The molecular mechanism of how hepatocytes maintain cholesterol homeostasis has become much more transparent with the discovery of sterol regulatory element binding proteins (SREBPs) in recent years. These membrane pr...The molecular mechanism of how hepatocytes maintain cholesterol homeostasis has become much more transparent with the discovery of sterol regulatory element binding proteins (SREBPs) in recent years. These membrane proteins aremembers of the basic helix-loop-helix-leucine zipper (bHLHZip) family of transcription factors. They activate the expression of at least 30 genes involved in the synthesis of cholesterol and lipids. SREBPs are synthesized as precursor proteins in the endoplasmic reticulum (ER), where they form a complex with another protein, SREBP cleavage activating protein (SCAP). The SCAP molecule contains a sterol sensory domain. In the presence of high cellular sterol concentrations SCAP confines SREBP to the ER. With low cellular concentrations, SCAP escorts SREBP to activation in the Golgi. There, SREBP undergoes two proteolytic cleavage steps to release the mature, biologically active transcription factor, nuclear SREBP (nSREBP). nSREBP translocates to the nucleus and binds to sterol response elements (SRE) in the promoter/enhancer regions of target genes. Additional transcription factors are required to activate transcription of these genes. Three different SREBPs are known, SREBPs-1a, -1c and -2. SREBP-1a and -1c are isoforms produced from a single gene by alternate splicing. SREBP-2 is encoded by a different gene and does not display any isoforms. It appears that SREBPs alone, in the sequence described above, can exert complete control over cholesterol synthesis, whereas many additional factors (hormones, cytokines, etc.) are required for complete control of lipid metabolism. Medicinal manipulation of the SREBP/SCAP system is expected to prove highly beneficial in the management of cholesterol-related disease.展开更多
Dehydration-responsive element-binding (DREB) proteins specifically binding with dehydration-responsive element (DRE) have been identified as a kind of important transcription activator of plants under drought, high s...Dehydration-responsive element-binding (DREB) proteins specifically binding with dehydration-responsive element (DRE) have been identified as a kind of important transcription activator of plants under drought, high salt and cold stress. The conserved amino, acid residues of Val (14th residue) and Glu (19th residue) in AP2/EREBP domain of DREB1A have been identified to be two key points in determining the binding ability of DREB gene with DRE element. Using the yeast one-hybrid system, we isolated one maize DREB gene named maDREB1 by screening cDNA library. Trans-activation experiment in yeast reporter strain demonstrated that maDREB1 protein could function as a DREB transcription factor activating target gene expression by specifically binding to the DRE cis-element. To assess the functional significance of these two residues in maDREB1, the V14 and E19 were substituted individually or doubly by Ala and Asp. Point mutation analysis showed that V14 substitution made significant loss of binding ability with DRE element, while point mutation of E19 had less effect. If the substitution happened simultaneously to these two residues, it would lead to great loss of the ability of binding with DRE element. It suggested that V14 and E19 were both important in protein-DNA interacting in maDREB1, though 14V was more essential. The copy number and expression pattern of maDREB1 was discussed.展开更多
The recently proposed weak form quadrature element method (QEM) is applied to flexural and vibrational analysis of thin plates The integrals involved in the variational description of a thin plate are evaluated by a...The recently proposed weak form quadrature element method (QEM) is applied to flexural and vibrational analysis of thin plates The integrals involved in the variational description of a thin plate are evaluated by an efficient numerical scheme and the par- tial derivatives at the integration sampling points are then approximated using differential quadrature analogs. Neither the grid pattern nor the number of nodes is fixed, being adjustable according to convergence need. The C~ continuity conditions char- acterizing the thin plate theory are discussed and the robustness of the weak form quadrature element for thin plates against shape distortion is examined. Examples are presented and comparisons with analytical solutions and the results of the finite element method are made to demonstrate the convergence and computational efficiency of the weak form quadrature element method. It is shown that the present formulation is applicable to thin plates with varying thickness as well as uniform plates.展开更多
