The Photometric and Kinematic Structure of Face-On Disk Galaxies. I. Sample Definition, H-alpha Integral Field Spectroscopy, and HI Line-Widths

We present a survey of the photometric and kinematic properties of 39 nearby, nearly face-on disk galaxies. Our approach exploits echelle-resolution integral-field spectroscopy of the H-alpha regions, obtained with DensePak on the WIYN 3.5m telescope Bench Spectrograph. This data is complemented by HI line-profiles observed with the Nancay radio telescope for 25 of these sample galaxies. Twelve additional line-widths are available for sample galaxies from the literature. In this paper, we introduce the goals of this survey, define the sample selection algorithm, and amass the integral field spectroscopic data and HI line-widths. We establish spatially-integrated H-alpha line-widths for the sample. We test the veracity of these spatially-integrated line profiles by convolving narrow-band imaging data with velocity field information for one of the sample galaxies, PGC 38268, and also by comparing to HI line profiles. We find HI and H-alpha line profiles to be similar in width but different in shape, indicating we are observing different spatial distributions of ionized and neutral gas in largely axisymmetric systems with flat outer rotation-curves. We also find vertical velocity dispersions of the ionized disk gas within several disk scale-lengths have a median value of 18 km/s and an 80% range of 12-26 km/s. This is only a factor of ~2 larger than what is observed for neutral atomic and molecular gas. With standard assumptions for intrinsic and thermal broadening for H-alpha, this translates into a factor of three range in turbulent velocities, between 8 and 25 km/s.Comment: 29 pages, 20 figures; accepted for publication in ApJ Supplement Serie

Hiding Cusps in Cores: Kinematics of Disk Galaxies in Triaxial Dark Matter Halos

We study the kinematics of gaseous disks in triaxial dark matter halos using the closed-loop orbit solutions in non-axisymmetric potentials. The orbits are in general non-circular and, for given triaxiality, their ellipticity depends on the ratio of escape to circular velocities, V_esc^2/V_c^2. This ratio increases steeply towards the center for cold dark matter (CDM) halo density profiles, implying that even minor deviations from spherical symmetry may induce large deviations from circular orbits in the velocity field of a gaseous disk, especially near the center. This result suggests that caution should be exercised when interpreting constraints on the presence of density cusps in the dark halo derived from the innermost velocity profile. Simulated long-slit rotation curves vary greatly in shape, depending primarily on the viewing angle of the disk and on its orientation relative to the principal axes of the potential. "Solid-body" rotation curves - typically interpreted as a signature of a constant density core in the dark matter distribution - are often obtained when the slit samples velocities near the major axis of the closed loop orbits. Triaxial potentials imprint specific symmetries in 2D velocity fields, generally inducing "twists" in the isovelocity contours and anti-symmetric patterns in opposite quadrants. We suggest that triaxial halos may be responsible for the variety of shapes of long-slit rotation curves of low surface brightness (LSB) galaxies, as well as for the complex central kinematics of LSBs, which are sometimes ascribed to the presence of "radial motions" in the gas. We argue that LSB rotation curves might be reconciled with the structure of CDM halos once the effects of halo triaxiality on the dynamics of gaseous disks are properly taken into account.Comment: fixed color bar in Fig. 4. 9 pages, 4 figures, accepted for publication in MNRAS, high resolution version avaliable at http://www.mpa-garching.mpg.de/~ehayashi/hiding

Free 25-Hydroxyvitamin D: Impact of Vitamin D Binding Protein Assays on Racial-Genotypic Associations

Context: Total 25-hydroxyvitamin D (25OHD) is a marker of vitamin D status and is lower in African Americans than in whites. Whether this difference holds for free 25OHOD (f25OHD) is unclear, considering reported genetic-racial differences in vitamin D binding protein (DBP) used to calculate f25OHD.  Objectives: Our objective was to assess racial-geographic differences in f25OHD and to understand inconsistencies in racial associations with DBP and calculated f25OHD.  Design: This study used a cross-sectional design.  Setting: The general community in the United States, United Kingdom, and The Gambia were included in this study.  Participants: Men in Osteoporotic Fractures in Men and Medical Research Council studies (N = 1057) were included.  Exposures: Total 25OHD concentration, race, and DBP (GC) genotype exposures were included.  Outcome Measures: Directly measured f25OHD, DBP assessed by proteomics, monoclonal and polyclonal immunoassays, and calculated f25OHD were the outcome measures.  Results: Total 25OHD correlated strongly with directly measured f25OHD (Spearman r = 0.84). Measured by monoclonal assay, mean DBP in African-ancestry subjects was approximately 50% lower than in whites, whereas DBP measured by polyclonal DBP antibodies or proteomic methods was not lower in African-ancestry. Calculated f25OHD (using polyclonal DBP assays) correlated strongly with directly measured f25OHD (r = 0.80–0.83). Free 25OHD, measured or calculated from polyclonal DBP assays, reflected total 25OHD concentration irrespective of race and was lower in African Americans than in US whites.  Conclusions: Previously reported racial differences in DBP concentration are likely from monoclonal assay bias, as there was no racial difference in DBP concentration by other methods. This confirms the poor vitamin D status of many African-Americans and the utility of total 25OHD in assessing vitamin D in the general population

