In this study, a comparative analysis of the codon usage bias was performed in Aeropyrum pernix K1 and two other phylogenetically related Crenarchaeota microorganisms （i.e., Pyrobaculum aerophilum str. IM2 and Sulfol...In this study, a comparative analysis of the codon usage bias was performed in Aeropyrum pernix K1 and two other phylogenetically related Crenarchaeota microorganisms （i.e., Pyrobaculum aerophilum str. IM2 and Sulfolobus acidocaldarius DSM 639）. The results indicated that the synonymous codon usage in A. pernix K1 was less biased, which was highly correlated with the GC3s value. The codon usage patterns were phylogenetically conserved among these Crenarchaeota microorganisms. Comparatively, it is the species function rather than the gene function that determines their gene codon usage patterns. A. pernix K1, P. aerophilum str. IM2, and S. acidocaldarius DSM 639 live in differently extreme conditions. It is presumed that the hving environment played an important role in determining the codon usage pattern of these microorganisms. Besides, there was no strain-specific codon usage among these microorganisms. The extent of codon bias in A. pernix K1 and S. acidocaldarius DSM 639 were highly correlated with the gene expression level, but no such association was detected in P. aerophilum str. IM2 genomes.展开更多
Apple（Malus×domestica） has been proposed as an important woody plant and the major cultivated fruit trees in temperate regions. Apple whole genome sequencing has been completed, which provided an excellent oppo...Apple（Malus×domestica） has been proposed as an important woody plant and the major cultivated fruit trees in temperate regions. Apple whole genome sequencing has been completed, which provided an excellent opportunity for genome-wide analysis of the synonymous codon usage patterns. In this study, a multivariate bioinformatics analysis was performed to reveal the characteristics of synonymous codon usage and the main factors affecting codon bias in apple. The neutrality, correspondence, and correlation analyses were performed by Codon W and SPSS（Statistical Product and Service Solutions） programs, indicating that the apple genome codon usage patterns were affected by mutational pressure and selective constraint. Meanwhile, coding sequence length and the hydrophobicity of proteins could also influence the codon usage patterns. In short, codon usage pattern analysis and determination of optimal codons has laid an important theoretical basis for genetic engineering, gene prediction and molecular evolution studies in apple.展开更多
A comparative analysis of the codon usage bias was conducted in Methanosarcina mazei str. Goel and two related Euryarchaeota microorganisms （Picrophilus torridus str. DSM 9790 and Natronomonas pharaonis str. DSM 2160...A comparative analysis of the codon usage bias was conducted in Methanosarcina mazei str. Goel and two related Euryarchaeota microorganisms （Picrophilus torridus str. DSM 9790 and Natronomonas pharaonis str. DSM 2160）. Results revealed that synonymous codon usage in Methanosarcina mazei str. Goel was less biased, which was highly correlated with the GC3S value. And the codon usage patterns were phylogenetically conserved among those Euryarchaeota microorganisms. By employing a hierarchical clustering analysis, it can be seen that it is more the species than the gene function that determines their gene codon usage pattems. Considering that those microorganisms live in different environments where the pH conditions vary quite a lot, it can be presumed that their living environments, especially the pH conditions, play an important role in determining those microorganisms＇ codon usage pattems.展开更多
Objective:Autosomal dominant polycystic kidney disease(ADPKD)is mainly caused by the pathogenic mutation of PKD1 or PKD2 gene and usually affects bilateral kidneys.Synonymous mutations are generally assumed to be neut...Objective:Autosomal dominant polycystic kidney disease(ADPKD)is mainly caused by the pathogenic mutation of PKD1 or PKD2 gene and usually affects bilateral kidneys.Synonymous mutations are generally assumed to be neutral as they do not alter amino acids.Herein,we described an extremely rare ADPKD child caused by a heterozygous synonymous mutation of PKD2 gene accompanied by massive proteinuria and congenital solitary kidney.Methods:Clinical characteristics of the patients were summarized.Whole-exome sequencing was performed to screen the disease-causing gene mutation,and reverse transcription polymerase chain reaction(RT-PCR)and Sanger sequencing were applied to analyze the impact of the identified mutation on gene transcription and splicing.Results:Polycystic changes were found in the solitary kidney of a girl initially presented with nephrotic-range proteinuria.Thereafter her mother and 2 other family members were diagnosed to be ADPKD.Whole-exome sequencing of the proband identified a heterozygous synonymous mutation(c.1716G>A,p.Lys572=)located in the splicing site of exon 7 in PKD2 gene,which was co-segregated with the PKD phenotype in the family.RT-PCR and direct sequencing of amplified products revealed that this heterozygous synonymous mutation led to exon7 skipping in PKD2 gene.Conclusion:We reported an extremely rare child case of ADPKD2 in combination with solitary kidney and nephrotic-range proteinuria,and firstly confirmed the pathogenicity of a heterozygous synonymous mutation(c.1716G>A)in PKD2 gene.The results indicate that synonymous mutations should not be excluded from disease-causing if they are located in splicing site of an exon.展开更多
