Duplex formation between the template and the nascent strand in the transcription-regulating sequences determines the site of template switching in SARS – CoV-2

2020 ◽  
Author(s):  
Aaron R. D’souza ◽  
Amanda Buckingham ◽  
Fanny Salasc ◽  
Carin Ingemarsdotter ◽  
Gennaro Iaconis ◽  
...  
Keyword(s):  
Leader Sequence ◽  
Template Switching ◽  
Subgenomic Rna ◽  
Fusion Junction ◽  
Steady State Levels ◽  
The Common ◽  
The Stability ◽  
Duplex Formation ◽  
Flanking Regions

ABSTRACTRecently published transcriptomic data of the SARS-CoV-2 coronavirus show that there is a large variation in the frequency and steady state levels of subgenomic mRNA sequences. This variation is derived from discontinuous subgenomic RNA synthesis where the polymerase switches template from a 3’ proximal genome body sequence to a 5’ untranslated leader sequence. This leads to a fusion between the common 5’ leader sequence and a 3’ proximal body sequence in the RNA product. This process revolves around a common core sequence (CS) that is present at both the template sites that make up the fusion junction. Base-pairing between the leader CS and the nascent complementary minus strand body CS, and flanking regions (together called the transcription regulating sequence, TRS) is vital for this template switching event. However, various factors can influence the site of template switching within the same TRS duplex. Here, we model the duplexes formed between the leader and complementary body TRS regions, hypothesising the role of the stability of the TRS duplex in determining the major sites of template switching for the most abundant mRNAs. We indicate that the stability of secondary structures and the speed of transcription play key roles in determining the probability of template switching in the production of subgenomic RNAs.

scholarly journals Nidovirus transcription: how to make sense…?

2006 ◽  
Vol 87 (6) ◽  
pp. 1403-1421 ◽  
Author(s):  
Alexander O. Pasternak ◽  
Willy J. M. Spaan ◽  
Eric J. Snijder
Keyword(s):  
Leader Sequence ◽  
Minus Strand ◽  
Rna Recombination ◽  
Subgenomic Rna ◽  
Experimental Systems ◽  
The Common ◽  
Complementary Set ◽  
The Impact ◽  
Common Leader ◽  
Considerable Support

Many positive-stranded RNA viruses use subgenomic mRNAs to express part of their genetic information. To produce structural and accessory proteins, members of the order Nidovirales (corona-, toro-, arteri- and roniviruses) generate a 3′ co-terminal nested set of at least three and often seven to nine mRNAs. Coronavirus and arterivirus subgenomic transcripts are not only 3′ co-terminal but also contain a common 5′ leader sequence, which is derived from the genomic 5′ end. Their synthesis involves a process of discontinuous RNA synthesis that resembles similarity-assisted RNA recombination. Most models proposed over the past 25 years assume co-transcriptional fusion of subgenomic RNA leader and body sequences, but there has been controversy over the question of whether this occurs during plus- or minus-strand synthesis. In the latter model, which has now gained considerable support, subgenomic mRNA synthesis takes place from a complementary set of subgenome-size minus-strand RNAs, produced by discontinuous minus-strand synthesis. Sense–antisense base-pairing interactions between short conserved sequences play a key regulatory role in this process. In view of the presumed common ancestry of nidoviruses, the recent finding that ronivirus and torovirus mRNAs do not contain a common 5′ leader sequence is surprising. Apparently, major mechanistic differences must exist between nidoviruses, which raises questions about the functions of the common leader sequence and nidovirus transcriptase proteins and the evolution of nidovirus transcription. In this review, nidovirus transcription mechanisms are compared, the experimental systems used are critically assessed and, in particular, the impact of recently developed reverse genetic systems is discussed.

scholarly journals Approaches to Reforming Pension Systems in the World and Recommendations for Russia

2021 ◽  
Vol 13 (1) ◽  
pp. 125-135
Author(s):  
Kristina V. Shvandar ◽  
◽  
Anastasia A. Anisimova ◽  
Keyword(s):  
Pension System ◽  
Effective Interaction ◽  
Pension Plans ◽  
Population Coverage ◽  
Global Trends ◽  
Pension Systems ◽  
The Common ◽  
The Stability ◽  
Main Components

