Humans and dogs are the two major hosts of Strongyloides stercoralis, an intestinal parasitic nematode. To better understand the phylogenetic relationships among S. stercoralis isolates infecting humans and dogs and to assess the zoonotic potential of this parasite, we analyzed mitochondrial Cox1, nuclear 18S rDNA, 28S rDNA, and a major sperm protein domain-containing protein genes. Overall, our analyses indicated the presence of two distinct lineages of S. stercoralis (referred to as type A and type B). While type A parasites were isolated both from humans and dogs in different countries, type B parasites were found exclusively in dogs, indicating that the type B has not adapted to infect humans. These epidemiological data, together with the close phylogenetic relationship of S. stercoralis with S. procyonis, a Strongyloides parasite of raccoons, possibly indicates that S. stercoralis originally evolved as a canid parasite, and later spread into humans. The inability to infect humans might be an ancestral character of this species and the type B might be surmised to be an origin population from which human-infecting strains are derived.

Despite their outstanding antitumour activity in mice, the limited supply from the natural sources has prevented drug discovery/development based on intact halichondrins. We achieved a total synthesis of C52-halichondrin-B amine (E7130) on a >10 g scale with >99.8% purity under GMP conditions. Interestingly, E7130 not only is a novel microtubule dynamics inhibitor but can also increase intratumoural CD31-positive endothelial cells and reduce α-SMA-positive cancer-associated fibroblasts at pharmacologically relevant compound concentrations. According to these unique effects, E7130 significantly augment the effect of antitumour treatments in mouse models and is currently in a clinical trial. Overall, our work demonstrates that a total synthesis can address the issue of limited material supply in drug discovery/development even for the cases of complex natural products.

Standard-Nutzungsbedingungen:Die Dokumente auf EconStor dürfen zu eigenen wissenschaftlichen Zwecken und zum Privatgebrauch gespeichert und kopiert werden.Sie dürfen die Dokumente nicht für öffentliche oder kommerzielle Zwecke vervielfältigen, öffentlich ausstellen, öffentlich zugänglich machen, vertreiben oder anderweitig nutzen.Sofern die Verfasser die Dokumente unter Open-Content-Lizenzen (insbesondere CC-Lizenzen) zur Verfügung gestellt haben sollten, gelten abweichend von diesen Nutzungsbedingungen die in der dort genannten Lizenz gewährten Nutzungsrechte. www.econstor.eu Using a unique new cross-national survey of Japanese and Korean workers, we report the first systematic evidence on the effects on employee voice of High Performance Work Practices (HPWPs) from the two economies which are noted for the wide use of HPWPs. We find for both nations that: (i) workers in firms with HPWPs aimed at creating opportunities for employees to get involved (such as shopfloor committees and small group activities) are indeed more likely to have stronger senses of influence and voice on shopfloor decision making than other workers; (ii) workers whose pay is tied to firm performance are more likely to have a stake in firm performance and hence demand such influence and voice; and (iii) consequently workers in firms with HPWPs are more likely to make frequent suggestions for productivity increase and quality improvement. As such, this paper contributes to a small yet growing new empirical literature which tries to understand the actual process and mechanism through which HPWPs lead to better enterprise performance. Terms of use: Documents in D I S C U S S I O N P A P E R S E R I E SJEL Classification: J53, M54, M52

The streamlined assembly of the ansamacrolide framework of the kedarcidin chromophore via an efficient atropselective Sonogashira coupling step is described. To this end, two newly improved practical syntheses of the cyclopentene and diyne fragments have been developed, which feature 0.2 mol % catalytic loadings for an RCM step and i-PrMgCl/CH 2 I 2 as a new entry to gem-disubstituted epoxides from ketones, both being applicable to 49-g scales.The kedarcidin chromophore (1) is a highly unstable, complex natural product that possesses, among other structural challenges, a conformationally defined ansamacrocyclic bridge. 1 Although 1 has yet to be completed in its entirety, Myers et al. have constructed the whole aglycon unit of 1 through an impressive transannulation protocol. 2 In our work, we have developed direct R-selective protocols for both of the 2-deoxysugars 3 and have centered on the established success of the CeCl 3 /LiN(TMS) 2 -mediated cyclization protocol to form the nine-membered, bicyclic core. 4 As part of our intensive efforts to provide gram quantities of late-stage targets, we describe in this letter the practical preparation of both the cyclopentene and diyne fragments and the advantage of having an appropriate C4-stereochemistry 5 for the efficient assembly of the ansamacrolide framework 2. 6 In this and our earlier work, the kedarcidin chromophore 1 was retrosynthetically stripped of its sugar components and reduced to the ansamacrolide subtargets 2 and 3 (Scheme 1). Among several macrolide-forming methods tested, the intramolecular Sonogashira coupling was the only method found powerful enough to successfully prepare ansamacrolides such as 3. In the earlier cases tested, the C4-epimer of 3 was targeted and yields fell into the 40-45% range. Subsequent efforts at improving the coupling yield were † Current address: Department of Chemistry, 3 Science Drive 3, National University of Singapore, Republic of Singapore 117543. Email: chmlmj@ nus.edu.sg.(1) Isolation of kedarcidin and chromophore structure (1) (5) This structural change also arose from unforeseen stereochemical difficulties that occurred during advanced stages directed toward the synthesis of the aglycon of 1. This work will be detailed elsewhere.(6) For our preliminary synthetic study of the C4-epimer of 3, see: Yoshimura, F.; Kawata, S.; Hirama, M. Tetrahedron Lett. 1999, 40, 8281.

The spontaneous aromatization of the enediyne chromophore of the potent antitumor agent C‐1027 generates a p‐benzyne biradical, which cleaves double‐stranded DNA. The title reaction was developed for the construction of nine‐membered‐ring enediynes and applied as the final step in the synthesis of the exceptionally unstable core structure of the C‐1027 chromophore (see scheme; Boc, MOM, MPM, and TES are protecting groups; Ms=methanesulfonyl).