Because S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) are the substrate and product of essential methyltransferase reactions; the ratio of SAM:SAH is frequently used as an indicator of cellular methylation potential. However, it is not clear from the ratio whether substrate insufficiency, product inhibition or both are required to negatively affect cellular methylation capacity. A combined genetic and dietary approach was used to modulate intracellular concentrations of SAM and SAH. Wild-type (WT) or heterozygous cystathionine beta-synthase (CBS +/-) mice consumed a control or methyl-deficient diet for 24 wk. The independent and combined effect of genotype and diet on SAM, SAH and the SAM:SAH ratio were assessed in liver, kidney, brain and testes and were correlated with relative changes in tissue-specific global DNA methylation. The combined results from the different tissues indicated that a decrease in SAM alone was not sufficient to affect DNA methylation in this model, whereas an increase in SAH, either alone or associated with a decrease in SAM, was most consistently associated with DNA hypomethylation. A decrease in SAM:SAH ratio was predictive of reduced methylation capacity only when associated with an increase in SAH; a decrease in the SAM:SAH ratio due to SAM depletion alone was not sufficient to affect DNA methylation in this model. Plasma homocysteine levels were positively correlated with intracellular SAH levels in all tissues except kidney. These results support the possibility that plasma SAH concentrations may provide a sensitive biomarker for cellular methylation status.
Although the forces required to support the body mass are not elevated when moving up an incline, kinematic studies, in vivo tendon and bone studies and kinetic studies suggest there is a shift in forces from the fore-to the hindlimbs in quadrupeds. However, there are no wholeanimal kinetic measurements of incline locomotion. Based on previous related research, we hypothesized that there would be a shift in forces to the hindlimb. The present study measured the force produced by the fore-and hindlimbs of horses while trotting over a range of speeds (2.5 to 5·m·s -1 ) on both level and up an inclined (10%) surface.On the level, forelimb peak forces increased with trotting speed, but hindlimb peak force remained constant. On the incline, both fore-and hindlimb peak forces increased with speed, but the sum of the peak forces was lower than on the level. On the level, over the range of speeds tested, total force was consistently distributed between the limbs as 57% forelimb and 43% hindlimb, similar to the weight distribution of the horses during static weight tests. On the incline, the force distribution during locomotion shifted to 52% forelimb and 48% hindlimb.Time of contact and duty factor decreased with speed for both limbs. Time of contact was longer for the forelimb than the hindlimb, a finding not previously reported for quadrupeds. Time of contact of both limbs tended to be longer when traveling up the incline than on the level, but duty factor for both limbs was similar under both conditions. Duty factor decreased slightly with increased speed for the hindlimb on the level, and the corresponding small, predicted increase in peak vertical force could not be detected statistically.
A common genetic variant in the methylenetetrahydrofolate reductase (MTHFR) gene involving a cytosine to thymidine (C-->T) transition at nucleotide 677 is associated with reduced enzyme activity, altered folate status and potentially higher folate requirements. The objectives of this study were to investigate the effect of the MTHFR 677 T allele on folate status variables in Mexican women (n = 43; 18-45 y) and to assess the adequacy of the 1998 folate U.S. Recommended Dietary Allowance (RDA), 400 micro g/d as dietary folate equivalents (DFE). Subjects (14 CC, 12 CT, 17 TT genotypes) consumed a low folate diet (135 micro g/d DFE) for 7 wk followed by repletion with 400 micro g/d DFE (7 CC, 6 CT, 9 TT) or 800 micro g/d DFE (7 CC, 6 CT, 8 TT) for 7 wk. Throughout repletion with 400 micro g/d DFE, the TT genotype had lower (P = 0.05) serum folate and higher (P = 0.05) plasma total homocysteine (tHcy) concentrations than the CC genotype. CT heterozygotes did not differ (P > 0.05) in their response relative to the CC genotype. Throughout repletion with 800 micro g/d DFE, the CT genotype had lower (P = 0.05) serum folate concentrations and excreted less (P = 0.05) urinary folate than the CC genotype. However, there were no differences (P > 0.05) in the measured variables between the TT and CC genotypes. Repletion with 400 micro g/d DFE led to normal blood folate and desirable plasma tHcy concentrations, regardless of MTHFR C677T genotype. Collectively, these data demonstrate that the MTHFR C-->T variant modulates folate status response to controlled folate intakes and support the adequacy of the 1998 folate U.S. RDA for all three MTHFR C677T genotypes.