Global trends in the pension sector show that a funded pension, in addition to a pay-as-you-go component, increases the reliability of pension protection for retired people and improves the stability of the pension system. The article analyzes the main directions of reforms of both distribution and funded components. The common features of the considered pension systems are the presence of several levels and their effective interaction as well as the expansion of the role of accumulative pension systems. Reforms related to increasing the population coverage with accumulative pension plans are among the most common ones in the framework of the analysis. The main directions for improving the Russian funded pension system are highlighted, among which the voluntary payment of contributions and the ability to set the desired amount of contributions are the main components of the proposed changes, based on the analysis of international experience in reforming pension systems.

scholarly journals Straightness Detection Method and Accuracy Analysis of Guide Rail Parts

2021 ◽  
Vol 2133 (1) ◽  
pp. 012020
Author(s):  
Xiaoying Wang
Keyword(s):  
Machine Tools ◽  
Detection Method ◽  
Detection Methods ◽  
Detection Accuracy ◽  
Accuracy Analysis ◽  
Geometric Accuracy ◽  
Guide Rail ◽  
The Common ◽  
The Stability

Abstract Guide rail is widely used in various machine tools. It mainly plays the role of guidance and support. The geometric accuracy of the guide rail, especially the straightness accuracy, directly affects the stability of the machine tool and the accuracy of the workpiece. By analyzing the common detection methods, application scope and detection accuracy of straightness of guide rail parts, the application occasions and detection accuracy of each detection method are clarified. It provides a theoretical basis and guidance for testers to detect straightness and deal with errors.

scholarly journals Dipole collapse in rotating stratified dynamos

2019 ◽  
Vol 82 ◽  
pp. 357-363
Author(s):  
L. Petitdemange ◽  
R. Raynaud
Keyword(s):  
Numerical Modelling ◽  
Outer Surface ◽  
Boussinesq Approximation ◽  
Force Balance ◽  
Density Stratification ◽  
Ekman Number ◽  
Background Density ◽  
The Common ◽  
The Stability

Numerical modelling of convection driven dynamos in the Boussinesq approximation revealed fundamental characteristics of the dynamo-generated magnetic fields, but the relevance of these results remains to be assessed for highly stratified systems, like gas planets and stars. The common approach is then to rely on the anelastic approximation to model the background density stratification. A conclusion from different anelastic studies is that dipolar solutions seem more difficult to obtain in presence of a substantial density contrast. We review some important results obtained by Raynaud et al. (2015), who investigated the influence of the density stratification on the stability of dipolar dynamos. This study indicates that the loss of the dipolar branch does not ensue from a specific modification of the dynamo mechanisms related to the background stratification, but could instead result from a bias as our observations naturally favour a certain domain in the parameter space characterized by moderate values of the Ekman number. In strongly stratified systems, the force balance may vary with depth, and a local increase of inertia close to the outer surface can explain the loss of the dipolar branch, while volume-averaged measures may underestimate the role of inertia on the field topology.

On everyday academic research

2017 ◽  
pp. 98-134 ◽  
Author(s):  
J. Tirole
Keyword(s):  
Common Good ◽  
Academic Research ◽  
Research Quality ◽  
Economic Research ◽  
Relevant Research ◽  
The Common ◽  
Verification Of Models ◽  
Science And Research

In the fourth chapter of the book “The economy of the common good”, the nature of economics as a science and research practices in their theoretical and empirical aspects are discussed. The author considers the processes of modeling, empirical verification of models and evaluation of research quality. In addition, the features of economic cognition and the role of mathematics in economic research are analyzed, including the example of relevant research in game theory and information theory.

