多聚腺苷酸结合蛋白相互作用蛋白1[Poly(A)-binding protein-interacting protein 1,Paip1]是哺乳动物特有的蛋白质,可有效参与真核生物基因表达及细胞周期调控,并与肿瘤演进及预后密切相关。近年来Paip1成为肿瘤研究热点,Paip1与肿瘤...多聚腺苷酸结合蛋白相互作用蛋白1[Poly(A)-binding protein-interacting protein 1,Paip1]是哺乳动物特有的蛋白质,可有效参与真核生物基因表达及细胞周期调控,并与肿瘤演进及预后密切相关。近年来Paip1成为肿瘤研究热点,Paip1与肿瘤细胞增殖、迁移、侵袭和上皮间质转化进程密切相关,可能是肿瘤进展及预后不良的潜在生物标志和新的治疗靶点。但其具体作用机制尚未阐明。本文就Paip1的结构、功能、泛素化和降解及其与肿瘤的关系等方面作一综述,为其在肿瘤中的研究提供新思路。展开更多
Aptamers are a type of single-chain oligonucleotide that can combine with a specific target.Due to their simple preparation,easy modification,stable structure and reusability,aptamers have been widely applied as bioch...Aptamers are a type of single-chain oligonucleotide that can combine with a specific target.Due to their simple preparation,easy modification,stable structure and reusability,aptamers have been widely applied as biochemical sensors for medicine,food safety and environmental monitoring.However,there is little research on aptamer-target binding mechanisms,which limits their application and development.Computational simulation has gained much attention for revealing aptamer-target binding mechanisms at the atomic level.This work summarizes the main simulation methods used in the mechanistic analysis of aptamer-target complexes,the characteristics of binding between aptamers and different targets(metal ions,small organic molecules,biomacromolecules,cells,bacteria and viruses),the types of aptamer-target interactions and the factors influencing their strength.It provides a reference for further use of simulations in understanding aptamer-target binding mechanisms.展开更多
The seismic safety of offshore wind turbines is an important issue that needs to be solved urgently.Based on a unified computing framework,this paper develops a set of seawater-seabed-wind turbine zoning coupling anal...The seismic safety of offshore wind turbines is an important issue that needs to be solved urgently.Based on a unified computing framework,this paper develops a set of seawater-seabed-wind turbine zoning coupling analysis methods.A 5 MW wind turbine and a site analysis model are established,and a seismic wave is selected to analyze the changes in the seismic response of offshore monopile wind turbines under the change of seawater depth,seabed wave velocity and seismic wave incidence angle.The analysis results show that when the seawater increases to a certain depth,the seismic response of the wind turbine increases.The shear wave velocity of the seabed affects the bending moment and displacement at the bottom of the tower.When the angle of incidence increases,the vertical displacement and the acceleration of the top of the tower increase in varying degrees.展开更多
The interfacial interaction existing in the Ni ZrO 2 composite plating has been investigated. The experimental results show that no new phases were formed in the interfacial regions between matrix Ni and ZrO 2 part...The interfacial interaction existing in the Ni ZrO 2 composite plating has been investigated. The experimental results show that no new phases were formed in the interfacial regions between matrix Ni and ZrO 2 particles, but an orbital interaction through the mutual overlap of the d orbits does exist in the interfacial regions between Ni atoms and Zr 3+ ions.展开更多
Influenza A(A/H_(x)N_(y))is a significant public health concern due to its high infectiousness and mortality.Neuraminidase,which interacts with sialic acid(SIA)in host cells,has become an essential target since its hi...Influenza A(A/H_(x)N_(y))is a significant public health concern due to its high infectiousness and mortality.Neuraminidase,which interacts with sialic acid(SIA)in host cells,has become an essential target since its highly conserved catalytic center structure,while resistance mutations have already generated.Here,a detailed investigation of the drug resistance mechanism caused by mutations was performed for subtype N9(A/H7N9).Molecular dynamics simulation and alanine-scanning-interaction-entropy method(ASIE)were used to explore the critical differences between N9 and Zanamivir(ZMR)before and after R294K mutation.The results