scholarly journals The codon usage code for co-translational folding of viral capsids

2021 ◽  
Author(s):  
Rosa M Pintó ◽  
Albert Bosch
Keyword(s):  
Codon Usage ◽  
Codon Bias ◽  
Hepatitis A Virus ◽  
Rna Virus ◽  
Experimental Studies ◽  
Viral Capsids ◽  
Selection For ◽  
Computational Analyses ◽  
Codon Evolution

Abstract Codon bias is common to all organisms and is the result of mutation, drift, and selection. Selection for the efficiency and accuracy of translation is well recognized as a factor shaping the codon usage. In contrast, fewer studies report the control of the rate of translation as an additional selective pressure influencing the codon usage of an organism. Experimental molecular evolution using RNA virus populations is a powerful tool for the identification of mechanisms underlying the codon bias. Indeed, the role of deoptimized codons on the co-translational folding has been proven in the capsids of two fecal-orally transmitted picornaviruses, poliovirus and the hepatitis A virus, emphasizing the role of the frequency of codons in determining the phenotype. However, most studies on virus codon usage rely only on computational analyses, and experimental studies should be encouraged to clearly define the role of selection on codon evolution.

Computational studies of the mitochondrial carrier family SLC25. Present status and future perspectives

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Andrea Pasquadibisceglie ◽  
Fabio Polticelli
Keyword(s):  
Transport Mechanism ◽  
Experimental Studies ◽  
Intermembrane Space ◽  
Mitochondrial Carrier ◽  
Mitochondrial Homeostasis ◽  
The Matrix ◽  
Mitochondrial Carrier Family ◽  
Mitochondrial Intermembrane Space ◽  
Computational Analyses

Abstract The members of the mitochondrial carrier family, also known as solute carrier family 25 (SLC25), are transmembrane proteins involved in the translocation of a plethora of small molecules between the mitochondrial intermembrane space and the matrix. These transporters are characterized by three homologous domains structure and a transport mechanism that involves the transition between different conformations. Mutations in regions critical for these transporters’ function often cause several diseases, given the crucial role of these proteins in the mitochondrial homeostasis. Experimental studies can be problematic in the case of membrane proteins, in particular concerning the characterization of the structure–function relationships. For this reason, computational methods are often applied in order to develop new hypotheses or to support/explain experimental evidence. Here the computational analyses carried out on the SLC25 members are reviewed, describing the main techniques used and the outcome in terms of improved knowledge of the transport mechanism. Potential future applications on this protein family of more recent and advanced in silico methods are also suggested.

scholarly journals The Critical Role of Codon Composition on the Translation Efficiency Robustness of the Hepatitis A Virus Capsid

2019 ◽  
Vol 11 (9) ◽  
pp. 2439-2456 ◽  
Author(s):  
Lucía D’Andrea ◽  
Francisco-Javier Pérez-Rodríguez ◽  
Montserrat de Castellarnau ◽  
Susana Guix ◽  
Enric Ribes ◽  
...  
Keyword(s):  
Codon Usage ◽  
Sequence Space ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Critical Role ◽  
Translation Efficiency ◽  
Rare Codons ◽  
Codon Composition ◽  
Cellular Genome

AbstractHepatoviruses show an intriguing deviated codon usage, suggesting an evolutionary signature. Abundant and rare codons in the cellular genome are scarce in the human hepatitis A virus (HAV) genome, while intermediately abundant host codons are abundant in the virus. Genotype–phenotype maps, or fitness landscapes, are a means of representing a genotype position in sequence space and uncovering how genotype relates to phenotype and fitness. Using genotype–phenotype maps of the translation efficiency, we have shown the critical role of the HAV capsid codon composition in regulating translation and determining its robustness. Adaptation to an environmental perturbation such as the artificial induction of cellular shutoff—not naturally occurring in HAV infection—involved movements in the sequence space and dramatic changes of the translation efficiency. Capsid rare codons, including abundant and rare codons of the cellular genome, slowed down the translation efficiency in conditions of no cellular shutoff. In contrast, rare capsid codons that are abundant in the cellular genome were efficiently translated in conditions of shutoff. Capsid regions very rich in slowly translated codons adapt to shutoff through sequence space movements from positions with highly robust translation to others with diminished translation robustness. These movements paralleled decreases of the capsid physical and biological robustness, and resulted in the diversification of capsid phenotypes. The deviated codon usage of extant hepatoviruses compared with that of their hosts may suggest the occurrence of a virus ancestor with an optimized codon usage with respect to an unknown ancient host.

