Naturally occurring mutations in surface proteins of Hepatitis B virus(HBV) usually result in altered hepatitis B surface antigen(HBsAg) secretion efficiency.In the present study,we reported two conserved residues,M75...Naturally occurring mutations in surface proteins of Hepatitis B virus(HBV) usually result in altered hepatitis B surface antigen(HBsAg) secretion efficiency.In the present study,we reported two conserved residues,M75 and M103 with respect to HBsAg,mutations of which not only attenuated HBsAg secretion(M75 only),but also suppressed HBV genome replication without compromising the overlapping p-gene product.We also found M75 and M103 can initiate truncated surface protein(TSPs) synthesis upon over-expression of full-length surface proteins,which may possibly contribute to HBV genome replication.However,attempts to rescue replicationdefective HBV mutant by co-expression of TSPs initiated from M75 or M103 were unsuccessful,which indicated surface proteins rather than the putative TSPs were involved in regulation of HBV genome replication.展开更多
The p27Kip1 is a cell cycle repressor protein that regulates primarily the cell cycle transition from G1 to S phase and hence the DNA replication is in the S phase and cell division in the M phase. Expression of p27Ki...The p27Kip1 is a cell cycle repressor protein that regulates primarily the cell cycle transition from G1 to S phase and hence the DNA replication is in the S phase and cell division in the M phase. Expression of p27Kip1 protein has dual roles for both cancer prevention and promotion. For example, numerous nutritional and chemopreventive anti-cancer agents specifically increase the expression of p27Kip1 protein without directly affecting the expression of any other cell cycle regulatory proteins. On the other hand, pro-cancer agents (like glucose, insulin and other growth factors frequently seen in obesity and/or diabetes) specifically decrease the expression of p27Kip1 protein without directly affecting the expression of any other cell cycle regulatory proteins. Unlike expression of any other cell cycle regulatory proteins, expression of p27Kip1 protein is very unusual. The mRNA of p27Kip1 has a very long and unusual 5’-untranslated region (from -575 to -1 in human). It appears that the 5’-untranslated region of p27Kip1 mRNA forms two alternative secondary structures. One increases the expression of p27Kip1 protein when anti-cancer agents are added and another decrease the expression of p27K1p1 when pro-cancer agents are added. For this short concept proposal, Dr. Albert Einstein’s “visualized thought experiments (German: Gedanken experiment)” were used as a fundamental tool for understanding how either anti- or pro-cancer agents bring the primary structure of the 5’-untranslated region of p27Kip1 mRNA into two alternative secondary structures, thereby either increasing or decreasing, respectively, the translation initiation of p27Kip1 protein.展开更多
Research Aims: Obesity and type 2 diabetes are known to be associated with increased risk of various types of cancer. However, the molecular biological mechanism of how the risk of cancer is increased in obesity or ty...Research Aims: Obesity and type 2 diabetes are known to be associated with increased risk of various types of cancer. However, the molecular biological mechanism of how the risk of cancer is increased in obesity or type 2 diabetes is not known. The aim this research is to investigate if the decreased expression of p27Kip1, a cell cycle repressor protein, plays a central role in this mechanism. Research Methods, Previous Studies and Theoretical Backgrounds: It is well known that the expression of p27Kip1 is increased by numerous nutritional or chemopreventive anti-cancer agents. But it has never been known that the expression of p27Kip1 could be decreased, rather than increased, and the risk of cancer could be increased, rather than decreased. This problem was solved recently and this new analytical method was used in this study. Results: 1) The expression of p27Kip1 was indeed significantly decreased in human obese type 2 diabetic individuals relative to the lean normal controls. 2) The expression of p27Kip1 was also significantly decreased in genetically obese rodents relative to the lean normal controls. Additionally, in obese rodents, the concentrations of glucose or insulin were significantly increased relative to the lean normal controls. 3) Using human cells cultured in vitro it was found that the increased concentrations of glucose or insulin decrease the expression of p27Kip1. Conclusions: These results suggest that higher concentrations of glucose or insulin increase the risk of various types of cancer in obesity or type 2 diabetes by decreasing the expression of p27Kip1.展开更多
