Stroke research in GenomEUtwin.

Stroke is one of the leading causes of severe disability and death in the world. In the present article we outline possibilities and limitations for future stroke research within the GenomEUtwin. The combined sample of twins born before 1958 from Denmark, Finland, and Sweden, and available for follow-up into the second millennium for non-fatal and fatal stroke events through national inpatient and death registers exceeds 70,000 twin pairs. This sample size will enable the study of genetic influences on stroke and major stroke subtypes. Large samples of twins in GenomEUtwin have been followed up repeatedly through interviews and questionnaires concerning a variety of exposures and potential risk factors for stroke. We briefly outline how this information can be combined with the health register information for epidemiologic and genetic epidemiologic studies of stroke. We also present the number of twin pairs concordant and discordant for stroke in Denmark, Finland and Sweden, and time lags between events for twins concordant for stroke. This information illustrates that the number of affected sib pairs for linkage studies is relatively limited, but the sample sizes are promising for association studies.     

Effects of glucose, glucose plus branched-chain amino acids, or placebo on bike performance over 100km

Madsen, Klavs, Dave A. MacLean, Bente Kiens, and DirkChristensen. Effects of glucose, glucose plus branched-chain aminoacids, or placebo on bike performance over 100 km. J. Appl. Physiol. 81(6): 2644-2650, 1996.This studywas undertaken to determine the effects of ingesting either glucose(trial G) or glucose plusbranched-chain amino acids (BCAA; trialB), compared with placebo (trialP), during prolonged exercise. Nine well-trained cyclists with a maximal oxygen uptake of 63.1 ± 1.5 mlO₂ ^· min^{1 ·} kg¹performed three laboratory trials consisting of 100 km of cycling separated by 7 days between each trial. During these trials, the subjects were encouraged to complete the 100 km as fast as possible ontheir own bicycles connected to a magnetic brake. No differences inperformance times were observed between the three trials (160.1 ± 4.1, 157.2 ± 4.5, and 159.8 ± 3.7 min, respectively). Intrial B, plasma BCAA levels increased from339 ± 28 µM at rest to 1,026 ± 62 µM after exercise(P < 0.01). Plasma ammoniaconcentrations increased during the entire exercise period for allthree trials and were significantly higher intrial B compared withtrials G andP (P < 0.05). The respiratory exchange ratio was similar in the threetrials during the first 90 min of exercise; thereafter, it tended todrop more in trial P than intrials G andB. These data suggest that neitherglucose nor glucose plus BCAA ingestion during 100 km of cyclingenhance performance in well-trained cyclists.

     

Relative role of low- and high pressure reflexes on sympathetic activity in humans during simulated gravitational stress

In order to determine the relative role of low- and high-pressure reflexes, respectively, on forearm sympathetic nerve activity (fSNA), 10 normal male subjects underwent a 4-step (5 min each) graded lower body negative pressure (LBNP) from -10 to -50 mmHg. Central venous pressure (CVP) and stroke volume gradually decreased (p<0.05), and arterial pulse pressure (PP) abruptly decreased at LBNP of -50 mmHg. Mean arterial pressure (MAP) remained unchanged. Forearm venous plasma norepinephrine concentration (fvNE) increased significantly at LBNP of -35 mmHg (p<0.05) and with a further sharp increase during LBNP of -50 mmHg (p<0.05). High degrees of intra-individual correlations were observed between changes in Log [fvNE] and CVP (r-values from -0.78 to -0.96, p<0.01). We conclude that low-pressure reflexes are the major determinants of fSNA during non-hypotensive gravitational stress (MAP and PP unchanged). When the gravitational stress is more pronounced, a decrease in PP further augments fSNA through inhibition of high-pressure arterial baroreflexes.     

Predicting chlorophyll vertical distribution in response to epilimnetic nutrient enrichment in small stratified lakes

Light-limited metalimnetic phytoplankton communities are thoughtto be negatively impacted by epilimnetic nutrient enrichmentbecause of shading by increased epilimnetic phytoplankton biomass.We tested this expectation with a dynamic simulation model thatwas calibrated to three lakes undergoing whole-lake nutrientand food web manipulations. Total areal chlorophyll increaseddue to nutrient enrichment in each lake, but the magnitude ofthe response varied between lakes. Modeling experiments, whichallowed analysis of separate components of each lake's responseto nutrient enrichment, indicated that the response to enrichmentdepended on lake water color and food web structure. In weaklystained lakes ({small tilde}10 mg Pt 1^–1, k₄ = 0.4 m^–1),metalimnetic chlorophyll was stimulated by nutrient enrichmentup to moderate levels (1 µg Pt1^–1 day^–1).In more strongly colored lakes (25 mg Pt 1^–1, k₄ = 1.0),metalimnetic chlorophyll responded negatively to nutrient enrichmentat all P loading rates. Food web structure, as expressed byrates of zooplanktivory, interacted with water color in twoways. One impact was through direct grazing losses on metalimneticchlorophyll. The other process involved was indirect impactfrom grazing on epilimnetic phytoplankton, which reduced shadingon metalimnetic chlorophyll. Vertical redistribution of chlorophyllbetween the epilimnion and the metalimnion led to little accumulationof areal chlorophyll with increased P loading over limited rangesof water color and nutrient input rates. Model predictions maybe most effectively tested with whole-lake experiments contrastingfood web structure, water color and nutrient loading.     