The SAURON project. II. Sample and early results

Early results are reported from the SAURON survey of the kinematics and stellar populations of a representative sample of nearby E, S0 and Sa galaxies. The survey is aimed at determining the intrinsic shape of the galaxies, their orbital structure, the mass-to-light ratio as a function of radius, the age and metallicity of the stellar populations, and the frequency of kinematically decoupled cores and nuclear black holes. The construction of the representative sample is described, and its properties are illustrated. A comparison with long-slit spectroscopic data establishes that the SAURON measurements are comparable to, or better than, the highest-quality determinations. Comparisons are presented for NGC 3384 and NGC 4365 where stellar velocities and velocity dispersions are determined to a precision of 6 km/s, and the h3 and h4 parameters of the line-of-sight velocity distribution to a precision of better than 0.02. Extraction of accurate gas emission-line intensities, velocities and line widths from the datacubes is illustrated for NGC 5813. Comparisons with published line-strengths for NGC 3384 and NGC 5813 reveal uncertainties of < 0.1 A on the measurements of the Hbeta, Mgb and Fe5270 indices. Integral-field mapping uniquely connects measurements of the kinematics and stellar populations to the galaxy morphology. The maps presented here illustrate the rich stellar kinematics, gaseous kinematics, and line-strength distributions of early-type galaxies. The results include the discovery of a thin, edge-on, disk in NGC 3623, confirm the axisymmetric shape of the central region of M32, illustrate the LINER nucleus and surrounding counter-rotating star-forming ring in NGC 7742, and suggest a uniform stellar population in the decoupled core galaxy NGC 5813.Comment: 20 pages, 17 figures. To be published in MNRAS. Version with full resolution images available at http://www.strw.leidenuniv.nl/~dynamics/Instruments/Sauron/pub_list.htm

CDK19 is disrupted in a female patient with bilateral congenital retinal folds, microcephaly and mild mental retardation

Microcephaly, mental retardation and congenital retinal folds along with other systemic features have previously been reported as a separate clinical entity. The sporadic nature of the syndrome and lack of clear inheritance patterns pointed to a genetic heterogeneity. Here, we report a genetic analysis of a female patient with microcephaly, congenital bilateral falciform retinal folds, nystagmus, and mental retardation. Karyotyping revealed a de novo pericentric inversion in chromosome 6 with breakpoints in 6p12.1 and 6q21. Fluorescence in situ hybridization analysis narrowed down the region around the breakpoints, and the breakpoint at 6q21 was found to disrupt the CDK19 gene. CDK19 was found to be expressed in a diverse range of tissues including fetal eye and fetal brain. Quantitative PCR of the CDK19 transcript from Epstein–Barr virus-transformed lymphoblastoid cell lines of the patient revealed ~50% reduction in the transcript (p = 0.02), suggesting haploinsufficiency of the gene. cdk8, the closest orthologue of human CDK19 in Drosophila has been shown to play a major role in eye development. Conditional knock-down of Drosophila cdk8 in multiple dendrite (md) neurons resulted in 35% reduced dendritic branching and altered morphology of the dendritic arbour, which appeared to be due in part to a loss of small higher order branches. In addition, Cdk8 mutant md neurons showed diminished dendritic fields revealing an important role of the CDK19 orthologue in the developing nervous system of Drosophila. This is the first time the CDK19 gene, a component of the mediator co-activator complex, has been linked to a human disease

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Regulation of the MiTF/TFE bHLH-LZ transcription factors through restricted spatial expression and alternative splicing of functional domains

The MiTF/TFE (MiT) family of basic helix–loop–helix leucine zipper transcription factors is composed of four closely related members, MiTF, TFE3, TFEB and TFEC, which can bind target DNA both as homo- or heterodimers. Using real-time RT–PCR, we have analyzed the relative expression levels of the four members in a broad range of human tissues, and found that their ratio of expression is tissue-dependent. We found that, similar to the MiTF gene, the genes for TFEB and TFEC contain multiple alternative first exons with restricted and differential tissue distributions. Seven alternative 5′ exons were identified in the TFEB gene, of which three displayed specific expression in placenta and brain, respectively. A novel TFEC transcript (TFEC-C) encodes an N-terminally truncated TFEC isoform lacking the acidic activation domain (AAD), and is exclusively expressed in kidney and small intestine. Furthermore, we observed that a considerable proportion of the TFEC transcripts splice out protein-coding exons, resulting in transcription factor isoforms lacking one or more functional domains, primarily the basic region and/or the AAD. These isoforms were always co-expressed with the intact transcription factors and may act as negative regulators of MiTF/TFE proteins. Our data reveal that multiple levels of regulation exist for the MiTF/TFE family of transcription factors, which indicates how these transcription factors may participate in various cellular processes in different tissues