Prionet Canada coming to a close in 2012, a sad day for TSE Prion science in North America
This issue of PrioNews marks the final newsletter for PrioNet as a Network of Centres of Excellence. It is with great sadness that we witness our Network come to a close in 2012, but we are confident the great research we have helped support over the last seven years will flourish for many years to come through new opportunities.
PrioNet Canada was a $35 million initiative launched in 2005 by the Government of Canada’s Networks of Centres of Excellence (NCE) program established to coordinate Canada’s research and policy response to the impact of prion diseases in Canada. Since that time, PrioNet has conducted fundamental, applied, and social research to help solve the food, health safety, and socioeconomic problems associated with prion diseases such as BSE, CWD, and CJD. We recently expanded our mission to include groundbreaking research implicating prion disease mechanisms in other neurological disorders such as Alzheimer’s and Parkinson’s diseases, and amyotrophic lateral sclerosis (ALS), largely in part driven by PrioNet investigators.
PrioNet exemplified a functional, cohesive, and responsive network supporting research projects and partnerships to deliver maximum impact. PrioNet developed the foundation, partners, capacity and expertise to convert major health and economic burdens from prion and prion related disease into public policy and commercializable solutions for the benefit of Canada.
PrioNet’s achievements put Canada at the global forefront of prion research, made possible by its community of scientists, students, and other young professionals networking with stakeholders and partners. PrioNet’s approach of leveraging its multidisciplinary research program for maximum results, liaising synergistic activities with international partners, training highly skilled people for Canada’s workforce, and translating knowledge into practical solutions to derive socioeconomic benefits to Canadians was a uniquely Canadian solution that produced great results.
Like parts of a complex puzzle, PrioNet discoveries, assembled together, have helped to answer questions surrounding prion and prion-like diseases.
Like parts of a complex puzzle, PrioNet discoveries, assembled together, have helped to answer some of the major risk, socioeconomic, and biological questions surrounding prion and prion-like diseases. In the pages of this final newsletter, you will read a few selected examples of our success in our “Research Reflections” story.
On behalf of all Canadians who have benefited from these discoveries, PrioNet wishes to thank each and every member of the network community for their contributions over the last seven years. We know Canada will continue to benefit from the knowledge our network has created well into the future, and we look forward to seeing what remains to be discovered in this crucial field of research.
Dr. Neil Cashman, Scientific Director
Dr. Michelle Wong, Executive Director
THIS is a sad day for Transmissible Spongiform Encephalopathy TSE PRION research, a sad day indeed. Actually, it’s worse than that, it’s a loss for TSE Prion Scientific research.
To the youngsters getting into the field of TSE Prion research, GO FOR IT. we need you.
PRIONET Canada folks put out some fantastic work, Thank You Prionet Canada et al, we WILL miss you, North America will miss you.
Sadly, the work is not finished yet. ... TSS
Employment Listings position: Post Doctoral Fellow | Atypical BSE in Cattle
Closing date: December 24, 2009
Anticipated start date: January/February 2010
Employer: Canadian and OIE Reference Laboratories for BSE CFIA Lethbridge Laboratory, Lethbridge/Alberta
The Canadian and OIE reference laboratories for BSE are extensively involved in prion diseases diagnosis and research. With a recent increase in research activities and funding, the laboratory is looking to fill two post doctoral fellow positions. Both positions will be located at the Canadian Food Inspection Agency (CFIA) Lethbridge Laboratory which offers biosaftey level 3 (BSL3) and BSL2 laboratory space and is well equipped for molecular and morphologic prion research. The facility also has a BSL3 large animal housing wing and a state of the art post mortem room certified for prion work. Successful candidates will have the opportunity to visit other laboratories to cooperate in various aspects of the projects and to be trained in new techniques and acquire new skills. With a recent increase in prion disease expertise and research in Alberta and Canada, these positions will offer significant exposure to cutting edge prion science via videoconferencing, meetings, workshops and conferences. These interactions will also provide a valuable opportunity to present research findings and discuss potential future work opportunities and collaborations with other Canadian and international research groups.
Atypical BSE in Cattle
BSE has been linked to the human disease variant Creutzfeldt Jakob Disease (vCJD). The known exposure pathways for humans contracting vCJD are through the consumption of beef and beef products contaminated by the BSE agent and through blood transfusions. However, recent scientific evidence suggests that the BSE agent may play a role in the development of other forms of human prion diseases as well. These studies suggest that classical type of BSE may cause type 2 sporadic CJD and that H-type atypical BSE is connected with a familial form of CJD.
