Upregulated sirtuin 1 by miRNA-34a is required for smooth muscle cell differentiation from pluripotent stem cells

© 2015 Macmillan Publishers Limited. All rights reserved. microRNA-34a (miR-34a) and sirtuin 1 (SirT1) have been extensively studied in tumour biology and longevityaging, but little is known about their functional roles in smooth muscle cell (SMC) differentiation from pluripotent stem cells. Using well-established SMC differentiation models, we have demonstrated that miR-34a has an important role in SMC differentiation from murine and human embryonic stem cells. Surprisingly, deacetylase sirtuin 1 (SirT1), one of the top predicted targets, was positively regulated by miR-34a during SMC differentiation. Mechanistically, we demonstrated that miR-34a promoted differentiating stem cells' arrest at G0G1 phase and observed a significantly decreased incorporation of miR-34a and SirT1 RNA into Ago2-RISC complex upon SMC differentiation. Importantly, we have identified SirT1 as a transcriptional activator in the regulation of SMC gene programme. Finally, our data showed that SirT1 modulated the enrichment of H3K9 tri-methylation around the SMC gene-promoter regions. Taken together, our data reveal a specific regulatory pathway that miR-34a positively regulates its target gene SirT1 in a cellular context-dependent and sequence-specific manner and suggest a functional role for this pathway in SMC differentiation from stem cells in vitro and in vivo

Animal modelling for inherited central vision loss.

Disease-causing variants of a large number of genes trigger inherited retinal degeneration leading to photoreceptor loss. Because cones are essential for daylight and central vision such as reading, mobility, and face recognition, this review focuses on a variety of animal models for cone diseases. The pertinence of using these models to reveal genotype/phenotype correlations and to evaluate new therapeutic strategies is discussed. Interestingly, several large animal models recapitulate human diseases and can serve as a strong base from which to study the biology of disease and to assess the scale-up of new therapies. Examples of innovative approaches will be presented such as lentiviral-based transgenesis in pigs and adeno-associated virus (AAV)-gene transfer into the monkey eye to investigate the neural circuitry plasticity of the visual system. The models reported herein permit the exploration of common mechanisms that exist between different species and the identification and highlighting of pathways that may be specific to primates, including humans

A laboratory study on risk assessment of microcystin-RR in cropland

The persistence time and risk of microcystin-RR (MC-RR) in cropland via irrigation were investigated under laboratory conditions. In order to evaluate the efficiency of the potential adsorption and biodegradation of MC-RR in cropland and the persistence time of MC-RR for crop irrigation, high performance liquid chromatography (HPLC) was used to quantify the amount of MC-RR in solutions. Our study indicated that MC-RR could be adsorbed and biodegraded in cropland soils. MC-RR at 6.5 mg/L could be completely degraded within 6 days with a lag phase of 1 - 2 days. In the presence of humic acid, the same amount of MC-RR could be degraded within 4 days without a lag phase. Accordingly, the persistence time of MC-RR in cropland soils should be about 6 days. This result also suggested the beneficial effects of the organic fertilizer utilization for the biodegradation of MC-RR in cropland soils. Our studies also demonstrated that MC-RR at low concentration ( 100 mu g/L) significantly inhibited the growth of plants. High sensitivity of the sprouting stage plants to MC-RR treatments as well as the strong inhibitory effects resulting from prolonged irrigation further indicated that this MC-RR growth-inhibition may vary with the duration of irrigation and life stage of the plants. (c) 2007 Published by Elsevier Ltd.The persistence time and risk of microcystin-RR (MC-RR) in cropland via irrigation were investigated under laboratory conditions. In order to evaluate the efficiency of the potential adsorption and biodegradation of MC-RR in cropland and the persistence time of MC-RR for crop irrigation, high performance liquid chromatography (HPLC) was used to quantify the amount of MC-RR in solutions. Our study indicated that MC-RR could be adsorbed and biodegraded in cropland soils. MC-RR at 6.5 mg/L could be completely degraded within 6 days with a lag phase of 1 - 2 days. In the presence of humic acid, the same amount of MC-RR could be degraded within 4 days without a lag phase. Accordingly, the persistence time of MC-RR in cropland soils should be about 6 days. This result also suggested the beneficial effects of the organic fertilizer utilization for the biodegradation of MC-RR in cropland soils. Our studies also demonstrated that MC-RR at low concentration ( 100 mu g/L) significantly inhibited the growth of plants. High sensitivity of the sprouting stage plants to MC-RR treatments as well as the strong inhibitory effects resulting from prolonged irrigation further indicated that this MC-RR growth-inhibition may vary with the duration of irrigation and life stage of the plants. (c) 2007 Published by Elsevier Ltd

