Spatiotemporal expression of zic genes during vertebrate inner ear development

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98245/1/dvdy23978.pd

Characterization of Three-Dimensional Retinal Tissue Derived from Human Embryonic Stem Cells in Adherent Monolayer Cultures

Stem cell-based therapy of retinal degenerative conditions is a promising modality to treat blindness, but requires new strategies to improve the number of functionally integrating cells. Grafting semidifferentiated retinal tissue rather than progenitors allows preservation of tissue structure and connectivity in retinal grafts, mandatory for vision restoration. Using human embryonic stem cells (hESCs), we derived retinal tissue growing in adherent conditions consisting of conjoined neural retina and retinal pigment epithelial (RPE) cells and evaluated cell fate determination and maturation in this tissue. We found that deriving such tissue in adherent conditions robustly induces all eye field genes (RX, PAX6, LHX2, SIX3, SIX6) and produces four layers of pure populations of retinal cells: RPE (expressing NHERF1, EZRIN, RPE65, DCT, TYR, TYRP, MITF, PMEL), early photoreceptors (PRs) (coexpressing CRX and RCVRN), inner nuclear layer neurons (expressing CALB2), and retinal ganglion cells [RGCs, expressing BRN3B and Neurofilament (NF) 200]. Furthermore, we found that retinal progenitors divide at the apical side of the hESC-derived retinal tissue (next to the RPE layer) and then migrate toward the basal side, similar to that found during embryonic retinogenesis. We detected synaptogenesis in hESC-derived retinal tissue, and found neurons containing many synaptophysin-positive boutons within the RGC and PR layers. We also observed long NF200-positive axons projected by RGCs toward the apical side. Whole-cell recordings demonstrated that putative amacrine and/or ganglion cells exhibited electrophysiological responses reminiscent of those in normal retinal neurons. These responses included voltage-gated Na+ and K+ currents, depolarization-induced spiking, and responses to neurotransmitter receptor agonists. Differentiation in adherent conditions allows generation of long and flexible pieces of 3D retinal tissue suitable for isolating transplantable slices of tissue for retinal replacement therapies.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140208/1/scd.2015.0144.pd

The Design, Implementation, and Performance of the Astro-H SXS Calorimeter Array and Anti-Coincidence Detector

The calorimeter array of the JAXA Astro-H (renamed Hitomi) Soft X-ray Spectrometer (SXS) was designed to provide unprecedented spectral resolution of spatially extended cosmic x-ray sources and of all cosmic x-ray sources in the Fe-K band around 6 keV, enabling essential plasma diagnostics. The SXS has a square array of 36 microcalorimeters at the focal plane. These calorimeters consist of ion-implanted silicon thermistors and HgTe thermalizing x-ray absorbers. These devices have demonstrated a resolution of better than 4.5 eV at 6 keV when operated at a heat-sink temperature of 50 mK. We will discuss the basic physical parameters of this array, including the array layout, thermal conductance of the link to the heat sink, resistance function, absorber details, and means of attaching the absorber to the thermistor-bearing element. We will also present the thermal characterization of the whole array, including thermal conductance and crosstalk measurements and the results of pulsing the frame temperature via alpha particles, heat pulses, and the environmental background. A silicon ionization detector is located behind the calorimeter array and serves to reject events due to cosmic rays. We will briefly describe this anti-coincidence detector and its performance

The Atacama Cosmology Telescope: Cosmology from Galaxy Clusters Detected via the Sunyaev-Zel'dovich Effect

