Effect of Correlated TRAN Abundances on Translation Errors and Evolution of Codon Usage Bias

Abstract Despite the fact that tRNA abundances are thought to play a major role in determining translation error rates, their distribution across the genetic code and the resulting implications have received little attention. In general, studies of codon usage bias (CUB) assume that codons with higher tRNA abundance have lower missense error rates. Using a model of protein translation based on tRNA competition and intra-ribosomal kinetics, we show that this assumption can be violated when tRNA abundances are positively correlated across the genetic code. Examining the distribution of tRNA abundances across 73 bacterial genomes from 20 different genera, we find a consistent positive correlation between tRNA abundances across the genetic code. This work challenges one of the fundamental assumptions made in over 30 years of research on CUB that codons with higher tRNA abundances have lower missense error rates and that missense errors are the primary selective force responsible for CUB. Author Summary Codon usage bias (CUB) is a ubiquitous and important phenomenon. CUB is thought to be driven primarily due to selection against missense errors. For over 30 years, the standard model of translation errors has implicitly assumed that the relationship between translation errors and tRNA abundances are inversely related. This is based on an implicit and unstated assumption that the distribution of tRNA abundances across the genetic code are uncorrelated. Examining these abundance distributions across 73 bacterial genomes from 20 different genera, we find a consistent positive correlation between tRNA abundances across the genetic code. We further show that codons with higher tRNA abundances are not always “optimal” with respect to reducing the missense error rate and hence cannot explain the observed patterns of CUB. DOI: 10.1371/journal.pgen.100112

Distance measures to compare real and ideal quantum processes

With growing success in experimental implementations it is critical to identify a "gold standard" for quantum information processing, a single measure of distance that can be used to compare and contrast different experiments. We enumerate a set of criteria such a distance measure must satisfy to be both experimentally and theoretically meaningful. We then assess a wide range of possible measures against these criteria, before making a recommendation as to the best measures to use in characterizing quantum information processing.Comment: 15 pages; this version in line with published versio

A Check on the Validity of Magnetic Field Reconstructions

We investigate a method to test whether a numerically computed model coronal magnetic field B departs from the divergence-free condition (also known as the solenoidality condition). The test requires a potential field B0 to be calculated, subject to Neumann boundary conditions, given by the normal components of the model field B at the boundaries. The free energy of the model field may be calculated using the volume integral of (B-B0)^2, where the integral is over the computational volume of the model field. A second estimate of the free energy is provided by calculating the difference between the volume integral of B^2 and the volume integral of B0^2. If B is divergence-free, the two estimates of the free energy should be the same. A difference between the two estimates indicates a departure from div B = 0 in the volume. The test is an implementation of a procedure proposed by Moraitis et al. (Sol. Phys. 289, 4453, 2014) and is a simpler version of the Helmholtz decomposition procedure presented by Valori et al. (Astron. Astrophys. 553, A38, 2013). We demonstrate the test in application to previously published nonlinear force-free model fields, and also investigate the influence on the results of the test of a departure from flux balance over the boundaries of the model field. Our results underline the fact that, to make meaningful statements about magnetic free energy in the corona, it is necessary to have model magnetic fields which satisfy the divergence-free condition to a good approximation.Australian Research Counci

Jurassic Redbeds of the Connecticut Valley: (1) Brownstones of the Portland Formation; and (2) Playa-Playa Lake-Oligomictic Lake Model for Parts of the East Berlin, Shuttle Meadow, and Portland Formations

Guidebook for field trips in Connecticut and south central Massachusetts: New England Intercollegiate Geological Conference 74th annual meeting, University of Connecticut, Storrs Connecticut , October 2 and 3, 1982: Trip M-

A practical scheme for quantum computation with any two-qubit entangling gate

Which gates are universal for quantum computation? Although it is well known that certain gates on two-level quantum systems (qubits), such as the controlled-not (CNOT), are universal when assisted by arbitrary one-qubit gates, it has only recently become clear precisely what class of two-qubit gates is universal in this sense. Here we present an elementary proof that any entangling two-qubit gate is universal for quantum computation, when assisted by one-qubit gates. A proof of this important result for systems of arbitrary finite dimension has been provided by J. L. and R. Brylinski [arXiv:quant-ph/0108062, 2001]; however, their proof relies upon a long argument using advanced mathematics. In contrast, our proof provides a simple constructive procedure which is close to optimal and experimentally practical [C. M. Dawson and A. Gilchrist, online implementation of the procedure described herein (2002), http://www.physics.uq.edu.au/gqc/].Comment: 3 pages, online implementation of procedure described can be found at http://www.physics.uq.edu.au/gqc

