A Presumed Synonymous Mutation of PKD2 Caused Autosomal Dominant Polycystic Kidney Disease in a Chinese Family

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.

Delayed-onset adenosine deaminase deficiency with a novel synonymous mutation and a case series from China

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.

Traditional Chinese Medicine Synonymous Term Conversion:A Bidirectional Encoder Representations from Transformers-Based Model for Converting Synonymous Terms in Traditional Chinese Medicine

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.

Is there a close relationship between synonymous codon bias and codon-anticodon binding strength in human genes?

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.

A single synonymous mutation determines the phosphorylation and stability of the nascent protein

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.

A Corpus-Driven Perspective on the Verb Valency Structure of Chinese EFL Learners:A Case Study of“Suggest”and“Advise”

This paper investigates the verb valency structure of English that is used by English as Foreign Language(EFL)learners from a corpus-driven perspective.Specifically,it focuses on the usage of the verbs“suggest”and“advise”in a selected corpus.By analyzing a sample of written and spoken texts,this study attempts to investigate the similarities and differences in the patterns of verb valency between native English speakers and Chinese EFL learners.The findings of this research can contribute to a better understanding of the challenges faced by Chinese EFL learners in acquiring accurate verb valency structures and provide insights for language teachers in designing effective pedagogical approaches.

Type-2 Diabetes Mellitus and Glucagon-Like Peptide-1 Receptor toward Predicting Possible Association

Aim: This study aimed to investigate the effect of non-synonymous SNPs (nsSNPs) of the Glucagon-like peptide-1 Receptor (GLP-1R) gene in protein function and structure using different computational software. Introduction: The GLP1R gene provides the necessary instruction for the synthesis of the insulin hormones which is needed for glucose catabolism. Polymorphisms in this gene are associated with diabetes. The protein is an important drug target for the treatment of type-2 diabetes and stroke. Material and Methods: Different nsSNPs and protein-related sequences were obtained from NCBI and ExPASY database. Gene associations and interactions were predicted using GeneMANIA software. Deleterious and damaging effects of nsSNPs were analyzed using SIFT, Provean, and Polyphen-2. The association of the nsSNPs with the disease was predicted using SNPs & GO software. Protein stability was investigated using I-Mutant and MUpro software. The structural and functional impact of point mutations was predicted using Project Hope software. Project Hope analyzes the mutations according to their size, charge, hydrophobicity, and conservancy. Results: The GLP1R gene was found to have an association with 20 other different genes. Among the most important ones is the GCG (glucagon) gene which is also a trans membrane protein. Overall 7229 variants were seen, and the missense variants or nsSNPs (146) were selected for further analysis. The total number of nsSNPs obtained in this study was 146. After being subjected to SIFT software (27 Deleterious and 119 Tolerated) were predicted. Analysis with Provean showed that (20 deleterious and 7 neutral). Analysis using Polyphen-2 revealed 17 probably damaging, 2 possibly damaging and 1 benign nsSNPs. Using two additional software SNPs & GO and PHD-SNPs showed that 14 and 17 nsSNPs had a disease effect, respectively. Project Hope software predicts the effect of the 14 nsSNPs on the protein function due to differences in charge, size, hydrophobicity, and conservancy between the wild and mutant types. Conclusion: In this study, the 14 nsSNPs which were highly affected the protein function. This protein is providing the necessary instruction for the synthesis of the insulin hormones which is needed for glucose catabolism. Polymorphisms in this gene are associated with diabetes and also affect the treatment of diabetic patients due to the fact that the protein acts as an important drug target.

A Comparative Study of the Usage of Synonyms Based on BNC-Taking Assessment and Evaluation as Examples

The discrimination of synonyms has always been one of the great challenges for English learners.Taking assessment and evaluation as examples,this study analyses the similarities and differences of the two words,as well as their usage from the perspectives of frequency,stylistics,collocation and semantic prosody with the help of British National Corpus,and demonstrates the importance of corpus retrieval tools in synonyms discrimination.Furthermore,this paper will give some suggestions for English learners and teachers in English vocabulary teaching.