We present constraints on cosmological parameters based on a sample of Sunyaev-Zel'dovich-selected galaxy clusters detected in a millimeter-wave survey by the Atacama Cosmology Telescope. The cluster sample used in this analysis consists of 9 optically-confirmed high-mass clusters comprising the high-significance end of the total cluster sample identified in 455 square degrees of sky surveyed during 2008 at 148 GHz. We focus on the most massive systems to reduce the degeneracy between unknown cluster astrophysics and cosmology derived from SZ surveys. We describe the scaling relation between cluster mass and SZ signal with a 4-parameter fit. Marginalizing over the values of the parameters in this fit with conservative priors gives sigma_8 = 0.851 +/- 0.115 and w = -1.14 +/- 0.35 for a spatially-flat wCDM cosmological model with WMAP 7-year priors on cosmological parameters. This gives a modest improvement in statistical uncertainty over WMAP 7-year constraints alone. Fixing the scaling relation between cluster mass and SZ signal to a fiducial relation obtained from numerical simulations and calibrated by X-ray observations, we find sigma_8 = 0.821 +/- 0.044 and w = -1.05 +/- 0.20. These results are consistent with constraints from WMAP 7 plus baryon acoustic oscillations plus type Ia supernoava which give sigma_8 = 0.802 +/- 0.038 and w = -0.98 +/- 0.053. A stacking analysis of the clusters in this sample compared to clusters simulated assuming the fiducial model also shows good agreement. These results suggest that, given the sample of clusters used here, both the astrophysics of massive clusters and the cosmological parameters derived from them are broadly consistent with current models.Comment: 12 pages, 7 figures. Submitted to Ap

Melatonin Suppression by Light in Humans Is More Sensitive Than Previously Reported

Peer reviewe

The Role of Zic Genes in Inner Ear Development in the Mouse: Exploring Mutant Mouse Phenotypes

Background: Murine Zic genes (Zic1-5) are expressed in the dorsal hindbrain and in periotic mesenchyme (POM) adjacent to the developing inner ear. Zic genes are involved in developmental signaling pathways in many organ systems, including the ear, although their exact roles haven't been fully elucidated. This report examines the role of Zic1, Zic2, and Zic4 during inner ear development in mouse mutants in which these Zic genes are affected. Results: Zic1/Zic4 double mutants don't exhibit any apparent defects in inner ear morphology. By contrast, inner ears from Zic2kd/kd and Zic2Ku/Ku mutants have severe but variable morphological defects in endolymphatic duct/sac and semicircular canal formation and in cochlear extension in the inner ear. Analysis of otocyst patterning in the Zic2Ku/Ku mutants by in situ hybridization showed changes in the expression patterns of Gbx2 and Pax2. Conclusions: The experiments provide the first genetic evidence that the Zic genes are required for morphogenesis of the inner ear. Zic2 loss-of-function doesn't prevent initial otocyst patterning but leads to molecular abnormalities concomitant with morphogenesis of the endolymphatic duct. Functional hearing deficits often accompany inner ear dysmorphologies, making Zic2 a novel candidate gene for ongoing efforts to identify the genetic basis of human hearing loss

The design, implementation, and performance of the Atro-H SXS calorimeter array and anti-coincidence detector

The calorimeter array of the JAXA Astro-H (renamed Hitomi) Soft X-ray Spectrometer (SXS) was designed to provide unprecedented spectral resolution of spatially extended cosmic x-ray sources and of all cosmic x-ray sources in the Fe-K band around 6 keV, enabling essential plasma diagnostics. The SXS has a square array of 36 microcalorimeters at the focal plane. These calorimeters consist of ion-implanted silicon thermistors and HgTe thermalizing x-ray absorbers. These devices have demonstrated a resolution of better than 4.5 eV at 6 keV when operated at a heat-sink temperature of 50 mK. We will discuss the basic physical parameters of this array, including the array layout, thermal conductance of the link to the heat sink, resistance function, absorber details, and means of attaching the absorber to the thermistorbearing element. We will also present the thermal characterization of the whole array, including thermal conductance and crosstalk measurements and the results of pulsing the frame temperature via alpha particles, heat pulses, and the environmental background. A silicon ionization detector is located behind the calorimeter array and serves to reject events due to cosmic rays. We will briefly describe this anti-coincidence detector and its performance