even skipped is required to produce a trans-acting signal for larval neuroblast proliferation that can be mimicked by ecdysone

Development of a multicellular organism requires precise coordination of cell division and cell type determination. The selector homeoprotein Even skipped (Eve) plays a very specific role in determining cell identity in the Drosophila embryo, both during segmentation and in neuronal development. However, studies of gene expression in eve mutant embryos suggest that eve regulates the embryonic expression of the vast majority of genes. We present here genetic interaction and phenotypic analysis showing that eve functions in the trol pathway to regulate the onset of neuroblast division in the larval CNS. Surprisingly, Eve is not detected in the regulated neuroblasts, and culture experiments reveal that Eve is required in the body, not the CNS. Furthermore, the effect of an eve mutation can be rescued both in vivo and in culture by the hormone ecdysone. These results suggest that eve is required to produce a trans-acting factor that stimulates cell division in the larval brain.     

A novel class of inhibitors for steroid 5alpha-reductase: synthesis and evaluation of umbelliferone derivatives

A series of umbelliferone derivatives was prepared and their 5alpha-reductase type 1 inhibitory activities were evaluated in cell culture systems. Our studies have identified a new series of potent 5alpha-reductase type 1 inhibitors and provided the basis for further development for the treatment of human endocrine disorders associated with overproduction of DHT by 5alpha-reductase type 1. The preliminary structure-activity relationship was described to elucidate the essential structural requirements.     

Pimarane cyclooxygenase 2 (COX-2) inhibitor and its structure-activity relationship

The structure-activity relationship and molecular modelings of a novel pimarane COX-2 inhibitor are reported. Particularly, a series of linker extended analogues designed on the basis of these studies exhibited significantly enhanced COX-2 inhibitory activities and selectivities.     

A hot pepper cDNA encoding a pathogenesis-related protein 4 is induced during the resistance response to tobacco mosaic virus

Hot pepper (Capsicum annuum) plants exhibit a hypersensitive response (HR) against infection by many tobamoviruses. A clone (CaPR-4) encoding a putative pathogenesis-related protein 4 was isolated by differential screening of a cDNA library prepared from resistant pepper plant leaves inoculated with tobacco mosaic virus (TMV) pathotype P0. The predicted amino acid sequence of CaPR-4 is very similar to those of other plant PR-4s. Southern blot analysis showed that small gene families of PR-4-related sequences were present in the pepper genome. Hot pepper cultivar Bugang, resistant to TMV-P0 and susceptible to TMV-P1.2, induced CaPR-4 expression by pathotype P0 inoculation in inoculated and systemic leaves, but not by pathotype P1.2. Effects of exogenously applied abiotic elicitors upon the CaPR-4 expression were also examined. The expression of the CaPR-4 gene was stimulated by methyl jasmonate (MeJA), ethephon and wounding treatment. However, application of salicylic acid (SA) did not trigger the expression. Evidence is emerging that jasmonic acid and ethylene play key roles in the SA-independent pathways of plant-pathogen interaction. Taken together, these results suggest that the CaPR-4 gene is one of the defense-related genes conferring resistance on pepper plants by the SA-independent pathway and the cross-talk between signaling compounds, jasmonic acid and ethylene could have a great regulatory potential in a plant's defense against TMV.     

Production of nuclear transfer-derived swine that express the enhanced green fluorescent protein.

The ability to add or delete specific genes in swine will likely provide considerable benefits not just to agriculture but also to medicine, where pigs have potential as models for human disease and as organ donors. Here we have transferred nuclei from a genetically modified fibroblast cell line to porcine oocytes, matured in vitro under defined culture conditions, to create piglets expressing enhanced green fluorescent protein. The nuclear transfer-derived piglets were of normal size, although some mild symptoms of "large offspring syndrome" were evident. These experiments represent a next step towards creating swine with more useful genetic modifications.     

Selection of the recipient vessel in the free flap around the knee: the superior medial genicular vessels and the descending genicular vessels

In reconstructions around the knee, the use of a free flap is indicated in a limited number of cases, but it plays a critical role in cases of extensive defects or unavailability of local flaps. The selection of the recipient vessel is an essential and challenging step for a successful free tissue transfer. Popliteal vessels and other small vessels around the knee have been reported to be used as recipient vessels, but the choice of recipient vessels around the knee has not been established. In this study, after a thorough investigation of the vascular anatomy at the knee region, the superior medial genicular vessels and the descending genicular vessels were considered to be the proper recipient vessels, and a clinical application was tried. From July of 1997 to July of 1999, a total of seven cases of soft-tissue defects around the knee-four cases in the posterior region and three cases in the anterior region-were reconstructed with free flaps, using the superior medial genicular vessels and the descending genicular vessels, respectively. All flaps survived completely, with no flap loss. The advantages of these vessels are their proximity to the knee and their reliability, versatility, simplicity, and size match. The outstanding characteristic of this combination of vessels is their versatility, because the combination can cover all defects around the knee. The clinical application and the versatility of the combination of the superior medial genicular vessels and the descending genicular vessels as the recipient vessels was confirmed for the reconstruction of posterior and anterior knee defects.     

Total ear reconstruction in the devascularized temporoparietal region: I. Use of the contralateral temporoparietal fascial free flap

Total ear reconstruction by the use of contralateral temporoparietal fascial free flap and autogenous costal cartilage was performed in 16 patients presenting with a devascularized temporoparietal region resulting from trauma or prior surgery. The microsurgical success rate was 87.5 percent (14 of 16 transplants). On evaluation of the final aesthetic result in 11 patients followed up for more than 3 years, nine patients were graded good-to-excellent and two patients exhibited fair-to-poor results. Despite the relatively long operating hours and the comparatively low microsurgical success rate, ear reconstruction by autogenous tissue transplantation has proved to be an encouraging and worthwhile experience. This article presents the clinical cases and discusses the technical details.     

Light and brassinosteroid signals are integrated via a dark-induced small G protein in etiolated seedling growth

Plant growth and development are regulated through coordinated interactions between light and phytohormones. Here, we demonstrate that a dark-induced small G protein, pea Pra2, regulates a variant cytochrome P450 that catalyzes C-2 hydroxylation in brassinosteroid biosynthesis. The cytochrome P450 is dark-induced and predominantly expressed in the rapidly elongating zone of etiolated pea epicotyls, where Pra2 is also most abundant. Transgenic plants with reduced Pra2 exhibit a dark-specific dwarfism, which is completely rescued by exogenous brassinolide. Overexpression of the cytochrome P450 results in enhanced hypocotyl growth even in the light, which phenocopies the etiolated hypocotyls. We therefore propose that Pra2 and its orthologs are molecular mediators for the cross-talk between light and brassinosteroids in the etiolation process in plants.     

Structural basis of caspase inhibition by XIAP: differential roles of the linker versus the BIR domain

The inhibitor of apoptosis proteins (IAPs) represent the only endogenous caspase inhibitors and are characterized by the presence of baculoviral IAP repeats (BIRs). Here, we report the crystal structure of the complex between human caspase-7 and XIAP (BIR2 and the proceeding linker). The structure surprisingly reveals that the linker is the only contacting element for the caspase, while the BIR2 domain is invisible in the crystal. The linker interacts with and blocks the substrate groove of the caspase in a backward fashion, distinct from substrate recognition. Structural analyses suggest that the linker is the energetic and specificity determinant of the interaction. Further biochemical characterizations clearly establish that the linker harbors the major energetic determinant, while the BIR2 domain serves as a regulatory element for caspase binding and Smac neutralization.