Paleoearthquakes Determination of Magnitude~6.5 on the North Tehran Fault, Iran

The North Tehran Fault is located at the southernmost piedmont of Central Alborz, north of Iran. It stands out as a major active fault menacing directly the city of Tehran, a 12 million people metropolis, and would have been the source of several major historical earthquakes in the past. The fault zone extends up to 110km and corresponds mainly to a reverse fault mostly crossing the northern suburbs of the Tehran metropolis, although NTF in its eastern part is characterized more as a left lateral strike slip active fault. We carried out a paleoseismological study of the fault zone in order to determine whether the fault was activated during the Holocene, and to define the characteristics of its activity in terms of kinematics and magnitude. Here in this paper we present only a part of our paleoseismological investigations trench TE2. Observations fromtwo trenches dug across the North Tehran fault scarp reveal evidence for a maximum of six surface-rupturing events within the late quaternary. According to the empirical relationships among average displacement per event and Moment magnitude [25], we can estimate six events Mw~ 6.5 associated with these ruptures in TE2 trench

NKX2-5 mutations causative for congenital heart disease retain functionality and are directed to hundreds of targets

We take a functional genomics approach to congenital heart disease mechanism. We used DamID to establish a robust set of target genes for NKX2-5 wild type and disease associated NKX2-5 mutations to model loss-of-function in gene regulatory networks. NKX2-5 mutants, including those with a crippled homeodomain, bound hundreds of targets including NKX2-5 wild type targets and a unique set of "off-targets", and retained partial functionality. NKXΔHD, which lacks the homeodomain completely, could heterodimerize with NKX2-5 wild type and its cofactors, including E26 transformation-specific (ETS) family members, through a tyrosine-rich homophilic interaction domain (YRD). Off-targets of NKX2-5 mutants, but not those of an NKX2-5 YRD mutant, showed overrepresentation of ETS binding sites and were occupied by ETS proteins, as determined by DamID. Analysis of kernel transcription factor and ETS targets show that ETS proteins are highly embedded within the cardiac gene regulatory network. Our study reveals binding and activities of NKX2-5 mutations on WT target and off-targets, guided by interactions with their normal cardiac and general cofactors, and suggest a novel type of gain-of-function in congenital heart disease