miRNAs Regulate hERG.

BACKGROUND: The human ether-a-go-go-related gene (hERG) is the major molecular component of the rapidly activating delayed rectifier K+ current (Ikr ). Impairment of hERG function is believed to be a mechanism causing long-QT syndromes (LQTS). Growing evidences have shown that microRNAs (miRNAs) are involved in functional modulation of the hERG pathway. The purpose of this study was to screen and validate miRNAs that regulate the hERG pathway. The miRNAs identified in this study will provide new tools to assess the mechanism of LQTS. METHODS: Six miRNAs were selected by algorithm predictions based on potential interaction with hERG. The effects of each miRNA on hERG were assessed by use of the Dual-Luciferase Reporter assay system, qRT-PCR, Western blotting, and confocal fluorescence microscopy. Furthermore, whole-cell patch clamp technique was used to validate the effect of miR-103a-1 on the electrophysiological characteristic of the Ikr of the hERG protein channel. RESULTS: miR-134, miR-103a-1, miR-143, and miR-3619 significantly downregulated luciferase activity (P < 0.05) in a reporter test system. These 4 miRNAs significantly suppressed expression of hERG mRNA and protein in U2OS cells (P < 0.05).Corresponding AMOs rescued expression of hERG mRNA and protein. Confocal microscopy showed that all 4 miRNAs reduced the expression of both immature and mature hERG protein. miR-103a-1 decreased the maximum current and tail current amplitudes of hERG channel. CONCLUSIONS: Expression and functions of hERG are regulated by specific miRNAs.

Blue Light for Inactivation of Meatborne Pathogens and Maintaining the Freshness of Beef.

ABSTRACT: Beef is rich in various nutrients but easily spoils due to bacterial contamination; thus, a bactericidal method is needed to inactivate meatborne pathogens while maintaining the freshness of beef. The present study was conducted to investigate for the first time the bactericidal effect of blue light (BL) at 415 nm against four meatborne pathogens (methicillin-resistant Staphylococcus aureus, Escherichia coli, Salmonella Typhimurium, and Listeria monocytogenes) both in vitro and inoculated onto the surface of fresh beef. The populations of the four pathogens on the nonirradiated control beef did not change significantly (P > 0.05), whereas a dose-dependent inactivation effect was found for BL-treated beef both in vitro and in vivo. On the beef cuts, BL at 109.44 J/cm2 inactivated 90% of inoculated cells of the tested strains (P < 0.05), and this inactivation effect was sustained during 7 days of cold storage. Insignificant changes in lipid oxidation rate, water holding capacity, and cooking loss were found during storage between the control beef and the beef irradiated at 109.44 J/cm2 at the same time. BL had a minor and nonsignificant effect on surface color and free amino acid concentrations. The pH of the treated beef increased more slowly (P < 0.05) than did that of untreated beef. These results suggest that BL could be a novel bactericide and could help maintain the freshness of beef.

Fractality and the law of the wall.

Fluid motions in the inertial range of isotropic turbulence are fractal, with their space-filling capacity slightly below regular three-dimensional objects, which is a consequence of the energy cascade. Besides the energy cascade, the other often encountered cascading process is the momentum cascade in wall-bounded flows. Despite the long-existing analogy between the two processes, many of the thoroughly investigated aspects of the energy cascade have so far received little attention in studies of the momentum counterpart, e.g., the possibility of the momentum-transferring scales in the logarithmic region being fractal has not been considered. In this work, this possibility is pursued, and we discuss one of its implications. Following the same dimensional arguments that lead to the D=2.33 fractal dimension of wrinkled surfaces in isotropic turbulence, we show that the large-scale momentum-carrying eddies may also be fractal and non-space-filling, which then leads to the power-law scaling of the mean velocity profile. The logarithmic law of the wall, on the other hand, corresponds to space-filling eddies, as suggested by Townsend [The Structure of Turbulent Shear Flow (Cambridge University Press, Cambridge, 1980)]. Because the space-filling capacity is an integral geometric quantity, the analysis presented in this work provides us with a low-order quantity, with which, one would be able to distinguish between the logarithmic law and the power law.

A multifractal model for the momentum transfer process in wall-bounded flows.

The cascading process of turbulent kinetic energy from large-scale fluid motions to small-scale and lesser-scale fluid motions in isotropic turbulence may be modelled as a hierarchical random multiplicative process according to the multifractal formalism. In this work, we show that the same formalism might also be used to model the cascading process of momentum in wall-bounded turbulent flows. However, instead of being a multiplicative process, the momentum cascade process is additive. The proposed multifractal model is used for describing the flow kinematics of the low-pass filtered streamwise wall-shear stress fluctuation τ l ' , where l is the filtering length scale. According to the multifractal formalism, 〈 τ ' 2 〉 ~ log ( R e τ ) and 〈 exp ( p τ l ' ) 〉 ~ ( L / l ) ζ p in the log-region, where Re τ is the friction Reynolds number, p is a real number, L is an outer length scale and ζ p is the anomalous exponent of the momentum cascade. These scalings are supported by the data from a direct numerical simulation of channel flow at Re τ = 4200.

Modelling turbulent boundary layer flow over fractal-like multiscale terrain using large-eddy simulations and analytical tools.