To investigate how synonymous codons have been adapted to the formation of ribonucleic acid(RNA)G-quadruplex(rG4)structure,a computational searching algorithm G4Hunter was applied to detect rG4 structures in protein-c...To investigate how synonymous codons have been adapted to the formation of ribonucleic acid(RNA)G-quadruplex(rG4)structure,a computational searching algorithm G4Hunter was applied to detect rG4 structures in protein-coding sequences of mRNAs in five eukaryotic species.The native sequences forming rG4s were then compared with randomized sequences to evaluate selection on synonymous codons.Factors that may influence the formation of rG4 were also investigated,and the selection pressures of rG4 in different gene regions were compared to explore its potential roles in gene regulation.The results show universal selective pressure acts on synonymous codons in rG4 regions to facilitate rG4 formation in five eukaryotic organisms.While G-rich codon combinations are preferred in the rG4 structural region,C-rich codon combinations are selectively unfavorable for rG4 formation.Gene's codon usage bias,nucleotide composition,and evolutionary rate can account for the selective variations on synonymous codons among rG4 structures within a species.Moreover,rG4 structures in the translational initiation region showed significantly higher selective pressures than those in the translational elongation region.展开更多
In this work,an approach is proposed to acquire synonymous attribute phrases of named entities(NEs) from an online encyclopedia.Synonymous attribute phrases are the phrases that express the same attribute with differe...In this work,an approach is proposed to acquire synonymous attribute phrases of named entities(NEs) from an online encyclopedia.Synonymous attribute phrases are the phrases that express the same attribute with different surface forms for a class of NEs.Specifically,the proposed approach is composed of three stages.Firstly,the entries related to a given NE class are automatically selected from an online encyclopedia.Secondly,attribute phrases are extracted based on the statistics of phrase frequency.Thirdly,synonymous attributes are identified in a pairwise manner through a classification framework combining multiple features.The proposed approach is applied on Baidu Baike,a Chinese online encyclopedia,for four different NE classes.Experimental results show that the approach obtains an average precision of 74%and an average F-value of 65%for the four NE classes.In particular,thousands of synonymous attribute phrase pairs are acquired for each class,which demonstrates the effectiveness of the proposed approach.展开更多
The APCDDI （adenomatosis polyposis coli down-regulated 1） gene is an inhibitor of the Wnt signaling pathway, and a rare mutation of this gene has been associated with hereditary hypotrichosis simplex. In this study,...The APCDDI （adenomatosis polyposis coli down-regulated 1） gene is an inhibitor of the Wnt signaling pathway, and a rare mutation of this gene has been associated with hereditary hypotrichosis simplex. In this study, the authors aimed to investigate whether common APCDD1 gene polymorphisms contribute to the development of androgenic alopecia. Patients （n = 210） with androgenic alopecia and 98 controls were investigated. SNPs （Single nucleotide polymorphisms） in the coding region of the gene were sequenced. A significant difference in genotype distribution was found for the c. 1781C/T, p.L476L SNP （rs3185480） of the APCDD1 gene. This SNP is located in exon 5 and is associated with a 3.5- and a 2.8-fold increase in risk for the development of androgenic alopecia for homozygote （CI 0.933-13.125; nominal regression P = 0.063） and heterozygote （CI 1.086-7.217; nominal regression P = 0.033） carriers, respectively. These data suggest that the rs3185480 polymorphism contributes to the development of androgenic alopecia. Protein expression experiments revealed that the polymorphism is associated with reduced APCDDI protein abundance. This reduction is likely due to altered codon usage for leucine from a preferred codon （CTC） to a rare codon （CTT）, which might influence translation efficiency and, thus, APCDDI protein level.展开更多
Mutations in fibrillin-1 gene(FBN1)have been shown to be associated with Marfan syndrome and most FBN1 mutations display missense or nonsense.Recently,reports on synonymous mutation-related diseases have attracted wid...Mutations in fibrillin-1 gene(FBN1)have been shown to be associated with Marfan syndrome and most FBN1 mutations display missense or nonsense.Recently,reports on synonymous mutation-related diseases have attracted widespread attention.Zhang et al demonstrated that synonymous mutations in saccharomyces cerevisiae have pathogenicity like non-synonymous mutations.1 Based on a special Marfan syndrome patient with a novel synonymous mutation in FNB1.展开更多
Methods for estimating synonymous and nonsynonymous substitution rates among protein-coding sequences adopt different mutation (substitution) models with subtle yet significant differences, which lead to different est...Methods for estimating synonymous and nonsynonymous substitution rates among protein-coding sequences adopt different mutation (substitution) models with subtle yet significant differences, which lead to different estimates of evolutionary information. Little attention has been devoted to the comparison of methods for obtaining reliable estimates since the amount of sequence variations within targeted datasets is always unpredictable. To our knowledge, there is little information available in literature about evaluation of these different methods. In this study, we compared six widely used methods and provided with evaluation results using simulated sequences. The results indicate that incorporating sequence features (such as transition/transversion bias and nucleotide/codon frequency bias) into methods could yield better performance. We recommend that conclusions related to or derived from Ka and Ks analyses should not be readily drawn only according to results from one method.展开更多