showed that the mutation caused the hydrogen bond between Arg294 and ZMR to break,then the hydrogen bonding network was disrupted,leading to weakened binding ability and resistance.While in wild type(A/H7N9^(WT)),this hydrogen bond was initially stable.Meanwhile,N9 derived from A/H11N9 was obtained as an R292K mutation.Then the relative binding free energy of N9 with five inhibitors(SIA,DAN,ZMR,G28,and G39)was predicted,basically consistent with experimental values,indicating that the calculated results were reliable by ASIE.In addition,Arg292 and Tyr406 were hot spots in the A/H11N9^(WT)-drugs.However,Lys292 was not observed as a favorable contributing residue in A/H11N9^(R292K),which may promote resistance.In comparison,Tyr406 remained the hotspot feature when SIA,ZMR,and G28 binding to A/H11N9^(R292K).Combining the two groups,we speculate that the resistance was mainly caused by the disruption of the hydrogen bonding network and the transformation of hotspots.This study could guide novel drug delivery of drug-resistant mutations in the treatment of A/H_(x)N9.展开更多
In Saccharomyces cerevisiae, the essential gene CDC13 encodes a telomeric single-stranded DNA-binding protein that interacts with Stnlp and Tenlp genetically and physically, and is required for telomere end protection...In Saccharomyces cerevisiae, the essential gene CDC13 encodes a telomeric single-stranded DNA-binding protein that interacts with Stnlp and Tenlp genetically and physically, and is required for telomere end protection and telomere length control. The molecular mechanism by which Tenl participates in telomere length regulation and chromosome end protection remains elusive. In this work, we observed a weak interaction of Cdc13p and Tenlp in a gelfiltration analysis using purified recombinant Cdc13p and Tenlp. Tenlp itself exhibits a weak DNA-binding activity, but enhances the telomeric TG1-3 DNA-binding ability of Cdc13p. Cdc13p is communoprecipitated with Tenlp. In the mutant ten1-55 or ten1-66 cells, the impaired interaction between Tenlp and Cdc13p results in much longer telomeres, as well as a decreased association of Cdc13p with telomeric DNA. Consistently, the Ten1-55 and Ten1-66 mutant proteins fail to stimulate the telomeric DNA-binding activity of Cdc13p in vitro. These results suggest that Tenlp enhances the telomeric DNA-binding activity of Cdc13p to negatively regulate telomere length.展开更多
Most protein-ligand interactions take place on surfaces and include but not limited to factors such as chemical composition, hydrophobicity, electronegavitiy and shape complementarity. Past studies showed that protein...Most protein-ligand interactions take place on surfaces and include but not limited to factors such as chemical composition, hydrophobicity, electronegavitiy and shape complementarity. Past studies showed that protein-protein interactions occur on comparatively fiat regions whereas protein-ligand bindings involve crevices. In the search for such sites various approaches have been designed and developed each of which is algorithmically unique. The use of grid units or voxels has been demonstrated in early studies with relatively good results obtained. We present here an approximated approach comprising of the use of voxels and computer vision methods in the search for ligand-binding areas. Each test protein is modelled and analysed in 2D with all corresponding residues graphically presented for successfully identified sites. The study was carried out on 2 sets of proteins: FK506-bound proteins and heme-bound proteins with promising results obtained for all test cases.展开更多