SUMMARY The net work of the limbs during constant speed over level ground should be zero. However, the partitioning of negative and positive work between the fore- and hindlimbs of a quadruped is not likely to be equal because the forelimb produces a net braking force while the hindlimb produces a net propulsive force. It was hypothesized that the forelimb would do net negative work while the hindlimb did net positive work during trotting in the horse. Because vertical and horizontal impulses remain unchanged across speeds it was hypothesized that net work of both limbs would be independent of speed. Additionally because the major mass of limb musculature is located proximally,it was hypothesized that proximal joints would do more work than distal joints. Kinetic and kinematic analysis were combined using inverse dynamics to calculate work and power for each joint of horses trotting at between 2.5 and 5.0 m s–1. Work done by the hindlimb was indeed positive (consistently 0.34 J kg–1 across all speeds), but, contrary to our hypothesis, net work by the forelimb was essentially zero (but also independent of trotting speed). The zero net work of the forelimb may be the consequence of our not being able to account, experimentally, for the negative work done by the extrinsic muscles connecting the scapula and the thorax. The distal three joints of both limbs behaved elastically with a period of energy absorption followed by energy return. Proximal forelimb joints (elbow and shoulder) did no net work, because there was very little movement of the elbow and shoulder during the portion of stance when an extensor moment was greatest. Of the two proximal hindlimb joints, the hip did positive work during the stride,generating energy almost throughout stance. The knee did some work, but like the forelimb proximal joints, had little movement during the middle of stance when the flexion moment was the greatest, probably serving to allow the efficient transmission of energy from the hip musculature to the ground.
One of the most obvious locomotory behaviors is gait transition (changing from walk to trot/run and changing from trot to gallop). There have been numerous attempts to explain gait transitions. These include considerations of muscle function (Taylor, 1978(Taylor, , 1985 and bone strain (Biewener and Taylor, 1986;Rubin and Lanyon, 1982), theoretical explanations based on mathematical models (Alexander, 1989;Alexander and Jayes, 1983), psychological factors (Diedrich and Warren, 1995) and engineering models (Schoner et al., 1990;Vilensky et al., 1991).The walk-trot and trot-gallop gait transitions were originally explained on the basis of metabolic economy (Hoyt and Taylor, 1981). In ponies (Equus caballus), metabolism increased curvilinearly for walking and trotting, and the gait transitions occurred at the speeds where the metabolism curves intersected. This is referred to as the 'energetically optimal transition speed' (EOTS; Hreljac, 1993) because, when the animals extended their gaits beyond the normal transition speeds, the metabolic rate was higher in the extended gait than in the normal gait. Hoyt and Taylor concluded that ponies changed gaits to minimize energetic costs. However, one limitation of this study was that gait transition speeds were not rigorously determined.Subsequently, this explanation was challenged by the 'force trigger' hypothesis. Farley and Taylor (1991) showed that the transition from trotting to galloping in ponies is correlated with musculoskeletal forces by demonstrating that the transition occurs at a slower speed when a pony carries a load. Measurements of oxygen consumption (again observed to be a curvilinear function of speed) indicated that the ponies were making the transition to a gallop at speeds where it is energetically more expensive to gallop than to trot -at speeds slower than the EOTS. In some studies, the walk-run transition in humans occurs at the EOTS (Mercier et al., 1994;Diedrich and Warren, 1995) and in others it does not (Hreljac, 1993; Minetti et al., 1994a,b). Hreljac (1993) ruled out muscle stress as the trigger for the walk-run transition in humans and suggested that the trigger is kinematic (Hreljac, 1995).In a study of horses and preferred speed , the energetics of trotting were measured on the level and up a 10% incline. In the preliminary portion of this study, we determined the speeds at which the horses would trot. We noted that, when trotting up an incline, the horses made the transition to a gallop at a slower speed than they would when on the level. Because forces are not expected to be higher when Two studies have focused on potential triggers for the trot-gallop transition in the horse. One study concluded that the transition was triggered by metabolic economy. The second study found that it was not metabolic factors but, rather, peak musculoskeletal forces that determine gait transition speeds. In theory, peak musculoskeletal forces should be the same when trotting up an incline as when trotting at the same speed on the level. Assuming this is ...
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