Synonymous codon bias has been examined in 78 human genes (19967 codons) and measured by relative synonymous codon usage (RSCU). Relative frequencies of all kinds of dinucleotides in 2,3 or 3,4 codon positions have be...Synonymous codon bias has been examined in 78 human genes (19967 codons) and measured by relative synonymous codon usage (RSCU). Relative frequencies of all kinds of dinucleotides in 2,3 or 3,4 codon positions have been calculated, and codon-anticodon binding strength has been estimated by the stacking energies of codon-anticodon bases in Watson-Crick pairs. The data show common features in synonymous codon bias for all codon families in human genes: all C-ending codons, which possess the strongest codon-anticodon binding energies, are the most favored codons in almost all codon families, and those codons with medium codon-anticodon binding energies are avoided. Data analysis suggests that besides isochore and genome signature, codon-anticodon binding strength may be closely related to synonymous codon choice in human genes. The join-effect of these factors on human genes results in the common features in codon bias.展开更多
p53 is an intrinsically disordered protein with a large number of post-translational modifications and interacting partners.The hierarchical order and subcellular location of these events are still poorly understood.T...p53 is an intrinsically disordered protein with a large number of post-translational modifications and interacting partners.The hierarchical order and subcellular location of these events are still poorly understood.The activation of p53 during the DNA damage response(DDR)requires a switch in the activity of the E3 ubiquitin ligase MDM2 from a negative to a positive regulator of p53.This is mediated by the ATM kinase that regulates the binding of MDM2 to the p53 mRNA facilitating an increase in p53 synthesis.Here we show that the binding of MDM2 to the p53 mRNA brings ATM to the p53 polysome where it phosphorylates the nascent p53 at serine 15 and prevents MDM2-mediated degradation of p53.A single synonymous mutation in p53 codon 22(L22L)prevents the phosphorylation of the nascent p53 protein and the stabilization of p53 following genotoxic stress.The ATM trafficking from the nucleus to the p53 polysome is mediated by MDM2,which requires its interaction with the ribosomal proteins RPL5 and RPL11.These results show how the ATM kinase phosphorylates the p53 protein while it is bang synthesized and offer a novel mechanism whereby a single synonymous mutation controls the stability and activity of the encoded protein.展开更多
In the English language, there are many words which are considered synonymous in that dictionaries and thesauruses often define them in identical meanings. Under such circumstances, EFL learners are confronted with a ...In the English language, there are many words which are considered synonymous in that dictionaries and thesauruses often define them in identical meanings. Under such circumstances, EFL learners are confronted with a big difficulty in acquiring these words of similar meanings. They often regard synonymous words as equivalents and use them alternately, which sometimes result in ambiguity or awkwardness of their language. However, with the advent of corpora and concordancing programs, a new way of investigating and learning English synonymous words has emerged. This paper explores colligational patterns, collocational behavior and semantic prosody of two seemingly synonymous verbs, gain and obtain, in two native speaker corpora, the Brown Corpus and the LOB Corpus, in order to show how these 'equivalencies' can be misleading because 'synonymous' words are typically used in different ways. The study also examines EFL learners' behavior in using synonymous words by investigating the Chinese Learner English Corpus (CLEC). From the results of the study, it can be seen that Chinese EFL learners have not yet acquired a full understanding of the usage of gain and obtain with respect to colligation, collocation and semantic prosody. Their underuses and overuses of some grammatical forms and lexical patterns of the two target synonymous words might be influenced either by their mother tongue or by the registers of their English writing or by both. The paper finally discusses the implications of corpus-based study in vocabulary teaching and learning in general.展开更多
Background Adenosine deaminase(ADA)is a key enzyme in the purine salvage pathway.Genetic defects of the ADA gene can cause a subtype of severe combined immunodeficiency.To date,few Chinese cases have been reported.Met...Background Adenosine deaminase(ADA)is a key enzyme in the purine salvage pathway.Genetic defects of the ADA gene can cause a subtype of severe combined immunodeficiency.To date,few Chinese cases have been reported.Methods We retrospectively reviewed the medical records of patients diagnosed with ADA deficiency in Beijing Children's Hospital and summarized the previously published ADA deficiency cases from China in the literature.Results Nine patients were identified with two novel mutations(W272X and Q202=).Early-onset infection,thymic abnor-malities and failure to thrive were the most common manifestations of Chinese ADA-deficient patients.The ADA genotype has a major effect on the clinical phenotype.Notably,a novel synonymous mutation(c.606G>A,p.Q202=)was identified in a delayed-onset patient,which affected pre-mRNA splicing leading to a frameshift and premature truncation of the protein.Furthermore,the patient showed γδT cells expansion with an increased effect or phenotype,which may be associated with the delayed onset of disease.In addition,we reported cerebral aneurysm and intracranial artery stenosis for the first time in ADA deficiency.Five patients died with a median age of four months,while two patients received stem cell transplantation and are alive.Conclusions This study described the first case series of Chinese ADA-deficient patients.Early-onset infection,thymic abnormalities and failure to thrive were the most common manifestations in our patients.We identified a synonymous muta-tion that affected pre-mRNA splicing in the ADA gene,which had never been reported in ADA deficiency.Furthermore,we reported cerebral aneurysm in a delayed-onset patient for the first time.Further study is warranted to investigate the underlying mechanisms.展开更多
