Translational Selection Research Articles

D-stem mutation in an essential tRNA increases translation speed at the cost of fidelity.

The efficiency with which aminoacyl-tRNA and GTP-bound translation elongation factor EF-Tu recognizes the A-site codon of the ribosome is dependent on codons and tRNA species present in the polypeptide (P) and exit (E) codon sites. To understand how codon context affects the efficiency of codon recognition by tRNA-bound EF-Tu, a genetic system was developed to select for fast translation through slow-translating codon combinations. Selection for fast translation through the slow-translated UCA-UAC pair, flanked by histidine codons, resulted in the isolation of an A25G base substitution mutant in the D-stem of an essential tRNA LeuZ, which recognizes the UUA and UUG leucine codons. The LeuZ(A25G) substitution allowed for faster translation through all codon pairs tested that included the UCA codon. Insertion of leucine at the UCA serine codon was enhanced in the presence of LeuZ(A25G) tRNA. This work, taken in context with the Hirsh UGA nonsense suppressor G24A mutation in TrpT tRNA, provides genetic evidence that the post-GTP hydrolysis proofreading step by elongation factor Tu may be controlled by structural interactions in the hinge region of tRNA species. Our results support a model in which the tRNA bending component of the accommodation step in mRNA translation allows EF Tu time to enhance its ability to differentiate tRNA interactions between cognate and near-cognate mRNA codons.

Discovery of a Potent Triazole-Based Reversible Targeted Covalent Inhibitor of Cruzipain.

Cruzipain (CZP) is an essential cysteine protease of Trypanosoma cruzi, the etiological agent of Chagas disease, and a promising druggable target. To date, no CZP inhibitors have reached clinical use, with research efforts mostly hampered by insufficient potency, limited target selectivity or lack of bioactivity translation from the isolated enzyme to the parasite in cellular environments. In this study, we report the design of SH-1, a 1,2,3-triazole-based targeted covalent inhibitor with nanomolar potency (IC50 = 28 nM) and null inhibition of human cathepsin L. SH-1 demonstrates bioactivity translation comparable to that of K777 (1-10 μM), a CZP inhibitor previously advanced to clinical trials. Experimental findings indicate that SH-1 forms a reversible covalent bond with Cys25 in CZP, while in silico and structure-activity relationship studies suggest that this interaction is guided by acid-base equilibrium dynamics. The potential of SH-1 for preclinical development is discussed alongside detailed structure-activity relationships for the further optimization of CZP inhibitors.

Tatar translations of the Lord’s Prayer (1803–2015) [Part 2

The Bible is the world’s most translated book. Throughout history it has been translated into a great many languages, and these translations have in recent years begun to attract wider attention. This article in‑ vestigates a selection of historical translations of the Lord’s Prayer from the Gospel of Matthew in a language called Tatar, and one contempo‑ rary translation, Volga Tatar. The timespan of the translations extends to over two hundred years: from 1803 to 2015. The translations are com‑ pared on a variety of linguistic levels, with special attention given to the lexicon. Orthography presents a noteworthy challenge, since most are in the Arabic script, not reflecting the nuances of the vowels. Fea‑ tures common to the translations are described, and those distinctive to each text are analysed. I discovered that many of the translations adhere to strict norms of literary language, clearly differing from spoken vari‑ ants. Up to the 20th century many Turkic literary languages were “tran‑ sregional”, that is, similar established literary norms extended over many Turkic peoples, whose spoken languages displayed a far greater variety. Interacting with the biblical text gives us a valuable glimpse of the multiple voices represented by the translations, and the circum‑ stances in which they were created.

Decoding Multidrug Resistance: Genetic Architecture and Codon Usage Patterns in ESKAPE Pathogens

