4,401 research outputs found

    Highly sensitive luminescence detection of photosensitized singlet oxygen within photonic crystal fibre

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    Highly sensitive, quantitative detection of singlet oxygen (1O2) is required for the evaluation of newly developed photosensitizers and the elucidation of the mechanisms of many processes in which singlet oxygen is known, or believed, to be involved. The direct detection of 1O2, via its intrinsic phosphorescence at 1270 nm, is challenging because of the extremely low intensity of this emission, coupled with the low quantum efficiency of currently available photodetectors at this wavelength. We introduce hollowcore photonic crystal fibre (HC-PCF) as a novel optofluidic modality for photosensitization and detection of 1O2. We report the use of this approach to achieve highly sensitive detection of the luminescence decay of 1O2, produced using two common photosensitizers, Rose Bengal and Hypericin, within the 60-m diameter core of a 15-cm length of HC-PCF. We demonstrate the feasibility of directly detecting sub-picomole quantities of 1O2 using this methodology, and identify some aspects of the HC-PCF technology that can be improved to yield even higher detection sensitivity

    Intervertebral disc cells as competent phagocytes in vitro: implications for cell death in disc degeneration

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    INTRODUCTION: Apoptosis has been reported to occur in the intervertebral disc. Elsewhere in the body, apoptotic cells are cleared from the system via phagocytosis by committed phagocytes such as macrophages, reducing the chance of subsequent inflammation. These cells, however, are not normally present in the disc. We investigated whether disc cells themselves can be induced to become phagocytic and so have the ability to ingest and remove apoptotic disc cells, minimising the damage to their environment. METHOD: Bovine nucleus pulposus cells from caudal intervertebral discs were grown in culture and exposed to both latex particles (which are ingested by committed phagocytes) and apoptotic cells. Their response was monitored via microscopy, including both fluorescent and video microscopy, and compared with that seen by cell lines of monocytes/macrophages (THP-1 and J774 cells), considered to be committed phagocytes, in addition to a nonmacrophage cell line (L929 fibroblasts). Immunostaining for the monocyte/macrophage marker, CD68, was also carried out. RESULTS: Disc cells were able to ingest latex beads at least as efficiently, if not more so, than phagocytic THP-1 and J774 cells. Disc cells ingested a greater number of beads per cell than the committed phagocytes in a similar time scale. In addition, disc cells were able to ingest apoptotic cells when cocultured in monolayer with a UV-treated population of HeLa cells. Apoptotic disc cells, in turn, were able to stimulate phagocytosis by the committed macrophages. CD68 immunostaining was strong for THP-1 cells but negligible for disc cells, even those that had ingested beads. CONCLUSION: In this study, we have shown that intervertebral disc cells are capable of behaving as competent phagocytes (that is, ingesting latex beads) and apoptotic cells. In terms of number of particles, they ingest more than the monocyte/macrophage cells, possibly due to their greater size. The fact that disc cells clearly can undergo phagocytosis has implications for the intervertebral disc in vivo. Here, where cell death is reported to be common yet there is normally no easy access to a macrophage population, the endogenous disc cells may be encouraged to undergo phagocytosis (for example, of neighbouring cells within cell clusters)

    Which anthropometric and lower body power variables are predictive of professional and amateur playing status in male rugby union players?

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    The purpose of this study was to compare anthropometric and lower body power measurements between current professional and amateur male rugby union players. The present study also sought to determine which anthropometric and physical performance variables were predictive of playing standard. Thirty professional and 30 amateur RU players performed Wattbike 6 s maximal effort (WB6S) and countermovement (CMJ) and squat jump (SJ) assessments, anthropometric measures were also taken. Dependant variables recorded and analysed including: body mass, stature, Σ8 site skinfolds, WB6S absolute and relative peak power, CMJ and SJ average concentric force, jump height, peak velocity, time to peak force, rate of force development (RFD) and absolute and relative peak force and power. Professional players were heavier, taller and leaner than their amateur counterparts (p < 0.05). Professional players performed significantly better in all physical performance measures except CMJ and SJ time to peak force, CMJ RFD and SJ relative peak force. Variables which were predictive of playing standard were: Σ8 skinfolds, CMJ peak velocity and WB6S absolute and relative peak power (p < 0.05). These findings indicate that the current body of male professional RU players is anthropometrically and physically superior to their amateur counterparts, although not all variables assessed here were predictive of playing standard. Data presented here indicate that Σ8 skinfolds, WB6S absolute and relative power and CMJ peak velocity are predictive of playing standard, whereas other anthropometric and strength and power variables are not