Observation of eight-photon entanglement

Using ultra-bright sources of pure-state entangled photons from parametric down conversion, an eight-photon interferometer and post-selection detection, we demonstrate the ability to experimentally manipulate eight individual photons and report the creation of an eight-photon Schr\"odinger cat state with an observed fidelity of $0.708 \pm 0.016$.Comment: 6 pages, 4 figure

Comparisons of host mitochondrial, nuclear and endosymbiont bacterial genes reveal cryptic fig wasp species and the effects of Wolbachia on host mtDNA evolution and diversity

Background Figs and fig-pollinating wasp species usually display a highly specific one-to-one association. However, more and more studies have revealed that the "one-to-one" rule has been broken. Co-pollinators have been reported, but we do not yet know how they evolve. They may evolve from insect speciation induced or facilitated by Wolbachia which can manipulate host reproduction and induce reproductive isolation. In addition, Wolbachia can affect host mitochondrial DNA evolution, because of the linkage between Wolbachia and associated mitochondrial haplotypes, and thus confound host phylogeny based on mtDNA. Previous research has shown that fig wasps have the highest incidence of Wolbachia infection in all insect taxa, and Wolbachia may have great influence on fig wasp biology. Therefore, we look forward to understanding the influence of Wolbachia on mitochondrial DNA evolution and speciation in fig wasps. Results We surveyed 76 pollinator wasp specimens from nine Ficus microcarpa trees each growing at a different location in Hainan and Fujian Provinces, China. We found that all wasps were morphologically identified as Eupristina verticillata, but diverged into three clades with 4.22-5.28% mtDNA divergence and 2.29-20.72% nuclear gene divergence. We also found very strong concordance between E. verticillata clades and Wolbachia infection status, and the predicted effects of Wolbachia on both mtDNA diversity and evolution by decreasing mitochondrial haplotypes. Conclusions Our study reveals that the pollinating wasp E. verticillata on F. microcarpa has diverged into three cryptic species, and Wolbachia may have a role in this divergence. The results also indicate that Wolbachia strains infecting E. verticillata have likely resulted in selective sweeps on host mitochondrial DNA

Demon-like Algorithmic Quantum Cooling and its Realization with Quantum Optics

The simulation of low-temperature properties of many-body systems remains one of the major challenges in theoretical and experimental quantum information science. We present, and demonstrate experimentally, a universal cooling method which is applicable to any physical system that can be simulated by a quantum computer. This method allows us to distill and eliminate hot components of quantum states, i.e., a quantum Maxwell's demon. The experimental implementation is realized with a quantum-optical network, and the results are in full agreement with theoretical predictions (with fidelity higher than 0.978). These results open a new path for simulating low-temperature properties of physical and chemical systems that are intractable with classical methods.Comment: 7 pages, 5 figures, plus supplementarity material