Two methods currently available for evaluating the probability of Multiple Site Damage(MSD)occurrence were studied in this paper.One of the methods is a probabilistic analysis approach based on the statistical theory ...Two methods currently available for evaluating the probability of Multiple Site Damage(MSD)occurrence were studied in this paper.One of the methods is a probabilistic analysis approach based on the statistical theory and fatigue characteristics of each structural detail,and the other is an approach which defines the initial damage scenario by means of Monte-Carlo simulation,and multiple initial crack scenarios are randomly generated.A modified method based on the Monte-Carlo simulation was proposed in this paper,in which the random fluctuation of the stress was considered to give more accurate evaluation results.In the presented method,the probability of MSD occurrence in a structural element containing multiple details was calculated based on the Monte-Carlo simulation and the p-S-N curve of a single structural detail.Fatigue tests were accomplished using specimens containing 21-similar-details to obtain the fatigue life corresponding to MSD occurrence.Tests on single-detail specimens and static calibration tests were also conducted to get the basic fatigue properties of the material and the degree of stress fluctuation.The aforementioned three methods were compared and validated via the test results.The influence of the stress random fluctuation degree on the probability of MSD occurrence and influence of the distribution types on evaluating the MSD occurrence probability were discussed.展开更多
Plant mitochondrial genes are often transcribed into complex sets of mRNA. To characterize the transcription initiation and promoter structure, the transcript termini of four mitochondrial genes, atpl, atp6, cob, rps7...Plant mitochondrial genes are often transcribed into complex sets of mRNA. To characterize the transcription initiation and promoter structure, the transcript termini of four mitochondrial genes, atpl, atp6, cob, rps7, in rice （Oryza sativa L.）, were determined by using a modified circularized RNA reverse transcription- polymerase chain reaction method. The results revealed that three genes （atp1, atp6, rps7） were transcribed from multiple initiation sites, indicating the presence of multiple promoters. Two transcription termination sites were detected in three genes （atp6, cob, rps7）, respectively. Analysis on the promoter architecture showed that the YRTA （Y=T or C, R=A or G） motifs that are widely present in the mitochondrlal promoters of other monocot and dicot plant species were detected only in two of the 12 analyzed promoters. Our data suggest that the promoter sequences in the rice mitochondrial genome are highly diverged in comparison to those in other plants, and the YRTA motif is not an essential element for the promoter activity.展开更多
Carbamyl phosphate synthetase I (CPSI for short )is the first key enzyme of the urea cycle and mainly located in mitochondria of hepatocytes. It is the tissue specific enzyme of liver and involved in the differentiati...Carbamyl phosphate synthetase I (CPSI for short )is the first key enzyme of the urea cycle and mainly located in mitochondria of hepatocytes. It is the tissue specific enzyme of liver and involved in the differentiation of hepatocytes. We have observed the decrease of the activity of CPSI during hepatocarcinogenesis. A series of experiments suggest that CPSI gene be regulated at transcriptional level. Transcription regulation of eukaryotic genes is mediated by interaction of trans-acting factors and cis-acting elements. Cis-acting elements are展开更多
基金supported by the National Basic Research Program of China(2007CB512900)
文摘Naturally occurring mutations in surface proteins of Hepatitis B virus(HBV) usually result in altered hepatitis B surface antigen(HBsAg) secretion efficiency.In the present study,we reported two conserved residues,M75 and M103 with respect to HBsAg,mutations of which not only attenuated HBsAg secretion(M75 only),but also suppressed HBV genome replication without compromising the overlapping p-gene product.We also found M75 and M103 can initiate truncated surface protein(TSPs) synthesis upon over-expression of full-length surface proteins,which may possibly contribute to HBV genome replication.However,attempts to rescue replicationdefective HBV mutant by co-expression of TSPs initiated from M75 or M103 were unsuccessful,which indicated surface proteins rather than the putative TSPs were involved in regulation of HBV genome replication.
文摘The p27Kip1 is a cell cycle repressor protein that regulates primarily the cell cycle transition from G1 to S phase and hence the DNA replication is in the S phase and cell division in the M phase. Expression of p27Kip1 protein has dual roles for both cancer prevention and promotion. For example, numerous nutritional and chemopreventive anti-cancer agents specifically increase the expression of p27Kip1 protein without directly affecting the expression of any other cell cycle regulatory proteins. On the other hand, pro-cancer agents (like glucose, insulin and other growth factors frequently seen in obesity and/or diabetes) specifically decrease the expression of p27Kip1 protein without directly affecting the expression of any other cell cycle regulatory proteins. Unlike expression of any other cell cycle regulatory proteins, expression of p27Kip1 protein is very unusual. The mRNA of p27Kip1 has a very long and unusual 5’-untranslated region (from -575 to -1 in human). It appears that the 5’-untranslated region of p27Kip1 mRNA forms two alternative secondary structures. One increases the expression of p27Kip1 protein when anti-cancer agents are added and another decrease the expression of p27K1p1 when pro-cancer agents are added. For this short concept proposal, Dr. Albert Einstein’s “visualized thought experiments (German: Gedanken experiment)” were used as a fundamental tool for understanding how either anti- or pro-cancer agents bring the primary structure of the 5’-untranslated region of p27Kip1 mRNA into two alternative secondary structures, thereby either increasing or decreasing, respectively, the translation initiation of p27Kip1 protein.
