All-carbon multi-electrode array for real-time in vitro measurements of oxidizable neurotransmitters

We report on the ion beam fabrication of all-carbon multi electrode arrays (MEAs) based on 16 graphitic micro-channels embedded in single-crystal diamond (SCD) substrates. The fabricated SCD-MEAs are systematically employed for the in vitro simultaneous amperometric detection of the secretory activity from populations of chromaffin cells, demonstrating a new sensing approach with respect to standard techniques. The biochemical stability and biocompatibility of the SCD-based device combined with the parallel recording of multi-electrodes array allow: i) a significant time saving in data collection during drug screening and/or pharmacological tests over a large number of cells, ii) the possibility of comparing altered cell functionality among cell populations, and iii) the repeatition of acquisition runs over many cycles with a fully non-toxic and chemically robust bio-sensitive substrate.Comment: 24 pages, 5 figure

Deciphering large-scale superposed fold systems at shallow crustal levels in collision zones: insights from the Marguareis Massif (southwestern Alps)

We present and discuss the results of a field-based approach including accurate geological mapping and micro- to map-scale structural analysis to highlight the finite strain pattern recorded in Marguareis Unit, a massif deformed at shallow crustal levels at the boundary between Maritime and Ligurian Alps. We describe superposed tectonic structures developed under low-grade metamorphic conditions during the Alpine collision and nowadays exceptionally well recorded in the area of interest. We demonstrate that the structural frame of the Marguareis Unit results from superposition of fourfold systems, later segmented, but without significant displacements, by brittle faults

Numerical simulations of an ocean/continent convergent system: influence of subduction geometry and mantle wedge hydration on crustal recycling

The effects of the hydration mechanism on continental crust recycling are analyzed through a 2D finite element thermo-mechanical model. Oceanic slab dehydration and consequent mantle wedge hydration are implemented using a dynamic method. Hydration is accomplished by lawsonite and serpentine breakdown; topography is treated as a free surface. Subduction rates of 1, 3, 5, 7.5 and 10 cm/y, slab angles of 30o, 45o and 60o and a mantle rheology represented by dry dunite and dry olivine flow laws, have been taken into account during successive numerical experiments. Model predictions pointed out that a direct relationship exists between mantle rheology and the amount of recycled crustal material: the larger the viscosity contrast between hydrated and dry mantle, the larger the percentage of recycled material into the mantle wedge. Slab dip variation has a moderate impact on the recycling. Metamorphic evolution of recycled material is influenced by subduction style. TPmax, generally representative of eclogite facies conditions, is sensitive to changes in slab dip. A direct relationship between subduction rate and exhumation rate results for different slab dips that does not depend on the used mantle flow law. Thermal regimes predicted by different numerical models are compared to PT paths followed by continental crustal slices involved in ancient and recent subduction zones, making ablative subduction a suitable pre-collisional mechanism for burial and exhumation of continental crust.Comment: 10 figures, 3 table

Catechol O-methyl transferase and dopamine D2 receptor gene polymorphisms: evidence of positive heterosis and gene–gene interaction on working memory functioning.

The COMT Va

Exploring the functional role of the CHRM2 gene in human cognition: results from a dense genotyping and brain expression study

<p>Abstract</p> <p>Background</p> <p>The <it>CHRM2 </it>gene, located on the long arm of chromosome 7 (7q31-35), is involved in neuronal excitability, synaptic plasticity and feedback regulation of acetylcholine release, and has been implicated in higher cognitive processing. The aim of this study is the identification of functional (non)coding variants underlying cognitive phenotypic variation.</p> <p>Methods</p> <p>We previously reported an association between polymorphisms in the 5'UTR regions of the <it>CHRM2 </it>gene and intelligence.. However, no functional variants within this area have currently been identified. In order to identify the relevant functional variant(s), we conducted a denser coverage of SNPs, using two independent Dutch cohorts, consisting of a children's sample (N = 371 ss; mean age 12.4) and an adult sample (N= 391 ss; mean age 37.6). For all individuals standardized intelligence measures were available. Subsequently, we investigated genotype-dependent <it>CHRM2 </it>gene expression levels in the brain, to explore putative enhancer/inhibition activity exerted by variants within the muscarinic acetylcholinergic receptor.</p> <p>Results</p> <p>Using a test of within-family association two of the previously reported variants – rs2061174, and rs324650 – were again strongly associated with intelligence (<it>P </it>< 0.01). A new SNP (rs2350780) showed a trend towards significance. SNP rs324650, is located within a short interspersed repeat (SINE). Although the function of short interspersed repeats remains contentious, recent research revealed potential functionality of SINE repeats in a gene-regulatory context. Gene-expression levels in post-mortem brain material, however were not dependent on rs324650 genotype.</p> <p>Conclusion</p> <p>Using a denser coverage of SNPs in the <it>CHRM2 </it>gene, we confirmed the 5'UTR regions to be most interesting in the context of intelligence, and ruled out other regions of this gene. Although no correlation between genomic variants and gene expression was found, it would be interesting to examine allele-specific effects on CHRM2 transcripts expression in much more detail, for example in relation to transcripts specific halve-life and their relation to LTP and memory.</p

