Spectroscopy and Time Variability of Absorption Lines in the Direction of the Vela Supernova Remnant

We present high resolution (R~75,000), high signal-to-noise (S/N~100) Ca II $\lambda$3933.663 and Na I $\lambda\lambda$5889.951, 5895.924 spectra of 68 stars in the direction of the Vela supernova remnant. The spectra comprise the most complete high resolution, high S/N, optical survey of early type stars in this region of the sky. A subset of the sight lines has been observed at multiple epochs, 1993/1994 and 1996. Of the thirteen stars observed twice, seven have spectra revealing changes in the equivalent width and/or velocity structure of lines, most of which arise from remnant gas. Such time variability has been reported previously for the sight lines towards HD 72089 and HD 72997 by Danks & Sembach (1995) and for HD 72127 by Hobbs et al. (1991). We have confirmed the ongoing time variability of these spectra and present new evidence of variability in the spectra of HD 73658, HD 74455, HD 75309 and HD 75821. We have tabulated Na I and Ca II absorption line information for the sight lines in our sample to serve as a benchmark for further investigations of the dynamics and evolution of the Vela SNR.Comment: 8 pages of text, 4 tables, 16 pages of figures Accepted and to be published in ApJ

Galactic Structure Toward the Carina Tangent

This investigation presents a photometric study of the Galactic structure toward the Carina arm tangent. The field is located between 280 deg and 286 deg galactic longitude and -4 deg to 4 deg galactic latitude. All currently available uvbybeta data is used to obtain homogeneous color excesses and distances for more than 260 stars of spectral types O to G. We present revised distances and average extinction for the open clusters and cluster candidates NGC 3293, NGC 3114, Loden 46 and Loden 112. The cluster candidate Loden 112 appears to be a very compact group at a true distance modulus of 11.06 +\- 0.11 (s.e.) (1629 +84,-80 pc), significantly closer than previous estimates. We found other OB stars at that same distance and, based on their proper motions, suggest a new OB association at coordinates 282 deg < l < 285 deg, -2 deg < b < 2 deg. Utilizing BV photometry and spectral classification of the known O-type stars in the very young open cluster Wd 2 we provide a new distance estimate of 14.13 +\-0.16 (s.e.) (6698 +512,-475 pc), in excellent agreement with recent distance determinations to the giant molecular structures in this direction. We also discuss a possible connection between the HII region RCW 45 and the highly-reddened B+ star CPD -55 3036 and provide a revised distance for the luminous blue variable HR Car.Comment: accepted to PAS

An Analysis of the Shapes of Interstellar Extinction Curves. V. The IR-Through-UV Curve Morphology

We study the IR-through-UV interstellar extinction curves towards 328 Galactic B and late-O stars. We use a new technique which employs stellar atmosphere models in lieu of unreddened "standard" stars. This technique is capable of virtually eliminating spectral mismatch errors in the curves. It also allows a quantitative assessment of the errors and enables a rigorous testing of the significance of relationships between various curve parameters, regardless of whether their uncertainties are correlated. Analysis of the curves gives the following results: (1) In accord with our previous findings, the central position of the 2175 A extinction bump is mildly variable, its width is highly variable, and the two variations are unrelated. (2) Strong correlations are found among some extinction properties within the UV region, and within the IR region. (3) With the exception of a few curves with extreme (i.e., large) values of R(V), the UV and IR portions of Galactic extinction curves are not correlated with each other. (4) The large sightline-to-sightline variation seen in our sample implies that any average Galactic extinction curve will always reflect the biases of its parent sample. (5) The use of an average curve to deredden a spectral energy distribution (SED) will result in significant errors, and a realistic error budget for the dereddened SED must include the observed variance of Galactic curves. While the observed large sightline-to-sightline variations, and the lack of correlation among the various features of the curves, make it difficult to meaningfully characterize average extinction properties, they demonstrate that extinction curves respond sensitively to local conditions. Thus, each curve contains potentially unique information about the grains along its sightline.Comment: To appear in the Astrophysical Journal, Part 1, July 1, 2007. Figures and Tables which will appear only in the electronic version of the Journal can be obtained via anonymous ftp from ftp://ftp.astronomy.villanova.edu . After logging in, change directories to "fitz/FMV_EXTINCTION". A README file describes the various files present in the director

VarGoats project: a dataset of 1159 whole-genome sequences to dissect Capra hircus global diversity

Background: Since their domestication 10,500&nbsp;years ago, goat populations with distinctive genetic backgrounds have adapted to a broad variety of environments and breeding conditions. The VarGoats project is an international 1000-genome resequencing program designed to understand the consequences of domestication and breeding on the genetic diversity of domestic goats and to elucidate how speciation and hybridization have modeled the genomes of a set of species representative of the genus Capra. Findings: A dataset comprising 652 sequenced goats and 507 public goat sequences, including 35 animals representing eight wild species, has been collected worldwide. We identified 74,274,427 single nucleotide polymorphisms (SNPs) and 13,607,850 insertion-deletions (InDels) by aligning these sequences to the latest version of the goat reference genome (ARS1). A Neighbor-joining tree based on Reynolds genetic distances showed that goats from Africa, Asia and Europe tend to group into independent clusters. Because goat breeds from Oceania and Caribbean (Creole) all derive from imported animals, they are distributed along the tree according to their ancestral geographic origin. Conclusions: We report on an unprecedented international effort to characterize the genome-wide diversity of domestic goats. This large range of sequenced individuals represents a unique opportunity to ascertain how the demographic and selection processes associated with post-domestication history have shaped the diversity of this species. Data generated for the project will also be extremely useful to identify deleterious mutations and polymorphisms with causal effects on complex traits, and thus will contribute to new knowledge that could be used in genomic prediction and genome-wide association studies

