A pre-metazoan origin of the CRK gene family and co-opted signaling network.

CRK and CRKL adapter proteins play essential roles in development and cancer through their SRC homology 2 and 3 (SH2 and SH3) domains. To gain insight into the origin of their shared functions, we have investigated their evolutionary history. We propose a term, crk/crkl ancestral (crka), for orthologs in invertebrates before the divergence of CRK and CRKL in the vertebrate ancestor. We have isolated two orthologs expressed in the choanoflagellate Monosiga brevicollis, a unicellular relative to the metazoans. Consistent with its highly-conserved three-dimensional structure, the SH2 domain of M. brevicollis crka1 can bind to the mammalian CRK/CRKL SH2 binding consensus phospho-YxxP, and to the SRC substrate/focal adhesion protein BCAR1 (p130(CAS)) in the presence of activated SRC. These results demonstrate an ancient origin of the CRK/CRKL SH2-target recognition specificity. Although BCAR1 orthologs exist only in metazoans as identified by an N-terminal SH3 domain, YxxP motifs, and a C-terminal FAT-like domain, some pre-metazoan transmembrane proteins include several YxxP repeats in their cytosolic region, suggesting that they are remotely related to the BCAR1 substrate domain. Since the tyrosine kinase SRC also has a pre-metazoan origin, co-option of BCAR1-related sequences may have rewired the crka-dependent network to mediate adhesion signals in the metazoan ancestor

Survival related to lymph node involvement in lung cancer after sleeve lobectomy compared with pneumonectomy

AbstractObjective: The purpose of this study was to compare the outcomes after sleeve lobectomy and pneumonectomy for patients with non–small cell lung cancer distributed according to their nodal involvement status. Methods: Of 1172 patients in whom primary non–small cell lung carcinoma, including mediastinal lymph nodes, was completely excised, 151 patients underwent sleeve lobectomy and 60 underwent pneumonectomy. For bias reduction in comparison with a nonrandomized control group, we paired 60 patients undergoing sleeve lobectomy with 60 patients undergoing pneumonectomy by using the nearest available matching method. Results: The 30-day postoperative mortality was 2% (1/60) in the pneumonectomy group and 0% in the sleeve lobectomy group. Postoperative complications occurred in 13% of patients in the sleeve lobectomy group and in 22% of those in the pneumonectomy group. Local recurrences occurred in 8% of patients in the sleeve lobectomy group and in 10% of those in the pneumonectomy group. The overall 5- and 10-year survivals for the sleeve lobectomy group were 48% and 36%, respectively, whereas those for the pneumonectomy group were 28% and 19%, respectively (P = .005). Multivariable analysis showed that the operative procedure, T factor, and N factor were significant independent prognostic factors and revealed that survival after sleeve lobectomy was significantly longer than that after pneumonectomy (P = .03). Conclusions: These data suggest that sleeve lobectomy should be performed instead of pneumonectomy in patients with non–small cell lung cancer regardless of their nodal status whenever complete resection can be achieved because this is a lung-saving procedure with lower postoperative risks and is as curative as pneumonectomy. (J Thorac Cardiovasc Surg 2000;119:814-9

Population-neuroscience study of the Tokyo TEEN Cohort (pn-TTC):Cohort longitudinal study to explore the neurobiological substrates of adolescent psychological and behavioral development.

Adolescence is a crucial stage of psychological development and is critically vulnerable to the onset of psychopathology. However, our understanding of how maturation of endocrine, epigenetics, and brain circuit may underlie the psychological development in adolescence has not been integrated. Here, we introduce our research project, the "population-neuroscience study of the Tokyo TEEN Cohort (pn-TTC)," a longitudinal study to explore the neurobiological substrates of development during adolescence