The receptor tyrosine kinase regulator sprouty1 is a target of the tumor suppressor WT1 and important for kidney development

WT1 encodes a transcription factor involved in kidney development and tumorigenesis. Using representational difference analysis, we identified a new set of WT1 targets, including a homologue of the Drosophila receptor tyrosine kinase regulator, sprouty. Sprouty1 was up-regulated in cell lines expressing wild-type but not mutant WT1. WT1 bound to the endogenous sprouty1 promoter in vivo and directly regulated sprouty1 through an early growth response gene-1 binding site. Expression of Sprouty1 and WT1 overlapped in the developing metanephric mesenchyme, and Sprouty1, like WT1, plays a key role in the early steps of glomerulus formation. Disruption of Sprouty1 expression in embryonic kidney explants by antisense oligonucleotides reduced condensation of the metanephric mesenchyme, leading to a decreased number of glomeruli. In addition, sprouty1 was expressed in the ureteric tree and antisense-treated ureteric trees had cystic lumens. Therefore, sprouty1 represents a physiologically relevant target gene of WT1 during kidney development.

Microstructural evolution of the Serido Belt, NE-Brazil: the effect of two tectonic events on development of c-axis preferred orientation in quartz

The polyphase evolution of the Serido Belt (NE-Brazil) includes D, crust formation at 2.3-2.1 Ga, D-2 thrust tectonics at 1.9 Ga and crustal reworking by D-3 strike-slip shear zones at 600 Ma. Microstructural investigations within mylonites associated with D-2 and D-3 events were used to constrain the tectono-thermal evolution of the belt. D-2 shear zones commenced at deeper crustal levels and high amphibolite facies conditions (600-650 degreesC) through grain boundary migration, subgrain rotation and operation of quartz Q-prism slip. Continued shearing and exhumation of the terrain forced the re-equilibration of high-T fabrics and the switching of slip systems from (c)-prism to positive and negative (a)-rhombs. During D-3, enhancement of ductility by dissipation of heat that came from syn-D-3 granites developed wide belts of amphibolite facies mylonites. Continued shearing, uplift and cooling of the region induced D-3 shear zones to act in ductile-brittle regimes, marked by fracturing and development of thinner belts of greenschist facies mylonites. During this event, switching from (a)-prism to a basal slip indicates a thermal path from 600 to 350 degreesC. Therefore, microstructures and quartz c-axis fabrics in polydeformed rocks from the Serido Belt preserve the record of two major events, which includes contrasting deformation mechanisms and thermal paths. (C) 2003 Elsevier Ltd. All rights reserved.

Will chymase inhibitors be the next major development for the treatment of cardiovascular disorders?

Chymase is contained in the secretory granules of mast cells. In addition to the synthesis of angiotensin II, chymase is involved in transforming growth factor-beta activation and cleaves Type I procollagen to produce collagen. NK301 and BCEAB are orally-active inhibitors of chymase. NK301 was tested in a dog model of vascular intimal hyperplasia after balloon injury and shown to reduce the increased chymase activity in the injured arteries and prevent intimal thickening. In a hamster model of cardiac fibrosis associated with cardiomyopathy, BCEAB reduced the increased cardiac chymase activity in cardiomyopathy and reduced fibrosis. Chymase inhibitors may be an important development for the treatment of cardiovascular injury associated with mast cell degranulation.

Development of a quality use of medicines coding system to rate clinical pharmacists' medication review recommendations

Objective: To develop a 'quality use of medicines' coding system for the assessment of pharmacists' medication reviews and to apply it to an appropriate cohort. Method: A 'quality use of medicines' coding system was developed based on findings in the literature. These codes were then applied to 216 (111 intervention, 105 control) veterans' medication profiles by an independent clinical pharmacist who was supported by a clinical pharmacologist with the aim to assess the appropriateness of pharmacy interventions. The profiles were provided for veterans participating in a randomised, controlled trial in private hospitals evaluating the effect of medication review and discharge counselling. The reliability of the coding was tested by two independent clinical pharmacists in a random sample of 23 veterans from the study population. Main outcome measure: Interrater reliability was assessed by applying Cohen's kappa score on aggregated codes. Results: The coding system based on the literature consisted of 19 codes. The results from the three clinical pharmacists suggested that the original coding system had two major problems: (a) a lack of discrimination for certain recommendations e. g. adverse drug reactions, toxicity and mortality may be seen as variations in degree of a single effect and (b) certain codes e. g. essential therapy were in low prevalence. The interrater reliability for an aggregation of all codes into positive, negative and clinically non-significant codes ranged from 0.49-0.58 (good to fair). The interrater reliability increased to 0.72-0.79 (excellent) when all negative codes were excluded. Analysis of the sample of 216 profiles showed that the most prevalent recommendations from the clinical pharmacists were a positive impact in reducing adverse responses (31.9%), an improvement in good clinical pharmacy practice (25.5%) and a positive impact in reducing drug toxicity (11.1%). Most medications were assigned the clinically non-significant code (96.6%). In fact, the interventions led to a statistically significant difference in pharmacist recommendations in the categories; adverse response, toxicity and good clinical pharmacy practice measured by the quality use of medicine coding system. Conclusion: It was possible to use the quality use of medicine coding system to rate the quality and potential health impact of pharmacists' medication reviews, and the system did pick up differences between intervention and control patients. The interrater reliability for the summarised coding system was fair, but a larger sample of medication regimens is needed to assess the non-summarised quality use of medicines coding system.