To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.
This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.
Driving research at the National and OIE BSE reference lab to ensure project milestones are met successfully. Contributing to the preparation of project progress reports. Directing technical staff working on the project. Communicating and discussing results, progress and future direction with project principle investigator(s). Communicating with collaborative project partners.
Successful completion of a PhD degree in an area focusing on or related to prion diseases. Extensive experience with molecular and/or morphologic techniques used in studying prion diseases and/or other protein misfolding disorders. Ability to think independently and contribute new ideas. Excellent written and oral communication skills. Ability to multitask, prioritize, and meet challenges in a timely manner. Proficiency with Microsoft Office, especially Word, PowerPoint and Excel.
How to apply:
Please send your application and/or inquiry to: Dr. Stefanie Czub, DVM, Ph.D. Head, National and OIE BSE Reference Laboratory Canadian Food Inspection Agency Lethbridge Laboratory P.O. Box 640, Township Road 9-1 Lethbridge, AB, T1J 3Z4 Canada
phone: +1-403-382-5500 +1-403-382-5500 ext. 5549 email: email@example.com
Last Updated: 12/10/2009 1:35:18 PM
Thursday, August 12, 2010
Seven main threats for the future linked to prions
The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.
***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.
MAD COW USDA ATYPICAL L-TYPE BASE BSE, the rest of the story...
***Oral Transmission of L-type Bovine Spongiform Encephalopathy in Primate Model
***Infectivity in skeletal muscle of BASE-infected cattle
***feedstuffs- It also suggests a similar cause or source for atypical BSE in these countries.
***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans.
full text ;
atypical L-type BASE BSE
Tuesday, May 1, 2012
BSE MAD COW LETTERS TO USDA (Tom Vilsack, Secretary of Agriculture) and FDA (Magaret Hamburg, Commissioner of FDA) May 1, 2012
Wednesday, May 2, 2012
ARS FLIP FLOPS ON SRM REMOVAL FOR ATYPICAL L-TYPE BASE BSE RISK HUMAN AND ANIMAL HEALTH
Friday, May 4, 2012
May 2, 2012: Update from APHIS Regarding a Detection of Bovine Spongiform Encephalopathy (BSE) in the United States
Sunday, March 11, 2012
APHIS Proposes New Bovine Spongiform Encephalopathy Import Regulations in Line with International Animal Health Standards Proposal Aims to Ensure Health of the U.S. Beef Herd, Assist in Negotiations
Wednesday, April 4, 2012
Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products APHIS-2008-0010-0008 RIN:0579-AC68
Sunday, May 6, 2012
Bovine Spongiform Encephalopathy Mad Cow Disease, BSE May 2, 2012 IOWA State University OIE
SPONTANEOUS ??? NOT...
How the California cow got the disease remains unknown. Government officials expressed confidence that contaminated food was not the source, saying the animal had atypical L-type BSE, a rare variant not generally associated with an animal consuming infected feed.
However, a BSE expert said that consumption of infected material is the only known way that cattle get the disease under natural conditons.
“In view of what we know about BSE after almost 20 years experience, contaminated feed has been the source of the epidemic,” said Paul Brown, a scientist retired from the National Institute of Neurological Diseases and Stroke.
BSE is not caused by a microbe. It is caused by the misfolding of the so-called “prion protein” that is a normal constituent of brain and other tissues. If a diseased version of the protein enters the brain somehow, it can slowly cause all the normal versions to become misfolded.
It is possible the disease could arise spontaneously, though such an event has never been recorded, Brown said.
