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https://www.readbyqxmd.com/read/28636656/selective-propagation-of-mouse-passaged-scrapie-prions-with-long-incubation-period-from-a-mixed-prion-population-using-gt1-7-cells
#1
Kohtaro Miyazawa, Kentaro Masujin, Hiroyuki Okada, Yuko Ushiki-Kaku, Yuichi Matsuura, Takashi Yokoyama
In our previous study, we demonstrated the propagation of mouse-passaged scrapie isolates with long incubation periods (L-type) derived from natural Japanese sheep scrapie cases in murine hypothalamic GT1-7 cells, along with disease-associated prion protein (PrPSc) accumulation. We here analyzed the susceptibility of GT1-7 cells to scrapie prions by exposure to infected mouse brains at different passages, following interspecies transmission. Wild-type mice challenged with a natural sheep scrapie case (Kanagawa) exhibited heterogeneity of transmitted scrapie prions in early passages, and this mixed population converged upon one with a short incubation period (S-type) following subsequent passages...
2017: PloS One
https://www.readbyqxmd.com/read/28619160/protein-misfolding-cyclic-amplification-corroborates-the-absence-of-prp-sc-accumulation-in-placenta-from-foetuses-with-the-arr-arq-genotype-in-natural-scrapie
#2
María Carmen Garza, Hasier Eraña, Joaquín Castilla, Cristina Acín, Antonia Vargas, Juan José Badiola, Eva Monleón
Ovine scrapie is a worldwide spread prion disease that is transmitted horizontally under field conditions. Placenta from scrapie-infected ewes is an important source of infection, since this tissue can accumulate high amounts of PrP(Sc) depending on the foetal genotype. Therefore, placentas carrying susceptible foetuses can accumulate PrP(Sc) but there is not PrP(Sc) accumulation in presence of foetuses with at least one ARR haplotype. In scrapie eradication programs, ARR/ARR males are used for breeding to increase the resistant progeny and reduce the horizontal transmission of the disease through the placenta...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28613153/precision-in-the-design-of-an-experimental-study-deflects-the-significance-of-proteinase-activated-receptor-2-expression-in-scrapie-inoculated-mice
#3
Zdenka Hanusova, Tibor Mosko, Radoslav Matej, Karel Holada
Proteinase-activated receptor 2 (PAR2) is suspected to modulate the pathogenesis of various neurodegenerative conditions. We previously described delayed onset of clinical symptoms and prolonged survival of PAR2-deficient mice after intracerebral inoculation with prions. Here we report the results from a refined blinded study that aimed to investigate the effects of PAR2 deletion on scrapie pathogenesis after peripheral infection. This study failed to confirm that PAR2 deficiency impacts on the length of the incubation period, with PAR2-/- and PAR2+/+ littermates developing scrapie at the same time...
June 14, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28605958/the-first-report-of-prion-related-protein-gene-prnt-polymorphisms-in-goat
#4
Yong-Chan Kim, Byung-Hoon Jeong
Prion protein is encoded by the prion protein gene (PRNP). Polymorphisms of several members of the prion gene family have shown association with prion diseases in several species. Recent studies on a novel member of the prion gene family in rams have shown that prion-related protein gene (PRNT) has a linkage with codon 26 of prion-like protein (PRND). In a previous study, codon 26 polymorphism of PRND has shown connection with PRNP haplotype which is strongly associated with scrapie vulnerability. In addition, the genotype of a single nucleotide polymorphism (SNP) at codon 26 of PRND is related to fertilisation capacity...
