Identification of the gene encoding Brain Cell Membrane Protein 1 (BCMP1), a putative four-transmembrane protein distantly related to the Peripheral Myelin Protein 22 / Epithelial Membrane Proteins and the Claudins

BACKGROUND: A partial cDNA clone from dog thyroid presenting a very significant similarity with an uncharacterized mouse EST sequence was isolated fortuitously. We report here the identification of the complete mRNA and of the gene, the product of which was termed "brain cell membrane protein 1" (BCMP1). RESULTS: The 4 kb-long mRNA sequence exhibited an open-reading frame of only 543 b followed by a 3.2 kb-long 3' untranslated region containing several AUUUA instability motifs. Analysis of the encoded protein sequence identified the presence of four putative transmembrane domains. Similarity searches in protein domain databases identified partial sequence conservations with peripheral myelin protein 22 (PMP22)/ epithelial membrane proteins (EMPs) and Claudins, defining the encoded protein as representative of the existence of a novel subclass in this protein family. Northern-blot analysis of the expression of the corresponding mRNA in adult dog tissues revealed the presence of a huge amount of the 4 kb transcript in the brain. An EGFP-BCMP1 fusion protein expressed in transfected COS-7 cells exhibited a membranous localization as expected. The sequences encoding BCMP1 were assigned to chromosome X in dog, man and rat using radiation hybrid panels and were partly localized in the currently available human genome sequence. CONCLUSIONS: We have identified the existence in several mammalian species of a gene encoding a putative four-transmembrane protein, BCMP1, wich defines a novel subclass in this family of proteins. In dog at least, the corresponding mRNA is highly present in brain cells. The chromosomal localization of the gene in man makes of it a likely candidate gene for X-linked mental retardation

Millisecond Exoplanet Imaging, I: Method and Simulation Results

One of the top remaining science challenges in astronomical optics is the direct imaging and characterization of extrasolar planets and planetary systems. Directly imaging exoplanets from ground-based observatories requires combining high-order adaptive optics with a stellar coronagraph observing at wavelengths ranging from the visible to the mid-IR. A limiting factor in achieving the required contrast (planet-to-star intensity ratio) is quasi-static speckles, caused largely by non-common path aberrations (NCPA) in the coronagraph. Starting with a realistic simulator of a telescope with an AO system and a coronagraph, this article provides simulations of several closely related millisecond regression models requiring inputs of the measured wavefronts and science camera images. The simplest regression model, called the naive estimator, does not treat the noise and other sources of information loss in the WFS. The naive estimator provided a useful estimate of the NCPA of $\sim$ 0.5 radian RMS, with an accuracy of $\sim$ 0.06 radian RMS in one minute of simulated sky time on a magnitude 8 star. The bias-corrected estimator generalizes the regression model to account for the noise and information loss in the WFS. A simulation of the bias-corrected estimator with four minutes of sky time included an NCPA of $\sim 0.05 \,$ radian RMS and an extended exoplanet scene. The joint regression of the bias-corrected estimator simultaneously achieved an NCPA estimate with an accuracy of $\sim 5\times10^{-3} \,$radian and contrast of $\sim 10^{-5}$ on the exoplanet scene. In addition, the estimate of the exoplanet image was completely free of the subtraction artifacts that always plague differential imaging. The estimate of the exoplanet image obtained by the joint regression was nearly identical to the image obtained by subtraction of a perfectly known point-spread function.Comment: 16 pages, 18 Figures, 4 Tables, submitted to JOSA

Analysis of six candidate genes as potential modifiers of disease expression in canine XLPRA1, a model for human X-linked retinitis pigmentosa 3