Background:The medical records of traditional Chinese medicine(TCM)contain numerous synonymous terms with different descriptions,which is not conducive to computer-aided data mining of TCM.However,there is a lack of m...Background:The medical records of traditional Chinese medicine(TCM)contain numerous synonymous terms with different descriptions,which is not conducive to computer-aided data mining of TCM.However,there is a lack of models available to normalize synonymous TCM terms.Therefore,construction of a synonymous term conversion(STC)model for normalizing synonymous TCM terms is necessary.Methods:Based on the neural networks of bidirectional encoder representations from transformers(BERT),four types of TCM STC models were designed:Models based on BERT and text classification,text sequence generation,named entity recognition,and text matching.The superior STC model was selected on the basis of its performance in converting synonymous terms.Moreover,three misjudgment inspection methods for the conversion results of the STC model based on inconsistency were proposed to find incorrect term conversion:Neuron random deactivation,output comparison of multiple isomorphic models,and output comparison of multiple heterogeneous models(OCMH).Results:The classification-based STC model outperformed the other STC task models.It achieved F1 scores of 0.91,0.91,and 0.83 for performing symptoms,patterns,and treatments STC tasks,respectively.The OCMH method showed the best performance in misjudgment inspection,with wrong detection rates of 0.80,0.84,and 0.90 in the term conversion results for symptoms,patterns,and treatments,respectively.Conclusion:The TCM STC model based on classification achieved superior performance in converting synonymous terms for symptoms,patterns,and treatments.The misjudgment inspection method based on OCMH showed superior performance in identifying incorrect outputs.展开更多
The study of synonyms based on corpus has become a hot topic in recent years,and the task of differentiating synonyms has always been a complex issue.The current study made an attempt to investigate the differences am...The study of synonyms based on corpus has become a hot topic in recent years,and the task of differentiating synonyms has always been a complex issue.The current study made an attempt to investigate the differences among English noun synonyms“opposition”,“resistance”and“defiance”from the perspective of frequency distribution,collocation and semantic prosody based on COCA.This research shows that in terms of frequency distribution,“opposition”and“resistance”are more frequently used than“defiance”.Both of the two are most commonly used in academic journals while“defiance”is most frequently used in fiction.All of these three words rarely appear in TV and movie subtitles.Second,from the perspective of collocation,“opposition”often collocates with words about politics and personal state,“resistance”usually appears with words concerning politics and medicine,and“defiance”mainly shows up in the fields of military,medicine,personal state and others.Third,from the dimension of semantic prosody,“opposition”presents negative semantic prosody,“resistance”has neutral semantic prosody,and“defiance”indicates mixed semantic prosody.The present study is able to enrich the relevant study on synonym differentiation,and highlight the importance of understanding the subtle differences among synonyms.展开更多
This paper explores the differences between the near-synonyms“initially”and“firstly”using the Corpus of Contemporary American English(COCA)and the theory of extended units of meaning.The study analyzes the two wor...This paper explores the differences between the near-synonyms“initially”and“firstly”using the Corpus of Contemporary American English(COCA)and the theory of extended units of meaning.The study analyzes the two words from five perspectives:word frequency,collocation,colligation,semantic preference,and semantic prosody.Results show that“initially”is more frequent,especially in academic writing,while“firstly”is common in blogs and informal contexts.“Firstly”often collocates with nouns and expresses logical sequence,while“initially”collocates with adjectives and describes initial states or scientific processes,often with negative connotations.This study highlights the effectiveness of corpora in distinguishing near-synonyms and offers insights for English vocabulary learning.展开更多
Dear Editor,Recombinant protein therapeutics and gene therapies can help rescue monogenic disease phenotypes(Ebrahimi and Samanta,2023).Sufficient/high expression of a therapeutic product is an important consideration...Dear Editor,Recombinant protein therapeutics and gene therapies can help rescue monogenic disease phenotypes(Ebrahimi and Samanta,2023).Sufficient/high expression of a therapeutic product is an important consideration in this regard,which is usually achieved by gene redesign,focused on altering synonymous codon usage/codon context,aimed at enhancing translational rates(Alexaki et al.,2019).Different approaches exist to adjust synonymous codon usage and boost protein expression levels(Katneni et al.,2022).As these strategies do not alter the primary sequence of a protein(Liu et al.,2021)they are not expected to alter protein structure and function.However。展开更多
Trogloneta yuensis Lin&Li,2013 is one of interesting member in morphology of the spider family Mysmenidae,and it should be possible for it to be widespread in the Southern China based on the currently known field ...Trogloneta yuensis Lin&Li,2013 is one of interesting member in morphology of the spider family Mysmenidae,and it should be possible for it to be widespread in the Southern China based on the currently known field survey records.Phricotelus yangaciong Lin&Li,2024 is a recent described mysmenid species.Through detailed morphological comparison,we firmly believe that it belongs to the same species as Trogloneta yuensis.According to the principle of priorty law of the Internation Code of Zoological nomenclature,a new synonymy,Phricotelus yangaiong Lin&Li,2024 syn.nov.,is formally proposed for Trogloneta yuensis Lin&Li,2013,and provided a brief retrospect for the genus Trogloneta in this paper.展开更多
基金The work is supported by National Natural Science Foundation of China (No. 60121101).
