Obesity and type-2 diabetes as inducers of premature cellular senescence and ageing

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Cellular senescence is now considered as a major mechanism in the development and progression of various diseases and this may include metabolic diseases such as obesity and type-2 diabetes. The presence of obesity and diabetes is a major risk factor in the development of additional health conditions, such as cardiovascular disease, kidney disease and cancer. Since senescent cells can drive disease development, obesity and diabetes can potentially create an environment that accelerates cell senescence within other tissues of the body. This can consequently manifest as age-related biological impairments and secondary diseases. Cell senescence in cell types linked with obesity and diabetes, namely adipocytes and pancreatic beta cells will be explored, followed by a discussion on the role of obesity and diabetes in accelerating ageing through induction of premature cell senescence mediated by high glucose levels and oxidised low-density lipoproteins. Particular emphasis will be placed on accelerated cell senescence in endothelial progenitor cells, endothelial cells and vascular smooth muscle cells with relation to cardiovascular disease and proximal tubular cells with relation to kidney disease. A summary of the potential strategies for therapeutically targeting senescent cells for improving health is also presented

The use of ratiometric fluorescence measurements of the voltage sensitive dye Di-4-ANEPPS to examine action potential characteristics and drug effects on human induced pluripotent stem cell-derived cardiomyocytes

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and higher throughput platforms have emerged as potential tools to advance cardiac drug safety screening. This study evaluated the use of high bandwidth photometry applied to voltage-sensitive fluorescent dyes (VSDs) to assess drug-induced changes in action potential characteristics of spontaneously active hiPSC-CM. Human iPSC-CM from 2 commercial sources (Cor.4U and iCell Cardiomyocytes) were stained with the VSD di-4-ANEPPS and placed in a specialized photometry system that simultaneously monitors 2 wavebands of emitted fluorescence, allowing ratiometric measurement of membrane voltage. Signals were acquired at 10 kHz and analyzed using custom software. Action potential duration (APD) values were normally distributed in cardiomyocytes (CMC) from both sources though the mean and variance differed significantly (APD90: 229 ± 15 ms vs 427 ± 49 ms [mean ± SD, P < 0.01]; average spontaneous cycle length: 0.99 ± 0.02 s vs 1.47 ± 0.35 s [mean ± SD, P < 0.01], Cor.4U vs iCell CMC, respectively). The 10–90% rise time of the AP (Trise) was ∼6 ms and was normally distributed when expressed as 1/T2riseTrise2 in both cell preparations. Both cell types showed a rate dependence analogous to that of adult human cardiac cells. Furthermore, nifedipine, ranolazine, and E4031 had similar effects on cardiomyocyte electrophysiology in both cell types. However, ranolazine and E4031 induced early after depolarization-like events and high intrinsic firing rates at lower concentrations in iCell CMC. These data show that VSDs provide a minimally invasive, quantitative, and accurate method to assess hiPSC-CM electrophysiology and detect subtle drug-induced effects for drug safety screening while highlighting a need to standardize experimental protocols across preparations

Multibeam Maser Survey of methanol and excited OH in the Magellanic clouds: new detections and maser abundance estimates

‘The definitive version is available at www.blackwell-synergy.com.’ Copyright Blackwell Publishing DOI: 10.1111/j.1365-2966.2008.12888.xPeer reviewe

Stability of the monoclinic phase in the ferroelectric perovskite PbZr(1-x)TixO3

Recent structural studies of ferroelectric PbZr(1-x)TixO3 (PZT) with x= 0.48, have revealed a new monoclinic phase in the vicinity of the morphotropic phase boundary (MPB), previously regarded as the the boundary separating the rhombohedral and tetragonal regions of the PZT phase diagram. In the present paper, the stability region of all three phases has been established from high resolution synchrotron x-ray powder diffraction measurements on a series of highly homogeneous samples with 0.42 <=x<= 0.52. At 20K the monoclinic phase is stable in the range 0.46 <=x<= 0.51, and this range narrows as the temperature is increased. A first-order phase transition from tetragonal to rhombohedral symmetry is observed only for x= 0.45. The MPB, therefore, corresponds not to the tetragonal-rhombohedral phase boundary, but instead to the boundary between the tetragonal and monoclinic phases for 0.46 <=x<= 0.51. This result provides important insight into the close relationship between the monoclinic phase and the striking piezoelectric properties of PZT; in particular, investigations of poled samples have shown that the monoclinic distortion is the origin of the unusually high piezoelectric response of PZT.Comment: REVTeX file, 7 figures embedde

Magnetic trapping of ultracold neutrons

Three-dimensional magnetic confinement of neutrons is reported. Neutrons are loaded into an Ioffe-type superconducting magnetic trap through inelastic scattering of cold neutrons with 4He. Scattered neutrons with sufficiently low energy and in the appropriate spin state are confined by the magnetic field until they decay. The electron resulting from neutron decay produces scintillations in the liquid helium bath that results in a pulse of extreme ultraviolet light. This light is frequency downconverted to the visible and detected. Results are presented in which 500 +/- 155 neutrons are magnetically trapped in each loading cycle, consistent with theoretical predictions. The lifetime of the observed signal, 660 s +290/-170 s, is consistent with the neutron beta-decay lifetime.Comment: 17 pages, 18 figures, accepted for publication in Physical Review