scholarly journals Proliferation specific codon usage facilitates oncogene translation

2019 ◽  
Author(s):  
Hannah Benisty ◽  
Marc Weber ◽  
Xavier Hernandez-Alias ◽  
Martin H. Schaefer ◽  
Luis Serrano
Keyword(s):  
Cell Proliferation ◽  
Codon Usage ◽  
Codon Bias ◽  
Expression Profiles ◽  
Gene Mutations ◽  
Translation Efficiency ◽  
Cancer Genes ◽  
Kras Mutations ◽  
Related Family ◽  
Selection For

SummaryTumors evolve under selection for gene mutations that give a growth advantage to the cancer cell. Intriguingly, some cancer genes are more often found mutated in tumors than their closely related family members. For example, KRAS mutations are more frequently observed in cancer in comparison to HRAS and NRAS. Here, we find that for RAS and six oncogene families, the most prevalent mutated members in cancer have a codon usage characteristic of genes involved in proliferation. The codon usage of KRAS is more adapted to be efficiently translated in proliferative cells than the codon usage of HRAS. We also show that the translation efficiency of KRAS varies between cell lines in a manner related to their tRNA expression. Altogether, our study demonstrates that a dynamic translation program contributes to shaping the expression profiles of oncogenes. We propose that codon bias related to cell proliferation contributes to the prevalence of mutations in certain members of oncogene families.

The nature of evolution and adaptation: resolving the unity–diversity paradox

1988 ◽  
Vol 66 (5) ◽  
pp. 1146-1152 ◽  
Author(s):  
P. W. Hochachka
Keyword(s):  
Species Diversity ◽  
Current Literature ◽  
Experimental Studies ◽  
Living Systems ◽  
Current Status ◽  
Biochemical Adaptation ◽  
Biochemical Systems ◽  
Regulatory Loci ◽  
Selection For

The concept of the unity of biochemical structures and functions creates the problem for biology of how to account for the pervasive species diversity and obvious adaptedness of living systems. A review of the current literature indicates that four principles, (i) the principle of conservation of critical sequences in both structural and regulatory loci, (ii) the principle of unique assembly of parts via unique (tissue-specific and temporal) activation of regulatory loci, (iii) the principle of genetic innovation via mechanisms internal or external to the genome, and (iv) the principle of biochemical adaptation via selection for favourable alleles of structural and regulatory genes or selection for advantageous genetic innovations, seem capable of resolving the paradox of the unity of biochemical systems despite patently vast species diversity and species adaptation. Evaluation of the current status of each of these principles suggests the especial need for more experimental studies of the role of regulatory loci in species diversification and adaptation.

scholarly journals Evolution of Codon Usage Bias in Diatoms

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 894 ◽  
Author(s):  
Marc Krasovec ◽  
Dmitry A. Filatov
Keyword(s):  
Codon Usage ◽  
Codon Usage Bias ◽  
Codon Bias ◽  
Diatom Species ◽  
Effective Population ◽  
Weak Selection ◽  
Optimal Codons ◽  
Wide Range ◽  
Population Sizes ◽  
Selection For

