Zinc transporter ZIP10 forms a heteromer with ZIP6 which regulates embryonic development and cell migration

There is growing evidence that zinc and its transporters are involved in cell migration during development and in cancer. In the present study, we show that zinc transporter ZIP10 (SLC39A10) stimulates cell motility and proliferation, both in mammalian cells and in the zebrafish embryo. This is associated with inactivation of GSK-3α and -3ß and downregulation of E-cadherin (CDH1). Morpholino-mediated knock-down of zip10 causes delayed epiboly and deformities of the head, eye, heart and tail. Furthermore, zip10 deficiency results in overexpression of cdh1, zip6 and stat3, the latter gene product driving transcription of both zip6 and zip10. The non-reduntant requirement of Zip6 and Zip10 for epithelial to mesenchymal transition (EMT) is consistent with our finding that they exist as a heteromer. We postulate that a subset of ZIPs carrying PrP-like ectodomains, including ZIP6 and ZIP10, are integral to cellular pathways and plasticity programs, such as EMT

The effect of a dominant kinase-dead Csf1r mutation associated with adult-onset leukoencephalopathy on brain development and neuropathology

Amino acid substitutions in the kinase domain of the human CSF1R protein are associated with autosomal dominant adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). To model the human disease, we created a disease-associated mutation (Glu631Lys; E631K) in the mouse Csf1r locus. Previous analysis demonstrated that heterozygous mutation (Csf1rE631K/+) had a dominant inhibitory effect on CSF1R signaling in vitro and in vivo but did not recapitulate the pathology of the human disease. We speculated that leukoencephalopathy in humans requires an environmental trigger and/or epistatic interaction with common neurodegenerative disease-associated alleles. Here we examine the impact of heterozygous Csf1r mutation on microglial phenotype, normal postnatal brain development, age-related changes in gene expression and on two distinct pathologies in which microgliosis is a prominent feature, prion disease and experimental autoimmune encephalitis (EAE). The heterozygous Csf1rE631K/+ mutation reduced microglial abundance and the expression of microglial-associated transcripts relative to wild-type controls at 12 weeks and 43 weeks of age but had no selective effect on homeostatic markers such as P2ry12. An epistatic interaction was demonstrated between Csf1rE631K/+ and Cxc3r1EGFP/+ genotypes leading to dysregulated microglial and neuronal gene expression in both hippocampus and striatum. Heterozygous Csf1rE631K mutation reduced the microgliosis associated with both diseases. There was no significant impact on disease severity or progression in prion disease. In EAE, induced expression of inflammation-associated transcripts in the hippocampus and striatum was suppressed in parallel with microglia-specific transcripts, but spinal cord demyelination was exacerbated. The results support a dominant-negative model of CSF1R-associated leukoencephalopathy and likely contributions of an environmental trigger and/or genetic background to neuropathology

Standard Galactic Field RR Lyrae II: A Gaia DR2 calibration of the period-Wesenheit-metallicity relation

RR Lyrae stars have long been popular standard candles, but significant advances in methodology and technology have been made in recent years to increase their precision as distance indicators. We present multi-wavelength (optical $UBVR_cI_c$ and Gaia $G, BP, RP$; near-infrared $JHK_s$; mid-infrared $[3.6], [4.5]$) period-luminosity-metallicity (PLZ), period-Wesenheit-metallicity (PWZ) relations, calibrated using photometry obtained from The Carnegie RR Lyrae Program and parallaxes from the Gaia second data release for 55 Galactic field RR Lyrae stars. The metallicity slope, which has long been predicted by theoretical relations, can now be measured in all passbands. The scatter in the PLZ relations is on the order of 0.2 mag, and is still dominated by uncertainties in the parallaxes. As a consistency check of our PLZ relations, we also measure the distance modulus to the globular cluster M4, the Large Magellanic Cloud (LMC) and the Small Magellanic Cloud (SMC), and our results are in excellent agreement with estimates from previous studies.Comment: Accepted for publication in MNRAS, 15 pages, 14 figure

