260 research outputs found

    A novel tag-recovery model with two size classes for estimating fishing and natural mortality, with implications for the southern rock lobster (Jasus edwardsii) in Tasmania, Australia

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    Multi-year tag-recovery models can be used to derive estimates of age- and year-specific annual survival rates and year-specific instantaneous fishing and natural mortality rates. The latter, which are often of interest to fisheries managers, usually can only be estimated when the tag-reporting rate (lambda) and the short-term tag-induced mortality and tag-shedding rate (phi) are known a priori. We present a new multi-year tagging model that permits estimation of instantaneous mortality rates independently of philambda provided tagged animals from two adjacent size groups are released simultaneously. If the two size groups comprise animals just above and below the minimum harvestable size limit, then it is possible to estimate year-specific instantaneous fishing and natural mortality rates after 2 yr of tagging and tag-recovery. In addition to the standard assumptions of multi-year tag-recovery models, it is necessary to assume that recruited animals have equal selectivity, pre-recruited animals become fully recruited in 1 or 2 yr, and the size groups experience the same natural mortality rate. Applicability of the model to the Tasmania southern rock lobster (Jasus edwardsii) fishery is evaluated using a simulation model and parameters based on data from the lobster fishery; assumptions are likely to be met and precision should be adequate if at least 1000 animals are tagged per year in each size group. (C) 2003 International Council for the Exploration of the Sea

    Hydrophobic guar gum derivatives prepared by controlled grafting processes for hydraulic facturing applications

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    The synthesis of new water soluble guar gum derivatives is described. Introduction of polyalkoxyalkyleneamide grafts to guar gum or hydroxyopropyl guar was achieved in a three step process: carboxymethylation with sodium chloroacetate, esterification with dimethyl sulfate and amidation with a series of polyalkoxyalkylene-amines. The process steps were followed using infrared spectroscopy; the grafted guar derivatives were characterized using FT-IR and 1H NMR. A series of hydroxypropyl guar derivatives with degrees of carboxymethylations ranging from 0.15-0.25 were modified with polyalkoxyalkyleneamines with molecular weights ranging from 300-3000. The ratio of oxypropylene to oxoethylene units in the polyalkoxyalkyleneamines was varied from 9/1 to 8/58 to adjust the hydrophobicity of the grafts. In addition, predominating hydrophobic grafts from the same family were produced. The percent grafting of the isolated products were in the range of 0.03 to 28 percent depending on the type of guar gum derivative and polyalkoxyalkyleneamines used. The grafted derivatives were evaluated for hydraulic fracturing application in oil industry. The viscosity properties of the grafted derivatives were compared with the parent carboxymethyl and carboxymethylhydroxypropyl guar gum. Aqueous solutions of the graft copolymers exhibit viscosities one to two orders of magnitude lower than corresponding solutions of the parent materials. The aqueous solutions of the graft copolymers when crosslinked with zirconium crosslinking agent at high pH; exhibited comparable or better viscosity properties to the crosslinking solutions of parent materials. To facilitate the clean up process the crosslinked fluids were treated with an enzyme breaker system. The viscosity of the resultant fluid after the treatment was very low. The degraded parts of some of these derivatives with hydrophobic grafts created emulsions when extracted with toluene

    Activation of the Listeria monocytogenes Virulence Program by a Reducing Environment.

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    Upon entry into the host cell cytosol, the facultative intracellular pathogen Listeria monocytogenes coordinates the expression of numerous essential virulence factors by allosteric binding of glutathione (GSH) to the Crp-Fnr family transcriptional regulator PrfA. Here, we report that robust virulence gene expression can be recapitulated by growing bacteria in a synthetic medium containing GSH or other chemical reducing agents. Bacteria grown under these conditions were 45-fold more virulent in an acute murine infection model and conferred greater immunity to a subsequent lethal challenge than bacteria grown in conventional media. During cultivation in vitro, PrfA activation was completely dependent on the intracellular levels of GSH, as a glutathione synthase mutant (ฮ”gshF) was activated by exogenous GSH but not reducing agents. PrfA activation was repressed in a synthetic medium supplemented with oligopeptides, but the repression was relieved by stimulation of the stringent response. These data suggest that cytosolic L.ย monocytogenes interprets a combination of metabolic and redox cues as a signal to initiate robust virulence gene expression in vivoIMPORTANCE Intracellular pathogens are responsible for much of the worldwide morbidity and mortality from infectious diseases. These pathogens have evolved various strategies to proliferate within individual cells of the host and avoid the host immune response. Through cellular invasion or the use of specialized secretion machinery, all intracellular pathogens must access the host cell cytosol to establish their replicative niches. Determining how these pathogens sense and respond to the intracellular compartment to establish a successful infection is critical to our basic understanding of the pathogenesis of each organism and for the rational design of therapeutic interventions. Listeria monocytogenes is a model intracellular pathogen with robust in vitro and in vivo infection models. Studies of the host-sensing and downstream signaling mechanisms evolved by L.ย monocytogenes often describe themes of pathogenesis that are broadly applicable to less tractable pathogens. Here, we describe how bacteria use external redox states as a cue to activate virulence

