The Role of Trim58 in Erythropoiesis

Red blood cells (erythrocytes) deliver oxygen to all tissues of the body. Defects in red blood cell production (erythropoiesis) can cause disease. Mammalian erythropoiesis culminates in enucleation, an incompletely understood process that entails the physical separation of the nucleus and cytoplasm. The work in this thesis investigated the role of a previously uncharacterized protein named Trim58 in erythropoiesis. Human genetic studies suggested that TRIM58 played an important role in erythroid development. In humans and mice, Trim58 expression was found to be restricted to red blood cell precursors during late stage maturation. In fact, murine Trim58 was upregulated just prior to enucleation. Using short hairpin RNAs, Trim58 expression was inhibited in cultured murine erythroblasts. Through a variety of analyses, it was demonstrated that Trim58 is dispensable for early erythroid maturation. However, Trim58 knockdown impaired movement of the nucleus, thereby inhibiting enucleation. Trim58 is a member of the tripartite motif-containing family of proteins, many of which function as E3 ubiquitin ligases that can facilitate protein degradation. Protein interaction studies demonstrated that Trim58 bound directly to the molecular motor protein complex dynein. Consistent with its putative role as an E3 ubiquitin ligase, ectopic Trim58 expression in HeLa cells caused dynein degradation in a proteasome-dependent fashion. Furthermore, dynein loss and efficient enucleation were coincident and dependent upon Trim58 induction during erythroid culture maturation. Dynein mediates unidirectional nuclear movement toward the microtubule organizing center. Erythroid enucleation requires nuclear movement in the opposite direction. Hence, Trim58-mediated dynein degradation may be responsible for nuclear movement during enucleation. Our findings identify Trim58 as the first erythroid-specific protein that regulates this process. More broadly, regulated proteolysis represents a previously unappreciated mode of regulation for dynein, which is critical for many cellular processes

Environmental Inequity: Economic Causes, Economic Solutions

The article examines one such shortcoming: namely, that existing research fails to account for the dynamic nature of the housing market. Analyzing data from the St. Louis metropolitan area, this study finds that economic factors--not siting discrimination--are behind many claims of environmental racism. This phenomenon suggests the need to develop public policies that fit the economic nature of the problem. In particular, a policy that compensates individuals living near industrial sites is the key to securing environmental justice

The Last Eight-Billion Years of Intergalactic SiIV Evolution

We identified 24 SiIV absorption systems with z <~ 1 from a blind survey of 49 low-redshift quasars with archival Hubble Space Telescope ultraviolet spectra. We relied solely on the characteristic wavelength separation of the doublet to automatically detect candidates. After visual inspection, we defined a sample of 20 definite (group G = 1) and 4 "highly-likely" (G = 2) doublets with rest equivalent widths W_r for both lines detected at > 3 sigma. The absorber line density of the G = 1 doublets was dN_SiIV/dX = 1.4+0.4/-0.3 for log N(Si+3) > 12.9. The best-fit power law to the G = 1 frequency distribution of column densities f(N(Si+3)) had normalization k = (1.2+0.5/-0.4) x 10^-14 cm2 and slope alpha = -1.6+0.3/-0.3. Using the power-law model of f(N(Si+3)), we measured the Si+3 mass density relative to the critical density: Omega(Si+3) = (3.7+2.8/-1.7) x 10^-8 for 13 < log N(Si+3) < 15. From Monte Carlo sampling of the distributions, we estimated our value to be a factor of 4.8+3.0/-1.9 higher than the 2 . From a simple linear fit to Omega(Si+3) over the age of the Universe, we estimated a slow and steady increase from z = 5.5 --> 0 with dOmega/dt_age = (0.61+/-0.23) x 10^-8 Gyr^-1. We compared our ionic ratios N(Si+3)/N(C+3) to a 2 < z < 4.5 sample and concluded, from survival analysis, that the two populations are similar, with median = 0.16.Comment: 18 pages, 9 figures, 4 tables, added figures and new analysis, results have changed, accepted to Ap

Design of value and value of design: the roles of strategic design in (traditionally) non-design disciplines

