Association of the lipoprotein receptor-related protein 2 gene with gout and non-additive interaction with alcohol consumption

Introduction

The T allele of a single nucleotide polymorphism (SNP: rs2544390) in lipoprotein receptor-related protein 2 (LRP2) is associated with higher serum urate and risk of gout in Japanese individuals. SNP rs2544390 also interacts with alcohol consumption in determining hyperuricemia in this population. We investigated the association of rs2544390 with gout, and interaction with all types of alcohol consumption in European and New Zealand (NZ) Māori and Pacific subjects, and a Māori study cohort from the East Coast region of NZ’s North Island.

Methods

Rs2544390 was genotyped by Taqman®. From NZ a total of 1205 controls and 1431 gout cases clinically ascertained were used. Publicly available genotype and serum urate data were utilized from the Atherosclerosis Risk in Communities (ARIC) study and the Framingham Heart Study (FHS). Alcohol consumption data were obtained by consumption frequency questions in all study cohorts. Multivariate adjusted logistic regression was done using STATA.

Results

The T allele of rs2544390 was associated with increased risk of gout in the combined Māori and Pacific Island cohort (OR = 1.20, P = 0.009), and associated with gout in the European subjects, but with a protective effect (OR = 0.79, P_Unadjusted = 0.02). Alcohol consumption was positively associated with risk of gout in Māori and Pacific subjects (0.2% increased risk/g/week, P = 0.004). There was a non-additive interaction between any alcohol intake and the risk of gout in the combined Māori and Pacific cohorts (P_Interaction = 0.001), where any alcohol intake was associated with a 4.18-fold increased risk in the CC genotype group (P = 6.6x10^-5), compared with a 1.14-fold increased risk in the CT/TT genotype group (P = 0.40). These effects were not observed in European subjects.

Conclusions

Association of the T-allele with gout risk in the Māori and Pacific subjects was consistent with this allele increasing serum urate in Japanese individuals. The non-additive interaction in the Māori and Pacific subjects showed that alcohol consumption over-rides any protective effect conferred by the CC genotype. Further exploration of the mechanism underlying this interaction should generate new understanding of the biological role of alcohol in gout, in addition to strengthening the evidence base for reduction of alcohol consumption in the management of gout.     

Memory and prediction in natural gaze control

In addition to stimulus properties and task factors, memory is an important determinant of the allocation of attention and gaze in the natural world. One way that the role of memory is revealed is by predictive eye movements. Both smooth pursuit and saccadic eye movements demonstrate predictive effects based on previous experience. We have previously shown that unskilled subjects make highly accurate predictive saccades to the anticipated location of a ball prior to a bounce in a virtual racquetball setting. In this experiment, we examined this predictive behaviour. We asked whether the period after the bounce provides subjects with visual information about the ball trajectory that is used to programme the pursuit movement initiated when the ball passes through the fixation point. We occluded a 100 ms period of the ball''s trajectory immediately after the bounce, and found very little effect on the subsequent pursuit movement. Subjects did not appear to modify their strategy to prolong the fixation. Neither were we able to find an effect on interception performance. Thus, it is possible that the occluded trajectory information is not critical for subsequent pursuit, and subjects may use an estimate of the ball''s trajectory to programme pursuit. These results provide further support for the role of memory in eye movements.     

Biological effects of power frequency magnetic fields: Neurochemical and toxicological changes in developing chick embryos

BACKGROUND: There are several reports that indicate a linkage between exposure to power frequency (50 - 60 Hz) magnetic fields with abnormalities in the early embryonic development of the chicken. The present study was designed to understand whether power frequency electromagnetic fields could act as an environmental insult and invoke any neurochemical or toxicological changes in developing chick embryo model. METHODS: Fertilized chicken eggs were subjected to continuous exposure to magnetic fields (50 Hz) of varying intensities (5, 50 or 100 microT) for a period of up to 15 days. The embryos were taken out of the eggs on day 5, day 10 and day 15. Neurochemical (norepinephrine and 5-hydroxytryptamine) and amino acid (tyrosine, glutamine and tryptophan) contents were measured, along with an assay of the enzyme glutamine synthetase in the brain. Preliminary toxicological investigations were carried out based on aminotransferases (AST and ALT) and lactate dehydrogenase activities in the whole embryo as well as in the liver. RESULTS: The study revealed that there was a significant increase (p < 0.01 and p < 0.001) in the level of norepinephrine accompanied by a significant decrease (p < 0.01 and p < 0.001) in the tyrosine content in the brain on day 15 following exposure to 5, 50 and 100 microT magnetic fields. There was a significant increase (p < 0.001) in glutamine synthetase activity resulting in the significantly enhanced (p < 0.001) level of glutamine in the brain on day 15 (for 100 microT only). The possible mechanisms for these alterations are discussed. Further, magnetic fields had no effect on the levels of tryptophan and 5-hydroxytryptamine in the brain. Similarly, there was no effect on the activity of either aminotransferases or lactate dehydrogenase in the whole embryo or liver due to magnetic field exposure. CONCLUSIONS: Based on these studies we conclude that magnetic field-induced changes in norepinephrine levels might help explain alterations in the circadian rhythm, observed during magnetic field stress. Also, the enhanced level of glutamine can act as a contributing factor for developmental abnormalities.     