    ‘Priming’ exercise and O2 uptake kinetics during treadmill running

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    We tested the hypothesis that priming exercise would speed kinetics during treadmill running. Eight subjects completed a square-wave protocol, involving two bouts of treadmill running at 70% of the difference between the running speeds at lactate threshold (LT) and max, separated by 6-min of walking at 4 km h−1, on two occasions. Oxygen uptake was measured breath-by-breath and subsequently modelled using non-linear regression techniques. Heart rate and blood lactate concentration were significantly elevated prior to the second exercise bout compared to the first. However, kinetics was not significantly different between the first and second exercise bouts (mean ± S.D., phase II time constant, Bout 1: 16 ± 3 s vs. Bout 2: 16 ± 4 s; slow component amplitude, Bout 1: 0.24 ± 0.10 L min−1vs. Bout 2: 0.20 ± 0.12 L min−1; mean response time, Bout 1: 34 ± 4 s vs. Bout 2: 34 ± 6 s; P > 0.05 for all comparisons). These results indicate that, contrary to previous findings with other exercise modalities, priming exercise does not alter kinetics during high-intensity treadmill running, at least in physically active young subjects. We speculate that the relatively fast kinetics and the relatively small slow component in the control (‘un-primed’) condition negated any enhancement of kinetics by priming exercise in this exercise modality

    Developing a Tanshinone IIA Memetic by Targeting MIOS to Regulate mTORC1 and Autophagy in Glioblastoma

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    Tanshinone IIA (T2A) is a bioactive compound that provides promise in the treatment of Glioblastoma multiforme (GBM), with a range of molecular mechanisms including inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) and the induction of autophagy. Recently, T2A has been demonstrated to function through sestrin 2 (SESN) to inhibit mTORC1 activity, but this pathway has not been investigated regarding autophagy. Here we employed the model system Dictyostelium discoideum and GBM cell lines to investigate the role of T2A in autophagy induction, focusing on the regulation of SESN via a GATOR2 component MIOS, to mTORC1. We show that in D. discoideum, T2A treatment induces autophagy, and both this effect and mTORC1 inhibition is lost upon ablation of either SESN (sesn-) or MIOS (mios-). We then investigated targeting MIOS to reproduce this effect of T2A. Here, computational analysis identified 25 novel compounds predicted to strongly bind the human MIOS protein, and one compound (MIOS inhibitor 3; Mi3) that reduced cell proliferation in two GBM cell lines. Furthermore, Mi3 specificity was demonstrated through the reduction of D. discoideum cell proliferation and induced autophagy, dependent upon MIOS. These effects were also confirmed in GBM cells, where Mi3 treatment also inhibited mTORC1 activity and induced autophagy. Thus, we identify a potential T2A mimetic with demonstrated effects on inhibition of mTORC1 and induction of autophagy in GBM cells

    Reconciling atmospheric and oceanic views of the transient climate response to emissions

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    The Transient Climate Response to Emissions (TCRE), the ratio of surface warming and cumulative carbon emissions, is controlled by a product of thermal and carbon contributions. The carbon contribution involves the airborne fraction and the ratio of ocean saturated and atmospheric carbon inventories, with this ratio controlled by ocean carbonate chemistry. The evolution of the carbon contribution to the TCRE is illustrated in a hierarchy of models: a box model of the atmosphere‐ocean and an Earth system model, both integrated for 1,000 years, and a suite of Earth system models integrated for 140 years. For all models, there is the same generic carbonate chemistry response: An acidifying ocean during emissions leads to a decrease in the ratio of the ocean saturated and atmospheric carbon inventories and the carbon contribution to the TCRE. Hence, ocean carbonate chemistry is important in controlling the magnitude of the TCRE and its evolution in time

    Image Flux Ratios of Gravitationally Lensed HS 0810+2554 with High Resolution Infrared Imaging

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    We report near simultaneous imaging using LMIRCam on the LBTI of the quadruply imaged lensed quasar HS 0810+2554 at wavelengths of 2.16, 3.7 and 4.78 μ4.78~\mum with a Full Width Half Max (FWHM) spatial resolution of 0 ⁣ ⁣.130^{\prime\prime}\!\!.13, 0 ⁣ ⁣.120^{\prime\prime}\!\!.12 and 0 ⁣ ⁣.150^{\prime\prime}\!\!.15 respectively, comparable to HST optical imaging. In the z=1.5\rm{z} = 1.5 rest frame of the quasar, the observed wavelengths correspond to 0.86, 1.48, and 1.91 μ1.91~\mum respectively. The two brightest images in the quad, A and B, are clearly resolved from each other with a separation of 0.1870.187^{\prime\prime}. The flux ratio of these two images (A/B) trends from 1.79 to 1.23 from 2.16 to 4.78 μ4.78~\mum. The trend in flux ratio is consistent with the 2.16 μ2.16~\mum flux originating from a small sized accretion disk in the quasar that experiences only microlensing. The excess flux above the contribution from the accretion disk at the two longer wavelengths originates from a larger sized region that experiences no microlensing. A simple model employing multiplicative factors for image B due to stellar microlensing (m)(m) and sub-structure millilensing (M)(M) is presented. The result is tightly constrained to the product m×M=1.79m\times M=1.79. Given the observational errors, the 60\% probability contour for this product stretches from m=2.6m= 2.6, M=0.69M = 0.69 to m=1.79m= 1.79, M=1.0M = 1.0, where the later is consistent with microlensing only.Comment: accepted A
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