Scanning electron microscope observations on the Telotylenchinae Siddiqi, 1960 (Nematoda: Belonolaimidae)

Two species of the genus Trichotylenchus from the semi-arid region of West Africa, T. falciformis, type-species, and T. palustris, previously belonging to the genus Uliginotylenchus, were studied under the scanning electron microscope. Eight characters are common to both species: (i) head continuous with body contour; (ii) four to six cephalic annules present; (iii) first cephalic annule ovoid, laterally elongate and fused with the second cephalic annule at the level of the amphid; (iv) lateral cephalic sectors absent; (v) submedian cephalic sectors dorsally and ventrally fused; (vi) amphidial apertures elongate, ovoid and with longer axis obliquely dorso-ventrally directed; (vii) lateral fields areolated with three incisures; and (viii) spicules with an indentation or a small trapezoidal process on the dorsal side and a short rounded process on the lateral side, both being close to the distal extremity. The synonymy of Uliginotylenchus and Trichotylenchus is confirmed. The definition of Trichotylenchus is amended.     

Experimental Oesophagostomum dentatum infection in the pig: Worm populations resulting from single infections with three doses of larvae

This report describes the effect of different dose levels of infection upon worm burdens and development and fecundity of the parasites. Three groups each of 40, 9-week-old, helminth naïve pigs were inoculated once with either 2000 (group A), 20,000 (group B), or 200,000 (group C) infective third stage larvae of Oesophagostomum dentatum. Subgroups of 5 pigs from each major group were killed 3, 6, 11, 14, 18, 25, 34 and 47 days post inoculation (p.i.) and the large intestinal worm burdens were determined. Faecal egg counts were determined at frequent intervals after day 13 p.i. There were no overt clinical signs of gastrointestinal helminthosis during the experiment. Faecal egg counts became positive in groups A and B at around day 19 p.i., whereas most pigs in the high dose group C did not have positive egg counts until day 27–33 p.i. and some pigs remained with zero egg counts until the end of the study. Throughout the experiment the worm populations in group C consisted mainly of immature larval stages, while those in groups A and B were predominantly adult stages after days 14–18. Adult worms from the low dose group A were significantly longer than those from group C. At high population densities, stunted development of worms and reduced fecundity among female worms were found. Furthermore, there was a tendency for the distribution of the worms within the intestine to be altered with increasing population size.     

Restriction Fragment Length Polymorphism Mapping of Quantitative Trait Loci for Malaria Parasite Susceptibility in the Mosquito Aedes Aegypti

Susceptibility of the mosquito Aedes aegypti to the malarial parasite Plasmodium gallinaceum was investigated as a quantitative trait using restriction fragment length polymorphisms (RFLP). Two F(2) populations of mosquitoes were independently prepared from pairwise matings between a highly susceptible and a refractory strain of A. aegypti. RFLP were tested for association with oocyst development on the mosquito midgut. Two putative quantitative trait loci (QTL) were identified that significantly affect susceptibility. One QTL, pgs[2,LF98], is located on chromosome 2 and accounted for 65 and 49% of the observed phenotypic variance in the two populations, respectively. A second QTL, pgs[3,MalI], is located on chromosome 3 and accounted for 14 and 10% of the observed phenotypic variance in the two populations, respectively. Both QTL exhibit a partial dominance effect on susceptibility, wherein the dominance effect is derived from the refractory parent. No indication of epistasis between these QTL was detected. Evidence suggests that either a tightly linked cluster of independent genes or a single locus affecting susceptibility to various mosquito-borne parasites and pathogens has evolved near the LF98 locus; in addition to P. gallinaceum susceptibility, this general genome region has previously been implicated in susceptibility to the filarial nematode Brugia malayi and the yellow fever virus.     

The Triplo-Lethal Locus of Drosophila: Reexamination of Mutants and Discovery of a Second-Site Suppressor

In the genome of Drosophila melanogaster there is a single locus, Triplo-lethal (Tpl), that causes lethality when present in either one or three copies in an otherwise diploid animal. Previous attempts to mutagenize Tpl produced alleles that were viable over a chromosome bearing a duplication of Tpl, but were not lethal in combination with a wild-type chromosome, as deficiencies for Tpl are. These mutations were interpreted as hypomorphic alleles of Tpl. In this work, we show that these alleles are not mutations at Tpl; rather, they are dominant mutations in a tightly linked, but cytologically distant, locus that we have named Suppressor-of-Tpl (Su(Tpl)). Su(Tpl) mutations suppress the lethality associated with three copies of the Triplo-lethal locus and are recessive lethal. We have mapped Su(Tpl) to the approximate map position 3-46.5, within the cytological region 76B-76D.     

Change in social status and risk of low birth weight in Denmark: population based cohort study.

OBJECTIVE: To estimate the risk of having a low birthweight infant associated with changes in social, environmental, and genetic factors. DESIGN: Population based, historical cohort study using the Danish medical birth registry and Statistic Denmark''s fertility database. SUBJECTS: All women who had a low birthweight infant (< 2500 g) (index birth) and a subsequent liveborn infant (outcome birth) in Denmark between 1980 and 1992 (exposed cohort, n = 11,069) and a random sample of the population who gave birth to an infant weighing > or = 2500 g and to a subsequent liveborn infant (unexposed cohort, n = 10,211). MAIN OUTCOME MEASURES: Risk of having a low birthweight infant in the outcome birth as a function of changes in male partner, area of residence, type of job, and social status between the two births. RESULTS: Women in the exposed cohort showed a high risk (18.5%) of having a subsequent low birthweight infant while women in the unexposed cohort had a risk of 2.8%. After adjustment for initial social status, a decline in social status increased the absolute risk of having a low birthweight infant by about 5% in both cohorts, though this was significant only in the unexposed cohort. Change of male partner did not modify the risk of low birth weight in either cohort. CONCLUSION: Having had a low birthweight infant and a decline in social status are strong risk factors for having a low birthweight infant subsequently.