    Development and functionalization of quantum dots as luminescent labels towards mycotoxin detection

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    Experimental Study on Light Weight Concrete-Filled Steel Tubes

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    Tests on steel tubular columns of rectangular and circular sections filled with normal and lightweight concrete were performed to investigate the behavior of such columns under axial loadings. Comparison between normal and lightweight concrete filled steel columns for different column cross-sections using Euro Code 4 and BS 5400 codes was also conducted. The test results showed that both types of filled columns failed due to overall buckling; while hollow steel columns failed due to local buckling at the ends. According to these results, further interest was taken onto the replacement of normal concrete by lightweight concrete due to its low specific gravity and thermal conductivity

    Acute neuroinflammation induces AIS structural plasticity in a NOX2-dependent manner

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    Background Chronic microglia-mediated inflammation and oxidative stress are well-characterized underlying factors in neurodegenerative disease, whereby reactive inflammatory microglia enhance ROS production and impact neuronal integrity. Recently, it has been shown that during chronic inflammation, neuronal integrity is compromised through targeted disruption of the axon initial segment (AIS), the axonal domain critical for action potential initiation. AIS disruption was associated with contact by reactive inflammatory microglia which wrap around the AIS, increasing association with disease progression. While it is clear that chronic microglial inflammation and enhanced ROS production impact neuronal integrity, little is known about how acute microglial inflammation influences AIS stability. Here, we demonstrate that acute neuroinflammation induces AIS structural plasticity in a ROS-mediated and calpain-dependent manner. Methods C57BL/6J and NOX2โˆ’/โˆ’ mice were given a single injection of lipopolysaccharide (LPS; 5 mg/kg) or vehicle (0.9% saline, 10 mL/kg) and analyzed at 6 hโ€“2 weeks post-injection. Anti-inflammatory Didox (250 mg/kg) or vehicle (0.9% saline, 10 mL/kg) was administered beginning 24 h post-LPS injection and continued for 5 days; animals were analyzed 1 week post-injection. Microglial inflammation was assessed using immunohistochemistry (IHC) and RT-qPCR, and AIS integrity was quantitatively analyzed using ankyrinG immunolabeling. Data were statistically compared by one-way or two-way ANOVA where mean differences were significant as assessed using Tukeyโ€™s post hoc analysis. Results LPS-induced neuroinflammation, characterized by enhanced microglial inflammation and increased expression of ROS-producing enzymes, altered AIS protein clustering. Importantly, inflammation-induced AIS changes were reversed following resolution of microglial inflammation. Modulation of the inflammatory response using anti-inflammatory Didox, even after significant AIS disruption occurred, increased the rate of AIS recovery. qPCR and IHC analysis revealed that expression of microglial NOX2, a ROS-producing enzyme, was significantly increased correlating with AIS disruption. Furthermore, ablation of NOX2 prevented inflammation-induced AIS plasticity, suggesting that ROS drive AIS structural plasticity. Conclusions In the presence of acute microglial inflammation, the AIS undergoes an adaptive change that is capable of spontaneous recovery. Moreover, recovery can be therapeutically accelerated. Together, these findings underscore the dynamic capabilities of this domain in the presence of a pathological insult and provide evidence that the AIS is a viable therapeutic target

    Co_3O_4 Nanoparticle Water-Oxidation Catalysts Made by Pulsed-Laser Ablation in Liquids

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    Surfactant-free, size- and composition-controlled, unsupported, <5-nm, quantum-confined cobalt oxide nanoparticles with high electrocatalytic oxygen-evolution activity were synthesized by pulsed laser ablation in liquids. These crystalline Co_3O_4 nanoparticles have a turnover frequency per cobalt surface site among the highest ever reported for Co_3O_4 nanoparticle oxygen evolution catalysts in base and overpotentials competitive with the best electrodeposited cobalt oxides, with the advantage that they are suitable for mechanical deposition on photoanode materials and incorporation in integrated solar water-splitting devices

