Evaluation of facial aesthetics by laypersons in patients undergoing intraoral quadrangular Le Fort II osteotomy compared with conventional Le Fort I osteotomy.

In this study we compared the aesthetic outcome of (1) Le Fort I (LFI) osteotomy and (2) intraoral quadrangular Le Fort II (IQLFII) osteotomy for surgical correction of skeletal class III dysgnathia involving midfacial deficiency. The aim was to investigate whether laypersons see differences in facial changes that occur due to variations of the osteotomy cuts. The patient collectives consisted of 23 patients in each group. Pre- and postoperative photographs were presented in a random sequence to 40 layperson raters. The rating procedure was conducted with a four-point Likert scale. Assessed characteristics were 'attractiveness' ('Attraktivität'), 'likeability' ('Sympathie'), 'intelligence' ('Intelligenz'), 'aggressiveness' ('Aggressivität') and 'dominance' ('Dominanz'). For preoperative photographs we found a significant difference for 'likeability' with lower ratings for the IQLFII group; all other criteria were rated similarly. For the IQLFII group we found a significantly larger shift from lower to higher ratings for 'attractiveness' and 'likeability' and a significantly larger shift from higher to lower ratings for 'aggressiveness' and 'dominance' than for the LF I group. Our study shows that lay raters detect significant differences between the two surgical groups. Thus, IQLFII osteotomy, when indicated, represents a favourable alternative to conventional LFI osteotomy, if patients desire the expectable change in recognition by their social circle.

Serial regulation of transcriptional regulators in the yeast cell cycle.

Genome-wide location analysis was used to determine how the yeast cell cycle gene expression program is regulated by each of the nine known cell cycle transcriptional activators. We found that cell cycle transcriptional activators that function during one stage of the cell cycle regulate transcriptional activators that function during the next stage. This serial regulation of transcriptional activators forms a connected regulatory network that is itself a cycle. Our results also reveal how the nine transcriptional regulators coordinately regulate global gene expression and diverse stage-specific functions to produce a continuous cycle of cellular events. This information forms the foundation for a complete map of the transcriptional regulatory network that controls the cell cycle.

Parthenogenetic flatworms have more symbionts than their coexisting, sexual conspecifics, but does this support the Red Queen?

The Red Queen hypothesis predicts that sexuality is favoured when virulent parasites adapt quickly to host genotypes. We studied a population of the flatworm Schmidtea polychroa in which obligate sexual and parthenogenetic individuals coexist. Infection rates by an amoeboid protozoan were consistently higher in parthenogens than in sexuals. Allozyme analysis showed that infection was genotype specific, with the second most common clone most infected. A laboratory measurement of fitness components failed to reveal high infection costs as required for the Red Queen. Although fertility was lower in more infected parthenogens, this effect can also be explained by the accumulation of mutations. We discuss these and other characteristics of our model system that may explain how a parasite with low virulence can show this pattern.

Genome-wide location and function of DNA binding proteins.

Understanding how DNA binding proteins control global gene expression and chromosomal maintenance requires knowledge of the chromosomal locations at which these proteins function in vivo. We developed a microarray method that reveals the genome-wide location of DNA-bound proteins and used this method to monitor binding of gene-specific transcription activators in yeast. A combination of location and expression profiles was used to identify genes whose expression is directly controlled by Gal4 and Ste12 as cells respond to changes in carbon source and mating pheromone, respectively. The results identify pathways that are coordinately regulated by each of the two activators and reveal previously unknown functions for Gal4 and Ste12. Genome-wide location analysis will facilitate investigation of gene regulatory networks, gene function, and genome maintenance.

Thorax closure in Drosophila: involvement of Fos and the JNK pathway.

