Atomic Structures of the 30S Subunit and Its Complexes with Ligands and Antibiotics

The two subunits that make up the ribosome have both distinct and cooperative functions. The 30S ribosomal subunit binds messenger RNA (mRNA) and is involved in the selection of cognate transfer RNA (tRNA) by monitoring codon–anticodon base-pairing during the decoding process. The 50S subunit catalyzes peptide-bond formation. Both subunits work in concert to move tRNAs and mRNAs relative to the ribosome in translocation, and both are the target of a large number of naturally occurring antibiotics. Thus, useful information about the mechanism of translation can be gleaned from structures of both individual subunits and the intact ribosome. In this paper, we describe our work on the determination of the atomic structure of the 30S ribosomal subunit and its complexes with RNA ligands, antibiotics, and initiation factor IF1. The results provide structural insights into how the ribosome recognizes cognate tRNA and discriminates against near-cognate tRNA. They also provide a structural basis for understanding the action of various antibiotics that target the 30S subunit

Atomic Structures of the 30S Subunit and Its Complexes with Ligands and Antibiotics

The two subunits that make up the ribosome have both distinct and cooperative functions. The 30S ribosomal subunit binds messenger RNA (mRNA) and is involved in the selection of cognate transfer RNA (tRNA) by monitoring codon–anticodon base-pairing during the decoding process. The 50S subunit catalyzes peptide-bond formation. Both subunits work in concert to move tRNAs and mRNAs relative to the ribosome in translocation, and both are the target of a large number of naturally occurring antibiotics. Thus, useful information about the mechanism of translation can be gleaned from structures of both individual subunits and the intact ribosome. In this paper, we describe our work on the determination of the atomic structure of the 30S ribosomal subunit and its complexes with RNA ligands, antibiotics, and initiation factor IF1. The results provide structural insights into how the ribosome recognizes cognate tRNA and discriminates against near-cognate tRNA. They also provide a structural basis for understanding the action of various antibiotics that target the 30S subunit

Planck 2013 results. XXII. Constraints on inflation

We analyse the implications of the Planck data for cosmic inflation. The Planck nominal mission temperature anisotropy measurements, combined with the WMAP large-angle polarization, constrain the scalar spectral index to be ns = 0:9603 _ 0:0073, ruling out exact scale invariance at over 5_: Planck establishes an upper bound on the tensor-to-scalar ratio of r < 0:11 (95% CL). The Planck data thus shrink the space of allowed standard inflationary models, preferring potentials with V00 < 0. Exponential potential models, the simplest hybrid inflationary models, and monomial potential models of degree n _ 2 do not provide a good fit to the data. Planck does not find statistically significant running of the scalar spectral index, obtaining dns=dln k = 0:0134 _ 0:0090. We verify these conclusions through a numerical analysis, which makes no slowroll approximation, and carry out a Bayesian parameter estimation and model-selection analysis for a number of inflationary models including monomial, natural, and hilltop potentials. For each model, we present the Planck constraints on the parameters of the potential and explore several possibilities for the post-inflationary entropy generation epoch, thus obtaining nontrivial data-driven constraints. We also present a direct reconstruction of the observable range of the inflaton potential. Unless a quartic term is allowed in the potential, we find results consistent with second-order slow-roll predictions. We also investigate whether the primordial power spectrum contains any features. We find that models with a parameterized oscillatory feature improve the fit by __2 e_ _ 10; however, Bayesian evidence does not prefer these models. We constrain several single-field inflation models with generalized Lagrangians by combining power spectrum data with Planck bounds on fNL. Planck constrains with unprecedented accuracy the amplitude and possible correlation (with the adiabatic mode) of non-decaying isocurvature fluctuations. The fractional primordial contributions of cold dark matter (CDM) isocurvature modes of the types expected in the curvaton and axion scenarios have upper bounds of 0.25% and 3.9% (95% CL), respectively. In models with arbitrarily correlated CDM or neutrino isocurvature modes, an anticorrelated isocurvature component can improve the _2 e_ by approximately 4 as a result of slightly lowering the theoretical prediction for the ` <_ 40 multipoles relative to the higher multipoles. Nonetheless, the data are consistent with adiabatic initial conditions

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

Alterations in voltage-sensing of the mitochondrial permeability transition pore in ANT1-deficient cells

The probability of mitochondrial permeability transition (mPT) pore opening is inversely related to the magnitude of the proton electrochemical gradient. The module conferring sensitivity of the pore to this gradient has not been identified. We investigated mPT's voltage-sensing properties elicited by calcimycin or H2O2 in human fibroblasts exhibiting partial or complete lack of ANT1 and in C2C12 myotubes with knocked-down ANT1 expression. mPT onset was assessed by measuring in situ mitochondrial volume using the 'thinness ratio' and the 'cobalt-calcein' technique. De-energization hastened calcimycin-induced swelling in control and partially-expressing ANT1 fibroblasts, but not in cells lacking ANT1, despite greater losses of mitochondrial membrane potential. Matrix Ca(2+) levels measured by X-rhod-1 or mitochondrially-targeted ratiometric biosensor 4mtD3cpv, or ADP-ATP exchange rates did not differ among cell types. ANT1-null fibroblasts were also resistant to H2O2-induced mitochondrial swelling. Permeabilized C2C12 myotubes with knocked-down ANT1 exhibited higher calcium uptake capacity and voltage-thresholds of mPT opening inferred from cytochrome c release, but intact cells showed no differences in calcimycin-induced onset of mPT, irrespective of energization and ANT1 expression, albeit the number of cells undergoing mPT increased less significantly upon chemically-induced hypoxia than control cells. We conclude that ANT1 confers sensitivity of the pore to the electrochemical gradient

