AIM:To investigate the reciprocal modulation between microRNA(miRNA) and DNA methylation via exploring the correlation between miR-373 and methyl-CpGbinding domain protein(MBD)2.METHODS:MiR-373 expression was examined...AIM:To investigate the reciprocal modulation between microRNA(miRNA) and DNA methylation via exploring the correlation between miR-373 and methyl-CpGbinding domain protein(MBD)2.METHODS:MiR-373 expression was examined using the TaqMan miRNA assay.Methylation of miR-373 was investigated using methylation-specific polymerase chain reaction,and recruitment of methyl binding proteins was studied using the chromatin immunoprecipitation assay.Mutation analysis was conducted using the QuikChange Site-Directed Mutagenesis kit.The activity of miR-373 gene promoter constructs and targeting at MBD2-three prime untranslated region(3'UTR) by miR-373 were evaluated by a dual-luciferase reporter gene assay.RESULTS:In hilar cholangiocarcinoma,miR-373 decreased and was closely associated with poor cell differentiation,advanced clinical stage,and shorter survival.The promoter-associated CpG island of miR-373 gene was hypermethylated and inhibited expression of miR-373.MBD2 was up-regulated and enriched at the promoter-associated CpG island of miR-373.Methylation-mediated suppression of miR-373 required MBD2 enrichment at the promoter-associated CpG island,and miR-373 negatively regulated MBD2 expression through targeting the 3'UTR.CONCLUSION:MiR-373 behaves as a direct transcriptional target and negative regulator of MBD2 activity through a feedback loop of CpG island methylation.展开更多
In the history of mathematics different methods have been used to detect if a number is prime or not. In this paper a new one will be shown. It will be demonstrated that if the following equation is zero for a certain...In the history of mathematics different methods have been used to detect if a number is prime or not. In this paper a new one will be shown. It will be demonstrated that if the following equation is zero for a certain number p, this number p would be prime. And being m an integer number higher than (the lowest, the most efficient the operation). . If the result is an integer, this result will tell us how many permutations of two divisors, the input number has. As you can check, no recurrent division by odd or prime numbers is done, to check if the number is prime or has divisors. To get to this point, we will do the following. First, we will create a domain with all the composite numbers. This is easy, as you can just multiply one by one all the integers (greater or equal than 2) in that domain. So, you will get all the composite numbers (not getting any prime) in that domain. Then, we will use the Fourier transform to change from this original domain (called discrete time domain in this regards) to the frequency domain. There, we can check, using Parseval’s theorem, if a certain number is there or not. The use of Parseval’s theorem leads to the above integral. If the number p that we want to check is not in the domain, the result of the integral is zero and the number is a prime. If instead, the result is an integer, this integer will tell us how many permutations of two divisors the number p has. And, in consequence information how many factors, the number p has. So, for any number p lower than 2m?- 1, you can check if it is prime or not, just making the numerical definite integration. We will apply this integral in a computer program to check the efficiency of the operation. We will check, if no further developments are done, the numerical integration is inefficient computing-wise compared with brute-force checking. To be added, is the question regarding the level of accuracy needed (number of decimals and number of steps in the numerical integration) to have a reliable result for large numbers. This will be commented on the paper, but a separate study will be needed to have detailed conclusions. Of course, the best would be that in the future, an analytical result (or at least an approximation) for the summation or for the integration is achieved.展开更多
基金Supported by National Natural Science Foundation of China,No. 81071998Hubei Natural Science Foundation,No.2008CDB159Specialized Research Fund for the Doctoral Program of Higher Education,No. 20070487114
文摘AIM:To investigate the reciprocal modulation between microRNA(miRNA) and DNA methylation via exploring the correlation between miR-373 and methyl-CpGbinding domain protein(MBD)2.METHODS:MiR-373 expression was examined using the TaqMan miRNA assay.Methylation of miR-373 was investigated using methylation-specific polymerase chain reaction,and recruitment of methyl binding proteins was studied using the chromatin immunoprecipitation assay.Mutation analysis was conducted using the QuikChange Site-Directed Mutagenesis kit.The activity of miR-373 gene promoter constructs and targeting at MBD2-three prime untranslated region(3'UTR) by miR-373 were evaluated by a dual-luciferase reporter gene assay.RESULTS:In hilar cholangiocarcinoma,miR-373 decreased and was closely associated with poor cell differentiation,advanced clinical stage,and shorter survival.The promoter-associated CpG island of miR-373 gene was hypermethylated and inhibited expression of miR-373.MBD2 was up-regulated and enriched at the promoter-associated CpG island of miR-373.Methylation-mediated suppression of miR-373 required MBD2 enrichment at the promoter-associated CpG island,and miR-373 negatively regulated MBD2 expression through targeting the 3'UTR.CONCLUSION:MiR-373 behaves as a direct transcriptional target and negative regulator of MBD2 activity through a feedback loop of CpG island methylation.
文摘In the history of mathematics different methods have been used to detect if a number is prime or not. In this paper a new one will be shown. It will be demonstrated that if the following equation is zero for a certain number p, this number p would be prime. And being m an integer number higher than (the lowest, the most efficient the operation). . If the result is an integer, this result will tell us how many permutations of two divisors, the input number has. As you can check, no recurrent division by odd or prime numbers is done, to check if the number is prime or has divisors. To get to this point, we will do the following. First, we will create a domain with all the composite numbers. This is easy, as you can just multiply one by one all the integers (greater or equal than 2) in that domain. So, you will get all the composite numbers (not getting any prime) in that domain. Then, we will use the Fourier transform to change from this original domain (called discrete time domain in this regards) to the frequency domain. There, we can check, using Parseval’s theorem, if a certain number is there or not. The use of Parseval’s theorem leads to the above integral. If the number p that we want to check is not in the domain, the result of the integral is zero and the number is a prime. If instead, the result is an integer, this integer will tell us how many permutations of two divisors the number p has. And, in consequence information how many factors, the number p has. So, for any number p lower than 2m?- 1, you can check if it is prime or not, just making the numerical definite integration. We will apply this integral in a computer program to check the efficiency of the operation. We will check, if no further developments are done, the numerical integration is inefficient computing-wise compared with brute-force checking. To be added, is the question regarding the level of accuracy needed (number of decimals and number of steps in the numerical integration) to have a reliable result for large numbers. This will be commented on the paper, but a separate study will be needed to have detailed conclusions. Of course, the best would be that in the future, an analytical result (or at least an approximation) for the summation or for the integration is achieved.
