714 research outputs found

    Pink1 and Parkin regulate Drosophila intestinal stem cell proliferation during stress and aging.

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    Intestinal stem cells (ISCs) maintain the midgut epithelium in Drosophila melanogaster Proper cellular turnover and tissue function rely on tightly regulated rates of ISC division and appropriate differentiation of daughter cells. However, aging and epithelial injury cause elevated ISC proliferation and decreased capacity for terminal differentiation of daughter enteroblasts (EBs). The mechanisms causing functional decline of stem cells with age remain elusive; however, recent findings suggest that stem cell metabolism plays an important role in the regulation of stem cell activity. Here, we investigate how alterations in mitochondrial homeostasis modulate stem cell behavior in vivo via RNA interference-mediated knockdown of factors involved in mitochondrial dynamics. ISC/EB-specific knockdown of the mitophagy-related genes Pink1 or Parkin suppresses the age-related loss of tissue homeostasis, despite dramatic changes in mitochondrial ultrastructure and mitochondrial damage in ISCs/EBs. Maintenance of tissue homeostasis upon reduction of Pink1 or Parkin appears to result from reduction of age- and stress-induced ISC proliferation, in part, through induction of ISC senescence. Our results indicate an uncoupling of cellular, tissue, and organismal aging through inhibition of ISC proliferation and provide insight into strategies used by stem cells to maintain tissue homeostasis despite severe damage to organelles

    Local control of intestinal stem cell homeostasis by enteroendocrine cells in the adult <i>Drosophila</i> midgut

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    Background: Enteroendocrine cells populate gastrointestinal tissues and are known to translate local cues into systemic responses through the release of hormones into the bloodstream.&lt;p&gt;&lt;/p&gt; Results: Here we report a novel function of enteroendocrine cells acting as local regulators of intestinal stem cell (ISC) proliferation through modulation of the mesenchymal stem cell niche in the &lt;i&gt;Drosophila&lt;/i&gt; midgut. This paracrine signaling acts to constrain ISC proliferation within the epithelial compartment. Mechanistically, midgut enteroendocrine cells secrete the neuroendocrine hormone Bursicon, which acts—beyond its known roles in development—as a paracrine factor on the visceral muscle (VM). Bursicon binding to its receptor, DLGR2, the ortholog of mammalian leucine-rich repeat-containing G protein-coupled receptors (LGR4-6), represses the production of the VM-derived EGF-like growth factor Vein through activation of cAMP.&lt;p&gt;&lt;/p&gt; Conclusions: We therefore identify a novel paradigm in the regulation of ISC quiescence involving the conserved ligand/receptor Bursicon/DLGR2 and a previously unrecognized tissue-intrinsic role of enteroendocrine cells.&lt;p&gt;&lt;/p&gt

    Development of a SiPM Camera for a Schwarzschild-Couder Cherenkov Telescope for the Cherenkov Telescope Array

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    We present the development of a novel 11328 pixel silicon photomultiplier (SiPM) camera for use with a ground-based Cherenkov telescope with Schwarzschild-Couder optics as a possible medium-sized telescope for the Cherenkov Telescope Array (CTA). The finely pixelated camera samples air-shower images with more than twice the optical resolution of cameras that are used in current Cherenkov telescopes. Advantages of the higher resolution will be a better event reconstruction yielding improved background suppression and angular resolution of the reconstructed gamma-ray events, which is crucial in morphology studies of, for example, Galactic particle accelerators and the search for gamma-ray halos around extragalactic sources. Packing such a large number of pixels into an area of only half a square meter and having a fast readout directly attached to the back of the sensors is a challenging task. For the prototype camera development, SiPMs from Hamamatsu with through silicon via (TSV) technology are used. We give a status report of the camera design and highlight a number of technological advancements that made this development possible.Comment: 8 pages, 5 figures, In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