Alterations in voltage-sensing of the mitochondrial permeability transition pore in ANT1-deficient cells

The probability of mitochondrial permeability transition (mPT) pore opening is inversely related to the magnitude of the proton electrochemical gradient. The module conferring sensitivity of the pore to this gradient has not been identified. We investigated mPT's voltage-sensing properties elicited by calcimycin or H2O2 in human fibroblasts exhibiting partial or complete lack of ANT1 and in C2C12 myotubes with knocked-down ANT1 expression. mPT onset was assessed by measuring in situ mitochondrial volume using the 'thinness ratio' and the 'cobalt-calcein' technique. De-energization hastened calcimycin-induced swelling in control and partially-expressing ANT1 fibroblasts, but not in cells lacking ANT1, despite greater losses of mitochondrial membrane potential. Matrix Ca(2+) levels measured by X-rhod-1 or mitochondrially-targeted ratiometric biosensor 4mtD3cpv, or ADP-ATP exchange rates did not differ among cell types. ANT1-null fibroblasts were also resistant to H2O2-induced mitochondrial swelling. Permeabilized C2C12 myotubes with knocked-down ANT1 exhibited higher calcium uptake capacity and voltage-thresholds of mPT opening inferred from cytochrome c release, but intact cells showed no differences in calcimycin-induced onset of mPT, irrespective of energization and ANT1 expression, albeit the number of cells undergoing mPT increased less significantly upon chemically-induced hypoxia than control cells. We conclude that ANT1 confers sensitivity of the pore to the electrochemical gradient

Planck 2015 results. V. LFI calibration

We present a description of the pipeline used to calibrate the Planck Low Frequency Instrument (LFI) timelines into thermodynamic temperatures for the Planck 2015 data release, covering four years of uninterrupted operations. As in the 2013 data release, our calibrator is provided by the spin-synchronous modulation of the cosmic microwave background dipole, but we now use the orbital component, rather than adopting the Wilkinson Microwave Anisotropy Probe (WMAP) solar dipole. This allows our 2015 LFI analysis to provide an independent Solar dipole estimate, which is in excellent agreement with that of HFI and within 1σ (0.3% in amplitude) of the WMAP value. This 0.3% shift in the peak-to-peak dipole temperature from WMAP and a general overhaul of the iterative calibration code increases the overall level of the LFI maps by 0.45% (30 GHz), 0.64% (44 GHz), and 0.82% (70 GHz) in temperature with respect to the 2013 Planck data release, thus reducing the discrepancy with the power spectrum measured by WMAP. We estimate that the LFI calibration uncertainty is now at the level of 0.20% for the 70 GHz map, 0.26% for the 44 GHz map, and 0.35% for the 30 GHz map. We provide a detailed description of the impact of all the changes implemented in the calibration since the previous data release

Planck 2015 results. IV. Low Frequency Instrument beams and window functions

This paper presents the characterization of the in-flight beams, the beam window functions, and the associated uncertainties for the Planck Low Frequency Instrument (LFI). The structure of the paper is similar to that presented in the 2013 Planck release; the main differences concern the beam normalization and the delivery of the window functions to be used for polarization analysis. The in-flight assessment of the LFI main beams relies on measurements performed during observations of Jupiter. By stacking data from seven Jupiter transits, the main beam profiles are measured down to –25 dB at 30 and 44 GHz, and down to –30 dB at 70 GHz. It has been confirmed that the agreement between the simulated beams and the measured beams is better than 1% at each LFI frequency band (within the 20 dB contour from the peak, the rms values are 0.1% at 30 and 70 GHz; 0.2% at 44 GHz). Simulated polarized beams are used for the computation of the effective beam window functions. The error budget for the window functions is estimated from both main beam and sidelobe contributions, and accounts for the radiometer band shapes. The total uncertainties in the effective beam window functions are 0.7% and 1% at 30 and 44 GHz, respectively (at ℓ ≈ 600); and 0.5% at 70 GHz (at ℓ ≈ 1000)

Planck 2013 results. IX. HFI spectral response

The Planck High Frequency Instrument (HFI) spectral response was determined through a series of ground based tests conducted with the HFI focal plane in a cryogenic environment prior to launch. The main goal of the spectral transmission tests was to measure the relative spectral response (including out-of-band signal rejection) of all HFI detectors. This was determined by measuring the output of a continuously scanned Fourier transform spectrometer coupled with all HFI detectors. As there is no on-board spectrometer within HFI, the ground-based spectral response experiments provide the definitive data set for the relative spectral calibration of the HFI. The spectral response of the HFI is used in Planck data analysis and component separation, this includes extraction of CO emission observed within Planck bands, dust emission, Sunyaev-Zeldovich sources, and intensity to polarization leakage. The HFI spectral response data have also been used to provide unit conversion and colour correction analysis tools. Verifications of the HFI spectral response data are provided through comparisons with photometric HFI flight data. This validation includes use of HFI zodiacal emission observations to demonstrate out-of-band spectral signal rejection better than 10^8. The accuracy of the HFI relative spectral response data is verified through comparison with complementary flight-data based unit conversion coefficients and colour correction coefficients. These coefficients include those based upon HFI observations of CO, dust, and Sunyaev-Zeldovich emission. General agreement is observed between the ground-based spectral characterization of HFI and corresponding in-flight observations, within the quoted uncertainty of each; explanations are provided for any discrepancies.Comment: 27 pages, 28 figures, one of the papers associated with the 2013 Planck data releas