic the human bone marrow niche. Thus, we have established a human leukemia xenograft mouse model in which a large cohort of patient samples successfully engrafted, which covered all of the important genetic and risk subgroups. We found that by providing a humanized environment, stem cell self-renewal properties were better maintained as determined by serial transplantation assays and genome-wide transcriptome studies, and less clonal drift was observed as determined by exome sequencing. The human leukemia xenograft mouse models that we have established here will serve as an excellent resource for future studies aimed at exploring novel therapeutic approaches

    Antimicrobial usage and resistance in beef production

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    United States Special Operations Command South Training Program’s Effectiveness: A Case Study

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    United States Special Operations Command South (SOCSOUTH) plans and coordinates Special Operations to find and fix threats and enable the Interagency, Intelligence Community, and Partner Nations to counter threats to US interests, maintain regional stability and compete in a complex environment. Physical readiness, performance optimization, and injury prevention are critical to the individual operator. SOCSOUTH has allocated significant financial resources associated with operational training and human performance programs in order to improve and maintain operators’ tactical and physical readiness. Whether these efforts are pointed to the right direction are under evaluation. PURPOSE: To evaluate the effectiveness of a 3 months’ customized training program on SOCSOUTH operators. METHODS: Retrospective data of ten operators (Age 41.1 ± 6.6) who participated in a customized training program for 3 months were analyzed to evaluate program’s effectiveness. Program was designed to improve operational training and human performance, while reducing the risk of musculoskeletal injuries based on microcycle periodization. Pre/Post testing was performed on selected tests, reflective of important mission qualities, to assess upper body muscular endurance (# chin-ups), lower body muscular endurance (150-yard shuttle test), and agility (30-yard sprint). A repeated-measures design for pre/post examined variables performed using SPSSÓ. RESULTS: There was a significant effect of post-training compared to pre-training on operators’ number of chin-ups performed (F1,9=10.42, p=.01, η2=.54), 150-yard shuttle time (F1,9=38.29, pη2=.81), and 30-yard time (F1,9=16.29, p=.003, η2=.64) respectively. CONCLUSION: The current SOCSOUTH’s efforts on improving operational performance by applying a customized training program was successful. Operators’ selected mission quality capacities for upper- and lower-body performance and agility were improved. SOCSOUTH needs to continue supporting operators’ training based on these data analytics

    Following Scoliosis Progression in the Spine using Ultrasound Imaging

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    Scoliosis is a three-dimensional deformation of the spine which is characterized by a lateral deviation of the spine and axial rotation of the vertebrae. It must be monitored frequently to be in time to start the treatment in case of progression. Nowadays, X-ray is used, but has a detrimental effect and provide only 2D data. Ultrasound would allow a frequent and 3D view on the spine and thus is ideal to follow scoliosis progression. A feasibility study on ultrasound is presented. A freehand 3D ultrasound system was used to scan the back of a volunteer. In the resulting ultrasound volume, the vertebral features such as transverse processes, laminae, and superior articular processes appear prominently along with the non-vertebral features like muscles, head of the ribs and parts of the pleura. The 3D orientation of the vertebrae, determined by the axial rotation and vertebral tilt was determined semiautomatically. The axial rotation and vertebral tilt measurements in the region of the thoracic vertebrae T4-T9 delivered good accuracy, in other regions the accuracy was acceptable. In conclusion, imaging the human spine using ultrasound is feasible. The result provides a basis towards the aim to follow scoliosis progression using ultrasound
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