Objective:Pulmonary hypertension(PH)is a severe pulmonary vascular disease that eventually leads to right ventricular failure and death.The purpose of this study was to investigate the mechanism by which pachymic acid...Objective:Pulmonary hypertension(PH)is a severe pulmonary vascular disease that eventually leads to right ventricular failure and death.The purpose of this study was to investigate the mechanism by which pachymic acid(PA)pretreatment affects PH and pulmonary vascular remodeling in rats.Methods:PH was induced via hypoxia exposure and administration of PA(5 mg/kg per day)in male Sprague-Dawley rats.Hemodynamic parameters were measured using a right ventricular floating catheter and pulmonary vascular morphometry was measured by hematoxylin-eosin(HE),a-SMA and Masson staining.MTT assays and EdU staining were used to detect cell proliferation,and apoptosis was analyzed by TUNEL staining.Western blotting and immunohistochemistry were used to detect the expression of proteins related to the Nrf2-Keapl-ARE pathway.展开更多
This paper generalizes two nonconforming rectangular elements of the Reissner-Mindlin plate to the quadrilateral mesh. The first quadrilateral element uses the usual conforming bilinear element to approximate both com...This paper generalizes two nonconforming rectangular elements of the Reissner-Mindlin plate to the quadrilateral mesh. The first quadrilateral element uses the usual conforming bilinear element to approximate both components of the rotation, and the modified nonconforming rotated Q1 element enriched with the intersected term on each element to approximate the displacement, whereas the second one uses the enriched modified nonconforming rotated Q1 element to approximate both the rotation and the displacement. Both elements employ a more complicated shear force space to overcome the shear force locking, which will be described in detail in the introduction. We prove that both methods converge at optimal rates uniformly in the plate thickness t and the mesh distortion parameter in both the H1-and the L2-norms, and consequently they are locking free.展开更多
The oxidation behaviour of molten ZK60 and ME20 magnesium alloys in 1% 1,1,1,2-tetrafluoroethane/air atmospheres at 720 °C was compared with that of molten magnesium. The oxidation kinetics of these three melts w...The oxidation behaviour of molten ZK60 and ME20 magnesium alloys in 1% 1,1,1,2-tetrafluoroethane/air atmospheres at 720 °C was compared with that of molten magnesium. The oxidation kinetics of these three melts was determined by thermograyimetric measuring instrument, and the surface films of the oxidized samples were examined by scanning electron microscope (SEM), X-ray diffractometry (XRD) and X-ray photoelectron spectroscopy (XPS). The results show that the oxidation rate of molten ZK60 or ME20 alloys is much lower than that of molten magnesium in 1% 1,1,1,2-tetrafluoroethane/air atmospheres. The surface film formed on the molten magnesium is composed of MgF2, MgO and C, while the film formed on ZK60 melt mainly consists of MgF2, MgO, C and some ZrF4, and the film on ME20 mainly consists of MgF2, MgO, C and a small amount of CeF4. The good oxidation resistances of ZK60 and ME20 alloy melts may be caused by their major alloying elements Zr and Ce, respectively.展开更多
文摘The molecular mechanism of how hepatocytes maintain cholesterol homeostasis has become much more transparent with the discovery of sterol regulatory element binding proteins (SREBPs) in recent years. These membrane proteins aremembers of the basic helix-loop-helix-leucine zipper (bHLHZip) family of transcription factors. They activate the expression of at least 30 genes involved in the synthesis of cholesterol and lipids. SREBPs are synthesized as precursor proteins in the endoplasmic reticulum (ER), where they form a complex with another protein, SREBP cleavage activating protein (SCAP). The SCAP molecule contains a sterol sensory domain. In the presence of high cellular sterol concentrations SCAP confines SREBP to the ER. With low cellular concentrations, SCAP escorts SREBP to activation in the Golgi. There, SREBP undergoes two proteolytic cleavage steps to release the mature, biologically active transcription factor, nuclear SREBP (nSREBP). nSREBP translocates to the nucleus and binds to sterol response elements (SRE) in the promoter/enhancer regions of target genes. Additional transcription factors are required to activate transcription of these genes. Three different SREBPs are known, SREBPs-1a, -1c and -2. SREBP-1a and -1c are isoforms produced from a single gene by alternate splicing. SREBP-2 is encoded by a different gene and does not display any isoforms. It appears that SREBPs alone, in the sequence described above, can exert complete control over cholesterol synthesis, whereas many additional factors (hormones, cytokines, etc.) are required for complete control of lipid metabolism. Medicinal manipulation of the SREBP/SCAP system is expected to prove highly beneficial in the management of cholesterol-related disease.