Introduction: The escalating challenge of multidrug resistance among ESKAPE pathogens has become a prominent concern for global healthcare providers, leading to amplified morbidity and mortality rates. Method: We conducted this study to elucidate the genetic architecture of ESKAPE constituents with the intent of ameliorating pathogenicity and facilitating drug development efforts. A comprehensive array of computational tools and statistical methodologies were employed to scrutinize the genomes of ESKAPE pathogens. Result: Translational selection profoundly influences the codon usage bias within this pathogenic cohort. Notably, leucine emerged as the predominant amino acid, except in the case of Acinetobacter baumannii, where arginine exhibited preeminence. There was a universal preference for at least one histidine codon across all ESKAPE pathogens. GpC emerged as the most prominently overrepresented dinucleotide at the codon pair junction in all ESKAPE pathogens. Furthermore, a comparison of gyrB gene sequences and phylogenic tree construction showed a distinct evolutionary relationship between AT-rich and GC-rich ESKAPE pathogens. Additionally, identification, characterization, and phylogenetic analysis of multiple antibiotic resistance genes revealed distinct evolutionary relationships. Conclusion: It was discerned that despite substantial variability amongst antibiotic resistance genes of pathogens, leucine emerged as the predominant amino acid.

Spatiotemporal dynamics and selectivity of mRNA translation during mouse pre-implantation development.

Translational regulation is pivotal during preimplantation development. However, how mRNAs are selected for temporal regulation and their dynamic utilization and fate during this period are still unknown. Using a high-resolution ribosome profiling approach, we analyzed the transcriptome, as well as monosome- and polysome-bound RNAs of mouse oocytes and embryos, defining an unprecedented extent of spatiotemporal translational landscapes during this rapid developmental phase. We observed previously unknown mechanisms of translational selectivity, i.e., stage-wise deferral of loading monosome-bound mRNAs to polysome for active translation, continuous translation of both monosome and polysome-bound mRNAs at the same developmental stage, and priming to monosomes after initial activation. We showed that a eukaryotic initiation factor Eif1ad3, which is exclusively translated in the 2-Cell embryo, is required for ribosome biogenesis post embryonic genome activation. Our study thus provides genome-wide datasets and analyses of spatiotemporal translational dynamics accompanying mammalian germ cell and embryonic development and reveals the contribution of a novel translation initiation factor to mammalian pre-implantation development.

Genomic factors shaping codon usage across the Saccharomycotina subphylum.

Codon usage bias, or the unequal use of synonymous codons, is observed across genes, genomes, and between species. It has been implicated in many cellular functions, such as translation dynamics and transcript stability, but can also be shaped by neutral forces. We characterized codon usage across 1,154 strains from 1,051 species from the fungal subphylum Saccharomycotina to gain insight into the biases, molecular mechanisms, evolution, and genomic features contributing to codon usage patterns. We found a general preference for A/T-ending codons and correlations between codon usage bias, GC content, and tRNA-ome size. Codon usage bias is distinct between the 12 orders to such a degree that yeasts can be classified with an accuracy >90% using a machine learning algorithm. We also characterized the degree to which codon usage bias is impacted by translational selection. We found it was influenced by a combination of features, including the number of coding sequences, BUSCO count, and genome length. Our analysis also revealed an extreme bias in codon usage in the Saccharomycodales associated with a lack of predicted arginine tRNAs that decode CGN codons, leaving only the AGN codons to encode arginine. Analysis of Saccharomycodales gene expression, tRNA sequences, and codon evolution suggests that avoidance of the CGN codons is associated with a decline in arginine tRNA function. Consistent with previous findings, codon usage bias within the Saccharomycotina is shaped by genomic features and GC bias. However, we find cases of extreme codon usage preference and avoidance along yeast lineages, suggesting additional forces may be shaping the evolution of specific codons.

Translation selection and the consecration of Dylan Thomas’s poetry in China

Abstract Dylan Thomas’s poetry can be seen both as minor Welsh literature and world literature. Drawing on Bourdieu’s concepts of field and capital, this article explores the mechanism of translation selection and consecration of Thomas’s poetry in China by using his poetry published by Foreign Language Teaching and Research Press as an illustrative case study. In so doing, it is argued that the integrated forms of linguistic, economic, and symbolic capital associated with Thomas’s poetry, along with the expiration of its copyright, prompted the publisher to select his poetry for translation to maintain its own dominant position in the Chinese publishing field. The publisher, translator, and other agents have consecrated Thomas’s poetry as world literature in China. This article expands research on inter-peripheral translation flows and ‘sociologies of poetry translation’ and advances interdisciplinary studies of translation and world literature.

