No abstract

This study was designed to investigate the effect of exercise intensity on cardiorespiratory fitness and coronary heart disease risk factors. Maximum oxygen consumption (Vo(2 max)), lipid, lipoprotein, and fibrinogen concentrations were measured in 64 previously sedentary men before random allocation to a nonexercise control group, a moderate-intensity exercise group (three 400-kcal sessions per week at 60% of Vo(2 max)), or a high-intensity exercise group (three 400-kcal sessions per week at 80% of Vo(2 max)). Subjects were instructed to maintain their normal dietary habits, and training heart rates were represcribed after monthly fitness tests. Forty-two men finished the study. After 24 wk, Vo(2 max) increased by 0.38 +/- 0.14 l/min in the moderate-intensity group and by 0.55 +/- 0.27 l/min in the high-intensity group. Repeated-measures analysis of variance identified a significant interaction between monthly Vo(2 max) score and exercise group (F = 3.37, P < 0.05), indicating that Vo(2 max) responded differently to moderate- and high-intensity exercise. Trend analysis showed that total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and fibrinogen concentrations changed favorably across control, moderate-intensity, and high-intensity groups. However, significant changes in total cholesterol (-0.55 +/- 0.81 mmol/l), low-density lipoprotein cholesterol (-0.52 +/- 0.80 mmol/l), and non-high-density lipoprotein cholesterol (-0.54 +/- 0.86 mmol/l) were only observed in the high-intensity group (all P < 0.05 vs. controls). These data suggest that high-intensity training is more effective in improving cardiorespiratory fitness than moderate-intensity training of equal energy cost. These data also suggest that changes in coronary heart disease risk factors are influenced by exercise intensity.

No abstract

The activity of G protein-coupled receptors is regulated via hyperphosphorylation following agonist stimulation. Despite the universal nature of this regulatory process, the physiological impact of receptor phosphorylation remains poorly studied. To address this question, we have generated a knock-in mouse strain that expresses a phosphorylation-deficient mutant of the M 3 -muscarinic receptor, a prototypical G q/11 -coupled receptor. This mutant mouse strain was used here to investigate the role of M 3 -muscarinic receptor phosphorylation in the regulation of insulin secretion from pancreatic islets. Importantly, the phosphorylation deficient receptor coupled to G q/11 -signaling pathways but was uncoupled from phosphorylation-dependent processes, such as receptor internalization and β-arrestin recruitment. The knock-in mice showed impaired glucose tolerance and insulin secretion, indicating that M 3 -muscarinic receptors expressed on pancreatic islets regulate glucose homeostasis via receptor phosphorylation-/arrestin-dependent signaling. The mechanism centers on the activation of protein kinase D1, which operates downstream of the recruitment of β-arrestin to the phosphorylated M 3 -muscarinic receptor. In conclusion, our findings support the unique concept that M 3 -muscarinic receptor-mediated augmentation of sustained insulin release is largely independent of G protein-coupling but involves phosphorylation-/ arrestin-dependent coupling of the receptor to protein kinase D1. G-protein coupled receptor | ligand biasT he vast majority of G protein-coupled receptors (GPCRs) respond to agonist occupation by becoming rapidly hyperphosphorylated within intracellular domains (1-3). This process not only leads to the uncoupling of the receptor from its cognate G proteins, but also allows for the activation of G proteinindependent signaling, a process that is driven largely by the recruitment of β-arrestin adaptor proteins (4-7). As a consequence, GPCRs regulate an extensive array of signaling pathways and biological responses (3). G protein-independent signaling pathways have mostly been studied in recombinant systems. However, the current challenge is to understand to what extent these processes are involved in the regulation of key physiological responses.In the present study, we examined the in vivo role of GPCR phosphorylation by generating a knock-in mouse strain expressing a phosphorylation-deficient GPCR. Specifically, we used the M 3 -muscarinic acetylcholine receptor, a prototypic G q/11 -coupled GPCR, as a model system (8, 9). We and others have previously demonstrated that the M 3 -muscarinic receptor is rapidly phosphorylated on agonist occupation by a range of protein kinases that include members of the GPCR kinase (GRK) family, as well as casein kinase 1α and protein kinase CK2 (10-13). To define the potential physiological role of M 3 -muscarinic receptor phosphorylation, we generated a mouse strain where the wild-type M 3 -muscarinic receptor gene had been replaced by a phosphorylationdeficient mutan...