A comparison of model laws as a starting point for the development of an enforceable international consumer protection regime

This article is concerned primarily with an examination and comparison of select aspects of the model international consumer protection laws proposed by the United Nations (UN), the European Union (EU), and the Organisation for Economic Co-operation and Development (OECD), using the Trade Practices Act 1974 (Australia) as a basis for examination and comparison. As a secondary consideration, it also broadly examines the content of, and differences between, the model laws. The motive for this article is that any future enforceable international consumer protection regime (possibly in the form of an international treaty or convention) would need to take into account the UN, EU and OECD guidelines. A cross-comparison of those model laws, and a comparison of them with the consumer protection provisions of a well established national consumer protection law, should provide a useful starting point for the development of such a regime. The 'select aspects' of the model laws in question are the various provisions of those laws which could relate to situations involving the wrong delivery or non-delivery of goods.

Sport-specific practice and the development of expert decision-making in team ball sports

The role of sport-specific practice in the development of decision-making expertise in the sports of field hockey, netball, and basketball was examined. Fifteen expert decision-makers and 13 experienced non-expert athletes provided detailed information about the quantity and type of sport-specific and other related practice activities they had undertaken throughout their careers. Experts accumulated more hours of sport-specific practice from age 12 years onwards than did non-experts, spending on average some 13 years and 4,000 hours on concentrated sport-specific practice before reaching international standard. A significant negative correlation existed between the number of additional activities undertaken and the hours of sportspecific training required before attaining expertise, suggesting a functional role for activities other than sport-specific training in the development of expert decision-making.

A retrospective analysis of leadership development through sport

The purpose of this study was to examine the development of six leader-athletes. In-depth qualitative interviews were used to explore the various activities that leader athletes engaged in from an early age as well as the roles and influences that peers, coaches, and parents played within these activities. Results indicated that leadership development in sport focused on developing four central components: high skill, strong work ethic, enriched cognitive sport knowledge, and good rapport with people. The types of activities engaged in throughout development as well as receiving feedback, acknowledgement, support, cognitive engagement, mature conversations with adults, and physical encounters with older peers are important social influences that can play an instrumental role in the formation of these four central tenets.

Applied physiology and game analysis of rugby union

Increased professionalism in rugby has elicited rapid changes in the fitness profile of elite players. Recent research, focusing on the physiological and anthropometrical characteristics of rugby players, and the demands of competition are reviewed. The paucity of research on contemporary elite rugby players is highlighted, along with the need for standardised testing protocols. Recent data reinforce the pronounced differences in the anthropometric and physical characteristics of the forwards and backs. Forwards are typically heavier, taller, and have a greater proportion of body fat than backs. These characteristics are changing, with forwards developing greater total mass and higher muscularity. The forwards demonstrate superior absolute aerobic and anaerobic power, and Muscular strength. Results favour the backs when body mass is taken into account. The scaling of results to body mass can be problematic and future investigations should present results using power function ratios. Recommended tests for elite players include body mass and skinfolds, vertical jump, speed, and the multi-stage shuttle run. Repeat sprint testing is a possible avenue for more specific evaluation of players. During competition, high-intensity efforts are often followed by periods of incomplete recovery. The total work over the duration of a game is lower in the backs compared with the forwards; forwards spend greater time in physical contact with the opposition while the backs spend more time in free running, allowing them to cover greater distances. The intense efforts undertaken by rugby players place considerable stress on anaerobic energy sources, while the aerobic system provides energy during repeated efforts and for recovery. Training should focus on repeated brief high-intensity efforts with short rest intervals to condition players to the demands of the game. Training for the forwards should emphasise the higher work rates of the game, while extended rest periods can be provided to the backs. Players should not only be prepared for the demands of competition, but also the stress of travel and extreme environmental conditions. The greater professionalism of rugby union has increased scientific research in the sport; however, there is scope for significant refinement of investigations on the physiological demands of the game, and sports-specific testing procedures.

The development of chromatography for the characterization of protein interactions: a personal perspective

This article reviews the progress of a personal endeavour to develop chromatography as a quantitative procedure for the determination of reaction stoichiometries and equilibrium constants governing protein interactions. As well as affording insight into an aspect of chromatography with which many protein chemists are unfamiliar, it shows the way in which minor adaptations of conventional chromatographic practices have rendered the technique one of the most powerful methods available for the characterization of interactions. That pathway towards quantification is followed from the introduction of frontal gel filtration for the study of protein self-association to the characterization of ligand binding by the biosensor variant of quantitative affinity chromatography.

Use of confocal microscopy to follow the development of penetrative hyphae during growth of Rhizopus oligosporus in an artificial solid-state fermentation system

Two methods were compared for determining the concentration of penetrative biomass during growth of Rhizopus oligosporus on an artificial solid substrate consisting of an inert gel and starch as the sole source of carbon and energy. The first method was based on the use of a hand microtome to make sections of approximately 0.2- to 0.4-mm thickness parallel to the substrate surface and the determination of the glucosamine content in each slice. Use of glucosamine measurements to estimate biomass concentrations was shown to be problematic due to the large variations in glucosamine content with mycelial age. The second method was a novel method based on the use of confocal scanning laser microscopy to estimate the fractional volume occupied by the biomass. Although it is not simple to translate fractional volumes into dry weights of hyphae due to the lack of experimentally determined conversion factors, measurement of the fractional volumes in themselves is useful for characterizing fungal penetration into the substrate. Growth of penetrative biomass in the artificial model substrate showed two forms of growth with an indistinct mass in the region close to the substrate surface and a few hyphae penetrating perpendicularly to the surface in regions further away from the substrate surface. The biomass profiles against depth obtained from the confocal microscopy showed two linear regions on log-linear plots, which are possibly related to different oxygen availability at different depths within the substrate. Confocal microscopy has the potential to be a powerful tool in the investigation of fungal growth mechanisms in solid-state fermentation. (C) 2003 Wiley Periodicals, Inc.