62 research outputs found

    The lncRNA HOTAIR transcription is controlled by HNF4α-induced chromatin topology modulation

    Get PDF
    The expression of the long noncoding RNA HOTAIR (HOX Transcript Antisense Intergenic RNA) is largely deregulated in epithelial cancers and positively correlates with poor prognosis and progression of hepatocellular carcinoma and gastrointestinal cancers. Furthermore, functional studies revealed a pivotal role for HOTAIR in the epithelial-to-mesenchymal transition, as this RNA is causal for the repressive activity of the master factor SNAIL on epithelial genes. Despite the proven oncogenic role of HOTAIR, its transcriptional regulation is still poorly understood. Here hepatocyte nuclear factor 4-α (HNF4α), as inducer of epithelial differentiation, was demonstrated to directly repress HOTAIR transcription in the mesenchymal-to epithelial transition. Mechanistically, HNF4α was found to cause the release of a chromatin loop on HOTAIR regulatory elements thus exerting an enhancer-blocking activity

    Inner-sphere oxidation of ternary iminodiacetatochromium(III) complexes involving DL-valine and L-arginine as secondary ligands. Isokinetic relationship for the oxidation of ternary iminodiacetato-chromium(III) complexes by periodate

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>In this paper, the kinetics of oxidation of [Cr<sup>III</sup>(HIDA)(Val)(H<sub>2</sub>O)<sub>2</sub>]<sup>+ </sup>and [Cr<sup>III</sup>(HIDA)(Arg)(H<sub>2</sub>O)<sub>2</sub>]<sup>+ </sup>(HIDA = iminodiacetic acid, Val = DL-valine and Arg = L-arginine) were studied. The choice of ternary complexes was attributed to two considerations. Firstly, in order to study the effect of the secondary ligands DL-valine and L-arginine on the stability of binary complex [Cr<sup>III</sup>(HIDA)(IDA)(H<sub>2</sub>O)] towards oxidation. Secondly, transition metal ternary complexes have received particular focus and have been employed in mapping protein surfaces as probes for biological redox centers and in protein capture for both purification and study.</p> <p>Results</p> <p>The results have shown that the reaction is first order with respect to both [IO<sub>4</sub><sup>-</sup>] and the complex concentration, and the rate increases over the pH range 2.62 – 3.68 in both cases. The experimental rate law is consistent with a mechanism in which both the deprotonated forms of the complexes [Cr<sup>III</sup>(IDA)(Val)(H<sub>2</sub>O)<sub>2</sub>] and [Cr<sup>III</sup>(IDA)(Arg)(H<sub>2</sub>O)<sub>2</sub>] are significantly more reactive than the conjugate acids. The value of the intramolecular electron transfer rate constant for the oxidation of [Cr<sup>III</sup>(HIDA)(Arg)(H<sub>2</sub>O)<sub>2</sub>]<sup>+</sup>, <it>k</it><sub>3 </sub>(1.82 × 10<sup>-3 </sup>s<sup>-1</sup>), is greater than the value of <it>k</it><sub>1 </sub>(1.22 × 10<sup>-3 </sup>s<sup>-1</sup>) for the oxidation of [Cr<sup>III</sup>(HIDA)(Val)(H<sub>2</sub>O)<sub>2</sub>]<sup>+ </sup>at 45.0°C and <it>I </it>= 0.20 mol dm<sup>-3</sup>. It is proposed that electron transfer proceeds through an inner-sphere mechanism <it>via </it>coordination of IO<sub>4</sub><sup>- </sup>to chromium(III).</p> <p>Conclusion</p> <p>The oxidation of [Cr<sup>III</sup>(HIDA)(Val)(H<sub>2</sub>O)<sub>2</sub>]<sup>+ </sup>and [Cr<sup>III</sup>(HIDA)(Arg)(H<sub>2</sub>O)<sub>2</sub>]<sup>+ </sup>by periodate may proceed through an inner-sphere mechanism via two electron transfer giving chromium(VI). The value of the intramolecular electron transfer rate constant for the oxidation of [Cr<sup>III</sup>(HIDA)(Arg)(H<sub>2</sub>O)<sub>2</sub>]<sup>+</sup>, <it>k</it><sub>3</sub>, is greater than the value of <it>k</it><sub>1 </sub>for the oxidation of [Cr<sup>III</sup>(HIDA)(Val)(H<sub>2</sub>O)<sub>2</sub>]<sup>+</sup>. A common mechanism for the oxidation of ternary iminodiacetatochromium(III) complexes by periodate is proposed, and this is supported by an excellent isokinetic relationship between ΔH* and ΔS* values for these reactions.</p

