Methyl jasmonate, salicylic acid, and oxalic acid affects growth, inducible defenses, and pine weevil resistance in Norway spruce.

The large pine weevil (Hylobius abietis) is a major regeneration pest in commercial forestry. Pesticide application has historically been the preferred control method, but pesticides are now being phased out in several countries for environmental reasons. There is, thus, a need for alternative plant protection strategies. We applied methyl jasmonate (MeJA), salicylic acid (SA) or oxalic acid (OxA) on the stem of 2-year-old Norway spruce (Picea abies) plants to determine effects on inducible defenses and plant growth. Anatomical examination of stem cross-sections 9 weeks after application of 100 mM MeJA revealed massive formation of traumatic resin ducts and greatly reduced sapwood growth. Application of high concentrations of SA or OxA (500 and 200 mM, respectively) induced much weaker physiological responses than 100 mM MeJA. All three treatments reduced plant height growth significantly, but the reduction was larger for MeJA (~55%) than for SA and OxA (34-35%). Lower MeJA concentrations (5-50 mM) induced comparable traumatic resin duct formation as the high MeJA concentration but caused moderate (and non-significant) reductions in plant growth. Two-year-old spruce plants treated with 100 mM MeJA showed reduced mortality after exposure to pine weevils in the field, and this enhanced resistance-effect was statistically significant for three years after treatment.

Utilizing X-ray fluorescence (XRF) method to evaluate the content of metal elements in soil and their effects on the total phenolic and flavonoid contents of some medicinal plants.

Soil factors, especially metal elements in the soil, play a significant role in forming and accumulating secondary metabolites, which determine the medicinal properties of medicinal herbs. In this study, the concentrations of some metal elements (K, Mn, Fe, Cu, Zn, and Cr) in Cam Mountain and Tinh Bien Town, An Giang Province, Vietnam, were determined using the XRF method. We simultaneously determined the total phenolic and flavonoid content of some medicinal herbs collected from the collected soil sample areas, thereby assessing the influence of these elements on the formation of secondary metabolites in medicinal plants. The results showed that K, Mn, and Cr were mainly concentrated in the topsoil and transition layers; Fe and Cu elements tended to concentrate in the transition layer and the subsoil when surveying the soil profile. K, Mn, Cu, and Cr concentrations were more focused in Tinh Bien area, while Fe and Zn had higher concentrations at Cam Mountain. Additionally, results from evaluating the relationship between the content of the elements in the soil and the content of two active compounds also showed the correlation regression model between Zn and flavonoid expression by level 4 at the 5% significance level. Thus, the nonlinear model is suitable for evaluating the relationship between the content of metal elements in the soil and the active compound in medicinal plants.

Combined sequence-based and genetic mapping analysis of complex traits in outbred rats.

Genetic mapping on fully sequenced individuals is transforming understanding of the relationship between molecular variation and variation in complex traits. Here we report a combined sequence and genetic mapping analysis in outbred rats that maps 355 quantitative trait loci for 122 phenotypes. We identify 35 causal genes involved in 31 phenotypes, implicating new genes in models of anxiety, heart disease and multiple sclerosis. The relationship between sequence and genetic variation is unexpectedly complex: at approximately 40% of quantitative trait loci, a single sequence variant cannot account for the phenotypic effect. Using comparable sequence and mapping data from mice, we show that the extent and spatial pattern of variation in inbred rats differ substantially from those of inbred mice and that the genetic variants in orthologous genes rarely contribute to the same phenotype in both species.

A randomized open-label trial with a crossover comparison of sexual self-confidence and other treatment outcomes following tadalafil once a day vs. tadalafil or sildenafil on-demand in men with erectile dysfunction.

