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

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

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

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

Delivery of the 135kb human frataxin genomic DNA locus gives rise to different frataxin isoforms

© 2015 Elsevier Inc. Friedreich's ataxia (FRDA) is the most common form of hereditary ataxia caused by recessive mutations in the FXN gene. Recent results have indicated the presence of different frataxin isoforms due to alternative gene expression mechanisms. Our previous studies demonstrated the advantages of using high-capacity herpes simplex virus type 1 (HSV-1) amplicon vectors containing the entire FXN genomic locus (iBAC-FXN) as a gene-delivery vehicle capable of ensuring physiologically-regulated and long-term persistence. Here we describe how expression from the 135. kb human FXN genomic locus produces the three frataxin isoforms both in cultured neuronal cells and also in vivo. Moreover, we also observed the correct expression of these frataxin isoforms in patient-derived cells after delivery of the iBAC-. FXN. These results lend further support to the potential use of HSV-1 vectors containing entire genomic loci whose expression is mediated by complex transcriptional and posttranscriptional mechanisms for gene therapy applications.Spanish National Research Plan (SAF 2012-38042) and the Autonomous Government of Madrid (S2010/BMD-2331). The Center for Biomedical Research on Rare Diseases (“Centro de Investigación Biomédica en Red sobre Enfermedades Raras”, CIBERER) is an initiative supported by the “Instituto de Salud Carlos III”.Peer Reviewe

Discovery Of A Magnetic Field In The Rapidly Rotating O-Type Secondary Of The Colliding-Wind Binary HD 47129 (Plaskett\u27s Star)

We report the detection of a strong, organized magnetic field in the secondary component of the massive O8III/I+O7.5V/III double-lined spectroscopic binary system HD 47129 (Plaskett\u27s star) in the context of the Magnetism in Massive Stars survey. Eight independent Stokes V observations were acquired using the Echelle SpectroPolarimetric Device for the Observations of Stars (ESPaDOnS) spectropolarimeter at the Canada-France-Hawaii Telescope and the Narval spectropolarimeter at the Telescope Bernard Lyot. Using least-squares deconvolution we obtain definite detections of signal in Stokes V in three observations. No significant signal is detected in the diagnostic null (N) spectra. The Zeeman signatures are broad and track the radial velocity of the secondary component; we therefore conclude that the rapidly rotating secondary component is the magnetized star. Correcting the polarized spectra for the line and continuum of the (sharp-lined) primary, we measured the longitudinal magnetic field from each observation. The longitudinal field of the secondary is variable and exhibits extreme values of -810 +/- 150 and +680 +/- 190 G, implying a minimum surface dipole polar strength of 2850 +/- 500 G. In contrast, we derive an upper limit (3 sigma) to the primary\u27s surface magnetic field of 230 G. The combination of a strong magnetic field and rapid rotation leads us to conclude that the secondary hosts a centrifugal magnetosphere fed through a magnetically confined wind. We revisit the properties of the optical line profiles and X-ray emission - previously interpreted as a consequence of colliding stellar winds - in this context. We conclude that HD 47129 represents a heretofore unique stellar system - a close, massive binary with a rapidly rotating, magnetized component - that will be a rich target for further study

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

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

The writing on the wall: the concealed communities of the East Yorkshire horselads

This paper examines the graffiti found within late nineteenth and early-twentieth century farm buildings in the Wolds of East Yorkshire. It suggests that the graffiti were created by a group of young men at the bottom of the social hierarchy - the horselads – and was one of the ways in which they constructed a distinctive sense of communal identity, at a particular stage in their lives. Whilst it tells us much about changing agricultural regimes and social structures, it also informs us about experiences and attitudes often hidden from official histories and biographies. In this way, the graffiti are argued to inform our understanding, not only of a concealed community, but also about their hidden histor

Excess α-synuclein compromises phagocytosis in iPSC-derived macrophages

To examine the pathogenic role of α-synuclein (αS) in Parkinson's Disease, we have generated induced Pluripotent Stem Cell lines from early onset Parkinson's Disease patients with SNCA A53T and SNCA Triplication mutations, and in this study have differentiated them to PSC-macrophages (pMac), which recapitulate many features of their brain-resident cousins, microglia. We show that SNCA Triplication pMac, but not A53T pMac, have significantly increased intracellular αS versus controls and release significantly more αS to the medium. SNCA Triplication pMac, but not A53T pMac, show significantly reduced phagocytosis capability and this can be phenocopied by adding monomeric αS to the cell culture medium of control pMac. Fibrillar αS is taken up by pMac by actin-rearrangement-dependent pathways, and monomeric αS by actin-independent pathways. Finally, pMac degrade αS and this can be arrested by blocking lysosomal and proteasomal pathways. Together, these results show that macrophages are capable of clearing αS, but that high levels of exogenous or endogenous αS compromise this ability, likely a vicious cycle scenario faced by microglia in Parkinson's disease

