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.
Responsibilities include:
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.
Qualifications:
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:
stefanie.czub@inspection.gc.ca
Contact Info:
Last Updated: 12/10/2009 1:35:18 PM
Thursday, August 12, 2010
Seven main threats for the future linked to prions
First threat
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.
Second threat
snip...
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
flounder9@verizon.net
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