Ever since the low energy N+ ion beam has been accepted that the mutation effects of ionizing radiation are attributed mainly to direct or indirect damage to DNA. Evidences based on naked DNA irradiation in support of...Ever since the low energy N+ ion beam has been accepted that the mutation effects of ionizing radiation are attributed mainly to direct or indirect damage to DNA. Evidences based on naked DNA irradiation in support of a mutation spectrum appears to be consistent, but direct proof of such results in vivo are limited. Using mutS, dam and/or dcm defective Eschericha coli imitator strains, an preliminary experimental system on induction of in vivo mutation spectra of low energy N+ ion beam has been established in this study. It was observed that the mutation rates of rifampicin resistance induced by N+ implantation were quite high, ranging from 9.2 x 10~8 to 4.9× 10~5 at the dosage of 5.2×1014 ions/cm2. Strains all had more than 90-fold higher mutation rate than its spontaneous mutation rate determined by this method. It reveals that base substitutions involve in induction of mutation of low energy nitrogen ion beam implantation. The mutation rates of mutator strains were nearly 500-fold (GM2929), 400-fold (GM5864) and 6-fold larger than that of AB1157. The GM2929 and GM5864 both lose the ability of repair DNA mismatch damage by virtue of both dam and dcm pathways defective (GM2929) or failing to assemble the repair complex (GM5864) respectively. It may explain the both strains had a similar higher mutation rate than GM124 did. It indicated that DNA cytosine methylase might play an important role in mismatch repair of DNA damage induced by N+ implantation. The further related research were also discussed.展开更多
A series of novel imidazo[1,2-b]isoxazoles 3 and their Mannich bases 4–6 were synthesized via convenient reactions. The reaction of 3-aminoisoxazole 1 with substituted phenacyl bromides 2 in dry ethanol afforded the ...A series of novel imidazo[1,2-b]isoxazoles 3 and their Mannich bases 4–6 were synthesized via convenient reactions. The reaction of 3-aminoisoxazole 1 with substituted phenacyl bromides 2 in dry ethanol afforded the corresponding 6-methyl-3-aryl imidazo[1,2-b]isoxazoles 3 in good yields.Compounds 3 on treatment with 37% formaline and secondary amines furnished the corresponding novel Mannich bases viz., 6-methyl-3-aryl-2-（morpholine/pyrrolidin-1-yl/piperidin-1-yl）-methyl-imidazo[1,2-b]isoxazoles 4–6.展开更多
Ever since the low energy N + ion beam has been accepted, the mutations of ionizing radiation are attributable mainly to avoidance of DNA damages repair. Evidences based on in vivo proof results are limited. Using the...Ever since the low energy N + ion beam has been accepted, the mutations of ionizing radiation are attributable mainly to avoidance of DNA damages repair. Evidences based on in vivo proof results are limited. Using the E.coli wild type and mutator strains, the mutant frequencies suggest that base substitutions in rpoB gene are induced by the N + implantation. A highly conserved region is selected to get the direct evidence for base substitutions by sequence of the high fidelity PCR amplification products in mutants. Most of the mutants (90.9%, 40/44) have at least one base substitution in the amplification region. The evidences for CG to TA (55%, 22/40), AT to GC (20%, 8/40) and TA to CG (5%, 2/40) transitions are identified. The transversions are AT to TA (15%, 6/40) and GC to CG (5%, 2/40). It is suggested that DNA cytosine methylase might play an important role in mismatch repair of DNA damage induced by N + implantation by analysis of the mutant frequencies of mutator strains.展开更多
BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a cancer with a poor prognosis,characterized by distinct geographical distribution and family clustering.AIM To investigate if ethnic differences(Han vs Kazakh)cau...BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a cancer with a poor prognosis,characterized by distinct geographical distribution and family clustering.AIM To investigate if ethnic differences(Han vs Kazakh)cause molecular variations in ESCC patients via genomic sequencing 299 samples.METHODS Here,we sequenced samples from 299 ESCC patients collected from Henan Key Laboratory for Esophageal Cancer Research and National Key Laboratory of Metabolic Dysregulation and Esophageal Cancer Prevention and Treatment,The First Affiliated Hospital of Zhengzhou University,including Han and Kazakh ethnic groups,and performed a genomic comparative analysis of these two ethnic cohorts.RESULTS ESCC