The effect of site practices on the integrity of large diameter bored piles

In South Africa, concrete in large diameter bored piles is generally placed by discharging a high flow concrete mix directly from the truck mixer and allowing the concrete to fall freely to the base of the pile hole. While certain site practices have been used by piling contractors for years, many engineers are not convinced of their acceptability. This paper discusses the results of an investigation which assessed the effect of site practices on the integrity of cast in-situ bored piles. Such practices include the method of concrete placement and the amount of water and/or loose spoil in the pile hole at the time of casting. The results of this investigation dispel the myth that the free fall placement of concrete in clean, dry pile holes has a detrimental effect on the degree of compaction and compressive strength of the concrete

Sympatric and allopatric Alcolapia soda lake cichlid species show similar levels of assortative mating

Characterising reproductive barriers such as mating preferences within rapid evolutionary radiations is crucial for understanding the early stages of speciation. Cichlid fishes are well-known for their adaptive radiations and capacity for rapid speciation and as such we investigate assortative mating among Alcolapia species; a recent (<10,000 years), small adaptive radiation, endemic to the extreme soda lakes, Magadi (one species) and Natron (three species), in East Africa. In seminatural aquarium conditions, we observed both courtship and mate choice (tested by microsatellite paternity analysis) to be significantly assortative among the three sympatric Natron species in a three-way choice experiment. This was also the case between allopatric species from Natron and Magadi, as found in a two-way choice experiment. However, the proportion of disassortative matings was substantial in both of these experiments, with hybrids comprising 29% of offspring in sympatric species and 11.4% in allopatric species comparisons. . Previous work suggests that the Natron/Magadi split might not be much older than the radiation within Natron, so the similar rate of hybridisation in the allopatric comparison is surprising and inconsistent with predictions of reinforcement theory, which predicts a faster rate of accumulation of premating isolation in sympatry. The relatively weak assortative mating in sympatry suggests that additional reproductive barriers, such as microhabitat preferences or spatial structuring may contribute to genetic isolation in nature

Gravin Orchestrates Protein Kinase A and β2-Adrenergic Receptor Signaling Critical for Synaptic Plasticity and Memory

A kinase-anchoring proteins (AKAPs) organize compartmentalized pools of protein kinase A (PKA) to enable localized signaling events within neurons. However, it is unclear which of the many expressed AKAPs in neurons target PKA to signaling complexes important for long-lasting forms of synaptic plasticity and memory storage. In the forebrain, the anchoring protein gravin recruits a signaling complex containing PKA, PKC, calmodulin, and PDE4D (phosphodiesterase 4D) to the β2-adrenergic receptor. Here, we show that mice lacking the α-isoform of gravin have deficits in PKA-dependent long-lasting forms of hippocampal synaptic plasticity including β2-adrenergic receptor-mediated plasticity, and selective impairments of long-term memory storage. Furthermore, both hippocampal β2-adrenergic receptor phosphorylation by PKA, and learning-induced activation of ERK in the CA1 region of the hippocampus are attenuated in mice lacking gravin-α. We conclude that gravin compartmentalizes a significant pool of PKA that regulates learning-induced β2-adrenergic receptor signaling and ERK activation in the hippocampus in vivo, thereby organizing molecular interactions between glutamatergic and noradrenergic signaling pathways for long-lasting synaptic plasticity, and memory storage

IRS2 is a candidate driver oncogene on 13q34 in colorectal cancer

Copy number alterations are frequently found in colorectal cancer (CRC), and recurrent gains or losses are likely to correspond to regions harbouring genes that promote or impede carcinogenesis respectively. Gain of chromosome 13q is common in CRC but, because the region of gain is frequently large, identification of the driver gene(s) has hitherto proved difficult. We used array comparative genomic hybridization to analyse 124 primary CRCs, demonstrating that 13q34 is a region of gain in 35% of CRCs, with focal gains in 4% and amplification in a further 1.6% of cases. To reduce the number of potential driver genes to consider, it was necessary to refine the boundaries of the narrowest copy number changes seen in this series and hence define the minimal copy region (MCR). This was performed using molecular copy-number counting, identifying IRS2 as the only complete gene, and therefore the likely driver oncogene, within the refined MCR. Analysis of available colorectal neoplasia data sets confirmed IRS2 gene gain as a common event. Furthermore, IRS2 protein and mRNA expression in colorectal neoplasia was assessed and was positively correlated with progression from normal through adenoma to carcinoma. In functional in vitro experiments, we demonstrate that deregulated expression of IRS2 activates the oncogenic PI3 kinase pathway and increases cell adhesion, both characteristics of invasive CRC cells. Together, these data identify IRS2 as a likely driver oncogene in the prevalent 13q34 region of gain/amplification and suggest that IRS2 over-expression may provide an additional mechanism of PI3 kinase pathway activation in CRC