EFFECT OF IMPACT SURFACE ON EQUESTRIAN FALLS

This study examines the effect of impact surface on head kinematic response and maximum principal strain (MPS) for equestrian falls. A helmeted Hybrid Ill headform was dropped unrestrained onto three impact surfaces (steel, turf and sand) and three locations. Peak resultant linear acceleration, rotational acceleration and duration of the impact events were measured. A finite element brain model was used to calculate MPS. The results revealed that drops onto steel produced higher peak linear acceleration, rotational acceleration and MPS but lower impact durations than drops to turf and sand. However, despite lower MPS values, turf and sand impacts compared to steel impacts still represented a risk of concussion. This suggests that equestrian helmets standards do not properly account for the loading conditions experienced in equestrian accidents

Evidence for Finely-Regulated Asynchronous Growth of Toxoplasma gondii Cysts Based on Data-Driven Model Selection

Toxoplasma gondii establishes a chronic infection by forming cysts preferentially in the brain. This chronic infection is one of the most common parasitic infections in humans and can be reactivated to develop life-threatening toxoplasmic encephalitis in immunocompromised patients. Host-pathogen interactions during the chronic infection include growth of the cysts and their removal by both natural rupture and elimination by the immune system. Analyzing these interactions is important for understanding the pathogenesis of this common infection. We developed a differential equation framework of cyst growth and employed Akaike Information Criteria (AIC) to determine the growth and removal functions that best describe the distribution of cyst sizes measured from the brains of chronically infected mice. The AIC strongly support models in which T. gondii cysts grow at a constant rate such that the per capita growth rate of the parasite is inversely proportional to the number of parasites within a cyst, suggesting finely-regulated asynchronous replication of the parasites. Our analyses were also able to reject the models where cyst removal rate increases linearly or quadratically in association with increase in cyst size. The modeling and analysis framework may provide a useful tool for understanding the pathogenesis of infections with other cyst producing parasites

Transcriptional regulation of Caenorhabditis elegans FOXO/DAF-16 modulates lifespan

BACKGROUND: Insulin/IGF-1 signaling plays a central role in longevity across phylogeny. In C. elegans, the forkhead box O (FOXO) transcription factor, DAF-16, is the primary target of insulin/IGF-1 signaling, and multiple isoforms of DAF-16 (a, b, and d/f) modulate lifespan, metabolism, dauer formation, and stress resistance. Thus far, across phylogeny modulation of mammalian FOXOs and DAF-16 have focused on post-translational regulation with little focus on transcriptional regulation. In C. elegans, we have previously shown that DAF-16d/f cooperates with DAF-16a to promote longevity. In this study, we generated transgenic strains expressing near-endogenous levels of either daf-16a or daf-16d/f, and examined temporal expression of the isoforms to further define how these isoforms contribute to lifespan regulation. RESULTS: Here, we show that DAF-16a is sensitive both to changes in gene dosage and to alterations in the level of insulin/IGF-1 signaling. Interestingly, we find that as worms age, the intestinal expression of daf-16d/f but not daf-16a is dramatically upregulated at the level of transcription. Preventing this transcriptional upregulation shortens lifespan, indicating that transcriptional regulation of daf-16d/f promotes longevity. In an RNAi screen of transcriptional regulators, we identify elt-2 (GATA transcription factor) and swsn-1 (core subunit of SWI/SNF complex) as key modulators of daf-16d/f gene expression. ELT-2 and another GATA factor, ELT-4, promote longevity via both DAF-16a and DAF-16d/f while the components of SWI/SNF complex promote longevity specifically via DAF-16d/f. CONCLUSIONS: Our findings indicate that transcriptional control of C. elegans FOXO/daf-16 is an essential regulatory event. Considering the conservation of FOXO across species, our findings identify a new layer of FOXO regulation as a potential determinant of mammalian longevity and age-related diseases such as cancer and diabetes