A characteristic optical variability time scale in astrophysical accretion disks.

Accretion disks around supermassive black holes in active galactic nuclei produce continuum radiation at ultraviolet and optical wavelengths. Physical processes in the accretion flow lead to stochastic variability of this emission on a wide range of time scales. We measured the optical continuum variability observed in 67 active galactic nuclei and the characteristic time scale at which the variability power spectrum flattens. We found a correlation between this time scale and the black hole mass extending over the entire mass range of supermassive black holes. This time scale is consistent with the expected thermal time scale at the ultraviolet-emitting radius in standard accretion disk theory. Accreting white dwarfs lie close to this correlation, suggesting a common process for all accretion disks.

A novel compound AB38b attenuates oxidative stress and ECM protein accumulation in kidneys of diabetic mice through modulation of Keap1/Nrf2 signaling.

Extracellular matrix (ECM) deposition following reactive oxygen species (ROS) overproduction has a key role in diabetic nephropathy (DN), thus, antioxidant therapy is considered as a promising strategy for treating DN. Here, we investigated the therapeutic effects of AB38b, a novel synthetic α, ß-unsaturated ketone compound, on the oxidative stress (OS) and ECM accumulation in type 2 diabetes mice, and tried to clarify the mechanisms underlying the effects in high glucose (HG, 30 mM)-treated mouse glomerular mesangial cells (GMCs). Type 2 diabetes model was established in mice with high-fat diet feeding combined with streptozocin intraperitoneal administration. The diabetic mice were then treated with AB38b (10, 20, 40 mg· kg-1· d-1, ig) or a positive control drug resveratrol (40 mg· kg-1· d-1, ig) for 8 weeks. We showed that administration of AB38b or resveratrol prevented the increases in malondialdehyde level, lactate dehydrogenase release, and laminin and type IV collagen deposition in the diabetic kidney. Simultaneously, AB38b or resveratrol markedly lowered the level of Keap1, accompanied by evident activation of Nrf2 signaling in the diabetic kidney. The underlying mechanisms of antioxidant effect of AB38b were explored in HG-treated mouse GMCs. AB38b (2.5-10 µM) or resveratrol (10 µM) significantly alleviated OS and ECM accumulation in HG-treated GMCs. Furthermore, AB38b or resveratrol treatment effectively activated Nrf2 signaling by inhibiting Keap1 expression without affecting the interaction between Keap1 and Nrf2. Besides, AB38b treatment effectively suppressed the ubiquitination of Nrf2. Taken together, this study demonstrates that AB38b ameliorates experimental DN through antioxidation and modulation of Keap1/Nrf2 signaling pathway.

Outbursts of luminous blue variable stars from variations in the helium opacity.

Luminous blue variables are massive, evolved stars that exhibit large variations in luminosity and size on timescales from months to years, with high associated rates of mass loss1-5. In addition to this on-going variability, these stars exhibit outburst phases, during which their size increases and as a result their effective temperature decreases, typically to about 9,000 kelvin3,6. Outbursts are believed to be caused by the radiation force on the cooler, more opaque, outer layers of the star balancing or even exceeding the force of gravity, although the exact mechanisms are unknown and cannot be determined using one-dimensional, spherically symmetric models of stars because such models cannot determine the physical processes that occur in this regime7. Here we report three-dimensional simulations of massive, radiation-dominated stars, which show that helium opacity has an important role in triggering outbursts and setting the observed effective temperature during outbursts of about 9,000 kelvin. It probably also triggers the episodic mass loss at rates of 10-7 to 10-5 solar masses per year. The peak in helium opacity is evident in our three-dimensional simulations only because the density and temperature of the stellar envelope (the outer part of the star near the photosphere) need to be determined self-consistently with convection, which cannot be done in one-dimensional models that assume spherical symmetry. The simulations reproduce observations of long-timescale variability, and predict that convection causes irregular oscillations in the radii of the stars and variations in brightness of 10-30 per cent on a typical timescale of a few days. The amplitudes of these short-timescale variations are predicted to be even larger for cooler stars (in the outburst phase). This short-timescale variability should be observable with high-cadence observations.

