为探究脯氨酸(Proline,Pro)、谷氨酸(Glutamic Acid,Glu)二肽与鲜味受体分子相互作用,该研究合成了12个Pro、Glu二肽,以感官评价为基础,利用同源建模、分子对接技术研究Pro、Glu二肽与味觉受体第一家族亚型1(Taste Receptor Type 1 Memb...为探究脯氨酸(Proline,Pro)、谷氨酸(Glutamic Acid,Glu)二肽与鲜味受体分子相互作用,该研究合成了12个Pro、Glu二肽,以感官评价为基础,利用同源建模、分子对接技术研究Pro、Glu二肽与味觉受体第一家族亚型1(Taste Receptor Type 1 Member 1,T1R1)、味觉受体第一家族亚型3(Taste Receptor Type 1 Member 3,T1R3)和钙敏感受体(Calcium Sensitive Receptor,CaSR)的构效关系。结果表明:除脯氨酸-丝氨酸(Proline-serine,Pro-Ser)、缬氨酸-脯氨酸(Valine-proline,Val-Pro)和亮氨酸-谷氨酸(Leucine-glutamic Acid,Leu-Glu)不呈鲜,其余二肽的呈鲜阈值均低于谷氨酸钠阈值(0.3 mg/mL),其中γ-谷氨酸-蛋氨酸(γ-Glutamic Acid-methionine,γ-Glu-Met)和甘氨酸-谷氨酸(Glycine-glutamic Acid,Gly-Glu)的呈鲜阈值最低,为0.07 mg/mL。二肽与T1R1的关键结合位点为Asp147、Thr149、Ser172和Arg277,T1R1是Glu二肽呈鲜的重要受体;与T1R3的关键结合位点为Glu45、Ser147、Val277和His278,Ser147是N-γ-Glu二肽与T1R3受体的关键结合位点;与CaSR的关键结合位点为Leu173、Asn176、Gln179、Arg220、Ser244和Asp275,Glu二肽比Pro二肽更易与CaSR受体结合。二肽与受体主要通过氢键与疏水相互作用结合,呈味较强的二肽在对接时多嵌于受体结合口袋深处;呈味较弱的二肽有的位于结合口袋较浅的位置,有的其疏水区或亲水区暴露于受体表面。该研究有助于阐明鲜味肽与鲜味受体相互作用机制,为深入研究鲜味肽呈鲜机理奠定基础。展开更多
目的·筛查青少年的成人起病型糖尿病(maturity-onset diabetes of the young,MODY)家系中NEUROD1基因突变,分析突变与中国人MODY6发病的相关性及其潜在的致病机制。方法·采用PCR-直接测序法对96例GCK/MODY2、HNF1A/MODY3、HNF...目的·筛查青少年的成人起病型糖尿病(maturity-onset diabetes of the young,MODY)家系中NEUROD1基因突变,分析突变与中国人MODY6发病的相关性及其潜在的致病机制。方法·采用PCR-直接测序法对96例GCK/MODY2、HNF1A/MODY3、HNF1B/MODY5突变阴性的中国MODY先证者进行NEUROD1突变筛查,同时比较96例MODY先证者与100例非糖尿病对照者NEUROD1基因变异的基因型频率。采用从头建模法构建NEUROD1蛋白野生型和突变体的3D结构,采用双荧光素酶报告基因系统检测野生型和突变体蛋白对胰岛素基因转录活性的影响。结果·在一个MODY家系中发现NEUROD1基因杂合错义突变Glu59Gln (NM_002500.5,c.175G>C)。3D结构分析发现,该突变将野生型中带负电荷的Glu59转化为突变中不带电荷的Gln59,导致两个盐桥键Glu59-Arg54和Glu59-Lys88缺失,并形成一个新的氢键Gln59-Arg54。与野生型相比,Glu59Gln突变体的胰岛素基因转录活性下降36.3%(P<0.05)。与非糖尿病对照相比,96例MODY先证者中Ala45Thr (G-A)变异的AA+GA基因型频率显著升高(P=0.002)。结论·Glu59Gln突变改变了NEUROD1蛋白N端的分子构象,导致其胰岛素基因转录活性显著下降,是该家系突变携带者胰岛素分泌缺陷的原因。Ala45Thr变异与MODY6先证者糖尿病发病年龄的提前有关。展开更多
The performance of engineered wood products is highly associated with proper bonding and an efficient cutting method.This paper investigates the influence of CO_(2) laser cutting on the wetting properties,the modified ch...The performance of engineered wood products is highly associated with proper bonding and an efficient cutting method.This paper investigates the influence of CO_(2) laser cutting on the wetting properties,the modified che-mical component of the laser-cut surface,and the strength and adhesive penetration near the bondline.Beech-wood is cut by the laser with varying processing parameters,cutting speeds,gas pressures,and focal point positions.The laser-cut samples were divided into two groups,sanded and non-sanded samples.Polyvinyl acetate adhesive(PVAc)was used to bond the groups of laser-cut samples.After assembly with cold pressing,the tensile shear test was