In recent years, there has been growing interest in large-eddy simulation (LES) modelling of atmospheric boundary layers interacting with arrays of wind turbines on complex terrain. However, such terrain typically contains geometric features and roughness elements reaching down to small scales that typically cannot be resolved numerically. Thus subgrid-scale models for the unresolved features of the bottom roughness are needed for LES. Such knowledge is also required to model the effects of the ground surface 'underneath' a wind farm. Here we adapt a dynamic approach to determine subgrid-scale roughness parametrizations and apply it for the case of rough surfaces composed of cuboidal elements with broad size distributions, containing many scales. We first investigate the flow response to ground roughness of a few scales. LES with the dynamic roughness model which accounts for the drag of unresolved roughness is shown to provide resolution-independent results for the mean velocity distribution. Moreover, we develop an analytical roughness model that accounts for the sheltering effects of large-scale on small-scale roughness elements. Taking into account the shading effect, constraints from fundamental conservation laws, and assumptions of geometric self-similarity, the analytical roughness model is shown to provide analytical predictions that agree well with roughness parameters determined from LES.This article is part of the themed issue 'Wind energy in complex terrains'.

Association of MDM2 promoter T309G polymorphism with oral cancer risk: A meta-analysis of 3,536 subjects.

The mouse double minute 2 (MDM2) gene is an important regulator of the p53 suppressor gene. To date, evidence concerning the association of the MDM2 single nucleotide polymorphism (SNP) 309T>G (rs2279744) with the risk of developing oral squamous cell carcinoma (OSCC) remains controversial. Therefore, a meta-analysis of all the eligible studies was performed, in order to derive a more precise estimation of this association. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the degree of association in 5 previous studies, including a total of 1,369 OSCC cases and 2,167 controls. The overall analysis revealed a significant association between MDM2 SNP309 and OSCC risk in the heterozygote (TG vs. TT: OR=0.81; 95% CI: 0.68-0.96; P=0.02) and dominant models (TG+GG vs. TT: OR=0.82; 95% CI: 0.69-0.97; P=0.02). The subgroup analysis based on the source of the controls revealed a significant association between population-based controls and the heterozygote model (TG vs. TT: OR=0.75; 95% CI: 0.62-0.91; P=0.004), dominant model (TG+GG vs. TT: OR=0.76; 95% CI: 0.63-0.91; P=0.003) and allele comparison (G vs. T: OR=0.89; 95% CI: 0.79-0.99; P=0.04). Importantly, no evidence of publication bias or obvious heterogeneity were observed in the meta-analysis. The results of the present study demonstrated a decreased risk of developing OSCC for the MDM2 SNP309 group, suggesting MDM2 SNP309 may be a protection-associated genetic variation for OSCC. Additional well-designed studies, with larger sample sizes, are required to further elucidate this association.

Association of the XPA A23G polymorphism with the risk of head and neck carcinomas: Evidence from 5,491 subjects.

The XPA gene participates in modulating DNA damage recognition during the DNA nucleotide excision repair process. Current data regarding the association of the XPA A23G polymorphism with the risk of head and neck squamous cell carcinoma (HNSCC) remain controversial, and meta-analyses focusing on the HNSCC risk and this polymorphism are limited. Therefore, the aim of the present study was to derive a more precise estimation of this association by a meta-analysis of all the eligible studies. Odds ratios (ORs) with 95% confidence intervals (CI) were assessed for the strength of the associations in eight studies, including 5,491 subjects (2,409 HNSCC cases and 3,082 controls). The overall analysis revealed that the XPA A23G polymorphism was not significantly associated with the overall HNSCC risk. Consistently, there was no evidence for the association between the XPA A23G polymorphism and HNSCC risk in subgroup analyses based on ethnicity and the source of controls. However, the significant associations in oral carcinoma with the increased risk among the XPA heterozygote (AG vs. AA: OR, 1.58; 95% CI, 1.06-2.37; Pheterogeneity=0.23, I2=30%) and dominant (AG +GG vs. AA: OR, 1.53; 95% CI, 1.04-2.23; Pheterogeneity=0.21, I2=36%) models were observed in the subgroup analysis by tumor site. In conclusion, the meta-analysis suggested that the XPA A23G polymorphism was not associated with overall HNSCC susceptibility, but it was associated with oral carcinoma susceptibility and it may be a risk factor for oral carcinoma. Further well-designed and large studies are required to confirm these associations.

Genome-wide analysis revealed the complex regulatory network of brassinosteroid effects in photomorphogenesis.

Light and brassinosteroids (BRs) have been proved to be crucial in regulating plant growth and development; however, the mechanism of how they synergistically function is still largely unknown. To explore the underlying mechanisms in photomorphogenesis, genome-wide analyses were carried out through examining the gene expressions of the dark-grown WT or BR biosynthesis-defective mutant det2 seedlings in the presence of light stimuli or exogenous Brassinolide (BL). Results showed that BR deficiency stimulates, while BL treatment suppresses, the expressions of light-responsive genes and photomorphogenesis, confirming the negative effects of BR in photomorphogenesis. This is consistent with the specific effects of BR on the expression of genes involved in cell wall modification, cellular metabolism and energy utilization during dark-light transition. Further analysis revealed that hormone biosynthesis and signaling-related genes, especially those of auxin, were altered under BL treatment or light stimuli, indicating that BR may modulate photomorphogenesis through synergetic regulation with other hormones. Additionally, suppressed ubiquitin-cycle pathway during light-dark transition hinted the presence of a complicated network among light, hormone, and protein degradation. The study provides the direct evidence of BR effects in photomorphogenesis and identified the genes involved in BR and light signaling pathway, which will help to elucidate the molecular mechanism of plant photomorphogenesis.