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Although pedobarography has been widely used in quantitative clinical gait analysis for children, the collection, processing, analysis, and interpretation of the data vary widely. In most cases in children, foot dysfunction during gait is primarily a consequence of skeletal segmental malalignment, which can be characterized by the location and duration of the center of pressure progression (COPP) relative to the foot. This study determines the validity and reliability of a technique using the COPP and establishes a normative database for the COPP in children.Prospective case series to evaluate a diagnostic test.Simultaneous pedobarograph and kinematic data collection was performed on 23 children (46 feet) who were neurologically healthy. The validity of the COPP technique was determined by comparing the pedobarograph- and kinematic-based determinations of the orientation of the longitudinal (or long) axis of the foot, an essential component of the COPP approach. Intrarater and interrater reliability for the pedobarograph-based technique were determined by comparing repeated measures of the long axis of the foot from 4 analysts. Normative data for the location and duration of the COPP were generated from this cohort of neurologically healthy children.The mean difference for the long axis of the foot between the pedobarograph- and kinematic-based methods was 2.3 degrees (P0.001). The mean difference between first and second determinations of the long axis of the foot by the same analyst was 1.0 degrees (P0.001; correlation coefficient, 0.975). The mean difference between the 4 analysts' determinations of the long axis of the foot was 1.9 degrees (P0.001; correlation coefficient, 0.969). The normal COPP is located under the heel segment for 23.7% of stance, under the midfoot segment for 28.7% of stance, and under the forefoot segment for 47.5% of stance.This study establishes clinically acceptable validity and reliability for the pedobarograph COPP technique and determines the location and duration of the COPP in a cohort of neurologically healthy children.This standardized approach to the determination of foot loading patterns, based upon normative data, should facilitate the characterization of abnormal foot loading patterns, clinical decision making, and the assessment of outcome after a variety of interventions.

Drosophila CREB-binding protein (dCBP) is a very large multidomain protein, which belongs to the CBP/p300 family of proteins that were first identified by their ability to bind the CREB transcription factor and the adenoviral protein E1. Since then CBP has been shown to bind to >100 additional proteins and functions in a multitude of different developmental contexts. Among other activities, CBP is known to influence development by remodeling chromatin, by serving as a transcriptional coactivator, and by interacting with terminal members of several signaling transduction cascades. Reductions in CBP activity are the underlying cause of Rubinstein-Taybi syndrome, which is, in part, characterized by several eye defects, including strabismus, cataracts, juvenile glaucoma, and coloboma of the eyelid, iris, and lens. Development of the Drosophila melanogaster compound eye is also inhibited in flies that are mutant for CBP. However, the vast array of putative protein interactions and the wide-ranging roles played by CBP within a single tissue such as the retina can often complicate the analysis of CBP loss-of-function mutants. Through a series of genetic screens we have identified several genes that could either serve as downstream transcriptional targets or encode for potential CBP-binding partners and whose association with eye development has hitherto been unknown. The identification of these new components may provide new insight into the roles that CBP plays in retinal development. Of particular interest is the identification that the CREB transcription factor appears to function with CBP at multiple stages of retinal development.

An extract of the sponge Rhabdastrella globostellifera was active in an assay measuring stabilization of the binding of DNA with DNA polymerase β. From this extract, four isomalabaricane triterpenoids were isolated and characterized, three of which were active in the binding assay. All compounds were active in the A2780 ovarian cancer cell line assay. Bioassay-guided fractionation of an extract of a sponge of species Dysidea using the A2780 bioassay yielded the known scalarane sesterterpenoid heteronemin in good yield. Four derivatives of heteronemin were prepared semisynthetically from the natural product, tested for their bioactivity, and their structure-activity dependence was observed. Bioassay guided-fractionation of an extract of a Tuemoya sp. green alga, using an assay for inhibitors of the enzyme Tie2 kinase, afforded a two sulfated cycloartanol triterpenoids. Both the major and minor compounds were identified by spectroscopic methods. Bioassay-guided fractionation of an extract of Petalonyx parryi yielded three known oleanane triterpenoids which inhibited the lyase domain of DNA polymerase β. The structures were confirmed by NMR spectroscopic techniques. This is the first reported study of the chemical components of Petalonyx parryi. As part of our antitumor natural product drug discovery efforts, several extracts were selected for bioassay-guided fractionation based on their activity in initial in vitro screens. A new dereplication method using aminopropyl SPE cartridges was applied to six of these extracts, and four of the extracts were dropped due to the presence of long-chain fatty acids (LCFAs). We present results for the testing and application of this SPE-based method for LCFA dereplication. The cell cycle kinase Chk1 is an interesting target for the development of agents which might potentiate DNA damaging agents. Typical assays for Chk1 involve the use of expensive or radioactive reagents. To facilitate the development of new assays using shorter peptide substrates, small libraries of peptides have been synthesized and tested for their activity as Chk1 substrates. Several of the substrates synthesized displayed activity in the Chk1 assay. Ph. D.