Codon usage bias (CUB)—preferential use of one of the synonymous codons, has been described in a wide range of organisms from bacteria to mammals, but it has not yet been studied in marine phytoplankton. CUB is thought to be caused by weak selection for translational accuracy and efficiency. Weak selection can overpower genetic drift only in species with large effective population sizes, such as Drosophila that has relatively strong CUB, while organisms with smaller population sizes (e.g., mammals) have weak CUB. Marine plankton species tend to have extremely large populations, suggesting that CUB should be very strong. Here we test this prediction and describe the patterns of codon usage in a wide range of diatom species belonging to 35 genera from 4 classes. We report that most of the diatom species studied have surprisingly modest CUB (mean Effective Number of Codons, ENC = 56), with some exceptions showing stronger codon bias (ENC = 44). Modest codon bias in most studied diatom species may reflect extreme disparity between astronomically large census and modest effective population size (Ne), with fluctuations in population size and linked selection limiting long-term Ne and rendering selection for optimal codons less efficient. For example, genetic diversity (pi ~0.02 at silent sites) in Skeletonema marinoi corresponds to Ne of about 10 million individuals, which is likely many orders of magnitude lower than its census size. Still, Ne ~107 should be large enough to make selection for optimal codons efficient. Thus, we propose that an alternative process—frequent changes of preferred codons, may be a more plausible reason for low CUB despite highly efficient selection for preferred codons in diatom populations. The shifts in the set of optimal codons should result in the changes of the direction of selection for codon usage, so the actual codon usage never catches up with the moving target of the optimal set of codons and the species never develop strong CUB. Indeed, we detected strong shifts in preferential codon usage within some diatom genera, with switches between preferentially GC-rich and AT-rich 3rd codon positions (GC3). For example, GC3 ranges from 0.6 to 1 in most Chaetoceros species, while for Chaetoceros dichaeta GC3 = 0.1. Both variation in selection intensity and mutation spectrum may drive such shifts in codon usage and limit the observed CUB. Our study represents the first genome-wide analysis of CUB in diatoms and the first such analysis for a major phytoplankton group.

Calculation-and-experimental estimation of the role of the frequency ratio in changing the endurance at two-frequency deformation modes

2019 ◽  
Vol 85 (1(I)) ◽  
pp. 64-71 ◽  
Author(s):  
M. M. Gadenin
Keyword(s):  
High Frequency ◽  
Experimental Studies ◽  
Low Frequency ◽  
Reduction Factor ◽  
Single Frequency ◽  
Cyclic Loads ◽  
Small Ratio ◽  
Harmonic Components ◽  
Deformation Modes

The cycle configuration at two-frequency loading regimes depends on the number of parameters including the absolute values of the frequencies and amplitudes of the low-frequency and high-frequency loads added during this mode, the ratio of their frequencies and amplitudes, as well as the phase shift between these harmonic components, the latter having a significant effect only with a small ratio of frequencies. Presence of such two-frequency regimes or service loading conditions for parts of machines and structures schematized by them can significantly reduce their endurance. Using the results of experimental studies of changes in the endurance of a two-frequency loading of specimens of cyclically stable, cyclically softened and cyclically hardened steels under rigid conditions we have shown that decrease in the endurance under the aforementioned conditions depends on the ratio of frequencies and amplitudes of operation low-frequency low-cycle and high-frequency vibration stresses, and, moreover, the higher the level of the ratios of amplitudes and frequencies of those stacked harmonic processes of loading the greater the effect. It is shown that estimation of such a decrease in the endurance compared to a single frequency loading equal in the total stress (strains) amplitudes can be carried out using an exponential expression coupling those endurances through a parameter (reduction factor) containing the ratio of frequencies and amplitudes of operation cyclic loads and characteristic of the material. The reduction is illustrated by a set of calculation-experimental curves on the corresponding diagrams for each of the considered types of materials and compared with the experimental data.

Helping when desire is low: The role of Expectancy in helping

2020 ◽  
Author(s):  
Małgorzata Kossowska
Keyword(s):  
Experimental Studies ◽  
Helping Behavior ◽  
Perceived Effectiveness ◽  
Do So

One might assume that the desire to help (here described as Want) is the essential driver of helping declarations and/or behaviors. However, even if desire to help is low, helping behavior may still occur if the expectancy regarding the perceived effectiveness of helping is high. We tested these predictions in a set of three experimental studies. In all three, we measured the desire to help (Want) and the Expectancy that the aid would be impactful for the victim; in addition, we manipulated Expectancy in Study 3. In Studies 1 and 3, we measured the participants’ declaration to help while in Study 2, their helping behavior was examined. In all three studies, we used variations of the same story about a victim. The results supported our hypothesis. Thus, the studies help to tease apart the determinants of helping behavior under conditions of lowered desire to do so, an issue of great importance in public policymaking.