文摘In this study, a comparative analysis of the codon usage bias was performed in Aeropyrum pernix K1 and two other phylogenetically related Crenarchaeota microorganisms （i.e., Pyrobaculum aerophilum str. IM2 and Sulfolobus acidocaldarius DSM 639）. The results indicated that the synonymous codon usage in A. pernix K1 was less biased, which was highly correlated with the GC3s value. The codon usage patterns were phylogenetically conserved among these Crenarchaeota microorganisms. Comparatively, it is the species function rather than the gene function that determines their gene codon usage patterns. A. pernix K1, P. aerophilum str. IM2, and S. acidocaldarius DSM 639 live in differently extreme conditions. It is presumed that the hving environment played an important role in determining the codon usage pattern of these microorganisms. Besides, there was no strain-specific codon usage among these microorganisms. The extent of codon bias in A. pernix K1 and S. acidocaldarius DSM 639 were highly correlated with the gene expression level, but no such association was detected in P. aerophilum str. IM2 genomes.
基金supported by the National Natural Science Foundation of China (31401822)
文摘Apple（Malus×domestica） has been proposed as an important woody plant and the major cultivated fruit trees in temperate regions. Apple whole genome sequencing has been completed, which provided an excellent opportunity for genome-wide analysis of the synonymous codon usage patterns. In this study, a multivariate bioinformatics analysis was performed to reveal the characteristics of synonymous codon usage and the main factors affecting codon bias in apple. The neutrality, correspondence, and correlation analyses were performed by Codon W and SPSS（Statistical Product and Service Solutions） programs, indicating that the apple genome codon usage patterns were affected by mutational pressure and selective constraint. Meanwhile, coding sequence length and the hydrophobicity of proteins could also influence the codon usage patterns. In short, codon usage pattern analysis and determination of optimal codons has laid an important theoretical basis for genetic engineering, gene prediction and molecular evolution studies in apple.
文摘A comparative analysis of the codon usage bias was conducted in Methanosarcina mazei str. Goel and two related Euryarchaeota microorganisms （Picrophilus torridus str. DSM 9790 and Natronomonas pharaonis str. DSM 2160）. Results revealed that synonymous codon usage in Methanosarcina mazei str. Goel was less biased, which was highly correlated with the GC3S value. And the codon usage patterns were phylogenetically conserved among those Euryarchaeota microorganisms. By employing a hierarchical clustering analysis, it can be seen that it is more the species than the gene function that determines their gene codon usage pattems. Considering that those microorganisms live in different environments where the pH conditions vary quite a lot, it can be presumed that their living environments, especially the pH conditions, play an important role in determining those microorganisms＇ codon usage pattems.
基金supported by the National Natural Science Foundation of China(No.81873596).
文摘Objective:Autosomal dominant polycystic kidney disease(ADPKD)is mainly caused by the pathogenic mutation of PKD1 or PKD2 gene and usually affects bilateral kidneys.Synonymous mutations are generally assumed to be neutral as they do not alter amino acids.Herein,we described an extremely rare ADPKD child caused by a heterozygous synonymous mutation of PKD2 gene accompanied by massive proteinuria and congenital solitary kidney.Methods:Clinical characteristics of the patients were summarized.Whole-exome sequencing was performed to screen the disease-causing gene mutation,and reverse transcription polymerase chain reaction(RT-PCR)and Sanger sequencing were applied to analyze the impact of the identified mutation on gene transcription and splicing.Results:Polycystic changes were found in the solitary kidney of a girl initially presented with nephrotic-range proteinuria.Thereafter her mother and 2 other family members were diagnosed to be ADPKD.Whole-exome sequencing of the proband identified a heterozygous synonymous mutation(c.1716G>A,p.Lys572=)located in the splicing site of exon 7 in PKD2 gene,which was co-segregated with the PKD phenotype in the family.RT-PCR and direct sequencing of amplified products revealed that this heterozygous synonymous mutation led to exon7 skipping in PKD2 gene.Conclusion:We reported an extremely rare child case of ADPKD2 in combination with solitary kidney and nephrotic-range proteinuria,and firstly confirmed the pathogenicity of a heterozygous synonymous mutation(c.1716G>A)in PKD2 gene.The results indicate that synonymous mutations should not be excluded from disease-causing if they are located in splicing site of an exon.
