Piccolo is a novel component of the presynaptic cytoskeletal matrix (PCM) assembled at the active zone of neurotransmitter release. Analysis of its primary structure reveals that Piccolo is a multidomain zinc finger protein structurally related to Bassoon, another PCM protein. Both proteins were found to be shared components of glutamatergic and GABAergic CNS synapses but not of the cholinergic neuromuscular junction. The Piccolo zinc fingers were found to interact with the dual prenylated rab3A and VAMP2/Synaptobrevin II receptor PRA1. We show that PRA1 is a synaptic vesicle-associated protein that is colocalized with Piccolo in nerve terminals of hippocampal primary neurons. These data suggest that Piccolo plays a role in the trafficking of synaptic vesicles (SVs) at the active zone.

Repair of medial meniscus root tears, as compared with total meniscectomy and nonsurgical treatment, leads to less osteoarthritis and is a cost-saving intervention. While small confirmatory randomized clinical head-to-head trials are warranted, the presented evidence seems to point relatively clearly toward adopting meniscus repair as the preferred initial intervention for medial meniscus root tears.

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cDNA clones encoding microtubule-associated proteins 1 (MAP1/MAP1A) and 5 (MAP5/MAP1B) were isolated and have been used to study their structural relationship as well as their regulated expression in developing rat brain. cDNA clones specific for MAP1 hybridized to a single 10-kb rat brain mRNA, and analysis of genomic DNA by Southern blotting indicated the existence of a single MAP1 gene. A second set of cDNAs specific for MAP5 hybridized to a single 11-kb mRNA in rat brain and also detected a single gene. By analysis of hybrid mouse-hamster cell lines, the MAP1 gene was located to mouse chromosome 2, designated Mtap-1, and the MAP5 gene to chromosome 13, designated Mtap-5. MAP1 and MAP5 mRNAs were expressed with different temporal patterns during rat brain development that mirrored the appearance of their protein products, suggesting that expression of these proteins is under transcriptional control. These results taken together demonstrate that although MAP1 and MAP5 have some properties that are similar, they are structurally distinct proteins whose transcription is differently regulated from separate genes.

The model suggests that catheter-based renal denervation, over a wide range of assumptions, is a cost-effective strategy for resistant hypertension that might result in lower cardiovascular morbidity and mortality.