Prions in Variably Protease-Sensitive Prionopathy: An Update
Zou, W.Q. ; Gambetti, P. ; Xiao, X. ; Yuan, J. ; Langeveld, J.P.M. ; Pirisinu, L. - \ 2013
Pathogens 2 (2013)3. - ISSN 2076-0817 - p. 457 - 471.
Human prion diseases, including sporadic, familial, and acquired forms such as Creutzfeldt-Jakob disease (CJD), are caused by prions in which an abnormal prion protein (PrPSc) derived from its normal cellular isoform (PrPC) is the only known component. The recently-identified variably protease-sensitive prionopathy (VPSPr) is characterized not only by an atypical clinical phenotype and neuropathology but also by the deposition in the brain of a peculiar PrPSc. Like other forms of human prion disease, the pathogenesis of VPSPr also currently remains unclear. However, the findings of the peculiar features of prions from VPSPr and of the possible association of VPSPr with a known genetic prion disease linked with a valine to isoleucine mutation at residue 180 of PrP reported recently, may be of great importance in enhancing our understanding of not only this atypical human prion disease in particular, but also other prion diseases in general. In this review, we highlight the physicochemical and biological properties of prions from VPSPr and discuss the pathogenesis of VPSPr including the origin and formation of the peculiar prions.
Glycoform-selective prion formation in sporadic and familial forms of prion disease
Xiao, X. ; Yuan, J. ; Haïk, S. ; Cali, I. ; Zhan, Y. ; Moudjou, M. ; Li, B. ; Laplanche, J.L. ; Laude, H. ; Langeveld, J.P.M. ; Gambetti, P. - \ 2013
PLoS ONE 8 (2013)3. - ISSN 1932-6203 - 9 p.
creutzfeldt-jakob-disease - prpsc formation - protein - scrapie - glycosylation - mutation - antibody - cells - susceptibility - conformers
The four glycoforms of the cellular prion protein (PrP(C)) variably glycosylated at the two N-linked glycosylation sites are converted into their pathological forms (PrP(Sc)) in most cases of sporadic prion diseases. However, a prominent molecular characteristic of PrP(Sc) in the recently identified variably protease-sensitive prionopathy (VPSPr) is the absence of a diglycosylated form, also notable in familial Creutzfeldt-Jakob disease (fCJD), which is linked to mutations in PrP either from Val to Ile at residue 180 (fCJD(V180I)) or from Thr to Ala at residue 183 (fCJD(T183A)). Here we report that fCJD(V180I), but not fCJD(T183A), exhibits a proteinase K (PK)-resistant PrP (PrP(res)) that is markedly similar to that observed in VPSPr, which exhibits a five-step ladder-like electrophoretic profile, a molecular hallmark of VPSPr. Remarkably, the absence of the diglycosylated PrP(res) species in both fCJD(V180I) and VPSPr is likewise attributable to the absence of PrP(res) glycosylated at the first N-linked glycosylation site at residue 181, as in fCJD(T183A). In contrast to fCJD(T183A), both VPSPr and fCJD(V180I) exhibit glycosylation at residue 181 on di- and monoglycosylated (mono181) PrP prior to PK-treatment. Furthermore, PrP(V180I) with a typical glycoform profile from cultured cells generates detectable PrP(res) that also contains the diglycosylated PrP in addition to mono- and unglycosylated forms upon PK-treatment. Taken together, our current in vivo and in vitro studies indicate that sporadic VPSPr and familial CJD(V180I) share a unique glycoform-selective prion formation pathway in which the conversion of diglycosylated and mono181 PrP(C) to PrP(Sc) is inhibited, probably by a dominant-negative effect, or by other co-factors.
