Regulation of sonic hedgehog-GLI1 downstream target genes PTCH1, Cyclin D2, Plakoglobin, PAX6 and NKX2.2 and their epigenetic status in medulloblastoma and astrocytoma

Abstract Background The Sonic hedgehog (Shh) signaling pathway is critical for cell growth and differentiation. Impairment of this pathway can result in both birth defects and cancer. Despite its importance in cancer development, the Shh pathway has not been thoroughly investigated in tumorigenesis of brain tumors. In this study, we sought to understand the regulatory roles of GLI1, the immediate downstream activator of the Shh signaling pathway on its downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6 in medulloblastoma and astrocytic tumors. Methods We silenced GLI1 expression in medulloblastoma and astrocytic cell lines by transfection of siRNA against GLI1. Subsequently, we performed RT-PCR and quantitative real time RT-PCR (qRT-PCR) to assay the expression of downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6. We also attempted to correlate the pattern of expression of GLI1 and its regulated genes in 14 cell lines and 41 primary medulloblastoma and astrocytoma tumor samples. We also assessed the methylation status of the Cyclin D2 and PTCH1 promoters in these 14 cell lines and 58 primary tumor samples. Results Silencing expression of GLI1 resulted up-regulation of all target genes in the medulloblastoma cell line, while only PTCH1 was up-regulated in astrocytoma. We also observed methylation of the cyclin D2 promoter in a significant number of astrocytoma cell lines (63%) and primary astrocytoma tumor samples (32%), but not at all in any medulloblastoma samples. PTCH1 promoter methylation was less frequently observed than Cyclin D2 promoter methylation in astrocytomas, and not at all in medulloblastomas. Conclusions Our results demonstrate different regulatory mechanisms of Shh-GLI1 signaling. These differences vary according to the downstream target gene affected, the origin of the tissue, as well as epigenetic regulation of some of these genes.http://deepblue.lib.umich.edu/bitstream/2027.42/78313/1/1471-2407-10-614.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78313/2/1471-2407-10-614.pdfPeer Reviewe

Topology of the Spin-polarized Charge Density in bcc and fcc Iron

We investigate the topology of the spin-polarized charge density in bcc and fcc iron. While the total spin-density is found to possess the topology of the non-magnetic prototypical structures, in some cases the spin-polarized densities are characterized by unique topologies; for example, the spin-polarized charge densities of bcc and high-spin fcc iron are atypical of any known for non-magnetic materials. In these cases, the two spin-densities are correlated: the spin-minority electrons have directional bond paths with deep minima in the minority density, while the spin-majority electrons fill these holes, reducing bond directionality. The presence of two distinct spin topologies suggests that a well-known magnetic phase transition in iron can be fruitfully reexamined in light of these topological changes. We show that the two phase changes seen in fcc iron (paramagnetic to low-spin and low-spin to high-spin) are different. The former follows the Landau symmetry-breaking paradigm and proceeds without a topological transformation, while the latter also involves a topological catastrophe.Comment: 5 pages, 3 figures. Phys. Rev. Lett. (in press

Revealing common artifacts due to ferromagnetic inclusions in highly-oriented pyrolytic graphite

We report on an extensive investigation to figure out the origin of room-temperature ferromagnetism that is commonly observed by SQUID magnetometry in highly-oriented pyrolytic graphite (HOPG). Electron backscattering and X-ray microanalysis revealed the presence of micron-size magnetic clusters (predominantly Fe) that are rare and would be difficult to detect without careful search in a scanning electron microscope in the backscattering mode. The clusters pin to crystal boundaries and their quantities match the amplitude of typical ferromagnetic signals. No ferromagnetic response is detected in samples where we could not find such magnetic inclusions. Our experiments show that the frequently reported ferromagnetism in pristine HOPG is most likely to originate from contamination with Fe-rich inclusions introduced presumably during crystal growth.Comment: 8 pages, 7 figure

Elucidating the crystal-chemistry of Jbel Rhassoul stevensite (Morocco) by advanced analytical techniques

The composition of Rhassoul clay is controversial regarding the nature of the puremineral clay fraction which is claimed to be stevensite rather than saponite. In this study, the raw and mineral fractions were characterized using various techniques including Fourier transform infrared spectroscopy and magic angle spinning nuclear magnetic resonance (MAS NMR). The isolated fine clay mineral fraction contained a larger amount of Al (>1 wt.%) than that reported for other stevensite occurrences. The 27Al MAS NMR technique confirmed that the mineral is stevensite in which the Al is equally split between the tetrahedral and octahedral coordination sites. The 29Si NMR spectrum showed a single unresolved resonance indicating little or no short-range ordering of silicon. The chemical composition of the stevensite from Jbel Rhassoul was determined to be ((Na0.25K0.20 (Mg5.04Al0.37Fe0.20&0.21)5.61(Si7.76Al0.24)8O20(OH)4). This formula differs from previous compositions described from this locality and shows it to be an Al-bearing lacustrine clay mineral

