Synthesis and propagation of complement C3 by microglia/monocytes in the aging retina

INTRODUCTION Complement activation is thought to contribute to the pathogenesis of age-related macular degeneration (AMD), which may be mediated in part by para-inflammatory processes. We aimed to investigate the expression and localization of C3, a crucial component of the complement system, in the retina during the course of aging. METHODS SD rats were born and reared in low-light conditions, and euthanized at post-natal (P) days 100, 450, or 750. Expression of C3, IBA1, and Ccl- and Cxcl- chemokines was assessed by qPCR, and in situ hybridization. Thickness of the ONL was assessed in retinal sections as a measure of photoreceptor loss, and counts were made of C3-expressing monocytes. RESULTS C3 expression increased significantly at P750, and correlated with thinning of the ONL, at P750, and up-regulation of GFAP. In situ hybridization showed that C3 was expressed by microglia/monocytes, mainly from within the retinal vasculature, and occasionally the ONL. The number of C3-expressing microglia increased significantly by P750, and coincided spatiotemporally with thinning of the ONL, and up-regulation of Ccl- and Cxcl- chemokines. CONCLUSIONS Our data suggest that recruited microglia/monocytes contribute to activation of complement in the aging retina, through local expression of C3 mRNA. C3 expression coincides with age-related thinning of the ONL at P750, although it is unclear whether the C3-expressing monocytes are a cause or consequence. These findings provide evidence of activation of complement during natural aging, and may have relevance to cellular events underling the pathogenesis of age-related retinal diseases.Funding provided by Australian Research Council Centres of Excellence Program Grant (CE0561903)

Measurement of the radiative decay of polarized muons in the MEG experiment

We studied the radiative muon decay $\mu^+ \to e^+\nu\bar{\nu}\gamma$ by using for the first time an almost fully polarized muon source. We identified a large sample (~13000) of these decays in a total sample of 1.8x10^14 positive muon decays collected in the MEG experiment in the years 2009--2010 and measured the branching ratio B($\mu^+ \to e^+\nu\bar{\nu}\gamma$) = (6.03+-0.14(stat.)+-0.53(sys.))x10^-8 for E_e > 45 MeV and E_{\gamma} > 40 MeV, consistent with the Standard Model prediction. The precise measurement of this decay mode provides a basic tool for the timing calibration, a normalization channel, and a strong quality check of the complete MEG experiment in the search for $\mu^+ \to e^+\gamma$ process.Comment: 8 pages, 7 figures. Added an introduction to NLO calculation which was recently calculated. Published versio

670-nm light treatment reduces complement propagation following retinal degeneration

AIM: Complement activation is associated with the pathogenesis of age-related macular degeneration (AMD). We aimed to investigate whether 670-nm light treatment reduces the propagation of complement in a light-induced model of atrophic AMD. METHODS: Sprague–Dawley (SD) rats were pretreated with 9 J/cm(2) 670-nm light for 3 minutes daily over 5 days; other animals were sham treated. Animals were exposed to white light (1,000 lux) for 24 h, after which animals were kept in dim light (5 lux) for 7 days. Expression of complement genes was assessed by quantitative polymerase chain reaction (qPCR), and immunohistochemistry. Counts were made of C3-expressing monocytes/microglia using in situ hybridization. Photoreceptor death was also assessed using outer nuclear layer (ONL) thickness measurements, and oxidative stress using immunohistochemistry for 4-hydroxynonenal (4-HNE). RESULTS: Following light damage, retinas pretreated with 670-nm light had reduced immunoreactivity for the oxidative damage maker 4-HNE in the ONL and outer segments, compared to controls. In conjunction, there was significant reduction in retinal expression of complement genes C1s, C2, C3, C4b, C3aR1, and C5r1 following 670 nm treatment. In situ hybridization, coupled with immunoreactivity for the marker ionized calcium binding adaptor molecule 1 (IBA1), revealed that C3 is expressed by infiltrating microglia/monocytes in subretinal space following light damage, which were significantly reduced in number after 670 nm treatment. Additionally, immunohistochemistry for C3 revealed a decrease in C3 deposition in the ONL following 670 nm treatment. CONCLUSIONS: Our data indicate that 670-nm light pretreatment reduces lipid peroxidation and complement propagation in the degenerating retina. These findings have relevance to the cellular events of complement activation underling the pathogenesis of AMD, and highlight the potential of 670-nm light as a non-invasive anti-inflammatory therapy