No abstract

Fifty-six subjects (19 men and 37 woman) aged between 40 and 66 completed the study. They were allocated into three walking groups and a control group (C). The three walking groups performed the same total amount of walking for 18 weeks, but completed it in bouts of differing durations and frequencies. These were Long Walkers (LW; 20-40 min/bout), Intermediate Walkers (IW; 10-15 min/bout) and Short Walkers (SW; 5-10 min/bout); with the IW and SW performing more than one bout of walking a day. Following the 18 week walking programme, compared to the C group all walking groups showed similar improvements in fitness as determined by a reduction in blood lactate during a graded treadmill walking test (LW 1.0 mmol/l; IW 0. 8 mmol/l; SW 1.2 mmol/l; C 0.2 mmol/l; P = 0.003) and reduction in final heart rate (LW 8 beats/min; IW 6 beats/min; SW 10 beats/min; C 0 beats/min; P = 0.056). Also compared to the C group, the LW and IW groups recorded statistically significant decreases in low-density lipoprotein cholesterol (LW 0.29 mmol/l; IW 0.41 mmol/l; P = 0.024), whereas the control group showed a mean increase of 0.22 mmol/l. The LW and IW groups also showed significant reductions in apolipoprotein (apo) A-II (LW 0.05 g/l; IW 0.02 g/l; SW 0.01 g/l; C 0.00 g/l; P = 0.012) with the LW recording a statistically significant increase in the ratio of apo A-I/A-II (LW, 0.19, P = 0. 044). In conclusion, some health benefits were achieved from all walking programmes. However, whilst the changes in aerobic fitness were similar, the effects upon blood lipid profiles were not. The findings from this study suggest that the LW regimen was most effective in benefiting blood lipid profile, followed by the IW regimen, with the SW being least potent. Nevertheless, for the sedentary/low-active members of society, any improvement in health may be considered as important. Therefore accumulated bouts of moderate intensity exercise, which according to theories of exercise behaviour may be more easily incorporated into an individual's lifestyle than single prolonged bouts, may be advocated for health promotion but may not be as effective as the traditionally prescribed 20-40 min bouts.

1987). Growth and carcass characteristics of crossbred lambs by ten sire breeds, compared at the same estimated carcass subcutaneous fat proportion. Animal Production, 44, pp 83-98 ABSTRACT An evaluation was carried out over a 5-year period in 10 commercial flocks of Scottish Blackface, Scottish Half-bred and Mule ewes to evaluate 10 sire breeds: Border Leicester, Dorset Down, Hampshire Down, He de France, North Country Cheviot, Oxford Down, Southdown, Suffolk, Texel and Wensleydale. An average of 43 sires was used per sire breed.The analysis involved a total of 3360 lambs of which one-third had the left side dissected. Sire breeds were compared when their progeny were slaughtered at the same estimated carcass subcutaneous fat proportion (approx. 120 g/kg).Carcass weights were related to the adult body size of the sire breeds with a range of 4 kg between Southdown and Wensleydale crosses. Crosses by the conventional meat sire breeds tended to have higher daily carcass-weight and lean-tissue gains than those by Border Leicester and Wensleydale sires. Texel and Suffolk crosses did not differ significantly in carcass weight, daily carcass-weight gain, daily lean gain or age at slaughter (P > 0-05).Significant sire-breed x dam-breed interactions were recorded for daily carcass-weight gain and daily lean gain (P < 0-05). Dorset Down and Southdown crosses tended to grow relatively faster when from Mule dams; Texel crosses grew relatively faster when from Blackface dams.There was relatively little difference between sire breeds in visually assessed carcass conformation; all the means were within two points on a 15-point scale. Texel crosses had a higher carcass lean proportion than other crosses: their advantage over Suffolk crosses was 22 g/kg.

Summary We have developed a whole blood thrombin generation (TG) assay whereby TG is initiated with a low‐tissue factor concentration and monitored using a fluorogenic thrombin substrate. Significantly higher values were found in blood samples from 50 patients with a history of venous thromboembolism (VTE) compared with 31 healthy controls (HC), for peak height (P = 0·0034) and endogenous thrombin potential (ETP) (P = 0·0027). Results from 31 VTE patients and the 31 controls in the absence of corn trypsin inhibitor (CTI) showed significantly higher values in the VTE group for peak height (P = 0·0013) and ETP (P = 0·002). In the presence of CTI, significantly higher values were only seen in ETP (P = 0·024). No significant increases in TG were found using platelet poor (PPP) or ‐rich (PRP) plasma with or without CTI. The whole blood TG assay in the absence or presence of CTI showed a higher proportion (25/50 and 12/31, respectively) of raised peak height and/or ETP values than plasma assays (PPP 9/50 and 5/31 respectively and PRP 13/50 and 6/31, respectively). Our results show the whole blood TG assay is more sensitive for determining the increases in TG in patients with a history of VTE than PPP and PRP TG assays.