High-Throughput Analysis of Promoter Occupancy Reveals New Targets for Arx, a Gene Mutated in Mental Retardation and Interneuronopathies

Genetic investigations of X-linked intellectual disabilities have implicated the ARX (Aristaless-related homeobox) gene in a wide spectrum of disorders extending from phenotypes characterised by severe neuronal migration defects such as lissencephaly, to mild or moderate forms of mental retardation without apparent brain abnormalities but with associated features of dystonia and epilepsy. Analysis of Arx spatio-temporal localisation profile in mouse revealed expression in telencephalic structures, mainly restricted to populations of GABAergic neurons at all stages of development. Furthermore, studies of the effects of ARX loss of function in humans and animal models revealed varying defects, suggesting multiple roles of this gene during brain development. However, to date, little is known about how ARX functions as a transcription factor and the nature of its targets. To better understand its role, we combined chromatin immunoprecipitation and mRNA expression with microarray analysis and identified a total of 1006 gene promoters bound by Arx in transfected neuroblastoma (N2a) cells and in mouse embryonic brain. Approximately 24% of Arx-bound genes were found to show expression changes following Arx overexpression or knock-down. Several of the Arx target genes we identified are known to be important for a variety of functions in brain development and some of them suggest new functions for Arx. Overall, these results identified multiple new candidate targets for Arx and should help to better understand the pathophysiological mechanisms of intellectual disability and epilepsy associated with ARX mutations

Measuring Risk Attitudes Controlling for Personality Traits*

Abstract: This study measures risk attitudes using two paid experiments: the Holt and Laury (2002) procedure and a variation of the game show Deal or No Deal. The participants also completed a series of personality questionnaires developed in the psychology literature including the risk domains of Weber, Blais, and Betz (2002). As in previous studies risk attitudes vary within subjects across elicitation methods. However, this variation can be explained by individual personality traits. Specifically, subjects behave as though the Holt and Laury task is an investment decision while the Deal or No Deal task is a gambling decision

Interfacial Adhesion of Fully Transient, Mussel‐Inspired Hydrogels with Different Network Crosslink Modalities

In fully transient, mussel-inspired hydrogels, metal-coordinate complexes form supramolecular crosslinks, which offer tunable viscoelastic properties and mechanical reversibility. The metal-coordination complexation that comprises the crosslinks can take on tris-, bis-, mono-, and free-state modalities (3, 2, 1, or 0 ligands per ion, respectively). Although prior work has established relationships between network crosslinking and mechanical properties, the effect of crosslink and ligand modalities on gel-surface adhesion is not well understood for fully transient hydrogels. Using glass and nickel-coated spherical probes, the effect of network crosslinking modalities on the adhesive strength of hydrogels based on histidine-Ni2+ and nitrodopamine-Fe3+ ion crosslinks is investigated. Since crosslink modalities have a strong impact on the mechanical properties of the bulk network, it is first determined how adhesion relates to the mechanical properties, regardless of the distribution of crosslinking modalities and ligand type. It is ultimately found that the peak adhesive stress increases with decreasing percentage of ligands in tris-crosslinks