Feasibility study of a regional EEW system for the Eastern Caribbean Region

A feasibility study of an earthquake early warning (EEW) system was conducted for Antigua and Barbuda (Eastern Caribbean Region) testing two interface earthquake scenarios corresponding to the maximum credible earthquake and to the earthquake scenario associated with a return period of 475 years. Broadband synthetic seismograms were produced at three selected sensitive facilities, where there is possible interest in the installation of an EEW system. The expected damage was retrieved from the synthetic seismograms and compared with the lead-time determined for a regional EEW, configured to a first approximation based on the principles of geometrical optics. Next, the Virtual Seismologist EEW algorithm, as included in SeisComp3, was tested. Additional broadband synthetic seismograms were produced for the stations in the Eastern Caribbean seismic networks in order to simulate the real time behaviour of the seismic networks during the occurrence of the synthetic earthquakes and to assess the predictive capacity of the selected ground motion prediction equation. Expected peak ground accelerations and lead-times at the critical infrastructures constitute the major outcome of the stud

Characterisation of a novel NR4A2 mutation in Parkinson's disease brain

OBJECTIVE: We performed a mutation screen of NR4A2 (also known as NURR1) in 409 Parkinson’s disease (PD) patients. We identified a novel single base substitution in the 5′UTR of the NR4A2 (also known as NURR1) gene (c.-309C > T). RESULTS: We have performed expression studies in neuronal cell lines showing that the c.-309C > T mutation reduces NR4A2 mRNA expression in vitro. We have confirmed this finding in vivo by performing allele specific real-time PCR from brain tissue harbouring the 309C > T mutation and show a 3.48 ± 1.62 fold reduction in mRNA expression of the mutant allele compared to wild-type. In addition we have undertaken genome wide expression analysis of the mutant NR4A2 brain and shown underexpressed genes were significantly enriched for gene ontology categories in nervous system development and synaptic transmission and overexpressed genes were enriched for unfolded protein response and morphogenesis. Lastly we have shown that the c.-309C > T mutation abrogates the protective effect of wild-type NR4A2 against apoptopic stress. CONCLUSIONS: Our findings indicate the c.-309C > T mutation reduces NR4A2 expression resulting in the downregulation of genes involved in the development and maintenance of the nervous system and synaptic transmission. These downregulated pathways contained genes known to be transactivated by NR4A2 and were not disrupted in idiopathic PD brain suggesting causality of the mutation