Visual/infrared interferometry of Orion Trapezium stars: Preliminary dynamical orbit and aperture synthesis imaging of the Theta 1 Orionis C system

Located in the Orion Trapezium cluster, Theta 1 Orionis C is one of the youngest and nearest high-mass stars (O5-O7) and also known to be a close binary system. Using new multi-epoch visual and near-infrared bispectrum speckle interferometric observations obtained at the BTA 6 m telescope, and IOTA near-infrared long-baseline interferometry, we trace the orbital motion of the Theta 1 Ori C components over the interval 1997.8 to 2005.9, covering a significant arc of the orbit. Besides fitting the relative position and the flux ratio, we apply aperture synthesis techniques to our IOTA data to reconstruct a model-independent image of the Theta 1 Ori C binary system. The orbital solutions suggest a high eccentricity (e approx. 0.91) and short-period (P approx. 10.9 yrs) orbit. As the current astrometric data only allows rather weak constraints on the total dynamical mass, we present the two best-fit orbits. From these orbital solutions one can be favoured, implying a system mass of 48 M_sun and a distance to the Trapezium cluster of 434 pc. When also taking the measured flux ratio and the derived location in the HR-diagram into account, we find good agreement for all observables, assuming a spectral type of O5.5 for Theta 1 Ori C1 (M=34.0 M_sun) and O9.5 for C2 (M=15.5 M_sun). We find indications that the companion C2 is massive itself, which makes it likely that its contribution to the intense UV radiation field of the Trapezium cluster is non-negligible. Furthermore, the high eccentricity of the preliminary orbit solution predicts a very small physical separation during periastron passage (approx. 1.5 AU, next passage around 2007.5), suggesting strong wind-wind interaction between the two O stars.Comment: 13 pages, 9 figures, Accepted for publication in Astronomy & Astrophysic

A highly efficient human pluripotent stem cell microglia model displays a neuronal-co-culture-specific expression profile and inflammatory response

Microglia are increasingly implicated in brain pathology, particularly neurodegenerative disease, with many genes implicated in Alzheimer's, Parkinson's, and motor neuron disease expressed in microglia. There is, therefore, a need for authentic, efficient in vitro models to study human microglial pathological mechanisms. Microglia originate from the yolk sac as MYB-independent macrophages, migrating into the developing brain to complete differentiation. Here, we recapitulate microglial ontogeny by highly efficient differentiation of embryonic MYB-independent iPSC-derived macrophages then co-culture them with iPSC-derived cortical neurons. Co-cultures retain neuronal maturity and functionality for many weeks. Co-culture microglia express key microglia-specific markers and neurodegenerative disease-relevant genes, develop highly dynamic ramifications, and are phagocytic. Upon activation they become more ameboid, releasing multiple microglia-relevant cytokines. Importantly, co-culture microglia downregulate pathogen-response pathways, upregulate homeostatic function pathways, and promote a more anti-inflammatory and pro-remodeling cytokine response than corresponding monocultures, demonstrating that co-cultures are preferable for modeling authentic microglial physiology

Investigating the spectroscopic, magnetic and circumstellar variability of the O9 subgiant star HD 57682

The O9IV star HD 57682, discovered to be magnetic within the context of the MiMeS survey in 2009, is one of only eight convincingly detected magnetic O-type stars. Among this select group, it stands out due to its sharp-lined photospheric spectrum. Since its discovery, the MiMeS Collaboration has continued to obtain spectroscopic and magnetic observations in order to refine our knowledge of its magnetic field strength and geometry, rotational period, and spectral properties and variability. In this paper we report new ESPaDOnS spectropolarimetric observations of HD 57682, which are combined with previously published ESPaDOnS data and archival H{\alpha} spectroscopy. This dataset is used to determine the rotational period (63.5708 \pm 0.0057 d), refine the longitudinal magnetic field variation and magnetic geometry (dipole surface field strength of 880\pm50 G and magnetic obliquity of 79\pm4\circ as measured from the magnetic longitudinal field variations, assuming an inclination of 60\circ), and examine the phase variation of various lines. In particular, we demonstrate that the H{\alpha} equivalent width undergoes a double-wave variation during a single rotation of the star, consistent with the derived magnetic geometry. We group the variable lines into two classes: those that, like H{\alpha}, exhibit non-sinusoidal variability, often with multiple maxima during the rotation cycle, and those that vary essentially sinusoidally. Based on our modelling of the H{\alpha} emission, we show that the variability is consistent with emission being generated from an optically thick, flattened distribution of magnetically-confined plasma that is roughly distributed about the magnetic equator. Finally, we discuss our findings in the magnetospheric framework proposed in our earlier study.Comment: 21 pages, 19 figures, Accepted for publication in MNRA