Purpose: Canine X-linked progressive retinal atrophy (XLPRA) is caused by mutations in RPGR exon ORF15, which is also a mutation hotspot in human X-linked retinitis pigmentosa 3 (RP3). The XLPRA1 form of disease has shown extensive phenotypic variability in a colony of dogs that all inherited the same mutant X-chromosome. This variability in onset and severity makes XLPRA1 a valuable model to use to identify genes influencing photoreceptors degeneration in dog and to elucidate molecular mechanisms underlying RP in its human homolog. In this study, RPGRIP1, RANBP2, NPM1, PDE6D, NPHP5, and ABCA4 genes were selected on the basis of interaction with RPGR or RPGRIP1 or their implication in related retinal diseases, and were investigated as candidate genetic modifiers of XLPRA1. Methods: A pedigree derived from an affected male dog outcrossed to unrelated normal mix bred or purebred females was used. Morphologic examination revealed phenotypic variability in the affected dogs characterized as mild, moderate, or severe. Single nucleotide polymorphisms (SNPs) and indel-containing markers spanning the entire genes were designed, based on the canine sequence and the Broad Institute SNP library, and genotyped on the pedigree. For each candidate gene, haplotypes were identified and their frequencies in severely and moderately affected dogs were compared to detect a putative correlation between a gene-specific haplotype(s), and severity level of the disease. Primers were derived from expressed sequence tags (ESTs) and predicted transcripts to assess the relative retinal expression of the six genes of interest in normal and affected retinas of different ages. Results: Four to seven haplotypes per gene were identified. None of the haplotypes of RPGRIP1, NPM1, PDE6D, NPHP5, RANBP2, and ABCA4 were found to co-segregate with the moderate or severe phenotype. No significant difference in the retinal expression levels of the candidate genes was observed between normal and affected dogs. Conclusions: The haplotype distribution of RPGRIP1, NPM1, PDE6D, NPHP5, RANBP2, and ABCA4 suggests these genes are not modifiers of the disease phenotype observed in the XLPRA1 pedigree. The RPGRORF15 stop mutation does not affect the retinal expression of these genes at the mRNA level in the pre-degenerate stage of disease, but no conclusions can be made at this time about changes that may occur at the protein level

EXCEDE Technology Development III: First Vacuum Tests

This paper is the third in the series on the technology development for the EXCEDE (EXoplanetary Circumstellar Environments and Disk Explorer) mission concept, which in 2011 was selected by NASA's Explorer program for technology development (Category III). EXCEDE is a 0.7m space telescope concept designed to achieve raw contrasts of 1e6 at an inner working angle of 1.2 l/D and 1e7 at 2 l/D and beyond. This will allow it to directly detect and spatially resolve low surface brightness circumstellar debris disks as well as image giant planets as close as in the habitable zones of their host stars. In addition to doing fundamental science on debris disks, EXCEDE will also serve as a technological and scientific precursor for any future exo-Earth imaging mission. EXCEDE uses a Starlight Suppression System (SSS) based on the PIAA coronagraph, enabling aggressive performance. We report on our continuing progress of developing the SSS for EXCEDE, and in particular (a) the reconfiguration of our system into a more flight-like layout, with an upstream deformable mirror and an inverse PIAA system, as well as a LOWFS, and (b) testing this system in a vacuum chamber, including IWA, contrast, and stability performance. The results achieved so far are 2.9e-7 contrast between 1.2-2.0 l/D and 9.7e-8 contrast between 2.0-6.0 l/D in monochromatic light; as well as 1.4e-6 between 2.0-6.0 l/D in a 10% band, all with a PIAA coronagraph operating at an inner working angle of 1.2 l/D. This constitutes better contrast than EXCEDE requirements (in those regions) in monochromatic light, and progress towards requirements in broadband light. Even though this technology development is primarily targeted towards EXCEDE, it is also germane to any exoplanet direct imaging space-based telescopes because of the many challenges common to different coronagraph architectures and mission requirements.Comment: 12 pages, 12 figures, to be published in proceedings of SPIE Astronomical Telescopes + Instrumentation (2014

The Robo-AO-2 facility for rapid visible/near-infrared AO imaging and the demonstration of hybrid techniques

We are building a next-generation laser adaptive optics system, Robo-AO-2, for the UH 2.2-m telescope that will deliver robotic, diffraction-limited observations at visible and near-infrared wavelengths in unprecedented numbers. The superior Maunakea observing site, expanded spectral range and rapid response to high-priority events represent a significant advance over the prototype. Robo-AO-2 will include a new reconfigurable natural guide star sensor for exquisite wavefront correction on bright targets and the demonstration of potentially transformative hybrid AO techniques that promise to extend the faintness limit on current and future exoplanet adaptive optics systems.Comment: 15 page

An integrated 4249 marker FISH/RH map of the canine genome

BACKGROUND: The 156 breeds of dog recognized by the American Kennel Club offer a unique opportunity to map genes important in genetic variation. Each breed features a defining constellation of morphological and behavioral traits, often generated by deliberate crossing of closely related individuals, leading to a high rate of genetic disease in many breeds. Understanding the genetic basis of both phenotypic variation and disease susceptibility in the dog provides new ways in which to dissect the genetics of human health and biology. RESULTS: To facilitate both genetic mapping and cloning efforts, we have constructed an integrated canine genome map that is both dense and accurate. The resulting resource encompasses 4249 markers, and was constructed using the RHDF5000-2 whole genome radiation hybrid panel. The radiation hybrid (RH) map features a density of one marker every 900 Kb and contains 1760 bacterial artificial chromosome clones (BACs) localized to 1423 unique positions, 851 of which have also been mapped by fluorescence in situ hybridization (FISH). The two data sets show excellent concordance. Excluding the Y chromosome, the map features an RH/FISH mapped BAC every 3.5 Mb and an RH mapped BAC-end, on average, every 2 Mb. For 2233 markers, the orthologous human genes have been established, allowing the identification of 79 conserved segments (CS) between the dog and human genomes, dramatically extending the length of most previously described CS. CONCLUSIONS: These results provide a necessary resource for the canine genome mapping community to undertake positional cloning experiments and provide new insights into the comparative canine-human genome maps

