The Pattern of Occurrence of Cytosine in the Genetic Code Minimizes Deleterious Mutations and Favors Proper Function of the Translational Machinery

The standard genetic code consists of 64 combinations of base triplets made from four different bases. The research aim of this study was to investigate the pattern of occurrence of cytosine in the genetic code. By exploring the base composition and sequence of all 64 codons, the author found some important features based on the instability of cytosine. Because cytosine undergoes spontaneous deamination that converts it into uracil, it is evolutionarily favorable to exclude cytosine from codons critical to the initiation and termination of translation. For amino acids that have one to three synonymous codons (also called synonyms), the frequency of occurrence of C in the first and second positions of their mRNA codons is significantly lower than the frequencies of A, U, and G. For mRNA codons that encode amino acids with four synonyms, the trend of base composition is opposite to those encoding amino acids with one to three synonyms;the instability of C could be inhibited or reduced via formation of hydrogen bonds with a G and/or with a protonated C, and the secondary structure of the resultant mRNA could be adjusted via the multiple synonymous alternates at the third position of their codons to facilitate the translation process. The overall pattern of occurrence for C in the genetic code not only minimizes deleterious mutations and favors proper function of the translational machinery by excluding C from certain positions within codons, but also allows the occurrence of genetic diversity via mutation by including C in less-critical positions.

Does mRNA structure contain genetic information for regulating co-translational protein folding？

Currently many facets of genetic information are illdefined. In particular, how protein folding is genetically regulated has been a long-standing issue for genetics and protein biology. And a generic mechanistic model with supports of genomic data is still lacking. Recent technological advances have enabled much needed genome-wide experiments. While putting the effect of codon optimality on debate, these studies have supplied mounting evidence suggesting a role of m RNA structure in the regulation of protein folding by modulating translational elongation rate. In conjunctions with previous theories, this mechanistic model of protein folding guided by m RNA structure shall expand our understandings of genetic information and offer new insights into various biomedical puzzles.

Genetic interactions in translational research on cancer

Genetic interactions are functional crosstalk among different genetic loci that lead to phenotypic changes,such as health or viability alterations.A disease or lethal phenotype that results from the combined effects of gene mutations at different loci is termed a synthetic sickness or synthetic lethality,respectively.Studies of genetic interaction have provided insight on the relationships among biochemical processes or pathways.Cancer results from genetic interactions and is a major focus of current studies in genetic interactions.Various basic and translational cancer studies have explored the concept of genetic interactions,including studies of the mechanistic characterization of genes,drug discovery,biomarker identification and the rational design of combination therapies.This review discusses the implications of genetic interactions in the development of personalized cancer therapies,the identification of treatment-responsive genes,the delineation of mechanisms of chemoresistance and the rational design of combined therapeutic strategies to overcome drug resistance.

Genetic algorithm for λ-optimal translation sequence of rough communication

In rough communication, because each agent has a different language and can not provide precise communication to each other, the concept translated among multi-agents will loss some information, and this results in a less or rougher concept. With different translation sequences the amount of the missed knowledge is varied. The λ-optimal translation sequence of rough communication, which concerns both every agent and the last agent taking part in rough communication to get information as much as he （or she） can, is given. In order to get the λ-optimal translation sequence, a genetic algorithm is used. Analysis and simulation of the algorithm demonstrate the effectiveness of the approach.

Pharmacogenetics of type 2 diabetes mellitus: An example of success in clinical and translational medicine

The pharmacological interventions currently available to control type 2 diabetes mellitus(T2DM) show a wide interindividual variability in drug response, emphasizing the importance of a personalized, more effective medical treatment for each individual patient. In this context, a growing interest has emerged in recent years and has focused on pharmacogenetics, a discipline aimed at understanding the variability in patients' drug response, making it possible to predict which drug is best for each patient and at what doses. Recent pharmacological and clinical evidences indicate that genetic polymorphisms(or genetic variations) of certain genes can adversely affect drug response and therapeutic efficacy of oral hypoglycemic agents in patients with T2 DM, through pharmacokinetic- and/or pharmacodynamic-based mechanisms that may reduce the therapeutic effects or increase toxicity. For example, genetic variants in genes encoding enzymes of the cytochrome P-450 superfamily, or proteins of the ATP-sensitive potassium channel on the beta-cell of the pancreas, are responsible for the interindividual variability of drug response to sulfonylureas in patients with T2 DM. Instead, genetic variants in the genes that encode for the organic cation transporters of metformin have been related to changes in both pharmacodynamic and pharmacokinetic responses to metformin in metformin-treated patients. Thus, based on the individual's genotype, the possibility, in these subjects, of a personalized therapy constitutes the main goal of pharmacogenetics, directly leading to the development of the right medicine for the right patient. Undoubtedly, this represents an integral part of the translational medicine network.