Comparative Analysis of Online Translators in the Machine Translation System

The article presents a comparative analysis of various online translators in the machine translation system. The author of the study focused on finding out the effectiveness and accuracy of the translation, identifying the strengths and weaknesses of the three most common online translators: Google Translate, DeepL and Microsoft Translator. The article begins with an overview of current trends in the field of machine translation and the need for online translations based on this context. The research methodology is selected in the article, in particular, the selection of individual online translators for comparison and the criteria for evaluating their work. The researcher analyzes the quality of translations for various types of texts, including common phrases, technical terms, complex sentences, etc. Attention is also paid to different language pairs and ensuring the availability of rarer languages in electronic translation. The article reveals such aspects as accuracy of translation, speed of work, recognition of context and idiomatic expressions, availability of additional functions and capabilities that ensure better translation quality. The author thoroughly highlights the strengths and weaknesses of each system, provides clear information about the use of integrations, available functions and additional capabilities of each translator. In the final part of the article, the author provides conclusions and recommendations regarding the use of online translators in the machine translation system. The research highlights that each electronic translator has its own advantages and limitations, and the choice depends on the specific needs of the user. In addition, the author emphasizes the need for constant updating and improvement of online translators to increase their accuracy and efficiency. This comparative analysis will help simplify the selection of the optimal translation software for users who require high-quality machine translation for their professional activities or everyday needs.

Spatial selectivity of ATase inhibition in mouse models of Charcot-Marie-Tooth disease.

The endoplasmic reticulum acetylation machinery has emerged as a new branch of the larger endoplasmic reticulum quality control system. It regulates the selection of correctly folded polypeptides as well as reticulophagy-mediated removal of toxic protein aggregates with the former being a particularly important aspect of the proteostatic functions of endoplasmic reticulum acetylation. Essential to this function is the Nε-lysine acetyltransferase activity of acetyltransferase 1 and acetyltransferase 2, which regulates the induction of endoplasmic reticulum-specific autophagy through the acetylation of the autophagy-related protein 9A. Here, we used three mouse models of Charcot-Marie-Tooth disease, peripheral myelin protein 22/Tr-J, C3-peripheral myelin protein 22 and myelin protein zero/ttrr, to study spatial and translational selectivity of endoplasmic reticulum acetyltransferase inhibitors. The results show that inhibition of the endoplasmic reticulum acetyltransferases selectively targets misfolding/pro-aggregating events occurring in the lumen of the organelle. Therefore, they establish acetyltransferase 1 and acetyltransferase 2 as the first proven targets for disease-causing proteotoxic states that initiate within the lumen of the endoplasmic reticulum/secretory pathway.

Exploring Cultural Adaptation and Symbolism in English Versions of “The Peony Pavilion”

Background: "The Peony Pavilion" by Tang Xianzu is a classical Chinese play renowned for its profound cultural and literary significance. Over the centuries, it has been translated into English numerous times, each rendition reflecting the translator's interpretation and cultural context. Materials and Methods: This reflective study examines a selection of English translations of "The Peony Pavilion" spanning different time periods and translators. Utilizing textual analysis and comparative study, we assess linguistic fidelity, cultural nuances, and the translators' approaches to bridging the gap between the source and target languages. Results: Our analysis reveals varying degrees of linguistic and cultural fidelity across translations. Quantitative metrics indicate a spectrum of fidelity, with scores ranging from 1 to 10, reflecting the extent to which translations capture the essence of the original text. Cultural nuances are often lost or altered, reflecting the influence of the translator's cultural background and the target audience's expectations. Conclusion: English translations of "The Peony Pavilion" present a dynamic interplay between linguistic accuracy and cultural interpretation. While some translations excel in preserving the original text's nuances, others diverge significantly, reflecting the translator's creative license and cultural context. This study underscores the importance of considering both linguistic and cultural fidelity in translating classical works, enriching cross-cultural understanding and appreciation.