    Cognitive function and drivers of cognitive impairment in a European and a Korean cohort of people living with HIV

    Get PDF
    Although cognitive impairments are still prevalent in the current antiretroviral therapy era, limited investigations have compared the prevalence of cognitive disorder in people living with HIV (PLWH) and its determinants in different regions and ethnicities. We compared cognitive performance across six domains using comparable batteries in 134 PLWH aged ≥45 years from the COBRA study (Netherlands, UK), and 194 PLWH aged ≥18 years from the NeuroAIDS Project (South Korea). Cognitive scores were standardized and averaged to obtain domain and global T-scores. Associations with global T-scores were evaluated using multivariable regression and the ability of individual tests to detect cognitive impairment (global T-score ≤45) was assessed using the area-under-the-receiver-operating-characteristic curve (AUROC). The median (interquartile range) age of participants was 56 (51, 62) years in COBRA (88% white ethnicity, 93% male) and 45 (37, 52) years in NeuroAIDS (100% Korean ethnicity, 94% male). The rate of cognitive impairment was 18.8% and 18.0%, respectively (p = 0.86). In COBRA, Black-African ethnicity was the factor most strongly associated with cognitive function (11.1 [7.7, 14.5] lower scores vs. white ethnicity, p < 0.01), whereas in NeuroAIDS, age (0.6 [0.1, 1.3] per 10-year, p<0.01) and education (0.7 [0.5, 0.9] per year, p<0.01) were significantly associated with cognitive function with anemia showing only a weak association (−1.2 [−2.6, 0.3], p=0.12). Cognitive domains most associated with cognitive impairment were attention (AUROC = 0.86) and executive function (AUROC = 0.87) in COBRA and processing speed (AUROC = 0.80), motor function (AUROC = 0.78) and language (AUROC = 0.78) in NeuroAIDS. Two cohorts of PLWH from different geographical regions report similar rates of cognitive impairment but different risk factors and cognitive profiles of impairment

    Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment

    Get PDF
    Background. The optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patientreported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts.Methods. Differences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria.Results. The prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P&lt;.05). There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P&lt;.05), as well as smaller brain volumes (P&lt;.01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker.Conclusion. Different methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer selfreported health status. This may be due to the statistical advantage of using a multivariate approach

    Preparing for low surface brightness science with the Vera C. Rubin Observatory: characterisation of tidal features from mock images

    Get PDF
    Tidal features in the outskirts of galaxies yield unique information about their past interactions and are a key prediction of the hierarchical structure formation paradigm. The Vera C. Rubin Observatory is poised to deliver deep observations for potentially of millions of objects with visible tidal features, but the inference of galaxy interaction histories from such features is not straightforward. Utilising automated techniques and human visual classification in conjunction with realistic mock images produced using the NEWHORIZON cosmological simulation, we investigate the nature, frequency and visibility of tidal features and debris across a range of environments and stellar masses. In our simulated sample, around 80 per cent of the flux in the tidal features around Milky Way or greater mass galaxies is detected at the 10-year depth of the Legacy Survey of Space and Time (30-31 mag / sq. arcsec), falling to 60 per cent assuming a shallower final depth of 29.5 mag / sq. arcsec. The fraction of total flux found in tidal features increases towards higher masses, rising to 10 per cent for the most massive objects in our sample (M*~10^{11.5} Msun). When observed at sufficient depth, such objects frequently exhibit many distinct tidal features with complex shapes. The interpretation and characterisation of such features varies significantly with image depth and object orientation, introducing significant biases in their classification. Assuming the data reduction pipeline is properly optimised, we expect the Rubin Observatory to be capable of recovering much of the flux found in the outskirts of Milky Way mass galaxies, even at intermediate redshifts (z<0.2)

