Search

Your search keyword '"Miller, M.W."' showing total 253 results
Start Over Author "Miller, M.W."
253 results on '"Miller, M.W."'

11. CUE: CpG impUtation ensemble for DNA methylation levels across the human methylation450 (HM450) and EPIC (HM850) BeadChip platforms

Author

Li, Y., Fry, R.C., O'Shea, T.M., Li, G., Santos, H.P., Jr., Miller, M.W., Raffield, L., and Logue, M.

Abstract

DNA methylation at CpG dinucleotides is one of the most extensively studied epigenetic marks. With technological advancements, geneticists can profile DNA methylation with multiple reliable approaches. However, profiling platforms can differ substantially in the CpGs they assess, consequently hindering integrated analysis across platforms. Here, we present CpG impUtation Ensemble (CUE), which leverages multiple classical statistical and modern machine learning methods, to impute from the Illumina HumanMethylation450 (HM450) BeadChip to the Illumina HumanMethylationEPIC (HM850) BeadChip. Data were analysed from two population cohorts with methylation measured both by HM450 and HM850: the Extremely Low Gestational Age Newborns (ELGAN) study (n = 127, placenta) and the VA Boston Posttraumatic Stress Disorder (PTSD) genetics repository (n = 144, whole blood). Cross-validation results show that CUE achieves the lowest predicted root-mean-square error (RMSE) (0.026 in PTSD) and the highest accuracy (99.97% in PTSD) compared with five individual methods tested, including k-nearest-neighbours, logistic regression, penalized functional regression, random forest, and XGBoost. Finally, among all 339,033 HM850-only CpG sites shared between ELGAN and PTSD, CUE successfully imputed 289,604 (85.4%) sites, where success was defined as RMSE < 0.05 and accuracy >95% in PTSD. In summary, CUE is a valuable tool for imputing CpG methylation from the HM450 to HM850 platform.

Published
2021
Full Text
View/download PDF

14. Contributors

Author

Akshoomoff, N., primary, Bauer, P.J., additional, Beltz, A.M., additional, Berenbaum, S.A., additional, Blakemore, J.E.O., additional, Bowman, A.B., additional, Bramen, J.E., additional, Brooks-Kayal, A.R., additional, Casey, B.J., additional, Cohen, M.M., additional, Colby, J.B., additional, Colonnese, M., additional, Cordeaux, C., additional, Cubells, J.F., additional, Davis, E.P., additional, Decety, J., additional, Ess, K.C., additional, Feldman, D.E., additional, Fernandez, L., additional, Fitch, R.H., additional, Fox, N.A., additional, Franklin, N., additional, Gillespie, D.C., additional, Gunnar, M.R., additional, Gweon, H., additional, Hagerman, R.J., additional, Haist, F., additional, Hughes, C., additional, Johnson, M.H., additional, Johnson, S.P., additional, Kano, M., additional, Khazipov, R., additional, Kim, S.-J., additional, King, A.J., additional, Kumar, K.K., additional, Lahat, A., additional, Lany, J., additional, Leigh, M.J., additional, Lein, P.J., additional, Lepousez, G., additional, Lewis, M., additional, Lledo, P.-M., additional, Michalska, K.J., additional, Miller, M.W., additional, Minlebaev, M., additional, Molnár, Z., additional, Mooney, S.M., additional, Moreno-De-Luca, D., additional, Muller, D., additional, Nelson, C.A., additional, Nikonenko, I., additional, Niswander, L., additional, O'Hare, E.D., additional, Pelphrey, K., additional, Persico, A.M., additional, Polley, D.B., additional, Posner, M.I., additional, Pyrgaki, C., additional, Reiter, L.T., additional, Righi, G., additional, Rothbart, M.K., additional, Rubenstein, E., additional, Rueda, M.R., additional, Saffran, J.R., additional, Sanchez, J.T., additional, Saxe, R., additional, Seery, A.M., additional, Seidl, A.H., additional, Sherr, E.H., additional, Shulz, D.E., additional, Sowell, E.R., additional, Stanford, T.R., additional, Stein, B.E., additional, Stiles, J., additional, Summar, K.L., additional, Tager-Flusberg, H., additional, Thomas, A.X., additional, Tirrell, J., additional, Urraca, N., additional, Veenstra-VanderWeele, J., additional, Voos, A., additional, Wang, Y., additional, and Watanabe, M., additional

Published
2013
Full Text
View/download PDF

15. Observations on fisheries activities at Navassa Island

Author

Miller, M.W., McClellan, D.B., and Begin, C.

