Differentiation and fiber type-specific activity of a muscle creatine kinase intronic enhancer

Background: Hundreds of genes, including muscle creatine kinase (MCK), are differentially expressed in fast- and slow-twitch muscle fibers, but the fiber type-specific regulatory mechanisms are not well understood. Results: Modulatory region 1 (MR1) is a 1-kb regulatory region within MCK intron 1 that is highly active in terminally differentiating skeletal myocytes in vitro. A MCK small intronic enhancer (MCK-SIE) containing a paired E-box/myocyte enhancer factor 2 (MEF2) regulatory motif resides within MR1. The SIE's transcriptional activity equals that of the extensively characterized 206-bp MCK 5'-enhancer, but the MCK-SIE is flanked by regions that can repress its activity via the individual and combined effects of about 15 different but highly conserved 9- to 24-bp sequences. ChIP and ChIP-Seq analyses indicate that the SIE and the MCK 5'-enhancer are occupied by MyoD, myogenin and MEF2. Many other E-boxes located within or immediately adjacent to intron 1 are not occupied by MyoD or myogenin. Transgenic analysis of a 6.5-kb MCK genomic fragment containing the 5'-enhancer and proximal promoter plus the 3.2-kb intron 1, with and without MR1, indicates that MR1 is critical for MCK expression in slow- and intermediate-twitch muscle fibers (types I and IIa, respectively), but is not required for expression in fast-twitch muscle fibers (types IIb and IId). Conclusions: In this study, we discovered that MR1 is critical for MCK expression in slow- and intermediate-twitch muscle fibers and that MR1's positive transcriptional activity depends on a paired E-box MEF2 site motif within a SIE. This is the first study to delineate the DNA controls for MCK expression in different skeletal muscle fiber types

Consistency of cosmic microwave background temperature measurements in three frequency bands in the 2500-square-degree SPT-SZ survey

We present an internal consistency test of South Pole Telescope (SPT) measurements of the cosmic microwave background (CMB) temperature anisotropy using three-band data from the SPT-SZ survey. These measurements are made from observations of ~2500 deg^2 of sky in three frequency bands centered at 95, 150, and 220 GHz. We combine the information from these three bands into six semi-independent estimates of the CMB power spectrum (three single-frequency power spectra and three cross-frequency spectra) over the multipole range 650 < l < 3000. We subtract an estimate of foreground power from each power spectrum and evaluate the consistency among the resulting CMB-only spectra. We determine that the six foreground-cleaned power spectra are consistent with the null hypothesis, in which the six cleaned spectra contain only CMB power and noise. A fit of the data to this model results in a chi-squared value of 236.3 for 235 degrees of freedom, and the probability to exceed this chi-squared value is 46%.Comment: 21 pages, 4 figures, current version matches version published in JCA

A Comparison of Maps and Power Spectra Determined from South Pole Telescope and Planck Data

We study the consistency of 150 GHz data from the South Pole Telescope (SPT) and 143 GHz data from the Planck satellite over the patch of sky covered by the SPT-SZ survey. We first visually compare the maps and find that the residuals appear consistent with noise after accounting for differences in angular resolution and filtering. We then calculate (1) the cross-spectrum between two independent halves of SPT data, (2) the cross-spectrum between two independent halves of Planck data, and (3) the cross-spectrum between SPT and Planck data. We find the three cross-spectra are well-fit (PTE = 0.30) by the null hypothesis in which both experiments have measured the same sky map up to a single free calibration parameter---i.e., we find no evidence for systematic errors in either data set. As a by-product, we improve the precision of the SPT calibration by nearly an order of magnitude, from 2.6% to 0.3% in power. Finally, we compare all three cross-spectra to the full-sky Planck power spectrum and find marginal evidence for differences between the power spectra from the SPT-SZ footprint and the full sky. We model these differences as a power law in spherical harmonic multipole number. The best-fit value of this tilt is consistent among the three cross-spectra in the SPT-SZ footprint, implying that the source of this tilt is a sample variance fluctuation in the SPT-SZ region relative to the full sky. The consistency of cosmological parameters derived from these datasets is discussed in a companion paper.Comment: 15 pages, 9 figures. Published in The Astrophysical Journal. Current arxiv version matches published versio

A Comparison of Cosmological Parameters Determined from CMB Temperature Power Spectra from the South Pole Telescope and the Planck Satellite

The Planck cosmic microwave background (CMB) temperature data are best fit with a LCDM model that is in mild tension with constraints from other cosmological probes. The South Pole Telescope (SPT) 2540 $\text{deg}^2$ SPT-SZ survey offers measurements on sub-degree angular scales (multipoles $650 \leq \ell \leq 2500$) with sufficient precision to use as an independent check of the Planck data. Here we build on the recent joint analysis of the SPT-SZ and Planck data in \citet{hou17} by comparing LCDM parameter estimates using the temperature power spectrum from both data sets in the SPT-SZ survey region. We also restrict the multipole range used in parameter fitting to focus on modes measured well by both SPT and Planck, thereby greatly reducing sample variance as a driver of parameter differences and creating a stringent test for systematic errors. We find no evidence of systematic errors from such tests. When we expand the maximum multipole of SPT data used, we see low-significance shifts in the angular scale of the sound horizon and the physical baryon and cold dark matter densities, with a resulting trend to higher Hubble constant. When we compare SPT and Planck data on the SPT-SZ sky patch to Planck full-sky data but keep the multipole range restricted, we find differences in the parameters $n_s$ and $A_se^{-2\tau}$. We perform further checks, investigating instrumental effects and modeling assumptions, and we find no evidence that the effects investigated are responsible for any of the parameter shifts. Taken together, these tests reveal no evidence for systematic errors in SPT or Planck data in the overlapping sky coverage and multipole range and, at most, weak evidence for a breakdown of LCDM or systematic errors influencing either the Planck data outside the SPT-SZ survey area or the SPT data at $\ell >2000$.Comment: 14 pages, 7 figures. Updated 1 figure and expanded on the reasoning for fixing the affect of lensing on the power spectrum instead of varying Alen

