Scientists Prove Plausibility of New Pathway to Life's Chemical Building Blocks

For decades, chemists considered a chemical pathway known as the formose reaction the only route for producing sugars essential for life to begin, but more recent research has called into question the plausibility of such thinking. Now a group from The Scripps Research Institute has proven an alternative pathway to those sugars called the glyoxylate scenario, which may push the field of pre-life chemistry past the formose reaction hurdle.
Science Daily, Jan. 31, 2012

Vasudeva Naidu Sagi, et al.

Exploratory Experiments on the Chemistry of the “Glyoxylate Scenario”: Formation of Ketosugars from Dihydroxyfumarate. 

Journal of the American Chemical Society, 2012; : 120113151919003 DOI:10.1021/ja211383c

Scientists Discover New Clue to Chemical Origins of Life

Organic chemists at the University of York have made a significant advance towards establishing the origin of the carbohydrates (sugars) that form the building blocks of life.  A team led by Dr Paul Clarke at York has re-created a process which could have occurred in the prebiotic world.  They have made the first step towards showing how simple sugars -- threose and erythrose -- developed.   All biological molecules have an ability to exist as left-handed forms or right-handed forms. All sugars in biology are made up of the right-handed form of molecules and yet all the amino acids that make up the peptides and proteins are made up of the left-handed form. The researchers found using simple left-handed amino acids to catalyse the formation of sugars resulted in the production of predominately right-handed form of sugars. It could explain how carbohydrates originated and why the right-handed form dominates in nature.
Science Daily, Jan. 24, 2012

Laurence Burroughs, et al.

Asymmetric organocatalytic formation of protected and unprotected tetroses under potentially prebiotic conditions. 

Organic & Biomolecular Chemistry, 2012; DOI: 10.1039/C1OB06798B

Epigenetic understanding of gene-environment interactions in psychiatric disorders: a new concept of clinical genetics

Epigenetics is a mechanism that regulates gene expression independently of the underlying DNA sequence, relying instead on the chemical modification of DNA and histone proteins. Although environmental and genetic factors were thought to be independently associated with disorders, several recent lines of evidence suggest that epigenetics bridges these two factors. Epigenetic gene regulation is essential for normal development, thus defects in epigenetics cause various rare congenital diseases. Because epigenetics is a reversible system that can be affected by various environmental factors, such as drugs, nutrition, and mental stress, the epigenetic disorders also include common diseases induced by environmental factors. In this review, we discuss the nature of epigenetic disorders, particularly psychiatric disorders, on the basis of recent findings: 1) susceptibility of the conditions to environmental factors, 2) treatment by taking advantage of their reversible nature, and 3) transgenerational inheritance of epigenetic changes, that is, acquired adaptive epigenetic changes that are passed on to offspring. These recently discovered aspects of epigenetics provide a new concept of clinical genetics.

Takeo Kubota, Kunio Miyake and Takae Hirasawa

Clin Epigenetics. 2012; 4(1): 1.
Published online 2012 January 20. doi: 10.1186/1868-7083-4-1

Interneuron dysfunction in psychiatric disorders

Schizophrenia, autism and intellectual disabilities are best understood as spectrums of diseases that have broad sets of causes. However, it is becoming evident that these conditions also have overlapping phenotypes and genetics, which is suggestive of common deficits. In this context, the idea that the disruption of inhibitory circuits might be responsible for some of the clinical features of these disorders is gaining support. Recent studies in animal models demonstrate that the molecular basis of such disruption is linked to specific defects in the development and function of interneurons — the cells that are responsible for establishing inhibitory circuits in the brain. These insights are leading to a better understanding of the causes of schizophrenia, autism and intellectual disabilities, and may contribute to the development of more-effective therapeutic interventions.

Oscar Marín
Nature Reviews Neuroscience 13, 107-120 (February 2012) |doi:10.1038/nrn3155

Pattern separation in the hippocampus

The ability to discriminate among similar experiences is a crucial feature of episodic memory. This ability has long been hypothesized to require the hippocampus, and computational models suggest that it is dependent on pattern separation. However, empirical data for the role of the hippocampus in pattern separation have not been available until recently. This review summarizes data from electrophysiological recordings, lesion studies, immediate-early gene imaging, transgenic mouse models, as well as human functional neuroimaging, that provide convergent evidence for the involvement of particular hippocampal subfields in this key process. We discuss the impact of aging and adult neurogenesis on pattern separation, and also highlight several challenges to linking across species and approaches, and suggest future directions for investigation.

Michael A. Yassa, Craig E.L. Stark
Trends in Neurosciences, Volume 34, Issue 10, October 2011, Pages 515–525
http://dx.doi.org/10.1016/j.tins.2011.06.006, How to Cite or Link Using DOI

Epigenetics in C. elegans: Facts and challenges

Epigenetics is defined as the study of heritable changes in gene expression that are not accompanied by changes in the DNA sequence. Epigenetic mechanisms include histone post-translational modifications, histone variant incorporation, non-coding RNAs, and nucleosome remodeling and exchange. In addition, the functional compartmentalization of the nucleus also contributes to epigenetic regulation of gene expression. Studies on the molecular mechanisms underlying epigenetic phenomena and their biological function have relied on various model systems, including yeast, plants, flies, and cultured mammalian cells. Here we will expose the reader to the current understanding of epigenetic regulation in the roundworm C. elegans. We will review recent models of nuclear organization and its impact on gene expression, the biological role of enzymes modifying core histones, and the function of chromatin-associated factors, with special emphasis on Polycomb (PcG) and Trithorax (Trx-G) group proteins. We will discuss how the C. elegans model has provided novel insight into mechanisms of epigenetic regulation as well as suggest directions for future research.

Dirk Wenze et al.
genesis 49:647–661, 2011. 

Epigenetic Mechanisms in Cognition

Although the critical role for epigenetic mechanisms in development and cell differentiation has long been appreciated, recent evidence reveals that these mechanisms are also employed in postmitotic neurons as a means of consolidating and stabilizing cognitive-behavioral memories. In this review, we discuss evidence for an “epigenetic code” in the central nervous system that mediates synaptic plasticity, learning, and memory. We consider how specific epigenetic changes are regulated and may interact with each other during memory formation and how these changes manifest functionally at the cellular and circuit levels. We also describe a central role for mitogen-activated protein kinases in controlling chromatin signaling in plasticity and memory. Finally, we consider how aberrant epigenetic modifications may lead to cognitive disorders that affect learning and memory, and we review the therapeutic potential of epigenetic treatments for the amelioration of these conditions.

Jeremy J. Day,J. David Sweatt
Neuron, Volume 70, Issue 5, 813-829, 9 June 2011, 10.1016/j.neuron.2011.05.019

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