Reverse Genetic Analysis of Transcription Factor Os Hox9, a Member of Homeobox Family, in Rice

Homeobox transcription factors participate in the growth and development of plants by regulating cell differentiation, morphogenesis and environmental signal response. To reveal the functions of these transcription factors in rice, we constructed the RNAi vectors of OsHox9, a member of homeobox family, and analyzed the function of OsHox9 using reverse genetics. The plant height and tillering number of RNAi transgenic plants decreased compared with those of wild-type plants. Reverse transcdption-polymerase chain reaction analysis showed that OsHox9 expression reduced in the transgenic plants with phenotypic variance, whereas that in the transgenic plants without phenotypic variance was similar to that in the wild-type plants. This result suggests that the phenotypes of the transgenic plants were caused by RNAi effects. The tissue-specificity of OsHox9 expression indicated that it was expressed in different organs, with high expression in stem apical medstem and young panicles. Subcellular location of OsHox9 demonstrated that it was localized on the cell membrane.

Transcriptional regulation of endothelial dysfunction in atherosclerosis:an epigenetic perspective

Atherosclerosis is a progressive human pathology that encompasses several stages of development. Endothelial dysfunction represents an early sign of lesion within the vasculature. A number of risk factors for atherosclero- sis, including hyperlipidemia, diabetes, and hypertension, target the vascular endothelium by re-programming its transcriptome. These profound alterations taking place on the chromatin rely on the interplay between sequence specific transcription factors and the epigenetic machinery. The epigenetic machinery, in turn, tailor individual transcription events key to atherogenesis to intrinsic and extrinsic insults dictating the development of atheroscle- rotic lesions. This review summarizes our current understanding of the involvement of the epigenetic machinery in endothelial injury during atherogenesis.

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.

Optimization of the bioconversion of glycerol to ethanol using Escherichia coli by implementing a bi-level programming framework for proposing gene transcription control strategies based on genetic algorithms

In silico approaches for metabolites optimization have been derived from the flood of sequenced and annotated genomes. However, there exist still numerous degrees of freedom in terms of optimization algorithm approaches that can be exploited in order to enhance yield of processes which are based on biological reactions. Here, we propose an evolutionary approach aiming to suggest different mutant for augmenting ethanol yield using glycerol as substrate in Escherichia coli. We found that this algorithm, even though is far from providing the global optimum, is able to uncover genes that a global optimizer would be incapable of. By over-expressing accB, eno, dapE, and accA mutants in ethanol production was augmented up to 2 fold compared to its counterpart E. coli BW25113.

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.

Application of Genetic Algorithm to the QSAR Research of Pyrrolobenzothiazepinones and Pyrrolobenzoxazepinones-Novel and Specific Non-Nucleoside HIV-1 Reverse Transcription Inhibitors

Genetic Algorithm (GA) was used to study the quantitative structural parameters and activity relationship of pyrrolobenzothizepinones and pyrrolobenzoxazepinones's inhibitory activities with non-nucleoside HIV-1 reverse transcriptase (RT). A group of linear polynomial models with good relationship have been built to get some useful information that other methods can not offer.

Genetic analysis of transcription factors in dopaminergic neuronal development in Parkinson’s disease

Background:Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease(PD)risk factors;however,no comprehensive analyses of these genes in patients with PD have been undertaken.Therefore,we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods:Whole-exome sequencing(WES)was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls.Additionally,whole-genome sequencing(WGS)was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results:We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts,respectively.Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD.However,the significance did not pass the Bonferroni correction.Meanwhile,72 and 1730 common variants were found in the WES and WGS cohorts,respectively.Unfortunately,single-variant logistic association analyses did not identify significant associations between common variants and PD.Conclusions:Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients.However,we highlight the complexity of PD and the need for extensive research elucidating its etiology.

Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population:An integrated genomic and transcriptional analysis

Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully investigated.This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.Methods:A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled.HRD status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered HRD-positive.Genomic,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were analyzed.Results:Of the patients,25.1%(89/355)were HRD-positive.Compared to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(P<0.001),and fewer driver gene mutations(P<0.001).Furthermore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC.HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity.HRD-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T cells.HRD-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.Conclusions:Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC.Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC.This study highlights potential actionable alterations in HRD-positive NSCLC,suggesting possible combinational therapeutic strategies for these patients.