June 2017: Acta Veterinaria Hungarica
https://www.readbyqxmd.com/read/28596963/prion-diagnosis-application-of-real-time-quaking-induced-conversion
#5
REVIEW
Hae-Eun Kang, Youngwon Mo, Raihah Abd Rahim, Hye-Mi Lee, Chongsuk Ryou
Prions composed of pathogenic scrapie prion protein (PrP(Sc)) are infectious pathogens that cause progressive neurological conditions known as prion diseases or transmissible spongiform encephalopathies. Although these diseases pose considerable risk to public health, procedures for early diagnosis have not been established. One of the most recent attempts at sensitive and specific detection of prions is the real-time quaking-induced conversion (RT-QuIC) method, which measures the activity of PrP(Sc) aggregates or amyloid formation triggered by PrP(Sc) seeds in the presence of recombinant PrP...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28549342/mgr1-antigen-37-kda-laminin-receptor-precursor-promotes-cellular-prion-protein-induced-multi-drug-resistance-of-gastric-cancer
#6
Guanhong Luo, Weijie Wang, Qiong Wu, Yuanyuan Lu, Tao Su, Nan Gu, Kai Li, Jingbo Wang, Rui Du, Xiaodi Zhao, Xiaohua Li, Rui Fan, Hongbo Zhang, Yongzhan Nie, Xinmin Zhou, Yongquan Shi, Jie Liang, Xin Wang, Daiming Fan
Cellular prion protein (PrPC), the infective agent of transmissible spongiform encephalopathies, is thought to be related to several cellular physiological and physiopathological processes. We have previously reported that PrPC participates in multi-drug-resistance of gastric cancer. As the salient ligand molecule of PrP for participating in internalization and propagation of the scrapie form of prion protein (PrPSc), 37 kDa laminin receptor precursor protein (37LRP) shared the same gene coding sequence of MGr1-Ag, another protein previously found to be involved in multi-drug-resistance of gastric cancer in our lab...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28545141/prion-pathogenesis-is-unaltered-in-the-absence-of-sirp%C3%AE-mediated-don-t-eat-me-signaling
#7
Mario Nuvolone, Marta Paolucci, Silvia Sorce, Veronika Kana, Rita Moos, Takashi Matozaki, Adriano Aguzzi
Prion diseases are neurodegenerative conditions caused by misfolding of the prion protein, leading to conspicuous neuronal loss and intense microgliosis. Recent experimental evidence point towards a protective role of microglia against prion-induced neurodegeneration, possibly through elimination of prion-containing apoptotic bodies. The molecular mechanisms by which microglia recognize and eliminate apoptotic cells in the context of prion diseases are poorly defined. Here we investigated the possible involvement of signal regulatory protein α (SIRPα), a key modulator of host cell phagocytosis; SIRPα is encoded by the Sirpa gene that is genetically linked to the prion gene Prnp...
2017: PloS One
https://www.readbyqxmd.com/read/28540665/different-molecular-mechanisms-mediate-direct-or-glia-dependent-prion-protein-fragment-90-231-neurotoxic-effects-in-cerebellar-granule-neurons
#8
Stefano Thellung, Elena Gatta, Francesca Pellistri, Valentina Villa, Alessandro Corsaro, Mario Nizzari, Mauro Robello, Tullio Florio
Glia over-stimulation associates with amyloid deposition contributing to the progression of central nervous system neurodegenerative disorders. Here we analyze the molecular mechanisms mediating microglia-dependent neurotoxicity induced by prion protein (PrP)90-231, an amyloidogenic polypeptide corresponding to the protease-resistant portion of the pathological prion protein scrapie (PrP(Sc)). PrP90-231 neurotoxicity is enhanced by the presence of microglia within neuronal culture, and associated to a rapid neuronal [Ca(++)] i increase...
May 25, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28507517/the-role-of-unfolded-protein-response-and-mitogen-activated-protein-kinase-signaling-in-neurodegenerative-diseases-with-special-focus-on-prion-diseases
#9
REVIEW
Syed Zahid Ali Shah, Deming Zhao, Tariq Hussain, Lifeng Yang
Prion diseases are neurodegenerative pathologies characterized by the accumulation of a protease-resistant form of the cellular prion protein named prion protein scrapie (PrP(Sc)) in the brain. PrP(Sc) accumulation in the endoplasmic reticulum (ER) result in a dysregulated calcium (Ca(2+)) homeostasis and subsequent initiation of unfolded protein response (UPR) leading to neuronal dysfunction and apoptosis. The molecular mechanisms for the transition between adaptation to ER stress and ER stress-induced apoptosis are still unclear...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28472956/codon-141-polymorphisms-of-the-ovine-prion-protein-gene-affect-the-phenotype-of-classical-scrapie-transmitted-from-goats-to-sheep
#10
Timm Konold, Laura J Phelan, Ben R Donnachie, Melanie J Chaplin, Saira Cawthraw, Lorenzo González
BACKGROUND: A study to investigate transmission of classical scrapie via goat milk was carried out in sheep: firstly, lambs were challenged orally with goat scrapie brain homogenate to confirm transmission of scrapie from goats to sheep. In the second study phase, milk from scrapie-infected goats was fed to lambs. Lambs were selected according to their prion protein gene (PRNP) genotype, which was either VRQ/VRQ or ARQ/ARQ, with or without additional polymorphisms at codon 141 (FF141, LF141 or LL141) of the ovine PRNP...
