Atrichia caused by mutations in the vitamin D receptor gene is a phenocopy of generalized atrichia caused by mutations in the hairless gene. J Invest Dermatol 117:612-7 Mu ¨ller-Ro ¨ver S, Handjiski B, van der Veen C, Eichmu ¨ller S, Foitzik K, McKay IA et al. (2001) A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages.
BackgroundFilaggrin (FLG) mutations result in reduced stratum corneum (SC) natural moisturizing factor (NMF) components and consequent increased SC pH. Because higher pH activates SC protease activity, we hypothesized an enhanced release of proinflammatory IL-1 cytokines from corneocytes in patients with atopic dermatitis (AD) with FLG mutations (ADFLG) compared with that seen in patients with AD without these mutations (ADNON-FLG).ObjectivesWe sought to investigate SC IL-1 cytokine profiles in the uninvolved skin of controls and patients with ADFLG versus patients with ADNON-FLG. We also sought to examine the same profiles in a murine model of filaggrin deficiency (Flgft/Flgft [FlgdelAPfal] mice).MethodsOne hundred thirty-seven patients were studied. NMF levels were ascertained using confocal Raman spectroscopy; transepidermal water loss and skin surface pH were measured. IL-1α, IL-1β, IL-18, IL-1 receptor antagonist (IL-1RA), and IL-8 levels were determined in SC tape strips from 93 patients. All subjects were screened for 9 FLG mutations. Flgft/Flgft (FlgdelAPfal) mice, separated from maFlgft/maFlgft (flaky tail) mice, were used for the preparation and culture of primary murine keratinocytes and as a source of murine skin. RT-PCR was performed using primers specific for murine IL-1α, IL-1β, and IL-1RA.ResultsSC IL-1 levels were increased in patients with ADFLG; these levels were inversely correlated with NMF levels. NMF values were also inversely correlated with skin surface pH. Skin and keratinocytes from Flgft/Flgft mice had upregulated expression of IL-1β and IL-1RA mRNA.ConclusionsADFLG is associated with an increased SC IL-1 cytokine profile; this profile is also seen in a murine homologue of filaggrin deficiency. These findings might have importance in understanding the influence of FLG mutations on the inflammasome in the pathogenesis of AD and help individualize therapeutic approaches.
Although partly active aeolian sand sheets and dunes cover large areas in the zones of (disjcontinuous permafrost, little precise information is available about the influence of cold-climate conditions on modern aeolian processes. This means that palaeoenvironmental reconstructions in the stabilised, mainly Late Pleistocene dune fields and cover sand regions in the 'sand belts' of the European Lowlands and the Northern Great Plains of the USA and Canada, are necessarily still based on ancient evidence. Cold-climate wind deposits are typically derived from areas of abundant sediment supply like unvegetated flood plains, glacial outwash plains, till plains and lake shores. The common parabolic and transverse dune forms resemble those observed in temperate regions.Although a variety of periglacial features has been identified in Late Pleistocene dune and cover sands none of them indicate that permafrost is crucial to aeolian activity. Specific structures in aeolian strata permit tentative interpretation of the moisture content of depositional sand surfaces, the nature of annual sedimentation cycles and the processes by which strata were deposited and/or contorted. But surprisingly little is known about the role of vegetation in the process of sand accumulation. Dunes are most informative with respect to reconstructions of past wind regimes, which offer important data for verification of palaeoclimatic simulations.
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