826 research outputs found

    Physiologically-Regulated Expression Vectors for Gene Therapy

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    Observational effects of magnetism in O stars: surface nitrogen abundances

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    We investigate the surface nitrogen content of the six magnetic O stars known to date as well as of the early B-type star tau Sco. We compare these abundances to predictions of evolutionary models to isolate the effects of magnetic field on the transport of elements in stellar interiors. We conduct a quantitative spectroscopic analysis of the sample stars with state-of-the-art atmosphere models. We rely on high signal-to-noise ratio, high resolution optical spectra obtained with ESPADONS at CFHT and NARVAL at TBL. Atmosphere models and synthetic spectra are computed with the code CMFGEN. Values of N/H together with their uncertainties are determined and compared to predictions of evolutionary models. We find that the magnetic stars can be divided into two groups: one with stars displaying no N enrichment (one object); and one with stars most likely showing extra N enrichment (5 objects). For one star (Theta1 Ori C) no robust conclusion can be drawn due to its young age. The star with no N enrichment is the one with the weakest magnetic field, possibly of dynamo origin. It might be a star having experienced strong magnetic braking under the condition of solid body rotation, but its rotational velocity is still relatively large. The five stars with high N content were probably slow rotators on the zero age main sequence, but they have surface N/H typical of normal O stars, indicating that the presence of a (probably fossil) magnetic field leads to extra enrichment. These stars may have a strong differential rotation inducing shear mixing. Our results should be viewed as a basis on which new theoretical simulations can rely to better understand the effect of magnetism on the evolution of massive stars.Comment: 14 pages, 6 figures. Accepted by A&

    Discovery of the first tau Sco analogues: HD 66665 and HD 63425

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    The B0.2 V magnetic star tau Sco stands out from the larger population of massive OB stars due to its high X-ray activity, peculiar wind diagnostics and highly complex magnetic field. This paper presents the discovery of the first two tau Sco analogues - HD 66665 and HD 63425, identified by the striking similarity of their UV spectra to that of tau Sco. ESPaDOnS spectropolarimetric observations were secured by the Magnetism in Massive Stars CFHT Large Program, in order to characterize the stellar and magnetic properties of these stars. CMFGEN modelling of optical ESPaDOnS spectra and archived IUE UV spectra showed that these stars have stellar parameters similar to those of tau Sco. A magnetic field of similar surface strength is found on both stars, reinforcing the connection between the presence of a magnetic field and wind peculiarities. However, additional phase-resolved observations will be required in order to assess the potential complexity of the magnetic fields, and verify if the wind anomalies are linked to this property.Comment: 6 pages, 2 tables, 3 figures. Accepted for publication in MNRAS. The definitive version will be available at www.blackwel-synergy.co

    Of?p stars: a class of slowly rotating magnetic massive stars

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    Only 5 Of?p stars have been identified in the Galaxy. Of these, 3 have been studied in detail, and within the past 5 years magnetic fields have been detected in each of them. The observed magnetic and spectral characteristics are indicative of organised magnetic fields, likely of fossil origin, confining their supersonic stellar winds into dense, structured magnetospheres. The systematic detection of magnetic fields in these stars strongly suggests that the Of?p stars represent a general class of magnetic O-type stars.Comment: Proceedings of IAUS 272: Active OB star

    The spectral variability and magnetic field characteristics of the Of?p star HD 148937

