基因定点诱变删除及天然α型心钠素的分泌型表达

用基因定点诱变技术,删除了pO_1α ANF表达质粒中的33对碱基,使人α型心钠素结构基因直接与大肠杆菌分泌型表达质粒pIN-Ⅲ-OmPA中的信号肽酶切位点编码区相连,构成天然人α型心钠素的表达质粒pANF,在IPTG诱导下表达28肽的天然人α型心钠素。纯化后的表达产物具有天然心钠素的放免活性和很强的舒张血管的生物活性。     

Active site conformation in myoglobin as determined by X-ray absorption spectroscopy

X-ray absorption fine structure experiments were performed to study structural and dynamic aspects of the active site of various forms of myoglobin. The structures determined for deoxyMb, MbCO, and MbO2 are consistent with the structure established by X-ray absorption fine structure experiment and X-ray crystallography. The first shell of ferrous MbNO determined contains 5 nitrogens located at 2.02 A and a short NO bond length of 1.76 A. This study focuses on the change of the XAFS Debye-Waller factor with temperature, which is a measure of thermal and static disorder. It was found that the changes of Debye-Waller factor with temperature for the Mb proteins, except deoxyMb, are consistent with a simple Einstein model, in which a single frequency was assumed for the bond stretching modes. In contrast, the temperature dependence of deoxyMb cannot be fitted to the Einstein model and a large disorder was found at low temperatures, which indicates the existence of conformational substates of the active site.     

Age‐related memory vulnerability to interfering stimuli is caused by gradual loss of MAPK‐dependent protection in Drosophila

Age‐related memory impairment (AMI) is a common phenomenon across species. Vulnerability to interfering stimuli has been proposed to be an important cause of AMI. However, the molecular mechanisms underlying this vulnerability‐related AMI remain unknown. Here we show that learning‐activated MAPK signals are gradually lost with age, leading to vulnerability‐related AMI in Drosophila. Young flies (2‐ or 3‐day‐old) exhibited a significant increase in phosphorylated MAPK levels within 15 min after learning, whereas aged flies (25‐day‐old) did not. Compared to 3‐day‐old flies, significant 1 h memory impairments were observed in 15‐, 20‐, and 30‐day‐old flies, but not in 10‐day‐old flies. However, with post‐learning interfering stimuli such as cooling or electric stimuli, 10‐day‐old flies had worse memory performance at 1 h than 3‐day‐old flies, showing a premature AMI phenomenon. Increasing learning‐activated MAPK signals through acute transgene expression in mushroom body (MB) neurons restored physiological trace of 1 h memory in a pair of MB output neurons in aged flies. Decreasing such signals in young flies mimicked the impairment of 1 h memory trace in aged flies. Restoring learning‐activated MAPK signals in MB neurons in aged flies significantly suppressed AMI even with interfering stimuli. Thus, our data suggest that age‐related loss of learning‐activated neuronal MAPK signals causes memory vulnerability to interfering stimuli, thereby leading to AMI.     

Rhabdomyolysis happened after the start of dabigatran etexilate treatment: A case report

There are few reports of rhabdomyolysis caused by anticoagulants, and it is extremely rare for it to be caused by dabigatran etexilate. An 86-year-old female experienced sudden muscle weakness and pain, a significant increase in Creatine kinase, and renal impairment after oral administration of dabigatran etexilate for 3 weeks. The enhanced thigh MRI showed abnormal signal in multiple thigh muscle groups, indicating that the lesions should be considered inflammatory diseases. In conclusion, the possibility of rhabdomyolysis should be ruled out when muscle weakness and myalgia occur at the beginning of dabigatran etexilate treatment.     

谭清苏铁性别相关的RAPD标记研究

以谭清苏铁(Cycas tanqingii D.Y.Wang)雌雄植株半年生羽叶为材料,用优化的CTAB法分别提取其全基因组DNA,进行RAPD单因子梯度实验和正交实验以优化扩增条件。应用160个RAPD随机引物检测基因组DNA,雌雄植株均扩增出1450多条带,其中引物S0465扩增出与谭清苏铁雌株高度相关的RAPD标记,其大小约为500bp,该标记与雄株没有关联。     

Mechanisms of the acute ischemia-induced arrhythmogenesis--a simulation study

The underlying ionic mechanisms of ischemic-induced arrhythmia were studied by the computer simulation method. To approximate the real situation, ischemic cells were simulated by considering the three major component conditions of acute ischemia (elevated extracellular K(+) concentration, acidosis and anoxia) at the level of ionic currents and ionic concentrations, and a round ischemic zone was introduced into a homogeneous healthy sheet to avoid sharp angle of the ischemic tissue. The constructed models were solved using the operator splitting and adaptive time step methods, and the perturbation finite difference (PFD) scheme was first used to integrate the partial differential equations (PDEs) in the model. The numerical experiments showed that the action potential durations (APDs) of ischemic cells did not exhibited rate adaptation characteristic, resulting in flattening of the APD restitution curve. With reduction of sodium channel availability and long recovery of excitability, refractory period of the ischemic tissue was significantly prolonged, and could no longer be considered as same as APD. Slope of the conduction velocity (CV) restitution curve increased both in normal and ischemic region when pacing cycle length (PCL) was short, and refractory period dispersion increased with shortening of PCL as well. Therefore, dynamic changes of CV and dispersion of refractory period rather than APD were suggested to be the fundamental mechanisms of arrhythmia in regional ischemic myocardium.