11.5

Question 1

What is the brain pathology in transmissible spongiform encephalopathies

Answer 1

Spongiosis: spongey appearance with neuronal loss

Question 2

Three forms of TSEs

Answer 2

Genetic
Infectious
Sporadic

Question 3

What are some TSEs (4)

Answer 3

Creutzveldt-Jakob Disease
Fatal familial insomnia
Gerstmann-traussler-Scheinker Disease
Kuru

Question 4

How did bovine spongiform encephalopathy become an issue

Answer 4

Transmission from sheep to cows by infectious agent in meat

Question 5

What was the infectious material in TSEs

Answer 5

Protein aggregate with B-sheet amyloid nature

Question 6

How can scrapie infectivity be reduced

Answer 6

Procedures that hydrolyse or modify proteins

Question 7

What is the prion protein in normal animals

Answer 7

Membrane anchored glycoprotein

Question 8

What is the only difference identifiable between normal PrP and PrPSc

Answer 8

Normal soluble prion protein is readily digestable by Proteinase K but infectious, aggregated PrPSc is resistant

Question 9

Conversion of PrP to PrPSc

Answer 9

1) Spontaneous conversion through contact

2) Inoculation with infectious . material

Question 10

What are some characteristics of aggregated form (2)

Answer 10

Cross-B core

Short peptide from N-terminal critical

Question 11

How are phenotypes of prion diseases passed from infected animals

Answer 11

Current hypothesis is there are distinct forms of prion aggregate which recruit normal cellular form into growing aggregate

Question 12

What makes some individuals more suscepitble to vCJD

Answer 12

Individuals who have SNP, MM or VV at codon 129 in PrP

Question 13

What are some functional amyloid fibrils (3)Wher

Answer 13

1) Yeast prions
2) Filamentous fungi
3) Mammalion amyloid - Pmel

Question 14

What was the change in phenotype observed in different prion strains

Answer 14

Prion strains form white colonies

Prion deficient appear red

Question 15

How have prions been ‘cured’ in yeast cultures

Answer 15

Where aggregated prion material is converted back to soluble form by growing cell on plates containing protein denaturants such as guanidine hydrochloride

Question 16

What does prion inheritance in yeast depend on

Answer 16

Whether aggregated material is passed when yeast divide

Question 17

What is Sup35 in yeast

Answer 17

Component of translation termination machinery

Question 18

What does the aggregated state of Sup35 result in

Answer 18

Reduced fidelity with which ribosomes terminate translation at stop codons
Prion propagates and can capture newly made Sup35 to perpetuate loss of function

Question 19

What is an occasional benefit of non-functional Sup35

Answer 19

Diverse phenotypic effects, allows yeast to try phenotypes

Question 20

Prion formation and loss was affected by (2)

Answer 20

Stress (which upregulates_

Action of chaperone

Question 21

What are some functions of amyloid in filamentous fungi (4)

Answer 21

1) Reducing surface tension at the air:water interface
2) Coating spores for aerial dispersal
3) Mediating attachment to surfaces
4) Interaction with host

Question 22

What is the function of the RodA layer re: immune system

Answer 22

Masks recognition of cell wall from host immune system

Question 23

Where are functional amyloids found in mammalian cells

Answer 23

Organelles within melanocytes

Question 24

What is the role of Pmel17 fibrils in melanocytes (2)

Answer 24

1) Template melanin synthesis along fibrils

2) Prevent toxic melanin precursors leaking out and doing damage