PLCß介导的钙调腺苷酸环化酶在突触可塑性相关基因转录中的作用和FE65对海马依赖学习及LTP的调节

Gene regulation is required for activity-dependent changes in synaptic plasticity and remodeling. The metabotropic glutamate receptors (mGluRs) contribute to different brain functions, including learning/memory, mental disorders, drug addiction, and persistent pain in the CNS. We found that Gp I mGluRs activate PLCß through Gq and then lead to activation of several calcium-dependent signaling pathways, including ERK, which play an important role in gene transcription. These findings support a calcium-dependent role for Gq in release of Calcium and activation of calcium-stimulated adenylyl cyclases I in activity-dependent transcription in response to application of group I metabotropic glutamate receptors agonist and may provide insights into group I mGluRs-dependent synaptic plasticity through MAP kinases signaling. Moreover, the present study investigated the transcription-dependent changes of Arc in response to the activation of group I mGluRs and suggested the central role of ERK1/2 in group I mGluR-mediated Arc transcription. Further, we selected APP-interaction protein FE65 to investigate the mechanism of transcription-related process in synaptic plasticity. FE65 is expressed predominantly in the brain, and interacts with the C-terminal domain of β-amyloid precursor protein (APP). We examined hippocampus-dependent memory and in vivo long-term potentiation (LTP) at the CA1 synapses with the isoform-specific FE65 knock-out (p97FE65-/-) mice. p97FE65 knock-out mice showed impaired short-term memory for both TDPA and CFC when tested 10min after training, which is transcription-independent. Consistently, at the Schaffer collateral-CA1 synapses, p97FE65 knock-out mice showed defective early phase LTP. These results demonstrate novel roles of FE65 in synaptic plasticity, acquisition, and retention for certain forms of memory formation.

企业经营风险决策的组织行为学研究

This thesis has investigated the risk preferences of the Chinese company managers in kinds of simulated decision situations and their perceptions of risk concerning types of business decisions. Four studies are conducted: Study I is utility analysis. 214 company managers and 46 middle - school headmasters have responded to Utility Measurement Survey. The results indicate: (1) The risk preferences of the managers vary in the different decision situations. In most of the situations, most of the managers are risk aversion; In few situations, they are risk-seeking. (2) In some of the decision situations, there are significant differences on risk preference between business managers and school headmasters, male managers and female managers, senior managers and junior managers, managers with high qualifications and managers with low qualifications, non-state-owned firms' managers and state-owned firms' managers, medium-small sized firms' managers and large-sized firms' managers. In the other situations there aren't significant differences between them. (3) In all of the decision situations, so significant differences on risk preference are found among managers with different marriage, experience, age and education. Study II is risky decision simulation. The Risky Decision Situations Simulation Survey is administered to 82 company managers. The result indicates that firm culture, business condition, survival limit and risk preference of the superior influence the managers' risk decision-making behavior. Study III is perceptions of business decision risks. 68 company managers have filled in Decision Cases Risk Perception Inventory. The results indicate: (1) Inaccurate market analysis and prediction, instable politics and the changes of economic policy are the more risky elements to strategy decision. (2) Erroneous market analysis and prediction, appearance of new technology and the changes of market demands are the more risky elements to investment decision. (3) Poor quality control, backward technology and too large stocks are the more risky elements to production decision. (4) Shortage of development fund, wrong choice in development project and limitation of the development ability are the more risky elements to new production development decision. (5) No payment of the foreign partner's capital, the changes of national relevant policy, difficulty in marketing, too high selling prices of foreign partner's equipments are the more risky elements to joint-venture decision. (6) Unfamilarity with oneself and misjudgement in qualification of oneself are the more risky elements to personnel decision. (7) Bad market of the product, defects in product quality and the changes of consumers demands are the more risky elements to marketing decision. (8) Wrong strategy and ambiguous goals are the more risky elements to public relation decision. (9) Violation of the law, ambiguous goals and poor creation are the more risky elements to advertisement decision. (10) Deterioration of diplomatic relations, unsuitable products for foreign consumers and unfamilarity with foreign market are the more risky elements to international business decision. Study IV is structured interview. 5 company managers have answered all questions of the Interview Questionnaire. The results indicate: (1) The managers think that risks are the possible unfavourable consequences of decisions; (2) The self-ratings of the managers coordinate with the results of utility measurement; (3) The managers admit that risks always accompany bussiness decision; (4) Individual difference is found among managers on risk perception. This thesis has also pointed out the important implications of the research and discussed several further questions.