EFFECTS OF HUMAN ACTIVITIES ON STRUCTURE AND COMPOSITION OF WOODY SPECIES OF THE NOKREK BIOSPHERE RESERVE OF MEGHALAYA,NORTHEAST INDIA

Aims Our study was conducted in the Nokrek Biosphere Reserve (NBR) in the Garo hills districts of Meghalaya, Northeast India. Our aim was to assess the effects of human activities on plant diversity,population structure and regeneration.Methods We selected a representative 1.2 hm2 stand in both the core and buffer zones of NBR. Structure and composition were determined by randomly sampling square quadrats, population structure was assessed by determining age structure, and regeneration was assessed by measuring densities of seedling, sapling and adult trees.Important findings More woody species were recorded from the core zone than the buffer zone (87 vs. 81 species), and there were a large number of tropical, temperate, and Sino-Himalayan, Burma-Malaysian and Malayan elements, primitive families and primitive genera. The trees were distributed in three distinct strata,canopy, subcanopy and sapling. Subcanopy and sapling layers had the highest species richness (81％ -88％ ). Lauraceae and Euphorbiaceae were the dominant families in terms of the number of species, and a large number of families were represented by single species. Most woody species (57 ％ - 79 ％ ) were contagiously distributed and had low frequency ( ＜ 20％ ). Although stand density was high in the buffer zone, its basal area was low compared to the stand in the core zone. Low similarity and high β-diversity indicate marked differences in species composition of the stands. Shannon diversity index was high in both the stands, while Simpson dominance index was low. The diameter-class distribution for dominant species revealed that the most had a large number of young individuals in their populations. Preponderance of tree seedlings, followed by a steep decline in population density of saplings and adult trees, indicated that the seedling to sapling stage was the most critical in the life cycle of the tree populations. Most species (42 ％ - 48 ％ ) had no regeneration,25 ％ - 35 ％ had good/fair regeneration, and the rest had poor regeneration or reoccurred as immigrants.     

Analysis of spatial and yearly variation in winter survival of winter wheat

 Four years of winter survival data for winter wheat (Triticum aestivum L.) were collected on a loam soil located on the Central Experimental Farm at Ottawa, Ontario (45° 23′N, 75° 43′W). The site was low-lying and subject to frequent winter flooding and ice sheet formation. It appeared level although there was microtopographic variation with a range in elevation of approximately 0.15 m. The objective of the study was to gain insight into factors which might affect winter survival. Two varieties, a soft white and a hard red winter wheat, were planted in September. Crop establishment was measured in late fall and the percentage survival was measured in April of the following year. We assumed the large spatial differences in survival were not totally random, but rather were affected by spatial variation in environmental factors such as snow and ice depth, soil moisture and temperature. Hourly measurements of soil temperature at a depth of 0.05 m were recorded throughout the fall, winter and spring. Fall and spring soil moisture at the same depth were measured on the plot, as well as snow and ice depth at selected times throughout the winter. Measurements were taken on a grid covering the plot to help explain spatial variation in survival. In addition, detailed measurements of elevation were taken on a grid. Meteorological data were available from the nearby weather site. While soil temperatures were never low enough to kill plants according to the CERES model, the spatial variation in winter survival was associated with differences in elevation and the resulting surface drainage patterns. Received: 23 March 1998/Accepted: 21 October 1998     

Antisense inhibition of the sucrose transporter in potato: effects on amount and activity

The sucrose proton-cotransporter gene from potato (StSUT1) is mainly expressed in the phloem of mature, exporting leaves. To study the in vivo role of the protein, potato plants were transformed with antisense constructs of the sucrose transporter cDNA under control of the CaMV35S and the rolC promoters, respectively. Both types of transgenic plant develop symptoms characteristic of an inhibition of phloem loading. To determine the level of inhibition, immunological and transport studies were performed. Purified antibodies directed against a peptide from the central loop of SUT1 recognized a transporter with an apparent molecular mass of 47 kDa in leaf plasma membrane vesicles. Antisense repression under control of the non-specific CaMV35S promoter led to a strong reduction in SUT1 protein, whereas no such reduction could be detected when the companion cell-specific rolC promoter was used. Similarily. sucrose uptake in plasma membrane vesicles was reduced by 50–75% in CaMV35S but not in rolC plants. These data suggest that, unlike the rolC promoter, the sucrose transporter is expressed not only in the companion cells but also in other leaf cells. However, inhibition of the transporter by rolC-controlled antisense repression is sufficient to impair phloem loading.