    ๋Œ€ํ˜• ๊ฐ•์ž…์ž ์ถฉ๋Œ๊ธฐ์— ์œ„์น˜ํ•œ CMS ๊ฒ€์ถœ๊ธฐ๋ฅผ ์ด์šฉํ•ด, ์งˆ๋Ÿ‰ ์ค‘์‹ฌ ์—๋„ˆ์ง€ 13 TeV์˜ ์–‘์„ฑ์ž-์–‘์„ฑ์ž ์ถฉ๋Œ์—์„œ ๋งŒ๋“ค์–ด์ง€๋Š” ๋ฌด๊ฑฐ์šด ์ค‘์„ฑ๋ฏธ์ž๋ฅผ ํƒ์ƒ‰ํ•จ.

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    ํ•™์œ„๋…ผ๋ฌธ (๋ฐ•์‚ฌ) -- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ์ž์—ฐ๊ณผํ•™๋Œ€ํ•™ ๋ฌผ๋ฆฌยท์ฒœ๋ฌธํ•™๋ถ€(๋ฌผ๋ฆฌํ•™์ „๊ณต), 2021. 2. ์–‘์šด๊ธฐ.ํ‘œ์ค€๋ชจํ˜•์ด ์ˆ˜๋งŽ์€ ์‹คํ—˜๊ฒฐ๊ณผ๋ฅผ ์„ฑ๊ณต์ ์œผ๋กœ ์„ค๋ช…ํ•จ์—๋„ ๋ถˆ๊ตฌํ•˜๊ณ , ์ž์—ฐ์—๋Š” ์—ฌ์ „ํžˆ ์œ„ ๋ชจํ˜•์œผ๋กœ๋Š” ์„ค๋ช… ๋ถˆ๊ฐ€๋Šฅํ•œ ๊ฒƒ๋“ค์ด ๋งŽ์ด ๋‚จ์•„์žˆ๋‹ค. ์ค‘์„ฑ๋ฏธ์ž์˜ ์ง„๋™๋ณ€ํ™˜์˜ ๋ฐœ๊ฒฌ์€, ์ค‘์„ฑ๋ฏธ์ž์˜ ์งˆ๋Ÿ‰์„ ์„ค๋ช…ํ•˜์ง€ ๋ชปํ•˜๋Š” ํ‘œ์ค€๋ชจํ˜•์„ ๋„˜์–ด์„œ๋Š”, ์ƒˆ๋กœ์šด ๋ฌผ๋ฆฌ๊ฐ€ ๋ฐ˜๋“œ์‹œ ์กด์žฌํ•œ๋‹ค๋Š” ๊ฒƒ์„ ์•”์‹œํ•œ๋‹ค. ์ˆ˜๋งŽ์€ ์ด๋ก ๋ชจํ˜•๋“ค์ด ์ค‘์„ฑ๋ฏธ์ž์˜ ์งˆ๋Ÿ‰ ์„ค๋ช…ํ•˜๊ธฐ์œ„ํ•ด ์ œ์‹œ๋˜์—ˆ์ง€๋งŒ, ์˜ค๋ฅธ์†์žก์ด ์ค‘์„ฑ๋ฏธ์ž์˜ ๋ถ€์žฌ๋Š” ์ค‘์„ฑ๋ฏธ์ž ๋ฌผ๋ฆฌํ•™์˜ ํฐ ๊ฑธ๋ฆผ๋Œ์ด ๋˜๊ณ ์žˆ์œผ๋ฉฐ, ์ด๋Ÿฌํ•œ ์ž…์ž๋ฅผ ๋ฐœ๊ฒฌํ•˜๊ธฐ์œ„ํ•ด ๋งŽ์€ ์‹คํ—˜๋“ค์ด ์ง„ํ–‰๋˜๊ณ  ์žˆ๋‹ค. ์‹œ์†Œ ๋ชจํ˜•์€ ์ค‘์„ฑ๋ฏธ์ž ์งˆ๋Ÿ‰์˜ ๊ธฐ์›์„ ์„ค๋ช…ํ•จ๊ณผ ๋™์‹œ์—, ๊ทธ ํฌ๊ธฐ๊ฐ€ ๋‹ค๋ฅธ ํŽ˜๋ฅด๋ฏธ์˜จ ์ž…์ž์™€ ๋น„๊ตํ–ˆ์„๋•Œ ์›”๋“ฑํžˆ ์ž‘์€ ์‚ฌ์‹ค๋„ ์„ค๋ช…ํ•  ์ˆ˜ ์žˆ๋Š” ๋ชจ๋ธ์ด๋‹ค. ์‹œ์†Œ ๋ชจํ˜•์—์„œ ์˜ˆ์ธก๋˜๋Š” ๋ฌด๊ฑฐ์šด ๋งˆ์š”๋ผ๋‚˜ ํƒ€์ž…์˜ ์ค‘์„ฑ๋ฏธ์ž๋Š” ํ‘œ์ค€๋ชจํ˜•์˜ ์ค‘์„ฑ๋ฏธ์ž์™€์˜ ์„ž์ž„์ด ๊ฐ€๋Šฅํ•˜๋‹ค. ๋˜ํ•œ, ๋” ๋†’์€ ์—๋„ˆ์ง€ ์Šค์ผ€์ผ์—์„œ ์™ผ์†์žก์ด-์˜ค๋ฅธ์†์žก์ด ๊ฐ„์˜ ๋Œ€์นญ์„ฑ์„ ๋„์ž…ํ•œ๋’ค, ์ž๋ฐœ์  ๋Œ€์นญ์„ฑ ๊นจ์ง์„ํ†ตํ•ด ์•ฝํ•œ์ƒํ˜ธ์ž‘์šฉ์˜ ํŒจ๋ฆฌํ‹ฐ ๋Œ€์นญ์„ฑ ๊นจ์ง์„ ์„ค๋ช…ํ•˜๋Š” ๋ชจ๋ธ์€ ์œ„์˜ ์‹œ์†Œ ๋ชจํ˜•์„ ์ž์—ฐ์Šค๋Ÿฝ๊ฒŒ ํฌํ•จํ•  ์ˆ˜ ์žˆ๋Š” ์žฅ์ ์ด์žˆ๋‹ค. ์ด ํ•™์œ„๋…ผ๋ฌธ์€ ๋Œ€ํ˜• ๊ฐ•์ž…์ž ์ถฉ๋Œ๊ธฐ์˜ CMS ๊ฒ€์ถœ๊ธฐ์—์„œ ์ˆ˜์ง‘๋œ ์–‘์„ฑ์ž-์–‘์„ฑ์ž ์ถฉ๋Œ ๋ฐ์ดํ„ฐ๋ฅผ ์ด์šฉํ•ด, ์œ„์—์„œ ์–ธ๊ธ‰๋œ ๋ฌด๊ฑฐ์šด ์ค‘์„ฑ๋ฏธ์ž์™€ ์˜ค๋ฅธ์†์žก์ด ๊ฒŒ์ด์ง€ ๋ณด์กด์„ ์ฐพ๋Š” ์—ฐ๊ตฌ๊ฒฐ๊ณผ๋ฅผ ํฌํ•จํ•œ๋‹ค. ์‹œ์†Œ๋ชจํ˜•์„ ๋‹ค๋ฃฌ ์—ฐ๊ตฌ๋Š” 2016๋…„์— ์ˆ˜์ง‘๋œ 35.9 fb-1์˜ ๋ฐ์ดํ„ฐ๋ฅผ ์ด์šฉํ–ˆ๋‹ค. ์ด ์—ฐ๊ตฌ๋Š”, ์ด์ „์— ์‹œํ–‰๋œ ์—ฐ๊ตฌ๋ฅผ ๋‘๊ฐ€์ง€ ๋ฐฉํ–ฅ์—์„œ ํ–ฅ์ƒ์‹œ์ผฐ๋‹ค. ์ฒซ์งธ, ๋” ๋ฌด๊ฑฐ์šด ์งˆ๋Ÿ‰์˜ ์‹œ๊ทธ๋„์—์„œ ๋” ๋งŽ์ด ์ƒ์„ฑ๋˜๋Š” ์ƒˆ๋กœ์šด ์ฑ„๋„์„ ์ถ”๊ฐ€ํ–ˆ๋‹ค. ๋‘˜์งธ, ์ด์ „ ์—ฐ๊ตฌ์—์„œ ๋†“์ณค๋˜ ์‹œ๊ทธ๋„ ์ด๋ฒคํŠธ๋ฅผ ํฌํ•จํ•  ์ˆ˜ ์žˆ๋Š” ์ƒˆ๋กœ์šด ์—ฐ๊ตฌ ์˜์—ญ์„ ์ถ”๊ฐ€ํ–ˆ๋‹ค. ๋‘๋ฒˆ์งธ ์—ฐ๊ตฌ๋Š” ์˜ค๋ฅธ์†์žก์ด ๊ฒŒ์ด์ง€ ๋ณด์กด๊ณผ ๋ฌด๊ฑฐ์šด ์ค‘์„ฑ๋ฏธ์ž๋ฅผ ํ•จ๊ป˜ ํƒ์ƒ‰ํ–ˆ์œผ๋ฉฐ, 2016๋…„ ๋ถ€ํ„ฐ 2018๋…„์— ๊ฑธ์ณ ์ˆ˜์ง‘๋œ 137 fb-1์˜ ๋ฐ์ดํ„ฐ๋ฅผ ๋ถ„์„ํ•œ ๊ฒฐ๊ณผ์ด๋‹ค. ์ด์ „์— ์‹œํ–‰๋œ ์—ฐ๊ตฌ์˜ ์•ฝ 4๋ฐฐ์— ํ•ด๋‹นํ•˜๋Š” ๋ฐ์ดํ„ฐ๋ฅผ ์‚ฌ์šฉํ–ˆ์œผ๋ฉฐ, ์ƒ๋Œ€์ ์œผ๋กœ ๊ฐ€๋ฒผ์šด ๋ฌด๊ฑฐ์šด ์ค‘์„ฑ๋ฏธ์ž๋ฅผ ํƒ์ƒ‰ํ•  ์ˆ˜ ์žˆ๋Š” ์ƒˆ๋กœ์šด ์—ฐ๊ตฌ ์˜์—ญ์„ ์ถ”๊ฐ€ํ•ด, ์‹œ๊ทธ๋„ ์ด๋ฒคํŠธ์˜ ๋ฐœ๊ฒฌ ๊ฐ€๋Šฅ์„ฑ์„ ํ–ฅ์ƒ์‹œ์ผฐ๋‹ค.Despite the success of the standard model, there are still unexplained phenomena that are not explained by the theory. The observation of the neutrino oscillation is a clear evidence of the physics beyond the standard model where the mass of the neutrinos are assumed to be zero. Multiple theories have been proposed to explain the existence of the neutrino masses, but the absence of the right-handed neutrinos is the stumbling block of the neutrino physics and the observation of such particles will open a new chapter of the particle physics. The seesaw mechanism is one of the most popular theories that explain the origin and the smallness of the neutrino masses. The model predicts a heavy Majorana neutrino which can mix with the SM neutrinos with a strength proportional to the size of the mixing matrix element. In addition, the left-right symmetric extension of the SM can explain the mechanism of the parity violation, and can incorporate the seesaw mechanism to explain the mass of the neutrino. The heavy neutrinos, which are predicted from both models, can be probed at the LHC thought the proton-proton collision. In this thesis, analyses that searched for the heavy neutrinos and the new charge gauge boson are presented, using the proton-proton collision data collected at the CMS detector, at a center-of-mass energy of 13 TeV. The former analysis used the data corresponds to the integrated luminosity of 35.9 fb-1. This analysis improved the previous analysis in two folds; adding new production channel of the signal that is dominant in the heavier mass, and adding new signal regions which restores the inefficiencies in the previous analysis. The latter analysis used the full Run 2 data of 137 fb-1. A new analysis region which enhances the sensitivity for small m(N)/m(WR) signals are introduced, and a significant improvement of the exclusion area is obtained.Abstract i 1 Introduction 1 2 The standard model 5 2.1 Lorentzgroupanditsrepresentations 6 2.2 TheDiracequation. 9 2.3 Quantumelectrodynamics. 11 2.4 Electroweak interaction and spontaneous symmetry breaking . . . . . 13 2.4.1 Themassesofgaugebosons 17 2.4.2 Electroweakinteraction 21 2.4.3 Themassesoffermions 24 3 The mass of neutrinos 29 3.1 Theneutrinooscillation 29 3.2 TheMajoranamass 32 3.3 Theseesawmechanism. 