carried out.Numerical modelling was carried out to determine the partial elongation and shear strain of the glue line.Based on this,the shear modulus and linear elasticity of the glue line were estimated.Scan-ning electron microscopy was used to assess the adhesive penetration into the porosity structure of the laser-cut samples,and the depth of the heat-affected zone.The laser-cut surface was analysed by Fourier transform infrared spectroscopy.The wetting properties of the laser-cut surface were investigated by using a contact angle goni-ometer.The numerical model of the strain-stress curve confirmed the experimental model.The highest modulus of the linear elasticity of the glue in the numerical calculation belongs to the joint containing laser-cut samples at a gas pressure of 21(bar).The penetration depth of PVAc adhesive into the porosity structure of the laser-cut sam-ples was similar to that of sawn samples.The deepest heat-affected zone in the laser-cut samples was 150µm.A PVAc drop disappeared immediately on the laser-cut surface without sanding,but gradually on the sanded surface.In contrast,the drop on the sawn surface remained with an angle of 32°–48°.The degradation of hemi-cellulose and lignin was proven by the lower intensity of the C=O and C-O Bonds,compared to the sawn surface.展开更多
帕金森病(parkinson's disease,PD)是一种常见的中老年神经系统退行性疾病,其中脑黑质致密部(substantia nigra pars compacta,SNpc)多巴胺(dopamine,DA)能神经元进行性丢失导致基底神经节(Basal ganglia,BG)皮质-纹状体谷氨酸(glut...帕金森病(parkinson's disease,PD)是一种常见的中老年神经系统退行性疾病,其中脑黑质致密部(substantia nigra pars compacta,SNpc)多巴胺(dopamine,DA)能神经元进行性丢失导致基底神经节(Basal ganglia,BG)皮质-纹状体谷氨酸(glutamate,Glu)能通路异常兴奋与PD进展有关。目前有相当多的研究集中在氧化Glu毒性,作为治疗PD的靶点。运动疗法作为一种安全、广谱的治疗手段,能够缓解PD相关行为功能障碍,其机制可能是通过降低氧化Glu毒性来实现的。本文就对目前运动通过降低氧化Glu毒作用改善PD相关行为功能障碍的研究现状进行综述,以期为PD运动防治神经生物学机制的研究以及靶向干预提供必要的理论依据和新的思路。展开更多
In the present paper,we study partial collapsing degeneration of Hamiltonian-perturbed Floer trajectories for an adiabatic ε-family and its reversal adiabatic gluing,as the prototype of the partial collapsing degener...In the present paper,we study partial collapsing degeneration of Hamiltonian-perturbed Floer trajectories for an adiabatic ε-family and its reversal adiabatic gluing,as the prototype of the partial collapsing degeneration of 2-dimensional(perturbed)J-holomorphic maps to 1-dimensional gradient segments.We consider the case when the Floer equations are S^(1)-invariant on parts of their domains whose adiabatic limit has positive length as ε→0,which we call thimble-flow-thimble configurations.The main gluing theorem we prove also applies to the case with Lagrangian boundaries such as in the problem of recovering holomorphic disks out of