AIM: To compare Sexual Self-Confidence and other treatment outcomes following 8 weeks of treatment with tadalafil 5 mg once a day (OaD) vs. tadalafil 20 mg or sildenafil 100 mg as needed (pro re nata [PRN]) in patients with erectile dysfunction (ED). METHODS: A randomized, open-label, crossover study in men ≥18 years of age with history of ED and satisfactory response to current oral phosphodiesterase 5 (PDE5) inhibitor PRN. Data were analyzed with a mixed effects model for crossover design. MAIN OUTCOME MEASURES: The primary outcome measure was the Sexual Self-Confidence domain of the Psychological and Interpersonal Relationship Scales (PAIRS) between tadalafil OaD and sildenafil PRN. SECONDARY OUTCOMES INCLUDED: Time Concerns and Spontaneity domains of PAIRS, and the Self-Esteem and Relationship (SEAR) scale. RESULTS: Men naive to tadalafil OaD were enrolled (N = 378), with 61-69% prior PDE5 inhibitor use. There were improvements in all PAIRS domains from baseline when comparing tadalafil OaD and PRN with sildenafil PRN (P < 0.001). The Sexual Self-Confidence domain improved from baseline and was 0.50 ± 0.78 following tadalafil OaD, 0.5 ± 0.72 for tadalafil PRN, and 0.39 ± 0.67 for sildenafil PRN. The difference in least-squares mean was 0.12 ± 0.04 (confidence interval [CI] = 0.04, 0.19; P = 0.001) between tadalafil OaD and sildenafil PRN and 0.01 ± 0.04 (CI = -0.06, 0.08; P = 0.872) between tadalafil OaD and tadalafil PRN. The Time Concerns domain score was lower with tadalafil OaD than tadalafil PRN (P < 0.001). There were no differences in SEAR scores between treatments. CONCLUSIONS: Tadalafil OaD and tadalafil PRN compared with sildenafil PRN demonstrated greater improvements in Sexual Self-Confidence, Time Concerns, and Spontaneity. There was no significant difference in Sexual Self-Confidence between tadalafil OaD and tadalafil PRN. Changes in SEAR, the erectile function domain of the International Index of Erectile Function, and the Erectile Dysfunction Inventory of Treatment Satisfaction scores from baseline to end point were similar.

Mitochondria-targeted antioxidant MitoQ10 improves endothelial function and attenuates cardiac hypertrophy.

Mitochondria are a major site of reactive oxygen species production, which may contribute to the development of cardiovascular disease. Protecting mitochondria from oxidative damage should be an effective therapeutic strategy; however, conventional antioxidants are ineffective, because they cannot penetrate the mitochondria. This study investigated the role of mitochondrial oxidative stress during development of hypertension in the stroke-prone spontaneously hypertensive rat, using the mitochondria-targeted antioxidant, MitoQ(10). Eight-week-old male stroke-prone spontaneously hypertensive rats were treated with MitoQ(10) (500 mumol/L; n=16), control compound decyltriphenylphosphonium (decylTPP; 500 mumol/L; n=8), or vehicle (n=9) in drinking water for 8 weeks. Systolic blood pressure was significantly reduced by approximately 25 mm Hg over the 8-week MitoQ(10) treatment period compared with decylTPP (F=5.94; P=0.029) or untreated controls (F=65.6; P=0.0001). MitoQ(10) treatment significantly improved thoracic aorta NO bioavailability (1.16+/-0.03 g/g; P=0.002, area under the curve) compared with both untreated controls (0.68+/-0.02 g/g) and decylTPP-treated rats (0.60+/-0.06 g/g). Cardiac hypertrophy was significantly reduced by MitoQ(10) treatment compared with untreated control and decylTPP treatment (MitoQ(10): 4.01+/-0.05 mg/g; control: 4.42+/-0.11 mg/g; and decylTPP: 4.40+/-0.09 mg/g; ANOVA P=0.002). Total MitoQ(10) content was measured in liver, heart, carotid artery, and kidney harvested from MitoQ(10)-treated rats by liquid chromatography-tandem mass spectrometry. All of the organs analyzed demonstrated detectable levels of MitoQ(10), with comparable accumulation in vascular and cardiac tissues. Administration of the mitochondria-targeted antioxidant MitoQ(10) protects against the development of hypertension, improves endothelial function, and reduces cardiac hypertrophy in young stroke-prone spontaneously hypertensive rats. MitoQ(10) provides a novel approach to attenuate mitochondrial-specific oxidative damage with the potential to become a new therapeutic intervention in human cardiovascular disease.