Genetic Regulation of Zfp30, CXCL1, and Neutrophilic Inflammation in Murine Lung

Allergic asthma is a complex disease characterized in part by granulocytic inflammation of the airways. In addition to eosinophils, neutrophils (PMN) are also present, particularly in cases of severe asthma. We sought to identify the genetic determinants of neutrophilic inflammation in a mouse model of house dust mite (HDM)-induced asthma. We applied an HDM model of allergic asthma to the eight founder strains of the Collaborative Cross (CC) and 151 incipient lines of the CC (preCC). Lung lavage fluid was analyzed for PMN count and the concentration of CXCL1, a hallmark PMN chemokine. PMN and CXCL1 were strongly correlated in preCC mice. We used quantitative trait locus (QTL) mapping to identify three variants affecting PMN, one of which colocalized with a QTL for CXCL1 on chromosome (Chr) 7. We used lung eQTL data to implicate a variant in the gene Zfp30 in the CXCL1/PMN response. This genetic variant regulates both CXCL1 and PMN by altering Zfp30 expression, and we model the relationships between the QTL and these three endophenotypes. We show that Zfp30 is expressed in airway epithelia in the normal mouse lung and that altering Zfp30 expression in vitro affects CXCL1 responses to an immune stimulus. Our results provide strong evidence that Zfp30 is a novel regulator of neutrophilic airway inflammation

Ecological Invasion, Roughened Fronts, and a Competitor's Extreme Advance: Integrating Stochastic Spatial-Growth Models

Both community ecology and conservation biology seek further understanding of factors governing the advance of an invasive species. We model biological invasion as an individual-based, stochastic process on a two-dimensional landscape. An ecologically superior invader and a resident species compete for space preemptively. Our general model includes the basic contact process and a variant of the Eden model as special cases. We employ the concept of a "roughened" front to quantify effects of discreteness and stochasticity on invasion; we emphasize the probability distribution of the front-runner's relative position. That is, we analyze the location of the most advanced invader as the extreme deviation about the front's mean position. We find that a class of models with different assumptions about neighborhood interactions exhibit universal characteristics. That is, key features of the invasion dynamics span a class of models, independently of locally detailed demographic rules. Our results integrate theories of invasive spatial growth and generate novel hypotheses linking habitat or landscape size (length of the invading front) to invasion velocity, and to the relative position of the most advanced invader.Comment: The original publication is available at www.springerlink.com/content/8528v8563r7u2742

Improving Cosmological Constraints from Galaxy Cluster Number Counts with CMB-cluster-lensing Data: Results from the SPT-SZ Survey and Forecasts for the Future

We show the improvement to cosmological constraints from galaxy cluster surveys with the addition of cosmic microwave background (CMB)-cluster lensing data. We explore the cosmological implications of adding mass information from the 3.1 sigma detection of gravitational lensing of the CMB by galaxy clusters to the Sunyaev-Zel'dovich (SZ) selected galaxy cluster sample from the 2500 deg(2) SPT-SZ survey and targeted optical and X-ray follow-up data. In the ACDM model, the combination of the cluster sample with the Planck power spectrum measurements prefers sigma(8) (Omega(m)/0.3)(0.5) = 0.831 +/- 0.020. Adding the cluster data reduces the uncertainty on this quantity by a factor of 1.4, which is unchanged whether the 3.1 sigma CMB-cluster lensing measurement is included or not. We then forecast the impact of CMB-cluster lensing measurements with future cluster catalogs. Adding CMB-cluster lensing measurements to the SZ cluster catalog of the ongoing SPT-3G survey is expected to improve the expected constraint on the dark energy equation of state w by a factor of 1.3 to sigma(w) = 0.19. We find the largest improvements from CMB-cluster lensing measurements to be for sigma(8), where adding CMB-cluster lensing data to the cluster number counts reduces the expected uncertainty on sigma(8) by respective factors of 2.4 and 3.6 for SPT-3G and CMB-S4

Maps of the Southern Millimeter-wave Sky from Combined 2500 deg2^2 SPT-SZ and Planck Temperature Data

We present three maps of the millimeter-wave sky created by combining data from the South Pole Telescope (SPT) and the Planck satellite. We use data from the SPT-SZ survey, a survey of 2540 deg$^2$ of the the sky with arcminute resolution in three bands centered at 95, 150, and 220 GHz, and the full-mission Planck temperature data in the 100, 143, and 217 GHz bands. A linear combination of the SPT-SZ and Planck data is computed in spherical harmonic space, with weights derived from the noise of both instruments. This weighting scheme results in Planck data providing most of the large-angular-scale information in the combined maps, with the smaller-scale information coming from SPT-SZ data. A number of tests have been done on the maps. We find their angular power spectra to agree very well with theoretically predicted spectra and previously published results.Comment: 21 pages, 12 figure