The synthesis and SAR of a series of benzothiophene piperazine and piperidine urea FAAH inhibitors is described.
The synthesis and structure–activity relationships (SAR) of a series of benzothiophene ...piperazine and piperidine urea FAAH inhibitors is described. These compounds inhibit FAAH by covalently modifying the enzyme’s active site serine nucleophile. Activity-based protein profiling (ABPP) revealed that these urea inhibitors were completely selective for FAAH relative to other mammalian serine hydrolases. Several compounds showed in vivo activity in a rat complete Freund’s adjuvant (CFA) model of inflammatory pain.
Studies of the Serengeti ecosystem and the Yellowstone ecosystem show many common ecological properties of grazing ecosystems. The grazing ecosystem is among the Earth's most endangered terrestrial ...habitats.
Despite high volumes of manure production in the Shenandoah Valley of Virginia, there are still areas of forage production that are nutrient deficient because manures have traditionally been applied ...to higher-value row crops. This study was conducted to compare the effects of poultry litter and inorganic fertilizers on soil fertility and forage production. Two sites had the same treatments applied for two consecutive years: (1) split application of litter (half in spring and half in summer); (2) inorganic fertilizer at the same N, P, and K rates as Treatment 1; (3) single spring application of litter; (4) inorganic fertilizer at the same N, P, and K rates as Treatment 3; and (5) unfertilized control. Forage yield, soil pH, Mehlich 1 phosphorus (M1P), P uptake, and water-soluble phosphorus (WSP) were measured during this experiment. On average, soil pH was 0.2 higher for litter than inorganic fertilizer treatments, but this difference wasn't significant. The M1P and WSP both increased throughout the 2 yr, but no significant differences were found among split and single application or litter and inorganic fertilizers. Fertilization increased yield 3.5 Mg ha–1 on average, and application timing and fertilizer types produced similar yields. The P balance revealed that, when using N-based applications, neither site removed adequate P from forage yield to prevent environmental concerns. Our data showed that poultry litter was comparable with inorganic fertilizer in terms of increasing soil WSP, M1P, and forage yield, and the timing of application made no difference.
Increasing species richness of temperate pastures beyond one or two forage species could improve grazing system productivity. An experiment in western Illinois, USA, was initiated in August 2001 to ...test this idea. The main study objective was to determine how pastures sown with increasing levels of species richness would affect herbage yield and cow‐calf performance. Three seed mixtures that contained three, five, or eight forage species were sown into 3‐ to 6‐ha pastures. Mixtures were replicated three times and rotationally stocked with beef cow–calf groups. Herbage mass and accumulation were estimated by a rising plate meter method and weight gain evaluated cow–calf performance. We also evaluated forage nutritive value indices and changes in forage species composition. After pasture establishment in 2001, herbage mass was marginally higher (P = 0.15) in eight‐species mixtures (98 g m−2) compared with three‐species mixes (43 g m−2). Once grazing started, pasture mix had no effect on herbage responses or stocking rate (P > 0.05). Cow–calf performance was also unaffected by pasture mix, although average daily gain (ADG) was higher in 2003 (P < 0.05). Cow and calf ADG averaged 0.33 and 1.17 kg d−1, respectively, in 2003 compared with 0.05 and 1.01 kg d−1 in other years. Overall, species richness in pastures had minimal effects on forage yield and cattle performance. Grazing management (e.g., stocking rate) and climatic conditions more strongly influence grazing system productivity.
Plant species composition of most managed pasture lands tends to be dominated by one or two species, usually a perennial grass and a legume. Recent ecological research suggests that increasing this ...forage diversity could increase pasture productivity and stability. We conducted a 4-yr field experiment to determine whether increasing the diversity of pasture mixtures would increase yields and improve interannual yield stability. Mixtures of cool-season pasture plants ranging from one to 15 species were planted into 2.25-m2 plots in May 1998. Interannual yield variation and yield responses to mowing frequency (2- vs. 4-wk frequency) were used to evaluate stability. Forage yields averaged <400 g m-2 yr-1 in mixtures having one or two species, while mixtures with three or more species averaged >1000 g m-2 yr-1. Increasing the diversity of mixtures beyond three sown species did not consistently improve yields. Interannual yield variation was lowest in the one- and two-species mixtures, and showed no consistent relationship with increasing species diversity. The number of species planted in each mixture declined by approximately 30% from 1999 to 2001, with the mixtures becoming dominated by perennial grasses. Although limitations in our experimental design prevent us from making strong conclusions about relationships between forage diversity and pasture productivity, our findings suggest that increased forage yield and stability may be best achieved by planting two or three forage species that are well matched to specific environmental conditions rather than planting a random assemblage of forage species in a complex mixture.