May 4, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28470584/myelin-basic-protein-citrullination-a-hallmark-of-central-nervous-system-demyelination-assessed-by-novel-monoclonal-antibodies-in-prion-diseases
#11
Byungki Jang, Yong-Chul Jeon, Hae-Young Shin, Yun-Jung Lee, Hyunji Kim, Yoshitaka Kondo, Akihito Ishigami, Yong-Sun Kim, Eun-Kyoung Choi
Myelin basic protein (MBP) citrullination by peptidylarginine deiminase (PAD) enzymes leads to incomplete protein-lipid bilayer interactions and vulnerability to proteolytic enzymes, resulting in disorganization of the myelin sheath in the central nervous system. Therefore, citrullinated MBP (citMBP) has been suggested as a hallmark of demyelination, but how citMBP is implicated in prion diseases remains unknown. For the first time, we developed mouse monoclonal anti-citMBP IgG1 (clones 1B8, 1H1, and 3C6) and IgM (clone 3G5) antibodies that recognize human citMBP at its R25, R122, and R130 residues and at its C-terminal region (or the corresponding sites in mouse MBP), respectively...
May 3, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28455699/an-in-vivo-11-c-r-pk11195-pet-and-in-vitro-pathology-study-of-microglia-activation-in-creutzfeldt-jakob-disease
#12
Leonardo Iaccarino, Rosa Maria Moresco, Luca Presotto, Orso Bugiani, Sandro Iannaccone, Giorgio Giaccone, Fabrizio Tagliavini, Daniela Perani
Microgliosis is part of the immunobiology of Creutzfeldt-Jakob disease (CJD). This is the first report using (11)C-(R)-PK11195 PET imaging in vivo to measure 18 kDa translocator protein (TSPO) expression, indexing microglia activation, in symptomatic CJD patients, followed by a postmortem neuropathology comparison. One genetic CJD (gCJD) patient, two sporadic CJD (sCJD) patients, one variant CJD (vCJD) patient (mean ± SD age, 47.50 ± 15.95 years), and nine healthy controls (mean ± SD age, 44.00 ± 11...
April 28, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28440453/scrg1-suppresses-lps-induced-ccl22-production-through-erk1-2-activation-in-mouse-macrophage-raw264-7-cells
#13
Manabu Inoue, Junko Yamada, Emiko Aomatsu-Kikuchi, Kazuro Satoh, Hisatomo Kondo, Akira Ishisaki, Naoyuki Chosa
Recently, we identified the scrapie responsive gene 1 (SCRG1) secreted from mesenchymal stem cells (MSCs) and its receptor bone marrow stromal cell antigen 1 (BST1) as positive regulators of stem cell qualities such as self‑renewal, migration abilities, and osteogenic differentiation potential. Here, we examined the effect of the paracrine activity of SCRG1 in macrophages. The mouse macrophage‑like cell line Raw264.7 expressed BST1/β1 or BST1/β2 integrin as possible SCRG1 receptors. Unexpectedly, recombinant SCRG1 did not enhance cell proliferation, migration, or adhesion in these macrophages...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28432247/do-we-need-to-explain-the-occurrence-of-atypical-scrapie
#14
Giuseppe Ru
No abstract text is available yet for this article.
April 22, 2017: Veterinary Record
https://www.readbyqxmd.com/read/28421536/lysosomal-quality-control-in-prion-diseases
#15
REVIEW
Priyanka Majumder, Oishee Chakrabarti
Prion diseases are transmissible, familial or sporadic. The prion protein (PrP), a normal cell surface glycoprotein, is ubiquitously expressed throughout the body. While loss of function of PrP does not elicit apparent phenotypes, generation of misfolded forms of the protein or its aberrant metabolic isoforms has been implicated in a number of neurodegenerative disorders such as scrapie, kuru, Creutzfeldt-Jakob disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker and bovine spongiform encephalopathy...
