Prions...?

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Profile Eric Ogletree

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Message 28266 - Posted: 23 Sep 2006, 15:12:32 UTC

I've been trying to do an essay for my Biology class about Prions (in particular, weither Prions are alive or not). In my search, I've found obscure references to Alzheimers and Parkensins disease.

So now I've got this big question in my head: Is Alzheimers and Parkensins considered as "Prion disease"? Now that I think about it, are most/all of the diseases that are being looked at here considered prion diseases? It's not necessary for my essay, but is definately something that peaked my curiosity.

I'll have to admit, I feel like a "newby" taking a swim in the deep end of things, but I guess every University student goes through that (or maybe I'm just a Bio-Geek in denial, hehe).
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Message 28332 - Posted: 24 Sep 2006, 10:12:47 UTC - in response to Message 28266.  

I've been trying to do an essay for my Biology class about Prions (in particular, weither Prions are alive or not). ...


as I understand it, as a physicist not a bio, they are even less "alive" than viruses.

While bacteria and all more advanced life forms reproduce by themselves (singly or in pairs), viruses need to co-opt a higher life form to reproduce them, and prions depend on the normal-state protein being made for them by a higher life form.

Some might say that reproduction-by-proxy does disqualify them from being considered alive.



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Message 28351 - Posted: 24 Sep 2006, 15:33:24 UTC - in response to Message 28266.  
Last modified: 24 Sep 2006, 15:34:43 UTC

So now I've got this big question in my head: Is Alzheimers and Parkensins considered as "Prion disease"? Now that I think about it, are most/all of the diseases that are being looked at here considered prion diseases?


No, Alzheimer's and Parkinson's are not considered prion diseases because they do not result from the same process as the Prion-related diseases. The reason that Alzheimer's (see Wikipedia ) and Parkinson's (see Wikipedia ) are often mentioned in the same discussion as Prion-related disease is that they are all diseases of the brain that result from a 'mis-folding' of proteins (not the same one, though).

Prion diseases are considered unusual since the prevailing view is that the mis-folding happens on it's own - "spontaneously" - while the other two mis-fold because there is something else in the brain that causes the misfolding.


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Message 28543 - Posted: 26 Sep 2006, 13:07:12 UTC - in response to Message 28351.  

So now I've got this big question in my head: Is Alzheimers and Parkensins considered as "Prion disease"? Now that I think about it, are most/all of the diseases that are being looked at here considered prion diseases?


No, Alzheimer's and Parkinson's are not considered prion diseases because they do not result from the same process as the Prion-related diseases. The reason that Alzheimer's (see Wikipedia ) and Parkinson's (see Wikipedia ) are often mentioned in the same discussion as Prion-related disease is that they are all diseases of the brain that result from a 'mis-folding' of proteins (not the same one, though).

Prion diseases are considered unusual since the prevailing view is that the mis-folding happens on it's own - "spontaneously" - while the other two mis-fold because there is something else in the brain that causes the misfolding.


Look up the latest news on the association of Diabetes as precursor to Alzheimer.


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Message 29118 - Posted: 10 Oct 2006, 15:40:12 UTC - in response to Message 28351.  

So now I've got this big question in my head: Is Alzheimers and Parkensins considered as "Prion disease"? Now that I think about it, are most/all of the diseases that are being looked at here considered prion diseases?


No, Alzheimer's and Parkinson's are not considered prion diseases because they do not result from the same process as the Prion-related diseases. The reason that Alzheimer's (see Wikipedia ) and Parkinson's (see Wikipedia ) are often mentioned in the same discussion as Prion-related disease is that they are all diseases of the brain that result from a 'mis-folding' of proteins (not the same one, though).

Prion diseases are considered unusual since the prevailing view is that the mis-folding happens on it's own - "spontaneously" - while the other two mis-fold because there is something else in the brain that causes the misfolding.


That makes me wonder something else then. The number-crunching that we're doing here, should there be some concern that one of these proteins, if reproduced in some of the shapes we're looking at, could cause some major problems (ie. a new disease)? I'm still going to participate so we can at least learn more about proteins in general, but can't help but wonder some of the implications involved here...

Sorry for sounding like a downer here, just curious about these pesky little critters here. :)
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Message 29121 - Posted: 10 Oct 2006, 16:23:24 UTC - in response to Message 29118.  
Last modified: 10 Oct 2006, 16:34:22 UTC


That makes me wonder something else then. The number-crunching that we're doing here, should there be some concern that one of these proteins, if reproduced in some of the shapes we're looking at, could cause some major problems (ie. a new disease)?