Subjects
Navassa Island -- Natural resources -- Location, Fisheries -- Equipment and supplies -- Management -- Production processes -- Research, Fish industry -- Management -- Production processes -- Research, Agricultural industry, Business, Company business management, Company process management, Production processes, Management, Observations, Location, Research, Natural resources
Abstract

Unmanaged and unquantified artisanal fishing is ongoing at Navassa Island, a small oceanic island about 70 km west of Haiti that is part of the U.S. Caribbean Islands National Wildlife Refuge. Concern has been expressed regarding the possible impact of these fishing activities on reef resources, and no quantitative catch or effort data are available. However, informal qualitative observations made during a cruise in November 2002 suggest that escalation in fishing activity (and impact) has occurred since previous observations made in April 2000. Namely, size structure of fish was markedly reduced and the adoption of net fishing has allowed the exploitation of queen conch, Strombas gigas, and hawksbill turtles, Eretmochelys imbricata., Introduction Despite extremely high rates of primary production in coral reef ecosystems, actual yield of coral reef fisheries is relatively low. In addition, the ecological complexity, richness, and specialized life [...]

Published
2003

16. Ecology of a corallivorous gastropod, Coralliophila abbreviata, on two scleractinian hosts. II. Feeding, respiration and growth

Author

Baums, I.B., Miller, M.W., and Szmant, A.M.

Subjects
Gastropoda -- Food and nutrition, Gastropoda -- Growth, Snails -- Food and nutrition, Snails -- Growth, Coral reef fauna -- Environmental aspects, Company growth, Biological sciences
Abstract

Coralliophila abbreviata is a corallivorous gastropod that has been observed to cause large feeding scars on reef-building corals on Floridian and Caribbean reefs. We detected differences in the population structure (length-frequency distribution and sex ratios) of C. abbreviata populations living on two coral host taxa, Acropora palmata and Montastraea spp., in the Florida Keys in a previous study. We hypothesize that diet (host) has a major influence on snail population structure and, thus, we characterize metabolism, feeding and growth for snails residing on these coral taxa. Here, we present results of a reciprocal transplant experiment demonstrating that the taxon of the host influences snail growth rates, as indicated by changes in shell and body tissue weight. Regardless of the host from which they were drawn, snails resident on A. palmata grew faster than those resident on Montastraea spp. Thus, diet influences snail population structure. However, the tissue of Montastraea spp. provides more N and C per area of tissue than that of A. palmata. Respiration rates and tissue composition of snails collected from the two host taxa did not differ. Therefore, snails feeding on Montastraea spp. should have to consume less tissue per day to satisfy their metabolic requirements compared to snails feeding on A. palmata. Feeding rates for snails on A. palmata were measured in the laboratory over 48 h (1-9 [cm.sup.2] coral tissue [snail.sup.-1] [day.sup.-1]) and estimated from feeding scars observed in the field (weekly mean rate of 1.07 [cm.sup.2] coral tissue [snail.sup.-1] [day.sup.-1]). The lack of definition of snail feeding scars on Montastraea spp. required the calculation of coral tissue consumption rates based on estimated minimum carbon requirements. Calculated feeding rates for C. abbreviata were 0.13-0.88 [cm.sup.2] coral tissue [day.sup.-1] [snail.sup.-1], when feeding on Montastraea spp., and 0.44-3.28 [cm.sup.2] coral tissue [day.sup.-1] [snail.sup.-1], when feeding on A. palmata. The calculated range for the latter is consistent with measured rates. Thus, C. abbreviata exhibits high variation in growth parameters in response to environmental variability and/or food source. At mean levels of snail density on reefs off Key Largo, Fla., 20% of A. palmata colonies lose between 1.32 and 9.84 [cm.sup.2] tissue day-1, while 50% of Montastraea spp. colonies lose between 1.04 and 7.04 [cm.sup.2] tissue [day.sup.-1]. Together with published coral tissue regeneration rates, these results suggest that if sustained, such rates of predation could have a serious effect on the viability of these coral populations on Florida's reefs.

