凡由朊毒(Prion)引起的人畜共患病(Zoonosis)统称为朊毒病，这种疾病均为中枢神经系统致死性的慢性退化性疾病(The fatal，chronic degradative disease of central nervous system)，其中包括20世纪20年代发现的人类克-雅氏病(Creuzfe...凡由朊毒(Prion)引起的人畜共患病(Zoonosis)统称为朊毒病，这种疾病均为中枢神经系统致死性的慢性退化性疾病(The fatal，chronic degradative disease of central nervous system)，其中包括20世纪20年代发现的人类克-雅氏病(Creuzfeldt—Jacob disease CJD)：1986年起源于英国。展开更多
Prion diseases are a group of neurodegenerative diseases that are fatal. The study of these unique diseases in China is hampered by a lack of resources. Amongst the most important resources for biological study are mo...Prion diseases are a group of neurodegenerative diseases that are fatal. The study of these unique diseases in China is hampered by a lack of resources. Amongst the most important resources for biological study are monoclonal antibodies. Here, we characterize a panel of monoclonal antibodies specific for cellular prion protein by enzyme-linked immunosorbent assay(ELISA), immunofluorescent staining, flow cytometry, and western blotting. We identify several antibodies that can be used for specific applications and we demonstrate that there is no prion protein expression in human pancreatic ductal epithelial cells(HPDC).展开更多
Prion diseases are infectious and fatal neurodegenerative diseases.The pathogenic agent is an abnormal prion protein aggregate.Microglial activation in the centre nervous system is a characteristic feature of prion di...Prion diseases are infectious and fatal neurodegenerative diseases.The pathogenic agent is an abnormal prion protein aggregate.Microglial activation in the centre nervous system is a characteristic feature of prion disease.In this study,we examined the effect of PrP 106-126 on PrP mRNA gene expression in Mouse microglia cells BV-2 by real-time quantitative PCR.PrP mRNA expression level was found to be significantly increased after 18 h exposure of BV-2 cells to PrP 106-126,with 3-fold increase after 18 h and 4.5-fold increase after 24 h and BV-2 cells proliferating occurred correspondingly.Our results provide the first in vitro evidence of the increase of PrP mRNA levels in microglial cells exposed to PrP 106-126,and indicate that microglial cells might play a critical role in prion pathogenesis.展开更多
A conformal structure of a prion protein is thought to cause a prion disease by S.B. Prusiner＇s theory. Knot theory in mathematics is useful in studying a topological difference of topological objects. In this articl...A conformal structure of a prion protein is thought to cause a prion disease by S.B. Prusiner＇s theory. Knot theory in mathematics is useful in studying a topological difference of topological objects. In this article, concerning this conjecture, a topological model of prion proteins （PrPc, PrPsc） called a prion-tangle is introduced to discuss a question of whether or not the prion proteins are easily entangled by an approach from the mathematical knot theory. It is noted that any prion-string with trivial loop which is a topological model of a prion protein can not be entangled topologically unless a certain restriction such as ＂Rotaxsane Property＂ is imposed on it. Nevertheless, it is shown that any two split prion-tangles can be changed by a one-crossing change into a non-split prion-tangle with the given prion-tangles contained while some attentions are paid to the loop systems. The proof is made by a mathematical argument on knot theory of spatial graphs. This means that the question above is answered affirmatively in this topological model of prion-tangles. Next, a question of what is the simplest topological situation of the non-split prion-tangles is considered. By a mathematical argument, it is determined for every n 〉 1 that the minimal crossing number of n-string non-split prion-tangles is 2n or 2n-2, respectively, according to whether or not the assumption that the loop system is a trivial link is counted.展开更多