April 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28407243/simulations-of-membrane-bound-diglycosylated-human-prion-protein-reveal-potential-protective-mechanisms-against-misfolding
#16
Chin Jung Cheng, Heidi Koldsø, Marc W Van der Kamp, Birgit Schiøtt, Valerie Daggett
Prion diseases are associated with the misfolding of the prion protein (PrP) from its normal cellular form (PrP(C) ) to its infectious scrapie form (PrP(S)(c) ). Post-translational modifications in PrP in vivo can play an important role in modulating the process of misfolding. To gain more insight into the effects of post-translational modifications in PrP structure and dynamics and to test the hypothesis that such modifications can interact with the protein, we have performed molecular dynamics simulations of diglycosylated human PrP(C) bound to a lipid bilayer via a glycophosphatidylinositol anchor...
July 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28362554/detection-of-a-new-20-bp-insertion-deletion-indel-within-sheep-prnd-gene-using-mathematical-expectation-me-method
#17
Jie Li, Xichun Zhu, Lin Ma, Hongwei Xu, Xin Cao, Renyun Luo, Hong Chen, Xiuzhu Sun, Yong Cai, Xianyong Lan
Prion-related protein doppel gene (PRND), as an essential member of the mammalian prion gene family, is associated with the scrapie susceptibility as well as phenotype traits, so the genetic variation of the PRND has been highly concerned recently, including the single nucleiotide polymorphism (SNP) and insertion/deletion (indel). Therefore, the objective of present study was to examine the possible indel variants by mathematical expectation (ME) detection method as well as explore its associations with phenotype traits...
March 4, 2017: Prion
https://www.readbyqxmd.com/read/28324664/limited-understanding-of-the-functional-diversity-of-n-linked-glycans-as-a-major-gap-of-prion-biology
#18
Ilia V Baskakov
Among a broad range of hypotheses on the molecular nature of transmissible spongiform encephalopathy or scrapie agents discussed in 1960s was a hypothesis of self-replicating polysaccharides. While the studies of the past 40 years provided unambiguous proof that this is not the case, emerging evidence suggests that carbohydrates in the form of sialylated N-linked glycans, which are a constitutive part of mammalian prions or PrP(Sc), are essential in determining prion fate in an organism. The current extra-view article discusses recent advancements on the role of N-linked glycans and specifically their sialylation status in controlling prion fate...
March 4, 2017: Prion
https://www.readbyqxmd.com/read/28268246/cerebellar-compartmentation-of-prion-pathogenesis
#19
Audrey Ragagnin, Juliette Ezpeleta, Aurélie Guillemain, François Boudet-Devaud, Anne-Marie Haeberlé, Valérie Demais, Catherine Vidal, Stanislas Demuth, Vincent Béringue, Odile Kellermann, Benoit Schneider, Nancy J Grant, Yannick Bailly
In prion diseases, the brain lesion profile is influenced by the prion "strain" properties, the invasion route to the brain, and still unknown host cell-specific parameters. To gain insight into those endogenous factors, we analyzed the histopathological alterations induced by distinct prion strains in the mouse cerebellum. We show that 22L and ME7 scrapie prion proteins (PrP(22L) , PrP(ME7) ), but not bovine spongiform encephalopathy PrP(6PB1) , accumulate in a reproducible parasagittal banding pattern in the cerebellar cortex of infected mice...
March 7, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28236170/pathogen-safety-of-a-new-intravenous-immune-globulin-10-liquid
#20
Kai Uwe Radomski, Georg Lattner, Torben Schmidt, Jürgen Römisch
BACKGROUND: The manufacturing process of a new intravenous immune globulin (IVIG) 10% liquid product incorporates two dedicated pathogen safety steps: solvent/detergent (S/D) treatment and nanofiltration (20 nm). Ion-exchange chromatography (IEC) during protein purification also contributes to pathogen safety. The ability of these three process steps to inactivate/remove viruses and prions was evaluated. OBJECTIVES: The objective of this study was to evaluate the virus and prion safety of the new IVIG 10% liquid...
April 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
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