The endothelial-enriched lncRNA LINC00607 mediates angiogenic function

Long non-coding RNAs (lncRNAs) can act as regulatory RNAs which, by altering the expression of target genes, impact on the cellular phenotype and cardiovascular disease development. Endothelial lncRNAs and their vascular functions are largely undefined. Deep RNA-Seq and FANTOM5 CAGE analysis revealed the lncRNA LINC00607 to be highly enriched in human endothelial cells. LINC00607 was induced in response to hypoxia, arteriosclerosis regression in non-human primates, post-atherosclerotic cultured endothelial cells from patients and also in response to propranolol used to induce regression of human arteriovenous malformations. siRNA knockdown or CRISPR/Cas9 knockout of LINC00607 attenuated VEGF-A-induced angiogenic sprouting. LINC00607 knockout in endothelial cells also integrated less into newly formed vascular networks in an in vivo assay in SCID mice. Overexpression of LINC00607 in CRISPR knockout cells restored normal endothelial function. RNA- and ATAC-Seq after LINC00607 knockout revealed changes in the transcription of endothelial gene sets linked to the endothelial phenotype and in chromatin accessibility around ERG-binding sites. Mechanistically, LINC00607 interacted with the SWI/SNF chromatin remodeling protein BRG1. CRISPR/Cas9-mediated knockout of BRG1 in HUVEC followed by CUT&RUN revealed that BRG1 is required to secure a stable chromatin state, mainly on ERG-binding sites. In conclusion, LINC00607 is an endothelial-enriched lncRNA that maintains ERG target gene transcription by interacting with the chromatin remodeler BRG1 to ultimately mediate angiogenesis

The GALAH Survey: Using galactic archaeology to refine our knowledge of TESS target stars

An unprecedented number of exoplanets are being discovered by the Transiting Exoplanet Survey Satellite (TESS). Determining the orbital parameters of these exoplanets, and especially their mass and radius, will depend heavily upon the measured physical characteristics of their host stars. We have cross-matched spectroscopic, photometric, and astrometric data from GALAH Data Release 2, the TESS Input Catalog and Gaia Data Release 2, to create a curated, self-consistent catalogue of physical and chemical properties for 47 285 stars. Using these data, we have derived isochrone masses and radii that are precise to within 5 per cent. We have revised the parameters of three confirmed, and twelve candidate, TESS planetary systems. These results cast doubt on whether CTOI-20125677 is indeed a planetary system, since the revised planetary radii are now comparable to stellar sizes. Our GALAH-TESS catalogue contains abundances for up to 23 elements. We have specifically analysed the molar ratios for C/O, Mg/Si, Fe/Si, and Fe/Mg, to assist in determining the composition and structure of planets with Rp < 4R⊕. From these ratios, 36 per cent fall within 2$\sigma$ sigma of the Sun/Earth values, suggesting that these stars may host rocky exoplanets with geological compositions similar to planets found within our own Solar system.JTC would like to thank SW, BC, and DN, and is supported by the Australian Government Research Training Program (RTP) Scholarship. JTC would also like to thank Vardan Adibekyan for their valuable comments which have significantly improved the science of this manuscript. JDS and SM acknowledges the support of the Australian Research Council through Discovery Project grant DP180101791. SB acknowledges funds from the Australian Research Council (grants DP150100250 and DP160103747). Parts of this research were supported by the Australian Research Council (ARC) Centre of Excellence for All Sky Astrophysics in 3 Dimensions (ASTRO 3D), through project number CE170100013. YST is grateful to be supported by the NASA Hubble Fellowship grant HSTHF2-51425.001 awarded by the Space Telescope Science Institute

Mactinin, a fragment of cytoskeletal α-actinin, is a novel inducer of heat shock protein (Hsp)-90 mediated monocyte activation

