Plasmacytoid Dendritic Cells Sequester High Prion Titres at Early Stages of Prion Infection

In most transmissible spongiform encephalopathies prions accumulate in the lymphoreticular system (LRS) long before they are detectable in the central nervous system. While a considerable body of evidence showed that B lymphocytes and follicular dendritic cells play a major role in prion colonization of lymphoid organs, the contribution of various other cell types, including antigen-presenting cells, to the accumulation and the spread of prions in the LRS are not well understood. A comprehensive study to compare prion titers of candidate cell types has not been performed to date, mainly due to limitations in the scope of animal bioassays where prohibitively large numbers of mice would be required to obtain sufficiently accurate data. By taking advantage of quantitative in vitro prion determination and magnetic-activated cell sorting, we studied the kinetics of prion accumulation in various splenic cell types at early stages of prion infection. Robust estimates for infectious titers were obtained by statistical modelling using a generalized linear model. Whilst prions were detectable in B and T lymphocytes and in antigen-presenting cells like dendritic cells and macrophages, highest infectious titers were determined in two cell types that have previously not been associated with prion pathogenesis, plasmacytoid dendritic (pDC) and natural killer (NK) cells. At 30 days after infection, NK cells were more than twice, and pDCs about seven-fold, as infectious as lymphocytes respectively. This result was unexpected since, in accordance to previous reports prion protein, an obligate requirement for prion replication, was undetectable in pDCs. This underscores the importance of prion sequestration and dissemination by antigen-presenting cells which are among the first cells of the immune system to encounter pathogens. We furthermore report the first evidence for a release of prions from lymphocytes and DCs of scrapie-infected mice ex vivo, a process that is associated with a release of exosome-like membrane vesicles

Exergaming: Not Just for Kids Anymore

One day a group of 15 adventuresome older adults, ages 67 to 87, gathered in a gymnasium at San Diego State University, which had been transformed into a video-gaming arcade, to engage in exercise using new interactive technology. Alongside the video screens, computers and game consoles, participants could be seen laughing, clapping hands, watching and encouraging each other. Participants tried virtual boxing and bowling with XaviX® equipment, snowboarded or hula hooped on the Wii Fit® balance board, jumped on the XaviX® J-MAT, played Wii® golf and bowling, or stepped to the beat of the music with Dancetown®

Donor Limb Functional Restoration via a Novel Clinical Care Pathway following Fibula Free Flap Harvest for Head and Neck Reconstruction

Summary:. Patients undergoing head and neck skeletal reconstruction (HNR) often require free tissue transfer from the extremities to ensure proper restoration of form and function. This requires a team-based, highly reliable medical system centered around the patient needs. Surgical intervention across multiple sites and harvesting of donor tissue results in short- and long-term physical impairments. There is a paucity of research objectively measuring impairments resulting from the graft donor site. There is a lack of research that objectively measures impairments and protocols for the management of these patients postoperatively. Patients undergo little, if any, formal approach to dealing with the vast impairments, which are sequelae to this surgery. This leads to large discrepancies in proposed functional progressions, return to duty timelines, and utilization of rehabilitative resources. At a major military medical center, an innovative clinical care pathway for patients undergoing HNR using free tissue transfer was implemented using a multidisciplinary model that focuses on early engagement with rehabilitation. This model, paired with a single surgery, will attempt to return service members to duty months earlier than the traditional approach. This report describes the conceptual framework and implementation of a new criteria-based, multidisciplinary clinical care pathway for HNR patients. The collaboration amongst the multidisciplinary care team has optimized the holistic health of the patient and communication with their support network, yielding faster return to normalization of daily life activities. The long-term goal is to further develop and formalize this pathway to best serve this patient population

DANPY (dimethylaminonaphthylpyridinium): an economical and biocompatible fluorophore

Dyes with nonlinear optical (NLO) properties enable new imaging techniques and photonic systems. We have developed a dye (DANPY-1) for photonics applications in biological substrates such as nucleic acids; however, the design specification also enables it to be used for visualizing biomolecules. It is a prototype dye demonstrating a water-soluble, NLO-active fluorophore with high photostability, a large Stokes shift, and a favorable toxicity profile. A practical and scalable synthetic route to DANPY salts has been optimized featuring: (1) convergent Pd-catalyzed Suzuki coupling with pyridine 4-boronic acid, (2) site-selective pyridyl N-methylation, and (3) direct recovery of crystalline intermediates without chromatography. We characterize the optical properties, biocompatibility, and biological staining behavior of DANPY-1. In addition to stability and solubility across a range of polar media, the DANPY-1 chromophore shows a first hyperpolarizability similar to common NLO dyes such as Disperse Red 1 and DAST, a large two-photon absorption cross section for its size, substantial affinity to nucleic acids in vitro, an ability to stain a variety of cellular components, and strong sensitivity of its fluorescence properties to its dielectric environment.status: publishe