Published
2003

21. Hybridization within the species complex of the scleractinan coral Montastraea annularis

Author

Szmant, A.M., Weil, E., Miller, M.W., and Colon, D.E.

Subjects
Hybridization -- Observations, Corals -- Physiological aspects, Biological sciences
Abstract

The Montastraea annularis reef coral has reclassified into three species based on morphology, behaviour, allele frequencies and life-history traits. Reciprocal intra- and inter-specific fertilization experiments were undertaken with gametes from each of the new classifications, and self fertilization rates were found to be low or nil. Within-species and inter-species crosses production planulae and there was variation in the succes of fertilization. This indicates that there is no pre-zygotic barrier to cross-fertilization.

Published
1997

30. International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci

Author

Schijven, D., Chen, C.-Y., Morey, R.A., Vermetten, E., Sanchez, S.E., Maihofer, A.X., Jett, M., Dale, A.M., Ratanatharathorn, A., McGlinchey, R.E., McLaughlin, K.A., Polimanti, R., Roberts, A.L., Williams, M.A., Nievergelt, C.M., Atkinson, E.G., Mors, O., Brashear, M., Gordon, S.D., Trapido, E., Haas, M., Lawford, B.R., Kimbrel, N.A., Sponheim, S.R., Daskalakis, N.P., Duncan, L.E., Rung, A., Orcutt, H.K., Pietrzak, R.H., Bustamante, A.C., Bisson, J.I., Koenen, K.C., McLean, S.A., Ripke, S., Kremen, W.S., Maples-Keller, J., Marmar, C., Sheerin, C.M., Calabrese, J.R., Andersen, S.B., Seligowski, A.V., Feeny, N.C., Polusny, M.A., Qin, X.-J., Daly, M.J., Ashley-Koch, A.E., Morris, C.P., Liberzon, I., Erbes, C.R., King, A.P., Zhao, H., Forbes, D., Jakovljevic, M., van den Heuvel, L.L., Peters, E.S., Evans, A., Boks, M.P., Aiello, A.E., Hougaard, D.M., Roy-Byrne, P., Bierut, L.J., Kranzler, H.R., Vinkers, C.H., Peterson, A.L., Wolf, C., Deckert, J., Linnstaedt, S.D., Stein, D.J., Levey, D.F., Almli, L.M., Martin, N.G., Williamson, D.E., Flory, J.D., Børglum, A.D., Guffanti, G., Stein, M.B., Lori, A., Khan, A., Baker, D.G., Ressler, K.J., Torres, K., Seedat, S., Andreassen, O.A., Neale, B.M., Werge, T., Mehta, D., Austin, S.B., Breen, G., Beckham, J.C., Geuze, E., Miller, M.W., Mortensen, P.B., Coleman, J.R.I., Provost, A.C., Norman, S.B., Garrett, M.E., McLeay, S., Van Hooff, M., Bolger, E.A., Franz, C.E., Luykx, J.J., Maurer, D., Wolff, J.D., Martin, A.R., Young, K.A., Lewis, C.E., Zoellner, L.A., Dennis, M.F., Delahanty, D.L., O’Donnell, M., Heath, A.C., Saccone, N.L., Domschke, K., Logue, M.W., Ursano, R.J., Smith, A.K., Rothbaum, A.O., Rutten, B.P.F., Harnal, S., Panizzon, M.S., Uddin, M., Babiat, D., Bryant, R.A., Gelernter, J., Smoller, J.W., Klengel, T., Bybjerg-Grauholm, J., Choi, K.W., Jovanovic, T., Caldas-de-Almeida, J.M., Nelson, E.C., Mavissakalian, M.R., Johnson, E.O., Hammamieh, R, Milberg, W.P., Nordentoft, M., Gillespie, C., Amstadter, A.B., Bradley, B., Teicher, M.H., Arbisi, P.A., Lebois, L.A.M., Hauser, M.A., Dzubur-Kulenovic, A., Hemmings, S.M.J., Gelaye, B., Sumner, J.A., Uka, A.G., Young, R.M.D., Voisey, J., Wang, Y., Galea, S., Wang, Z., Jones, I., Peverill, M., Disner, S.G., Seng, J.S., Kessler, R.C., Junglen, A.G., Wolf, E.J., Lugonja, B., Dalvie, S., Koen, N., Rice, J.P., Rothbaum, B.O., Thompson, W.K., Ruggiero, K., Karstoft, K.-I., Farrer, L.A., Stevens, J.S., Silove, D., Avdibegovic, E., Risbrough, V.B., Lyons, M.J., Bækvad-Hansen, M., and McFarlane, A.