In this paper, we study a quantum anti-Zeno effect (QAZE) purely induced by repetitive measurements for an artificial atom interacting with a structured bath. This bath can be artificially realized with coupled reso...In this paper, we study a quantum anti-Zeno effect (QAZE) purely induced by repetitive measurements for an artificial atom interacting with a structured bath. This bath can be artificially realized with coupled resonators in one dimension and possesses photonic band structure like Bloeh electron in a periodic potential. In the presence of repetitive measurements, the pure QAZE is discovered as the observable decay is not negligible even for the atomic energy level spacing outside of the energy band of the artificial bath. If there were no measurements, the decay would not happen outside of the band. In this sense, the enhanced decay is completely induced by measurements through the relaxation channels provided by the bath. Besides, we also discuss the controversial golden rule decay rates originated from the van Hove's singularities and the effects of the counter-rotating terms.展开更多
Carboxylmethyl cellulose(CMC) has become a commercial organic binder in agglomeration of iron ore concentrates. The relative molecular mass and degree of substitution(DS) of CMC have a large impact on its binding perf...Carboxylmethyl cellulose(CMC) has become a commercial organic binder in agglomeration of iron ore concentrates. The relative molecular mass and degree of substitution(DS) of CMC have a large impact on its binding performance. The interaction mechanism between CMC and iron ore particles was analyzed through Zeta potential measurements, adsorption measurements and infrared spectra. The results show that the interaction is chemical adsorption-oriented and the CMC's adsorption performance is related to the properties of CMC as well as the type of iron oxides. CMC has a greater affinity to Fe2O3 than Fe3O4, and CMC with higher relative molecular mass shows a higher adsorption isotherm. Pelletization of practical iron ore concentrates added with CMC further illustrates that CMC with higher relative molecular mass or DS exhibits a better binding performance, which is consistent with the results of adsorption tests.展开更多
In this study, one mononuclear zinc(II) complex with 1,2-bis CAP ((5-chlorosalicylidene amino)-phenylene): C22C13N2035Znl5 H0125 (Zn-CAP) was synthesized. The binding properties of Zn-CAP with G-quadruplex DN...In this study, one mononuclear zinc(II) complex with 1,2-bis CAP ((5-chlorosalicylidene amino)-phenylene): C22C13N2035Znl5 H0125 (Zn-CAP) was synthesized. The binding properties of Zn-CAP with G-quadruplex DNA and ctDNA (calf thymus DNA) were examined by fluorescence, CD (circular dichroism) spectroscopic and FRET (fluorescence resonance energy transfer) assay. In the fluorescence emission spectral analysis, the addition of three series of G-quadruplex DNA (G4-HTG21, G4-Pu27 and G4-c-kit-l) into the Zn-CAP solution induced moderate or add hypochromicity with total quenching ratios of 10.73%, 15.07% and 8.59% in the presence of K+ were achieved, respectively. While the addition of ctDNA under same condition only caused 7.08% quenching on the fluorescence emission of Zn-CAP. In the CD spectral analysis, the interaction with Zn-CAP could induce significant spectral changes on the CD absorption of G4-HTG21, G4-Pu27 and G4-c-kit-1, with 106.00%, 93.06%, 113.47% increment at 232 nm absorption, along with a 81.11%, 92.80%, 83.72% decrement at 295 nm or 270 nm absorption, which demonstrated that the antiparallel structure of G-quadruplex DNA is more stable in the presence of Zn-CAP. Comparatively, the addition of Zn-CAP could induce significant spectral changes on the CD absorption of double helix ctDNA, with 64.17% decrement on the positive peak absorption, along with a 90.91% increment on the negative peak absorption. On the other hand, in the FRET-melting assay analysis, it was clear that Zn-CAP at 0.5 equivalences could raise the melting temperature of G-quadruplex (F2 IT or FPul 8T) by 3.45℃ and 15.85℃, indicating an obvious stabilization effect of Zn-CAP on G-quadruplex in Pu27. All the results indicated that Zn-CAP exhibited higher binding affinity and binding intensity to G-quadruplex DNA than ctDNA, especially G-quadruplex Pu27.展开更多
