Formation of the high-affinity agonist state of the α1-adrenergic receptor at cold temperatures does not require a G-protein

AbstractTwo methods were employed to uncouple hepatic α1-adrenergic receptors from their associated G-protein (termed Gp) in order to determine wether locking of the α1-receptor in a high-affinity agonist state at cold temperatures (2°C) represents formation of a ternary complex. Uncoupling is defined as the inability to observe the GppNHp-sensitive, high-affinity agonist state of the receptor in [3H]prazosin competition binding studies performed at 25°C. The first method for achieving uncoupling involved brief alkalinization and resulted in greater 95% loss of several G-proteins. The second method involved proteolytic cleavage of either part or all of the α1-receptor coupling domain from the binding domain. Following either treatment, receptors were converted to the high-affinity agonist state at 2°C. Thus, while formation of the high-affinity state of the receptor at higher temperatures may require Gp, formation of this state at 2°C does not require Gp or even the entire α1-adregenic receptor

Pre-Steady-State Kinetic Analysis of Truncated and Full-Length Saccharomyces cerevisiae DNA Polymerase Eta

Understanding polymerase fidelity is an important objective towards ascertaining the overall stability of an organism's genome. Saccharomyces cerevisiae DNA polymerase η (yPolη), a Y-family DNA polymerase, is known to efficiently bypass DNA lesions (e.g., pyrimidine dimers) in vivo. Using pre-steady-state kinetic methods, we examined both full-length and a truncated version of yPolη which contains only the polymerase domain. In the absence of yPolη's C-terminal residues 514–632, the DNA binding affinity was weakened by 2-fold and the base substitution fidelity dropped by 3-fold. Thus, the C-terminus of yPolη may interact with DNA and slightly alter the conformation of the polymerase domain during catalysis. In general, yPolη discriminated between a correct and incorrect nucleotide more during the incorporation step (50-fold on average) than the ground-state binding step (18-fold on average). Blunt-end additions of dATP or pyrene nucleotide 5′-triphosphate revealed the importance of base stacking during the binding of incorrect incoming nucleotides

The C-Band All-Sky Survey: Instrument design, status, and first-look data

The C-Band All-Sky Survey (C-BASS) aims to produce sensitive, all-sky maps of diffuse Galactic emission at 5 GHz in total intensity and linear polarization. These maps will be used (with other surveys) to separate the several astrophysical components contributing to microwave emission, and in particular will allow an accurate map of synchrotron emission to be produced for the subtraction of foregrounds from measurements of the polarized Cosmic Microwave Background. We describe the design of the analog instrument, the optics of our 6.1 m dish at the Owens Valley Radio Observatory, the status of observations, and first-look data.Comment: 10 pages, 11 figures, published in Proceedings of SPIE MIllimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy V (2010), Vol. 7741, 77411I-1 - 77411I-1

UV-Optical Pixel Maps of Face-On Spiral Galaxies -- Clues for Dynamics and Star Formation Histories

UV and optical images of the face-on spiral galaxies NGC 6753 and NGC 6782 reveal regions of strong on-going star formation that are associated with structures traced by the old stellar populations. We make NUV--(NUV-I) pixel color-magnitude diagrams (pCMDs) that reveal plumes of pixels with strongly varying NUV surface brightness and nearly constant I surface brightness. The plumes correspond to sharply bounded radial ranges, with (NUV-I) at a given NUV surface brightness being bluer at larger radii. The plumes are parallel to the reddening vector and simple model mixtures of young and old populations, thus neither reddening nor the fraction of the young population can produce the observed separation between the plumes. The images, radial surface-brightness, and color plots indicate that the separate plumes are caused by sharp declines in the surface densities of the old populations at radii corresponding to disk resonances. The maximum surface brightness of the NUV light remains nearly constant with radius, while the maximum I surface brightness declines sharply with radius. An MUV image of NGC 6782 shows emission from the nuclear ring. The distribution of points in an (MUV-NUV) vs. (NUV-I) pixel color-color diagram is broadly consistent with the simple mixture model, but shows a residual trend that the bluest pixels in (MUV-NUV) are the reddest pixels in (NUV-I). This may be due to a combination of red continuum from late-type supergiants and [SIII] emission lines associated with HII regions in active star-forming regions. We have shown that pixel mapping is a powerful tool for studying the distribution and strength of on-going star formation in galaxies. Deep, multi-color imaging can extend this to studies of extinction, and the ages and metallicities of composite stellar populations in nearby galaxies.Comment: LaTeX with AASTeX style file, 29 pages with 12 figures (some color, some multi-part). Accepted for publication in The Astrophysical Journa

