A Positive Regulatory Loop between foxi3a and foxi3b Is Essential for Specification and Differentiation of Zebrafish Epidermal Ionocytes

BACKGROUND: Epidermal ionocytes play essential roles in the transepithelial transportation of ions, water, and acid-base balance in fish embryos before their branchial counterparts are fully functional. However, the mechanism controlling epidermal ionocyte specification and differentiation remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: In zebrafish, we demonstrated that Delta-Notch-mediated lateral inhibition plays a vital role in singling out epidermal ionocyte progenitors from epidermal stem cells. The entire epidermal ionocyte domain of genetic mutants and morphants, which failed to transmit the DeltaC-Notch1a/Notch3 signal from sending cells (epidermal ionocytes) to receiving cells (epidermal stem cells), differentiates into epidermal ionocytes. The low Notch activity in epidermal ionocyte progenitors is permissive for activating winged helix/forkhead box transcription factors of foxi3a and foxi3b. Through gain- and loss-of-function assays, we show that the foxi3a-foxi3b regulatory loop functions as a master regulator to mediate a dual role of specifying epidermal ionocyte progenitors as well as of subsequently promoting differentiation of Na(+),K(+)-ATPase-rich cells and H(+)-ATPase-rich cells in a concentration-dependent manner. CONCLUSIONS/SIGNIFICANCE: This study provides a framework to show the molecular mechanism controlling epidermal ionocyte specification and differentiation in a low vertebrate for the first time. We propose that the positive regulatory loop between foxi3a and foxi3b not only drives early ionocyte differentiation but also prevents the complete blockage of ionocyte differentiation when the master regulator of foxi3 function is unilaterally compromised

Seismic damage scenarios in Lefkas old town (W. Greece)

Damage scenarios were developed for the Lefkada old town (LOT). LOT is the historical center of the capital of Lefkas Island, part of the Ionian Islands, one of the most seismically prone areas within the Mediterranean region that suffered numerous devastating earthquakes in the past. The most recent strong earthquake with Mw = 6.2 occurred on 14 August 2003 at a distance of about 13 km from LOT. A peak ground acceleration (PGA) equal to 0.42 g was recorded in LOT, one of the highest values ever recorded in Greece. Nevertheless, the 2003 event produced limited damage to the buildings of LOT, comprising traditional construction practices of architectural significance and a high seismic behaviour. Towards the development of damage scenarios the following tasks were performed: (a) buildings inventory and vulnerability indices determination using EMS-98 along with behaviour modification scores, (b) subsoil response functions and 1D viscoelastic models calculation using microtremors and (c) stochastic PGA simulation using site amplification deduced from the subsoil response functions. Two scenarios were developed considering the sources of the 2003 M6.2 earthquake and a future M7 event, located at the same fault. The discrete damage probability was resolved by formulating a beta distribution of an average damage grade related to the vulnerability index and the simulated PGA through empirical equations. The deduced models are comparable with the observed 2003 damage distribution, hence they are likely useful for preparing future emergency plans. In the aftermath, although further investigation is needed to explain outliers, the implementation of the followed methodology into an automated procedure for near real time shake and damage maps generation in case of a seismic crisis is highly recommended. The work herein, with proper adaptations, is potentially fairly applicable for other towns and regions in Europe