pearly configuration.In particular,our gluing theorem gives rise to a new direct proof of the chain isomorphism property between the Morse-Bott version of Lagrangian intersection Floer complex of L by Fukaya-Oh-Ohta-Ono and the pearly complex of L Lalonde and Biran-Cornea.It also provides another proof of the present authors’earlier proof of the isomorphism property of the PSS map without involving the target rescaling and the scale-dependent gluing.展开更多
文摘为探究脯氨酸(Proline,Pro)、谷氨酸(Glutamic Acid,Glu)二肽与鲜味受体分子相互作用,该研究合成了12个Pro、Glu二肽,以感官评价为基础,利用同源建模、分子对接技术研究Pro、Glu二肽与味觉受体第一家族亚型1(Taste Receptor Type 1 Member 1,T1R1)、味觉受体第一家族亚型3(Taste Receptor Type 1 Member 3,T1R3)和钙敏感受体(Calcium Sensitive Receptor,CaSR)的构效关系。结果表明:除脯氨酸-丝氨酸(Proline-serine,Pro-Ser)、缬氨酸-脯氨酸(Valine-proline,Val-Pro)和亮氨酸-谷氨酸(Leucine-glutamic Acid,Leu-Glu)不呈鲜,其余二肽的呈鲜阈值均低于谷氨酸钠阈值(0.3 mg/mL),其中γ-谷氨酸-蛋氨酸(γ-Glutamic Acid-methionine,γ-Glu-Met)和甘氨酸-谷氨酸(Glycine-glutamic Acid,Gly-Glu)的呈鲜阈值最低,为0.07 mg/mL。二肽与T1R1的关键结合位点为Asp147、Thr149、Ser172和Arg277,T1R1是Glu二肽呈鲜的重要受体;与T1R3的关键结合位点为Glu45、Ser147、Val277和His278,Ser147是N-γ-Glu二肽与T1R3受体的关键结合位点;与CaSR的关键结合位点为Leu173、Asn176、Gln179、Arg220、Ser244和Asp275,Glu二肽比Pro二肽更易与CaSR受体结合。二肽与受体主要通过氢键与疏水相互作用结合,呈味较强的二肽在对接时多嵌于受体结合口袋深处;呈味较弱的二肽有的位于结合口袋较浅的位置,有的其疏水区或亲水区暴露于受体表面。该研究有助于阐明鲜味肽与鲜味受体相互作用机制,为深入研究鲜味肽呈鲜机理奠定基础。
文摘目的·筛查青少年的成人起病型糖尿病(maturity-onset diabetes of the young,MODY)家系中NEUROD1基因突变,分析突变与中国人MODY6发病的相关性及其潜在的致病机制。方法·采用PCR-直接测序法对96例GCK/MODY2、HNF1A/MODY3、HNF1B/MODY5突变阴性的中国MODY先证者进行NEUROD1突变筛查,同时比较96例MODY先证者与100例非糖尿病对照者NEUROD1基因变异的基因型频率。采用从头建模法构建NEUROD1蛋白野生型和突变体的3D结构,采用双荧光素酶报告基因系统检测野生型和突变体蛋白对胰岛素基因转录活性的影响。结果·在一个MODY家系中发现NEUROD1基因杂合错义突变Glu59Gln (NM_002500.5,c.175G>C)。3D结构分析发现,该突变将野生型中带负电荷的Glu59转化为突变中不带电荷的Gln59,导致两个盐桥键Glu59-Arg54和Glu59-Lys88缺失,并形成一个新的氢键Gln59-Arg54。与野生型相比,Glu59Gln突变体的胰岛素基因转录活性下降36.3%(P<0.05)。与非糖尿病对照相比,96例MODY先证者中Ala45Thr (G-A)变异的AA+GA基因型频率显著升高(P=0.002)。结论·Glu59Gln突变改变了NEUROD1蛋白N端的分子构象,导致其胰岛素基因转录活性显著下降,是该家系突变携带者胰岛素分泌缺陷的原因。Ala45Thr变异与MODY6先证者糖尿病发病年龄的提前有关。
文摘The performance of engineered wood products is highly associated with proper bonding and an efficient cutting method.This paper investigates the influence of CO_(2) laser cutting on the wetting properties,the modified che-mical component of the laser-cut surface,and the strength and adhesive penetration near the bondline.Beech-wood is cut by the laser with varying processing parameters,cutting speeds,gas pressures,and focal point positions.The laser-cut samples were divided into two groups,sanded and non-sanded samples.Polyvinyl acetate adhesive(PVAc)was used to bond the groups of laser-cut samples.After assembly with cold pressing,the tensile shear test was carried out.Numerical modelling was carried out to determine the