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

Symmetric invariants and cohomology of groups

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46235/1/208_2005_Article_BF01446902.pd

X-Ray and Radio Observations of Bright GeV Sources

We present X-ray and radio studies of sources which are brightabove 1 GeV (F_{>1GeV} > 4e-8 ph/cm^2/s. Only 11 out of ~30 of these gamma-ray sources have been identified with lower energy counterparts: 5 blazars and 6 pulsars. Three of these pulsars are surrounded by radio pulsar wind nebulae (PWN), two of which are also seen as bright, extended X-ray synchrotron nebulae. The ASCA X-ray telescope has observed 28 of the bright GeV sources, revealing an excess of F_{2-10keV} > 10e-12 ergs/cm^2/s sources within the {\it EGRET} error contours of the unidentified sources. Although several supernova remnants are positionally coincident with these sources, we find no X-ray evidence of high energy particle production in SNR shell shocks consistent with the GeV positions. We also present initial results from follow on radio imaging studies of several fields containing unidentified sources. We have discovered new X-ray/radio nebulae in three of these fields which are strong candidates for PWN. These sources, along with a similar nebula in CTA 1 and the PWN around PSR B1853+01 in W44, are all positionally coincident with variable EGRET sources. This suggests a class of variable gamma-ray sources associated with synchrotron emitting regions powered by the winds of young pulsars.Comment: 18 pages, 26 figures, To appear in the proceedings of the workshop: "The Nature of the Unidentified Galactic Gamma-Ray Sources" held at INAOE, Mexico, October 2000, (A.Carraminana, O. Reiner and D. Thompson,

Case-based learning: Predictive features in indexing

Interest in psychological experimentation from the Artificial Intelligence community often takes the form of rigorous post-hoc evaluation of completed computer models. Through an example of our own collaborative research, we advocate a different view of how psychology and AI may be mutually relevant, and propose an integrated approach to the study of learning in humans and machines. We begin with the problem of learning appropriate indices for storing and retrieving information from memory. From a planning task perspective, the most useful indices may be those that predict potential problems and access relevant plans in memory, improving the planner's ability to predict and avoid planning failures. This “predictive features” hypothesis is then supported as a psychological claim, with results showing that such features offer an advantage in terms of the selectivity of reminding because they more distinctively characterize planning situations where differing plans are appropriate.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46928/1/10994_2004_Article_BF00993173.pd

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Helium burning and neutron sources in the stars

Helium burning represents an important stage of stellar evolution as it contributes to the synthesis of key elements such as carbon, through the triple-alfa process, and oxygen, through the 12C(alfa, gamma)16O reaction. It is the ratio of carbon to oxygen at the end of the helium burning stage that governs the following phases of stellar evolution leading to different scenarios depending on the initial stellar mass. In addition, helium burning in Asymptotic Giant Branch stars, provides the two main sources of neutrons, namely the 13C(alfa, n)16O and the 22Ne(alfa, n)25Mg, for the synthesis of about half of all elements heavier than iron through the s-process. Given the importance of these reactions, much experimental work has been devoted to the study of their reaction rates over the last few decades. However, large uncertainties still remain at the energies of astrophysical interest which greatly limit the accuracy of stellar models predictions. Here, we review the current status on the latest experimental efforts and show how measurements of these important reaction cross sections can be significantly improved at next-generation deep underground laboratories