Spontaneous atopic dermatitis due to immune dysregulation in mice lacking Adamts2 and 14.

Since its first description, ADAMTS14 has been considered as an aminoprocollagen peptidase based on its high similarity with ADAMTS3 and ADAMTS2. As its importance for procollagen processing was never experimentally demonstrated in vivo, we generated Adamts14-deficient mice. They are healthy, fertile and display normal aminoprocollagen processing. They were further crossed with Adamts2-deficient mice to evaluate potential functional redundancies between these two highly related enzymes. Initial characterizations made on young Adamts2-Adamts14-deficient animals showed the same phenotype as that of Adamts2-deficient mice, with no further reduction of procollagen processing and no significant aggravation of the structural alterations of collagen fibrils. However, when evaluated at older age, Adamts2-Adamts14-deficient mice surprisingly displayed epidermal lesions, appearing in 2 month-old males and later in some females, and then worsening rapidly. Immunohistological evaluations of skin sections around the lesions revealed thickening of the epidermis, hypercellularity in the dermis and extensive infiltration by immune cells. Additional investigations, performed on young mice before the formation of the initial lesions, revealed that the primary cause of the phenotype was not related to alterations of the epidermal barrier but was rather the result of an abnormal activation and differentiation of T lymphocytes towards a Th1 profile. However, the primary molecular defect probably does not reside in the immune system itself since irradiated Adamts2-Adamts14-deficient mice grafted with WT immune cells still developed lesions. While originally created to better characterize the common and specific functions of ADAMTS2 and ADAMTS14 in extracellular matrix and connective tissues homeostasis, the Adamts2-Adamts14-deficient mice revealed an unexpected but significant role of ADAMTS in the regulation of immune system, possibly through a cross-talk involving mesenchymal cells and the TGFß pathways.

Localization in a spanwise-extended model of plane Couette flow.

We consider a nine-partial-differential-equation (1-space and 1-time) model of plane Couette flow in which the degrees of freedom are severely restricted in the streamwise and cross-stream directions to study spanwise localization in detail. Of the many steady Eckhaus (spanwise modulational) instabilities identified of global steady states, none lead to a localized state. Spatially localized, time-periodic solutions were found instead, which arise in saddle node bifurcations in the Reynolds number. These solutions appear global (domain filling) in narrow (small spanwise) domains yet can be smoothly continued out to fully spanwise-localized states in very wide domains. This smooth localization behavior, which has also been seen in fully resolved duct flow (S. Okino, Ph.D. thesis, Kyoto University, Kyoto, 2011), indicates that an apparently global flow structure does not have to suffer a modulational instability to localize in wide domains.

Genesis of streamwise-localized solutions from globally periodic traveling waves in pipe flow.

The aim in the dynamical systems approach to transitional turbulence is to construct a scaffold in phase space for the dynamics using simple invariant sets (exact solutions) and their stable and unstable manifolds. In large (realistic) domains where turbulence can coexist with laminar flow, this requires identifying exact localized solutions. In wall-bounded shear flows, the first of these has recently been found in pipe flow, but questions remain as to how they are connected to the many known streamwise-periodic solutions. Here we demonstrate that the origin of the first localized solution is in a modulational symmetry-breaking Hopf bifurcation from a known global traveling wave that has twofold rotational symmetry about the pipe axis. Similar behavior is found for a global wave of threefold rotational symmetry, this time leading to two localized relative periodic orbits. The clear implication is that many global solutions should be expected to lead to more realistic localized counterparts through such bifurcations, which provides a constructive route for their generation.