34 3.4 Left-rightsymmetricmodel 37 4 TheLHC 43 4.1 Thebeaminjectionchain . 43 4.2 ThearcoftheLHC 48 4.3 ThestraightsectionoftheLHC 49 5 The CMS detector 55 5.1 Thetrackersystem. 58 5.2 Theelectromagneticcalorimeter . 59 5.3 Thehadroncalorimeter 61 5.4 Themuonchamber. 66 5.5 Thetriggersystem . 69 5.5.1 TheL1trigger . 69 5.5.2 Thehigh-leveltrigger . 72 5.6 Offlinereconstruction . 74 6 Search for heavy Majorana neutrinos in same-sign dilepton channels 79 6.1 Introduction. 79 6.2 Datasetandsimulatedsamples 83 6.2.1 Dataset. 83 6.2.2 Simulatedsamples . 83 6.3 Objectidentification 86 6.3.1 Leptonselection 86 6.3.2 Jetselection. 90 6.4 Eventselection . 94 6.4.1 Preselectioncriteria 95 6.4.2 Signalregioncriteria 95 6.4.3 Controlregioncriteria . 99 6.5 Backgroundestimation. 100 6.5.1 Promptbackground 100 6.5.2 Backgroundwithmisidentifiedleptons . . . . . . . . . . . . . . 110 6.5.3 Background with charge-mismeasured leptons . . . . . . . . . . 121 6.6 Overlap between the misidentified lepton and charge-mismeasured lepton 129 6.7 Resultsinthecontrolregions . 129 6.8 Systematicuncertainties 129 6.8.1 Uncertainties on the background estimation . . . . . . . . . . . 131 6.8.2 Uncertaintiesonthesimulation 133 6.9 Results136 6.10 Summary 146 7 Search for a charged right-handed boson and heavy neutrino 147 7.1 Introduction. 147 7.2 Datasetandsimulatedsamples 149 7.2.1 Dataset.149 7.2.2 Simulatedsamples . 153 7.3 Objectidentification 154 7.3.1 Leptonidentification 154 7.3.2 Jetidentification 157 7.4 Eventselection . 161 7.4.1 Definitionofaresolvedevent . 161 7.4.2 Dilepton mass cut optimization for the resolved signal region . 162 7.4.3 Eventselections. 162 7.5 Backgroundestimation. 166 7.5.1 DY+jetsbackground 166 7.5.2 Pair top production and single top+W background estimation 180 7.6 Systematicuncertainties 190 7.7 Results197 7.8 Summary 204 8 Conclusion 207 A Diagonalizing the neutrino mass matrix 223 B Control region plots 227 B.1 Figures for same-sign dilepton with b-tagged jet (CR1) . . . . . . . . . 227 B.2 Figures for same-sign back-to-back dilepton without jets or b-tagged jets(includingjetsevenifclosetoalepton)(CR2) . . . . . . . . . . . 229 B.3 Figuresforlow-massCRs(CR3andCR4) 230 B.4 Figuresforhigh-massCRs(CR5andCR6) . . . . . . . . . . . . . . . 237 Abstract 244 Acknowledgements 246Docto

