Effects of paralytic shellfish toxins on the middle intestine of Oncorhynchus mykiss: Glutathione metabolism, oxidative status, lysosomal function and ATP-binding cassette class C (ABCC) proteins activity
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
Authors: Painefilu, Julio C.; Bianchi, Virginia A.; Krock, Bernd; De Anna, Julieta S.; Kristoff, Gisela; Luquet, Carlos M.
Abstract
We studied the absorption, cytotoxicity and oxidative stress markers of Paralytic Shellfish Toxins (PST) from three extracts from Alexandrium catenella and A. ostenfeldii, in middle Oncorhynchus mykiss intestine in vitro and ex vivo preparations. We measured glutathione (GSH) content, glutathione-S transferase (GST), glutathione reductase (GR) and catalase (CAT) enzymatic activity, and lipid peroxidation in isolated epithelium exposed to 0.13 and 1.3 mu M PST. ROS production and lysosomal membrane stability (as neutral red retention time 50%, NRRT50) were analyzed in isolated enterocytes exposed to PST alone or plus 3 mu M of the ABCC transport inhibitor MK571. In addition, the concentration-dependent effects of PST on NRRT50 were assayed in a concentration range from 0 to 1.3 mu M PST. We studied the effects of three different PST extracts on the transport rate of the ABCC substrate DNP-SG by isolated epithelium. The extract with highest inhibition capacity was selected for studying polarized DNP-SG transport in everted and non-everted intestinal segments. We registered lower GSH content and GST activity, and higher GR activity, with no significant changes in CAT activity, lipid peroxidation or ROS level. PST exposure decreased NRRT50 in a concentration-depend manner (IC50 = 0.0045 mu M), but PST effects were not augmented by addition of MK571. All the three PST extracts inhibited ABCC transport activity, but this inhibition was effective only when the toxins were applied to the apical side of the intestine and DNP-SG transport was measured at the basolateral side. Our results indicate that PST are absorbed by the enterocytes from the intestine lumen. Inside the enterocytes, these toxins decrease GSH content and inhibit the basolateral ABCC transporters affecting the normal functions of the cell. Furthermore, PST produce a strong cytotoxic effect to the enterocytes by damaging the lysosomal membrane, even at low, non-neumtoxic concentrations.
The missing link in gravitational-wave astronomy: discoveries waiting in the decihertz range
CLASSICAL AND QUANTUM GRAVITY
Authors: Sedda, Manuel Arca; Berry, Christopher P. L.; Jani, Karan; Amaro-Seoane, Pau; Auclair, Pierre; Baird, Jonathon; Baker, Tessa; Berti, Emanuele; Breivik, Katelyn; Burrows, Adam; Caprini, Chiara; Chen, Xian; Doneva, Daniela; Ezquiaga, Jose M.; Ford, K. E. Saavik; Katz, Michael L.; Kolkowitz, Shimon; McKernan, Barry; Mueller, Guido; Nardini, Germano; Pikovski, Igor; Rajendran, Surjeet; Sesana, Alberto; Shao, Lijing; Tamanini, Nicola; Vartanyan, David; Warburton, Niels; Witek, Helvi; Wong, Kaze; Zevin, Michael
Abstract
The gravitational-wave astronomical revolution began in 2015 with LIGO's observation of the coalescence of two stellar-mass black holes. Over the coming decades, ground-based detectors like laser interferometer gravitational-wave observatory (LIGO), Virgo and KAGRA will extend their reach, discovering thousands of stellar-mass binaries. In the 2030s, the space-basedlaser interferometer space antenna(LISA) will enable gravitational-wave observations of the massive black holes in galactic centres. Between ground-based observatories and LISA lies the unexplored dHz gravitational-wave frequency band. Here, we show the potential of adecihertz observatory(DO) which could cover this band, and complement discoveries made by other gravitational-wave observatories. The dHz range is uniquely suited to observation of intermediate-mass (similar to 10(2)-10(4)M(circle dot)) black holes, which may form the missing link between stellar-mass and massive black holes, offering an opportunity to measure their properties. DOs will be able to detect stellar-mass binaries days to years before they merge and are observed by ground-based detectors, providing early warning of nearby binary neutron star mergers, and enabling measurements of the eccentricity of binary black holes, providing revealing insights into their formation. Observing dHz gravitational-waves also opens the possibility of testing fundamental physics in a new laboratory, permitting unique tests of general relativity (GR) and the standard model of particle physics. Overall, a DO would answer outstanding questions about how black holes form and evolve across cosmic time, open new avenues for multimessenger astronomy, and advance our understanding of gravitation, particle physics and cosmology.