Testing gravity with the stacked phase space around galaxy clusters.

In general relativity, the average velocity field of dark matter around galaxy clusters is uniquely determined by the mass profile. The latter can be measured through weak lensing. We propose a new method of measuring the velocity field (phase space density) by stacking redshifts of surrounding galaxies from a spectroscopic sample. In combination with lensing, this yields a direct test of gravity on scales of 1-30 Mpc. Using N-body simulations, we show that this method can improve upon current constraints on f(R) and Dvali-Gabadadze-Porrati model parameters by several orders of magnitude when applied to upcoming imaging and redshift surveys.

Development of multiplex nucleic acid sequence-based amplification for detection of human respiratory tract viruses.

A group of common lower respiratory tract infections, influenza A, influenza B, human parainfluenza virus 1-4 (HPIV1-4), respiratory syncytial virus (RSV), rubella virus (RV) and Coxsackie virus (CSV), were selected for the development of a multiplex nucleic acid sequence-based amplification (NASBA) assay. Quantifiable measurement utilizing an enzyme-linked oligonucleotide capture (EOC) optical detection method, which was described previously, alleviated the requirement of specialized instrumentation that is commonly used in other molecular techniques. Multiplex NASBA-EOC provided rapid and specific detection of a single virus from a multiplexed group, reducing laboratory testing time and enabling high throughput screening. The uniquely designed primers and probes proved to be highly sensitive and specific, exemplifying the robustness of the multiplex NASBA-EOC technique.

Folic acid consumption reduces resistin level and restores blunted acetylcholine-induced aortic relaxation in obese/diabetic mice.

Folic acid supplementation provides beneficial effects on endothelial functions in patients with hyperhomocysteinemia. However, its effects on vascular functions under diabetic conditions are largely unknown. Therefore, the effect(s) of folic acid (5.7 and 71 microg/kg/day for 4 weeks) on aortic relaxation was investigated using obese/diabetic (+db/+db) mice and lean littermate (+db/+m) mice. Acetylcholine-induced relaxation in +db/+db mice was less than that observed in +db/+m mice. The reduced relaxation in +db/+db mice was restored by consumption of 71 microg/kg folic acid. Acetylcholine-induced relaxation (with and without folic acid treatment) was sensitive to N(G)-nitro-L-arginine methyl ester, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, geldanamycin and triciribine. In addition, acetylcholine-induced relaxation was attenuated by resistin. The plasma level of resistin in +db/+db mice was sevenfold higher than that measured in +db/+m mice, and the elevated plasma level of resistin in +db/+db mice was reduced by 25% after treatment with 71 microg/kg folic acid. Folic acid slightly increased the ratio of reduced glutathione to oxidized glutathione in +db/+db mice. Moreover, folic acid caused a reduction in PTEN (phosphatase and tensin homolog deleted on chromosome 10) expression, an increase in the phosphorylation of endothelial nitric oxide synthase (eNOS(Ser1177)) and Akt(Ser473), and an enhanced interaction of heat shock protein 90 (HSP90) with eNOS in both strains, with greater magnitude observed in +db/+db mice. In conclusion, folic acid consumption improved blunted acetylcholine-induced relaxation in +db/+db mice. The mechanism may be, at least partly, attributed to enhancement of PI3K/HSP90/eNOS/Akt cascade, reduction in plasma resistin level, down-regulation of PTEN and slight modification of oxidative state.

Folic acid supplementation modifies beta-adrenoceptor-mediated in vitro lipolysis of obese/diabetic (+db/+db) mice.

The effects of folic acid (5.7 and 71 microg/kg, 4 weeks) consumption on the beta-adrenoceptors (beta-ARs)-elicited lipolysis in vitro of the abdominal adipocytes of lean/control (+m/+db) and obese/diabetic (+db/+db) mice (female) were investigated. beta-AR agonists (salbutamol, a beta(2)-AR agonist; BRL 37344 and CGP 12177, beta(3)-AR agonists; adrenaline, a beta-AR agonist)-mediated lipolysis, beta(2)-, and beta(3)-ARs protein expression of the adipose tissues after folic acid consumption were evaluated. Our results demonstrate that a smaller magnitude of the basal (spontaneous) and the beta-AR agonists-triggered lipolysis was observed in +db/+db mice, and folic acid supplementation (71 microg/kg) resulted in an improvement of both the baseline and the beta-ARs-mediated lipolysis. In controls, a lower beta(2)-and beta(3)-ARs protein expression of the adipose tissues was detected in +db/+db mice, compared to +m/+db mice. In both strains fed with folic acid (71 microg/kg), a reduction of beta(2)-AR protein expression was observed compared to the respective controls. In +db/+db mice, folic acid (5.7 and 71 microg/kg) consumption caused a dose-dependent increase of beta(3)-AR protein expression compared to controls. We demonstrate that lipolysis elicited by beta-AR (beta(2)- and beta(3)-ARs) agonists was blunted in +db/+db mice. Folic acid consumption has significant modulatory effects on beta-ARs protein expression and lipolysis.