The BEL1-like transcription factor GhBLH5-A05 participates in cotton response to drought stress

Drought stress impairs crop growth and development.BEL1-like family transcription factors may be involved in plant response to drought stress,but little is known of the molecular mechanism by which these proteins regulate plant response and defense to drought stress.Here we show that the BEL1-like transcription factor GhBLH5-A05 functions in cotton(Gossypium hirsutum)response and defense to drought stress.Expression of GhBLH5-A05 in cotton was induced by drought stress.Overexpression of GhBLH5-A05 in both Arabidopsis and cotton increased drought tolerance,whereas silencing GhBLH5-A05 in cotton resulted in elevated sensitivity to drought stress.GhBLH5-A05 binds to cis elements in the promoters of GhRD20-A09 and GhDREB2C-D05 to activate the expression of these genes.GhBLH5-A05 interacted with the KNOX transcription factor GhKNAT6-A03.Co-expression of GhBLH5-A05 and GhKNAT6-A03 increased the transcription of GhRD20-A09 and GhDREB2C-D05.We conclude that GhBLH5-A05 acts as a regulatory factor with GhKNAT6-A03 functioning in cotton response to drought stress by activating the expression of the drought-responsive genes GhRD20-A09 and GhDREB2C-D05.

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.

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.

Decoding the genetic landscape of autism:A comprehensive review

BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental condition characterized by heterogeneous symptoms and genetic underpinnings.Recent advancements in genetic and epigenetic research have provided insights into the intricate mechanisms contributing to ASD,influencing both diagnosis and therapeutic strategies.AIM To explore the genetic architecture of ASD,elucidate mechanistic insights into genetic mutations,and examine gene-environment interactions.METHODS A comprehensive systematic review was conducted,integrating findings from studies on genetic variations,epigenetic mechanisms(such as DNA methylation and histone modifications),and emerging technologies[including Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)-Cas9 and single-cell RNA sequencing].Relevant articles were identified through systematic searches of databases such as PubMed and Google Scholar.RESULTS Genetic studies have identified numerous risk genes and mutations associated with ASD,yet many cases remain unexplained by known factors,suggesting undiscovered genetic components.Mechanistic insights into how these genetic mutations impact neural development and brain connectivity are still evolving.Epigenetic modifications,particularly DNA methylation and non-coding RNAs,also play significant roles in ASD pathogenesis.Emerging technologies like CRISPR-Cas9 and advanced bioinformatics are advancing our understanding by enabling precise genetic editing and analysis of complex genomic data.CONCLUSION Continued research into the genetic and epigenetic underpinnings of ASD is crucial for developing personalized and effective treatments.Collaborative efforts integrating multidisciplinary expertise and international collaborations are essential to address the complexity of ASD and translate genetic discoveries into clinical practice.Addressing unresolved questions and ethical considerations surrounding genetic research will pave the way for improved diagnostic tools and targeted therapies,ultimately enhancing outcomes for individuals affected by ASD.

Transcription factor OsSPL10 interacts with OsJAmyb to regulate blast resistance in rice

Transcription factors(TFs)play essential roles in transcriptional reprogramming during activation of plant immune responses to pathogens.OsSPL10(SQUAMOSA promoter binding protein-like10)is an important TF regulating trichome development and salt tolerance in rice.Here we report that knockout of OsSPL10 reduces whereas its overexpression enhances rice resistance to blast disease.OsSPL10 positively regulates chitin-induced immune responses including reactive oxygen species(ROS)burst and callose deposition.We show that OsSPL10 physically associates with OsJAmyb,an important TF involved in jasmonic acid(JA)signaling,and positively regulates its protein stability.We then prove that OsJAmyb positively regulates resistance to blast.Our results reveal a molecular module consisting of OsSPL10 and OsJAmyb that positively regulates blast resistance.

Phase separation and transcriptional regulation in cancer development

Liquid-liquid phase separation,a novel biochemical phenomenon,has been increasingly studied for its medical applications.It underlies the formation of membrane-less organelles and is involved in many cellular and biological processes.During transcriptional regulation,dynamic condensates are formed through interactions between transcriptional elements,such as transcription factors,coactivators,and mediators.Cancer is a disease characterized by uncontrolled cell proliferation,but the precise mechanisms underlying tumorigenesis often remain to be elucidated.Emerging evidence has linked abnormal transcriptional condensates to several diseases,especially cancer,implying that phase separation plays an important role in tumorigenesis.Condensates formed by phase separation may have an effect on gene transcription in tumors.In the present review,we focus on the correlation between phase separation and transcriptional regulation,as well as how this phenomenon contributes to cancer development.