The murine Ca2+-stimulated adenylyl cyclase (type I) (EC 4.6.1.1), which is expressed predominantly in brain, was inactivated by targeted mutagenesis. Ca2+-stimulated adenylyl cyclase activity was reduced 40-60% in the hippocampus, neocortex, and cerebellum. Long-term potentiation in the CAI region of the hippocampus from mutants was perturbed relative to controls. Both the initial slope and maximum extent of changes in synaptic response were reduced. Although mutant mice learned to find a hidden platform in the Morris water task normally, they did not display a preference for the region where the platform had been when it was removed. These results indicate that disruption of the gene for the type I adenylyl cyclase produces changes in behavior and that the cAMP signal transduction pathway may play an important role in synaptic plasticity.There is considerable interest in the molecular mechanisms underlying neuroplasticity. Gene disruption studies have demonstrated that calmodulin (CaM) kinase II-a, fyn-tyrosine kinase, and protein kinase C--y are important for spatial learning and long-term potentiation (LTP) in the hippocampus (1-5). The cAMP-dependent protein kinase (PKA) has also been implicated in the regulation of synaptic plasticity and may be required for some forms of LTP (6-9). However, the role of adenylyl cyclases (ACs; EC 4.6.1.1) in learning and memory in vertebrates is undefined. The importance of the type I adenylyl cyclase (I-AC) for learning and memory is of particular interest because it is neurospecific and expressed in areas of brain that show LTP (10, 11). Furthermore, the Drosophila mutant rutabaga has a learning defect and is deficient in a Ca2+/CaM-sensitive AC that is similar to . In this study, the role of I-AC in learning and memory was evaluated after the gene was inactivated by targeted mutagenesis. MATERIALS AND METHODSDisruption of the I-AC Gene in Mice. A mouse I-AC genomic clone, ZX3 (14.5 kb), encoding the N-terminal 210 amino acids of I-AC was isolated from a genomic library (OLA 129) provided by Anton Berns (Netherlands Cancer Institute, Amsterdam). The gene-targeting vector, 1126, was constructed by replacing a 0.5-kb Nar I-Pst I fragment of ZX3, which includes the coding region for the first 140 amino acids of I-AC, with neor cassette (15 (18). Free Ca2+ was determined using fura-2 fluorescence (18). The data are presented as mean ± SEM of triplicate assays. Primary cultures of cerebellar neurons were prepared from 6-day-old postnatal mice as described (19). Changes in intracellular cAMP levels were measured as described (20).Morris Water Task A circular pool (1.2 m in diameter) was filled with opaque water. Naive 7-week-old mice were subjected to an initial training session in with they swam in the pool for 60 sec, after which time they were placed on the platform for 45 sec. Mice were given two training sessions (three trials per session, with a 1-h interim between trials) per day separated by 3 h. During each trial, the mice were allowed to search for a visible ...

Investigation on the turbulence model for resistance calculation for autonomous underwater vehicles (AUV) with the typical Myring shape is presented in this paper using computational fluid dynamics (CFD) method. Resistance calculations of the 3D viscous flow over an AUV model are made by solving RANS equations with different viscous models. Comparison with experiments indicates that the SST k-ω two-equation viscous model is the most appropriate model for the resistance prediction.

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Through the prediction based on reliability counting method, identified weak links of automatic control system, achieved the reliability modeling of marine power station and structured reliability block diagrams and the reliability mathematical models, the reliability and mean time between failures (MTBF) of marine power station are obtained under different work conditions. The marine power station reliability modeling acquired from different work conditions accords with the actual operating mode, and all these work can supply more scientific theoretical support for study on reliability of marine power station.