Increasing plant species diversity could enhance forage yield, resistance to weed invasion, and soil C accumulation in grazed pastures. Three forage mixtures (2, 3, or 11 species) were established on ...a farm in eastern Pennsylvania and grazed by dairy heifers or managed under a three-cut hay system from 1999 to 2002. Net canopy photosynthesis was measured from early April to early October 2000 to 2002. Root distribution to a depth of 60 cm was measured in mid-September each year, and soil C and N concentrations to a 15-cm depth were determined in May 1999 and September 2002. The 11-species mixture yielded 43% more forage dry matter than the two-species mixture. This difference was mainly due to the inclusion of a few highly productive forage species in the 11-species mixture. Canopy photosynthesis did not differ among mixtures in the spring, but in the summer was 50% greater in the 3- and 11-species mixtures than the two-species mixture. The 11-species mixture also had 30 to 62% greater root biomass than the other two mixtures and a greater proportion of roots in deeper soil layers. Soil C either remained unchanged or decreased, depending on species composition, with the greatest decrease occurring in the 11-species mixture. No relationship existed between changes in soil C concentration and either canopy photosynthesis or above- and belowground productivity. Deeper rooting could reduce drought stress by increasing access to deep soil moisture. Selecting forage mixtures to include specific desirable traits, such as greater rooting depth, could result in improved pasture performance.
The length of time and form in which disturbances persist in systems depends on the intensity and frequency of disturbance and on the abilities of resident species to recover from such events. In ...grazed grasslands, trampling by large mammalian herbivores can periodically facilitate weed establishment by exposing patches of bare ground but whether an intense soil disturbance event results in a temporary increase in weed abundance or a persistent weed problem remains unclear. In May 2002, cattle trampling following heavy rain caused severe damage to nine-month old, rotationally grazed, cool-season pastures (Midwest USA). In September 2002, we compared the aboveground composition of paddocks (i. e., fenced pasture sections) that were heavily disturbed to those that received no damage. Relative to undisturbed paddocks, forage species relative cover was 17% lower in disturbed paddocks, and weed species and bare ground relative cover was 61% and 100% higher, respectively. By September 2004, paddock types did not differ in all above- ground community components. However, the abundance and species richness of weed seeds in the soil seed bank averaged respectively 82% and 30% higher in disturbed paddocks between 2003 and 2004. These findings indicate that a spatially extensive, intense soil disturbance event may soon become undetectable in components of aboveground pasture structure but can persist as an augmented weed seed bank. Because of high weed seed bank longevity, disturbances to formerly disturbed pastures would likely result in higher weed recruitment, with more species represented, than in those which lack previous disturbance. Disturbance history may thus be a useful predictor of weed community composition following subsequent disturbance. Based on empirical data supporting this proposition, we recommend that grassland managers explicitly incorporate disturbance history into dynamic management planning and do not rely exclusively on aboveground characters to evaluate the invasion status or colonization potential of an area by undesirable plants. We emphasize that the ecological legacies of past soil disturbance events cannot only influence the contemporary patterns and processes of grasslands, but importantly, affect their compositional trajectories following subsequent perturbation.
Physical exercise aids glycemic control and the prevention of diabetes-related complications. However, exercise beyond an individual's pulmonary functional capacity may be detrimental. To date, ...little is known about the relationship between pulmonary function and exercise capacity in people with type 2 diabetes (T2D). We investigated the relationship between pulmonary function and exercise capacity in T2D.
