N-WASP-Arp2/3 signaling controls multiple steps of dendrite maturation in Purkinje cells in vivo.

During neural development, the actin filament network must be precisely regulated to form elaborate neurite structures. N-WASP tightly controls actin polymerization dynamics by activating an actin nucleator Arp2/3. However, the importance of N-WASP-Arp2/3 signaling in the assembly of neurite architecture in vivo has not been clarified. Here, we demonstrate that N-WASP-Arp2/3 signaling plays a crucial role in the maturation of cerebellar Purkinje cell (PC) dendrites in vivo in mice. N-WASP was expressed and activated in developing PCs. Inhibition of Arp2/3 and N-WASP from the beginning of dendrite formation severely disrupted the establishment of a single stem dendrite, which is a characteristic basic structure of PC dendrites. Inhibition of Arp2/3 after stem dendrite formation resulted in hypoplasia of the PC dendritic tree. Cdc42, an upstream activator of N-WASP, is required for N-WASP-Arp2/3 signaling-mediated PC dendrite maturation. In addition, overactivation of N-WASP is also detrimental to dendrite formation in PCs. These findings reveal that proper activation of N-WASP-Arp2/3 signaling is crucial for multiple steps of PC dendrite maturation in vivo.

Efficient Synthesis of α-Trifluoromethyl Carboxylic Acids and Esters through Fluorocarboxylation of gem-Difluoroalkenes.

A facile synthetic procedure for the preparation of α-trifluoromethyl carboxylic acids and esters was achieved through multicomponent coupling reactions between gem-difluoroalkenes, cesium fluoride, and carbon dioxide. The products were generated in moderate to excellent yields, and the synthetic utility of this method was demonstrated through the preparation of trifluoromethylated versions of popular nonsteroidal anti-inflammatory drugs (NSAIDs).

[Outpatient chemotherapy and clinical pathway for non-small cell lung cancer].

We investigated the usefulness of outpatient chemotherapy in 54 cases of non-small cell lung cancer in which outpatient chemotherapy was performed between August 1999 and October 2001. This chemotherapy accounted for 67% of all chemotherapy. Assessment of therapeutic effect revealed a PR in 14 of the 54 cases, and the efficacy rate was 26%. Therapeutic effect according to chemotherapy regimen revealed the highest efficacy rate, 50%, for paclitaxel + CBDCA. The median survival time was 14.7 months, and the 1-year survival rate was 61.1%. On the basis of the above results, a 16-day inpatient clinical pathway using weekly paclitaxel + CBDCA was devised for non-small cell lung cancer. The aim was to shorten the number of inpatient days, standardize treatment, and introduce outpatient chemotherapy. The clinical pathway was introduced in 8 patients with recurrent non-small cell lung cancer between August and October 2002. Variance was found only in one patient whose hospital discharge had to be postponed by two days because of a Grade 3 side effect. Introduction of a clinical pathway with weekly paclitaxel + CBDCA successfully reduced the inpatient days to an average of 16.3 days.