The Carnegie-Chicago Hubble Program. VIII. An Independent Determination of the Hubble Constant Based on the Tip of the Red Giant Branch

We present a new and independent determination of the local value of the Hubble constant based on a calibration of the tip of the red giant branch (TRGB) applied to Type Ia supernovae (SNe Ia). We find a value of H0 = 69.8 ± 0.8 (±1.1% stat) ± 1.7 (±2.4% sys) km s−1 Mpc−1. The TRGB method is both precise and accurate and is parallel to but independent of the Cepheid distance scale. Our value sits midway in the range defined by the current Hubble tension. It agrees at the 1.2σ level with that of the Planck Collaboration et al. estimate and at the 1.7σ level with the Hubble Space Telescope (HST) SHoES measurement of H0 based on the Cepheid distance scale. The TRGB distances have been measured using deep HST Advanced Camera for Surveys imaging of galaxy halos. The zero-point of the TRGB calibration is set with a distance modulus to the Large Magellanic Cloud of 18.477 ± 0.004 (stat) ± 0.020 (sys) mag, based on measurement of 20 late-type detached eclipsing binary stars, combined with an HST parallax calibration of a 3.6 μm Cepheid Leavitt law based on Spitzer observations. We anchor the TRGB distances to galaxies that extend our measurement into the Hubble flow using the recently completed Carnegie Supernova Project I ( CSP-I ) sample containing about 100 well-observed SNe Ia . There are several advantages of halo TRGB distance measurements relative to Cepheid variables; these include low halo reddening, minimal effects of crowding or blending of the photometry, only a shallow (calibrated) sensitivity to metallicity in the I band, and no need for multiple epochs of observations or concerns of different slopes with period. In addition, the host masses of our TRGB host-galaxy sample are higher, on average, than those of the Cepheid sample, better matching the range of host-galaxy masses in the CSP-I distant sample and reducing potential systematic effects in the SNe Ia measurements

The Carnegie-Chicago Hubble Program. VIII. An Independent Determination of the Hubble Constant Based on the Tip of the Red Giant Branch

We present a new and independent determination of the local value of the Hubble constant based on a calibration of the Tip of the Red Giant Branch (TRGB) applied to Type Ia supernovae (SNeIa). We find a value of Ho = 69.8 +/- 0.8 (+/-1.1\% stat) +/- 1.7 (+/-2.4\% sys) km/sec/Mpc. The TRGB method is both precise and accurate, and is parallel to, but independent of the Cepheid distance scale. Our value sits midway in the range defined by the current Hubble tension. It agrees at the 1.2-sigma level with that of the Planck 2018 estimate, and at the 1.7-sigma level with the SHoES measurement of Ho based on the Cepheid distance scale. The TRGB distances have been measured using deep Hubble Space Telescope (HST) Advanced Camera for Surveys (ACS) imaging of galaxy halos. The zero point of the TRGB calibration is set with a distance modulus to the Large Magellanic Cloud of 18.477 +/- 0.004 (stat) +/-0.020 (sys) mag, based on measurement of 20 late-type detached eclipsing binary (DEB) stars, combined with an HST parallax calibration of a 3.6 micron Cepheid Leavitt law based on Spitzer observations. We anchor the TRGB distances to galaxies that extend our measurement into the Hubble flow using the recently completed Carnegie Supernova Project I sample containing about 100 well-observed SNeIa. There are several advantages of halo TRGB distance measurements relative to Cepheid variables: these include low halo reddening, minimal effects of crowding or blending of the photometry, only a shallow (calibrated) sensitivity to metallicity in the I-band, and no need for multiple epochs of observations or concerns of different slopes with period. In addition, the host masses of our TRGB host-galaxy sample are higher on average than the Cepheid sample, better matching the range of host-galaxy masses in the CSP distant sample, and reducing potential systematic effects in the SNeIa measurements.Comment: 60 pages, 20 figures, accepted for publication in the Astrophysical Journa

Asteroids Inside Out: Radar Tomography

n/