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Chimeric Investigations into the Diamide Binding Site on the Lepidopteran Ryanodine Receptor

Alterations to amino acid residues G4946 and I4790, associated with resistance to diamide insecticides, suggests a location of diamide interaction within the pVSD voltage sensor-like domain of the insect ryanodine receptor (RyR). To further delineate the interaction site(s), targeted alterations were made within the same pVSD region on the diamondback moth (Plutella xylostella) RyR channel. The editing of five amino acid positions to match those found in the diamide insensitive skeletal RyR1 of humans (hRyR1) in order to generate a human−Plutella chimeric construct showed that these alterations strongly reduce diamide efficacy when introduced in combination but cause only minor reductions when introduced individually. It is concluded that the sites of diamide interaction on insect RyRs lie proximal to the voltage sensor-like domain of the RyR and that the main site of interaction is at residues K4700, Y4701, I4790 and S4919 in the S1 to S4 transmembrane domains

Diamide insecticide resistance in transgenic Drosophila and Sf9-cells expressing a full-length diamondback moth ryanodine receptor carrying an I4790M mutation

BACKGROUNDResistance to diamide insecticides in Lepidoptera is known to be caused primarily by amino acid changes on the ryanodine receptor (RyR). Recently, two new target site mutations, G4946V and I4790M, have emerged in populations of diamondback moth, Plutella xylostella, as well as in other lepidopteran species, and both mutations have been shown empirically to decrease diamide efficacy. Here, we quantify the impact of the I4790M mutation on diamide activation of the receptor, as compared to alterations at the G4946 locus.RESULTSI4790M when introduced into P. xylostella RyR expressed in an insect-derived Sf9 cell line was found to mediate just a ten-fold reduction in chlorantraniliprole efficacy (compared to 104- and 146-fold reductions for the G4946E and G4946V variants, respectively), whilst in the field its presence is associated with a ≥150-fold reduction. I4790M-mediated resistance to flubendiamide was estimated to be >24-fold. When the entire coding sequence of P. xylostella RyR was integrated into Drosophila melanogaster, the I4790M variant conferred ~4.4-fold resistance to chlorantraniliprole and 22-fold resistance to flubendiamide in the 3rd instar larvae, confirming that it imparts only a moderate level of resistance to diamide insecticides. Although the I4790M substitution appears to bear no fitness costs in terms of the flies' reproductive capacity, when assessed in a noncompetitive environment, it does, however, have potentially major impacts on mobility at both the larval and adult stages.CONCLUSIONSI4790M imparts only a moderate level of resistance to diamide insecticides and potentially confers significant fitness costs to the insect

Vertical integration and firm boundaries : the evidence

Since Ronald H. Coase's (1937) seminal paper, a rich set of theories has been developed that deal with firm boundaries in vertical or input–output structures. In the last twenty-five years, empirical evidence that can shed light on those theories also has been accumulating. We review the findings of empirical studies that have addressed two main interrelated questions: First, what types of transactions are best brought within the firm and, second, what are the consequences of vertical integration decisions for economic outcomes such as prices, quantities, investment, and profits. Throughout, we highlight areas of potential cross-fertilization and promising areas for future work

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 Measurement of the Cosmic Microwave Background Damping Tail from the 2500-square-degree SPT-SZ survey

We present a measurement of the cosmic microwave background (CMB) temperature power spectrum using data from the recently completed South Pole Telescope Sunyaev-Zel'dovich (SPT-SZ) survey. This measurement is made from observations of 2540 deg$^2$ of sky with arcminute resolution at $150\,$GHz, and improves upon previous measurements using the SPT by tripling the sky area. We report CMB temperature anisotropy power over the multipole range $650<\ell<3000$. We fit the SPT bandpowers, combined with the seven-year Wilkinson Microwave Anisotropy Probe (WMAP7) data, with a six-parameter LCDM cosmological model and find that the two datasets are consistent and well fit by the model. Adding SPT measurements significantly improves LCDM parameter constraints; in particular, the constraint on $\theta_s$ tightens by a factor of 2.7. The impact of gravitational lensing is detected at $8.1\, \sigma$, the most significant detection to date. This sensitivity of the SPT+WMAP7 data to lensing by large-scale structure at low redshifts allows us to constrain the mean curvature of the observable universe with CMB data alone to be $\Omega_k=-0.003^{+0.014}_{-0.018}$. Using the SPT+WMAP7 data, we measure the spectral index of scalar fluctuations to be $n_s=0.9623 \pm 0.0097$ in the LCDM model, a $3.9\,\sigma$ preference for a scale-dependent spectrum with $n_s<1$. The SPT measurement of the CMB damping tail helps break the degeneracy that exists between the tensor-to-scalar ratio $r$ and $n_s$ in large-scale CMB measurements, leading to an upper limit of $r<0.18$ (95%,C.L.) in the LCDM+$r$ model. Adding low-redshift measurements of the Hubble constant ($H_0$) and the baryon acoustic oscillation (BAO) feature to the SPT+WMAP7 data leads to further improvements. The combination of SPT+WMAP7+$H_0$+BAO constrains $n_s=0.9538 \pm 0.0081$ in the LCDM model, a $5.7\,\sigma$ detection of $n_s < 1$, ... [abridged]Comment: 21 pages, 10 figures. Replaced with version accepted by ApJ. Data products are available at http://pole.uchicago.edu/public/data/story12

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