The development of the compound eye of Drosophila is controlled, in part, by the concerted actions of several nuclear proteins that form an intricate regulatory system. One member of this network is sine oculis (so), the founding member of the Six gene family. Mutations within so affect the entire visual system, including the compound eye. The vertebrate homologs Six3 and Six6 also appear to play crucial roles in retinal formation. Mutations in Six3 inhibit retinal formation in chickens and fish, whereas those in Six6 are the underlying cause of bilateral anophthalmia in humans. Together, these phenotypes suggest a conserved role for the Six genes in eye development. In this report, we describe the effects of a dominant-negative mutation of sine oculis on the development of the compound eye of Drosophila. The mutation resides within the Six domain and may have implications for eye development and disease.

The ISO intracutaneous reactivity test is the standard protocol for determining a medical device's potential for causing irritation. The authors present data indicating that the number of animals required per test can be reduced from three rabbits to two.

The large-footed myotis (Myotis macropus) feeds by trawling aquatic invertebrates and small fish from water surfaces, but little is known about what types of streams are used. We investigated habitat use by M. macropus in northern New South Wales (NSW) by analysing data-base records, conducting field surveys and assessing environmental variables on or near waterways. A GIS comparison of 222 data-base records of M. macropus with broad environmental patterns indicated that most records were near large and permanent waterways at low elevations, in flat or undulating terrain, usually surrounded by vegetation. Three different field surveys were carried-out. First, 25 waterways on the NSW mid-north coast were stratified into five size classes and sampled (December 1996-January 1997) using harp traps and ultrasonic detectors. Just two captures and 20 passes were recorded. No M. macropus were detected on either the smallest or largest waterways, although the latter may have been under-sampled due to their broad expanse. Records of M. macropus were significantly associated with larger, more permanent waterways (when the largest size class was omitted). Non-metric multi-dimensional scaling of sites, described by their environmental attributes, failed to separate sites on the basis of presence/absence of M. macropus. The second survey (February 1998) targeted 25 sites on waterways within 10 km of a known roost in Kerewong State Forest. Twenty-eight passes were recorded, all confined to just three sites on Upsalls Creek, a large 4th order stream. The third survey (February 2000) investigated the use of adjacent riparian vegetation in the vicinity of the Kerewong roost. At each of 12 sites, one detector was placed on the stream, one 10 m from it and a third 20 m into adjacent vegetation. An average of 11 M. macropus passes per night was recorded over streams (total passes = 273), whereas no passes were recorded in adjacent vegetation. We conclude that M. macropus is sparsely dispersed across streams in forests of north-east NSW and that they are most likely to be recorded on large streams in the lower end of catchments. Management implications for timber production forests include redirecting effort from pre-logging surveys to monitoring the changing status of M. macropus over time, especially at day roosts where local populations are concentrated.

The retinal determination gene dachshund is distantly related to the family of Ski/Sno proto-oncogenes and influences the development of a wide range of tissues including the embryonic head, optic lobes, brain, central nervous system as well as the post-embryonic leg, wing, genital and eye-antennal discs. We were interested in the regulatory mechanisms that control the dynamic expression pattern of dachshund and in this report we set out to ascertain how the transcription of dachshund is modulated in the embryonic head and developing eye-antennal imaginal disc. We demonstrate that the TGFβ signaling cascade, the transcription factor zerknullt and several other patterning genes prevent dachshund from being expressed inappropriately within the embryonic head. Additionally, we show that several members of the eye specification cascade influence the transcription of dachshund during normal and ectopic eye development. Our results suggest that dachshund is regulated by a complex combinatorial code of transcription factors and signaling pathways. Unraveling this code may lead to an understanding of how dachshund regulates the development of many diverse tissue types including the eye.