Analysis of <Emphasis Type="Italic">COQ2</Emphasis>gene in multiple system atrophy

Background

Loss of function COQ2 mutations results in primary CoQ10 deficiency. Recently, recessive mutations of the COQ2 gene have been identified in two unrelated Japanese families with multiple system atrophy (MSA). It has also been proposed that specific heterozygous variants in the COQ2 gene may confer susceptibility to sporadic MSA. To assess the frequency of COQ2 variants in patients with MSA, we sequenced the entire coding region and investigated all exonic copy number variants of the COQ2 gene in 97 pathologically-confirmed and 58 clinically-diagnosed MSA patients from the United States.

Results

We did not find any homozygous or compound heterozygous pathogenic COQ2 mutations including deletion or multiplication within our series of MSA patients. In two patients, we identified two heterozygous COQ2 variants (p.S54W and c.403?+?10G?>?T) of unknown significance, which were not observed in 360 control subjects. We also identified one heterozygous carrier of a known loss of function p.S146N substitution in a severe MSA-C pathologically-confirmed patient.

Conclusions

The COQ2 p.S146N substitution has been previously reported as a pathogenic mutation in primary CoQ10 deficiency (including infantile multisystem disorder) in a recessive manner. This variant is the third primary CoQ10 deficiency mutation observed in an MSA case (p.R387X and p.R197H). Therefore it is possible that in the heterozygous state it may increase susceptibility to MSA. Further studies, including reassessing family history in patients of primary CoQ10 deficiency for the possible occurrence of MSA, are now warranted to resolve the role of COQ2 variation in MSA.

     

Physiological responses to water-walking in middle aged women

The purpose of the present study was to examine the physiological responses to water-walking using the Flowmill, which has a treadmill at the base of a water-flume, in two groups of women. In the first group, the women were known to regularly swim and exercise in water (group A), while in the second, they did not routinely participate in water-exercise (group B). In both groups, twelve healthy female volunteers in their fifties participated in the study. All of the subjects walked in water using the Flowmill for the first time. Subjects completed four consecutive bouts of 4-minute duration at progressively increasing speeds (20, 30, 40, and 50 m.min-1), with 1-minute rests between each bout. In addition, water-velocity was adjusted to the walking speed of each bout. The water-depth of the Flowmill was the level of the xiphoid process. The water and room temperatures were 30.3 +/- 0.1 degrees C and 24.9 +/- 0.4 degrees C, respectively. In both groups, the relationship between walking speed and oxygen uptake (VO2) as well as that between walking speed and heart rate (HR) changed exponentially as the walking speed increased, and the relationship between HR and VO2 was linear. The relationship between HR and VO2 was similar in both groups, and there was no significant difference between the predicted maximal oxygen uptake (VO2max) of the two groups. VO2 and HR of group B during water-walking, however, were significantly higher than those of group A at all walking speeds. The results of this study clearly showed that experience in moving through the water strongly affects physiological responses to water-exercise, even when fitness levels are equivalent.     

% fat of Nepali children (ranging from 6 to 18 years old) having different living style

A comparative study of % fat was carried out on Nepali children (Ranging from 6 to 18 years old) to clarify the cause of obesity attended with modernization. 126 males and 79 females who have a natural living style, in rural district (KV) and 166 males and 133 who have a living style affected by the rapid urbanization, in suburban district (BV) were selected as subjects. %Fat was estimated from skinfold thickness according to the method of Nagamine (1975). The results summarized as follows. 1) Mean %Fat of BV in each age were clearly higher than those of KV with coincidental age, especially in male subjects. 2) According to the previous reports (Yoshimizu et al., 1990; Ito et al., 1989), it's considered physical activities in the subjects of BV were lower than those of the subjects in KV. But we could not found the nutritional factors to explain the difference of % fat between BV and KV. From these results, it's considered the difference of % fat in both districts is due to the difference of their physical activities.     

Role of outer coat in resistance of Bacillus megaterium spore

The outer coat fraction (OC-Fr) of Bacillus megaterium ATCC 12872 spore was isolated as a resistant residue after alkali extraction, sonic treatment, and pronase digestion of the spore coat preparation, and its backbone structure was determined by chemical analysis to be composed of galactosamine-6-phosphate (GalN-P) polymers with polypeptides and calcium. OC-Fr was not fully solubilized after ordinary acid hydrolysis. OC-Fr was insensitive to all hexosaminidases tested, and moreover, an isolated fragment, a pentamer of GalN-P, was also resistant to lysozyme and hexosaminidases even after N-acetylation, being sensitive to them to some extent after dephosphorylation. Molecular sieving experiments revealed that the outer coat limited the entry of compounds with a molecular weight of more than 2,000. Exchange of the metal on the spore surface also influenced the heat resistance. Spores of OC-Fr-deficient mutants were less resistant but were still much more resistant than the vegetative cells. These results suggest that the outer coat protects the contents of the spore against chemical, physical and enzymatic treatments owing to the chemical structure itself, composed mainly of GalN-P polymers, and the molecular sieving effect.