Dorsal closure, a morphogenetic movement during Drosophila embryogenesis, is controlled by the Drosophila JNK pathway, D-Fos and the phosphatase Puckered (Puc). To identify principles of epithelial closure processes, we studied another cell sheet movement that we term thorax closure, the joining of the parts of the wing imaginal discs which give rise to the adult thorax during metamorphosis. In thorax closure a special row of margin cells express puc and accumulate prominent actin fibres during midline attachment. Genetic data indicate a requirement of D-Fos and the JNK pathway for thorax closure, and a negative regulatory role of Puc. Furthermore, puc expression co-localises with elevated levels of D-Fos, is reduced in a JNK or D-Fos loss-of-function background and is ectopically induced after JNK activation. This suggests that Puc acts downstream of the JNK pathway and D-Fos to mediate a negative feed-back loop. Therefore, the molecular circuitry required for thorax closure is very similar to the one directing dorsal closure in the embryo, even though the tissues are not related. This finding supports the hypothesis that the mechanism controlling dorsal closure has been co-opted for thorax closure in the evolution of insect metamorphosis and may represent a more widely used functional module for tissue closure in other species as well.

Jun in Drosophila development: redundant and nonredundant functions and regulation by two MAPK signal transduction pathways.

Drosophila Jun is shown to be involved in different signal transduction pathways and developmental decisions. Dorsal closure, a morphogenetic process occurring during Drosophila embryogenesis, is regulated by Hemipterous (Hep) and Basket (Bsk), homologs of JNKK and JNK, respectively. Embryos lacking Jun activity exhibit a dorsal closure phenotype, very similar to that of bsk and hep mutants, indicating that Jun is a target of Hep/Bsk signaling. In eye and wing development Jun participates in a separate signaling pathway that is comprised of Ras, Raf, and the ERK-type kinase Rolled. In contrast to the strict requirement for Jun in dorsal closure, its role in the eye is redundant but can be uncovered by mutations in other signaling components. The redundant function of Jun in eye development may contribute to the precision of photoreceptor differentiation and ommatidial assembly.

Defective dorsal closure and loss of epidermal decapentaplegic expression in Drosophila fos mutants.

Drosophila kayak mutant embryos exhibit defects in dorsal closure, a morphogenetic cell sheet movement during embryogenesis. Here we show that kayak encodes D-Fos, the Drosophila homologue of the mammalian proto-oncogene product, c-Fos. D-Fos is shown to act in a similar manner to Drosophila Jun: in the cells of the leading edge it is required for the expression of the TGFbeta-like Decapentaplegic (Dpp) protein, which is believed to control the cell shape changes that take place during dorsal closure. Defects observed in mutant embryos, and adults with reduced Fos expression, are reminiscent of phenotypes caused by 'loss of function' mutations in the Drosophila JNKK homologue, hemipterous. These results indicate that D-Fos is required downstream of the Drosophila JNK signal transduction pathway, consistent with a role in heterodimerization with D-Jun, to activate downstream targets such as dpp.

Endogenous retinoids in the zebrafish embryo and adult.

Retinoic acid and its isoforms are considered to be endogenous compounds which regulate embryonic development. In the work reported here we have determined which retinoids are present in zebrafish embryos and how their levels change throughout development and into adulthood. All-trans-RA is present and its level does not change significantly during embryogenesis. We failed to detect other retinoic acid isomers such as 9-cis-RA and 4-oxo-RA, but we did observe a rapid rise in the level of didehydroretinol after gastrulation. The most striking result is that the zebrafish embryo, like Xenopus and tunicates, contains a vast excess of t-retinal whereas the embryos of higher vertebrates have an excess of t-retinol. However, as the zebrafish grows, the levels of t-retinol rise so that by adulthood t-retinol and t-retinal concentrations are more equivalent, indicating a changing pattern of retinoid metabolism with growth. To examine the significance of the use of t-retinal as a precursor of t-RA we treated embryos with disulphiram, an inhibitor of retinaldehyde dehydrogenase. This resulted in embryos with an undulating notochord and correspondingly abnormal somites and ventral floor plate. In contrast to this effect, 4-methylpyrazole, which inhibits alcohol dehydrogenases, had no effect on development. This effect of disulphiram suggests that t-RA may be involved in the establishment of the anteroposterior axis of the embryo.