Interleukin 7 Receptor Control of T Cell Receptor γ Gene Rearrangement: Role of Receptor-associated Chains and Locus Accessibility

VDJ recombination of T cell receptor and immunoglobulin loci occurs in immature lymphoid cells. Although the molecular mechanisms of DNA cleavage and ligation have become more clear, it is not understood what controls which target loci undergo rearrangement. In interleukin 7 receptor (IL-7R)α−/− murine thymocytes, it has been shown that rearrangement of the T cell receptor (TCR)-γ locus is virtually abrogated, whereas other rearranging loci are less severely affected. By examining different strains of mice with targeted mutations, we now observe that the signaling pathway leading from IL-7Rα to rearrangement of the TCR-γ locus requires the γc receptor chain and the γc-associated Janus kinase Jak3. Production of sterile transcripts from the TCR-γ locus, a process that generally precedes rearrangement of a locus, was greatly repressed in IL-7Rα−/− thymocytes. The repressed transcription was not due to a lack in transcription factors since the three transcription factors known to regulate this locus were readily detected in IL-7Rα−/− thymocytes. Instead, the TCR-γ locus was shown to be methylated in IL-7Rα−/− thymocytes. Treatment of IL-7Rα−/− precursor T cells with the specific histone deacetylase inhibitor trichostatin A released the block of TCR-γ gene rearrangement. This data supports the model that IL-7R promotes TCR-γ gene rearrangement by regulating accessibility of the locus via demethylation and histone acetylation of the locus

Issue Brief: Indiana’s Health Professions Workforce Shortages and Mal-distribution

Workforce shortages have been documented across a broad spectrum of health profession disciplines in Indiana. Currently, federal, state and local programs exist to recruit and retain health professionals in our state; however, these programs have had minimal impact on the underlying factors that contribute to the problem. Additional steps must be taken to expand the supply of health professionals to adequately meet the growing need for health care services among Indiana residents. While many health professional shortages exist, this brief will focus on the primary care physicians and nurses needed to provide medical homes for residents of our state

Computed microtomography of reservoir core samples

X-ray computed tomography (CT) is often utilized to evaluate and characterize structural characteristics within reservoir core material systems. Generally, medical CT scanners have been employed because of their availability and ease of use. Of interest lately has been the acquisition of three-dimensional, high resolution descriptions of rock and pore structures for characterization of the porous media and for modeling of single and multiphase transport processes. The spatial resolution of current medical CT scanners is too coarse for pore level imaging of most core samples. Recently developed high resolution computed microtomography (CMT) using synchrotron X-ray sources is analogous to conventional medical CT scanning and provides the ability to obtain three-dimensional images of specimens with a spatial resolution on the order of micrometers. Application of this technique to the study of core samples provides two- and three-dimensional high resolution description of pore structure and mineral distributions. Pore space and interconnectivity is accurately characterized and visualized. Computed microtomography data can serve as input into pore-level simulation techniques. A generalized explanation of the technique is provided, with comparison to conventional CT scanning techniques and results. Computed microtomographic results of several sandstone samples are presented and discussed. Bulk porosity values and mineralogical identification were obtained from the microtomograms and compared with gas porosity and scanning electron microscope results on tandem samples

Evaluation of Wiring Constructions for Space Applications

A NASA Office of Safety and Mission Assurance (OS&MA) program to develop lightweight, reliable, and safe wiring insulations for aerospace applications is being performed by the NASA Lewis Research Center (LeRC). As part of this effort, a new wiring construction utilizing high strength PTFE (poly tetrafluoroethylene) as the insulation has been tested and compared with the existing military standard polyimide-based MIL-W-81381 wire construction. Electrical properties which were investigated included ac corona inception and extinction voltages (sea level and 60,000 feet), time/current to smoke, and wire fusing time. The two constructions were also characterized in terms of their mechanical properties of flexural strength, abrasion resistance (23 C and 150 C), and dynamic cut-through (23 C and 200 C). The results obtained in this testing effort are presented and discussed in this paper

Genome-wide association study of Arabidopsis thaliana leaf microbial community

communit

Pore level imaging of fluid transport using synchrotron x-ray microtomography

Recently developed high resolution computed microtomography (CMI) using synchrotron X-ray sources is analogous to conventional medical Cr scanning and provides the ability to obtain three-dimensional images of specimens with a spatial resolution on the order of micrometers. Application of this technique to the study of core samples has previously been shown to provide excellent two- and three-dimensional high resolution descriptions of pore structure and mineral distributions of core material. Recently, computed microtomographic endpoint saturation images of a fluid filled sandstone core sample were obtained using a microtomographic apparatus and a high energy X-ray beam produced by a superconducting wiggler at the National Synchrotron Light Source at Brookhaven National Laboratory. Images of a 6 mm subsection of the one inch diameter core sample were obtained prior and subsequent to flooding to residual oil. Both oil and brine phases were observable within the imaged rock matrix. The rock matrix image data was used as input to a fluid transport simulator and the results compared with the end point saturation images and data. These high resolution images of the fluid filled pore space have not been previously available to researchers and will provide valuable insight to fluid flow, and provide data as input into and validation of high resolution porous media flow simulators, such as percolation-network and Lattice Boltzmann models

Potentials of Mean Force for Protein Structure Prediction Vindicated, Formalized and Generalized

Understanding protein structure is of crucial importance in science, medicine and biotechnology. For about two decades, knowledge based potentials based on pairwise distances -- so-called "potentials of mean force" (PMFs) -- have been center stage in the prediction and design of protein structure and the simulation of protein folding. However, the validity, scope and limitations of these potentials are still vigorously debated and disputed, and the optimal choice of the reference state -- a necessary component of these potentials -- is an unsolved problem. PMFs are loosely justified by analogy to the reversible work theorem in statistical physics, or by a statistical argument based on a likelihood function. Both justifications are insightful but leave many questions unanswered. Here, we show for the first time that PMFs can be seen as approximations to quantities that do have a rigorous probabilistic justification: they naturally arise when probability distributions over different features of proteins need to be combined. We call these quantities reference ratio distributions deriving from the application of the reference ratio method. This new view is not only of theoretical relevance, but leads to many insights that are of direct practical use: the reference state is uniquely defined and does not require external physical insights; the approach can be generalized beyond pairwise distances to arbitrary features of protein structure; and it becomes clear for which purposes the use of these quantities is justified. We illustrate these insights with two applications, involving the radius of gyration and hydrogen bonding. In the latter case, we also show how the reference ratio method can be iteratively applied to sculpt an energy funnel. Our results considerably increase the understanding and scope of energy functions derived from known biomolecular structures