Bovine spongiform encephalopathy （BSE） is thought to be caused by prions initially derived from sheep scrapie, and epidemiological studies suggest that new viriant form of CJD manifest in Great Britain may be caused...Bovine spongiform encephalopathy （BSE） is thought to be caused by prions initially derived from sheep scrapie, and epidemiological studies suggest that new viriant form of CJD manifest in Great Britain may be caused by BSE prions. PrP^Sc is thought to pathogenic factor of transmissible spongiform encephalopathy （TSE）, which invariably involve a post-translational modification process of PrPc encoded by the host euchromosome PrP gene during the period it converted into the pathogenic form （PrP^Sc）, PrP is nomal cellular protein which has been found in both neuronal and nonneuronal tissues. Since the crucial infectious event in protein-transmitted diseases is an induced misfolding of prion proteins （PrP^c） catalyzed by already misfolded PrP^Sc, it is of high importance that such collisions are enhanced by two-dimensional diffusion in cell membranes is of high importance compared to three-dimensional diffusion in solution. The level of PrP mRNA in brain is higher than other tissue, but purification of PrPc from rodent has been difficult. To understand the formation of PrP^Sc, it seemed useful to develop a system for produced a large quantities of PrPc since there is no nature source of PrP^c. The pCI-neo mammalian expression vector contains the neomycin phosphtransferase gene which serves as a marker for the selection of stable transfected cells with G418. COS-7 cells constitutively express simian viruse 40 （SV40） T-antigen and support replication of expression plasmids containing the SV40 origin of replication, amplifying the introduced expression cassettes, now become important routine of expression a large number of heterologous gene products. In this paper, the authors used pCI-neo vector to construct a recombnant pCIp264 （cotains mPrP, N-signalpeptide and C-GPI anchor） plasmid to express it in the COS-7 cells and meanwhile detect the expression fusion using IN-ELISA, IN-IFA and western blot, and obtain some approximative nature PrPc.展开更多
Dengue is a severe mosquito-borne viral infection causing half a million deaths annually. Dengue virus NS2B/NS3 protease is a validated target for anti-dengue drug design. A series of hitherto unreported 3,5-bis(aryli...Dengue is a severe mosquito-borne viral infection causing half a million deaths annually. Dengue virus NS2B/NS3 protease is a validated target for anti-dengue drug design. A series of hitherto unreported 3,5-bis(arylidene)-4-piperidones analogues 4a4j were synthesized and screened in silico against DENV2 NS2B/NS3 protease to elucidate their binding mechanism and orientation around the active sites. Results were validated through an in vitro DENV2 NS2B/NS3 protease assay using a fluorogenic Boc-Gly-Arg-Arg-AMC substrate. Nitro derivatives of 3,5-bis(arylidene)-4-piperidones (4e and 4j) emerged as promising lead molecules for novel protease inhibitors with an IC<sub>50</sub> of 15.22 and 16.23 µmol/L, respectively, compared to the standard, panduratin A, having IC<sub>50</sub> of 57.28 µmol/L.展开更多
文摘凡由朊毒(Prion)引起的人畜共患病(Zoonosis)统称为朊毒病，这种疾病均为中枢神经系统致死性的慢性退化性疾病(The fatal，chronic degradative disease of central nervous system)，其中包括20世纪20年代发现的人类克-雅氏病(Creuzfeldt—Jacob disease CJD)：1986年起源于英国。
基金the National Natural Sciences Foundation of China(81172376,31270209)the 100 talent-program of the Chinese Academy of Sciencesthe State Key Laboratory of Virology for financial support
文摘Prion diseases are a group of neurodegenerative diseases that are fatal. The study of these unique diseases in China is hampered by a lack of resources. Amongst the most important resources for biological study are monoclonal antibodies. Here, we characterize a panel of monoclonal antibodies specific for cellular prion protein by enzyme-linked immunosorbent assay(ELISA), immunofluorescent staining, flow cytometry, and western blotting. We identify several antibodies that can be used for specific applications and we demonstrate that there is no prion protein expression in human pancreatic ductal epithelial cells(HPDC).
基金National Natural Science Foundations ofChina (30871854)National Science and Technology Supporting Program of China (2006BAD06A13)
文摘Prion diseases are infectious and fatal neurodegenerative diseases.The pathogenic agent is an abnormal prion protein aggregate.Microglial activation in the centre nervous system is a characteristic feature of prion disease.In this study,we examined the effect of PrP 106-126 on PrP mRNA gene expression in Mouse microglia cells BV-2 by real-time quantitative PCR.PrP mRNA expression level was found to be significantly increased after 18 h exposure of BV-2 cells to PrP 106-126,with 3-fold increase after 18 h and 4.5-fold increase after 24 h and BV-2 cells proliferating occurred correspondingly.Our results provide the first in vitro evidence of the increase of PrP mRNA levels in microglial cells exposed to PrP 106-126,and indicate that microglial cells might play a critical role in prion pathogenesis.