相同知识背景下技能之间迁移机制的研究

Since the middle of 1980's, the mechanisms of transfer of training between cognitive subskills rest on the same body of declarative knowledge has been highly concerned. The dominant theory is theory of common element (Singley & Anderson, 1989) which predict that there will be little or no transfer between subskills within the same domain when knowledge is used in different ways, even though the subskills might rest on a common body of declarative knowledge. This idea is termed as "principle of use specificity of knowledge" (Anderson, 1987). Although this principle has gained some empirical evidence from different domains such as elementary geometry (Neves & Anderson, 1981) and computer programming (McKendree & Anderson, 1987), it is challenged by some research (Pennington et al., 1991; 1995) in which substantially larger amounts of transfer of training was found between substills that rest on a shared declarative knowledge but share little procedures (production rules). Pennington et al. (1995) provided evidence that this larger amounts of transfer are due to the elaboration of declarative knowledge. Our research provide a test of these two different explanation, by considering transfer between two subskills within the domain of elementary geometry and elementary algebra respectively, and the inference of learning method ("learning from examples" and "learning from declarative-text") and subject ability (high, middle, low) on the amounts of transfer. Within the domain of elementary geometry, the two subskills of generating proofs" (GP) and "explaining proofs" (EP) which are rest on the declarative knowledge of "theorems on the characters of parallelogram" share little procedures. Within the domain of elementary algebra, the two subskills of "calculation" (C) and "simplification" (S) which are rest on the declarative knowledge of "multiplication of radical" share some more procedures. The results demonstrate that: 1. Within the domain of elementary geometry, although little transfer was found between the two subskills of GP and EP within the total subjects, different results occurred when considering the factor of subject's ability. Within the high level subjects, significant positive transfer was found from EP to GP, while little transfer was found on the opposite direction (i. e. from GP to EP). Within the low level subjects, significant positive transfer was found from EP to GP, while significant negative transfer was found on the opposite direction. For the middle level subject, little transfer was found between the two subskills. 2. Within the domain of elementary algebra, significant positive transfer was found from S to C, while significant negative transfer was found on the opposite direction (i. e. from C to S), when considering the total subjects. The same pattern of transfer occurred within the middle level subjects and low level subject. Within the high level subjects, no transfer was found between the two subskills. 3. Within theses two domains, different learning methods yield little influence on transfer of training between subskills. Apparently, these results can not be attributed to either common procedures or elaboration of declarative knowledge. A kind of synthetic inspection is essential to construct a reasonable explanation of these results which should take into account the following three elements: (1) relations between the procedures of subskills; (2) elaboration of declarative knowledge; (3) elaboration of procedural knowledge. 排Excluding the factor of subject, transfer of training between subskills can be predicted and explained by analyzing the relations between the procedures of two subskills. However, when considering some certain subjects, the explanation of transfer of training between subskills must include subjects' elaboration of declarative knowledge and procedural knowledge, especially the influence of the elaboration on performing the other subskill. The fact that different learning methods yield little influence on transfer of training between subskills can be explained by the fact that these two methods did not effect the level of declarative knowledge. Protocol analysis provided evidence to support these hypothesis. From this research, we conclude that in order to expound the mechanisms of transfer of training between cognitive subskills rest on the same body of declarative knowledge, three elements must be considered synthetically which include: (1) relations between the procedures of subskills; (2) elaboration of declarative knowledge; (3) elaboration of procedural knowledge.

An in silico approach for screening flavonoids as P-glycoprotein inhibitors based on a Bayesian-regularized neural network

P-glycoprotein (P-gp), an ATP-binding cassette (ABC) transporter, functions as a biological barrier by extruding cytotoxic agents out of cells, resulting in an obstacle in chemotherapeutic treatment of cancer. In order to aid in the development of potential P-gp inhibitors, we constructed a quantitative structure-activity relationship (QSAR) model of flavonoids as P-gp inhibitors based on Bayesian-regularized neural network (BRNN). A dataset of 57 flavonoids collected from a literature binding to the C-terminal nucleotide-binding domain of mouse P-gp was compiled. The predictive ability of the model was assessed using a test set that was independent of the training set, which showed a standard error of prediction of 0.146 +/- 0.006 (data scaled from 0 to 1). Meanwhile, two other mathematical tools, back-propagation neural network (BPNN) and partial least squares (PLS) were also attempted to build QSAR models. The BRNN provided slightly better results for the test set compared to BPNN, but the difference was not significant according to F-statistic at p = 0.05. The PLS failed to build a reliable model in the present study. Our study indicates that the BRNN-based in silico model has good potential in facilitating the prediction of P-gp flavonoid inhibitors and might be applied in further drug design.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with a matrix of carbon nanotubes for the analysis of low-mass compounds in environmental samples

The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for environmental analysis has been mainly focused on qualitative analysis of high-mass molecules, such as toxins, humic acid, and microorganisms. Herein,we describe a novel MALDI-TOF-MS method with a matrix of oxidized carbon nanotubes for analysis of low-mass compounds in environmental samples. A number of chemicals in the environment were qualitatively analyzed by the present method, and it was found that most of them, especially the highly polar chemicals, were measurable with high sensitivity. With the intrinsic ability to measure high-mass chemicals, this method can compensate for the current shortage of methods for environmental analysis for the measurement of highly polar or high-mass chemicals. For sample analysis, arsenic speciation in Chinese traditional medicines was qualified and diphenylolpropane in water samples was quantified. With the relatively high tolerance of the method to interfering molecules, a simple pretreatment or even no pretreatment could be employed before MS detection. Furthermore, this method can be employed in a high-throughput format.

Purification and characterization of recombinant truncated human interleukin-11 expressed as fusion protein in Escherichia coli

Mature human interleukin-11 (HuIL-11) is a cytokine consisting of 178 amino acid residues that results from scission of the N-terminal signal peptide, consisting of 21 amino acid residaues, from the corresponding nascent polypeptide. A DNA fragment encoding a truncated HuIL-11 (trHuIL-11), with an additional 5 amino acid residues removed from the N-terminus, was cloned into vector pGEX-2T between the BamHI site and the EcoRI site. Upon transformation with Escherichia coli BL21, the construct over-produced a glutathione S-transferase (GST)-fused protein in a soluble form after IPTG induction. The fusion protein was initially fractionated with butyl-Sepharose 4 fast flow column and by affinity chromatography using a GSH-Sepharose 4B column. On-site enzymatic release with thrombin gave the target protein at 96% purity as judged by SDS-PAGE and HPLC. Expression of the interleukin as a GST-fused protein thus greatly improved downstream processing. Subsequent biological activity assay suggested that trHuIL-11 had similar activity profile to the naturally produced sample and may be a promising candidate for further development as biopharmaceutical.