[Preliminary Investigation of Medicinal Plant Resources in Kangle County, Gansu Province].

OBJECTIVE: To study the medicinal plant resources and their diversity in Kangle County, Gansu Province, and to provide scientific basis on utilization and protection of the medicinal plant resources of the county. METHODS: By field survey, sample collection, taxonomic identification and data verification methods. RESULTS: There were 258 species, 65 families in existing medicinal plants, of which 43 species, 39 genera and 24 families were national protection medicinal plants. Dominant families were mainly Asteraceae and Rosaceae. In this area,the plants used whole herbs and roots ( or rhizomes) as medicinal materials represented 40.31% and 25.19% respectively, and antipyretic and rheumatism medicine accounted for 28.68% and 12.79% respectively. 12 medicinal plants were cultivated and the cultivated area was 3,000 hectares. CONCLUSION: However, the reserves of most medicinal plants are less enough and the resources are diminishing increasingly in recent years. So we should accelerate the research progress as well as developing and utilizing rationally on the premise of protection.

RNASET2 tag SNP but not CCR6 polymorphisms is associated with autoimmune thyroid diseases in the Chinese Han population.

BACKGROUND: Polymorphisms of the CC chemokine receptor 6 (CCR6) and RNASET2 tag SNP have been shown to be associated with the susceptibility to several immune-related diseases. This study was conducted to identify the association of CCR6 and RNASET2 tag SNP with autoimmune thyroid diseases (AITDs) in the Chinese Han population. METHODS: We enrolled 1061 patients with AITDs, including 701 patients with Graves' disease (GD) and 360 patients with Hashimoto's thyroiditis (HT), and 938 healthy individuals for a case-control genetic association study. Three CCR6 single nucleotides polymorphisms (SNPs) (rs3093023/rs3093024/rs6902119) and one tagging SNP (rs9355610) within RNASET2 gene were selected for genotyping by multiplex polymerase chain reaction (PCR) and ligase detection reaction (LDR). RESULTS: The frequency of rs9355610 genotypes in the patients with GD differed significantly from that in the controls (p = 0.017). The frequency of the minor G allele of rs9355610 was significantly higher in the GD patients than in the healthy controls (p = 0.005, OR = 1.225, 95% CI:1.063-1.412). However, we could not find significant differences in the genotype or allele frequencies of HT patients compared with healthy controls. After gender stratification, the frequency of the minor G allele in both male and female GD patients was significantly higher than that in the healthy controls (p = 0.036, OR = 1.308, 95% CI:1.017-1.684 ; p = 0.048, OR = 1.19, 95% CI:1.001-1.413; respectively);. Furthermore, the frequency of haplotype AT in GD patients was significantly lower than that in their control groups (p = 0.003) and showed a protective effect against GD (OR = 0.806, 95% CI: 0.699-0.929). The frequency of haplotype GT in GD patients was significantly higher than that in their control groups (p = 0.048), indicating that GT was the risk haplotype to GD (OR = 1.267, 95% CI: 1.001-1.603). There were no significant differences in the allele or genotype frequencies of three SNPs of CCR6 (rs3093023/rs3093024/ rs6902119) gene between GD patients, HT patients and controls. CONCLUSIONS: Our results suggest that the rs9355610 tag SNP of RNASET2 gene is positively associated with susceptibility to GD in the Chinese Han population. No association was found for the tested CCR6 SNPs.

Confidence intervals for concentration and brightness from fluorescence fluctuation measurements.

