Stringent Nucleotide Recognition by the Ribosome at the Middle Codon Position.

Accurate translation of the genetic code depends on mRNA:tRNA codon:anticodon base pairing. Here we exploit an emissive, isosteric adenosine surrogate that allows direct measurement of the kinetics of codon:anticodon University of California base formation during protein synthesis. Our results suggest that codon:anticodon base pairing is subject to tighter constraints at the middle position than at the 5'- and 3'-positions, and further suggest a sequential mechanism of formation of the three base pairs in the codon:anticodon helix

Transport Coefficients of the Yukawa One Component Plasma

We present equilibrium molecular-dynamics computations of the thermal conductivity and the two viscosities of the Yukawa one-component plasma. The simulations were performed within periodic boundary conditions and Ewald sums were implemented for the potentials, the forces, and for all the currents which enter the Kubo formulas. For large values of the screening parameter, our estimates of the shear viscosity and the thermal conductivity are in good agreement with the predictions of the Chapman-Enskog theory.Comment: 11 pages, 2 figure

QED can explain the non-thermal emission from SGRs and AXPs : Variability

Owing to effects arising from quantum electrodynamics (QED), magnetohydrodynamical fast modes of sufficient strength will break down to form electron-positron pairs while traversing the magnetospheres of strongly magnetised neutron stars. The bulk of the energy of the fast mode fuels the development of an electron-positron fireball. However, a small, but potentially observable, fraction of the energy ($\sim 10^{33}$ ergs) can generate a non-thermal distribution of electrons and positrons far from the star. This paper examines the cooling and radiative output of these particles. Small-scale waves may produce only the non-thermal emission. The properties of this non-thermal emission in the absence of a fireball match those of the quiescent, non-thermal radiation recently observed non-thermal emission from several anomalous X-ray pulsars and soft-gamma repeaters. Initial estimates of the emission as a function of angle indicate that the non-thermal emission should be beamed and therefore one would expect this emission to be pulsed as well. According to this model the pulsation of the non-thermal emission should be between 90 and 180 degrees out of phase from the thermal emission from the stellar surface.Comment: 7 pages, 5 figures, to appear in the proceedings of the conference "Isolated Neutron Stars: from the Interior to the Surface" (April 2006, London), eds. D. Page, R. Turolla, & S. Zane, Astrophysics & Space Scienc

Higher media multi-tasking activity is associated with smaller gray-matter density in the anterior cingulate cortex

Media multitasking, or the concurrent consumption of multiple media forms, is increasingly prevalent in today’s society and has been associated with negative psychosocial and cognitive impacts. Individuals who engage in heavier media-multitasking are found to perform worse on cognitive control tasks and exhibit more socio-emotional difficulties. However, the neural processes associated with media multi-tasking remain unexplored. The present study investigated relationships between media multitasking activity and brain structure. Research has demonstrated that brain structure can be altered upon prolonged exposure to novel environments and experience. Thus, we expected differential engagements in media multitasking to correlate with brain structure variability. This was confirmed via Voxel-Based Morphometry (VBM) analyses: Individuals with higher Media Multitasking Index (MMI) scores had smaller gray matter density in the anterior cingulate cortex (ACC). Functional connectivity between this ACC region and the precuneus was negatively associated with MMI. Our findings suggest a possible structural correlate for the observed decreased cognitive control performance and socio-emotional regulation in heavy media-multitaskers. While the cross-sectional nature of our study does not allow us to specify the direction of causality, our results brought to light novel associations between individual media multitasking behaviors and ACC structure differences

Thermal Density Functional Theory in Context

This chapter introduces thermal density functional theory, starting from the ground-state theory and assuming a background in quantum mechanics and statistical mechanics. We review the foundations of density functional theory (DFT) by illustrating some of its key reformulations. The basics of DFT for thermal ensembles are explained in this context, as are tools useful for analysis and development of approximations. We close by discussing some key ideas relating thermal DFT and the ground state. This review emphasizes thermal DFT's strengths as a consistent and general framework.Comment: Submitted to Spring Verlag as chapter in "Computational Challenges in Warm Dense Matter", F. Graziani et al. ed

Cryo-EM structure of the small subunit of the mammalian mitochondrial ribosome

The mitochondrial ribosome (mitoribosome) is a macromolecular complex that plays a central role in mitochondrial protein synthesis. Its small subunit is involved directly in the recruitment and decoding of mitochondrial mRNAs. Defects in mitochondrial translation, including mutations in components of the mitoribosome, are known to cause numerous human genetic diseases. Thus, knowledge of the molecular architecture of the mitoribosome is essential for a better understanding of those diseases and of the process of translation. To our knowledge, this article describes the first detailed cryo-EM structure of the small subunit of the mammalian mitoribosome. The study provides important clues about the evolution of this macromolecular complex and reveals unique structural features that could be important in the translation of the unusual mitochondrial mRNAs