Three-year survival of single- and two-surface ART restorations in a high-caries child population

The aim of this study was to evaluate the survival of single- and two-surface atraumatic restorative treatment (ART) restorations in the primary and permanent dentitions of children from a high-caries population, in a field setting. The study was conducted in the rainforest of Suriname, South America. ART restorations, made by four Dutch dentists, were evaluated after 6 months, 1, 2, and 3 years. Four hundred seventy-five ART restorations were placed in the primary dentition and 54 in first permanent molars of 194 children (mean age 6.09 ± 0.48 years). Three-year cumulative survivals of single- and two-surface ART restorations in the primary dentition were 43.4 and 12.2%, respectively. Main failure characteristics were gross marginal defects and total or partial losses. Three-year cumulative survival for single-surface ART restorations in the permanent dentition was 29.6%. Main failure characteristics were secondary caries and gross marginal defects. An operator effect was found only for two-surface restorations. The results show extremely low survival rates for single- and two-surface ART restorations in the primary and permanent dentitions. The variable success for ART may initiate further discussion about alternative treatment strategies, especially in those situations where choices have to be made with respect to a well-balanced, cost-effective package of basic oral health care

Technical design of the phase I Mu3e experiment

The Mu3e experiment aims to find or exclude the lepton flavour violating decay μ→eee at branching fractions above 10−16. A first phase of the experiment using an existing beamline at the Paul Scherrer Institute (PSI) is designed to reach a single event sensitivity of 2⋅10−15. We present an overview of all aspects of the technical design and expected performance of the phase I Mu3e detector. The high rate of up to 108 muon decays per second and the low momenta of the decay electrons and positrons pose a unique set of challenges, which we tackle using an ultra thin tracking detector based on high-voltage monolithic active pixel sensors combined with scintillating fibres and tiles for precise timing measurements

Measurement of the radiative decay of polarized muons in the MEG experiment

We studied the radiative muon decay (Formula presented.) by using for the first time an almost fully polarized muon source. We identified a large sample ((Formula presented.) 13,000) of these decays in a total sample of (Formula presented.) positive muon decays collected in the MEG experiment in the years 2009–2010 and measured the branching ratio (Formula presented.) for (Formula presented.) and (Formula presented.) , consistent with the Standard Model prediction. The precise measurement of this decay mode provides a basic tool for the timing calibration, a normalization channel, and a strong quality check of the complete MEG experiment in the search for (Formula presented.) process

Technical design of the phase I Mu3e experiment

The Mu3e experiment aims to find or exclude the lepton flavour violating decay $\mu \rightarrow eee$ at branching fractions above $10^{-16}$. A first phase of the experiment using an existing beamline at the Paul Scherrer Institute (PSI) is designed to reach a single event sensitivity of $2\cdot 10^{-15}$. We present an overview of all aspects of the technical design and expected performance of the phase~I Mu3e detector. The high rate of up to $10^{8}$ muon decays per second and the low momenta of the decay electrons and positrons pose a unique set of challenges, which we tackle using an ultra thin tracking detector based on high-voltage monolithic active pixel sensors combined with scintillating fibres and tiles for precise timing measurements.Comment: 114 pages, 185 figures. Submitted to Nuclear Instruments and Methods A. Edited by Frank Meier Aeschbacher This version has many enhancements for better readability and more detail

Search for the lepton flavour violating decay μ+→ e +γ with the full dataset of the MEG experiment: MEG Collaboration

The final results of the search for the lepton flavour violating decay μ+→ e +γ based on the full dataset collected by the MEG experiment at the Paul Scherrer Institut in the period 2009–2013 and totalling 7.5 × 10 14 stopped muons on target are presented. No significant excess of events is observed in the dataset with respect to the expected background and a new upper limit on the branching ratio of this decay of B(μ+→ e +γ) < 4.2 × 10 - 13 (90 % confidence level) is established, which represents the most stringent limit on the existence of this decay to date

