Novel Identification of LYVE-1 Positive Macrophages in Rheumatoid Synovial Tissue

Objective: LYVE-1+ macrophages are observed in a range of cancers, where they play a role in tumour lymphangiogenesis. In rheumatoid arthritis (RA), lymphangiogenesis increases in the early stage of the disease and decreases as it progresses, potentially exacerbating inflammatory cell persistence. We investigated whether LYVE-1+ macrophages were present in RA synovium. Methods: Synovial tissue from RA patients was obtained at joint replacement surgery and immunohistochemistry was performed to visualise LYVE-1+ and CD68+ cells. Results: LYVE-1+ macrophages were present in rheumatoid synovial tissue, the first observation of this kind. Conclusion: Despite the reduction in lymphangiogenesis in chronic RA, LYVE-1 positive macrophages are present and there is a potential role for macrophages in the generation of lymphatic vessels

Effect of the G375C and G346E Achondroplasia Mutations on FGFR3 Activation

Two mutations in FGFR3, G380R and G375C are known to cause achondroplasia, the most common form of human dwarfism. The G380R mutation accounts for 98% of the achondroplasia cases, and thus has been studied extensively. Here we study the effect of the G375C mutation on the phosphorylation and the cross-linking propensity of full-length FGFR3 in HEK 293 cells, and we compare the results to previously published results for the G380R mutant. We observe identical behavior of the two achondroplasia mutants in these experiments, a finding which supports a direct link between the severity of dwarfism phenotypes and the level and mechanism of FGFR3 over-activation. The mutations do not increase the cross-linking propensity of FGFR3, contrary to previous expectations that the achondroplasia mutations stabilize the FGFR3 dimers. Instead, the phosphorylation efficiency within un-liganded FGFR3 dimers is increased, and this increase is likely the underlying cause for pathogenesis in achondroplasia. We further investigate the G346E mutation, which has been reported to cause achondroplasia in one case. We find that this mutation does not increase FGFR3 phosphorylation and decreases FGFR3 cross-linking propensity, a finding which raises questions whether this mutation is indeed a genetic cause for human dwarfism

The interplay between posture control and memory for spatial locations

Three experiments examined interactions between posture control in upright stance and a concurrent location memory task. Healthy young participants stood upright and memorized the locations of dots presented on a computer screen. In the retrieval phase, they indicated whether arrows presented on the screen would pass through any of the memorized locations. Postural sway variability was measured either during the retention period or during retrieval. Relative to not performing the memory task, postural sway variability increased in the retention period when the eyes were closed, but remained unaffected when the eyes were open. During retrieval, postural sway variability was reduced relative to the no-memory-task condition. Results were interpreted in terms of dual-task costs associated with maintaining multiple frames of reference