基金The National Key Research and Development Program of China(No.2018YFC1314900,2018YFC1314902)the National Natural Science Foundation of China(No.61571109)the Fundamental Research Funds for the Central Universities(No.2242017K3DN04).
文摘To investigate how synonymous codons have been adapted to the formation of ribonucleic acid(RNA)G-quadruplex(rG4)structure,a computational searching algorithm G4Hunter was applied to detect rG4 structures in protein-coding sequences of mRNAs in five eukaryotic species.The native sequences forming rG4s were then compared with randomized sequences to evaluate selection on synonymous codons.Factors that may influence the formation of rG4 were also investigated,and the selection pressures of rG4 in different gene regions were compared to explore its potential roles in gene regulation.The results show universal selective pressure acts on synonymous codons in rG4 regions to facilitate rG4 formation in five eukaryotic organisms.While G-rich codon combinations are preferred in the rG4 structural region,C-rich codon combinations are selectively unfavorable for rG4 formation.Gene's codon usage bias,nucleotide composition,and evolutionary rate can account for the selective variations on synonymous codons among rG4 structures within a species.Moreover,rG4 structures in the translational initiation region showed significantly higher selective pressures than those in the translational elongation region.
基金Supported by the National High Technology Research and Development Programme of China(No.2008AA01Z144)the National NaturalScience Foundation of China(No.61073126,61073129)
文摘In this work,an approach is proposed to acquire synonymous attribute phrases of named entities(NEs) from an online encyclopedia.Synonymous attribute phrases are the phrases that express the same attribute with different surface forms for a class of NEs.Specifically,the proposed approach is composed of three stages.Firstly,the entries related to a given NE class are automatically selected from an online encyclopedia.Secondly,attribute phrases are extracted based on the statistics of phrase frequency.Thirdly,synonymous attributes are identified in a pairwise manner through a classification framework combining multiple features.The proposed approach is applied on Baidu Baike,a Chinese online encyclopedia,for four different NE classes.Experimental results show that the approach obtains an average precision of 74%and an average F-value of 65%for the four NE classes.In particular,thousands of synonymous attribute phrase pairs are acquired for each class,which demonstrates the effectiveness of the proposed approach.
文摘The APCDDI （adenomatosis polyposis coli down-regulated 1） gene is an inhibitor of the Wnt signaling pathway, and a rare mutation of this gene has been associated with hereditary hypotrichosis simplex. In this study, the authors aimed to investigate whether common APCDD1 gene polymorphisms contribute to the development of androgenic alopecia. Patients （n = 210） with androgenic alopecia and 98 controls were investigated. SNPs （Single nucleotide polymorphisms） in the coding region of the gene were sequenced. A significant difference in genotype distribution was found for the c. 1781C/T, p.L476L SNP （rs3185480） of the APCDD1 gene. This SNP is located in exon 5 and is associated with a 3.5- and a 2.8-fold increase in risk for the development of androgenic alopecia for homozygote （CI 0.933-13.125; nominal regression P = 0.063） and heterozygote （CI 1.086-7.217; nominal regression P = 0.033） carriers, respectively. These data suggest that the rs3185480 polymorphism contributes to the development of androgenic alopecia. Protein expression experiments revealed that the polymorphism is associated with reduced APCDDI protein abundance. This reduction is likely due to altered codon usage for leucine from a preferred codon （CTC） to a rare codon （CTT）, which might influence translation efficiency and, thus, APCDDI protein level.
基金supported by the Fujian Provincial Health Technology Project(China)(No.2023QNA016)the Guidance in Medical and Health Program of Xiamen,China(No.3502Z20209120)Scientific Research Foundation for Advanced Talents,Xiang’an Hospital of Xiamen University(China)(No.PM201809170018).
文摘Mutations in fibrillin-1 gene(FBN1)have been shown to be associated with Marfan syndrome and most FBN1 mutations display missense or nonsense.Recently,reports on synonymous mutation-related diseases have attracted widespread attention.Zhang et al demonstrated that synonymous mutations in saccharomyces cerevisiae have pathogenicity like non-synonymous mutations.1 Based on a special Marfan syndrome patient with a novel synonymous mutation in FNB1.
基金This work was supported by the Ministry of Science and Technology of China(Grant No.2001AA231061)the National Natural Science Foundation of China(Grant No.30270748)awarded to JY.We thank Mr.Jun Li for valuable discussion.
文摘Methods for estimating synonymous and nonsynonymous substitution rates among protein-coding sequences adopt different mutation (substitution) models with subtle yet significant differences, which lead to different estimates of evolutionary information. Little attention has been devoted to the comparison of methods for obtaining reliable estimates since the amount of sequence variations within targeted datasets is always unpredictable. To our knowledge, there is little information available in literature about evaluation of these different methods. In this study, we compared six widely used methods and provided with evaluation results using simulated sequences. The results indicate that incorporating sequence features (such as transition/transversion bias and nucleotide/codon frequency bias) into methods could yield better performance. We recommend that conclusions related to or derived from Ka and Ks analyses should not be readily drawn only according to results from one method.