|Modeling Gross Primary Production of Savanna Woodlands in Southern Africa Using MODIS Imagery and CO2 Flux Tower Data
Jin, C. ; Xiao, X. ; Merbold, L. ; Arneth, A. ; Veenendaal, E.M. ; Kutsch, W. - \ 2012
Accurate estimation of gross primary production (GPP) of savanna ecosystem is valuable for evaluating the role of Africa in the global carbon cycle. An eddy flux observation network has been established to continuously measure the net CO2 fluxes (NEE) across various savanna vegetation types in Africa (CarboAfrica). Several publications have reported the seasonal dynamics and interannual variation of GPP for the savanna vegetation through partitioning of the measured NEE data. The satellite-based Production Efficiency Models (PEM), which calculate GPP as the product of absorbed photosynthetically active radiation (PAR) and light use efficiency (LUE), have been developed to scale up in situ GPP estimation from the eddy flux towers to regional scale. In this study, the Vegetation Photosynthesis Model (VPM) and the Moderate Resolution Imaging Spectroradiometer (MODIS) data were evaluated for their capacity to model GPP for savanna woodlands at two eddy flux towers in Botswana and Zambia, respectively. These two sites have different woodland types and precipitation pattern (Mopane woodlands vs. Miombo woodlands, semi-arid vs. semi-humid). In the VPM model, GPP is simulated as the product of photosynthetically active radiation (PAR), air temperature, Enhanced Vegetation Index (EVI), and Land Surface Water Index (LSWI). The results show that the simulated GPP by the VPM track well the temporal dynamic of GPP estimated from the eddy covariance measurements at these two sites. In addition, the land surface phenology of savanna woodlands, described by the satellite vegetation indices, especially the water-sensitive satellite indices-LSWI, are proved to match the phenology based on vegetation physiology activity measured by eddy covariance towers. The information of the timing and duration of vegetation growing season is useful for assisting the VPM modeling. Further evaluation of VPM simulations for and other savanna ecosystems is necessary before the VPM model is applied to estimate GPP of savanna ecosystems in Africa.
Variably protease-sensitive prionopathy: a new sporadic disease of the prion protein
Zou, W.Q. ; Puoti, G. ; Xiao, X. ; Yuan, J. ; Qing, L. ; Cali, I. ; Shimoji, M. ; Langeveld, J.P.M. ; Castellani, R. ; Notari, S. ; Crain, B. ; Schmidt, R. ; Geschwind, M. ; DeArmond, S.J. ; Cairns, N. ; Dickson, D. ; Honig, I. ; Torres, J.M. ; Mastrianni, J. ; Capellari, S. ; Giaccone, G. ; Belay, E.D. ; Schonberger, L.B. ; Cohen, M. ; Perry, G. ; Kong, Q. ; Parchi, P. ; Tagliavini, F. ; Gambetti, P. - \ 2010
Annals of Neurology 68 (2010)2. - ISSN 0364-5134 - p. 162 - 172.
creutzfeldt-jakob-disease - gerstmann-straussler-scheinker - codon 129 - prp - cjd - classification - transmission - phenotype - subtypes - brain
Objective: The objective of the study is to report 2 new genotypic forms of protease-sensitive prionopathy (PSPr), a novel prion disease described in 2008, in 11 subjects all homozygous for valine at codon 129 of the prion protein (PrP) gene (129VV). The 2 new PSPr forms affect individuals who are either homozygous for methionine (129MM) or heterozygous for methionine/valine (129MV). Methods: Fifteen affected subjects with 129MM, 129MV, and 129VV underwent comparative evaluation at the National Prion Disease Pathology Surveillance Center for clinical, histopathologic, immunohistochemical, genotypical, and PrP characteristics. Results: Disease duration (between 22 and 45 months) was significantly different in the 129VV and 129MV subjects. Most other phenotypic features along with the PrP electrophoretic profile were similar but distinguishable in the 3 129 genotypes. A major difference laid in the sensitivity to protease digestion of the disease-associated PrP, which was high in 129VV but much lower, or altogether lacking, in 129MV and 129MM. This difference prompted the substitution of the original designation with "variably protease-sensitive prionopathy" (VPSPr). None of the subjects had mutations in the PrP gene coding region. Interpretation: Because all 3 129 genotypes are involved, and are associated with distinguishable phenotypes, VPSPr becomes the second sporadic prion protein disease with this feature after Creutzfeldt-Jakob disease, originally reported in 1920. However, the characteristics of the abnormal prion protein suggest that VPSPr is different from typical prion diseases, and perhaps more akin to subtypes of Gerstmann-Straussler-Scheinker disease. ANN NEUROL 2010;68:162-172
PrP Conformational Transitions Alter Species Preference of a PrP-specific antibody
Zou, W.Q. ; Langeveld, J.P.M. ; Xiao, X. ; Chen, S. ; McGeer, P.L. ; Yuan, J. ; Payne, M.C. ; Kang, H.E. ; McGeehan, J.M. ; Sy, M.S. ; Greenspan, N.S. ; Kaplan, D. ; Wang, G.X. ; Parchi, P. ; Hoover, E.A. ; Kneale, G. ; Telling, G. ; Surewicz, W. ; Kong, Q. ; Guo, J. - \ 2010
Journal of Biological Chemistry 285 (2010). - ISSN 0021-9258 - p. 13874 - 13884.