The Energetics of Li Off-Centering in K1−x_{1-x}Lix_xTaO3_3; First Principles Calculations

K$_{1-x}$Li$_{x}$TaO$_3$ (KLT) solid solutions exhibit a variety of interesting physical phenomena related to large displacements of Li-ions from ideal perovskite A-site positions. First-principles calculations for KLT supercells were used to investigate these phenomena. Lattice dynamics calculations for KLT exhibit a Li off-centering instability. The energetics of Li-displacements for isolated Li-ions and for Li-Li pairs up to 4th neighbors were calculated. Interactions between nearest neighbor Li-ions, in a Li-Li pair, strongly favor ferroelectric alignment along the pair axis. Such Li-Li pairs can be considered "seeds" for polar nanoclusters in KLT. Electrostriction, local oxygen relaxation, coupling to the KT soft-mode, and interactions with neighboring Li-ions all enhance the polarization from Li off-centering. Calculated hopping barriers for isolated Li-ions and for nearest neighbor Li-Li pairs are in good agreement with Arrhenius fits to experimental dielectric data.Comment: 14 pages including 10 figures. To Physical Review B. Replaced after corrections due to referees' remark

Third party consultation: a method for the study and resolution of conflict

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66597/2/10.1177_002200277201600105.pd

The 6-GHz methanol multibeam maser catalogue - I. Galactic Centre region, longitudes 345? to 6?

We have conducted a Galactic plane survey of methanol masers at 6668 MHz using a sevenbeam receiver on the Parkes telescope. Here we present results from the first part, which provides sensitive unbiased coverage of a large region around the Galactic Centre. Details are given for 183 methanol maser sites in the longitude range 345◦ through the Galactic Centre to 6◦. Within 6◦ of the Galactic Centre, we found 88 maser sites, of which more than half (48) are new discoveries. The masers are confined to a narrow Galactic latitude range, indicative of many sources at the Galactic Centre distance and beyond, and confined to a thin disc population; there is no high-latitude population that might be ascribed to the Galactic bulge. Within 2◦ of the Galactic Centre the maser velocities all lie between −60 and +77 km s−1, a range much smaller than the 540 km s−1 range observed in CO. Elsewhere, the maser with highest positive velocity (+107 km s−1) occurs, surprisingly, near longitude 355◦ and is probably attributable to the Galactic bar. The maser with the most negative velocity (−127 km s−1) is near longitude 346◦, within the longitude–velocity locus of the near side of the ‘3-kpc arm’. It has the most extreme velocity of a clear population of masers associated with the near and far sides of the 3-kpc arm. Closer to the Galactic Centre the maser space density is generally low, except within 0.25 kpc of the Galactic Centre itself, the ‘Galactic Centre zone’, where it is 50 times higher, which is hinted at by the longitude distribution, and confirmed by the unusual velocities.AA and DW-McS acknowledge support from a Science and Technology Facilities Council (STFC) studentship. LQ acknowledges support from the EU Framework 6 Marie Curie Early Stage Training programme under contract MEST-CT-2005-19669 ‘ESTRELA’

Retrieval of optical and microphysical properties of transported Saharan dust over Athens and Granada based on multi-wavelength Raman lidar measurements: Study of the mixing processes

In this paper we extract the aerosol microphysical properties for a collection of mineral dust cases measured by multi-wavelength depolarization Raman lidar systems located at the National Technical University of Athens (NTUA, Athens, Greece) and the Andalusian Institute for Earth System Research (IISTA-CEAMA, Granada, Spain). The lidar-based retrievals were carried out with the Spheroidal Inversion eXperiments software tool (SphInX) developed at the University of Potsdam (Germany). The software uses regularized inversion of a two-dimensional enhancement of the Mie model based on the spheroid-particle approximation with the aspect ratio determining the particle shape. The selection of the cases was based on the transport time from the source regions to the measuring sites. The aerosol optical depth as measured by AERONET ranged from 0.27 to 0.54 (at 500 nm) depending on the intensity of each event. Our analysis showed the hourly mean particle linear depolarization ratio and particle lidar ratio values at 532 nm ranging from 11 to 34% and from 42 to 79 sr respectively, depending on the mixing status, the corresponding air mass pathways and their transport time. Cases with shorter transport time showed good agreement in terms of the optical and SphInX-retrieved microphysical properties between Athens and Granada providing a complex refractive index value equal to 1.4 + 0.004i. On the other hand, the results for cases with higher transport time deviated from the aforementioned ones as well as from each other, providing, in particular, an imaginary part of the refractive index ranging from 0.002 to 0.005. Reconstructions of two-dimensional shape-size distributions for each selected layer showed that the dominant effective particle shape was prolate with diverse spherical contributions. The retrieved volume concentrations reflect overall the intensity of the episodes.Spanish Ministry of Sciences, Innovation and Universities through project CGL2016-81092,Spanish Ministry of Education, Culture and Sports through grant FPU14/0368