Covariation of mutation pairs expressed in HIV-1 protease and reverse transcriptase genes subjected to varying treatments

A previous study, focused on the correlation of muta-tion pairs of synonymous (S) and asynonymous (A) mutations, distinguished only between the treated and untreated data of protease and reverse tran-scriptase (RT) of HIV-1 subtype B. It is well known that single mutation patterns in HIV-1 are treat-ment-specific. It logically follows that covariation between mutations will also be treatment specific. Thus, our motivation is to give a more in depth study of the covariation between mutation pairs, analyzing not only treated and untreated, but what specific treatments were used, and how they affected the co-variation between the mutations differently. We in-tended to further deepen this study by analyzing the covariation of mutations in protease and RT in dif-ferent subtypes of HIV-1. We found that virus sam-ples subjected to antiretroviral Protease- and RT- inhibitors do show different patterns of mutation covariation in B-subtype protease and RT of HIV-1, while maintaining the same overall trend. covariation will tend to be higher and more distinct from and covariation after treatment. The same trend continues in protease and RT re-gardless of subtype. We also found the highly cova-ried codon positions, position pairs, and position- covariation clusters in protease, affected by different treatments. Most of them are well known major drug-resistance sites for these treatments.

Analysis of Codon Usage Pattern of Banana Basic Secretory Protease Gene

[Objective] The objective of this study was to understand the codon usage bias pattern of banana pathogenesis-related 17 gene, Basic Secretory Protease gene(MaBSP). [Method] Relative codon usage patterns of MaBSP were calculated using the software CodonW version 1.4.2. and the web-based tool(http://kazusa.or.jp/codon/).[Result] Our findings showed that C-ended and G-ended codons were the most preferential except the TER codon UGA which was coded for by just one codon. The ENc value, relationship between AT bias and GC bias, Random synonymous codon usage(RSCU) and CAI all showed that codon bias usage existed in MaBSP gene.[Conclusion] The codon usage patterns of MaBSP gene is principally influenced by natural selection in the third position. However, other multiple factors also influence this pattern.

Surveillance of chikungunya virus in Andhra Pradesh,Southern India

Objective:The study involved survey and screening of areas suspected of chikungunya virus (CHIKV) infection,characterizing the causative agent and identifying the circulating CHIKV genotype.Methods:Acute phase samples were screened by the use of RTPCR using primer set DVRChk-F/DVRChk-R whereas convalescent samples were tested by CHIKV IgM strips. Results:Two hundred and seventy five acute phase samples were screened by RT-PCR.of which 149(54.18%) showed positivity for CHIKV.Later on 192 convalescent phase samples were tested for CHIKV specific antibodies in which 125(65.10%) samples were found to be positive.Four CHIKV strains were selected and subjected to cloning followed by nucleotide sequencing and were submitted to the Genbank DMA database with the Accession numbers(GQ119362,GQ119363, GQl 19364,and FJ225403).The Sequence analysis of "CHIK-Kadapa" strain(GQ119362) with other CHIKV isolates suggested that the present CHIKV strain has(99.23±0.52)%and 100%identity with Central East South African isolates(CESA) at nucleotide and amino acid levels respectively.Two unique non synonymous mutations S168L and D183V were depicted in El gene of the selected strains of the present study.Conclusions:The 14 months survey revealed the circulation of CHIKV in 2008-2009 in Andhra Pradesh and the causative agent is identified to be of Central East South African(CESA) origin.The importance of the non synonymous mutations(S168L and D183V) and their role in the mobility and strength of the El-El and E1-E2 interactions needs further investigations.The study also urges the need for intensifying the epidemiological and entomological surveillance to combat any such CHIKV outbreak in the near future.

翻译中实现社会语用等效(英文)

As a medium between two different languages, between peoples of two countries, translation is not only a matter of language, but also of cross-cultural transference. According to Professor He Ziran, socio-pragmatic translation is the kind of translation which examines the conditions on language use that stem from the social and cultural situations to serve cross-cultural communication. This paper focuses on the ways used to achieve socio-pragmatic equivalence in translation practice.

Genome-Wide Patterns of Codon Usage in the Pacific Oyster Genome

The use of synonymous codons with varying frequencies has been observed in many species,and the magnitude varies among closely related species and genes within the same genome.Mutational processes or natural selective pressures affect this bias.However,a systematic investigation of codon usage pattern for molluscan species and its association with the two factors hasn’t been conducted.In this study,the whole genome codon usage patterns in oyster genome is investigated using the relative synonymous codon usage(RSCU)method,and 17 putative optimal codons were identified,wherein most had either a cytosine(C)or guanine(G)residue at the third position.Results showed that codon bias was positively associated with gene expression levels and breadth.Optimal codons had different mutational bias patterns compared with nonoptimal codons.Moreover,the results show that codon bias is negatively associated with nucleotide diversity.In the oyster genome,the fourfold degenerate codons are affected by different selective pressures,which can be regarded as an evidence that natural selection shapes codon usage patterns.This research will help to understand how natural selection and mutation bias affect codon usage in Mollusca genomes.

