Mitochondrial DNA damage and atherosclerosis.

Mitochondria are often regarded as the cellular powerhouses through their ability to generate ATP, the universal fuel for metabolic processes. However, in recent years mitochondria have been recognised as critical regulators of cell death, inflammation, metabolism, and the generation of reactive oxygen species (ROS). Thus, mitochondrial dysfunction directly promotes cell death, inflammation, and oxidative stress and alters metabolism. These are key processes in atherosclerosis and there is now evidence that mitochondrial DNA (mtDNA) damage leads to mitochondrial dysfunction and promotes atherosclerosis directly. In this review we discuss the recent evidence for and mechanisms linking mtDNA defects and atherosclerosis and suggest areas of mitochondrial biology that are potential therapeutic targets.NoneThis is the Author Accepted Manuscript of the article "Mitochondrial DNA damage and atherosclerosis" published in Trends in Endocrinology and Metabolism on September 2104. This version is embargoed until September 2015 in line with publisher requirements. The published version of record is available on the journal website at http://dx.doi.org/10.1016/j.tem.2014.06.00

Settlement behaviour of hybrid asphalt-ballast railway tracks

The use of structural asphalt layers inside ballasted railway tracks is attractive because it can increase track bending stiffness. Therefore, for the first time, this paper investigates the long-term settlement characteristics of asphaltic track in the presence of a subgrade stiffness transition zone. Phased load cyclic compression laboratory tests are performed on a large-scale hybrid asphalt-ballast track, supported by subgrade with varying stiffness. It is found that an asphaltic layer acts as a bridge to shield the subgrade from high stresses. It is also found that the asphalt reduces track settlement, and is particularly effective when subgrade stiffness is low

Development of metal-containing polymers for optoelectronic applications

Most of the work in organic electroluminescent polymers has been focused on organic conjugated polymers. However, polymers attached with transition metal complex have received relatively less attention. We have synthesized and studied the light emitting properties of some metal containing polymers based on the polypyridine complexes of rhenium and ruthenium. These complexes exhibit long-lived excited states caused by the metal to ligand charge transfer transitions. By varying the structure of the ligand and/or the transition metal, we are able to fine-tune the electronic properties of the resulting metal complexes.We have synthesized a series of poly(phenylenevinylene) (PPV) derivatives which are functionalized with ruthenium polypyridine complexes at the polymer mainchain or side chain. These complexes are able to act as photosensitizers which enhance the photoconductivity of these polymers at longer wavelength. Both the conjugatedbackbone and the metal complex can emit light upon excitation. As a result, it is possible to tune the color by loading different amount of ruthenium complex to the polymer. Luminescence studies showed that the ruthenium complex could quench the emission of the conjugated backbone in some polymers, which suggests an energy transfer processbetween the backbone and the metal complexes. It was also found that the presence of metal complexes could enhance the charge carrier mobilities of the polymers, as the metal and/or ligands can act as extra charge carriers in the charge transport process.published_or_final_versio

Quantum Communications with Compressed Decoherence Using Bright Squeezed Light

We propose a scheme for long-distance distribution of quantum entanglement in which the entanglement between qubits at intermediate stations of the channel is established by using bright light pulses in squeezed states coupled to the qubits in cavities with a weak dispersive interaction. The fidelity of the entanglement between qubits at the neighbor stations (10 km apart from each other) obtained by postselection through the balanced homodyne detection of 7 dB squeezed pulses can reach F=0.99 without using entanglement purification, at same time, the probability of successful generation of entanglement is 0.34.Comment: 4 pages, 2 figure

Spin correlations in the electron-doped high-transition-temperature superconductor Nd{2-x}Ce{x}CuO{4+/-delta}

High-transition-temperature (high-Tc) superconductivity develops near antiferromagnetic phases, and it is possible that magnetic excitations contribute to the superconducting pairing mechanism. To assess the role of antiferromagnetism, it is essential to understand the doping and temperature dependence of the two-dimensional antiferromagnetic spin correlations. The phase diagram is asymmetric with respect to electron and hole doping, and for the comparatively less-studied electron-doped materials, the antiferromagnetic phase extends much further with doping [1, 2] and appears to overlap with the superconducting phase. The archetypical electron-doped compound Nd{2-x}Ce{x}CuO{4\pm\delta} (NCCO) shows bulk superconductivity above x \approx 0.13 [3, 4], while evidence for antiferromagnetic order has been found up to x \approx 0.17 [2, 5, 6]. Here we report inelastic magnetic neutron-scattering measurements that point to the distinct possibility that genuine long-range antiferromagnetism and superconductivity do not coexist. The data reveal a magnetic quantum critical point where superconductivity first appears, consistent with an exotic quantum phase transition between the two phases [7]. We also demonstrate that the pseudogap phenomenon in the electron-doped materials, which is associated with pronounced charge anomalies [8-11], arises from a build-up of spin correlations, in agreement with recent theoretical proposals [12, 13].Comment: 5 pages, 4 figure

