Impaired motor coordination correlates with persistent multiple climbing fiber innervation in PKC gamma mutant mice

It is generally believed that a smooth execution of a compound movement, or motor coordination, requires learning of component movements as well as experience-based refinement of the motor program as a whole. PKC gamma mutant mice display impaired motor coordination but intact eyeblink conditioning, a form of component movement learning. Cerebellar long-term depression, a putative cellular mechanism for component motor learning, is also unimpaired. Thus, PKC gamma mutant mice are defective in refinement of the motor program. In the accompanying paper, we demonstrate that innervation of multiple climbing fibers onto Purkinje cells persists in adulthood in these mutant mice. We propose that this defective elimination of surplus climbing fibers underlies motor discoordination.     

Design and synthesis of novel conformationally restricted HIV protease inhibitors

A set of HIV protease inhibitors represented by compound 2 has previously been described. Structural and conformational analysis of this compound suggested that conformational restriction of the P1/P2 portion of the molecule could lead to a novel set of potent protease inhibitors. Thus, probe compounds 3-7 were designed, synthesized, and found to be potent inhibitors of HIV protease.     

Effects of conceptions of ability on anxiety, self-efficacy, and learning in training

Octreotide is labeled with fluorine-18 as a potential radiopharmaceutical for quantitative in vivo mapping of somatostatin receptors. [18F]-fluoroacylation is achieved with n.c.a. 2-[18F]fluoropropionic acid 4-nitrophenylester which is reacted with epsilon-Boc-Lys5-octreotide. After deprotection the desired N alpha-[18F]fluoropropionylated octreotide ([18F]SDZ 223-228) is obtained. Final HPLC purification gives rise to radiochemical yields of 65 +/- 5% based on the fluoroacylation agent. Binding experiments using rat cortex membranes indicate an affinity for somatostatin receptors of pKi = 8.6 +/- 0.2. The biological activity of this SRIF analog is demonstrated by the inhibition of growth hormone release from cultured pituitary cells. The pIC50 in this test system is 8.75, indicating full biological activity. Biodistribution studies with NMRI mice show predominantly renal excretion, rapid blood clearance and only negligible bone activity, i.e. formation of free fluoride.     

Identification and cloning of the membrane-associated serine protease, hepsin, from mouse preimplantation embryos

Previous studies have suggested the existence of a membrane-associated serine protease expressed by mammalian preimplantation embryos. In this study, we have identified hepsin, a type II transmembrane serine protease, in early mouse blastocysts. Mouse hepsin was highly homologous to the previously identified human and rat cDNAs. Two isoforms, differing in their cytoplasmic domains, were detected. The tissue distribution of mouse hepsin was similar to that seen in humans, with prominent expression in liver and kidney. In mouse embryos, hepsin expression was observed in the two-cell stage, reached a maximal level at the early blastocyst stage, and decreased subsequent to blastocyst hatching. Expression of a soluble form of hepsin revealed its ability to autoactivate in a concentration-dependent manner. Catalytically inactive soluble hepsin was unable to autoactivate. These results suggest that hepsin may be the first serine protease expressed during mammalian development, making its ability to autoactivate critical to its function.