<p>Abstract</p> <p>Background</p> <p>Monocytes, their progeny such as dendritic cells and osteoclasts and products including tumor necrosis factor (TNF)-α, interleukin (IL)-1α and IL-1β play important roles in cancer, inflammation, immune response and atherosclerosis. We previously showed that mactinin, a degradative fragment of the cytoskeletal protein α-actinin, is present at sites of monocytic activation in vivo, has chemotactic activity for monocytes and promotes monocyte/macrophage maturation. We therefore sought to determine the mechanism by which mactinin stimulates monocytes.</p> <p>Results</p> <p>Radiolabeled mactinin bound to a heterocomplex on monocytes comprised of at least 3 proteins of molecular weight 88 kD, 79 kD and 68 kD. Affinity purification, mass spectroscopy and Western immunoblotting identified heat shock protein (Hsp)-90 as the 88 kD component of this complex. Hsp90 was responsible for mediating the functional effects of mactinin on monocytes, since Hsp90 inhibitors (geldanamycin and its analogues 17-allylamino-17-demethoxygeldanamycin [17-AAG] and 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin [17-DMAG]) almost completely abrogated the stimulatory activity of mactinin on monocytes (production of the pro-inflammatory cytokines IL-1α, IL-1β and TNF-α, as well as monocyte chemotaxis).</p> <p>Conclusion</p> <p>Mactinin is a novel inducer of Hsp90 activity on monocytes and may serve to perpetuate and augment monocytic activation, thereby functioning as a "matrikine." Blockage of this function of mactinin may be useful in diseases where monocyte/macrophage activation and/or Hsp90 activity are detrimental.</p

Enhancing the relevance of Shared Socioeconomic Pathways for climate change impacts, adaptation and vulnerability research

This paper discusses the role and relevance of the shared socioeconomic pathways (SSPs) and the new scenarios that combine SSPs with representative concentration pathways (RCPs) for climate change impacts, adaptation, and vulnerability (IAV) research. It first provides an overview of uses of social–environmental scenarios in IAV studies and identifies the main shortcomings of earlier such scenarios. Second, the paper elaborates on two aspects of the SSPs and new scenarios that would improve their usefulness for IAV studies compared to earlier scenario sets: (i) enhancing their applicability while retaining coherence across spatial scales, and (ii) adding indicators of importance for projecting vulnerability. The paper therefore presents an agenda for future research, recommending that SSPs incorporate not only the standard variables of population and gross domestic product, but also indicators such as income distribution, spatial population, human health and governance

The GALAH survey: using galactic archaeology to refine our knowledge of TESS target stars

An unprecedented number of exoplanets are being discovered by the Transiting Exoplanet Survey Satellite (TESS). Determining the orbital parameters of these exoplanets, and especially their mass and radius, will depend heavily upon the measured physical characteristics of their host stars. We have cross-matched spectroscopic, photometric, and astrometric data from GALAH Data Release 2, the TESS Input Catalog and Gaia Data Release 2, to create a curated, self-consistent catalogue of physical and chemical properties for 47 285 stars. Using these data, we have derived isochrone masses and radii that are precise to within 5 per cent. We have revised the parameters of three confirmed, and twelve candidate, TESS planetary systems. These results cast doubt on whether CTOI-20125677 is indeed a planetary system, since the revised planetary radii are now comparable to stellar sizes. Our GALAH-TESS catalogue contains abundances for up to 23 elements. We have specifically analysed the molar ratios for C/O, Mg/Si, Fe/Si, and Fe/Mg, to assist in determining the composition and structure of planets with Rp < 4R⊕. From these ratios, 36 per cent fall within 2$\sigma$ sigma of the Sun/Earth values, suggesting that these stars may host rocky exoplanets with geological compositions similar to planets found within our own Solar system

The Effect of Cash Flow Forecasts on Cost of Debt

I examine the impact of the presence and characteristics of equity analysts' cash flow forecasts on cost of debt. I find the presence of cash flow forecasts is associated with a lower cost of debt relative to firm-years with only earnings estimates or neither estimate. I also find cash flow forecast characteristics are associated with cost of debt after controlling for other known determinants of yield spreads. Additional analyses decomposing earnings forecast characteristics into cash flow and accruals components find the cash flow component is associated with cost of debt, but the accruals component is not. Overall, the results indicate that debt market participants find cash flow forecasts useful in reducing information asymmetry and/or providing monitoring, as well as being useful in providing information regarding expected default risk in determining expected returns