Topological Quantum Phase Transition in Synthetic Non-Abelian Gauge Potential

The method of synthetic gauge potentials opens up a new avenue for our understanding and discovering novel quantum states of matter. We investigate the topological quantum phase transition of Fermi gases trapped in a honeycomb lattice in the presence of a synthetic non- Abelian gauge potential. We develop a systematic fermionic effective field theory to describe a topological quantum phase transition tuned by the non-Abelian gauge potential and ex- plore its various important experimental consequences. Numerical calculations on lattice scales are performed to compare with the results achieved by the fermionic effective field theory. Several possible experimental detection methods of topological quantum phase tran- sition are proposed. In contrast to condensed matter experiments where only gauge invariant quantities can be measured, both gauge invariant and non-gauge invariant quantities can be measured by experimentally generating various non-Abelian gauges corresponding to the same set of Wilson loops

Evaluation of preoperative intra-aortic balloon pump in coronary patients with severe left ventricular dysfunction undergoing OPCAB surgery: early and mid-term outcomes

<p>Abstract</p> <p>Background</p> <p>The purpose of the present study was to evaluate the safety and the cost-effectiveness of using preoperative IABP as support compared with postoperative IABP treatment in coronary patients with severe left ventricular dysfunction (SLVD) who is undergoing off-pump coronary artery bypass surgery (OPCAB), including early outcomes, hospital mortality and morbidity, and mid-term follow-up outcomes.</p> <p>Methods</p> <p>Between March 2000 and December 2008, we prospectively and randomly studied the insertion of preoperative IABP in 115 (7.4%) and postoperative IABP in 106 (6.8%) of the 1560 consecutive patients. Group A is preoperative IABP therapy. Group B is postoperative IABP therapy.</p> <p>Results</p> <p>There was no significant difference in the number of grafts used between the two groups. Completeness of revascularization did not differ between the two groups. The statistically significant difference was hospital mortality (2.6% in group A vs. 3.8% in group B) (<it>p </it>< 0.05). And there was significant reduction in postoperative low cardiac output, malignant arrhythmia, acute renal failure and length of stay in ICU in group A, compared with group B (<it>p </it>< 0.05). In the two groups, six-, 12-, 24- and 48-month survival rates were similar. In the study the degree of improvement in angina and quality of life did not differ significantly between the two groups.</p> <p>Conclusion</p> <p>The use of preoperative IABP in SLVD patients undergoing OPCAB is of safety and effectiveness. The combined use of preoperative IABP and OPCAB allows complete revascularization in SLVD patients with an important reduction in operative mortality and excellent mid-term results.</p

High throughput mutagenesis for identification of residues regulating human prostacyclin (hIP) receptor

The human prostacyclin receptor (hIP receptor) is a seven-transmembrane G protein-coupled receptor (GPCR) that plays a critical role in vascular smooth muscle relaxation and platelet aggregation. hIP receptor dysfunction has been implicated in numerous cardiovascular abnormalities, including myocardial infarction, hypertension, thrombosis and atherosclerosis. Genomic sequencing has discovered several genetic variations in the PTGIR gene coding for hIP receptor, however, its structure-function relationship has not been sufficiently explored. Here we set out to investigate the applicability of high throughput random mutagenesis to study the structure-function relationship of hIP receptor. While chemical mutagenesis was not suitable to generate a mutagenesis library with sufficient coverage, our data demonstrate error-prone PCR (epPCR) mediated mutagenesis as a valuable method for the unbiased screening of residues regulating hIP receptor function and expression. Here we describe the generation and functional characterization of an epPCR derived mutagenesis library compromising >4000 mutants of the hIP receptor. We introduce next generation sequencing as a useful tool to validate the quality of mutagenesis libraries by providing information about the coverage, mutation rate and mutational bias. We identified 18 mutants of the hIP receptor that were expressed at the cell surface, but demonstrated impaired receptor function. A total of 38 non-synonymous mutations were identified within the coding region of the hIP receptor, mapping to 36 distinct residues, including several mutations previously reported to affect the signaling of the hIP receptor. Thus, our data demonstrates epPCR mediated random mutagenesis as a valuable and practical method to study the structurefunction relationship of GPCRs. © 2014 Bill et al