Abstract

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations. © 2019, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Published
2019
Full Text
View/download PDF

33. A putative causal relationship between genetically determined female body shape and posttraumatic stress disorder

Author

Morey, R.A., Garrett, M.E., Roberts, A.L., Ratanatharathorn, A., Kessler, R.C., Gelernter, J., Dalvie, S., Hauser, M.A., Almli, L.M., Psychiatric Genomics Consortium Posttraumatic Stress Disorder Workgroup, Smoller, J.W., Baker, D.G., Ashley-Koch, A.E., Chen, C.-Y., Nugent, N.R., Rice, J.P., Farrer, L.A., Miller, M.W., Aiello, A.E., Nievergelt, C.M., Duncan, L.E., Bierut, L.J., Bradley, B., Wildman, D.E., Daly, M.J., Koen, N., Polimanti, R., Amstadter, A.B., Ressler, K.J., Galea, S., King, A., Bisson, J., Guffanti, G., Sumner, J.A., Kimbrel, N.A., Johnson, E.O., Maihofer, A.X., Ripke, S., Kranzler, H.R., Yehuda, R., Koenen, K.C., Ursano, R.J., Beckham, J.C., Uddin, M., Gelernter, J.E., Liberzon, I., Zhao, H., Saccone, N.L., Stein, M.B., Martin, A.R., Stein, D.J., and Logue, M.W.

Abstract

Background: The nature and underlying mechanisms of the observed increased vulnerability to posttraumatic stress disorder (PTSD) in women are unclear. Methods: We investigated the genetic overlap of PTSD with anthropometric traits and reproductive behaviors and functions in women. The analysis was conducted using female-specific summary statistics from large genome-wide association studies (GWAS) and a cohort of 3577 European American women (966 PTSD cases and 2611 trauma-exposed controls). We applied a high-resolution polygenic score approach and Mendelian randomization analysis to investigate genetic correlations and causal relationships. Results: We observed an inverse association of PTSD with genetically determined anthropometric traits related to body shape, independent of body mass index (BMI). The top association was related to BMI-adjusted waist circumference (WCadj; R = -0.079, P < 0.001, Q = 0.011). We estimated a relative decrease of 64.6% (95% confidence interval = 27.5-82.7) in the risk of PTSD per 1-SD increase in WCadj. MR-Egger regression intercept analysis showed no evidence of pleiotropic effects in this association (Ppleiotropy = 0.979). We also observed associations of genetically determined WCadj with age at first sexual intercourse and number of sexual partners (P = 0.013 and P < 0.001, respectively). Conclusions: There is a putative causal relationship between genetically determined female body shape and PTSD, which could be mediated by evolutionary mechanisms involved in human sexual behaviors.

Published
2017
Full Text
View/download PDF

34. Discovery of MLi-2, an Orally Available and Selective LRRK2 Inhibitor that Reduces Brain Kinase Activity

Author

Scott, J.D., primary, DeMong, D.E., additional, Fell, M.J., additional, Mirescu, C., additional, Basu, K., additional, Greshock, T.J., additional, Morrow, J.A., additional, Xiao, L., additional, Hruza, A., additional, Harris, J., additional, Tiscia, H.E., additional, Chang, R.K., additional, Embrey, M.W., additional, McCauley, J.A., additional, Li, W., additional, Lin, S., additional, Liu, H., additional, Dai, X., additional, Baptista, M., additional, Agnihotri, G., additional, Columbus, J., additional, Mei, H., additional, Poirier, M., additional, Zhou, X., additional, Lin, Y., additional, Yin, Z., additional, Sanders, J.M., additional, Drolet, R.E., additional, Kern, J.T., additional, Kennedy, M.E., additional, Parker, E.M., additional, Stamford, A.W., additional, Nargund, R., additional, and Miller, M.W., additional