A Statistical Study of Process Variables to Optimize a High Speed Curtain Coater: Part I

TAPPI Journal ◽  
2009 ◽  
Vol 8 (1) ◽  
pp. 20-26 ◽  
Author(s):  
PEEYUSH TRIPATHI ◽  
MARGARET JOYCE ◽  
PAUL D. FLEMING ◽  
MASAHIRO SUGIHARA
Keyword(s):  
Boundary Layer ◽  
Experimental Design ◽  
High Speed ◽  
Statistical Study ◽  
Process Variables ◽  
High Speeds ◽  
The Stability ◽  
Air Removal ◽  
Removal System

Using an experimental design approach, researchers altered process parameters and material prop-erties to stabilize the curtain of a pilot curtain coater at high speeds. Part I of this paper identifies the four significant variables that influence curtain stability. The boundary layer air removal system was critical to the stability of the curtain and base sheet roughness was found to be very important. A shear thinning coating rheology and higher curtain heights improved the curtain stability at high speeds. The sizing of the base sheet affected coverage and cur-tain stability because of its effect on base sheet wettability. The role of surfactant was inconclusive. Part II of this paper will report on further optimization of curtain stability with these four variables using a D-optimal partial-facto-rial design.

Contemplative Principles of a Non-dual Praxis: the Unmediated Practices of the Tibetan ‘Heart Essence’ (sNying thig) Tradition

2015 ◽  
Vol 31 (2) ◽  
pp. 215-240
Author(s):  
Eran Laish
Keyword(s):  
Contemplative Practice ◽  
Tibetan Buddhist ◽  
Buddhist Tradition ◽  
The Common

This article focuses on the main contemplative principles of the ‘Heart Essence’ (sNying thig), a Tibetan Buddhist tradition that is characterized by a vision of non-duality and primordial wholeness. Due to this vision, which asserts an original reality that is not divided into perceiving subject and perceived object, the ‘Heart Essence’ advocates a contemplative practice that undermines the usual intuitions of temporality and enclosed selfhood. Hence, unlike the common principles of intentional praxis, such as deliberate concentration and gradual purification, the ‘Heart Essence’ affirms four contemplative principles of non-objectiveness, openness, spontaneity and singleness. As these principles transcend intentionality, temporality, and multiplicity, they are seen to directly disclose the nature of primordial awareness, in which the meanings of knowing and being are radically transformed. Therefore, the article will also consider the role of these non-dual contemplative principles in deeply changing our understanding of being and knowing alike.

The Role of Hydrophobicity in the Stability and pH-Switchability of (RXDX)4 and Coumarin-RXDX Conjugate β-Sheets

2020 ◽  
Author(s):  
Ryan Weber ◽  
Martin McCullagh
Keyword(s):  
Biological Imaging ◽  
Ph Sensing ◽  
Hydrophobic Residue ◽  
Ideal Candidate ◽  
Self Assembling ◽  
Sensing Applications ◽  
Β Sheets ◽  
The Stability ◽  
Dynamics Simulations

<p>pH-switchable, self-assembling materials are of interest in biological imaging and sensing applications. Here we propose that combining the pH-switchability of RXDX (X=Ala, Val, Leu, Ile, Phe) peptides and the optical properties of coumarin creates an ideal candidate for these materials. This suggestion is tested with a thorough set of all-atom molecular dynamics simulations. We first investigate the dependence of pH-switchabiliy on the identity of the hydrophobic residue, X, in the bare (RXDX)<sub>4</sub> systems. Increasing the hydrophobicity stabilizes the fiber which, in turn, reduces the pH-switchabilty of the system. This behavior is found to be somewhat transferable to systems in which a single hydrophobic residue is replaced with a coumarin containing amino acid. In this case, conjugates with X=Ala are found to be unstable and both pHs while conjugates with X=Val, Leu, Ile and Phe are found to form stable β-sheets at least at neutral pH. The (RFDF)<sub>4</sub>-coumarin conjugate is found to have the largest relative entropy value of 0.884 +/- 0.001 between neutral and acidic coumarin ordering distributions. Thus, we posit that coumarin-(RFDF)<sub>4</sub> containing peptide sequences are ideal candidates for pH-sensing bioelectronic materials.</p>

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