基金This work was supported by the National Natural Science Foundation of China (Grant No. 39970412) and the sub-project of the "95" Key Project of the Chinese Academy of Sciences.
文摘Synonymous codon bias has been examined in 78 human genes (19967 codons) and measured by relative synonymous codon usage (RSCU). Relative frequencies of all kinds of dinucleotides in 2,3 or 3,4 codon positions have been calculated, and codon-anticodon binding strength has been estimated by the stacking energies of codon-anticodon bases in Watson-Crick pairs. The data show common features in synonymous codon bias for all codon families in human genes: all C-ending codons, which possess the strongest codon-anticodon binding energies, are the most favored codons in almost all codon families, and those codons with medium codon-anticodon binding energies are avoided. Data analysis suggests that besides isochore and genome signature, codon-anticodon binding strength may be closely related to synonymous codon choice in human genes. The join-effect of these factors on human genes results in the common features in codon bias.
文摘p53 is an intrinsically disordered protein with a large number of post-translational modifications and interacting partners.The hierarchical order and subcellular location of these events are still poorly understood.The activation of p53 during the DNA damage response(DDR)requires a switch in the activity of the E3 ubiquitin ligase MDM2 from a negative to a positive regulator of p53.This is mediated by the ATM kinase that regulates the binding of MDM2 to the p53 mRNA facilitating an increase in p53 synthesis.Here we show that the binding of MDM2 to the p53 mRNA brings ATM to the p53 polysome where it phosphorylates the nascent p53 at serine 15 and prevents MDM2-mediated degradation of p53.A single synonymous mutation in p53 codon 22(L22L)prevents the phosphorylation of the nascent p53 protein and the stabilization of p53 following genotoxic stress.The ATM trafficking from the nucleus to the p53 polysome is mediated by MDM2,which requires its interaction with the ribosomal proteins RPL5 and RPL11.These results show how the ATM kinase phosphorylates the p53 protein while it is bang synthesized and offer a novel mechanism whereby a single synonymous mutation controls the stability and activity of the encoded protein.
文摘In the English language, there are many words which are considered synonymous in that dictionaries and thesauruses often define them in identical meanings. Under such circumstances, EFL learners are confronted with a big difficulty in acquiring these words of similar meanings. They often regard synonymous words as equivalents and use them alternately, which sometimes result in ambiguity or awkwardness of their language. However, with the advent of corpora and concordancing programs, a new way of investigating and learning English synonymous words has emerged. This paper explores colligational patterns, collocational behavior and semantic prosody of two seemingly synonymous verbs, gain and obtain, in two native speaker corpora, the Brown Corpus and the LOB Corpus, in order to show how these 'equivalencies' can be misleading because 'synonymous' words are typically used in different ways. The study also examines EFL learners' behavior in using synonymous words by investigating the Chinese Learner English Corpus (CLEC). From the results of the study, it can be seen that Chinese EFL learners have not yet acquired a full understanding of the usage of gain and obtain with respect to colligation, collocation and semantic prosody. Their underuses and overuses of some grammatical forms and lexical patterns of the two target synonymous words might be influenced either by their mother tongue or by the registers of their English writing or by both. The paper finally discusses the implications of corpus-based study in vocabulary teaching and learning in general.
基金the National Natural Science Foundation of China(81971547 and 81900136)Beijing Hospitals Authority's Ascent Plan(DFL20221001)+1 种基金National Key Research and Development Program of China(2021YFC2702005)Wu Jieping Medical Foundation(320.6750.2022-03-53).
文摘Background Adenosine deaminase(ADA)is a key enzyme in the purine salvage pathway.Genetic defects of the ADA gene can cause a subtype of severe combined immunodeficiency.To date,few Chinese cases have been reported.Methods We retrospectively reviewed the medical records of patients diagnosed with ADA deficiency in Beijing Children's Hospital and summarized the previously published ADA deficiency cases from China in the literature.Results Nine patients were identified with two novel mutations(W272X and Q202=).Early-onset infection,thymic abnor-malities and failure to thrive were the most common manifestations of Chinese ADA-deficient patients.The ADA genotype has a major effect on the clinical phenotype.Notably,a novel synonymous mutation(c.606G>A,p.Q202=)was identified in a delayed-onset patient,which affected pre-mRNA splicing leading to a frameshift and premature truncation of the protein.Furthermore,the patient showed γδT cells expansion with an increased effect or phenotype,which may be associated with the delayed onset of disease.In addition,we reported cerebral aneurysm and intracranial artery stenosis for the first time in ADA deficiency.Five patients died with a median age of four months,while two patients received stem cell transplantation and are alive.Conclusions This study described the first case series of Chinese ADA-deficient patients.Early-onset infection,thymic abnormalities and failure to thrive were the most common manifestations in our patients.We identified a synonymous muta-tion that affected pre-mRNA splicing in the ADA gene,which had never been reported in ADA deficiency.Furthermore,we reported cerebral aneurysm in a delayed-onset patient for the first time.Further study is warranted to investigate the underlying mechanisms.