文摘A conformal structure of a prion protein is thought to cause a prion disease by S.B. Prusiner＇s theory. Knot theory in mathematics is useful in studying a topological difference of topological objects. In this article, concerning this conjecture, a topological model of prion proteins （PrPc, PrPsc） called a prion-tangle is introduced to discuss a question of whether or not the prion proteins are easily entangled by an approach from the mathematical knot theory. It is noted that any prion-string with trivial loop which is a topological model of a prion protein can not be entangled topologically unless a certain restriction such as ＂Rotaxsane Property＂ is imposed on it. Nevertheless, it is shown that any two split prion-tangles can be changed by a one-crossing change into a non-split prion-tangle with the given prion-tangles contained while some attentions are paid to the loop systems. The proof is made by a mathematical argument on knot theory of spatial graphs. This means that the question above is answered affirmatively in this topological model of prion-tangles. Next, a question of what is the simplest topological situation of the non-split prion-tangles is considered. By a mathematical argument, it is determined for every n 〉 1 that the minimal crossing number of n-string non-split prion-tangles is 2n or 2n-2, respectively, according to whether or not the assumption that the loop system is a trivial link is counted.
基金Acknowledgment This work was supported by grants from the National Natural Science Foundation （30671563, 30700597） and Key Project of Science and Technology of Gansu Province （0801NKDA034） and by gifts from the Development Planning Project of Science and Technology of Lanzhou （07-2-12, 2008- l- 167）.
文摘Bovine spongiform encephalopathy （BSE） is thought to be caused by prions initially derived from sheep scrapie, and epidemiological studies suggest that new viriant form of CJD manifest in Great Britain may be caused by BSE prions. PrP^Sc is thought to pathogenic factor of transmissible spongiform encephalopathy （TSE）, which invariably involve a post-translational modification process of PrPc encoded by the host euchromosome PrP gene during the period it converted into the pathogenic form （PrP^Sc）, PrP is nomal cellular protein which has been found in both neuronal and nonneuronal tissues. Since the crucial infectious event in protein-transmitted diseases is an induced misfolding of prion proteins （PrP^c） catalyzed by already misfolded PrP^Sc, it is of high importance that such collisions are enhanced by two-dimensional diffusion in cell membranes is of high importance compared to three-dimensional diffusion in solution. The level of PrP mRNA in brain is higher than other tissue, but purification of PrPc from rodent has been difficult. To understand the formation of PrP^Sc, it seemed useful to develop a system for produced a large quantities of PrPc since there is no nature source of PrP^c. The pCI-neo mammalian expression vector contains the neomycin phosphtransferase gene which serves as a marker for the selection of stable transfected cells with G418. COS-7 cells constitutively express simian viruse 40 （SV40） T-antigen and support replication of expression plasmids containing the SV40 origin of replication, amplifying the introduced expression cassettes, now become important routine of expression a large number of heterologous gene products. In this paper, the authors used pCI-neo vector to construct a recombnant pCIp264 （cotains mPrP, N-signalpeptide and C-GPI anchor） plasmid to express it in the COS-7 cells and meanwhile detect the expression fusion using IN-ELISA, IN-IFA and western blot, and obtain some approximative nature PrPc.
基金The Research University Team Grant (RUT/1001/PKIMIA/855006) provided by Universiti Sains Malaysia(USM)
文摘Dengue is a severe mosquito-borne viral infection causing half a million deaths annually. Dengue virus NS2B/NS3 protease is a validated target for anti-dengue drug design. A series of hitherto unreported 3,5-bis(arylidene)-4-piperidones analogues 4a4j were synthesized and screened in silico against DENV2 NS2B/NS3 protease to elucidate their binding mechanism and orientation around the active sites. Results were validated through an in vitro DENV2 NS2B/NS3 protease assay using a fluorogenic Boc-Gly-Arg-Arg-AMC substrate. Nitro derivatives of 3,5-bis(arylidene)-4-piperidones (4e and 4j) emerged as promising lead molecules for novel protease inhibitors with an IC<sub>50</sub> of 15.22 and 16.23 µmol/L, respectively, compared to the standard, panduratin A, having IC<sub>50</sub> of 57.28 µmol/L.