Arginase II knockout mouse displays a hypertensive phenotype despite a decreased vasoconstrictory profile.

Arginase upregulation is associated with aging and cardiovascular diseases. In this study we report on the cardiovascular phenotype of the arginase II knockout (KO) mouse. We demonstrate that vascular sensitivity and reactivity altered over time in these animals such that no influence on responses to vasoconstrictor activity was observed in 7-week-old KO mice, but dampened responses to norepinephrine and phenylephrine were observed by 10 and 15 weeks with Rho kinase influencing these effects in the 15-week-old animals. Despite these dampened vasoconstrictory responses, KO mice demonstrated increased mean arterial pressure from 8 weeks old. This hypertensive phenotype was associated with an increase in left ventricular weight, left ventricular systolic pressure, and diminished diastolic function. KO mice also show enhanced plasma norepinephrine turnover, suggesting an increased sympathetic outflow. In conclusion, our data suggest that global loss of arginase II activity results in hypertension. We suggest that this strain of mouse warrants further investigation as a potentially novel model of hypertension.

Amino acids, arginase and nitric oxide in vascular health.

1. Nitric oxide (NO) plays a fundamental role in the vasculature because of its diverse influence in vascular protection, including its well-reported antiproliferative, anti-inflammatory, antithrombotic and vasodilator effects. In many vascular disease states, NO production is reduced as a result of endothelial dysfunction, in part caused by a decrease in substrate (L-arginine) availability. 2. The role of L-arginine and other amino acids important in nitrogen balance has been re-examined in the context of their effects on vascular health. The metabolism of L-arginine is complex because it is involved in a plethora of other pathways, such as urea, creatine and agmatine production. L-Arginine supplementation in patients with vascular disease is well reported to benefit patients therapeutically because of its effect on both NO-dependent and -independent mechanisms. 3. L-Arginine availability depends on the flux of other amino acids in the body, including L-glutamine, L-glutamate, L-ornithine, L-citrulline and L-lysine. The role of L-methionine and homocystine and their effect on NO also play an influential role in the body. 4. Recent data suggest that the key enzyme involved in the L-arginine-urea cycle, arginase, is coexpressed in NO-producing cells in the vasculature. In the present review, we examine the potential role of arginase as a therapeutic target for vascular health.

Short-term exercise training in humans reduces AMPK signalling during prolonged exercise independent of muscle glycogen.

We examined the effect of short-term exercise training on skeletal muscle AMP-activated protein kinase (AMPK) signalling and muscle metabolism during prolonged exercise in humans. Eight sedentary males completed 120 min of cycling at 66 +/- 1% , then exercise trained for 10 days, before repeating the exercise bout at the same absolute workload. Participants rested for 72 h before each trial while ingesting a high carbohydrate diet (HCHO). Exercise training significantly (P < 0.05) attenuated exercise-induced increases in skeletal muscle free AMP: ATP ratio and glucose disposal and increased fat oxidation. Exercise training abolished the 9-fold increase in AMPK alpha2 activity observed during pretraining exercise. Since training increased muscle glycogen content by 93 +/- 12% (P < 0.01), we conducted a second experiment in seven sedentary male participants where muscle glycogen content was essentially matched pre- and post-training by exercise and a low CHO diet (LCHO; post-training muscle glycogen 52 +/- 7% less than in HCHO, P < 0.001). Despite the difference in muscle glycogen levels in the two studies we obtained very similar results. In both studies the increase in ACCbeta Ser(221) phosphorylation was reduced during exercise after training. In conclusion, there is little activation of AMPK signalling during prolonged exercise following short-term exercise training suggesting that other factors are important in the regulation of glucose disposal and fat oxidation under these circumstances. It appears that muscle glycogen is not an important regulator of AMPK activation during exercise in humans when exercise is begun with normal or high muscle glycogen levels.