Genetic screening of liver cancer:State of the art

Liver cancer,primarily hepatocellular carcinoma,remains a global health challenge with rising incidence and limited therapeutic options.Genetic factors play a pivotal role in the development and progression of liver cancer.This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer.We discuss the genetic underpinnings of liver cancer,emphasizing the critical role of risk-associated genetic variants,somatic mutations,and epigenetic alterations.We also explore the intricate interplay between environmental factors and genetics,highlighting how genetic screening can aid in risk stratification and early detection via using liquid biopsy,and advancements in high-throughput sequencing technologies.By synthesizing the latest research findings,we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer,shedding light on their potential to revolutionize early detection,risk assessment,and targeted therapies in the fight against this devastating disease.

Effective extraction of polyribosomes from astrocytes enables future discoveries on translation regulation

Translation regulation is an important layer of gene expression:Generation of genome-wide expression datasets at multi-omics levels in spatial,temporal,and cell-type resolution is essential for deciphering brain complexity.Regulation of gene expression is a highly dynamic process aiming at the production of precise levels of gene products to guarantee optimal cellular function,in response to physiological cues.Speedy advances in next-generation sequencing enabled the understanding of epigenomic and transcriptomic dynamic landscapes of different brain regions along development,aging,and disease progression.However,the correlation of the“transcriptome”with protein levels is poor because numerous mRNAs are subjected to manipulation of their translation efficiency,to warrant a favorable result under certain conditions.Hence,it is widely accepted that regulation at the translation level is a vital layer of gene expression.Quantification of actively translated mRNA populations(i.e.,“translatome”)is a more reliable predictor of the“proteome”(Wang et al.,2020).

A Discussion on Possible Indicators Related to Genetic Structure Changes in Plant Germplasm Conservation

The purpose of the present paper is to study and develop indicators and procedures for the evaluation of genetic structure changes in germplasm conservation due to social and natural environment reasons. Some basic concepts in germplasm study were introduced at first. Then, six kinds of indicators for genetic diversity as a measure of genetic potential of a germplasm collection were presented, i.e., numbers of different entities at certain level, evenness of the entity distribution, genetic similarity and genetic distance, genetic variance and genetic coefficient of variation, multivariate genetic variation indices, and coefficient of parentage. It was pointed out that genetic dispersion did not provide a complete concept of genetic diversity if without any information from genetic richness. Based on the above, the indicators for genetic erosion as the genetic structure changes of germplasm conservation due to social reasons, the indicators of genetic vulnerability as the genetic structure changes of germplasm conservation due to environmental stresses, the measurement of genetic drift and genetic shift as the genetic structure changes of germplasm collection during reproduction or seed increase were reviewed and developed. Furthermore, the estimation procedures of the indicators by using molecular markers were suggested. Finally, the case studies on suitable conservation sample size of self-pollinated and open-pollinated populations were given for reference.

A literature review of genetics and epigenetics of HCV-related hepatocellular carcinoma: translational impact

