Reduced Inflammatory Threshold Indicates Skin Barrier Defect in Transglutaminase 3 Knockout Mice

Recently a transglutaminase 3 knockout (TGM3/KO) mouse was generated that showed impaired hair development, but no gross defects in the epidermal barrier, although increased fragility of isolated corneocytes was demonstrated. Here we investigated the functionality of skin barrier in vivo by percutaneous sensitization to fluorescein-isothiocyanate (FITC) in TGM3/KO (n=64) and C57BL/6 WT mice (n=36). Cutaneous inflammation was evaluated by mouse ear swelling test (MEST), histology, serum IgE levels, and by flow-cytometry from draining lymph nodes. Inflammation induced significant MEST difference (P<0.0001) was detected between KO and WT mice and was supported also by histopathology. A significant increase of CD4+ CD25+ activated T-cells (P<0.01) and elevated serum IgE levels (P<0.05) in KO mice indicated more the development of FITC sensibilization than an irritative reaction. P. acnes induced intracutaneous inflammation showed no difference (P=0.2254) between the reactivity of WT and KO immune system. As in vivo tracer, FITC penetration from skin surface followed by two-photon microscopy demonstrated a more invasive percutaneous penetration in KO mice. The clinically uninvolved skin in TGM3/KO mice showed impaired barrier function and higher susceptibility to FITC sensitization indicating that TGM3 has a significant contribution to the functionally intact cutaneous barrier.Journal of Investigative Dermatology accepted article preview online, 24 July 2013. doi:10.1038/jid.2013.307

Observing Solvation Dynamics with Simultaneous Femtosecond X-ray Emission Spectroscopy and X-ray Scattering

In liquid phase chemistry dynamic solute–solvent interactions often govern the path, ultimate outcome, and efficiency of chemical reactions. These steps involve many-body movements on subpicosecond time scales and thus ultrafast structural tools capable of capturing both intramolecular electronic and structural changes, and local solvent structural changes are desired. We have studied the intra- and intermolecular dynamics of a model chromophore, aqueous [Fe(bpy)3]2+, with complementary X-ray tools in a single experiment exploiting intense XFEL radiation as a probe. We monitored the ultrafast structural rearrangement of the solute with X-ray emission spectroscopy, thus establishing time zero for the ensuing X-ray diffuse scattering analysis. The simultaneously recorded X-ray diffuse scattering patterns reveal slower subpicosecond dynamics triggered by the intramolecular structural dynamics of the photoexcited solute. By simultaneous combination of both methods only, we can extract new information about the solvation dynamic processes unfolding during the first picosecond (ps). The measured bulk solvent density increase of 0.2% indicates a dramatic change of the solvation shell around each photoexcited solute, confirming previous ab initio molecular dynamics simulations. Structural changes in the aqueous solvent associated with density and temperature changes occur with ∼1 ps time constants, characteristic for structural dynamics in water. This slower time scale of the solvent response allows us to directly observe the structure of the excited solute molecules well before the solvent contributions become dominant