The capacity of short term memory from an evolutionary perspective

2019 ◽  
Author(s):  
Majid Manoochehri
Keyword(s):  
Short Term Memory ◽  
Memory Span ◽  
Critical Role ◽  
Experimental Studies ◽  
Cognitive System ◽  
Evolutionary Approach ◽  
Evolutionary Perspective ◽  
Short Term ◽  
Term Memory

Memory span in humans has been intensely studied for more than a century. In spite of the critical role of memory span in our cognitive system, which intensifies the importance of fundamental determinants of its evolution, few studies have investigated it by taking an evolutionary approach. Overall, we know hardly anything about the evolution of memory components. In the present study, I briefly review the experimental studies of memory span in humans and non-human animals and shortly discuss some of the relevant evolutionary hypotheses.

The methodology of experimental research of the feed components extrusion process in order to improve its energy performance

2020 ◽  
pp. 147-152
Author(s):  
E. M. Ratnikov ◽  
D. O. Milko
Keyword(s):  
Experimental Studies ◽  
Energy Performance ◽  
Extrusion Process ◽  
Mathematical Methods ◽  
Screw Extruder ◽  
Mathematical Planning ◽  
Factors Affecting ◽  
Extrusion Processing ◽  
Definition Of

Annotation Purpose. Development of a program and methods for conducting experimental studies of the extrusion process with the definition of parameters and modes of operation of the extruder to improve its energy performance. Methods. Methods of mathematical statistics, synthesis, analysis, description and modeling were used. Results. The application of mathematical methods, in particular mathematical planning, reduces the number of experiments several times, and allows to evaluate the role of influencing factors, obtain a mathematical model of the process and determine the optimal conditions for its parameters and modes, etc. Conclusions. The methodology for experimental studies of a screw extruder is presented with the necessary equipment and methodology for processing the obtained experimental data. A mathematical method of planning, which reduces the number of experiments several times, allows us to evaluate the role of factors affecting productivity and energy intensity is presented. Keywords: extruder, auger, nutrients, research methodology, extrusion, processing, feed.

ACE2/Angiotensin-(1-7)/Mas Receptor Axis in Human Cancer: Potential Role for Pediatric Tumors

2020 ◽  
Vol 21 (9) ◽  
pp. 892-901 ◽  
Author(s):  
Ana Luiza Ataide Carneiro de Paula Gonzaga ◽  
Vitória Andrade Palmeira ◽  
Thomas Felipe Silva Ribeiro ◽  
Larissa Braga Costa ◽  
Karla Emília de Sá Rodrigues ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Angiotensin Ii ◽  
Pediatric Cancer ◽  
Pediatric Patients ◽  
Human Cancer ◽  
Experimental Studies ◽  
At1 Receptor ◽  
Pediatric Tumors ◽  
Mas Receptor

Background: Pediatric tumors remain the highest cause of death in developed countries. Research on novel therapeutic strategies with lesser side effects is of utmost importance. In this scenario, the role of Renin-Angiotensin System (RAS) axes, the classical one formed by angiotensinconverting enzyme (ACE), Angiotensin II and AT1 receptor and the alternative axis composed by ACE2, Angiotensin-(1-7) and Mas receptor, have been investigated in cancer. Objective: This review aimed to summarize the pathophysiological role of RAS in cancer, evidence for anti-tumor effects of ACE2/Angiotensin-(1-7)/Mas receptor axis and future therapeutic perspectives for pediatric cancer. Methods: Pubmed, Scopus and Scielo were searched in regard to RAS molecules in human cancer and pediatric patients. The search terms were “RAS”, “ACE”, “Angiotensin-(1-7)”, “ACE2”, “Angiotensin II”, “AT1 receptor”, “Mas receptor”, “Pediatric”, “Cancer”. Results: Experimental studies have shown that Angiotensin-(1-7) inhibits the growth of tumor cells and reduces local inflammation and angiogenesis in several types of cancer. Clinical trials with Angiotensin-( 1-7) or TXA127, a pharmaceutical grade formulation of the naturally occurring peptide, have reported promising findings, but not enough to recommend medical use in human cancer. In regard to pediatric cancer, only three articles that marginally investigated RAS components were found and none of them evaluated molecules of the alternative RAS axis. Conclusion: Despite the potential applicability of Angiotensin-(1-7) in pediatric tumors, the role of this molecule was never tested. Further clinical trials are necessary, also including pediatric patients, to confirm safety and efficiency and to define therapeutic targets.

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