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    We report magnetic and spectroscopic observations and modeling of the Of?p star HD 148937 within the context of the MiMeS LP at the CFHT. Thirty-two high signal-to-noise ratio circularly polarised (Stokes V) spectra and 13 unpolarised (Stokes I) spectra of HD 148937 were acquired in 2009 and 2010. A definite detection of a Stokes V Zeeman signature is obtained in the grand mean of all observations (in both LSD mean profiles and individual spectral lines). The longitudinal magnetic field inferred from the Stokes V LSD profiles is consistently negative, in contrast to the essentially zero field strength measured from the diagnostic null profiles. A period search of equivalent width measurements confirms the previously-reported 7.03 d variability period. The variation of equivalent widths is not strictly periodic: we present evidence for evolution of the amount or distribution of circumstellar plasma. Interpreting the 7.03 d period as the stellar rotational period within the context of the ORM, we have phased the equivalent widths and longitudinal field measurements. The longitudinal field measurements show a weak sinusoidal variation of constant sign, with extrema out of phase with the H{\alpha} variation by about 0.25 cycles. The inferred magnetic configuration confirms the suggestion of Naz\'e et al (2010), who proposed that the weaker variability of HD 148937 as compared to other members of this class is a consequence of the stellar geometry. Based on the derived magnetic properties and published wind characteristics, we find a wind magnetic confinement parameter \eta\ast \simeq 20 and rotation parameter W = 0.12, supporting a picture in which the Halpha emission and other line variability have their origin in an oblique, rigidly rotating magnetospheric structure resulting from a magnetically channeled wind. (Abridged.)Comment: 13 pages, MNRAS. Version 2, small change to Fig. 1

    NGC 1624-2: A slowly rotating, X-ray luminous Of?cp star with an extraordinarily strong magnetic field

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    This paper presents a first observational investigation of the faint Of?cp star NGC 1624-2, yielding important new constraints on its spectral and physical characteristics, rotation, magnetic field strength, X-ray emission and magnetospheric properties. Modeling the spectrum and spectral energy distribution, we conclude that NGC 1624-2 is a main sequence star of mass M {\simeq} 30 M{\odot}, and infer an effective temperature of 35 {\pm} 2 kK and log g = 4.0 {\pm} 0.2. Based on an extensive time series of optical spectral observations we report significant variability of a large number of spectral lines, and infer a unique period of 157.99 {\pm} 0.94 d which we interpret as the rotational period of the star. We report the detection of a very strong - 5.35 {\pm} 0.5 kG - longitudinal magnetic field , coupled with probable Zeeman splitting of Stokes I profiles of metal lines confirming a surface field modulus of 14 {\pm} 1 kG, consistent with a surface dipole of polar strength >~ 20 kG. This is the largest magnetic field ever detected in an O-type star, and the first report of Zeeman splitting of Stokes I profiles in such an object. We also report the detection of reversed Stokes V profiles associated with weak, high-excitation emission lines of O iii, which we propose may form in the close magnetosphere of the star. We analyze archival Chandra ACIS-I X-ray data, inferring a very hard spectrum with an X-ray efficiency log Lx/Lbol = -6.4, a factor of 4 larger than the canonical value for O-type stars and comparable to that of the young magnetic O-type star {\theta}1 Ori C and other Of?p stars. Finally, we examine the probable magnetospheric properties of the star, reporting in particular very strong magnetic confinement of the stellar wind, with {\eta}* {\simeq} 1.5 {\times} 10^4, and a very large Alfven radius, RAlf = 11.4 R*.Comment: 17 pages, MNRAS accepted and in pres

    A common variant associated with dyslexia reduces expression of the KIAA0319 gene