patients of Kazakh ethnicity present with a later age of onset compared to Han.Kazakh patients exhibit a slightly higher tumor mutation burden compared to their Han counterparts.Three genes GIGYF1,CACNA1D,and ACOT11 exhibited mutation frequencies threefold higher in Kazakh patients than in Han.This enrichment may be associated with Kazakhs’adaptation to cold climates and consumption of high-calorie diets.Among Han patients,the apolipoprotein B messenger RNA-editing enzyme catalytic polypeptide(APOBEC)-associated single base substitutions(SBS)13 mutational signature is more prevalent,whereas SBS6,indicative of DNA mismatch repair deficiency,is more common in Kazakh patients.Additionally,Han Chinese patients with APOBEC-enriched tumors exhibit a significantly higher mutation load than those without.Moreover,patients lacking the APOBEC signature demonstrate superior survival probability compared to the APOBEC-enriched group.CONCLUSION Living environment and diet are major factors in the development of ESCC.Genomic difference may provide guidance for the formulation of clinical treatment plans for ESCC from different ethnics regions.展开更多
Base substitution is one of the raw fuels that produce genetic variation; drive evolution. Recent studies have shown that the genome components affect mutation patterns to some extent. In order to infer the correlatio...Base substitution is one of the raw fuels that produce genetic variation; drive evolution. Recent studies have shown that the genome components affect mutation patterns to some extent. In order to infer the correlation between the Transition/Transversion ratio (Ts/Tv); the number of immediately adjacent A&T nucleotides, we investigated 3611007 Oryza sativa SNPs (including 45462 coding SNPs,; 242811 intronic SNPs); 32019 Arabidopsis SNPs. The results show that Ts/Tv is negatively correlated with the number of immediately adjacent A&T in O. Sativa; Arabidopsis. We further calculated AT2 (the number of SNPs whose immediately adjacent nucleotides are either A or T); AT0 (the number of SNPs whose immediately adjacent nucleotides are either C or G) for all 6 types of SNPs. C/G SNP of O. sativa; Arabidopsis has the highest AT2/AT0, which denotes C/G SNP may be influenced by the adjacent A&T nucleotides mostly. For SNPs in O. sativa, the neighboring effect of A&T nucleotides is limited to 2 nucleotides on both sides; for SNPs in Arabidopsis, the effect extends no more than 4 nucleotides on both sides.展开更多
基金The project supported by the National Nature Science Foundation of China (No. 19890300)
文摘Ever since the low energy N+ ion beam has been accepted that the mutation effects of ionizing radiation are attributed mainly to direct or indirect damage to DNA. Evidences based on naked DNA irradiation in support of a mutation spectrum appears to be consistent, but direct proof of such results in vivo are limited. Using mutS, dam and/or dcm defective Eschericha coli imitator strains, an preliminary experimental system on induction of in vivo mutation spectra of low energy N+ ion beam has been established in this study. It was observed that the mutation rates of rifampicin resistance induced by N+ implantation were quite high, ranging from 9.2 x 10~8 to 4.9× 10~5 at the dosage of 5.2×1014 ions/cm2. Strains all had more than 90-fold higher mutation rate than its spontaneous mutation rate determined by this method. It reveals that base substitutions involve in induction of mutation of low energy nitrogen ion beam implantation. The mutation rates of mutator strains were nearly 500-fold (GM2929), 400-fold (GM5864) and 6-fold larger than that of AB1157. The GM2929 and GM5864 both lose the ability of repair DNA mismatch damage by virtue of both dam and dcm pathways defective (GM2929) or failing to assemble the repair complex (GM5864) respectively. It may explain the both strains had a similar higher mutation rate than GM124 did. It indicated that DNA cytosine methylase might play an important role in mismatch repair of DNA damage induced by N+ implantation. The further related research were also discussed.
文摘A series of novel imidazo[1,2-b]isoxazoles 3 and their Mannich bases 4–6 were synthesized via convenient reactions. The reaction of 3-aminoisoxazole 1 with substituted phenacyl bromides 2 in dry ethanol afforded the corresponding 6-methyl-3-aryl imidazo[1,2-b]isoxazoles 3 in good yields.Compounds 3 on treatment with 37% formaline and secondary amines furnished the corresponding novel Mannich bases viz., 6-methyl-3-aryl-2-（morpholine/pyrrolidin-1-yl/piperidin-1-yl）-methyl-imidazo[1,2-b]isoxazoles 4–6.