Sacrococcygeal Teratoma

Key Facts Synonyms:Sacrococcygeal teratoma(SGT),germ cell tumor of coccyx Definition:Tumors containing hair,teeth,cartilage,and fat extending from the coccyx and potentially growing both internally and externally.

Redesign Vocabulary Exercises In college English Intensive Reading Course book

Nowadays,more and more university students have Teacher’s Book for College English. They know answers of exercises from it before they do them. Some of them just copy down the right answers and wait for teacher’s praise. In this situation, College English teachers should redesign the exercises after each unit so that students will be interested and involved in learning. This study thus suggests several ways to redesign the vocabulary exercises from “ College English". It expects, on the one hand, to raise College English teachers’ awareness of the necessity to change the exercises. On the other hand, it expects to give them an inspiration, and example of designing more appropriate exercises so as to reinforce students’ vocabulary and enhance their language awareness.

Epidermoid Cyst of Cerebellopontine Angle

Synonyms: Epidermoid tumor,non-neoplastic inclusion cyst, congenital cholesteatoma of the cerebellopontine angle cistern.Definition: Congenital lesion arising from inclusion of ectodermal epithelial elements at time of neural tube closure during 3rd to 5th week of embryonic life, resulting in migration abnormalities of epiblastic cells.Classic imaging appearance:(1)Signal shows an insinuating cisternal lesion with low T1, high T2 close to that of cerebrospinal fluid (CSF).(2)FLAIR shows incomplete or absent attenuation.(3)Diffusion-weighted imaging shows epidermoid cyst has restricted diffusion(high-signal lesion).Other key facts:(1)3rd most common cerebellopontine angle-internal auditory canal (CPA-IAC) mass.(2)1% of all intracranial tumors.

Reversible Natural Language Watermarking Using Synonym Substitution and Arithmetic Coding

For protecting the copyright of a text and recovering its original content harmlessly,this paper proposes a novel reversible natural language watermarking method that combines arithmetic coding and synonym substitution operations.By analyzing relative frequencies of synonymous words,synonyms employed for carrying payload are quantized into an unbalanced and redundant binary sequence.The quantized binary sequence is compressed by adaptive binary arithmetic coding losslessly to provide a spare for accommodating additional data.Then,the compressed data appended with the watermark are embedded into the cover text via synonym substitutions in an invertible manner.On the receiver side,the watermark and compressed data can be extracted by decoding the values of synonyms in the watermarked text,as a result of which the original context can be perfectly recovered by decompressing the extracted compressed data and substituting the replaced synonyms with their original synonyms.Experimental results demonstrate that the proposed method can extract the watermark successfully and achieve a lossless recovery of the original text.Additionally,it achieves a high embedding capacity.

工程英语词汇的处理

工程英语词汇的概念明确，许多是单义词，很少有关联意义，也不带感情色彩，译员主要是要把它们在工程方面的准确意义掌握好，同时要重视工程英语词汇中出现的一些词汇现象。下面介绍几种工程英语翻译中常遇到的词汇现象的处理方法：一、一词多义的处理在英语里，一个词有...

论英语和美语同步发展的趋向

1.美语的发生及其所谓“独立性”在探讨两国语言的发展趋向以前,须对美语的发生有所认识。简单地说,所谓美语就是现在西半球的美洲——美利坚合众国所在人民说的英语,以别于欧洲不列颠人民(Britons)所讲的英语;前者是17世纪从欧洲不列颠岛传到美洲殖民地的英语的后裔,因此它同后者有着语源上的密不可分的关系。然即使如此,

A reassessment of Iteravis huchzermeyeri and Gansus zheni from the Jehol Biota in western Liaoning, China

The authors reassessed the taxonomic distinction of Iteravis huchzermeyeri and Gansus zheni,which are two species of Ornithuromorpha based on specimens from the same locality in western Liaoning and derive from the Jehol Biota.The detailed comparisons of the holotype and referred specimens of both species,reveal no anatomical features that distinguish these taxa as separate species.Some minor differences are considered to relate to ontogenetic or interspecific differences.The stratigraphic occurrence for both specimens is the Lower Cretaceous Jiufotang Formation.Accordingly,the authors conclude that Iteravis huchzermeyeri has priority,by 15 days,for this taxon and that Gansus zheni is a junior synonym.The diagnosis of Iteravis huchzermeyeri is revised based on further study on all specimens referred to this species.Its generic distinction from Gansus is maintained thereby removing a potential genus-level correlation linking Xiagou Formation in Gansu Province with the Jiufotang Formation in Liaoning Province.