Rapid Evolution of BRCA1 and BRCA2 in Humans and Other Primates

The maintenance of chromosomal integrity is an essential task of every living organism and cellular repair mechanisms exist to guard against insults to DNA. Given the importance of this process, it is expected that DNA repair proteins would be evolutionarily conserved, exhibiting very minimal sequence change over time. However, BRCA1, an essential gene involved in DNA repair, has been reported to be evolving rapidly despite the fact that many protein-altering mutations within this gene convey a significantly elevated risk for breast and ovarian cancers. Results: To obtain a deeper understanding of the evolutionary trajectory of BRCA1, we analyzed complete BRCA1 gene sequences from 23 primate species. We show that specific amino acid sites have experienced repeated selection for amino acid replacement over primate evolution. This selection has been focused specifically on humans and our closest living relatives, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus). After examining BRCA1 polymorphisms in 7 bonobo, 44 chimpanzee, and 44 rhesus macaque (Macaca mulatta) individuals, we find considerable variation within each of these species and evidence for recent selection in chimpanzee populations. Finally, we also sequenced and analyzed BRCA2 from 24 primate species and find that this gene has also evolved under positive selection. Conclusions: While mutations leading to truncated forms of BRCA1 are clearly linked to cancer phenotypes in humans, there is also an underlying selective pressure in favor of amino acid-altering substitutions in this gene. A hypothesis where viruses are the drivers of this natural selection is discussed.National Institutes of Health R01-GM-093086, 8U42OD011197-13National Science Foundation BCS-07115972Burroughs Wellcome FundMolecular Bioscience

10 New γ Doradus and δ Scuti Stars

We present high-resolution spectroscopy and precision photometry of five new γ Doradus and five new δ Scuti variables. The five new γ Doradus variables substantially increase the number of confirmed stars of this class. All 10 stars fall in the spectral class range F0–F2, but they are cleanly separated into two groups by their luminosity and photometric periods. However, the period gap between the γ Doradus and δ Scuti stars is becoming very narrow since we confirm that HD 155154 is a γ Doradus star with the shortest periods reported to date (the shortest of its four periods is ∼0.312 days). We do not find any evidence in our sample for stars exhibiting both δ Scuti– and γ Doradus–type pulsations

Wide-Field Chandra X-Ray Observations of AGN in Abell 85 & Abell 754

To better understand the mechanism or mechanisms that lead to AGN activity today, we measure the X-ray AGN fraction in a new sample of nearby clusters and examine how it varies with galaxy properties, projected cluster-centric radius, and cluster velocity dispersion. We present new wide-field Chandra X-ray Observatory observations of Abell 85, Abell 754 and the background cluster Abell 89B out to their virial radii. Out of seventeen X-ray sources associated with galaxies in these clusters, we classify seven as X-ray AGN with L_{X,B} > 10^{41} erg/s. Only two of these would be classified as AGN based on their optical spectra. We combine these observations with archival data to create a sample of X-ray AGN from six z < 0.08 clusters and find that 3.4+1.1/-0.8% of M_R 10^{41} erg/s. We find that more X-ray AGN are detected in more luminous galaxies and attribute this to larger spheriods in more luminous galaxies and increased sensitivity to lower Eddington-rate accretion from black holes in those spheroids. At a given X-ray luminosity limit, more massive black holes can be accreting less efficiently, yet still be detected. If interactions between galaxies are the principal drivers of AGN activity, then the AGN fraction should be higher in lower velocity dispersion clusters and the outskirts of clusters. However, the tendency of the most massive and early-type galaxies to lie in the centers of the richest clusters could dilute such trends. While we find no variation in the AGN fraction with projected cluster-centric radius, we do find that the AGN fraction increases significantly from 2.6+1.0/-0.8% in rich clusters to 10.0+6.2/-4.3% in those with lower velocity dispersions.Comment: Accepted by Astrophysical Journal, 17 pages using emulateapj.cls, 10 B & W Figures (degraded): Full resolution paper available at http://www.astronomy.ohio-state.edu/~sivakoff/AGN/XAGN_A85_A754.pd

Quantifying Grassland-to-Woodland Transitions and the Implications for Carbon and Nitrogen Dynamics in the Southwest United States