    Lady

    Get PDF
    Demo CD of folk music composed and performed by Virginia of Burkesville, Kentucky. Includes tracks: 1. Iowa Girl 2. Honor Your Tribe 3. Run for Cover 4. Match My Speed 5. What About Jenny? 6. Lady 7. Real Revolution 8. Playing on the Blondehttps://digitalcommons.wku.edu/pos05/1000/thumbnail.jp

    Deep extragalactic visible legacy survey (DEVILS): the emergence of bulges and decline of disc growth since z = 1

    Get PDF
    We present a complete structural analysis of the ellipticals (E), diffuse bulges (dB), compact bulges (cB), and discs (D) within a redshift range 0 &lt; z &lt; 1, and stellar mass log10(M&#x2217;/M&#x2299;) &#x2265; 9.5 volume-limited sample drawn from the combined DEVILS and HST-COSMOS region. We use the profit code to profile over &#x223C;35 000 galaxies for which visual classification into single or double component was pre-defined in Paper-I. Over this redshift range, we see a growth in the total stellar mass density (SMD) of a factor of 1.5. At all epochs we find that the dominant structure, contributing to the total SMD, is the disc, and holds a fairly constant share of &#x223C; 60 per cent of the total SMD from z = 0.8 to z = 0.2, dropping to &#x223C; 30 per cent at z = 0.0 (representing &#x223C; 33 per cent decline in the total disc SMD). Other classes (E, dB, and cB) show steady growth in their numbers and integrated stellar mass densities. By number, the most dramatic change across the full mass range is in the growth of diffuse bulges. In terms of total SMD, the biggest gain is an increase in massive elliptical systems, rising from 20 per cent at z = 0.8 to equal that of discs at z = 0.0 (30 per cent) representing an absolute mass growth of a factor of 2.5. Overall, we see a clear picture of the emergence and growth of all three classes of spheroids over the past 8 Gyr, and infer that in the later half of the Universe's timeline spheroid-forming processes and pathways (secular evolution, mass-accretion, and mergers) appear to dominate mass transformation over quiescent disc growth

    GAMA/DEVILS: constraining the cosmic star formation history from improved measurements of the 0.3-2.2 mu m extragalactic background light

    No full text
    We present a revised measurement of the optical extragalactic background light (EBL), based on the contribution of resolved galaxies to the integrated galaxy light (IGL). The cosmic optical background radiation (COB), encodes the light generated by star formation, and provides a wealth of information about the cosmic star formation history (CSFH). We combine wide and deep galaxy number counts from the Galaxy And Mass Assembly survey (GAMA) and Deep Extragalactic VIsible Legacy Survey (DEVILS), along with the Hubble Space Telescope (HST) archive and other deep survey data sets, in nine multiwavelength filters to measure the COB in the range from 0.35  μm to 2.2  μm. We derive the luminosity density in each band independently and show good agreement with recent and complementary estimates of the optical-EBL from very high-energy (VHE) experiments. Our error analysis suggests that the IGL and γ-ray measurements are now fully consistent to within ∼10 per cent⁠, suggesting little need for any additional source of diffuse light beyond the known galaxy population. We use our revised IGL measurements to constrain the CSFH, and place amplitude constraints on a number of recent estimates. As a consistency check, we can now demonstrate convincingly, that the CSFH, stellar mass growth, and the optical-EBL provide a fully consistent picture of galaxy evolution. We conclude that the peak of star formation rate lies in the range 0.066–0.076 M⊙ yr−1 Mpc−3 at a lookback time of 9.1 to 10.9 Gyr
    corecore