Published
2017
Full Text
View/download PDF

37. Continental Bedrock and Riverine Fluxes of Strontium and Neodymium Isotopes to the Oceans

Author

Peucker-Ehrenbrink, B., Miller, M.W, Arsouze, Thomas, Jeandel, C., Woods Hole Oceanographic Institution (WHOI), Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Laboratoire d'études en Géophysique et océanographie spatiales (LEGOS), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDU.OCEAN]Sciences of the Universe [physics]/Ocean, Atmosphere, 1022 Geochemistry: Composition of the hydrosphere, river, 5 tables seawater, 7 figures, strontium, continental runoff 1030 Geochemistry: Geochemical cycles (0330), 1040 Geochemistry: Radiogenic isotope geochemistry, isotope, ComputingMilieux_MISCELLANEOUS, 799 words, neodymium
Abstract

International audience

Published
2010
Full Text
View/download PDF

40. Emll M. Mrak

Author

Mccorkle, C.O., primary, Miller, M.W., additional, Pearl, R.C., additional, Phaff, H.J., additional, and Schweigert, B., additional

Published
1989
Full Text
View/download PDF

42. Recent region-wide declines in Caribbean reef fish abundance

Author

Paddack, M.J., Reynolds, J.D., Aguilar, C., Appeldoorn, R.S., Beets, J., Burkett, E.W., Chittaro, P.M., Clarke, K., Esteves, R., Fonseca, A.C., Forrester, G.E., Friedlander, A.M., Garcia-Sais, J. Jorge, Gonzalez-Sanson, G., Jordan, L.K.B., McClellan, D.B., Miller, M.W., Molloy, P.P., Mumby, P.J., Nagelkerken, I., Nemeth, M., Navas-Camacho, R., Pitt, J., Polunin, N.V.C., Reyes-Nivia, M.C., Robertson, D.R., Rodriguez-Ramirez, A., Salas, E., Smith, S.R., Spieler, R.E., Steele, M.A., Williams, I.D., Wormald, C.L., Watkinson, A.R., Cote, I.M., Paddack, M.J., Reynolds, J.D., Aguilar, C., Appeldoorn, R.S., Beets, J., Burkett, E.W., Chittaro, P.M., Clarke, K., Esteves, R., Fonseca, A.C., Forrester, G.E., Friedlander, A.M., Garcia-Sais, J. Jorge, Gonzalez-Sanson, G., Jordan, L.K.B., McClellan, D.B., Miller, M.W., Molloy, P.P., Mumby, P.J., Nagelkerken, I., Nemeth, M., Navas-Camacho, R., Pitt, J., Polunin, N.V.C., Reyes-Nivia, M.C., Robertson, D.R., Rodriguez-Ramirez, A., Salas, E., Smith, S.R., Spieler, R.E., Steele, M.A., Williams, I.D., Wormald, C.L., Watkinson, A.R., and Cote, I.M.

Abstract

Contains fulltext : 75983.pdf (publisher's version ) (Closed access)

Published
2009

45. Inhibition of protease-resistant prion protein formation in a transformed deer cell line infected with chronic wasting disease

Author

Raymond, G.J., Olsen, E.A., Lee, K.S., Raymond, L.D., Bryant, P.K., Baron, G.S., Caughey, W.S., Kocisko, D.A., McHolland, L.E., Favara, C., Langeveld, J.P.M., van Zijderveld, F.G., Mayer, R.T., Miller, M.W., Williams, E.S., Caughey, B., Raymond, G.J., Olsen, E.A., Lee, K.S., Raymond, L.D., Bryant, P.K., Baron, G.S., Caughey, W.S., Kocisko, D.A., McHolland, L.E., Favara, C., Langeveld, J.P.M., van Zijderveld, F.G., Mayer, R.T., Miller, M.W., Williams, E.S., and Caughey, B.