partial elongation and shear strain of the glue line.Based on this,the shear modulus and linear elasticity of the glue line were estimated.Scan-ning electron microscopy was used to assess the adhesive penetration into the porosity structure of the laser-cut samples,and the depth of the heat-affected zone.The laser-cut surface was analysed by Fourier transform infrared spectroscopy.The wetting properties of the laser-cut surface were investigated by using a contact angle goni-ometer.The numerical model of the strain-stress curve confirmed the experimental model.The highest modulus of the linear elasticity of the glue in the numerical calculation belongs to the joint containing laser-cut samples at a gas pressure of 21(bar).The penetration depth of PVAc adhesive into the porosity structure of the laser-cut sam-ples was similar to that of sawn samples.The deepest heat-affected zone in the laser-cut samples was 150µm.A PVAc drop disappeared immediately on the laser-cut surface without sanding,but gradually on the sanded surface.In contrast,the drop on the sawn surface remained with an angle of 32°–48°.The degradation of hemi-cellulose and lignin was proven by the lower intensity of the C=O and C-O Bonds,compared to the sawn surface.
文摘帕金森病(parkinson's disease,PD)是一种常见的中老年神经系统退行性疾病,其中脑黑质致密部(substantia nigra pars compacta,SNpc)多巴胺(dopamine,DA)能神经元进行性丢失导致基底神经节(Basal ganglia,BG)皮质-纹状体谷氨酸(glutamate,Glu)能通路异常兴奋与PD进展有关。目前有相当多的研究集中在氧化Glu毒性,作为治疗PD的靶点。运动疗法作为一种安全、广谱的治疗手段,能够缓解PD相关行为功能障碍,其机制可能是通过降低氧化Glu毒性来实现的。本文就对目前运动通过降低氧化Glu毒作用改善PD相关行为功能障碍的研究现状进行综述,以期为PD运动防治神经生物学机制的研究以及靶向干预提供必要的理论依据和新的思路。
文摘In the present paper,we study partial collapsing degeneration of Hamiltonian-perturbed Floer trajectories for an adiabatic ε-family and its reversal adiabatic gluing,as the prototype of the partial collapsing degeneration of 2-dimensional(perturbed)J-holomorphic maps to 1-dimensional gradient segments.We consider the case when the Floer equations are S^(1)-invariant on parts of their domains whose adiabatic limit has positive length as ε→0,which we call thimble-flow-thimble configurations.The main gluing theorem we prove also applies to the case with Lagrangian boundaries such as in the problem of recovering holomorphic disks out of pearly configuration.In particular,our gluing theorem gives rise to a new direct proof of the chain isomorphism property between the Morse-Bott version of Lagrangian intersection Floer complex of L by Fukaya-Oh-Ohta-Ono and the pearly complex of L Lalonde and Biran-Cornea.It also provides another proof of the present authors’earlier proof of the isomorphism property of the PSS map without involving the target rescaling and the scale-dependent gluing.