基金The National Key R&D Program of China supported this study(2017YFC1700303).
文摘Background:The medical records of traditional Chinese medicine(TCM)contain numerous synonymous terms with different descriptions,which is not conducive to computer-aided data mining of TCM.However,there is a lack of models available to normalize synonymous TCM terms.Therefore,construction of a synonymous term conversion(STC)model for normalizing synonymous TCM terms is necessary.Methods:Based on the neural networks of bidirectional encoder representations from transformers(BERT),four types of TCM STC models were designed:Models based on BERT and text classification,text sequence generation,named entity recognition,and text matching.The superior STC model was selected on the basis of its performance in converting synonymous terms.Moreover,three misjudgment inspection methods for the conversion results of the STC model based on inconsistency were proposed to find incorrect term conversion:Neuron random deactivation,output comparison of multiple isomorphic models,and output comparison of multiple heterogeneous models(OCMH).Results:The classification-based STC model outperformed the other STC task models.It achieved F1 scores of 0.91,0.91,and 0.83 for performing symptoms,patterns,and treatments STC tasks,respectively.The OCMH method showed the best performance in misjudgment inspection,with wrong detection rates of 0.80,0.84,and 0.90 in the term conversion results for symptoms,patterns,and treatments,respectively.Conclusion:The TCM STC model based on classification achieved superior performance in converting synonymous terms for symptoms,patterns,and treatments.The misjudgment inspection method based on OCMH showed superior performance in identifying incorrect outputs.
文摘The study of synonyms based on corpus has become a hot topic in recent years,and the task of differentiating synonyms has always been a complex issue.The current study made an attempt to investigate the differences among English noun synonyms“opposition”,“resistance”and“defiance”from the perspective of frequency distribution,collocation and semantic prosody based on COCA.This research shows that in terms of frequency distribution,“opposition”and“resistance”are more frequently used than“defiance”.Both of the two are most commonly used in academic journals while“defiance”is most frequently used in fiction.All of these three words rarely appear in TV and movie subtitles.Second,from the perspective of collocation,“opposition”often collocates with words about politics and personal state,“resistance”usually appears with words concerning politics and medicine,and“defiance”mainly shows up in the fields of military,medicine,personal state and others.Third,from the dimension of semantic prosody,“opposition”presents negative semantic prosody,“resistance”has neutral semantic prosody,and“defiance”indicates mixed semantic prosody.The present study is able to enrich the relevant study on synonym differentiation,and highlight the importance of understanding the subtle differences among synonyms.
文摘This paper explores the differences between the near-synonyms“initially”and“firstly”using the Corpus of Contemporary American English(COCA)and the theory of extended units of meaning.The study analyzes the two words from five perspectives:word frequency,collocation,colligation,semantic preference,and semantic prosody.Results show that“initially”is more frequent,especially in academic writing,while“firstly”is common in blogs and informal contexts.“Firstly”often collocates with nouns and expresses logical sequence,while“initially”collocates with adjectives and describes initial states or scientific processes,often with negative connotations.This study highlights the effectiveness of corpora in distinguishing near-synonyms and offers insights for English vocabulary learning.
基金supported by grant R01HL151392(to A.A.K)and AMED-CREST with Grant Number JP21gm1410008(to H.T.)supported by funds from the Center for Biologics Evaluation and Research,US Food and Drug Administration.
文摘Dear Editor,Recombinant protein therapeutics and gene therapies can help rescue monogenic disease phenotypes(Ebrahimi and Samanta,2023).Sufficient/high expression of a therapeutic product is an important consideration in this regard,which is usually achieved by gene redesign,focused on altering synonymous codon usage/codon context,aimed at enhancing translational rates(Alexaki et al.,2019).Different approaches exist to adjust synonymous codon usage and boost protein expression levels(Katneni et al.,2022).As these strategies do not alter the primary sequence of a protein(Liu et al.,2021)they are not expected to alter protein structure and function.However。
基金supported by the Nationa Natural Science Foundation of China(NSFC-31972870,31772410).
文摘Trogloneta yuensis Lin&Li,2013 is one of interesting member in morphology of the spider family Mysmenidae,and it should be possible for it to be widespread in the Southern China based on the currently known field survey records.Phricotelus yangaciong Lin&Li,2024 is a recent described mysmenid species.Through detailed morphological comparison,we firmly believe that it belongs to the same species as Trogloneta yuensis.According to the principle of priorty law of the Internation Code of Zoological nomenclature,a new synonymy,Phricotelus yangaiong Lin&Li,2024 syn.nov.,is formally proposed for Trogloneta yuensis Lin&Li,2013,and provided a brief retrospect for the genus Trogloneta in this paper.