Background and Objective:Hepatocellular carcinoma(HCC)poses a significant global health burden and ranks as the fifth most prevalent cancer on a global scale.Hepatitis C virus(HCV)infection remains one of the major risk factors for HCC development.HCC is a heterogeneous disease,and the development of HCC caused by HCV is intricate and involves various factors,including genetic susceptibility,viral factors,immune response due to chronic inflammation,alcohol abuse,and metabolic dysfunction associated with fatty liver disease.In this review,we provide a comprehensive and updated review of research on the genetics and epigenetic mechanisms implicated in developing HCC associated with HCV infection.We also discuss the potential translational implications,including novel biomarkers and drugs for treatment.Methods:A comprehensive literature search was conducted in June 2023 in PubMed and Embase databases.Key Content and Findings:Recent findings indicate that a variety of genetic and epigenetic processes are involved in the pathogenesis and continue to exist even after the complete elimination of HCV.The deregulation of the epigenome has been identified as a significant factor in the deletrious effects of liver disease,especially during the initial stages when genetic alterations are uncommon.The enduring“epigenetic memory”of gene expression is believed to be regulated by epigenetic mechanisms,indicating that alterations caused by HCV infection continue to exist and are linked to the risk of development of liver cancer even after successful treatment.Systems biology analytical methods will be required to delineate the magnitude and significance of both genetic and epigenomic alterations in tumor evolution.Conclusions:By facilitating a more profound understanding of these aspects,this will ultimately foster the advancement of novel therapies and ultimately improve outcomes for patients.

Genetic pathways in cerebral palsy:a review of the implications for precision diagnosis and understanding disease mechanisms

Ce rebral palsy is a diagnostic term utilized to describe a group of permanent disorders affecting movement and posture.Patients with cerebral palsy are often only capable of limited activity,resulting from non-progressive disturbances in the fetal or neonatal brain.These disturbances severely impact the child’s daily life and impose a substantial economic burden on the family.Although cerebral palsy encompasses various brain injuries leading to similar clinical outcomes,the unde rstanding of its etiological pathways remains incomplete owing to its complexity and heterogeneity.This review aims to summarize the current knowledge on the genetic factors influencing cerebral palsy development.It is now widely acknowledged that genetic mutations and alterations play a pivotal role in cerebral palsy development,which can be further influenced by environmental fa ctors.Des pite continuous research endeavors,the underlying fa ctors contributing to cerebral palsy remain are still elusive.However,significant progress has been made in genetic research that has markedly enhanced our comprehension of the genetic factors underlying cerebral palsy development.Moreove r,these genetic factors have been categorized based on the identified gene mutations in patients through clinical genotyping,including thrombosis,angiogenesis,mitochondrial and oxidative phosphorylation function,neuronal migration,and cellular autophagy.Furthermore,exploring targeted genotypes holds potential for precision treatment.In conclusion,advancements in genetic research have substantially improved our understanding of the genetic causes underlying cerebral palsy.These breakthroughs have the potential to pave the way for new treatments and therapies,consequently shaping the future of cerebral palsy research and its clinical management.The investigation of cerebral palsy genetics holds the potential to significantly advance treatments and management strategies.By elucidating the underlying cellular mechanisms,we can develop to rgeted interventions to optimize outcomes.A continued collaboration between researchers and clinicians is imperative to comprehensively unravel the intricate genetic etiology of cerebral palsy.

An efficient method for constructing a random insertional mutant library for forward genetics in Nannochloropsis oceanica

Insertional mutation,phenotypic evaluation,and mutated gene cloning are widely used to clone genes from scratch.Exogenous genes can be integrated into the genome during non-homologous end joining(NHEJ)of the double-strand breaks of DNA,causing insertional mutation.The random insertional mutant library constructed using this method has become a method of forward genetics for gene cloning.However,the establishment of a random insertional mutant library requires a high transformation efficiency of exogenous genes.Many microalgal species show a low transformation efficiency,making constructing random insertional mutant libraries difficult.In this study,we established a highly efficient transformation method for constructing a random insertional mutant library of Nannochloropsis oceanica,and tentatively tried to isolate its genes to prove the feasibility of the method.A gene that may control the growth rate and cell size was identified.This method will facilitate the genetic studies of N.oceanica,which should also be a reference for other microalgal species.

