Intracellular vesicle movement, cAMP and myosin II in Dictyostelium

Dictyostelium amoebae were analyzed before and after rapid addition of 10(-6) M cAMP for cellular motility, dynamic shape changes, and intracellular particle movement. Before cAMP addition, amoebae moved in a persistent anterior fashion and were elongate with F-actin localized predominantly in the anterior pseudopod. Intracellular particles moved rapidly and anteriorly. Within seconds after 10(-6) M cAMP addition, cells stopped translocating, pseudopod formation ceased, intracellular particle movement was depressed, and F-actin was lost from the pseudopod and concomitantly relocalized in the cell cortex. After 10 seconds, expansion zones reappeared but were small and no longer anteriorly localized. Vesicle movement partially rebounded but was no longer anteriorly directed. The myosin II null mutant HS2215 exhibited both depressed cellular translocation and vesicle movement. The addition of cAMP to HS2215 cells did not result in any detectable change in the random, depressed movement of particles. The results with HS2215 suggest that myosin II is essential for (1) rapid cellular translocation, (2) cellular polarity, (3) rapid particle movement, (4) anteriorly directed particle movement, and (5) the cAMP response. Electron micrographs suggest that at least half of the particles examined in this study contain in turn smaller membrane bound vesicles or multilamellar membrane bodies. The possible role of these vesicles is discussed.     

Determinants of Dominance in the Tree Lizard Urosaurus ornatus: the Relative Importance of Mass,Previous Experience and Coloration

A determination of some of the factors that predict the outcome of contests between male tree lizards, Urosaurus ornatus, was made using logistic regression modelling on matched-pair data. Two-day-long encounters were staged between pairs of males differing in size (snout-vent length and mass), previous contest status (previous winners and previous losers), and coloration (dorsal coloration during their previous contest and throat coloration, a fixed trait). Mass proved to be the best single predictor of contest outcome, resulting in an 80% correct classification rate for predicting winners and losers, far better than the less than 57% correct classification rate for snout-vent length. Previous social status (winner or loser) also was a powerful single predictor of contest outcome with a 793% correct classification rate, as was previous dorsal coloration (76.7%). When combined, mass and previous status produced the strongest combination of predictors with a better than 86% correct classification rate. Contrary to several previous studies, which implicated throat coloration as an important status signal of dominance, our results failed to show that throat coloration is a strong predictor of contest outcome. Possible reasons for this discrepancy with earlier findings are discussed. The logistic regression models also allow prediction of the magnitude of difference in mass between two contestants for there to be an equal chance of winning, given a second asymmetry in contest predictors.     

Modelling the spatial patterning of teeth primordia in the alligator

We propose a model mechanism for the initiation and spatial positioning of teeth primordia in the alligator, Alligator mississippiensis. Detailed embryological studies by Westergaard and Ferguson (1986, 1987, 1990) have shown that jaw growth plays a crucial role in the developmental patterning of the tooth initiation process. Based on biological data we develop a dynamic patterning mechanism, which crucially includes domain growth. The mechanism can reproduce the spatial pattern development of the first seven teeth primordia in each half jaw of A. mississippiensis. The results for the precise spatio-temporal sequence compare well with experiment. Simulation of the model also predicts that certain transplantations can alter the spatial sequence of teeth primordia initiation.     

Exclusion of epidermal growth factor and high-resolution physical mapping across the Rieger syndrome locus.

We have evaluated the 4q25-4q26 region where the autosomal dominant disorder Rieger syndrome has been previously mapped by linkage. We first excluded epidermal growth factor as a candidate gene by carrying out SSCP analysis of each of its 24 exons using a panel of seven unrelated individuals with Rieger syndrome. No evidence for etiologic mutations was detected in these individuals, although four polymorphic variants were identified, including three that resulted in amino acid changes. We next made use of two apparently balanced translocations, one familial and one sporadic, to identify a narrow physical localization likely to contain the gene or to be involved in regulation of gene function. Somatic cell hybrids were established from individuals with these balanced translocations, and these hybrids were used as a physical mapping resource for, first, preliminary mapping of the translocation breakpoints using known sequence tagged sites from chromosome 4 and then, after creating YAC and cosmids contigs encompassing the region, for fine mapping of those breakpoints. A cosmid contig spanning these breakpoints was identified and localized the gene to within approximately 150 kb of D4S193 on chromosome 4. The interval between the two independent translocations is approximately 50 kb in length and provides a powerful resource for gene identification.     