in geotechnical engineering, numerical simulation of problems is of great importance. This work proposes a new formulation of coupled finite-infinite elements which can be used in numerical simulation ofgeotechnical p...in geotechnical engineering, numerical simulation of problems is of great importance. This work proposes a new formulation of coupled finite-infinite elements which can be used in numerical simulation ofgeotechnical problems in both static and dynamic conditions. Formulation and various implementation aspects of the proposed coupled finite-infinite elements are carefully discussed. To the authors' knowledge, this approach that considers coupled finite-infinite elements is more efficient in the sense that appropriate and accurate results are obtained by using less elements. The accuracy and efficiency of the proposed approach is considered by comparing the obtained results with analytical and numerical results. In a static case, the problem of circular domain ol infinite length is considered. In a dynamic case, one dimensional wave propagation problems arising from the Heaviside step fimction and impulse functions are considered. In order to get a more complete picture, two dimensional wave propagation in a circular qtmrter space is considered and the results are presented. Finally, a soil-structure interaction system subjected to seismic excitation is analyzed. In the analysis of soil-structure interaction phenomenon, frames with different number of storeys and soil media with various stiffness characteristics have been taken into consideration. In the analysis, the finite element software ANSYS has been used. For the newly developed infinite element, the programming has been done by the help of the User Programmable Features of the ANSYS software, which enable creating new elements in the ANSYS software.展开更多
文摘多聚腺苷酸结合蛋白相互作用蛋白1[Poly(A)-binding protein-interacting protein 1,Paip1]是哺乳动物特有的蛋白质,可有效参与真核生物基因表达及细胞周期调控,并与肿瘤演进及预后密切相关。近年来Paip1成为肿瘤研究热点,Paip1与肿瘤细胞增殖、迁移、侵袭和上皮间质转化进程密切相关,可能是肿瘤进展及预后不良的潜在生物标志和新的治疗靶点。但其具体作用机制尚未阐明。本文就Paip1的结构、功能、泛素化和降解及其与肿瘤的关系等方面作一综述,为其在肿瘤中的研究提供新思路。
文摘Aptamers are a type of single-chain oligonucleotide that can combine with a specific target.Due to their simple preparation,easy modification,stable structure and reusability,aptamers have been widely applied as biochemical sensors for medicine,food safety and environmental monitoring.However,there is little research on aptamer-target binding mechanisms,which limits their application and development.Computational simulation has gained much attention for revealing aptamer-target binding mechanisms at the atomic level.This work summarizes the main simulation methods used in the mechanistic analysis of aptamer-target complexes,the characteristics of binding between aptamers and different targets(metal ions,small organic molecules,biomacromolecules,cells,bacteria and viruses),the types of aptamer-target interactions and the factors influencing their strength.It provides a reference for further use of simulations in understanding aptamer-target binding mechanisms.
基金supported in part by the National Natural Science Foundation of China(Nos.51978337,U2039209).
文摘The seismic safety of offshore wind turbines is an important issue that needs to be solved urgently.Based on a unified computing framework,this paper develops a set of seawater-seabed-wind turbine zoning coupling analysis methods.A 5 MW wind turbine and a site analysis model are established,and a seismic wave is selected to analyze the changes in the seismic response of offshore monopile wind turbines under the change of seawater depth,seabed wave velocity and seismic wave incidence angle.The analysis results show that when the seawater increases to a certain depth,the seismic response of the wind turbine increases.The shear wave velocity of the seabed affects the bending moment and displacement at the bottom of the tower.When the angle of incidence increases,the vertical displacement and the acceleration of the top of the tower increase in varying degrees.
文摘The interfacial interaction existing in the Ni ZrO 2 composite plating has been investigated. The experimental results show that no new phases were formed in the interfacial regions between matrix Ni and ZrO 2 particles, but an orbital interaction through the mutual overlap of the d orbits does exist in the interfacial regions between Ni atoms and Zr 3+ ions.