Identification of a second bovine amyloidotic spongiform encephalopathy: Molecular similarities with sporadic Creutzfeldt–Jakob disease
Cristina Casalone*†, Gianluigi Zanusso†‡, Pierluigi Acutis*, Sergio Ferrari‡, Lorenzo Capucci§, Fabrizio Tagliavini¶, Salvatore Monaco‡ , and Maria Caramelli* *Centro di Referenza Nazionale per le Encefalopatie Animali, Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d’Aosta, Via Bologna, 148, 10195 Turin, Italy; ‡Department of Neurological and Visual Science, Section of Clinical Neurology, Policlinico G.B. Rossi, Piazzale L.A. Scuro, 10, 37134 Verona, Italy; §Istituto Zooprofilattico Sperimentale della Lombardia ed Emilia Romagna, Via Bianchi, 9, 25124 Brescia, Italy; and ¶Istituto Nazionale Neurologico ‘‘Carlo Besta,’’ Via Celoria 11, 20133 Milan, Italy
Edited by Stanley B. Prusiner, University of California, San Francisco, CA, and approved December 23, 2003 (received for review September 9, 2003)
Transmissible spongiform encephalopathies (TSEs), or prion diseases, are mammalian neurodegenerative disorders characterized by a posttranslational conversion and brain accumulation of an insoluble, protease-resistant isoform (PrPSc) of the host-encoded cellular prion protein (PrPC). Human and animal TSE agents exist as different phenotypes that can be biochemically differentiated on the basis of the molecular mass of the protease-resistant PrPSc fragments and the degree of glycosylation. Epidemiological, molecular, and transmission studies strongly suggest that the single strain of agent responsible for bovine spongiform encephalopathy (BSE) has infected humans, causing variant Creutzfeldt–Jakob disease. The unprecedented biological properties of the BSE agent, which circumvents the so-called ‘‘species barrier’’ between cattle and humans and adapts to different mammalian species, has raised considerable concern for human health. To date, it is unknown whether more than one strain might be responsible for cattle TSE or whether the BSE agent undergoes phenotypic variation after natural transmission. Here we provide evidence of a second cattle TSE. The disorder was pathologically characterized by the presence of PrP-immunopositive amyloid plaques, as opposed to the lack of amyloid deposition in typical BSE cases, and by a different pattern of regional distribution and topology of brain PrPSc accumulation. In addition, Western blot analysis showed a PrPSc type with predominance of the low molecular mass glycoform and a protease- resistant fragment of lower molecular mass than BSE-PrPSc. Strikingly, the molecular signature of this previously undescribed bovine PrPSc was similar to that encountered in a distinct subtype of sporadic Creutzfeldt–Jakob disease.
Phenotypic Similarities Between BASE and sCJD. The transmissibility of CJD brains was initially demonstrated in primates (27), and classification of atypical cases as CJD was based on this property (28). To date, no systematic studies of strain typing in sCJD have been provided, and classification of different subtypes is based on clinical, neuropathological, and molecular features (the polymorphic PRNP codon 129 and the PrPSc glycotype) (8, 9, 15, 19). The importance of molecular PrPSc characterization in assessing the identity of TSE strains is underscored by several studies, showing that the stability of given disease-specific PrPSc types is maintained upon experimental propagation of sCJD, familial CJD, and vCJD isolates in transgenic PrP-humanized mice (8, 29). Similarly, biochemical properties of BSE- and vCJDassociated PrPSc molecules remain stable after passage to mice expressing bovine PrP (30). Recently, however, it has been reported that PrP-humanized mice inoculated with BSE tissues may also propagate a distinctive PrPSc type, with a ‘‘monoglycosylated- dominant’’ pattern and electrophoretic mobility of the unglycosylated fragment slower than that of vCJD and BSE (31). Strikingly, this PrPSc type shares its molecular properties with the a PrPSc molecule found in classical sCJD. This observation is at variance with the PrPSc type found in M V2 sCJD cases and in cattle BASE, showing a monoglycosylated-dominant pattern but faster electrophoretic mobility of the protease-resistant fragment as compared with BSE. In addition to molecular properties of PrPSc, BASE and M V2 sCJD share a distinctive pattern of intracerebral PrP deposition, which occurs as plaque-like and amyloid-kuru plaques. Differences were, however, observed in the regional distribution of PrPSc. While inM V2 sCJD cases the largest amounts of PrPSc were detected in the cerebellum, brainstem, and striatum, in cattle BASE these areas were less involved and the highest levels of PrPSc were recovered from the thalamus and olfactory regions.
In conclusion, decoding the biochemical PrPSc signature of individual human and animal TSE strains may allow the identification of potential risk factors for human disorders with unknown etiology, such as sCJD. However, although BASE and sCJD share several characteristics, caution is dictated in assessing a link between conditions affecting two different mammalian species, based on convergent biochemical properties of diseaseassociated PrPSc types. Strains of TSE agents may be better characterized upon passage to transgenic mice. In the interim until this is accomplished, our present findings suggest a strict epidemiological surveillance of cattle TSE and sCJD based on molecular criteria.
with sad regards,
I am Sincerely,
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518 firstname.lastname@example.org