Dpp Signaling Activity Requires Pentagone to Scale with Tissue Size in the Growing Drosophila Wing Imaginal Disc

The activity of the Dpp morphogen adapts to tissue size in the growing Drosophila wing imaginal disc, and Pentagone, an important secreted feedback regulator of the Dpp pathway, is required for this adaptation

Enhanced upper genital tract pathologies by blocking Tim-3 and PD-L1 signaling pathways in mice intravaginally infected with Chlamydia muridarum

<p>Abstract</p> <p>Background</p> <p>Although Tim-3 & PD-L1 signaling pathways play important roles in negatively regulating immune responses, their roles in chlamydial infection have not been evaluated.</p> <p>Methods</p> <p>Neutralization antibodies targeting Tim-3 and PD-L1 were used to treat mice. Following an intravaginal infection with <it>C. muridarum </it>organisms, mice with or without the dual antibody treatment were compared for live chlamydial organism shedding from the lower genital tract and inflammatory pathology in the upper genital tract.</p> <p>Results</p> <p>Mice treated with anti-Tim-3 and anti-PD-L1 antibodies displayed a time course of live organism shedding similar to that of mice treated with equivalent amounts of isotype-matched IgG molecules. The combined antibody blocking failed to alter either the lower genital tract cytokine or systemic humoral and cellular adaptive responses to <it>C. muridarum </it>infection. However, the antibody blocking significantly enhanced <it>C. muridarum</it>-induced pathologies in the upper genital tract, including more significant hydrosalpinx and inflammatory infiltration in uterine horn and oviduct tissues.</p> <p>Conclusions</p> <p>The Tim-3 and PD-L1-mediated signaling can significantly reduce pathologies in the upper genital tract without suppressing immunity against chlamydial infection, suggesting that Tim-3 and PD-L1-mediated negative regulation may be manipulated to attenuate tubal pathologies in women persistently infected with <it>C. trachomatis </it>organisms.</p

In Vivo Methods for the Assessment of Topical Drug Bioavailability

This paper reviews some current methods for the in vivo assessment of local cutaneous bioavailability in humans after topical drug application. After an introduction discussing the importance of local drug bioavailability assessment and the limitations of model-based predictions, the focus turns to the relevance of experimental studies. The available techniques are then reviewed in detail, with particular emphasis on the tape stripping and microdialysis methodologies. Other less developed techniques, including the skin biopsy, suction blister, follicle removal and confocal Raman spectroscopy techniques are also described