Translation Peculiarities of Religious Terminology in L.N.Tolstoy's Novel "Resurrection" into English

The subject of the study is L.N. Tolstoy's novel "Resurrection" and its translations into English. As part of this work, two English translations will be analized, one of them (“The Resurrection”) was made in 1899 by Louise Yakovlevna Mood and published by "Alice and Books". The second translation titled “The Awakening" was translated by William Smith and published in 1900 by "New York Street Publishing House". The subject of the study is to identify ways of interlanguage translation of religious terminology from Russian into English. The main focus of the work is on the lexical and semantic analysis of religious lexical units, as well as the analysis of types of translation transformations, of which the most frequent are the selection of equivalent correspondence, descriptive translation and transliteration. The work uses a comparative method that allows us to establish similarities and differences of lexical units in the text of the original novel "Resurrection" and its translations. By means of the contextual analysis method, the dependence of the meaning of these units on the context is analyzed. Using the continuous sampling method, religious terminology is selected and divided into thematic groups: "Names of the sacraments and lexemes associated with them", "Elements and forms of worship", "Elements of the church calendar", "Objects of worship", "Names of the Church hierarchy", "The Temple and its structure, parts", "Vestments of the clergy, their individual parts", "Prayers, texts of prayers and hymns and their components", "Names of church holidays", "Names of books of church content", "Names of ritual food" and "Names of persons of spiritual guarantors". The main difficulty in translation is the rather wide and diverse use of religious nominations, for which the translator needs to understand in detail the features and differences of religious terminology.

The evolutionary and genetic patterns of African swine fever virus

African swine fever (ASF) is a serious animal disease, and has spread to Africa, Europe and Asia, causing massive economic losses. African swine fever virus (ASFV) is transmitted from a reservoir host (warthog) to domestic pigs via a sylvatic cycle (transmission between warthogs and soft ticks) and a domestic cycle (transmission between domestic pigs) and survives by expressing a variety of genes related to virus–host interactions. We evaluated differences in codon usage patterns among ASFV genotypes and clades and explored the common and specific evolutionary and genetic characteristics of ASFV sequences. We analysed the evolutionary relationships, nucleotide compositions, codon usage patterns, selection pressures (mutational pressure and natural selection) and viral adaptation to host codon usage based on the coding sequences (CDS) of key functional genes of ASFV. AT bias was detected in the six genes analysed, irrespective of clade. The AT bias of genes (A224L, A179L, EP153R) encoding proteins involved in interaction with host cells after infection was high; among them, the AT bias of EP153R was the greatest at 78.3%. A large number of overrepresented codons were identified in EP153R, whereas there were no overrepresented codons with a relative synonymous codon usage (RSCU) value of ≥3 in B646L. In most genes, the pattern of selection pressure was similar for each clade, but in EP153R, diverse patterns of selection pressure were captured within the same clade and genotype. As a result of evaluating host adaptation based on the codon adaptation index (CAI), for B646L, E183L, CP204L and A179L, the codon usage patterns in all sequences were more similar to tick than domestic pig or wild boar. However, EP153R showed the lowest average CAI value of 0.52 when selecting tick as a reference set. The genes analysed in this study showed different magnitudes of selection pressure at the clade and genotype levels, which is likely to be related to the function of the encoded proteins and may determine key evolutionary traits of viruses, such as the level of genetic variation and host range. The diversity of codon adaptations at the genetic level in ASFV may account for differences in translational selection in ASFV hosts and provides insight into viral host adaptation and co-evolution.

The Patterns of Codon Usage between Chordates and Arthropods are Different but Co-evolving with Mutational Biases.

Different frequencies amongst codons that encode the same amino acid (i.e. synonymous codons) have been observed in multiple species. Studies focused on uncovering the forces that drive such codon usage showed that a combined effect of mutational biases and translational selection works to produce different frequencies of synonymous codons. However, only few have been able to measure and distinguish between these forces that may leave similar traces on the coding regions. Here, we have developed a codon model that allows the disentangling of mutation, selection on amino acids and synonymous codons, and GC-biased gene conversion (gBGC) which we employed on an extensive dataset of 415 chordates and 191 arthropods. We found that chordates need 15 more synonymous codon categories than arthropods to explain the empirical codon frequencies, which suggests that the extent of codon usage can vary greatly between animal phyla. Moreover, methylation at CpG sites seems to partially explain these patterns of codon usage in chordates but not in arthropods. Despite the differences between the two phyla, our findings demonstrate that in both, GC-rich codons are disfavored when mutations are GC-biased, and the opposite is true when mutations are AT-biased. This indicates that selection on the genomic coding regions might act primarily to stabilize its GC/AT content on a genome-wide level. Our study shows that the degree of synonymous codon usage varies considerably among animals, but is likely governed by a common underlying dynamic.