Genetic variability and trait association analysis in linseed(Linum usitatissimum L.)for yield and related traits

Diversity information mining about a crop for different attributes is an essential step for effective breeding programs.The present investigation evaluates the quantum of genetic variability and determines the relationship among the important agro-economic traits based on two years of phenotypic data of 210 accessions of linseed.The traits,capsule weight per plant,capsule per plant,husk weight per plant,and seed weight per plant exhibited comparatively higher genetic coefficient of variation(GCV)and phenotypic coefficient of variation(PCV).In contrast,oil content and seed per capsule exhibited a lower value.The high magnitude of broad sense heritability was observed for all traits except seeds per capsule and husk weight per plant.The trait,capsules per plant,plant height,and days to 50%flowering showed high genetic advance coupled with high heritability.Hierarchical cluster analysis grouped 210 accessions into six distinct clusters.Out of 210,144(68.57%)accessions were grouped into three clusters(I,II,and III),in which cluster-III was the largest,containing 64 accessions followed by cluster II and cluster-I.The highest inter-cluster distance was observed between clusters-I and V(127.85),while the lowest was between clusters-II and IV(27.09).The positive correlation of capsule weight per plant with the seed weight per plant and a negative correlation with the days to 50%flowering indicates that high yielding linseed varieties with early flowering/maturity could be developed through direct and indirect selection.Further,seed yield and oil content could be enhanced together as indicated by ghe positive association among these two important traits.In this study,high yielding accessions with moderate to high oil content such as GP36,GP31,GP14,GP54,GP26,GP24,GP34,GP21,GP37 and GP27 and early flowering(less than 70 days)accessions such as GP2,GP26,GP27,CG33,CG44,CG42,CG132,and CG31 identified as potential genetic materials that could be exploited for developing early maturing varieties with high yield.In addition,information’s on various genetic parameters will help breeders to devise suitable breeding methodology for linseed genetic improvement for targeted traits.

Genetic Variations and Nonalcoholic Fatty Liver Disease:Field Synopsis,Systematic Meta-Analysis,and Epidemiological Evidence

Objective To systematically summarize the published literature on the genetic variants associated with nonalcoholic fatty liver disease(NAFLD).Methods Literature from Web of Science,PubMed,and Embase between January 1980 and September 2022 was systematically searched.Meta-analyses of the genetic variants were conducted using at least five data sources.The epidemiologic credibility of the significant associations was graded using the Venice criteria.Results Based on literature screening,399 eligible studies were included,comprising 381 candidate gene association,16 genome-wide association,and 2 whole-exome sequencing studies.We identified 465 genetic variants in 173 genes in candidate gene association studies,and 25 genetic variants in 17 genes were included in the meta-analysis.The meta-analysis identified 11 variants in 10 genes that were significantly associated with NAFLD,with cumulative epidemiological evidence of an association graded as strong for two variants in two genes(HFE,TNF),moderate for four variants in three genes(TM6SF2,GCKR,and ADIPOQ),and weak for five variants in five genes(MBOAT7,PEMT,PNPLA3,LEPR,and MTHFR).Conclusion This study identified six variants in five genes that had moderate to strong evidence of an association with NAFLD,which may help understand the genetic architecture of NAFLD risk.

LociScan,a tool for screening genetic marker combinations for plant variety discrimination

To reduce the cost and increase the efficiency of plant genetic marker fingerprinting for variety discrimination,it is desirable to identify the optimal marker combinations.We describe a marker combination screening model based on the genetic algorithm(GA)and implemented in a software tool,Loci Scan.Ratio-based variety discrimination power provided the largest optimization space among multiple fitness functions.Among GA parameters,an increase in population size and generation number enlarged optimization depth but also calculation workload.Exhaustive algorithm afforded the same optimization depth as GA but vastly increased calculation time.In comparison with two other software tools,Loci Scan accommodated missing data,reduced calculation time,and offered more fitness functions.In large datasets,the sample size of training data exerted the strongest influence on calculation time,whereas the marker size of training data showed no effect,and target marker number had limited effect on analysis speed.

Age-specific heterogeneity of genetic susceptibility to cardiovascular disease might have opposite outcomes depending on the presence of prediabetes

Examining age-specific heterogeneity of susceptibility to cardiovascular disease is also essential in individuals without prediabetes to determine its relative size and direction compared to those with prediabetes.Of particular interest,age-specific heterogeneity in genetic susceptibility may exhibit opposite directions depending on the presence or absence of prediabetes.

