The role of multixenobiotic transporters in predatory marine molluscs as counter-defense mechanisms against dietary allelochemicals

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 152 (2010): 288-300, doi:10.1016/j.cbpc.2010.05.003.Multixenobiotic transporters have been extensively studied for their ability to modulate the disposition and toxicity of pharmacological agents, yet their influence in regulating the levels of dietary toxins within marine consumers has only recently been explored. This study presents functional and molecular evidence for multixenobiotic transporter-mediated efflux activity and expression in the generalist gastropod Cyphoma gibbosum, and the specialist nudibranch Tritonia hamnerorum, obligate predators of chemically defended gorgonian corals. Immunochemical analysis revealed that proteins with homology to permeability glycoprotein (P-gp) were highly expressed in T. hamnerorum whole animal homogenates and localized to the apical tips of the gut epithelium, a location consistent with a role in protection against ingested prey toxins. In vivo dye assays with specific inhibitors of efflux transporters demonstrated the activity of P-gp and multidrug resistance-associated protein (MRP) families of ABC transporters in T. hamnerorum. In addition, we identified eight partial cDNA sequences encoding two ABCB and two ABCC proteins from each molluscan species. Digestive gland transcripts of C. gibbosum MRP-1, which have homology to vertebrate glutathione-conjugate transporters, were constitutively expressed regardless of gorgonian diet. This constitutive expression may reflect the ubiquitous presence of high affinity substrates for C. gibbosum glutathione transferases in gorgonian tissues likely necessitating export by MRPs. Our results suggest that differences in multixenobiotic transporter expression patterns and activity in molluscan predators may stem from the divergent foraging strategies of each consumer.Financial support was provided by the Ocean Life Institute Tropical Research Initiative Grant (WHOI) to KEW and MEH; the Robert H. Cole Endowed Ocean Ventures Fund (WHOI) to KEW; the National Undersea Research Center – Program Development Proposal (CMRC-03PRMN0103A) to KEW; and the National Science Foundation (Graduate Research Fellowship to KEW and DEB-0919064 to EES)

Mechanical stability of the CMS strip tracker measured with a laser alignment system

Peer reviewe

The CMS Phase-1 pixel detector upgrade

The CMS detector at the CERN LHC features a silicon pixel detector as its innermost subdetector. The original CMS pixel detector has been replaced with an upgraded pixel system (CMS Phase-1 pixel detector) in the extended year-end technical stop of the LHC in 2016/2017. The upgraded CMS pixel detector is designed to cope with the higher instantaneous luminosities that have been achieved by the LHC after the upgrades to the accelerator during the first long shutdown in 2013–2014. Compared to the original pixel detector, the upgraded detector has a better tracking performance and lower mass with four barrel layers and three endcap disks on each side to provide hit coverage up to an absolute value of pseudorapidity of 2.5. This paper describes the design and construction of the CMS Phase-1 pixel detector as well as its performance from commissioning to early operation in collision data-taking.Peer reviewe

Characterisation of irradiated thin silicon sensors for the CMS phase II pixel upgrade

The high luminosity upgrade of the Large Hadron Collider, foreseen for 2026, necessitates the replacement of the CMS experiment's silicon tracker. The innermost layer of the new pixel detector will be exposed to severe radiation, corresponding to a 1 MeV neutron equivalent fluence of up to Phi(eq) = 2x10(16) cm(-2), and an ionising dose of approximate to 5 MGy after an integrated luminosity of 3000 fb(-1). Thin, planar silicon sensors are good candidates for this application, since the degradation of the signal produced by traversing particles is less severe than for thicker devices. In this paper, the results obtained from the characterisation of 100 and 200 mu m thick p-bulk pad diodes and strip sensors irradiated up to fluences of Phi(eq) = 1.3 x 10(16) cm(-2) are shown.Peer reviewe