A Computational Investigation on the Connection between Dynamics Properties of Ribosomal Proteins and Ribosome Assembly

Assembly of the ribosome from its protein and RNA constituents has been studied extensively over the past 50 years, and experimental evidence suggests that prokaryotic ribosomal proteins undergo conformational changes during assembly. However, to date, no studies have attempted to elucidate these conformational changes. The present work utilizes computational methods to analyze protein dynamics and to investigate the linkage between dynamics and binding of these proteins during the assembly of the ribosome. Ribosomal proteins are known to be positively charged and we find the percentage of positive residues in r-proteins to be about twice that of the average protein: Lys+Arg is 18.7% for E. coli and 21.2% for T. thermophilus. Also, positive residues constitute a large proportion of RNA contacting residues: 39% for E. coli and 46% for T. thermophilus. This affirms the known importance of charge-charge interactions in the assembly of the ribosome. We studied the dynamics of three primary proteins from E. coli and T. thermophilus 30S subunits that bind early in the assembly (S15, S17, and S20) with atomic molecular dynamic simulations, followed by a study of all r-proteins using elastic network models. Molecular dynamics simulations show that solvent-exposed proteins (S15 and S17) tend to adopt more stable solution conformations than an RNA-embedded protein (S20). We also find protein residues that contact the 16S rRNA are generally more mobile in comparison with the other residues. This is because there is a larger proportion of contacting residues located in flexible loop regions. By the use of elastic network models, which are computationally more efficient, we show that this trend holds for most of the 30S r-proteins

Can Social Policies Improve Health? A Systematic Review and Meta-Analysis of 38 Randomized Trials.

Policy Points Social policies might not only improve economic well-being, but also health. Health policy experts have therefore advocated for investments in social policies both to improve population health and potentially reduce health system costs. Since the 1960s, a large number of social policies have been experimentally evaluated in the United States. Some of these experiments include health outcomes, providing a unique opportunity to inform evidence-based policymaking. Our comprehensive review and meta-analysis of these experiments find suggestive evidence of health benefits associated with investments in early life, income support, and health insurance interventions. However, most studies were underpowered to detect health outcomes. CONTEXT: Insurers and health care providers are investing heavily in nonmedical social interventions in an effort to improve health and potentially reduce health care costs. METHODS: We performed a systematic review and meta-analysis of all known randomized social experiments in the United States that included health outcomes. We reviewed 5,880 papers, reports, and data sources, ultimately including 61 publications from 38 randomized social experiments. After synthesizing the main findings narratively, we conducted risk of bias analyses, power analyses, and random-effects meta-analyses where possible. Finally, we used multivariate regressions to determine which study characteristics were associated with statistically significant improvements in health outcomes. FINDINGS: The risk of bias was low in 17 studies, moderate in 11, and high in 33. Of the 451 parameter estimates reported, 77% were underpowered to detect health outcomes. Among adequately powered parameters, 49% demonstrated a significant health improvement, 44% had no effect on health, and 7% were associated with significant worsening of health. In meta-analyses, early life and education interventions were associated with a reduction in smoking (odds ratio [OR] = 0.92, 95% confidence interval [CI] 0.86-0.99). Income maintenance and health insurance interventions were associated with significant improvements in self-rated health (OR = 1.20, 95% CI 1.06-1.36, and OR = 1.38, 95% CI 1.10-1.73, respectively), whereas some welfare-to-work interventions had a negative impact on self-rated health (OR = 0.77, 95% CI 0.66-0.90). Housing and neighborhood trials had no effect on the outcomes included in the meta-analyses. A positive effect of the trial on its primary socioeconomic outcome was associated with higher odds of reporting health improvements. We found evidence of publication bias for studies with null findings. CONCLUSIONS: Early life, income, and health insurance interventions have the potential to improve health. However, many of the included studies were underpowered to detect health effects and were at high or moderate risk of bias. Future social policy experiments should be better designed to measure the association between interventions and health outcomes

A-Site Residues Move Independently from P-Site Residues in all-Atom Molecular Dynamics Simulations of the 70S Bacterial Ribosome

The ribosome is a large macromolecular machine, and correlated motion between residues is necessary for coordinating function across multiple protein and RNA chains. We ran two all-atom, explicit solvent molecular dynamics simulations of the bacterial ribosome and calculated correlated motion between residue pairs by using mutual information. Because of the short timescales of our simulation (ns), we expect that dynamics are largely local fluctuations around the crystal structure. We hypothesize that residues that show coupled dynamics are functionally related, even on longer timescales. We validate our model by showing that crystallographic B-factors correlate well with the entropy calculated as part of our mutual information calculations. We reveal that A-site residues move relatively independently from P-site residues, effectively insulating A-site functions from P-site functions during translation