Epigenetic impacts on neurodevelopment: pathophysiological mechanisms and genetic modes of action.

Disruptions of genes that are involved in epigenetic functions are known to be causative for several mental retardation/intellectual disability (MR/ID) syndromes. Recent work has highlighted genes with epigenetic functions as being implicated in autism spectrum disorders (ASDs) and schizophrenia (SCZ). The gene-environment interaction is an important factor of pathogenicity for these complex disorders. Epigenetic modifications offer a mechanism by which we can explain how the environment interacts with, and is able to dynamically regulate, the genome. This review aims to provide an overview of the role of epigenetic deregulation in the etiopathology for neurodevelopment disease.

Zahir FR, Brown CJ.

Pediatr Res. 2011 May;69(5 Pt 2):92R-100R. doi: 10.1203/PDR.0b013e318213565e.

Experimental and Theoretical Approaches to Conscious Processing

Recent experimental studies and theoretical models have begun to address the challenge of establishing a causal link between subjective conscious experience and measurable neuronal activity. The present review focuses on the well-delimited issue of how an external or internal piece of information goes beyond nonconscious processing and gains access to conscious processing, a transition characterized by the existence of a reportable subjective experience. Converging neuroimaging and neurophysiological data, acquired during minimal experimental contrasts between conscious and nonconscious processing, point to objective neural measures of conscious access: late amplification of relevant sensory activity, long-distance cortico-cortical synchronization at beta and gamma frequencies, and “ignition” of a large-scale prefronto-parietal network. The authors compare these findings to current theoretical models of conscious processing, including the Global Neuronal Workspace (GNW) model according to which conscious access occurs when incoming information is made globally available to multiple brain systems through a network of neurons with long-range axons densely distributed in prefrontal, parieto-temporal, and cingulate cortices. The clinical implications of these results for general anesthesia, coma, vegetative state, and schizophrenia are discussed.

Stanislas Dehaene, Jean-Pierre Changeux
Neuron, Volume 70, Issue 2, 28 April 2011, Pages 200–227

The Extraction of 3D Shape in the Visual System of Human and Nonhuman Primates

Depth structure, the third dimension of object shape, is extracted from disparity, motion, texture, and shading in the optic array. Gradient-selective neurons play a key role in this process. Such neurons occur in CIP, AIP, TEs, and F5 (for first- or second-order disparity gradients), in MT/V5, in FST (for speed gradients), and in CIP and TEs (for texture gradients). Most of these regions are activated during magnetic resonance scanning in alert monkeys by comparing 3D conditions with the 2D controls for the different cues. Similarities in activation patterns of monkeys and humans tested with identical paradigms suggest that like gradient-selective neurons are found in corresponding human cortical areas. This view gains credence as the homologies between such areas become more evident. Furthermore, 3D shape-processing networks are similar in the two species, with the exception of the greater involvement of human posterior parietal cortex in the extraction of 3D shape from motion. Thus we can begin to understand how depth structure is extracted from motion, disparity, and texture in the primate brain, but the extraction of depth structure from shading and that of wire-like objects requires further scrutiny.

Guy A. Orban
The Extraction of 3D Shape in the Visual System of Human and Nonhuman Primates
Annual Review of Neuroscience
Vol. 34: 361-388 (Volume publication date July 2011)
First published online as a Review in Advance on March 29, 2011
DOI: 10.1146/annurev-neuro-061010-113819

DNA methylation and memory formation

Memory formation and storage require long-lasting changes in memory-related neuronal circuits. Recent evidence indicates that DNA methylation may serve as a contributing mechanism in memory formation and storage. These emerging findings suggest a role for an epigenetic mechanism in learning and long-term memory maintenance and raise apparent conundrums and questions. For example, it is unclear how DNA methylation might be reversed during the formation of a memory, how changes in DNA methylation alter neuronal function to promote memory formation, and how DNA methylation patterns differ between neuronal structures to enable both consolidation and storage of memories. Here we evaluate the existing evidence supporting a role for DNA methylation in memory, discuss how DNA methylation may affect genetic and neuronal function to contribute to behavior, propose several future directions for the emerging subfield of neuroepigenetics, and begin to address some of the broader implications of this work.

Jeremy J Day & J David Sweatt
Nature Neuroscience 13, 1319–1323 (2010) doi:10.1038/nn.2666

Published online 26 October 2010

Hearing Impairment: A Panoply of Genes and Functions

Research in the genetics of hearing and deafness has evolved rapidly over the past years, providing the molecular foundation for different aspects of the mechanism of hearing. Considered to be the most common sensory disorder, hearing impairment is genetically heterogeneous. The multitude of genes affected encode proteins associated with many different functions, encompassing overarching areas of research. These include, but are not limited to, developmental biology, cell biology, physiology, and neurobiology. In this review, we discuss the broad categories of genes involved in hearing and deafness. Particular attention is paid to a subgroup of genes associated with inner ear gene regulation, fluid homeostasis, junctional complex and tight junctions, synaptic transmission, and auditory pathways. Overall, studies in genetics have provided research scientists and clinicians with insight regarding practical implications for the hearing impaired, while heralding hope for future development of therapeutics.