Abstract

Chronic wasting disease (CWD) is an emerging transmissible spongiform encephalopathy (prion disease) of North American cervids, i.e., mule deer, white-tailed deer, and elk (wapiti). To facilitate in vitro studies of CWD, we have developed a transformed deer cell line that is persistently infected with CWD. Primary cultures derived from uninfected mule deer brain tissue were transformed by transfection with a plasmid containing the simian virus 40 genome. A transformed cell line (MDB) was exposed to microsomes prepared from the brainstem of a CWD-affected mule deer. CWD-associated, protease-resistant prion protein (PrPCWD) was used as an indicator of CWD infection. Although no PrPCWD was detected in any of these cultures after two passes, dilution cloning of cells yielded one PrPCWD-positive clone out of 51. This clone, designated MDBCWD, has maintained stable PrPCWD production through 32 serial passes thus far. A second round of dilution cloning yielded 20 PrPCWD-positive subclones out of 30, one of which was designated MDBCWD2. The MDBCWD2 cell line was positive for fibronectin and negative for microtubule-associated protein 2 (a neuronal marker) and glial fibrillary acidic protein (an activated astrocyte marker), consistent with derivation from brain fibroblasts (e.g., meningeal fibroblasts). Two inhibitors of rodent scrapie protease-resistant PrP accumulation, pentosan polysulfate and a porphyrin compound, indium (III) meso-tetra(4-sulfonatophenyl)porphine chloride, potently blocked PrPCWD accumulation in MDBCWD cells. This demonstrates the utility of these cells in a rapid in vitro screening assay for PrPCWD inhibitors and suggests that these compounds have potential to be active against CWD in vivo.

Published
2006

47. Brodmann area 12

Author

Kawamura, M., primary, Miller, M.W., additional, Ichikawa, H., additional, Ishihara, K., additional, and Sugimoto, A., additional

Published
2011
Full Text
View/download PDF

49. PrPCWD lymphoid cell targets in early and advanced chronic wasting disease of mule deer

Author

Sigurdson, C.J., Barillas-Mury, C., Miller, M.W., Oesch, B., van Keulen, L.J.M., Langeveld, J.P.M., Hoover, E.A., Sigurdson, C.J., Barillas-Mury, C., Miller, M.W., Oesch, B., van Keulen, L.J.M., Langeveld, J.P.M., and Hoover, E.A.

Abstract

Up to 15% of free-ranging mule deer in northeastern Colorado and southeastern Wyoming, USA, are afflicted with a prion disease, or transmissible spongiform encephalopathy (TSE), known as chronic wasting disease (CWD). CWD is similar to a subset of TSEs including scrapie and variant Creutzfeldt¿Jakob disease in which the abnormal prion protein isoform, PrPCWD, accumulates in lymphoid tissue. Experimental scrapie studies have indicated that this early lymphoid phase is an important constituent of prion replication interposed between mucosal entry and central nervous system accumulation. To identify the lymphoid target cells associated with PrPCWD, we used triple-label immunofluorescence and high-resolution confocal microscopy on tonsils from naturally infected deer in advanced disease. We detected PrPCWD primarily extracellularly in association with follicular dendritic and B cell membranes as determined by frequent co-localization with antibodies against membrane bound immunoglobulin and CD21. There was minimal co-localization with cytoplasmic labels for follicular dendritic cells (FDC). This finding could indicate FDC capture of PrPCWD, potentially in association with immunoglobulin or complement, or PrPC conversion on FDC. In addition, scattered tingible body macrophages in the germinal centre contained coarse intracytoplasmic aggregates of PrPCWD, reflecting either phagocytosis of PrPCWD on FDC processes, apoptotic FDC or B cells, or actual PrPCWD replication within tingible body macrophages. To compare lymphoid cell targets in early and advanced disease, we also examined: (i) PrPCWD distribution in lymphoid cells of fawns within 3 months of oral CWD exposure and (ii) tonsil biopsies from preclinical deer with naturally acquired CWD. These studies revealed that the early lymphoid cellular distribution of PrPCWD was similar to that in advanced disease, i.e. in a pattern suggesting FDC association. We conclude that in deer, PrPCWD accumulates primarily extracellular

Published
2002

Catalog

Books, media, physical & digital resources
See catalog results