Search for the lepton flavour violating decay μ+→ e +γ with the full dataset of the MEG experiment: MEG Collaboration

none84siThe final results of the search for the lepton flavour violating decay mu(+) -> e(+)gamma based on the full dataset collected by the MEG experiment at the Paul Scherrer Institut in the period 2009-2013 and totalling 7.5x10(14) stopped muons on target are presented. Nosignificant excess of events is observed in the dataset with respect to the expected background and a new upper limit on the branching ratio of this decay of B(mu(+) -> e(+) gamma) < 4.2 x 10(-13) (90 % confidence level) is established, which represents the most stringent limit on the existence of this decay to date.Baldini, A.M.; Bao, Y.; Baracchini, E.; Bemporad, C.; Berg, F.; Biasotti, M.; Boca, G.; Cascella, M.; Cattaneo, P.W.; Cavoto, G.; Cei, F.; Cerri, C.; Chiarello, G.; Chiri, C.; Corvaglia, A.; de Bari, A.; De Gerone, M.; Doke, T.; D’Onofrio, A.; Dussoni, S.; Egger, J.; Fujii, Y.; Galli, L.; Gatti, F.; Grancagnolo, F.; Grassi, M.; Graziosi, A.; Grigoriev, D.N.; Haruyama, T.; Hildebrandt, M.; Hodge, Z.; Ieki, K.; Ignatov, F.; Iwamoto, T.; Kaneko, D.; Kang, T.I.; Kettle, P.-R.; Khazin, B.I.; Khomutov, N.; Korenchenko, A.; Kravchuk, N.; Lim, G.M.A.; Maki, A.; Mihara, S.; Molzon, W.; Mori, Toshinori; Morsani, F.; Mtchedilishvili, A.; Mzavia, D.; Nakaura, S.; Nardò, R.; Nicolò, D.; Nishiguchi, H.; Nishimura, M.; Ogawa, S.; Ootani, W.; Orito, S.; Panareo, M.; Papa, A.; Pazzi, R.; Pepino, A.; Piredda, G.; Pizzigoni, G.; Popov, A.; Raffaelli, F.; Renga, F.; Ripiccini, E.; Ritt, S.; Rossella, M.; Rutar, G.; Sawada, R.; Sergiampietri, F.; Signorelli, G.; Simonetta, M.; Tassielli, G.F.; Tenchini, F.; Uchiyama, Y.; Venturini, M.; Voena, C.; Yamamoto, A.; Yoshida, K.; You, Z.; Yudin, Yu. V.; Zanello, D.Baldini, A. M.; Bao, Y.; Baracchini, E.; Bemporad, C.; Berg, F.; Biasotti, M.; Boca, Gianluigi; Cascella, M.; Cattaneo, P. W.; Cavoto, G.; Cei, F.; Cerri, C.; Chiarello, G.; Chiri, C.; Corvaglia, A.; DE BARI, Antonio; De Gerone, M.; Doke, T.; D’Onofrio, A.; Dussoni, S.; Egger, J.; Fujii, Y.; Galli, L.; Gatti, F.; Grancagnolo, F.; Grassi, M.; Graziosi, A.; Grigoriev, D. N.; Haruyama, T.; Hildebrandt, M.; Hodge, Z.; Ieki, K.; Ignatov, F.; Iwamoto, T.; Kaneko, D.; Kang, T. I.; Kettle, P. R.; Khazin, B. I.; Khomutov, N.; Korenchenko, A.; Kravchuk, N.; Lim, G. M. A.; Maki, A.; Mihara, S.; Molzon, W.; Mori, Toshinori; Morsani, F.; Mtchedilishvili, A.; Mzavia, D.; Nakaura, S.; Nardo', Roberto; Nicolò, D.; Nishiguchi, H.; Nishimura, M.; Ogawa, S.; Ootani, W.; Orito, S.; Panareo, M.; Papa, A.; Pazzi, R.; Pepino, A.; Piredda, G.; Pizzigoni, G.; Popov, A.; Raffaelli, F.; Renga, F.; Ripiccini, E.; Ritt, S.; Rossella, M.; Rutar, G.; Sawada, R.; Sergiampietri, F.; Signorelli, G.; Simonetta, M.; Tassielli, G. F.; Tenchini, F.; Uchiyama, Y.; Venturini, M.; Voena, C.; Yamamoto, A.; Yoshida, K.; You, Z.; Yudin, Y. u. V.; Zanello, D