Replacement of grasslands and savannas by shrublands and woodlands has been widely reported in tropical, temperate and high-latitude rangelands worldwide (Archer 1994). These changes in vegetation structure may reflect historical shifts in climate and land use; and are likely to influence biodiversity, productivity, above- and below ground carbon and nitrogen sequestration and biophysical aspects of land surface-atmosphere interactions. The goal of our proposed research is to investigate how changes in the relative abundance of herbaceous and woody vegetation affect carbon and nitrogen dynamics across heterogeneous savannas and shrub/woodlands. By linking actual land-cover composition (derived through spectral mixture analysis of AVIRIS, TM, and AVHRR imagery) with a process-based ecosystem model, we will generate explicit predictions of the C and N storage in plants and soils resulting from changes in vegetation structure. Our specific objectives will be to (1) continue development and test applications of spectral mixture analysis across grassland-to-woodland transitions; (2) quantify temporal changes in plant and soil C and N storage and turnover for remote sensing and process model parameterization and verification; and (3) couple landscape fraction maps to an ecosystem simulation model to observe biogeochemical dynamics under changing landscape structure and climatological forcings

Receptor-Coupled Phosphoinositide Hydrolysis in Human Retinal Pigment Epithelium

Carbachol and histamine stimulated phosphoinositide (PPI) hydrolysis in cultured human retinal pigment epithelium (RPE), as reflected by an accumulation of 3 H-inositol phosphates in the presence of 10 m M Li + . Carbachol increased PPI hydrolysis to greater than 600% of basal with an EC 50 of 60 Μ M ; stimulation was linear up to 60 min. This activation likely occurred via the M 3 muscarinic cholinergic receptor based on the IC 50 values for 4-diphenylacetoxy- N -methylpiperidine methiodide (0.47 n M ), pirenzepine (280 n M ), and 11-[[2-[(diethylamino)methyl]-1-piperidinyl]-acetyl]-5,11-dihydro-6 H -pyrido[2,3- b ][1,4]benzodiazepin-6-one (1.4 Μ M ). Carbachol-mediated PPI hydrolysis was decreased by 80% in the absence of extracellular Ca 2+ . Histamine stimulated PPI turnover in a linear manner by 180% with an EC 50 of 20 Μ M by the H 1 histaminergic receptor. Serotonin, glutamate, norepinephrine, and dopamine were inactive. In human RPE, the resting cytoplasmic Ca 2+ concentration, as determined by fura-2 fluorescence, was 138 ± 24 n M . On the addition of carbachol, there was a 180% increase in peak intracellular Ca 2+ ; addition of histamine increased intracellular Ca 2+ by 187%. These results suggest receptor-mediated, inositol lipid hydrolysis is coupled to intracellular Ca 2+ flux in human RPE.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66430/1/j.1471-4159.1991.tb03471.x.pd

Stereotype Threat in Organizations: Implications for Equity and Performance

Abstract Over the past 20 years, a large body of laboratory and field research has shown that, when people perform in settings in which their group is negatively stereotyped, they may experience a phenomenon called stereotype threat that can undermine motivation and trust and cause underperformance. This review describes that research and places it into an organizational context. First, we describe the processes by which stereotype threat can impair outcomes among people in the workplace. Next, we delineate the situational cues in organizational settings that can exacerbate stereotype threat, and explain how and why these cues affect stereotyped individuals. Finally, we discuss relatively simple empirically based strategies that organizations can implement to reduce stereotype threat and create conditions in which employees and applicants from all groups can succeed

New Governance for Rural America: Creating Intergovernmental Partnerships

Throughout the 1990s public demand for a fundamental shift in the relationship between government and its citizens has intensified. In response, a new governance model has emerged, emphasizing decreased federal control in favor of intergovernmental collaboration and increased involvement of state, local, and private agencies. As the authors of this volume show, one of the best examples of new governance can be found in the National and State Rural Development Councils (NRDC and SRDC), created in 1990 as the result of President Bush\u27s Rural Development Initiative and now called the Rural Development Partnership. This effort was part of a move within policymaking circles to redefine a rural America that was no longer synonymous with family farming and that required innovative new solutions for economic revival. By 1994 twenty-nine states had created and ten other states were in the process of forming such councils. In this first detailed analysis of the NRDC and SRDCs, the authors examine the successes and failures of the original eight councils in Kansas, Maine, Mississippi, Oregon, South Carolina, South Dakota, Texas, and Washington; as well as eight other councils subsequently created in Iowa, New Mexico, North Carolina, Vermont, New York, North Dakota, Utah, and Wyoming. Combining empirical analysis with current theories about networks and inter-organizational relations, this volume should appeal to academics and practitioners interested in rural development policy, public administration, public policy and management, and intergovernmental relations. Description Beryl A. Radin is professor of Public Administration and Policy in the Graduate School of Public Affairs at Rockefeller College of the State University of New York at Albany. This Kansas Open Books title is funded by a grant from the National Endowment for the Humanities and the Andrew W. Mellon Foundation Humanities Open Book Program.https://digitalcommons.pittstate.edu/kansas_open_books/1051/thumbnail.jp