    Sphingomyelin and GM1 Influence Huntingtin Binding to, Disruption of, and Aggregation on Lipid Membranes

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    Huntington disease (HD) is an inherited neurodegenerative disease caused by the expansion beyond a critical threshold of a polyglutamine (polyQ) tract near the N-terminus of the huntingtin (htt) protein. Expanded polyQ promotes the formation of a variety of oligomeric and fibrillar aggregates of htt that accumulate into the hallmark proteinaceous inclusion bodies associated with HD. htt is also highly associated with numerous cellular and subcellular membranes that contain a variety of lipids. As lipid homeostasis and metabolism abnormalities are observed in HD patients, we investigated how varying both the sphingomyelin (SM) and ganglioside (GM1) contents modifies the interactions between htt and lipid membranes. SM composition is altered in HD, and GM1 has been shown to have protective effects in animal models of HD. A combination of Langmuir trough monolayer techniques, vesicle permeability and binding assays, and in situ atomic force microscopy (AFM) were used to directly monitor the interaction of a model, synthetic htt peptide and a full-length htt-exon1 recombinant protein with model membranes comprised of total brain lipid extract (TBLE) and varying amounts of exogenously added SM or GM1. The addition of either SM or GM1 decreased htt insertion into the lipid monolayers. However, TBLE vesicles with an increased SM content were more susceptible to htt-induced permeabilization, whereas GM1 had no effect on permeablization. Pure TBLE bilayers and TBLE bilayers enriched with GM1 developed regions of roughened, granular morphologies upon exposure to htt-exon1, but plateau-like domains with a smoother appearance formed in bilayers enriched with SM. Oligomeric aggregates were observed on all bilayer systems regardless of induced morphology. Collectively, these observations suggest that the lipid composition and its subsequent effects on membrane material properties strongly influence htt binding and aggregation on lipid membranes
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