CD4 inhibits helper T cell activation at lower affinity threshold for full-length T cell receptors than single chain signaling constructs

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FAN1 activity on asymmetric repair intermediates is mediated by an atypical monomeric virus-type replication-repair nuclease domain

FAN1 is a structure-selective DNA repair nuclease with 5' flap endonuclease activity, involved in the repair of interstrand DNA crosslinks. It is the only eukaryotic protein with a virus-type replication-repair nuclease ("VRR-Nuc") "module" that commonly occurs as a standalone domain in many bacteria and viruses. Crystal structures of three representatives show that they structurally resemble Holliday junction resolvases (HJRs), are dimeric in solution, and are able to cleave symmetric four-way junctions. In contrast, FAN1 orthologs are monomeric and cleave 5' flap structures in vitro, but not Holliday junctions. Modeling of the VRR-Nuc domain of FAN1 reveals that it has an insertion, which packs against the dimerization interface observed in the structures of the viral/bacterial VRR-Nuc proteins. We propose that these additional structural elements in FAN1 prevent dimerization and bias specificity toward flap structures

Leveraging population admixture to characterize the heritability of complex traits.

Despite recent progress on estimating the heritability explained by genotyped SNPs (h(2)g), a large gap between h(2)g and estimates of total narrow-sense heritability (h(2)) remains. Explanations for this gap include rare variants or upward bias in family-based estimates of h(2) due to shared environment or epistasis. We estimate h(2) from unrelated individuals in admixed populations by first estimating the heritability explained by local ancestry (h(2)γ). We show that h(2)γ = 2FSTCθ(1 - θ)h(2), where FSTC measures frequency differences between populations at causal loci and θ is the genome-wide ancestry proportion. Our approach is not susceptible to biases caused by epistasis or shared environment. We applied this approach to the analysis of 13 phenotypes in 21,497 African-American individuals from 3 cohorts. For height and body mass index (BMI), we obtained h(2) estimates of 0.55 ± 0.09 and 0.23 ± 0.06, respectively, which are larger than estimates of h(2)g in these and other data but smaller than family-based estimates of h(2)

The Next Generation Virgo Cluster Survey - Infrared (NGVS-IR): I. A new Near-UV/Optical/Near-IR Globular Cluster selection tool

The NGVS-IR project (Next Generation Virgo Survey - Infrared) is a contiguous near-infrared imaging survey of the Virgo cluster of galaxies. It complements the optical wide-field survey of Virgo (NGVS). The current state of NGVS-IR consists of Ks-band imaging of 4 deg^2 centered on M87, and J and Ks-band imaging of 16 deg^2 covering the region between M49 and M87. In this paper, we present the observations of the central 4 deg^2 centered on Virgo's core region. The data were acquired with WIRCam on the Canada-France-Hawaii Telescope and the total integration time was 41 hours distributed in 34 contiguous tiles. A survey-specific strategy was designed to account for extended galaxies while still measuring accurate sky brightness within the survey area. The average 5\sigma limiting magnitude is Ks=24.4 AB mag and the 50% completeness limit is Ks=23.75 AB mag for point source detections, when using only images with better than 0.7" seeing (median seeing 0.54"). Star clusters are marginally resolved in these image stacks, and Virgo galaxies with \mu_Ks=24.4 AB mag arcsec^-2 are detected. Combining the Ks data with optical and ultraviolet data, we build the uiK color-color diagram which allows a very clean color-based selection of globular clusters in Virgo. This diagnostic plot will provide reliable globular cluster candidates for spectroscopic follow-up campaigns needed to continue the exploration of Virgo's photometric and kinematic sub-structures, and will help the design of future searches for globular clusters in extragalactic systems. Equipped with this powerful new tool, future NGVS-IR investigations based on the uiK diagram will address the mapping and analysis of extended structures and compact stellar systems in and around Virgo galaxies.Comment: 23 pages, 18 figures. Accepted for publication in ApJ