Impact of varying intensities of blue-light exposure on 3T3 cells

There is the need to develop a compatible sterilisation method for hybrid biomaterials. High-intensity blue light in the 405 nm region has been shown to be an effective bacterial decontamination method [1], to cause no noticeable damage to the gross structure of type-I collagen monomer (when treated at 10 mW/cm2) [2], and to have no noticeable effect on 3T3 cell viability, growth rate, redox state or lactate dehydrogenase (LDH) leakage (at 1.0 mW/cm2) [2]. The purpose of this research was to investigate the effect of varying the blue-light intensity on the 3T3 cell response parameters

Efficient state initialization by a quantum spectral filtering algorithm

An algorithm that initializes a quantum register to a state with a specified energy range is given, corresponding to a quantum implementation of the celebrated Feit-Fleck method. This is performed by introducing a nondeterministic quantum implementation of a standard spectral filtering procedure combined with an apodization technique, allowing for accurate state initialization. It is shown that the implementation requires only two ancilla qubits. A lower bound for the total probability of success of this algorithm is derived, showing that this scheme can be realized using a finite, relatively low number of trials. Assuming the time evolution can be performed efficiently and using a trial state polynomially close to the desired states, it is demonstrated that the number of operations required scales polynomially with the number of qubits. Tradeoffs between accuracy and performance are demonstrated in a simple example: the harmonic oscillator. This algorithm would be useful for the initialization phase of the simulation of quantum systems on digital quantum computers.Comment: 12 pages, 4 figures, revised versio

Novel signaling pathways in pulmonary arterial hypertension (2015 Grover Conference Series)

The proliferative endothelial and smooth muscle cell phenotype, inflammation, and pulmonary vascular remodeling are prominent features of pulmonary arterial hypertension (PAH). Mutations in bone morphogenetic protein type 2 receptor (BMPR2) have been identified as the most common genetic cause of PAH and females with BMPR2 mutations are 2.5 times as likely to develop heritable forms of PAH than males. Higher levels of estrogen have also been observed in males with PAH, implicating sex hormones in PAH pathogenesis. Recently, the estrogen metabolite 16α-OHE1 (hydroxyestrone) was implicated in the regulation of miR29, a microRNA involved in modulating energy metabolism. In females, decreased miR96 enhances serotonin’s effect by upregulating the 5-hydroxytryptamine 1B (5HT1B) receptor. Because PAH is characterized as a quasi-malignant disease, likely due to BMPR2 loss of function, altered signaling pathways that sustain this cancer-like phenotype are being explored. Extracellular signal–regulated kinases 1 and 2 and p38 mitogen-activated protein kinases (MAPKs) play a critical role in proliferation and cell motility, and dysregulated MAPK signaling is observed in various experimental models of PAH. Wnt signaling pathways preserve pulmonary vascular homeostasis, and dysregulation of this pathway could contribute to limited vascular regeneration in response to injury. In this review, we take a closer look at sex, sex hormones, and the interplay between sex hormones and microRNA regulation. We also focus on MAPK and Wnt signaling pathways in the emergence of a proproliferative, antiapoptotic endothelial phenotype, which then orchestrates an angioproliferative process of vascular remodeling, with the hope of developing novel therapies that could reverse the phenotype

Transient but not genetic loss of miR-451 attenuates the development of pulmonary arterial hypertension

<b>Rationale:</b> MicroRNAs are small non-coding RNAs involved in the regulation of gene expression and have recently been implicated in the development of pulmonary arterial hypertension (PAH). Previous work established that miR-451 is up-regulated in rodent models of PAH.<p></p> <b>Objectives:</b> The role of miR-451 in the pulmonary circulation is unknown. We therefore sought to assess the involvement of miR-451 in the development of pulmonary arterial hypertension.<p></p> <b>Methods:</b> Silencing of miR-451 was performed in vivo using miR-451 knockout mice and an antimiR targeting mature miR-451 in rats. Coupled with exposure to hypoxia, indices of pulmonary arterial hypertension were assessed. The effect of modulating miR-451 on human pulmonary artery smooth muscle cell proliferation and migration was analysed.<p></p> <b>Measurements and Main Results:</b> We observed a reduction in systolic right ventricular pressure in hypoxic rats pre-treated with antimiR-451 compared to hypoxia alone (47.7 ± 1.36mmHg and 56.0 ± 2.03mmHg respectively, p<0.01). In miR-451 knockout mice following exposure to chronic hypoxia, no significant differences were observed compared to wild type hypoxic mice. In vitro analysis demonstrated that over-expression of miR-451 in human pulmonary artery smooth muscle cells promoted migration under serum-free conditions. No effect on cellular proliferation was observed.<p></p> <b>Conclusions:</b> Transient inhibition of miR-451 attenuated the development of pulmonary arterial hypertension in hypoxia exposed rats. Genetic deletion of miR-451 had no beneficial effect on indices of pulmonary arterial hypertension, potentially due to pathway redundancy compensating for the loss of miR-451.<p></p&gt

Combined treatment of biomatrices with nisin and pulsed electric fields as a potential decontamination method?

Pulsed electric field (PEF) treatment has been shown to achieve bacterial inactivation in collagen gels whilst retaining the ability of the collagen to function as a biomaterial [1, 2]. Nisin, an antimicrobial peptide, has been used widely as a food preservative and has shown bactericidal action against a number of Gram-positive bacteria [3]. The potential of nisin to increase the efficacy of PEF disinfection of collagen gels to be used for tissue engineering applications was investigated