The CHARGE study: an epidemiologic investigation of genetic and environmental factors contributing to autism.

Causes and contributing factors for autism are poorly understood. Evidence suggests that prevalence is rising, but the extent to which diagnostic changes and improvements in ascertainment contribute to this increase is unclear. Both genetic and environmental factors are likely to contribute etiologically. Evidence from twin, family, and genetic studies supports a role for an inherited predisposition to the development of autism. Nonetheless, clinical, neuroanatomic, neurophysiologic, and epidemiologic studies suggest that gene penetrance and expression may be influenced, in some cases strongly, by the prenatal and early postnatal environmental milieu. Sporadic studies link autism to xenobiotic chemicals and/or viruses, but few methodologically rigorous investigations have been undertaken. In light of major gaps in understanding of autism, a large case-control investigation of underlying environmental and genetic causes for autism and triggers of regression has been launched. The CHARGE (Childhood Autism Risks from Genetics and Environment) study will address a wide spectrum of chemical and biologic exposures, susceptibility factors, and their interactions. Phenotypic variation among children with autism will be explored, as will similarities and differences with developmental delay. The CHARGE study infrastructure includes detailed developmental assessments, medical information, questionnaire data, and biologic specimens. The CHARGE study is linked to University of California-Davis Center for Children's Environmental Health laboratories in immunology, xenobiotic measurement, cell signaling, genomics, and proteomics. The goals, study design, and data collection protocols are described, as well as preliminary demographic data on study participants and on diagnoses of those recruited through the California Department of Developmental Services Regional Center System

Conditional expression in corticothalamic efferents reveals a developmental role for nicotinic acetylcholine receptors in modulation of passive avoidance behavior

Prenatal nicotine exposure has been linked to attention deficit hyperactivity disorder and cognitive impairment, but the sites of action for these effects of nicotine are still under investigation. High-affinity nicotinic acetylcholine receptors (nAChRs) contain the .2 subunit and modulate passive avoidance (PA) learning in mice. Using an inducible, tetracycline-regulated transgenic system, we generated lines of mice with expression of high-affinity nicotinic receptors restored in specific neuronal populations. One line of mice shows functional .2 subunit-containing nAChRs localized exclusively in corticothalamic efferents. Functional, presynaptic nAChRs are present in the thalamus of these mice as detected by nicotine-elicited rubidium efflux assays from synaptosomes. Knock-out mice lacking high-affinity nAChRs show elevated baseline PA learning, whereas normal baseline PA behavior is restored in mice with corticothalamic expression of these nAChRs. In contrast, nicotine can enhance PA learning in adult wild-type animals but not in corticothalamic-expressing transgenic mice. When these transgenic mice are treated with doxycycline in adulthood to switch off nAChR expression, baseline PA is maintained even after transgene expression is abolished. These data suggest that high-affinity nAChRs expressed on corticothalamic neurons during development are critical for baseline PA performance and provide a potential neuroanatomical substrate for changes induced by prenatal nicotine exposure leading to long-term behavioral and cognitive deficits

Impact of spin-orbit coupling on quantum Hall nematic phases

Anisotropic charge transport is observed in a two-dimensional (2D) hole system in a perpendicular magnetic field at filling factors nu=7/2, nu=11/2, and nu=13/2 at low temperature. In stark contrast, the transport at nu=9/2 is isotropic for all temperatures. Isotropic hole transport at nu=7/2 is restored for sufficiently low 2D densities or an asymmetric confining potential. The density and symmetry dependences of the observed anisotropies suggest that strong spin-orbit coupling in the hole system contributes to the unusual transport behavior.Comment: 4 pages, 4 figure

Observation of a One-Dimensional Spin-Orbit Gap in a Quantum Wire

Understanding the flow of spins in magnetic layered structures has enabled an increase in data storage density in hard drives over the past decade of more than two orders of magnitude1. Following this remarkable success, the field of 'spintronics' or spin-based electronics is moving beyond effects based on local spin polarisation and is turning its attention to spin-orbit interaction (SOI) effects, which hold promise for the production, detection and manipulation of spin currents, allowing coherent transmission of information within a device. While SOI-induced spin transport effects have been observed in two- and three-dimensional samples, these have been subtle and elusive, often detected only indirectly in electrical transport or else with more sophisticated techniques. Here we present the first observation of a predicted 'spin-orbit gap' in a one-dimensional sample, where counter-propagating spins, constituting a spin current, are accompanied by a clear signal in the easily-measured linear conductance of the system.Comment: 10 pages, 5 figures, supplementary informatio

Taxing the powerful, the rise of populism and the crisis in Europe: the case for the EU Common Consolidated Corporate Tax Base

Contemporary populism is rooted in a crisis of legitimacy. Corporate taxavoidance by multinationals is one cause of that crisi s. Although states tend to beincreasingly formally committed to tackling avoidance, they do so in a system thatpromotes contradictory sets of behaviour. This tends to undermine attempts to solvethe problem of avoidance unless a more transformative collective approach is taken.Ironically, despite its own democratic deficit, the European Comm ission has taken aleading role in promoting such a solution: the Common Consolidated Corporate TaxBase (CCCTB). In this paper, I set out the case for ‘unitary taxation’ based on theCCCTB and state some of its current problems. The problem of corporation taxraises a basic issue in terms of who is sovereignty for, and solving the problemprovides an important contribution to legitimacy of both the state and the EU