creutzfeldt-jakob-disease - pathological prion protein - monoclonal-antibody - n-terminus - scrapie - epitope - binding - brain - recognition - strain
The epitope of the 3F4 antibody most commonly used in human prion disease diagnosis is believed to consist of residues Met-Lys-His-Met (MKHM) corresponding to human PrP-(109–112). This assumption is based mainly on the observation that 3F4 reacts with human and hamster PrP but not with PrP from mouse, sheep, and cervids, in which Met at residue 112 is replaced by Val. Here we report that, by brain histoblotting, 3F4 did not react with PrP of uninfected transgenic mice expressing elk PrP; however, it did show distinct immunoreactivity in transgenic mice infected with chronic wasting disease. Compared with human PrP, the 3F4 reactivity with the recombinant elk PrP was 2 orders of magnitude weaker, as indicated by both Western blotting and surface plasmon resonance. To investigate the molecular basis of these species- and conformer-dependent preferences of 3F4, the epitope was probed by peptide membrane array and antigen competition experiments. Remarkably, the 3F4 antibody did not react with MKHM but reacted strongly with KTNMK (corresponding to human PrP-(106–110)), a sequence that is also present in cervids, sheep, and cattle. 3F4 also reacted with elk PrP peptides containing KTNMKHV. We concluded that the minimal sequence for the 3F4 epitope consists of residues KTNMK, and the species- and conformer-dependent preferences of 3F4 arise largely from the interactions between Met112 (human PrP) or Val115 (cervid PrP) and adjacent residues.
Linking flux network measurements to continental scale simulations: ecosystem carbon dioxide exchange capacity under non-water-stressed conditions
Owen, K.E. ; Tenhunen, J. ; Reichstein, M. ; Wang, Q. ; Falge, E. ; Geyer, R. ; Xiao, X. ; Stoy, P. ; Ammann, C. ; Arain, A. ; Aubinet, M. ; Aurela, M. ; Bernhofer, C. ; Chojnicki, B.H. ; Granier, A. ; Gruenwald, T. ; Hadley, J. ; Heinesch, B. ; Hollinger, D. ; Knohl, A. ; Kutsch, W. ; Lohila, A. ; Meyers, T. ; Moors, E.J. ; Moureaux, C. ; Pilegaard, K. ; Saigusa, N. ; Verma, S. ; Vesala, T. ; Vogel, C. - \ 2007
Global Change Biology 13 (2007)4. - ISSN 1354-1013 - p. 734 - 760.
kooldioxide - eddy-covariantie - netto ecosysteem uitwisseling - gewassen - bossen - graslanden - wetlands - carbon dioxide - eddy covariance - net ecosystem exchange - crops - forests - grasslands - wetlands - northern temperate grassland - gross primary production - atmosphere co2 exchange - eddy-covariance measurements - daily canopy photosynthesis - danish beech forest - leaf-area index - rain-fed maize - long-term - process model
This paper examines long-term eddy covariance data from 18 European and 17 North American and Asian forest, wetland, tundra, grassland, and cropland sites under non-water-stressed conditions with an empirical rectangular hyperbolic light response model and a single layer two light-class carboxylase-based model. Relationships according to ecosystem functional type are demonstrated between empirical and physiological parameters, suggesting linkages between easily estimated parameters and those with greater potential for process interpretation. Relatively sparse documentation of leaf area index dynamics at flux tower sites is found to be a major difficulty in model inversion and flux interpretation. Therefore, a simplification of the physiological model is carried out for a subset of European network sites with extensive ancillary data. The results from these selected sites are used to derive a new parameter and means for comparing empirical and physiologically based methods across all sites, regardless of ancillary data. The results from the European analysis are then compared with results from the other Northern Hemisphere sites and similar relationships for the simplified process-based parameter were found to hold for European, North American, and Asian temperate and boreal climate zones. This parameter is useful for bridging between flux network observations and continental scale spatial simulations of vegetation/atmosphere carbon dioxide exchange