The p.V37I Exclusive Genotype Of GJB2: A Genetic Risk-Indicator of Postnatal Permanent Childhood Hearing Impairment

Postnatal permanent childhood hearing impairment (PCHI) is frequent (0.25%–0.99%) and difficult to detect in the early stage, which may impede the speech, language and cognitive development of affected children. Genetic tests of common variants associated with postnatal PCHI in newborns may provide an efficient way to identify those at risk. In this study, we detected a strong association of the p.V37I exclusive genotype of GJB2 with postnatal PCHI in Chinese Hans (P = 1.4×10−10; OR 62.92, 95% CI 21.27–186.12). This common genotype in Eastern Asians was present in a substantial percentage (20%) of postnatal PCHI subjects, and its prevalence was significantly increased in normal-hearing newborns who failed at least one newborn hearing screen. Our results indicated that the p.V37I exclusive genotype of GJB2 may cause subclinical hearing impairment at birth and increases risk for postnatal PCHI. Genetic testing of GJB2 in East Asian newborns will facilitate prompt detection and intervention of postnatal PCHI

Zoledronic acid treatment impairs protein geranyl-geranylation for biological effects in prostatic cells

BACKGROUND: Nitrogen-containing bisphosphonates (N-BPs) have been designed to inhibit osteoclast-mediated bone resorption. However, it is now accepted that part of their anti-tumor activities is related to interference with the mevalonate pathway. METHODS: We investigated the effects of zoledronic acid (ZOL), on cell proliferation and protein isoprenylation in two tumoral (LnCAP, PC-3,), and one normal established (PNT1-A) prostatic cell line. To assess if inhibition of geranyl-geranylation by ZOL impairs the biological activity of RhoA GTPase, we studied the LPA-induced formation of stress fibers. The inhibitory effect of ZOL on geranyl geranyl transferase I was checked biochemically. Activity of ZOL on cholesterol biosynthesis was determined by measuring the incorporation of (14)C mevalonate in cholesterol. RESULTS: ZOL induced dose-dependent inhibition of proliferation of all the three cell lines although it appeared more efficient on the untransformed PNT1A. Whatever the cell line, 20 μM ZOL-induced inhibition was reversed by geranyl-geraniol (GGOH) but neither by farnesol nor mevalonate. After 48 hours treatment of cells with 20 μM ZOL, geranyl-geranylation of Rap1A was abolished whereas farnesylation of HDJ-2 was unaffected. Inhibition of Rap1A geranyl-geranylation by ZOL was rescued by GGOH and not by FOH. Indeed, as observed with treatment by a geranyl-geranyl transferase inhibitor, treatment of PNT1-A cells with 20 μM ZOL prevented the LPA-induced formation of stress fibers. We checked that in vitro ZOL did not inhibit geranyl-geranyl-transferase I. ZOL strongly inhibited cholesterol biosynthesis up to 24 hours but at 48 hours 90% of this biosynthesis was rescued. CONCLUSION: Although zoledronic acid is currently the most efficient bisphosphonate in metastatic prostate cancer management, its mechanism of action in prostatic cells remains unclear. We suggest in this work that although in first intention ZOL inhibits FPPsynthase its main biological actitivity is directed against protein Geranylgeranylation

BAAV Mediated GJB2 Gene Transfer Restores Gap Junction Coupling in Cochlear Organotypic Cultures from Deaf Cx26Sox10Cre Mice

The deafness locus DFNB1 contains GJB2, the gene encoding connexin26 and GJB6, encoding connexin30, which appear to be coordinately regulated in the inner ear. In this work, we investigated the expression and function of connexin26 and connexin30 from postnatal day 5 to adult age in double transgenic Cx26Sox10Cre mice, which we obtained by crossing connexin26 floxed mice with a deleter Sox10–Cre line. Cx26Sox10Cre mice presented with complete connexin26 ablation in the epithelial gap junction network of the cochlea, whereas connexin30 expression was developmentally delayed; immunolabeling patterns for both connexins were normal in the cochlear lateral wall. In vivo electrophysiological measurements in Cx26Sox10Cre mice revealed profound hearing loss accompanied by reduction of endocochlear potential, and functional experiments performed in postnatal cochlear organotypic cultures showed impaired gap junction coupling. Transduction of these cultures with a bovine adeno associated virus vector restored connexin26 protein expression and rescued gap junction coupling. These results suggest that restoration of normal connexin levels by gene delivery via recombinant adeno associated virus could be a way to rescue hearing function in DFNB1 mouse models and, in future, lead to the development of therapeutic interventions in humans

Examining the Relationship Between Genetic Counselors’ Attitudes Toward Deaf People and the Genetic Counseling Session

Given the medical and cultural perspectives on deafness it is important to determine if genetic counselors’ attitudes toward deaf people can affect counseling sessions for deafness genes. One hundred fifty-eight genetic counselors recruited through the National Society of Genetic Counselors Listserv completed an online survey assessing attitudes toward deaf people and scenario-specific comfort levels discussing and offering genetic testing for deafness. Respondents with deaf/Deaf friends or who work in prenatal or pediatric settings had more positive attitudes toward deaf people than those without deaf/Deaf friends or those working in ‘other’ settings. More positive attitudes toward deaf people correlated with higher comfort level talking about genetic testing for the two scenarios involving culturally Deaf clients; and correlated with higher comfort level offering genetic testing to culturally Deaf clients wishing to have a deaf child. Attitudes and comfort level were not correlated in the scenarios involving hearing or non-culturally deaf clients. These results suggest that genetic counselors’ attitudes could affect information provision and the decision making process of culturally Deaf clients. Cultural sensitivity workshops in genetic counseling training programs that incorporate personal interactions with culturally Deaf individuals are recommended. Additional suggestions for fostering personal interactions are provided