A functional polymorphism under positive evolutionary selection in ADRB2 is associated with human intelligence with opposite effects in the young and the elderly

Comparative genomics offers a novel approach to unravel the genetic basis of complex traits. We performed a two stage analysis where genes ascertained for enhanced protein evolution in primates are subsequently searched for the presence of non-synonymous coding SNPs in the current human population at amino acid sites that differ between humans and chimpanzee. Positively selected genes among primates are generally presumed to determine phenotypic differences between humans and chimpanzee, such as the enhanced cognitive ability of our species. Amino acid substitutions segregating in humans at positively selected amino acid sites are expected to affect phenotypic differences among humans. Therefore we conducted an association study in two family based cohorts and one population based cohort between cognitive ability and the most likely candidate gene among the five that harbored more than one such polymorphism. The derived, human-specific allele of the beta-2 adrenergic receptor Arg16Gly polymorphism was found to be the increaser allele for performance IQ in the young, family based cohort but the decreaser allele for two different measures of cognition in the large Scottish cohort of unrelated individuals. The polymorphism is known to affect signaling activity and modulation of beta-2 adrenergic signaling has been shown to adjust memory consolidation, a trait related to cognition. The opposite effect of the polymorphism on cognition in the two age classes observed in the different cohorts resembles the effect of ADRB2 on hypertension, which also has been reported to be age dependent. This result illustrates the relevance of comparative genomics to detect genes that are involved in human behavior. © 2008 Springer Science+Business Media, LLC

Association between the CHRM2 gene and intelligence in a sample of 304 Dutch families.

The CHRM2 gene is thought to be involved in neuronal excitability, synaptic plasticity and feedback regulation of acetylcholine release and has previously been implicated in higher cognitive processing. In a sample of 667 individuals from 304 families, we genotyped three singlenucleotide polymorphisms (SNPs) in the CHRM2 gene on 7q31–35. From all individuals, standardized intelligence measures were available. Using a test of within-family association, which controls for the possible effects of population stratification, a highly significant association was found between the CHRM2 gene and intelligence. The strongest association was between rs324650 and performance IQ (PIQ), where the T allele was associated with an increase of 4.6 PIQ points. In parallel with a large familybased association, we observed an attenuated – although still significant – population-based association, illustrating that population stratification may decrease our chances of detecting allele–trait associations. Such a mechanism has been predicted earlier, and this article is one of the first to empirically show that family-based association methods are not only needed to guard against false positives, but are also invaluable in guarding against false negatives

The Play Behaviours of Roma Children in Transylvania

The Roma children of Transylvania are probably the most materially deprived in Europe. They often live in one-room shacks made from wood and mud, with no running water, no sanitation, and sometimes no heating. Many rely on charity for their food and medicines. But, are they play deprived? This paper summarises an observational study of the play behaviours of children in a small Roma village. It highlights the striking contrast between the abject poverty that characterises their lives and the general happiness of the children. These children live their limited lives to the full. They ‘play everywhere and with everything’, but not in the generally accepted sense of that phrase. The usual niceties of privacy, personal possessions and property boundaries are irrelevant here. Their play is rich in imagination and creativity; it is living proof of Nicholson’s theory of loose parts

An Ancient Duplication of Exon 5 in the Snap25 Gene Is Required for Complex Neuronal Development/Function

Alternative splicing is an evolutionary innovation to create functionally diverse proteins from a limited number of genes. SNAP-25 plays a central role in neuroexocytosis by bridging synaptic vesicles to the plasma membrane during regulated exocytosis. The SNAP-25 polypeptide is encoded by a single copy gene, but in higher vertebrates a duplication of exon 5 has resulted in two mutually exclusive splice variants, SNAP-25a and SNAP-25b. To address a potential physiological difference between the two SNAP-25 proteins, we generated gene targeted SNAP-25b deficient mouse mutants by replacing the SNAP-25b specific exon with a second SNAP-25a equivalent. Elimination of SNAP-25b expression resulted in developmental defects, spontaneous seizures, and impaired short-term synaptic plasticity. In adult mutants, morphological changes in hippocampus and drastically altered neuropeptide expression were accompanied by severe impairment of spatial learning. We conclude that the ancient exon duplication in the Snap25 gene provides additional SNAP-25-function required for complex neuronal processes in higher eukaryotes