English Translation of Political Documents with Chinese Characteristics from the Perspective of Eco-Translatology

In today’s increasingly globalized world, foreign publicity is particularly important in the exchanges and cooperation between nations, among which the translation of political documents serves as a crucial channel. The Report on the Work of the Government summarizes China’s work over the past year and outlines the prospects for the coming year. Its English translation is often highly concerned both domestically and internationally, making it an important text for foreign publicity. Based on the theory of Eco-translatology, this study takes the English version of the Report on the Work of the Government (2023) as an example to explore how to highlight cultural confidence and achieve communicative purposes in the translation of foreign publicity represented by political documents. It is found that translators often employ translation strategies, such as free translation, addition, omission, combination and annotation to realize the adaptive selection of translation in linguistic, culture and communication, facilitating full interaction between the source and target cultures, thereby enhancing the international influence and dissemination power of Chinese discourse.

An Ecocritical Study of Gary Snyder’s Translation of Han Shan Poetry

Gary Snyder, a contemporary American ecological poet, is deeply influenced by East-West ecological wisdom, forming his own unique ecological philosophy. Gary Snyder’s ecological philosophy influences his selection of poems to translate and translation methods in his English translation of Han Shan poetry. In turn, Gary Snyder’s translation also promotes the formation of his ecological philosophy to a certain extent. Faced with the increasingly serious ecological crisis, this study attempts to examine Gary Snyder’s translation of Han Shan poetry from the ecocritical perspective, exploring its ecological connotations and values from three aspects: translation selection, translation methods, and translation impact. The ecocritical study in this article aims to insert an ecological dimension to the study on English translation of poetry, and give advice to the strategy “Chinese Culture Going Global”, especially “Chinese Ecological Culture Going Global”.

Semantic Choice in Translation from Morris' Modern Semiotic Theory

From the perspective of the Internet, this article focuses on semantic selection in translation, and delves into the semantic selection of translation in Morris's modern semiotic theory. After exploring the relevant theoretical concepts by dimensions, it is found that the semantics of translation in Morris' modern semiotic theory can be divided into three types: denotational semantics, pragmatic semantics and intra-verbal semantics. Finally, the choice of the three types of semantics: denotational semantics, pragmatic semantics and intra-verbal semantics is explored in depth to provide guidance for related theoretical research.

Molecular insights into codon usage analysis of mitochondrial fission and fusion gene: relevance to neurodegenerative diseases.

Mitochondrial dysfunction is the leading cause of neurodegenerative disorders like Alzheimer's disease and Parkinson's disease. Mitochondria is a highly dynamic organelle continuously undergoing the process of fission and fusion for even distribution of components and maintaining proper shape, number, and bioenergetic functionality. A set of genes governs the process of fission and fusion. OPA1, Mfn1, and Mfn2 govern fusion, while Drp1, Fis1, MIEF1, and MIEF2 genes control fission. Determination of specific molecular patterns of transcripts of these genes revealed the impact of compositional constraints on selecting optimal codons. AGA and CCA codons were over-represented, and CCC, GTC, TTC, GGG, ACG were under-represented in the fusion gene set. In contrast, CTG was over-represented, and GCG, CCG, and TCG were under-represented in the fission gene set. Hydropathicity analysis revealed non-polar protein products of both fission and fusion gene set transcripts. AGA codon repeats are an integral part of translational regulation machinery and present a distinct pattern of over-representation and under-representation in different transcripts within the gene sets, suggestive of selective translational force precisely controlling the occurrence of the codon. Out of six synonymous codons, five synonymous codons encoding for leucine were used differently in both gene sets. Hence, forces regulating the occurrence of AGA and five synonymous leucine-encoding codons suggest translational selection. A correlation of mutational bias with gene expression and codon bias and GRAVY and AROMA signifies the selection pressure in both gene sets, while the correlation of compositional bias with gene expression, codon bias, protein properties, and minimum free energy signifies the presence of compositional constraints. More than 25% of codons of both gene sets showed a significant difference in codon usage. The overall analysis shed light on molecular features of gene sets involved in fission and fusion.