Comparison of the canine and human olfactory receptor gene repertoires

BACKGROUND: Olfactory receptors (ORs), the first dedicated molecules with which odorants physically interact to arouse an olfactory sensation, constitute the largest gene family in vertebrates, including around 900 genes in human and 1,500 in the mouse. Whereas dogs, like many other mammals, have a much keener olfactory potential than humans, only 21 canine OR genes have been described to date. RESULTS: In this study, 817 novel canine OR sequences were identified, and 640 have been characterized. Of the 661 characterized OR sequences, representing half of the canine repertoire, 18% are predicted to be pseudogenes, compared with 63% in human and 20% in mouse. Phylogenetic analysis of 403 canine OR sequences identified 51 families, and radiation-hybrid mapping of 562 showed that they are distributed on 24 dog chromosomes, in 37 distinct regions. Most of these regions constitute clusters of 2 to 124 closely linked genes. The two largest clusters (124 and 109 OR genes) are located on canine chromosomes 18 and 21. They are orthologous to human clusters located on human chromosomes 11q11-q13 and HSA11p15, containing 174 and 115 ORs respectively. CONCLUSIONS: This study shows a strongly conserved genomic distribution of OR genes between dog and human, suggesting that OR genes evolved from a common mammalian ancestral repertoire by successive duplications. In addition, the dog repertoire appears to have expanded relative to that of humans, leading to the emergence of specific canine OR genes

\u3cem\u3eCOL9A2\u3c/em\u3e and \u3cem\u3eCOL9A3\u3c/em\u3e Mutations in Canine Autosomal Recessive Oculoskeletal Dysplasia

Oculoskeletal dysplasia segregates as an autosomal recessive trait in the Labrador retriever and Samoyed canine breeds, in which the causative loci have been termed drd1 and drd2, respectively. Affected dogs exhibit short-limbed dwarfism and severe ocular defects. The disease phenotype resembles human hereditary arthro-ophthalmopathies such as Stickler and Marshall syndromes, although these disorders are usually dominant. Linkage studies mapped drd1 to canine chromosome 24 and drd2 to canine chromosome 15. Positional candidate gene analysis then led to the identification of a 1-base insertional mutation in exon 1 of COL9A3 that cosegregates with drd1 and a 1,267-bp deletion mutation in the 5′ end of COL9A2 that cosegregates with drd2. Both mutations affect the COL3 domain of the respective gene. Northern analysis showed that RNA expression of the respective genes was reduced in affected retinas. These models offer potential for studies such as protein-protein interactions between different members of the collagen gene family, regulation and expression of these genes in retina and cartilage, and even opportunities for gene therapy

DECONbench: a benchmarking platform dedicated to deconvolution methods for tumor heterogeneity quantification

Quantifcation of tumor heterogeneity is essential to better understand cancer progression and to adapt therapeutic treatments to patient specifcities. Bioinformatic tools to assess the diferent cell populations from single-omic datasets as bulk transcriptome or methylome samples have been recently developed, including reference-based and reference-free methods. Improved methods using multi-omic datasets are yet to be developed in the future and the community would need systematic tools to perform a comparative evaluation of these algorithms on controlled data

A Search for H2O Megamasers in High-z Type-2 AGNs

We report a search for H2O megamasers in 274 SDSS type-2 AGNs (0.3 < z < 0.83), half of which can be classified as type-2 QSOs from their [OIII] 5007 luminosity, using the Robert C. Byrd Green Bank Telescope (GBT) and the Effelsberg 100-m radio telescope. Apart from the detection of the extremely luminous water vapor megamaser SDSS J080430.99+360718.1, already reported by Barvainis & Antonucci (2005), we do not find any additional line emission. This high rate of non-detections is compared to the water maser luminosity function created from the 78 water maser galaxies known to date and its extrapolation towards the higher luminosities of "gigamasers" that we would have been able to detect given the sensitivity of our survey. The properties of the known water masers are summarized and discussed with respect to the nature of high-z type-2 AGNs and megamasers in general. In the appendix, we list 173 additional objects (mainly radio galaxies, but also QSOs and galaxies) that were observed with the GBT, the Effelsberg 100-m radio telescope, or Arecibo Observatory without leading to the detection of water maser emission.Comment: 28 pages, 3 figures. Accepted for publication in the Astrophysical Journa