Evaluation of the Emergency Response Dose Assessment System(ERDAS)

The emergency response dose assessment system (ERDAS) is a protype software and hardware system configured to produce routine mesoscale meteorological forecasts and enhanced dispersion estimates on an operational basis for the Kennedy Space Center (KSC)/Cape Canaveral Air Station (CCAS) region. ERDAS provides emergency response guidance to operations at KSC/CCAS in the case of an accidental hazardous material release or an aborted vehicle launch. This report describes the evaluation of ERDAS including: evaluation of sea breeze predictions, comparison of launch plume location and concentration predictions, case study of a toxic release, evaluation of model sensitivity to varying input parameters, evaluation of the user interface, assessment of ERDA's operational capabilities, and a comparison of ERDAS models to the ocean breeze dry gultch diffusion model

Scalar brane backgrounds in higher order curvature gravity

We investigate maximally symmetric brane world solutions with a scalar field. Five-dimensional bulk gravity is described by a general lagrangian which yields field equations containing no higher than second order derivatives. This includes the Gauss-Bonnet combination for the graviton. Stability and gravitational properties of such solutions are considered, and we particularily emphasise the modifications induced by the higher order terms. In particular it is shown that higher curvature corrections to Einstein theory can give rise to instabilities in brane world solutions. A method for analytically obtaining the general solution for such actions is outlined. Genericaly, the requirement of a finite volume element together with the absence of a naked singularity in the bulk imposes fine-tuning of the brane tension. A model with a moduli scalar field is analysed in detail and we address questions of instability and non-singular self-tuning solutions. In particular, we discuss a case with a normalisable zero mode but infinite volume element.Comment: published versio

Effectiveness of measures to eradicate Staphylococcus aureus carriage in patients with community-associated skin and soft-tissue infections: A randomized trial

BACKGROUND: Despite a paucity of evidence, decolonization measures are prescribed for outpatients with recurrent Staphylococcus aureus skin and soft tissue infections (SSTI). OBJECTIVE: Compare the effectiveness of four regimens for eradicating S. aureus carriage. DESIGN: Open-label, randomized controlled trial. Colonization status and recurrent SSTI were ascertained at one and four months. SETTING: Barnes-Jewish and St. Louis Children’s Hospitals, St. Louis, Missouri, 2007–2009. PARTICIPANTS: Three hundred patients with community-onset SSTI and S. aureus colonization in the nares, axilla, or inguinal folds. INTERVENTIONS: Participants were randomized to receive no therapeutic intervention (controls) or perform one of three 5-day regimens: 2% mupirocin ointment applied to the nares twice daily, intranasal mupirocin plus daily 4% chlorhexidine body washes, or intranasal mupirocin plus daily dilute bleach water baths. RESULTS: Among 244 participants with one-month colonization data, modified intention-to-treat analysis revealed S. aureus eradication in 38% of participants in the education only (control) group; 56% in the mupirocin group (p=0.03 vs. controls); 55% in the mupirocin/chlorhexidine group (p=0.05); and 63% in the mupirocin/bleach group (p=0.006). Of 229 participants with four-month colonization data, eradication rates were 48% in controls; 56% for mupirocin only (p=0.40 vs. controls); 54% for mupirocin/chlorhexidine (p=0.51); and 71% for mupirocin/bleach (p=0.02). At one and four months, respectively, recurrent SSTI was reported by 20% and 36% of participants. CONCLUSIONS: An inexpensive regimen of dilute bleach baths, intranasal mupirocin, and hygiene education effectively eradicated S. aureus over four months. High rates of recurrent SSTI suggest factors other than endogenous colonization as important determinants of infection