True nature of an archetypal self-assembly system: Mobile Au-thiolate species on Au(111)

Alkanethiol self-assembled monolayer (SAM) phases on Au(111) have been assumed to involve direct S head group bonding to the substrate. Using x-ray standing wave experiments, we show the thiolate actually bonds to gold adatoms; self-organization in these archetypal SAM systems must therefore be governed by the movement of these Au-S-R moieties on the surface between two distinct local hollow sites on the surface. The results of recent ab initio total energy calculations provide strong support for this description, and a rationale for the implied significant molecular mobility in these systems

Restoring mitochondrial DNA copy number preserves mitochondrial function and delays vascular aging in mice.

Aging is the largest risk factor for cardiovascular disease, yet the molecular mechanisms underlying vascular aging remain unclear. Mitochondrial DNA (mtDNA) damage is linked to aging, but whether mtDNA damage or mitochondrial dysfunction is present and directly promotes vascular aging is unknown. Furthermore, mechanistic studies in mice are severely hampered by long study times and lack of sensitive, repeatable and reproducible parameters of arterial aging at standardized early time points. We examined the time course of multiple invasive and noninvasive arterial physiological parameters and structural changes of arterial aging in mice, how aging affects vessel mitochondrial function, and the effects of gain or loss of mitochondrial function on vascular aging. Vascular aging was first detected by 44 weeks (wk) of age, with reduced carotid compliance and distensibility, increased β-stiffness index and increased aortic pulse wave velocity (PWV). Aortic collagen content and elastin breaks also increased at 44 wk. Arterial mtDNA copy number (mtCN) and the mtCN-regulatory proteins TFAM, PGC1α and Twinkle were reduced by 44 wk, associated with reduced mitochondrial respiration. Overexpression of the mitochondrial helicase Twinkle (Tw+ ) increased mtCN and improved mitochondrial respiration in arteries, and delayed physiological and structural aging in all parameters studied. Conversely, mice with defective mitochondrial polymerase-gamma (PolG) and reduced mtDNA integrity demonstrated accelerated vascular aging. Our study identifies multiple early and reproducible parameters for assessing vascular aging in mice. Arterial mitochondrial respiration reduces markedly with age, and reduced mtDNA integrity and mitochondrial function directly promote vascular aging

Different cell kinetic changes in rat stomach cancer after treatment with celecoxib or indomethacin: Implications on chemoprevention

Aim: Mechanisms underlying the chemopreventive effects of cyclooxygenase (COX) inhibitors remain elusive. We have previously shown that celecoxib but not indomethacin could prevent carcinogen-induced gastric cancer development in Wistar rats. This chemopreventive effect appeared to be independent of COX-2 and prostaglandin (PG) E2 suppression since the lowest PGE2 was obtained in indomethacin group. This study compared the cell kinetic changes in stomachs of rats after treatment with celecoxib (5, 10, 20 mg/(kg·d)) or indomethacin (3 mg/(kg·d)) to gain more insights into the chemopreventive mechanism. Methods: The apoptosis and proliferation indexes in gastric tumor, adjacent non-cancer tissues and normal gastric tissues were determined. Apoptosis was quantified by apoptotic nuclei counting and TUNEL, whereas proliferation was determined by Ki67 immunostaining. Results: Treatment with either celecoxib or indomethacin inhibited gastric tumor proliferation by more than 65% (P<0.02). However, celecoxib caused a dose-dependent increase in apoptosis (P<0.05) which was not seen in indomethacin-treated tumors (P = 0.54). The highest apoptosis to proliferation ratio was seen in tumors treated with celecoxib at 10 mg/(kg·d). Treatment with this dose of celecoxib was associated with the lowest incidence of gastric cancer development. Conclusion: Our findings suggest that the difference in chemopreventive effects of indomethacin and celecoxib in this animal model of gastric carcinogenesis is largely due to the differential cell kinetic changes, which does not correlate with the degree of COX-2 and PG suppression. © 2005 The WJG Press and Elsevier Inc. All rights reserved.published_or_final_versio

Double In Situ Approach for the Preparation of Polymer Nanocomposite with Multi-functionality

A novel one-step synthetic route, the double in situ approach, is used to produce both TiO2nanoparticles and polymer (PET), and simultaneously forming a nanocomposite with multi-functionality. The method uses the release of water during esterification to hydrolyze titanium (IV) butoxide (Ti(OBu)4) forming nano-TiO2in the polymerization vessel. This new approach is of general significance in the preparation of polymer nanocomposites, and will lead to a new route in the synthesis of multi-functional polymer nanocomposites