基金supported by the National Natural Science Foundation of China(No.11774207)。
文摘Influenza A(A/H_(x)N_(y))is a significant public health concern due to its high infectiousness and mortality.Neuraminidase,which interacts with sialic acid(SIA)in host cells,has become an essential target since its highly conserved catalytic center structure,while resistance mutations have already generated.Here,a detailed investigation of the drug resistance mechanism caused by mutations was performed for subtype N9(A/H7N9).Molecular dynamics simulation and alanine-scanning-interaction-entropy method(ASIE)were used to explore the critical differences between N9 and Zanamivir(ZMR)before and after R294K mutation.The results showed that the mutation caused the hydrogen bond between Arg294 and ZMR to break,then the hydrogen bonding network was disrupted,leading to weakened binding ability and resistance.While in wild type(A/H7N9^(WT)),this hydrogen bond was initially stable.Meanwhile,N9 derived from A/H11N9 was obtained as an R292K mutation.Then the relative binding free energy of N9 with five inhibitors(SIA,DAN,ZMR,G28,and G39)was predicted,basically consistent with experimental values,indicating that the calculated results were reliable by ASIE.In addition,Arg292 and Tyr406 were hot spots in the A/H11N9^(WT)-drugs.However,Lys292 was not observed as a favorable contributing residue in A/H11N9^(R292K),which may promote resistance.In comparison,Tyr406 remained the hotspot feature when SIA,ZMR,and G28 binding to A/H11N9^(R292K).Combining the two groups,we speculate that the resistance was mainly caused by the disruption of the hydrogen bonding network and the transformation of hotspots.This study could guide novel drug delivery of drug-resistant mutations in the treatment of A/H_(x)N9.
基金Acknowledgments We thank Ms Lu-Xia Xu for the help in antibody preparation, and other members in the Zhou lab. This work is supported by a Chinese Academy of Sciences-Max Planck Society Professorship, and grants from the National Natural Science Foundation of China (NSFC 30630018) and the Ministry of Science and Technology of China (2007CB914502).
文摘In Saccharomyces cerevisiae, the essential gene CDC13 encodes a telomeric single-stranded DNA-binding protein that interacts with Stnlp and Tenlp genetically and physically, and is required for telomere end protection and telomere length control. The molecular mechanism by which Tenl participates in telomere length regulation and chromosome end protection remains elusive. In this work, we observed a weak interaction of Cdc13p and Tenlp in a gelfiltration analysis using purified recombinant Cdc13p and Tenlp. Tenlp itself exhibits a weak DNA-binding activity, but enhances the telomeric TG1-3 DNA-binding ability of Cdc13p. Cdc13p is communoprecipitated with Tenlp. In the mutant ten1-55 or ten1-66 cells, the impaired interaction between Tenlp and Cdc13p results in much longer telomeres, as well as a decreased association of Cdc13p with telomeric DNA. Consistently, the Ten1-55 and Ten1-66 mutant proteins fail to stimulate the telomeric DNA-binding activity of Cdc13p in vitro. These results suggest that Tenlp enhances the telomeric DNA-binding activity of Cdc13p to negatively regulate telomere length.
文摘Most protein-ligand interactions take place on surfaces and include but not limited to factors such as chemical composition, hydrophobicity, electronegavitiy and shape complementarity. Past studies showed that protein-protein interactions occur on comparatively fiat regions whereas protein-ligand bindings involve crevices. In the search for such sites various approaches have been designed and developed each of which is algorithmically unique. The use of grid units or voxels has been demonstrated in early studies with relatively good results obtained. We present here an approximated approach comprising of the use of voxels and computer vision methods in the search for ligand-binding areas. Each test protein is modelled and analysed in 2D with all corresponding residues graphically presented for successfully identified sites. The study was carried out on 2 sets of proteins: FK506-bound proteins and heme-bound proteins with promising results obtained for all test cases.
基金Supported by the Natural Science Foundation of China under Grant Nos.10974209 and 10935010 the National 973 Program under Grant No.2006CB921205China Postdoctoral Science Foundation under Grant No.20100470584
文摘In this paper, we study a quantum anti-Zeno effect (QAZE) purely induced by repetitive measurements for an artificial atom interacting with a structured bath. This bath can be artificially realized with coupled resonators in one dimension and possesses photonic band structure like Bloeh electron in a periodic potential. In the presence of repetitive measurements, the pure QAZE is discovered as the observable decay is not negligible even for the atomic energy level spacing outside of the energy band of the artificial bath. If there were no measurements, the decay would not happen outside of the band. In this sense, the enhanced decay is completely induced by measurements through the relaxation channels provided by the bath. Besides, we also discuss the controversial golden rule decay rates originated from the van Hove's singularities and the effects of the counter-rotating terms.