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    This work was supported by the Wellcome Trust (MYD, SP, TSS, JCK, RWM, PC, SB, and APM), the Intramural Research Programs of the National Human Genome Research Institute (MYD and EDG) and National Cancer Institute (MPO), and the NIH/Ox-Cam Graduate Partnership Program (MYD).Numerous genetic association studies have implicated the KIAA0319 gene on human chromosome 6p22 in dyslexia susceptibility. The causative variant(s) remains unknown but may modulate gene expression, given that (1) a dyslexia-associated haplotype has been implicated in the reduced expression of KIAA0319, and (2) the strongest association has been found for the region spanning exon 1 of KIAA0319. Here, we test the hypothesis that variant(s) responsible for reduced KIAA0319 expression resides on the risk haplotype close to the gene's transcription start site. We identified seven single-nucleotide polymorphisms on the risk haplotype immediately upstream of KIAA0319 and determined that three of these are strongly associated with multiple reading-related traits. Using luciferase-expressing constructs containing the KIAA0319 upstream region, we characterized the minimal promoter and additional putative transcriptional regulator regions. This revealed that the minor allele of rs9461045, which shows the strongest association with dyslexia in our sample (max p-value = 0.0001), confers reduced luciferase expression in both neuronal and non-neuronal cell lines. Additionally, we found that the presence of this rs9461045 dyslexia-associated allele creates a nuclear protein-binding site, likely for the transcriptional silencer OCT-1. Knocking down OCT-1 expression in the neuronal cell line SHSY5Y using an siRNA restores KIAA0319 expression from the risk haplotype to nearly that seen from the non-risk haplotype. Our study thus pinpoints a common variant as altering the function of a dyslexia candidate gene and provides an illustrative example of the strategic approach needed to dissect the molecular basis of complex genetic traits.PostprintPeer reviewe

    Combining M-FISH and Quantum Dot technology for fast chromosomal assignment of transgenic insertions

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    <p>Abstract</p> <p>Background</p> <p>Physical mapping of transgenic insertions by Fluorescence in situ Hybridization (FISH) is a reliable and cost-effective technique. Chromosomal assignment is commonly achieved either by concurrent G-banding or by a multi-color FISH approach consisting of iteratively co-hybridizing the transgenic sequence of interest with one or more chromosome-specific probes at a time, until the location of the transgenic insertion is identified.</p> <p>Results</p> <p>Here we report a technical development for fast chromosomal assignment of transgenic insertions at the single cell level in mouse and rat models. This comprises a simplified 'single denaturation mixed hybridization' procedure that combines multi-color karyotyping by Multiplex FISH (M-FISH), for simultaneous and unambiguous identification of all chromosomes at once, and the use of a Quantum Dot (QD) conjugate for the transgene detection.</p> <p>Conclusions</p> <p>Although the exploitation of the unique optical properties of QD nanocrystals, such as photo-stability and brightness, to improve FISH performance generally has been previously investigated, to our knowledge this is the first report of a purpose-designed molecular cytogenetic protocol in which the combined use of QDs and standard organic fluorophores is specifically tailored to assist gene transfer technology.</p

    Human‐specific transcriptome of ventral and dorsal midbrain dopamine neurons

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    Objective Neuronal loss in the substantia nigra pars compacta (SNpc) in Parkinson's disease (PD) is not uniform as dopamine neurons from the ventral tier are lost more rapidly than those of the dorsal tier. Identifying the intrinsic differences that account for this differential vulnerability may provide a key for developing new treatments for PD. Method Here we compared the RNA‐sequenced transcriptomes of ~100 laser captured micro‐dissected SNpc neurons from each tier from seven healthy controls. Results Expression levels of dopaminergic markers were similar across the tiers while markers specific to the neighbouring ventral tegmental area were virtually undetected. After accounting for unwanted sources of variation, we identified one hundred and six differentially expressed genes (DEGs) between the SNpc tiers. The genes higher in the dorsal/resistant SNpc tier neurons displayed coordinated patterns of expression across the human brain, their protein products had more interactions than expected by chance and they demonstrated evidence of functional convergence. No significant shared functionality was found for genes higher in the ventral/vulnerable SNpc tier. Surprisingly but importantly, none of the identified DEGs were among the familial PD genes or genome‐wide associated loci. Finally, we found some DEGs in opposite tier orientation between human and analogous mouse populations. Interpretation Our results highlight functional enrichments of vesicular trafficking, ion transport/homeostasis and oxidative stress genes showing higher expression in the resistant neurons of the SNpc dorsal tier. Furthermore, the comparison of gene expression variation in human and mouse SNpc populations strongly argues for the need of human‐focused Omics studies
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