Analysis of talpid3 and wild-type chicken embryos reveals roles for Hedgehog signalling in development of the limb bud vasculature

Chicken talpid mutant embryos have a wide range of Hedgehog-signalling related defects and it is now known that the talpid gene product encodes a novel protein essential for Hedgehog signalling which is required for both activator and repressor functions of Gli transcription factors (Davey, M.G., Paton, I.R., Yin, Y., Schmidt, M., Bangs, F.K., Morrice, D.R., Gordon-Smith, T., Buxton, P., Stamataki, D., Tanaka, M., Münsterberg, A.E., Briscoe, J., Tickle, C., Burt, D.W. (2006). The chicken talpid gene encodes a novel protein essential for Hedgehog signalling. Genes Dev 20 1365-77). Haemorrhaging, oedema and other severe vascular defects are a central aspect of the talpid phenotype (Ede, D.A. and Kelly, W.A (1964a). Developmental abnormalities in the head region of the talpid mutant fowl. J. Embryol. exp. Morp. 12:161-182) and, as Hedgehog (Hh) signalling has been implicated in every stage of development of the vascular system, the vascular defects seen in talpid are also likely to be attributable to abnormal Hedgehog signalling. Gene expression of members of the VEGF and Angiopoietin families of angiogenic growth factors has been linked to haemorrhaging and oedema and we find widespread expression of VEGF-D, rigf and Ang2a in the talpid limb. Furthermore, ectopic expression of these genes in talpid limbs points to regulation via Gli repression rather than activation. We monitored specification of vessel identity in talpid limb vasculature by examining expression of artery-specific genes, Np1 and EphrinB2, and the vein-specific genes, Np2a and Tie2. We show that there are supernumerary subclavian arteries in talpid limb buds and abnormal expression of an artery-specific gene in the venous submarginal sinus, despite the direction of blood flow being normal. Furthermore, we show that Shh can induce Np1 expression but has no effect on Np2a. Finally, we demonstrate that induction of VEGF and Ang2a expression by Shh in normal limb buds is accompanied by vascular remodelling. Thus Hedgehog signalling has a pivotal role in the cascade of angiogenic events in a growing embryonic organ which is similar to that proposed in tumours

Comparative mapping of human Chromosome 19 with the chicken show conserved synteny and vies an insight into chromosomal evolution

Human Chromosome 19 (HSA19) is virtually completely sequenced. A complete physical contig map made up of BACs and cosmids is also available for this chromosome. It is, therefore, a rich source of information that we have used as the basis for a comparative mapping study with the chicken. Various orthologs of genes known to map to HSA19 have been mapped in the chicken. Five chicken microchromosomes (two of which were previously undefined) are seen to show conserved synteny with this chromosome, along with individual gene homologs on Chr 1 and another tiny microchromosome. Compared with the mouse, which has 12 chromosomal regions homologous to HSA19, the chicken genotype displays fewer evolutionary rearrangements. The ancestral nature of the chicken karyotype is demonstrated and may prove to be an excellent tool for studying genome evolutio

Ion cyclotron resonance heating for tungsten control in various JET H-mode scenarios

Ion cyclotron resonance heating (ICRH) in the hydrogen minority scheme provides central ion heating and acts favorably on the core tungsten transport. Full wave modeling shows that, at medium power level (4 MW), after collisional redistribution, the ratio of power transferred to the ions and the electrons vary little with the minority (hydrogen) concentration n H/n e but the high-Z impurity screening provided by the fast ions temperature increases with the concentration. The power radiated by tungsten in the core of the JET discharges has been analyzed on a large database covering the 2013-2014 campaign. In the baseline scenario with moderate plasma current (I p = 2.5 MA) ICRH modifies efficiently tungsten transport to avoid its accumulation in the plasma centre and, when the ICRH power is increased, the tungsten radiation peaking evolves as predicted by the neo-classical theory. At higher current (3-4 MA), tungsten accumulation can be only avoided with 5 MW of ICRH power with high gas injection rate. For discharges in the hybrid scenario, the strong initial peaking of the density leads to strong tungsten accumulation. When this initial density peaking is slightly reduced, with an ICRH power in excess of 4 MW,very low tungsten concentration in the core (∼10-5) is maintained for 3 s. MHD activity plays a key role in tungsten transport and modulation of the tungsten radiation during a sawtooth cycle is correlated to the fishbone activity triggered by the fast ion pressure gradient

Calculations to support JET neutron yield calibration: Modelling of neutron emission from a compact DT neutron generator

At the Joint European Torus (JET) the ex-vessel fission chambers and in-vessel activation detectors are used as the neutron production rate and neutron yield monitors respectively. In order to ensure that these detectors produce accurate measurements they need to be experimentally calibrated. A new calibration of neutron detectors to 14 MeV neutrons, resulting from deuterium–tritium (DT) plasmas, is planned at JET using a compact accelerator based neutron generator (NG) in which a D/T beam impinges on a solid target containing T/D, producing neutrons by DT fusion reactions. This paper presents the analysis that was performed to model the neutron source characteristics in terms of energy spectrum, angle–energy distribution and the effect of the neutron generator geometry. Different codes capable of simulating the accelerator based DT neutron sources are compared and sensitivities to uncertainties in the generator's internal structure analysed. The analysis was performed to support preparation to the experimental measurements performed to characterize the NG as a calibration source. Further extensive neutronics analyses, performed with this model of the NG, will be needed to support the neutron calibration experiments and take into account various differences between the calibration experiment and experiments using the plasma as a source of neutrons

3D simulations of gas puff effects on edge plasma and ICRF coupling in JET

Recent JET (ITER-Like Wall) experiments have shown that the fueling gas puffed from different locations of the vessel can result in different scrape-off layer (SOL) density profiles and therefore different radio frequency (RF) coupling. To reproduce the experimental observations, to understand the associated physics and to optimize the gas puff methods, we have carried out three-dimensional (3D) simulations with the EMC3-EIRENE code in JET-ILW including a realistic description of the vessel geometry and the gas injection modules (GIMs) configuration. Various gas puffing methods have been investigated, in which the location of gas fueling is the only variable parameter. The simulation results are in quantitative agreement with the experimental measurements. They confirm that compared to divertor gas fueling, mid-plane gas puffing increases the SOL density most significantly but locally, while top gas puffing increases it uniformly in toroidal direction but to a lower degree. Moreover, the present analysis corroborates the experimental findings that combined gas puff scenarios - based on distributed main chamber gas puffing - can be effective in increasing the RF coupling for multiple antennas simultaneously. The results indicate that the spreading of the gas, the local ionization and the transport of the ionized gas along the magnetic field lines connecting the local gas cloud in front of the GIMs to the antennas are responsible for the enhanced SOL density and thus the larger RF coupling

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

10.1371/journal.pone.0139981PLoS ONE1010e013998