基金Project(2012zzts101)supported by the Fundamental Research Funds for the Central Universities,China
文摘Carboxylmethyl cellulose(CMC) has become a commercial organic binder in agglomeration of iron ore concentrates. The relative molecular mass and degree of substitution(DS) of CMC have a large impact on its binding performance. The interaction mechanism between CMC and iron ore particles was analyzed through Zeta potential measurements, adsorption measurements and infrared spectra. The results show that the interaction is chemical adsorption-oriented and the CMC's adsorption performance is related to the properties of CMC as well as the type of iron oxides. CMC has a greater affinity to Fe2O3 than Fe3O4, and CMC with higher relative molecular mass shows a higher adsorption isotherm. Pelletization of practical iron ore concentrates added with CMC further illustrates that CMC with higher relative molecular mass or DS exhibits a better binding performance, which is consistent with the results of adsorption tests.
文摘In this study, one mononuclear zinc(II) complex with 1,2-bis CAP ((5-chlorosalicylidene amino)-phenylene): C22C13N2035Znl5 H0125 (Zn-CAP) was synthesized. The binding properties of Zn-CAP with G-quadruplex DNA and ctDNA (calf thymus DNA) were examined by fluorescence, CD (circular dichroism) spectroscopic and FRET (fluorescence resonance energy transfer) assay. In the fluorescence emission spectral analysis, the addition of three series of G-quadruplex DNA (G4-HTG21, G4-Pu27 and G4-c-kit-l) into the Zn-CAP solution induced moderate or add hypochromicity with total quenching ratios of 10.73%, 15.07% and 8.59% in the presence of K+ were achieved, respectively. While the addition of ctDNA under same condition only caused 7.08% quenching on the fluorescence emission of Zn-CAP. In the CD spectral analysis, the interaction with Zn-CAP could induce significant spectral changes on the CD absorption of G4-HTG21, G4-Pu27 and G4-c-kit-1, with 106.00%, 93.06%, 113.47% increment at 232 nm absorption, along with a 81.11%, 92.80%, 83.72% decrement at 295 nm or 270 nm absorption, which demonstrated that the antiparallel structure of G-quadruplex DNA is more stable in the presence of Zn-CAP. Comparatively, the addition of Zn-CAP could induce significant spectral changes on the CD absorption of double helix ctDNA, with 64.17% decrement on the positive peak absorption, along with a 90.91% increment on the negative peak absorption. On the other hand, in the FRET-melting assay analysis, it was clear that Zn-CAP at 0.5 equivalences could raise the melting temperature of G-quadruplex (F2 IT or FPul 8T) by 3.45℃ and 15.85℃, indicating an obvious stabilization effect of Zn-CAP on G-quadruplex in Pu27. All the results indicated that Zn-CAP exhibited higher binding affinity and binding intensity to G-quadruplex DNA than ctDNA, especially G-quadruplex Pu27.
文摘in geotechnical engineering, numerical simulation of problems is of great importance. This work proposes a new formulation of coupled finite-infinite elements which can be used in numerical simulation ofgeotechnical problems in both static and dynamic conditions. Formulation and various implementation aspects of the proposed coupled finite-infinite elements are carefully discussed. To the authors' knowledge, this approach that considers coupled finite-infinite elements is more efficient in the sense that appropriate and accurate results are obtained by using less elements. The accuracy and efficiency of the proposed approach is considered by comparing the obtained results with analytical and numerical results. In a static case, the problem of circular domain ol infinite length is considered. In a dynamic case, one dimensional wave propagation problems arising from the Heaviside step fimction and impulse functions are considered. In order to get a more complete picture, two dimensional wave propagation in a circular qtmrter space is considered and the results are presented. Finally, a soil-structure interaction system subjected to seismic excitation is analyzed. In the analysis of soil-structure interaction phenomenon, frames with different number of storeys and soil media with various stiffness characteristics have been taken into consideration. In the analysis, the finite element software ANSYS has been used. For the newly developed infinite element, the programming has been done by the help of the User Programmable Features of the ANSYS software, which enable creating new elements in the ANSYS software.