Interrelationship between Dendritic Cell Trafficking and Francisella tularensis Dissemination following Airway Infection

Francisella tularensis, the etiological agent of the inhalation tularemia, multiplies in a variety of cultured mammalian cells. Nevertheless, evidence for its in vivo intracellular residence is less conclusive. Dendritic cells (DC) that are adapted for engulfing bacteria and migration towards lymphatic organs could serve as potential targets for bacterial residence and trafficking. Here, we focus on the in vivo interactions of F. tularensis with DC following airway infection of mice. Lethal airway infection of mice with the live vaccine strain (LVS) results in trafficking of a CD11bhigh/CD11cmed/autofluorescencelow DC subset from the respiratory tract to the draining mediastinal lymph node (MdLN). Simultaneously, a rapid, massive bacterial colonization of the MdLN occurs, characterized by large bacterial foci formation. Analysis of bacteria in the MdLN revealed a major population of extracellular bacteria, which co-exists with a substantial fraction of intracellular bacteria. The intracellular bacteria are viable and reside in cells sorted for DC marker expression. Moreover, in vivo vital staining experiments indicate that most of these intracellular bacteria (∼75%) reside in cells that have migrated from the airways to the MdLN after infection. The correlation between DC and bacteria accumulation in the MdLN was further demonstrated by manipulating DC migration to the MdLN through two independent pathways. Impairment of DC migration to the MdLN, either by a sphingosine-1-phosphate receptor agonist (FTY720) or by the D prostanoid receptor 1 agonist (BW245C), resulted in reduced bacterial colonization of MdLN. Moreover, BW245C treatment delayed the onset of morbidity and the time to death of the infected mice. Taken together, these results suggest that DC can serve as an inhabitation niche for F. tularensis in the early stages of infection, and that DC trafficking plays a role in pathogen dissemination. This underscores the therapeutic potential of DC migration impairing drugs in tularemia treatment

Knowledge Maps: an Online Tool for Knowledge Mapping with Automated Feedback

Concept and knowledge maps have been shown to improve students’ learning by emphasising meaningful relationships between phenomena. A user-friendly online tool that enables assessment of students’ maps with automated feedback might therefore have significant benefits for learning. For that purpose, we developed an online software platform known as Knowledge Maps. Two pilot studies were performed to evaluate the usability and efficacy of Knowledge Maps. Study A demonstrated significantly improved perceptions of learning after using Knowledge Maps to learn pathology. Study B showed significant improvement between pre-test and post-test scores in an anatomy course. These preliminary studies indicate that this software is readily accepted and may have potential benefits for learning

Two-dimensional MR spectroscopy of healthy and cancerous prostates in vivo

OBJECTIVES: A major goal of this article is to summarize the current status of evaluating prostate metabolites non-invasively using spatially resolved two-dimensional (2D) MR Spectroscopy (MRS). MATERIALS AND METHODS: Due to various technical challenges, the spatially resolved versions of 2D MRS techniques are currently going through the developmental stage. During the last decade, four different versions of 2D MRS sequences have been successfully implemented on 3T and 1.5T MRI scanners manufactured by three different vendors. These sequences include half and maximum echo sampled J-resolved spectroscopy (JPRESS), S-PRESS and L-COSY, which are single volume localizing sequences, and the multi-voxel based JPRESS sequence. RESULTS: Even though greater than 1ml voxels have been used, preliminary evaluations of 2D JPRESS, S-PRESS and L-COSY sequences have demonstrated unambiguous detection of citrate, creatine, choline, spermine and more metabolites in human prostates. ProFIT-based quantitation of JPRESS and L-COSY data clearly shows the superiority of 2D MRS over conventional one-dimensional (1D) MRS and more than six metabolites have been successfully quantified. These sequences have been evaluated in a small group of prostate pathologies and pilot investigations using these sequences show promising results in prostate pathologies. CONCLUSION: Implementation of the state-of-the-art 2D MRS techniques and preliminary evaluation in prostate pathologies are discussed in this review. Even though these techniques are going through developmental and early testing phases, it is evident that 2D MRS can be easily added on to any clinical Magnetic Resonance Imaging (MRI) protocol to non-invasively record the biochemical contents of the prostate

Hormones and growth factors in the pathogenesis of spinal ligament ossification

Ossification of the spinal ligaments (OSL) is a pathologic condition that causes ectopic bone formation and subsequently results in various degrees of neurological deficit, but the etiology of OSL remains almost unknown. Some systemic hormones, such as 1,25-dihydroxyvitamin D, parathyroid hormone (PTH), insulin and leptin, and local growth factors, such as transforming growth factor-β (TGF-β), and bone morphogenetic protein (BMP), have been studied and are thought to be involved in the initiation and development of OSL. This review article summarizes these studies, delineates the possible mechanisms, and puts forward doubts and new questions. The related findings from studies of genes and target cells in the ligament of OSL are also discussed. Although these findings may be helpful in understanding the pathogenesis of OSL, much more research needs to be conducted in order to investigate the nature of OSL