Spirometry and 6-min walk test (6MWT) were conducted for 263 systematically sampled adults with T2D without primary heart/lung disease. The primary measure of exercise capacity was the 6-min walk distance (6MWD); impaired exercise capacity was defined as 6MWD<400 m. Logistic regression analyses were used to assess the associations between spirometric measures and exercise capacity with adjustments for age, sex, height, body mass index, diabetes duration, glycated hemoglobin concentration, smoking, suboptimum blood pressure control, and total cholesterol concentration.
Compared with individuals with normal spirometry, those with pulmonary restriction/obstruction had significantly lower 6MWD (404.67 m vs. 451.70),p < 0.001). The proportion of individuals with impaired exercise capacity was higher in individuals with impaired pulmonary function compared with those with normal pulmonary function (39.8% vs. 20.7%,p = 0.001). In the unadjusted models, decreasing Z-score FEV1 odds ratio 1.40, 95% confidence interval (1.07–1.83),p = 0.013 and Z-score FVC 1.37 (1.06–1.76),0.016, but not Z-score FEV1/FVC ratio 1.00 (0.78–1.27),0.972 were significantly associated with impaired exercise capacity. In the fully adjusted model, the strength of association remained statistically significant for Z-score FEV1 1.60 (1.06–2.41),0.025 but not Z-score FVC 1.48 (0.98–2.23),0.065.
Our study shows inverse associations between FEV1 and impaired exercise capacity in T2D, Future research could characterize optimal exercise levels based on a patient's FEV1.
•Impaired exercise capacity was commoner in patients with type 2 diabetes with lung dysfunction than without lung dysfunction.•Lower forced expiratory volume in 1 s was positively associated with impaired exercise capacity.•The conventional cardiovascular and respiratory risk factors did not explain the observed associations.
•In West Africans with T2D, neuropathy was the commonest microvascular complication.•Hypertension was independently associated with neuropathy and nephropathy in T2D.•Increasing systolic BP was ...independently associated with nephropathy in T2D.•Increasing diastolic BP was independently associated with nephropathy in T2D.•Systolic/diastolic BP was not independently associated with neuropathy/retinopathy.
In type 2 diabetes mellitus (T2D), cardiovascular risk factors including glycemic control differentially affect various microcirculatory beds. To date, studies comparing the impact of blood pressure (BP) on various microvascular beds in T2D are limited. We assessed the associations of BP and its control with neural, renal, and retinal microvascular dysfunction.
This was a cross-sectional study among 403 adults with T2D. Microvascular dysfunction was based on nephropathy (albumin-creatinine ratio ≥ 30 mg/g), neuropathy (vibration perception threshold ≥ 25 V and/or Diabetic Neuropathy Symptom score > 1), and retinopathy (based on retinal photography). Logistic regression was used to examine the associations of hypertension, systolic BP, and diastolic BP with microvascular dysfunction with adjustments for age, sex, diabetes duration, smoking pack years, HbA1c concentration, total cholesterol concentration, and BMI.
The mean age (± SD), proportion of females, and proportion of hypertensives were 56.35 (± 9.91) years, 75.7%, and 49.1%, respectively. In a fully adjusted model, hypertension was significantly associated with neuropathy odds ratio 3.44, 95% confidence interval 1.96–6.04, P < 0.001 and nephropathy 2.05 (1.09–3.85), 0.026 but not for retinopathy 0.98 (0.42–2.31), 0.970. Increasing Z-score systolic BP was significantly associated with nephropathy 1.43 (1.05–1.97), 0.025 but not for neuropathy 1.28 (0.98–1.67), 0.075 or retinopathy 1.27 (0.84–1.91), 0.261. Increasing Z-score diastolic BP was significantly associated with nephropathy 1.81 (1.32 – 2.49), < 0.001 but not retinopathy 1.38 (0.92–2.05), 0.120 or neuropathy 0.86 (0.67–1.10), 0.230.
Our study shows varying strengths of associations of hypertension, systolic BP, and diastolic BP with microvascular dysfunction in different microcirculatory beds. Hypertension prevention and/or control may be valuable in the prevention/treatment of microvascular disease, especially nephropathy, and neuropathy.
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