文摘Research Aims: Obesity and type 2 diabetes are known to be associated with increased risk of various types of cancer. However, the molecular biological mechanism of how the risk of cancer is increased in obesity or type 2 diabetes is not known. The aim this research is to investigate if the decreased expression of p27Kip1, a cell cycle repressor protein, plays a central role in this mechanism. Research Methods, Previous Studies and Theoretical Backgrounds: It is well known that the expression of p27Kip1 is increased by numerous nutritional or chemopreventive anti-cancer agents. But it has never been known that the expression of p27Kip1 could be decreased, rather than increased, and the risk of cancer could be increased, rather than decreased. This problem was solved recently and this new analytical method was used in this study. Results: 1) The expression of p27Kip1 was indeed significantly decreased in human obese type 2 diabetic individuals relative to the lean normal controls. 2) The expression of p27Kip1 was also significantly decreased in genetically obese rodents relative to the lean normal controls. Additionally, in obese rodents, the concentrations of glucose or insulin were significantly increased relative to the lean normal controls. 3) Using human cells cultured in vitro it was found that the increased concentrations of glucose or insulin decrease the expression of p27Kip1. Conclusions: These results suggest that higher concentrations of glucose or insulin increase the risk of various types of cancer in obesity or type 2 diabetes by decreasing the expression of p27Kip1.
文摘Two methods currently available for evaluating the probability of Multiple Site Damage(MSD)occurrence were studied in this paper.One of the methods is a probabilistic analysis approach based on the statistical theory and fatigue characteristics of each structural detail,and the other is an approach which defines the initial damage scenario by means of Monte-Carlo simulation,and multiple initial crack scenarios are randomly generated.A modified method based on the Monte-Carlo simulation was proposed in this paper,in which the random fluctuation of the stress was considered to give more accurate evaluation results.In the presented method,the probability of MSD occurrence in a structural element containing multiple details was calculated based on the Monte-Carlo simulation and the p-S-N curve of a single structural detail.Fatigue tests were accomplished using specimens containing 21-similar-details to obtain the fatigue life corresponding to MSD occurrence.Tests on single-detail specimens and static calibration tests were also conducted to get the basic fatigue properties of the material and the degree of stress fluctuation.The aforementioned three methods were compared and validated via the test results.The influence of the stress random fluctuation degree on the probability of MSD occurrence and influence of the distribution types on evaluating the MSD occurrence probability were discussed.
基金Supported by the National Natural Science Foundation of China （30420340）.
文摘Plant mitochondrial genes are often transcribed into complex sets of mRNA. To characterize the transcription initiation and promoter structure, the transcript termini of four mitochondrial genes, atpl, atp6, cob, rps7, in rice （Oryza sativa L.）, were determined by using a modified circularized RNA reverse transcription- polymerase chain reaction method. The results revealed that three genes （atp1, atp6, rps7） were transcribed from multiple initiation sites, indicating the presence of multiple promoters. Two transcription termination sites were detected in three genes （atp6, cob, rps7）, respectively. Analysis on the promoter architecture showed that the YRTA （Y=T or C, R=A or G） motifs that are widely present in the mitochondrlal promoters of other monocot and dicot plant species were detected only in two of the 12 analyzed promoters. Our data suggest that the promoter sequences in the rice mitochondrial genome are highly diverged in comparison to those in other plants, and the YRTA motif is not an essential element for the promoter activity.
文摘Carbamyl phosphate synthetase I (CPSI for short )is the first key enzyme of the urea cycle and mainly located in mitochondria of hepatocytes. It is the tissue specific enzyme of liver and involved in the differentiation of hepatocytes. We have observed the decrease of the activity of CPSI during hepatocarcinogenesis. A series of experiments suggest that CPSI gene be regulated at transcriptional level. Transcription regulation of eukaryotic genes is mediated by interaction of trans-acting factors and cis-acting elements. Cis-acting elements are