P-Type Silicon Strip Sensors for the new CMS Tracker at HL-L-HC

Abstract: The upgrade of the LHC to the High-Luminosity LHC (HL-LHC) is expected to increase the LHC design luminosity by an order of magnitude. This will require silicon tracking detectors with a significantly higher radiation hardness. The CMS Tracker Collaboration has conducted an irradiation and measurement campaign to identify suitable silicon sensor materials and strip designs for the future outer tracker at the CMS experiment. Based on these results, the collaboration has chosen to use n-in-p type silicon sensors and focus further investigations on the optimization of that sensor type

Limited evidence of interactive disturbance and nutrient effects on the diversity of macrobenthic assemblages

The causes and consequences of the coexistence of a number of species in a given habitat have attracted ecological research for several decades. Numerous theories have been developed in this context, including the ‘intermediate disturbance hypothesis’ (IDH), but supportive experimental evidence remains scarce and contradictory, leading scientists to propose the existence of an interaction between disturbance and productivity. This study assessed the interactive effects of disturbance and nutrient enrichment at 1 oligotrophic (Arraial do Cabo) and 1 eutrophic (Guanabara Bay) site on the coast of Brazil. At each site, an epibenthic assemblage was allowed to establish on settlement panels (PVC) for 3 mo prior to a 6 mo manipulation phase comprising nutrient enrichment and disturbance (biomass removal). Our results revealed site-specific diversity-driving processes in the absence of disturbance. Nevertheless, diversity and species richness peaked at both sites at some intermediate level of disturbance, corroborating the IDH. Nutrient enrichment increased total species richness and algal species richness in particular, but only at the oligotrophic site. Only here, did nutrient enrichment eliminate the unimodal species richness pattern observed along the disturbance gradient under ambient nutrient concentrations. Such interactive effects of disturbance and productivity on diversity confirm the general predictions of advanced IDH models, e.g. the Kondoh model. The present study indicates that interactive effects of ‘bottom-up’ and ‘top-down’ processes may explain more of the variation in community diversity than the separate models of disturbance–diversity and productivity–diversity relationships

The progestin levonorgestrel disrupts gonadotropin expression and sex steroid levels in pubertal roach (Rutilus rutilus).

The aim of the present study was to investigate the effects of the synthetic progestin levonorgestrel (LNG) on the reproductive endocrine system of a teleost fish, the roach (Rutilus rutilus). Pubertal roach were exposed for 28 days in a flow-through system to four concentrations of LNG (3, 31, 312, and 3124 ng/l). Both males and females treated with 3124 ng/l LNG exhibited the upregulated levels of vitellogenin and oestrogen receptor 1 mRNA in the liver. At the same concentration, LNG caused a significant upregulation of the mRNA expression of the gene encoding luteinising hormone β-subunit (lhβ) and the suppression of the mRNA expression of the gene encoding follicle-stimulating hormone β-subunit (fshβ) in the pituitary of both male and female roach. A lower LNG concentration (312 ng/l) suppressed mRNA expression of fshβ in males only. Females treated with 3124 ng/l LNG exhibited significantly lower plasma 11-ketotestosterone (11-KT) and oestradiol (E2) concentrations, whereas their testosterone (T) level was higher compared with the control. Females exposed to 312 ng/l LNG presented significantly lower plasma E2 concentrations. Males exposed to ≥31 ng/l LNG exhibited significantly reduced 11-KT levels. As determined through a histological analysis, the ovaries of females were not affected by LNG exposure, whereas the testes of males exposed to 31 and 312 ng/l LNG exhibited a significantly higher percentage of spermatogonia B compared with the control. The results of the present study demonstrate that LNG disrupts the reproductive system of pubertal roach by affecting the pituitary gonadotropin expression and the sex steroid levels. This disruption was determined to occur in males after exposure to an environmentally relevant concentration (31 ng/l). Moreover, the highest tested concentration of LNG (3124 ng/l) exerted an oestrogenic effect on fish of both sexes.info:eu-repo/semantics/publishe