    Active Galactic Nuclei under the scrutiny of CTA

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    Active Galactic Nuclei (hereafter AGN) produce powerful outflows which offer excellent conditions for efficient particle acceleration in internal and external shocks, turbulence, and magnetic reconnection events. The jets as well as particle accelerating regions close to the supermassive black holes (hereafter SMBH) at the intersection of plasma inflows and outflows, can produce readily detectable very high energy gamma-ray emission. As of now, more than 45 AGN including 41 blazars and 4 radiogalaxies have been detected by the present ground-based gamma-ray telescopes, which represents more than one third of the cosmic sources detected so far in the VHE gamma-ray regime. The future Cherenkov Telescope Array (CTA) should boost the sample of AGN detected in the VHE range by about one order of magnitude, shedding new light on AGN population studies, and AGN classification and unification schemes. CTA will be a unique tool to scrutinize the extreme high-energy tail of accelerated particles in SMBH environments, to revisit the central engines and their associated relativistic jets, and to study the particle acceleration and emission mechanisms, particularly exploring the missing link between accretion physics, SMBH magnetospheres and jet formation. Monitoring of distant AGN will be an extremely rewarding observing program which will inform us about the inner workings and evolution of AGN. Furthermore these AGN are bright beacons of gamma-rays which will allow us to constrain the extragalactic infrared and optical backgrounds as well as the intergalactic magnetic field, and will enable tests of quantum gravity and other "exotic" phenomena.Comment: 28 pages, 23 figure

    A calorimetric study of wildland fuels

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    The burning of two species of pine needles: Pinus halepensis and Pinus pinaster, was studied to characterize the behavior of the forest floor in wildland fires. These fuels are representative of the Mediterranean ecosystem and have very different shapes and surface-to-volume ratios. Calorimetry was performed using the FM-global fire propagation apparatus (FPA). To better understand the effects of transport in the fuel beds, the standard sample holder was replaced by a holder that allowed for the porous properties of the fuel to be studied in a systematic manner. These holders were designed with holes on the surface to allow for different air flow rates to pass through the holder and into the fuel sample. These characteristics created different internal fuel bed conditions and were the first such tests that could be identified that examined transport on this level in these types of wildland fuels. Tests were conducted under natural convection and forced flow. The test series results were analyzed with respect to the direct values of the measured variables and calculated values of heat release rate. Discrete variables of time to ignition, duration of flaming combustion and peak heat release rate were compared using an analysis of variance method. As the experiments were conducted under well-ventilated conditions, the heat release rate calculated by calorimetry was compared to mass loss rate and heat of combustion. CO concentration in time proved to be a good indicator of the combustion dynamics in the fuel bed. Heat release rate, time to ignition and time to reach peak heat release rate indicated a strong dependence on flow conditions and on fuel specie. It was shown that the transport processes in the fuel beds had a significant effect on the burning characteristics

    A Search for Very High-Energy Gamma Rays from the Missing Link Binary Pulsar J1023+0038 with VERITAS

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    The binary millisecond radio pulsar PSR J1023+0038 exhibits many characteristics similar to the gamma-ray binary system PSR B1259--63/LS 2883, making it an ideal candidate for the study of high-energy non-thermal emission. It has been the subject of multi-wavelength campaigns following the disappearance of the pulsed radio emission in 2013 June, which revealed the appearance of an accretion disk around the neutron star. We present the results of very high-energy gamma-ray observations carried out by VERITAS before and after this change of state. Searches for steady and pulsed emission of both data sets yield no significant gamma-ray signal above 100 GeV, and upper limits are given for both a steady and pulsed gamma-ray flux. These upper limits are used to constrain the magnetic field strength in the shock region of the PSR J1023+0038 system. Assuming that very high-energy gamma rays are produced via an inverse-Compton mechanism in the shock region, we constrain the shock magnetic field to be greater than ∼\sim2 G before the disappearance of the radio pulsar and greater than ∼\sim10 G afterwards.Comment: 7 pages, 3 figures, accepted for publication in Ap

    VERITAS and Multiwavelength Observations of the BL Lacertae Object 1ES 1741+196

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    We present results from multiwavelength observations of the BL Lacertae object 1ES 1741+196, including results in the very-high-energy γ\gamma-ray regime using the Very Energetic Radiation Imaging Telescope Array System (VERITAS). The VERITAS time-averaged spectrum, measured above 180 GeV, is well-modelled by a power law with a spectral index of 2.7±0.7stat±0.2syst2.7\pm0.7_{\mathrm{stat}}\pm0.2_{\mathrm{syst}}. The integral flux above 180 GeV is (3.9±0.8stat±1.0syst)×10−8(3.9\pm0.8_{\mathrm{stat}}\pm1.0_{\mathrm{syst}})\times 10^{-8} m−2^{-2} s−1^{-1}, corresponding to 1.6% of the Crab Nebula flux on average. The multiwavelength spectral energy distribution of the source suggests that 1ES 1741+196 is an extreme-high-frequency-peaked BL Lacertae object. The observations analysed in this paper extend over a period of six years, during which time no strong flares were observed in any band. This analysis is therefore one of the few characterizations of a blazar in a non-flaring state.Comment: 8 pages, 5 figures. Accepted for publication in MNRA
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