Codon usage bias of human papillomavirus type 33 and 58: A comprehensive analysis.

Cervical cancer is closely linked to specific strains of human papillomavirus (HPV), notably HPV-33 and HPV-58, which exhibit a significant prevalence among women in China. Nevertheless, the codon usage bias in HPV-33 and HPV-58 is not well comprehended. The objective of this research is to analyze the codon usage patterns HPV-33 and HPV-58, pinpoint the primary factors that influence codon preference. The overall preference for codon usage in two HPV genotypes is not significant. Both HPV genotypes exhibit a preference for codons that end with A/U. The GC3 content for HPV-33 is 25.43% ± 0.35%, and for HPV-58, it is 29.44% ± 0.57%. Out of the 26 favored codons in HPV-33 and HPV-58 (relative synonymous codon usage (RSCU) > 1), 25 conclude with A/U. Principal component analysis (PCA) shows a tight clustering of the entire genome sequences of HPV-33 and HPV-58, suggesting a similarity in their RSCU preferences. Moreover, an examination of dinucleotide abundance indicated that translation selection influenced the development of a distinctive dinucleotide usage pattern in HPV-33 and HPV-58. Additionally, a combined analysis involving an effective number of codons plot, parity rule 2, and neutrality analysis demonstrated that, for HPV-33 and HPV-58, the primary determinant influencing codon usage preference is natural selection. HPV-33 and HPV-58 exhibit a restricted set of favored codons in common with humans, potentially mitigating competition for translation resources. Our discoveries could provide valuable perspectives on the evolutionary patterns and codon usage preferences of HPV-33 and HPV-58 viruses, contributing to the development and application of relevant HPV subtype vaccines.

Selection on synonymous sites: the unwanted transcript hypothesis.

Although translational selection to favour codons that match the most abundant tRNAs is not readily observed in humans, there is nonetheless selection in humans on synonymous mutations. We hypothesize that much of this synonymous site selection can be explained in terms of protection against unwanted RNAs - spurious transcripts, mis-spliced forms or RNAs derived from transposable elements or viruses. We propose not only that selection on synonymous sites functions to reduce the rate of creation of unwanted transcripts (for example, through selection on exonic splice enhancers and cryptic splice sites) but also that high-GC content (but low-CpG content), together with intron presence and position, is both particular to functional native mRNAs and used to recognize transcripts as native. In support of this hypothesis, transcription, nuclear export, liquid phase condensation and RNA degradation have all recently been shown to promote GC-rich transcripts and suppress AU/CpG-rich ones. With such 'traps' being set against AU/CpG-rich transcripts, the codon usage of native genes has, in turn, evolved to avoid such suppression. That parallel filters against AU/CpG-rich transcripts also affect the endosomal import of RNAs further supports the unwanted transcript hypothesis of synonymous site selection and explains the similar design rules that have enabled the successful use of transgenes and RNA vaccines.

A reverse translational study of PPAR-α agonist efficacy in human and rodent models relevant to alcohol use disorder

Alcohol Use Disorder (AUD) is a chronic relapsing disorder affecting an estimated 283 million individuals worldwide, with substantial health and economic consequences. Peroxisome proliferator-activated receptors (PPARs), particularly PPAR-α and PPAR-γ, have shown promise in preclinical studies as potential therapeutic targets for AUD. In this human laboratory study, we aimed to translate preclinical findings on the PPAR-α agonist fenofibrate to a human population with current AUD. We hypothesized that, relative to placebo, fenofibrate at the highest FDA-approved dose of 145 mg/d would attenuate responsiveness to in vivo alcohol cues in the lab and reduce drinking under natural conditions. However, the results did not show significant differences in craving and alcohol consumption between the fenofibrate and placebo groups. Reverse translational studies in rodent models confirmed the lack of fenofibrate effect at human-equivalent doses. These findings suggest that inadequate translation of drug dose from rodents to humans may account for the lack of fenofibrate effects on alcohol craving and consumption in humans with AUD. The results highlight the need for new brain-penetrant PPAR-α agonists to adequately test the therapeutic potential of PPAR-α agonists for AUD, and the importance of reverse translational approaches and selection of human-equivalent doses in drug development.