Temperature is a cryptic factor shaping the geographical pattern of genetic variation in Ceratophyllum demersum across a subtropical freshwater lake

Macrophyte habitats exhibit remarkable heterogeneity,encompassing the spatial variation of abiotic and biotic components such as changes in water conditions and weather as well as anthropogenic stressors.Environmental factors are thought to be important drivers shaping the genetic and epigenetic variation of aquatic plants.However,the links among genetic diversity,epigenetic variation,and environmental variables remain largely unclear,especially for clonal aquatic plants.Here,we performed population genetic and epigenetic analyses in conjunction with habitat discrimination to elucidate the environmental factors driving intraspecies genetic and epigenetic variation in hornwort(Ceratophyllum demersum)in a subtropical lake.Environmental factors were highly correlated with the genetic and epigenetic variation of C.demersum,with temperature being a key driver of the genetic variation.Lower temperature was detected to be correlated with greater genetic and epigenetic variation.Genetic and epigenetic variation were positively driven by water temperature,but were negatively affected by ambient air temperature.These findings indicate that the genetic and epigenetic variation of this clonal aquatic herb is not related to the geographic feature but is instead driven by environmental conditions,and demonstrate the effects of temperature on local genetic and epigenetic variation in aquatic systems.

Implications of genetic testing and informed consent before and after genetic testing in individuals with cancer

Recent advancements in next generation sequencing have allowed for genetic information become more readily available in the clinical setting for those affected by cancer and by treating clinicians.Given the lack of access to geneticists,medical oncologists and other treating physicians have begun ordering and interpreting genetic tests for individuals with cancer through the process of"mainstreaming".While this process has allowed for quicker access to genetic tests,the process of"mainstreaming"has also brought several challenges including the dissemination of variants of unknown significance results,ordering of appropriate tests,and accurate interpretation of genetic results with appropriate followup testing and interventions.In this editorial,we seek to explore the process of informed consent of individuals before obtaining genetic testing and offer potential solutions to optimize the informed consent process including categorization of results as well as a layered consent model.

Translation Strategies of Red Tourism Terms in the Central Plains-Taking Red Central Plains as an Example

In recent years,the Red Tourism in Central Plains has gradually become a new type of thematic tourism form,which is an important carrier to carry out patriotism and revolutionary traditional education and carry forward the national spirit.The translation of red tourism publicity is an important window for spreading Chinese culture,and the translation of professional terms is an important link in the red tourism publicity.How to spread the red culture of the Central Plains,glow the charm of the Central Plains culture,enhance the influence of the Central Plains culture,and spread the Central Plains culture to the world has become the mission of every child of the Central Plains.This paper adopts the case analysis method,combined with the specific and typical cases in“Red Central Plains”,and uses different translation strategies and methods to explore the difficulties and solutions of the translation of terms in the red tourism text.

A Study of English Translation Strategies of Subtitles of the Domestic Animated Film Chang’an from the Perspective of Eco-translatology

This article conducts an analysis and exploration of the English subtitles translation of the domestic animated film Chang’an from the perspective of eco-translatology.Taking three-dimensional transformation as the entry point,it analyzes the adaptation and selection of subtitle translators in the translation process from the dimensions of language,culture,and communication in Chang’an,aiming to enrich the practical analysis of eco-translatology and provide valuable insights and references for the theoretical construction and practical application of eco-translatology.This article enriches the practical analysis of eco-translatology and also validates to a certain extent the applicability of“three-dimensional”transformation.

Epidemiological Surveillance: Genetic Diversity of Rotavirus Group A in the Pearl River Delta, Guangdong, China in 2019

Objective This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A(RVA)in the Pearl River Delta region of Guangdong Province,China.Methods This study included individuals aged 28 days–85 years.A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens,including RVA,using a Gastrointestinal Pathogen Panel,followed by genotyping,virus isolation,and complete sequencing to assess the genetic diversity of RVA.Results The overall RVA infection rate was 14.59%(103/706),with an irregular epidemiological pattern.The proportion of co-infection with RVA and other pathogens was 39.81%(41/103).Acute gastroenteritis is highly prevalent in young children aged 0–1 year,and RVA is the key pathogen circulating in patients 6–10 months of age with diarrhea.G9P[8](58.25%,60/103)was found to be the predominant genotype in the RVA strains,and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis.Recombination analysis showed that gene reassortment events,selection pressure,codon usage bias,gene polymorphism,and post-translational modifications(PTMs)occurred in the G9P[8]and G3P[8]strains.Conclusion This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China,further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity.Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.