Design skills such as Design Thinking, strategic design and service design are seen globally as skillsets that can help to innovate business, social, health, and environmental sectors in the 21stCentury (see Martin, 2009; Mootee, 2013; Brown and Wyatt, 2010). However, there is a difference between the perceived value of design in design practice versus academic design research. After decades of philosophical and conceptual discussions, design research has not yet found its academic position among the science and arts (see Faste and Faste, 2012; Jonas, 2012; Krippendorff 2007). Focusing on design based research, this paper proposes the Integrated People-Centred Design Model as the means to contribute new knowledge that navigates the common ground between practice and academia. This model has been generated from an industry funded research project that explores design as the means to unpack and provide possibilities to complex service delivery challenges in the disability sector. The model explores the value of design through the lenses of experiential, behavioural, procedural and functional innovation. The objective of this paper is to explore ways to bridge the gap between the value of design in practice and academia. This paper also discusses an on-going PhD project that applies the Integrated People-Centred Model, that has to date, bridge the gap of value between design practice and academic research

The Chemical Abundances Of Stars In The Halo (CASH) Project. II. A Sample Of 14 Extremely Metal-Poor Stars

We present a comprehensive abundance analysis of 20 elements for 16 new low-metallicity stars from the Chemical Abundances of Stars in the Halo (CASH) project. The abundances have been derived from both Hobby-Eberly Telescope High Resolution Spectrograph snapshot spectra (R similar to 15,000) and corresponding high-resolution (R similar to 35,000) Magellan Inamori Kyocera Echelle spectra. The stars span a metallicity range from [Fe/H] from -2.9 to -3.9, including four new stars with [Fe/H] < -3.7. We find four stars to be carbon-enhanced metal-poor (CEMP) stars, confirming the trend of increasing [C/Fe] abundance ratios with decreasing metallicity. Two of these objects can be classified as CEMP-no stars, adding to the growing number of these objects at [Fe/H]< -3. We also find four neutron-capture-enhanced stars in the sample, one of which has [Eu/Fe] of 0.8 with clear r-process signatures. These pilot sample stars are the most metal-poor ([Fe/H] less than or similar to -3.0) of the brightest stars included in CASH and are used to calibrate a newly developed, automated stellar parameter and abundance determination pipeline. This code will be used for the entire similar to 500 star CASH snapshot sample. We find that the pipeline results are statistically identical for snapshot spectra when compared to a traditional, manual analysis from a high-resolution spectrum.Physics Frontier Center/Joint Institute for Nuclear Astrophysics (JINA) PHY 02-16783, PHY 0822648Carnegie Institution of WashingtonNSF AST-0908978Astronom

Soft Materials under Air Blast Loading and Their Effect on Primary Blast Injury

Injury from blast is significant in both military and civilian environments. Although injuries from blast are well-documented, the mechanisms of injury are not well understood. Developing better protection requires knowledge of injury mechanisms and material response to blast loading. The importance of understanding how soft materials such as foams and fabrics behave under blast loading is further apparent when one realizes the capacity for some of these materials, frequently used in protective ensembles, to increase the potential for injury under some conditions. The ability for material configurations to amplify blast pressure and injury has been shown experimentally by other researches, and numerically in this study. Initially, 1-D finite element and mathematical models were developed to investigate a variety of soft materials commonly utilized in ballistic and blast protection. Foams, which have excellent characteristics in terms of energy absorption and density, can be used in conjunction with other materials to drastically reduce the amplitude of the transmitted pressure wave and corresponding injury. Additionally, a more fundamental examination of single layers of fabric was undertaken to investigate to the effects of parameters such as fabric porosity and density. Shock tube models were developed and validated against experimental results from the literature. After the models were validated, individual fabric properties were varied independently to isolate the influence of parameters in ways not possible experimentally. Fabric permeability was found to have the greatest influence on pressure amplification. Kevlar, a ballistic fabric, was modelled due to its frequent use for fragmentation protection (either stand-alone or in conjunction with a hard ballistic plate). The developed fabric and foam material models were then utilized in conjunction with a detailed torso model for the estimation of lung injury resulting from air blast. It was found that the torso model predicted both amplification and attenuation of injury, and all materials investigated as a part of the study had the capacity for both blast amplification and attenuation. The benefit of the models developed is that they allow for the evaluation of specific protection concepts