Different mechanisms of energy coupling for transport of various amino acids in cells of Mycobacterium phlei.

Whole cells of Mycobacterium phlei were shown to actively accumulate proline, leucine, lysine, tryptophan, histidine, glutamine, and glutamic acid to different steady state levels. The transport of proline, in contrast to that of other amino acids, was found to be insensitive to various respiratory inhibitors, e.g. cyanide, arsenate, azide, and sulfhydryl reagents. However, oxygen was an obligatory requirement for the uptake of proline, as well as for the other amino acids. The results indicate that the energy requirements for proline uptake are different from those of other amino acids. In contrast to the system from Escherichia coli, the mode of energy transduction for the uptake of proline, glutamine, and glutamic acid is different even though these amino acids are shock resistant in the M. phlei system.     

Large Scale Analysis of Phenotype-Pathway Relationships Based on GWAS Results

The widely used pathway-based approach for interpreting Genome Wide Association Studies (GWAS), assumes that since function is executed through the interactions of multiple genes, different perturbations of the same pathway would result in a similar phenotype. This assumption, however, was not systemically assessed on a large scale. To determine whether SNPs associated with a given complex phenotype affect the same pathways more than expected by chance, we analyzed 368 phenotypes that were studied in >5000 GWAS. We found 216 significant phenotype-pathway associations between 70 of the phenotypes we analyzed and known pathways. We also report 391 strong phenotype-phenotype associations between phenotypes that are affected by the same pathways. While some of these associations confirm previously reported connections, others are new and could shed light on the molecular basis of these diseases. Our findings confirm that phenotype-associated SNPs cluster into pathways much more than expected by chance. However, this is true for <20% (70/368) of the phenotypes. Different types of phenotypes show markedly different tendencies: Virtually all autoimmune phenotypes show strong clustering of SNPs into pathways, while most cancers and metabolic conditions, and all electrophysiological phenotypes, could not be significantly associated with any pathway despite being significantly associated with a large number of SNPs. While this may be due to missing data, it may also suggest that these phenotypes could result only from perturbations of specific genes and not from other perturbations of the same pathway. Further analysis of pathway-associated versus gene-associated phenotypes is, therefore, needed in order to understand disease etiology and in order to promote better drug target selection.     

History and dynamics of the crown-of-thorns starfish Acanthaster planci (L.) in the Suva area,Fiji

Annual recruitment of Acanthaster planci over a 13 year period in a known juvenile refuge substratum on Suva Reef was very patchy in time and space. Macroscale recruitment events resulted in outbreaks over many thousands of hectares over 100 km of coastline whereas localised but intensive mesoscale events resulted in concenrated aggregations over areas of several tens of hectares. A very low level of recruitment occurred in most years but three intensive, macroscale recruitment events occurred in 1977, 1984 and 1987, and two localised but intensive recruitment events occurred in 1982 and 1983. Annual recruitment of A. planci between 1975–89 had no overt relationship with rainfall events, as proposed in the terrestrial run-off hypothesis on the cause of primary out-breaks. Growth rates within monitored cohorts were highly variable, but mean growth rates of two cohorts 1984 and 1987 were relatively similar. Mortality rates of three monitored cohorts were variable. Longevity of the 1977 cohort was 7–8 years, while that of the 1984 cohort was 2–3 years. Mortality of the 1987 cohort has been low to date (i.e. 4 years of age). Disease, attributed to an undescribed sporozoan pathogen, was responsible for two mass mortalities in the 1984 cohort, in 1984 and in 1986, and eventually resulted in the extinction of this cohort. Anecdotal reports indicate that outbreaks of A. planci are increasing in frequency and severity. According to Fijian reef fishermen, the starfish were low to moderate in abundance in the Suva area from the 1920s to the 1960s. A progressive build up occurred on some reefs in 1963–67 leading to a major outbreak episode from 1967–1971. The outbreaks were in a chronic phase between 1977–1989. Our findings demonstrate that there is no invariable pattern or process involved in the population dynamics of A. planci and that a single explanation of the A. planci phenomenon is therefore unlikely.     

Synthesis of Benzodioxinopyrroles as selective α2-adrenoceptor antagonists

A novel series of tetrahydrobenzodioxinopyrroles has been identified as potent and selective α₂-adrenoceptor antagonists. Convergent syntheses have been developed that allowed the preparation of analogues and their enantiomers. A compound of particular interest is the 5-fluoro substituted analogue (fluparoxan).     

Effect of very low calorie diet on body composition and exercise response in sedentary women.

The effect of very low calorie diet (VLCD) on fat-free mass (FFM) and physiological response to exercise is a topic of current interest. Ten moderately obese women (aged 23-57 years) received VLCD (1695 kJ.day-1) for 6 weeks. FFM, estimated by four conventional techniques, and heart rate (fc), blood lactate (la(b)), mean arterial pressure (MAP), respiratory exchange ratio (R) and rating of perceived exertion (RPE) were measured during a submaximal cycle ergometry test 1 week before, in the 2nd and 6th week, and 1 week after VLCD treatment. Strength and muscular endurance of the quadriceps and hamstrings were tested by isokinetic dynamometry. The 11.5-kg reduction in body mass was approximately 63% fat and 37% FFM. The latter was attributed largely to the loss of water associated with glycogen. Whilst exercise fc increased by 9-14 beats.min-1 (P < 0.01), there were substantial decreases (P < 0.01) in submaximal MAP (1.07-1.73 kPa), la(b) (0.75-1.00 mmol.l-1 and R (0.07-0.09) during VLCD. R and fc returned to normal levels after VLCD. Gross strength decreased (P < 0.01) by 9 and 13% at 1.05 rad.s-1 and 3.14 rad.s-1, respectively. Strength expressed relative to body mass (Nm.kg-1) increased (P < 0.01) at the lower contraction velocity, but there was no change at the faster velocity. Muscular endurance also decreased (P < 0.01) by 62 and 82% for the hamstrings and quadriceps, respectively. We concluded that the strength decrease was a natural adaptation to the reduction in body mass as the ratio of strength to FFM was maintained.(ABSTRACT TRUNCATED AT 250 WORDS)