Amiel A. Dror, et al.
Neuron, Volume 68, Issue 2, 293-308, 21 October 2010
10.1016/j.neuron.2010.10.011

Human Brain Evolution: Harnessing the Genomics (R)evolution to Link Genes, Cognition, and Behavio

The evolution of the human brain has resulted in numerous specialized features including higher cognitive processes such as language. Knowledge of whole-genome sequence and structural variation via high-throughput sequencing technology provides an unprecedented opportunity to view human evolution at high resolution. However, phenotype discovery is a critical component of these endeavors and the use of nontraditional model organisms will also be critical for piecing together a complete picture. Ultimately, the union of developmental studies of the brain with studies of unique phenotypes in a myriad of species will result in a more thorough model of the groundwork the human brain was built upon. Furthermore, these integrative approaches should provide important insights into human diseases.

Genevieve Konopka, Daniel H. Geschwind
Neuron, 21 October, 2010 Volume 68, Issue 2

Epigenetic control of neural precursor cell fate during development

The temporally and spatially restricted nature of the differentiation capacity of cells in the neural lineage has been studied extensively in recent years. Epigenetic control of developmental genes, which is heritable through cell divisions, has emerged as a key mechanism defining the differentiation potential of cells. Short-term or reversible repression of developmental genes puts them in a 'poised state', ready to be activated in response to differentiation-inducing cues, whereas long-term or permanent repression of developmental genes restricts the cell fates they regulate. Here, the authors review the molecular mechanisms that underlie the establishment and regulation of differentiation potential along the neural lineage during development.

Yusuke Hirabayashi & Yukiko Gotoh

Nature Reviews Neuroscience 11, 377-388 (June 2010) | doi:10.1038/nrn2810

XENON100 announced the new results

The XENON100 collaboration submitted a paper with the first results of a 11.2 days background analysis to PRL, excluding previously unexplored parameter space and questioning the light WIMP interpretation of the DAMA and CoGeNT results.

The preprint can be found here:

arXiv:1005.0380.

These results are also covered in the media:
The New York Times
New Scientist
Nature Blog
Discover Magazine Blog
Scientific American

Wired - XENON100August 6, 2009: An article about the hunt for Dark Matter and XENON100 appeared in the UK version of the Wired magazine.

The evolutionary significance of ancient genome duplications

Many organisms are currently polyploid, or have a polyploid ancestry and now have secondarily 'diploidized' genomes. This finding is surprising because retained whole-genome duplications (WGDs) are exceedingly rare, suggesting that polyploidy is usually an evolutionary dead end. We argue that ancient genome doublings could probably have survived only under very specific conditions, but that, whenever established, they might have had a pronounced impact on species diversification, and led to an increase in biological complexity and the origin of evolutionary novelties.

Yves Van de Peer, et al.
Nature Reviews Genetics 10, 725-732 (October 2009) | doi:10.1038/nrg2600

'Junk' DNA Proves To Be Highly Valuable

What was once thought of as DNA with zero value in plants--dubbed "junk" DNA--may turn out to be key in helping scientists improve the control of gene expression in transgenic crops.  For more than 30 years, scientists have been perplexed by the workings of intergenic DNA, which is located between genes. Scientists have since found that, among other functions, some intergenic DNA plays a physical role in protecting and linking chromosomes. But after subtracting intergenic DNA, there was still leftover or "junk" DNA which seemed to have no purpose.  Cooper and collaborators investigated "junk" DNA in the model plant Arabidopsis thaliana, using a computer program to find short segments of DNA that appeared as molecular patterns. When comparing these patterns to genes, Cooper's team found that 50 percent of the genes had the exact same sequences as the molecular patterns. This discovery showed a sequence pattern link between "junk" and coding DNA. These linked patterns are called pyknons, which Cooper and his team believe might be evidence of something important that drives genome expansion in plants.

The researchers found that pyknons are also the same in sequence and size as small segments of RNA that regulate gene expression through a method known as gene silencing. This evidence suggests that these RNA segments are converted back into DNA and are integrated into the intergenic space. Over time, these sequences repeatedly accumulate. Prior to this discovery, pyknons were only known to exist in the human genome. Thus, this discovery in plants illustrates that the link between coding DNA and junk DNA crosses higher orders of biology and suggests a universal genetic mechanism at play that is not yet fully understood.  The data suggest that scientists might be able to use this information to determine which genes are regulated by gene silencing, and that there may be some application for the improvement of transgenic plants by using the pyknon information.

Science Daily - June 12, 2009
Feng et al. 

Coding DNA repeated throughout intergenic regions of the Arabidopsis thaliana genome: evolutionary footprints of RNA silencing. 

Molecular BioSystems, 2009; DOI: 10.1039/b903031j