Segmentation of Fault Networks Determined from Spatial Clustering of Earthquakes

We present a new method of data clustering applied to earthquake catalogs, with the goal of reconstructing the seismically active part of fault networks. We first use an original method to separate clustered events from uncorrelated seismicity using the distribution of volumes of tetrahedra defined by closest neighbor events in the original and randomized seismic catalogs. The spatial disorder of the complex geometry of fault networks is then taken into account by defining faults as probabilistic anisotropic kernels, whose structures are motivated by properties of discontinuous tectonic deformation and previous empirical observations of the geometry of faults and of earthquake clusters at many spatial and temporal scales. Combining this a priori knowledge with information theoretical arguments, we propose the Gaussian mixture approach implemented in an Expectation-Maximization (EM) procedure. A cross-validation scheme is then used and allows the determination of the number of kernels that should be used to provide an optimal data clustering of the catalog. This three-steps approach is applied to a high quality relocated catalog of the seismicity following the 1986 Mount Lewis ($M_l=5.7$) event in California and reveals that events cluster along planar patches of about 2 km$^2$, i.e. comparable to the size of the main event. The finite thickness of those clusters (about 290 m) suggests that events do not occur on well-defined euclidean fault core surfaces, but rather that the damage zone surrounding faults may be seismically active at depth. Finally, we propose a connection between our methodology and multi-scale spatial analysis, based on the derivation of spatial fractal dimension of about 1.8 for the set of hypocenters in the Mnt Lewis area, consistent with recent observations on relocated catalogs

An apicobasal gradient of Rac activity determines protrusion form and position

Each cell within a polarised epithelial sheet must align and correctly position a wide range of subcellular structures, including actin-based dynamic protrusions. Using in vivo inducible transgenes that can sense or modify Rac activity, we demonstrate an apicobasal gradient of Rac activity that is required to correctly form and position distinct classes of dynamic protrusion along the apicobasal axis of the cell. We show that we can modify the Rac activity gradient in genetic mutants for specific polarity proteins, with consequent changes in protrusion form and position and additionally show, using photoactivatable Rac transgenes, that it is the level of Rac activity that determines protrusion form. Thus, we demonstrate a mechanism by which polarity proteins can spatially regulate Rac activity and the actin cytoskeleton to ensure correct epithelial cell shape and prevent epithelial-to-mesenchymal transitions

Cushing's Syndrome and Fetal Features Resurgence in Adrenal Cortex–Specific Prkar1a Knockout Mice

Carney complex (CNC) is an inherited neoplasia syndrome with endocrine overactivity. Its most frequent endocrine manifestation is primary pigmented nodular adrenocortical disease (PPNAD), a bilateral adrenocortical hyperplasia causing pituitary-independent Cushing's syndrome. Inactivating mutations in PRKAR1A, a gene encoding the type 1 α-regulatory subunit (R1α) of the cAMP–dependent protein kinase (PKA) have been found in 80% of CNC patients with Cushing's syndrome. To demonstrate the implication of R1α loss in the initiation and development of PPNAD, we generated mice lacking Prkar1a specifically in the adrenal cortex (AdKO). AdKO mice develop pituitary-independent Cushing's syndrome with increased PKA activity. This leads to autonomous steroidogenic genes expression and deregulated adreno-cortical cells differentiation, increased proliferation and resistance to apoptosis. Unexpectedly, R1α loss results in improper maintenance and centrifugal expansion of cortisol-producing fetal adrenocortical cells with concomitant regression of adult cortex. Our data provide the first in vivo evidence that loss of R1α is sufficient to induce autonomous adrenal hyper-activity and bilateral hyperplasia, both observed in human PPNAD. Furthermore, this model demonstrates that deregulated PKA activity favors the emergence of a new cell population potentially arising from the fetal adrenal, giving new insight into the mechanisms leading to PPNAD

Mouse model for bilateral adrenal hyperplasia

International audienc

Dispatched mediates Hedgehog basolateral release to form the long-range morphogenetic gradient in the Drosophila wing disk epithelium

Hedgehog (Hh) moves from the producing cells to regulate the growth and development of distant cells in a variety of tissues. Here, we have investigated the mechanism of Hh release from the producing cells to form a morphogenetic gradient in the Drosophila wing imaginal disk epithelium. We describe that Hh reaches both apical and basolateral plasma membranes, but the apical Hh is subsequently internalized in the producing cells and routed to the basolateral surface, where Hh is released to form a long-range gradient. Functional analysis of the 12-transmembrane protein Dispatched, the glypican Dally-like (Dlp) protein, and the Ig-like and FNNIII domains of protein Interference Hh (Ihog) revealed that Dispatched could be involved in the regulation of vesicular trafficking necessary for basolateral release of Hh, Dlp, and Ihog. We also show that Dlp is needed in Hh-producing cells to allow for Hh release and that Ihog, which has been previously described as an Hh coreceptor, anchors Hh to the basolateral part of the disk epithelium