Role of monoamine oxidases in the exaggerated 5-hydroxytryptamine-induced tension development of human isolated preeclamptic umbilical artery.

We investigated the role(s) of monoamine oxidases (MAOs) on the altered 5-hydroxytryptamine (5-HT, serotonin)-induced tension development of the isolated umbilical artery of preeclamptic pregnancy of Chinese women. An enhanced 5-HT-induced tension development of the umbilical artery of preeclamptic pregnancy was observed when compared with that of normal pregnancy. The enhanced component of 5-HT-induced tension development was eradicated by clorgyline (a MAO-A inhibitor). Blockade of eNOS (endothelial isoform nitric oxide synthase) (N(omega)-nitro-L-arginine methyl ester), 5-HT transporter (citalopram), 5-HT receptor subtypes (5HT2B, SB 204741; 5-HT2C, RS 102221; 5-HT7, SB 269970), and endothelium denudation of the umbilical artery of normal pregnancy mimicked the enhanced 5-HT-induced tension development as observed in the preeclamptic tissues. In contrast, no apparent changes in 5-HT-induced tension development of the umbilical artery of preeclamptic pregnancy were observed with the same pharmacological manipulations. A decreased protein expression levels of MAO-A and eNOS (no iNOS and MAO-B expression was detected) and no change in caveolin-1 and 5-HT transporter expression were demonstrated in the umbilical artery (endothelium intact) lysate of preeclamptic pregnancy, compared to that of the umbilical artery of normal pregnancy. Thus, in the umbilical artery of preeclamptic pregnancy, a decrease of MAO-A and eNOS protein expression levels are probably associated with, or responsible for, the exaggerated 5-HT-induced tension development.

Comparison of vascular relaxation, lipolysis and glucose uptake by peroxisome proliferator-activated receptor-gamma activation in +db/+m and +db/+db mice.

In this study, we determined the in vitro effect of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activation on the aortic relaxation, lipolysis and insulin-induced [(3)H]-glucose uptake of the abdominal (omental) adipocytes of the non-diabetic (+db/+m) and obese/diabetic (+db/+db) mice. The expression of PPAR-gamma (mRNA and protein) in aorta and adipose tissues was evaluated and compared. Cumulative application of ciglitazone, pioglitazone and troglitazone (PPAR-gamma agonists) caused a concentration-dependent aortic relaxation (sensitive to 2-chloro-5-nitro-N-phenylbenzamide (GW9662) (1 microM, a selective PPAR-gamma antagonist) and N(omega)-nitro-l-arginine methyl ester (l-NAME) (20 microM, a nitric oxide synthase inhibitor)) with a maximum relaxation of approximately 30% (3 microM) in +db/+m mice, whereas no relaxation was observed in +db/+db mice. All PPAR-gamma agonists examined did not alter the basal lipolysis of both species, but forskolin caused a concentration-dependent lipolysis, with a greater magnitude observed in +db/+m mice. Insulin (0.1 and 1 microM) caused an enhancement of [(3)H]-glucose uptake into adipocytes with a greater magnitude in +db/+m mice. In contrast, none of the PPAR-gamma agonists tested (0.1, 1 and 10 microM) altered the basal and the insulin (0.1 microM)-induced [(3)H]-glucose uptake into adipocytes of both species. In addition, there was no difference in PPAR-gamma expression (mRNA and protein) in the aorta and adipose tissues between the species. In conclusion, our results demonstrate that PPAR-gamma is present in the abdominal (omental) adipose tissue and thoracic aorta. An acute activation of PPAR-gamma produced a small ( approximately 30%) aortic relaxation (nitric oxide/endothelium-dependent) of +db/+m mice. However, all PPAR-gamma agonists examined have no acute effect on lipolysis and the insulin-induced glucose uptake into adipocytes of both +db/+m and +db/+db mice.