Resolution of the stochastic strategy spatial prisoner's dilemma by means of particle swarm optimization

We study the evolution of cooperation among selfish individuals in the stochastic strategy spatial prisoner's dilemma game. We equip players with the particle swarm optimization technique, and find that it may lead to highly cooperative states even if the temptations to defect are strong. The concept of particle swarm optimization was originally introduced within a simple model of social dynamics that can describe the formation of a swarm, i.e., analogous to a swarm of bees searching for a food source. Essentially, particle swarm optimization foresees changes in the velocity profile of each player, such that the best locations are targeted and eventually occupied. In our case, each player keeps track of the highest payoff attained within a local topological neighborhood and its individual highest payoff. Thus, players make use of their own memory that keeps score of the most profitable strategy in previous actions, as well as use of the knowledge gained by the swarm as a whole, to find the best available strategy for themselves and the society. Following extensive simulations of this setup, we find a significant increase in the level of cooperation for a wide range of parameters, and also a full resolution of the prisoner's dilemma. We also demonstrate extreme efficiency of the optimization algorithm when dealing with environments that strongly favor the proliferation of defection, which in turn suggests that swarming could be an important phenomenon by means of which cooperation can be sustained even under highly unfavorable conditions. We thus present an alternative way of understanding the evolution of cooperative behavior and its ubiquitous presence in nature, and we hope that this study will be inspirational for future efforts aimed in this direction.Comment: 12 pages, 4 figures; accepted for publication in PLoS ON

State Transition Algorithm

In terms of the concepts of state and state transition, a new heuristic random search algorithm named state transition algorithm is proposed. For continuous function optimization problems, four special transformation operators called rotation, translation, expansion and axesion are designed. Adjusting measures of the transformations are mainly studied to keep the balance of exploration and exploitation. Convergence analysis is also discussed about the algorithm based on random search theory. In the meanwhile, to strengthen the search ability in high dimensional space, communication strategy is introduced into the basic algorithm and intermittent exchange is presented to prevent premature convergence. Finally, experiments are carried out for the algorithms. With 10 common benchmark unconstrained continuous functions used to test the performance, the results show that state transition algorithms are promising algorithms due to their good global search capability and convergence property when compared with some popular algorithms.Comment: 18 pages, 28 figure

High fidelity: extra-pair fertilisations in eight Charadrius plover species are not associated with parental relatedness or social mating system

Extra-pair paternity is a common reproductive strategy in many bird species. However, it remains unclear why extra-pair paternity occurs and why it varies among species and populations. Plovers (Charadrius spp.) exhibit considerable variation in reproductive behaviour and ecology, making them excellent models to investigate the evolution of social and genetic mating systems. We investigated inter- and intra-specific patterns of extra-pair parentage and evaluated three major hypotheses explaining extra-pair paternity using a comparative approach based on the microsatellite genotypes of 2049 individuals from 510 plover families sampled from twelve populations that constituted eight species. Extra-pair paternity rates were very low (0 to 4.1% of chicks per population). No evidence was found in support of the sexual conflict or genetic compatibility hypotheses, and there was no seasonal pattern of extra-pair paternity (EPP). The low prevalence of EPP is consistent with a number of alternative hypotheses, including the parental investment hypothesis, which suggests that high contribution to care by males restricts female plovers from engaging in extra-pair copulations. Further studies are needed to critically test the importance of this hypothesis for mate choice in plovers

A three-dimensional crustal seismic velocity model for southern California from a composite event method

We present a new crustal seismic velocity model for southern California derived from P and S arrival times from local earthquakes and explosions. To reduce the volume of data and ensure a more uniform source distribution, we compute "composite event" picks for 2597 distributed master events that include pick information for other events within spheres of 2 km radius. The approach reduces random picking error and maximizes the number of S wave picks. To constrain absolute event locations and shallow velocity structure, we also use times from controlled sources, including both refraction shots and quarries. We implement the SIMULPS tomography algorithm to obtain three-dimensional (3-D) V_p and V_p/V_s structure and hypocenter locations of the composite events. Our new velocity model in general agrees with previous studies, resolving low-velocity features at shallow depths in the basins and some high-velocity features in the midcrust. Using our velocity model and 3-D ray tracing, we relocate about 450,000 earthquakes from 1981 to 2005. We observe a weak correlation between seismic velocities and earthquake occurrence, with shallow earthquakes mostly occurring in high P velocity regions and midcrustal earthquakes occurring in low P velocity regions. In addition, most seismicity occurs in regions with relatively low V_p/V_s ratios, although aftershock sequences following large earthquakes are often an exception to this pattern