The theory of photon count histogram (PCH) analysis describes the distribution of fluorescence fluctuation amplitudes due to populations of fluorophores diffusing through a focused laser beam and provides a rigorous framework through which the brightnesses and concentrations of the fluorophores can be determined. In practice, however, the brightnesses and concentrations of only a few components can be identified. Brightnesses and concentrations are determined by a nonlinear least-squares fit of a theoretical model to the experimental PCH derived from a record of fluorescence intensity fluctuations. The χ(2) hypersurface in the neighborhood of the optimum parameter set can have varying degrees of curvature, due to the intrinsic curvature of the model, the specific parameter values of the system under study, and the relative noise in the data. Because of this varying curvature, parameters estimated from the least-squares analysis have varying degrees of uncertainty associated with them. There are several methods for assigning confidence intervals to the parameters, but these methods have different efficacies for PCH data. Here, we evaluate several approaches to confidence interval estimation for PCH data, including asymptotic standard error, likelihood joint-confidence region, likelihood confidence intervals, skew-corrected and accelerated bootstrap (BCa), and Monte Carlo residual resampling methods. We study these with a model two-dimensional membrane system for simplicity, but the principles are applicable as well to fluorophores diffusing in three-dimensional solution. Using simulated fluorescence fluctuation data, we find the BCa method to be particularly well-suited for estimating confidence intervals in PCH analysis, and several other methods to be less so. Using the BCa method and additional simulated fluctuation data, we find that confidence intervals can be reduced dramatically for a specific non-Gaussian beam profile.

A phage RNA-binding protein binds to a non-cognate structured RNA and stabilizes its core structure.

Recent studies suggest that some RNA-binding proteins facilitate the folding of non-cognate RNAs. Here, we report that bacteriophage MS2 coat protein (MS2 CP) bound and promoted the catalytic activity of Candida group I ribozyme. Cloning of the MS2-bound RNA segments showed that this protein primarily interacts with the P5ab-P5 structure. Ultraviolet cross-linking and the T1 footprinting assay further showed that MS2 binding stabilized tertiary interactions, including the conserved L9-P5 interaction, and led to a more compact core structure. This mechanism is similar to that of the yeast mitochondrial tyrosyl-tRNA synthetase on other group I introns, suggesting that different RNA-binding proteins may use common mechanisms to support RNA structures.

[Epidermal growth factor up-regulates the mRNA expression of endothelin-1 and its receptors in prostate cancer PC-3 cell lines].

OBJECTIVE: To investigate the effects of the epidermal growth factor on the mRNA expression of endothelin-1 and its receptors (ET(A)R, ET(B)R) in hormone refractory prostate cancer (HRPC) PC-3 cell lines. METHODS: PC-3 cells were cultured in vitro. After the treatment with EGF, the mRNA expressions of endothelin-1, ET(A)R and ET(B)R were detected by RT-PCR in PC-3 cell lines. The levels of the mRNA expression of endothelin-1 and its receptors were examined at different time points by RT-PCR. RESULTS: The expressions of endothelin-1 and ET(A)R mRNA but not the mRNA expression of ET(B)R was observed in PC-3 cell lines. After 24 hours of treatment with EGF, the expressions of endothelin-1 and ET(A)R in PC-3 cell lines were both up-regulated and there was significant difference (P < 0.05) between the experimental and control groups. Different expression levels of endothelin-1 and ET(A)R mRNA were noted at different time points of EGF intervention, up-regulated with the increase of treatment time, and with significant difference (P < 0.05). CONCLUSION: EGF can up-regulate the mRNA expressions of endothelin-1 and ET(A)R in PC-3 cell lines and play a great role in prostate cancer progression, which may offer a substructure of molecular biology for the treatment of HRPC.

Monovalent cations use multiple mechanisms to resolve ribozyme misfolding.

Recent efforts have been made to unravel the independent roles of monovalent cations in RNA folding, primarily using the Tetrahymena ribozyme as a model. Here we report how monovalent cations impact the folding of the Candida ribozyme. Interestingly, this ribozyme requires an order of magnitude less monovalent cations (Na+ and Tris+) to commit to a new folding starting state in which the J3/4:P6 base triple is partially formed and mispairing in the L2.1 and L6 terminal loops is resolved. When Mg2+-induced ribozyme folding proceeded on the same energy landscape, the altered starting state led to a rapid assembly of the correct ribozyme core and a fivefold to 10-fold increase in the ribozyme activity. Moreover, when the ribozyme folding was started from a misfolding-prone state, high millimolar concentrations of monovalent cations moderately elevated the ribozyme activity by efficiently resolving the misfolding of a peripheral element, P5abc.