Seasonal variation in the effects of hard substratum biofilming on settlement of marine invertebrate larvae

The effect of season on "biofilming";, as a cue for the settlement of marine invertebrate larvae, was investigated in a long-term field study during the years 1992-1994. The series of settlement experiments was conducted in a tidal rapid on the west coast of Scotland, and involved manipulations of artificial panels. Biofilming of substrata, whilst excluding larval settlement, was achieved by the enclosure of panels within tight-fitting (but removable) mesh screens so that the number of settlers on filmed and unfilmed substrata were counted in the initial absence of other incumbent post-larvae. Depending on larval species, the effects of biofilming were found to be either facilitatory or inhibitory. Significant within- and between-species seasonal differences in the settlement responses were detected, and a reversal of the effect of biofilming on larval settlement response, from inhibitory to facilitatory and vice versa, was noted with season in the case of some taxonomic groups and species (e.g. Tubulipora sp., Plagioecia sp., Electra pilosa (L.)). The present study emphasizes the need for extended field studies of larval responses to environmental cues, when the focus of interest is in drawing general inferences about naturally occurring behavioural patterns at settlement.     

Is hyperglycaemia an independent predictor of poor outcome after acute stroke? Results of a long-term follow up study.

OBJECTIVE: To determine whether raised plasma glucose concentration independently influences outcome after acute stroke or is a stress response reflecting increased stroke severity. DESIGN: Long-term follow up study of patients admitted to an acute stroke unit. SETTING: Western Infirmary, Glasgow. SUBJECTS: 811 patients with acute stroke confirmed by computed tomography. Analysis was restricted to the 750 non-diabetic patients. MAIN OUTCOME MEASURES: Survival time and placement three months after stroke. RESULTS: 645 patients (86%) had ischaemic stroke and 105 patients (14%) haemorrhagic stroke. Cox''s proportional hazards modelling with stratification according to Oxfordshire Community Stroke Project categories identified increased age (relative hazard 1.36 per decade; 95% confidence interval 1.21 to 1.53), haemorrhagic stroke (relative hazard 1.67; 1.22 to 2.28), time to resolution of symptoms > 72 hours (relative hazard 2.15; 1.15 to 4.05), and hyperglycaemia (relative hazard 1.87; 1.43 to 2.45) as predictors of mortality. The effect of glucose concentration on survival was greatest in the first month. CONCLUSIONS: Plasma glucose concentration above 8 mmol/l after acute stroke predicts a poor prognosis after correcting for age, stroke severity, and stroke subtype. Raised plasma glucose concentration is therefore unlikely to be solely a stress response and should arguably be treated actively. A randomised trial is warranted.     

Association of upper gastrointestinal toxicity of non-steroidal anti-inflammatory drugs with continued exposure: cohort study.

OBJECTIVES: To determine the profile of risk of upper gastrointestinal toxicity during continuous treatment with, and after cessation of, non-steroidal anti-inflammatory drugs. DESIGN: Cohort study with a prospectively constructed, population based, record linkage database containing details of exposure to all community dispensed non-steroidal anti-inflammatory drugs and also all admissions to hospital for upper gastrointestinal diagnoses. SETTING: The population of Tayside, Scotland. SUBJECTS: 52,293 subjects aged 50 and over who received one or more non-steroidal anti-inflammatory between 1 January 1989 and 31 December 1991 and 73,792 subjects who did not receive one during the same period (controls). MAIN OUTCOME MEASURES: Admission to hospital for upper gastrointestinal bleeding and perforation, and admission for other upper gastrointestinal diagnoses. RESULTS: About 2% of the non-steroidal anti-inflammatory cohort were admitted with an upper gastrointestinal event during the study period compared with 1.4% of controls. The risk of admission for upper gastrointestinal haemorrhage and perforation was constant during continuous non-steroidal anti-inflammatory exposure and carried over after the end of exposure. The results were similar for admissions for all upper gastrointestinal events. CONCLUSION: This study provides evidence that non-steroidal anti-inflammatory toxicity persists with continuous exposure. There seems to be carryover toxicity after the end of prescribing. These findings have implications for the management of patients requiring non-steroidal anti-inflammatory drugs.