文摘Ever since the low energy N + ion beam has been accepted, the mutations of ionizing radiation are attributable mainly to avoidance of DNA damages repair. Evidences based on in vivo proof results are limited. Using the E.coli wild type and mutator strains, the mutant frequencies suggest that base substitutions in rpoB gene are induced by the N + implantation. A highly conserved region is selected to get the direct evidence for base substitutions by sequence of the high fidelity PCR amplification products in mutants. Most of the mutants (90.9%, 40/44) have at least one base substitution in the amplification region. The evidences for CG to TA (55%, 22/40), AT to GC (20%, 8/40) and TA to CG (5%, 2/40) transitions are identified. The transversions are AT to TA (15%, 6/40) and GC to CG (5%, 2/40). It is suggested that DNA cytosine methylase might play an important role in mismatch repair of DNA damage induced by N + implantation by analysis of the mutant frequencies of mutator strains.
基金Supported by the National Natural Science Foundation of China,No.U1301227National Major Science and Technology Projects,No.2024ZD05209060Henan Province Jointly Built Science and Technology Key Projects,No.LHGJ20210337.
文摘BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a cancer with a poor prognosis,characterized by distinct geographical distribution and family clustering.AIM To investigate if ethnic differences(Han vs Kazakh)cause molecular variations in ESCC patients via genomic sequencing 299 samples.METHODS Here,we sequenced samples from 299 ESCC patients collected from Henan Key Laboratory for Esophageal Cancer Research and National Key Laboratory of Metabolic Dysregulation and Esophageal Cancer Prevention and Treatment,The First Affiliated Hospital of Zhengzhou University,including Han and Kazakh ethnic groups,and performed a genomic comparative analysis of these two ethnic cohorts.RESULTS ESCC patients of Kazakh ethnicity present with a later age of onset compared to Han.Kazakh patients exhibit a slightly higher tumor mutation burden compared to their Han counterparts.Three genes GIGYF1,CACNA1D,and ACOT11 exhibited mutation frequencies threefold higher in Kazakh patients than in Han.This enrichment may be associated with Kazakhs’adaptation to cold climates and consumption of high-calorie diets.Among Han patients,the apolipoprotein B messenger RNA-editing enzyme catalytic polypeptide(APOBEC)-associated single base substitutions(SBS)13 mutational signature is more prevalent,whereas SBS6,indicative of DNA mismatch repair deficiency,is more common in Kazakh patients.Additionally,Han Chinese patients with APOBEC-enriched tumors exhibit a significantly higher mutation load than those without.Moreover,patients lacking the APOBEC signature demonstrate superior survival probability compared to the APOBEC-enriched group.CONCLUSION Living environment and diet are major factors in the development of ESCC.Genomic difference may provide guidance for the formulation of clinical treatment plans for ESCC from different ethnics regions.
基金supported partly by the National 863 Project(Grant No.2003AA231050)National Natural Science Foundation of China(Grant No.10371126)Mega-projects of Science Research for the 10th Five-year Plan(Grant No.2002BA711A09).
文摘Base substitution is one of the raw fuels that produce genetic variation; drive evolution. Recent studies have shown that the genome components affect mutation patterns to some extent. In order to infer the correlation between the Transition/Transversion ratio (Ts/Tv); the number of immediately adjacent A&T nucleotides, we investigated 3611007 Oryza sativa SNPs (including 45462 coding SNPs,; 242811 intronic SNPs); 32019 Arabidopsis SNPs. The results show that Ts/Tv is negatively correlated with the number of immediately adjacent A&T in O. Sativa; Arabidopsis. We further calculated AT2 (the number of SNPs whose immediately adjacent nucleotides are either A or T); AT0 (the number of SNPs whose immediately adjacent nucleotides are either C or G) for all 6 types of SNPs. C/G SNP of O. sativa; Arabidopsis has the highest AT2/AT0, which denotes C/G SNP may be influenced by the adjacent A&T nucleotides mostly. For SNPs in O. sativa, the neighboring effect of A&T nucleotides is limited to 2 nucleotides on both sides; for SNPs in Arabidopsis, the effect extends no more than 4 nucleotides on both sides.
