Enlarged meristems and delayed growth in plp mutants result from lack of CaaX prenyltransferases

Meristems require a myriad of intercellular signaling pathways for coordination of cell division within and between functional zones and clonal cell layers. This control of cell division ensures a constant availability of stem cells throughout the life span of the meristem while limiting overproliferation of meristematic cells and maintaining the meristem structure. We have undertaken a genetic screen to identify additional components of meristem signaling pathways. We identified pluripetala (plp) mutants based on their dramatically larger meristems and increased floral organ number. PLURIPETALA encodes the alpha-subunit shared between protein farnesyltransferase and protein geranylgeranyltransferase-I. plp mutants also have altered abscisic acid responses and overall much slower growth rate. plp is epistatic to mutations in the beta-subunit of farnesyltransferase and shows a synergistic interaction with clavata3 mutants. plp mutants lead to insights into the mechanism of meristem homeostasis and provide a unique in vivo system for studying the functional role of prenylation in eukaryotes.     

Circadian and seasonal variation of malignant arrhythmias in a pediatric and congenital heart disease population

INTRODUCTION: Recent studies in adult populations have revealed seasonal variation in the frequency of acute cardiovascular events, including life-threatening arrhythmias, demonstrating increased events during winter and early spring. Trends in the time of day that arrhythmias occur also were noted. We sought to establish whether pediatric and young adult congenital heart disease implantable cardioverter defibrillator (ICD) recipients have circadian or seasonal variability in shock frequency, similar to adult populations. METHODS AND RESULTS: Data from ICD patients at six pediatric centers in North America were analyzed to assess the timing of life-threatening arrhythmias. The populations consisted of children and adults with congenital heart disease and ICDs placed for malignant arrhythmias. Data were considered in 46 patients who received appropriate therapy (total 139 episodes) for ventricular tachycardia or ventricular fibrillation. Multiple variables were analyzed, including time of day, day of week, and month of year. In contrast to previously studied adult patients, fewer events occurred in the early morning (7.5%), with the most therapies occurring between 6 P.M. and midnight (35%). An increased frequency of therapies was observed in the fall and winter (September-January), representing 60% of all appropriate shocks. Unlike adult populations, Mondays did not have an increased frequency of malignant arrhythmias. CONCLUSION: Pediatric and adult congenital heart disease populations have moderate seasonal and 24-hour variation in ICD event rate, with some distinctly different peaks than those seen in typical adult ICD populations. These findings suggest circadian variation in arrhythmia vulnerability that may differ from conventional occupational, physical, or emotional stressors. (J Cardiovasc Electrophysiol, Vol. 13, pp.     

Cloning and functional expression of venom prothrombin activator protease from Pseudonaja textilis with whole blood procoagulant activity

The snake venom group C prothrombin activators contain a number of components that enhance the rate of prothrombin activation. The cloning and expression of full-length cDNA for one of these components, an activated factor X (factor Xa)-like protease from Pseudonaja textilis as well as the generation of functional chimeric constructs with procoagulant activity were described. The complete cDNA codes for a propeptide, light chain, activation peptide (AP) and heavy chain related in sequence to mammalian factor X. Efficient expression of the protease was achieved with constructs where the AP was deleted and the cleavage sites between the heavy and light chains modified, or where the AP was replaced with a peptide involved in insulin receptor processing. In human kidney cells (H293F) transfected with these constructs, up to 80% of the pro-form was processed to heavy and light chains. Binding of the protease to barium citrate and use of specific antibodies demonstrated that gamma-carboxylation of glutamic acid residues had occurred on the light chain in both cases, as observed in human factor Xa and the native P. textilis protease. The recombinant protease caused efficient coagulation of whole citrated blood and citrated plasma that was enhanced by the presence of Ca2+. This study identified the complete cDNA sequence of a factor Xa-like protease from P. textilis and demonstrated for the first time the expression of a recombinant form of P. textilis protease capable of blood coagulation.     

Nebulisers or spacers for the administration of bronchodilators to those with asthma attending emergency departments?

BACKGROUND: Systematic reviews and national guidelines conclude that the nebulised route of administration of bronchodilators has no advantage over the use of a spacer in moderately severe exacerbations of asthma. Whether this recommendation is implemented and whether it might affect use of staff time is unknown. OBJECTIVES: To determine the current method of administration of bronchodilators to those with non-life-threatening asthma attending emergency departments (ED) in London, UK and to monitor the implementation of a new policy to administer bronchodilators by spacers in one ED with a special reference to the time taken by nurses to administer the therapy by two different routes. METHODS: Thirty-five EDs in Greater London were surveyed regarding their current practice. A time and motion study was then undertaken in one department observing nurses administering bronchodilators in the 3 weeks before and 3 weeks after a departmental policy change to favour the use of spacer devices rather than nebulisers. RESULTS: The majority of EDs (94.3%) in Greater London were using the nebulised route of administering bronchodilators to the majority of their adult patients. Spacers were more commonly used for the treatment of children (60.3% of departments using spacers and nebulisers or spacers alone). Over half of the hospitals surveyed (51.4%) were unaware that the British Guidelines on Asthma Management suggested that outcomes were the same and that there were potential advantages in the use of a spacer for both adults and children. Time and motion studies showed that the use of a spacer took no more nursing time than administration of the bronchodilator via a nebuliser; in fact treatment and set-up time were considerably lower for spacers. CONCLUSION: Spacer administration of bronchodilators to those with asthma attending EDs utilises less treatment time than use of a nebuliser. A survey of EDs in Greater London has shown that despite guideline conclusions there appears to be little evidence of reduction in use of nebulisers; a fear that use of alternatives might take nurses longer is not supported by this study.     

Insulin resistance is associated with increased serum levels of glycosylphosphatidylinositol-specific phospholipase D

The dyslipidemia of the metabolic syndrome is associated with alterations in triglyceride and high-density lipoprotein (HDL) metabolism. We examined the serum levels of glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD), a minor HDL-associated protein, in a cohort with a wide range of insulin sensitivity. The mean serum GPI-PLD mass from 109 subjects was 58.9 +/- 18.4 microg/mL (mean +/- SD). GPI-PLD levels directly correlated with cholesterol, apolipoprotein AI, triglycerides, insulin, and homeostasis model assessment (HOMA) but not C-reactive protein. These results suggest that increased serum GPI-PLD is associated with the insulin resistance.