文摘Dehydration-responsive element-binding (DREB) proteins specifically binding with dehydration-responsive element (DRE) have been identified as a kind of important transcription activator of plants under drought, high salt and cold stress. The conserved amino, acid residues of Val (14th residue) and Glu (19th residue) in AP2/EREBP domain of DREB1A have been identified to be two key points in determining the binding ability of DREB gene with DRE element. Using the yeast one-hybrid system, we isolated one maize DREB gene named maDREB1 by screening cDNA library. Trans-activation experiment in yeast reporter strain demonstrated that maDREB1 protein could function as a DREB transcription factor activating target gene expression by specifically binding to the DRE cis-element. To assess the functional significance of these two residues in maDREB1, the V14 and E19 were substituted individually or doubly by Ala and Asp. Point mutation analysis showed that V14 substitution made significant loss of binding ability with DRE element, while point mutation of E19 had less effect. If the substitution happened simultaneously to these two residues, it would lead to great loss of the ability of binding with DRE element. It suggested that V14 and E19 were both important in protein-DNA interacting in maDREB1, though 14V was more essential. The copy number and expression pattern of maDREB1 was discussed.
基金supported by the National Natural Science Foundation of China (Grant Nos.51178247 and 50778104)the National High Technology Research and Development Program of China (Grant No.2009AA04Z401)
文摘The recently proposed weak form quadrature element method (QEM) is applied to flexural and vibrational analysis of thin plates The integrals involved in the variational description of a thin plate are evaluated by an efficient numerical scheme and the par- tial derivatives at the integration sampling points are then approximated using differential quadrature analogs. Neither the grid pattern nor the number of nodes is fixed, being adjustable according to convergence need. The C~ continuity conditions char- acterizing the thin plate theory are discussed and the robustness of the weak form quadrature element for thin plates against shape distortion is examined. Examples are presented and comparisons with analytical solutions and the results of the finite element method are made to demonstrate the convergence and computational efficiency of the weak form quadrature element method. It is shown that the present formulation is applicable to thin plates with varying thickness as well as uniform plates.
基金This project was supported by the Natural Science Foundation of Hubei Province(No.2017CFB769).
文摘Objective:Pulmonary hypertension(PH)is a severe pulmonary vascular disease that eventually leads to right ventricular failure and death.The purpose of this study was to investigate the mechanism by which pachymic acid(PA)pretreatment affects PH and pulmonary vascular remodeling in rats.Methods:PH was induced via hypoxia exposure and administration of PA(5 mg/kg per day)in male Sprague-Dawley rats.Hemodynamic parameters were measured using a right ventricular floating catheter and pulmonary vascular morphometry was measured by hematoxylin-eosin(HE),a-SMA and Masson staining.MTT assays and EdU staining were used to detect cell proliferation,and apoptosis was analyzed by TUNEL staining.Western blotting and immunohistochemistry were used to detect the expression of proteins related to the Nrf2-Keapl-ARE pathway.
基金the National Natural Science Foundation of China (Grant No. 10601003)National Excellent Doctoral Dissertation of China (Grant No. 200718)
文摘This paper generalizes two nonconforming rectangular elements of the Reissner-Mindlin plate to the quadrilateral mesh. The first quadrilateral element uses the usual conforming bilinear element to approximate both components of the rotation, and the modified nonconforming rotated Q1 element enriched with the intersected term on each element to approximate the displacement, whereas the second one uses the enriched modified nonconforming rotated Q1 element to approximate both the rotation and the displacement. Both elements employ a more complicated shear force space to overcome the shear force locking, which will be described in detail in the introduction. We prove that both methods converge at optimal rates uniformly in the plate thickness t and the mesh distortion parameter in both the H1-and the L2-norms, and consequently they are locking free.
基金Project (SJ08-ZT05) supported by the Natural Science Basic Research Plan in Shaanxi Province of ChinaProject (ZK1050) supported by the Key Scientific Research Plan of Baoji University of Arts and Science, China
文摘The oxidation behaviour of molten ZK60 and ME20 magnesium alloys in 1% 1,1,1,2-tetrafluoroethane/air atmospheres at 720 °C was compared with that of molten magnesium. The oxidation kinetics of these three melts was determined by thermograyimetric measuring instrument, and the surface films of the oxidized samples were examined by scanning electron microscope (SEM), X-ray diffractometry (XRD) and X-ray photoelectron spectroscopy (XPS). The results show that the oxidation rate of molten ZK60 or ME20 alloys is much lower than that of molten magnesium in 1% 1,1,1,2-tetrafluoroethane/air atmospheres. The surface film formed on the molten magnesium is composed of MgF2, MgO and C, while the film formed on ZK60 melt mainly consists of MgF2, MgO, C and some ZrF4, and the film on ME20 mainly consists of MgF2, MgO, C and a small amount of CeF4. The good oxidation resistances of ZK60 and ME20 alloy melts may be caused by their major alloying elements Zr and Ce, respectively.