Hey, that's an interesting point! Very interesting.. It's a small possibility I suppose.

These diseases are associated w/ the insolubility of proteins in vivo, resulting in the plaques that fall out of solution and form on the various tissues. I would bet that if 'rogue molecule' would be designed that it would be really difficult w/ which to work in the lab and folks would give up on it long before it was put into any testing pipeline...

Not only that, I'd like to think that something like this would show up in the extensive testing that would be done to satisfy the FDA before any human saw anything developed here - and there is a LOT of testing that is required.

Hmm... an interesting idea though... I smell a M. Crichton book in the making... -KEL

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Message 29210 - Posted: 12 Oct 2006, 0:53:38 UTC - in response to Message 29121.  


That makes me wonder something else then. The number-crunching that we're doing here, should there be some concern that one of these proteins, if reproduced in some of the shapes we're looking at, could cause some major problems (ie. a new disease)?


Hey, that's an interesting point! Very interesting.. It's a small possibility I suppose.

These diseases are associated w/ the insolubility of proteins in vivo, resulting in the plaques that fall out of solution and form on the various tissues. I would bet that if 'rogue molecule' would be designed that it would be really difficult w/ which to work in the lab and folks would give up on it long before it was put into any testing pipeline...

Not only that, I'd like to think that something like this would show up in the extensive testing that would be done to satisfy the FDA before any human saw anything developed here - and there is a LOT of testing that is required.

Hmm... an interesting idea though... I smell a M. Crichton book in the making... -KEL


Like any new medicine / application it will have to go through clinical trials to determine bad side-effects....i'm sure in the case of the protein engineering, the side-effects will be considered....the cure worse than the decease is not unthinkable....the last few recent cases of medicine retraction from market come to mind.

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Message 29400 - Posted: 15 Oct 2006, 18:01:25 UTC - in response to Message 29210.  


Like any new medicine / application it will have to go through clinical trials to determine bad side-effects....i'm sure in the case of the protein engineering, the side-effects will be considered....the cure worse than the decease is not unthinkable....the last few recent cases of medicine retraction from market come to mind.


Hmmm... Seems kind of scairy... Going to keep working on Rosetta for the sake of learning more about proteins, of course, and hopefully any side affects won't be that bad. But if I grow a third arm, or an extra set of eyes, then I'd be the first one to yell out "COOL!" :P

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Message 30850 - Posted: 9 Nov 2006, 14:56:21 UTC

I've got another question regarding biology in general.

If a prion can be considered as "less living than Viruses", how can life be labelled as living or non-living? I'm not sure if I'm using the right words here or not, but how can something be considered as living or not? It almost sounds like there is a fine line between living and not living. What can be considered to be that fine line?

Sekerob, just curious, but when you said that certain medications were retracted from the market, per chance, were you refering to medications like Vioxx or Celebrex (SP??) for Ostioarthritis? I've followed up on those as much as I could, and all I got out of it is that they were known to have caused strokes (not sure if these can apply to what we're talking about here, but what the heck).

Ah, while I was typing here, a few more questions popped into my head regarding Prions... I've been told that, in the case of infected meats, that normal cooking methods would not get rid of prions. Aside from doing research on them, what are the current known methods of getting rid of prions? I've seem to be hitting a brick wall with my teacher regarding them, and just want to know what to say about them and how they react to the environment (ie. heat, acidicity, radiation, etc).

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Message 30892 - Posted: 10 Nov 2006, 9:17:53 UTC - in response to Message 30850.  
Last modified: 10 Nov 2006, 9:18:53 UTC

If a prion can be considered as "less living than Viruses", how can life be labelled as living or non-living? I'm not sure if I'm using the right words here or not, but how can something be considered as living or not? It almost sounds like there is a fine line between living and not living. What can be considered to be that fine line?

My view on this (as a physicist not a bio) is that there is no simple duality between life and non-life.

Bacteria, amoeba and upwards are clearly life

Rocks, cars, etc are clearly non-life

And then there is a grey zone between that exists because we created the duality with our minds oud of what is, in the real world, a continuous spectrum. Five examples of the grey zone are

1. Intermediate bio entities like prions and bio viruses

2. Higher animals while dying; including people. Our brain dies before our heart, otherwise transplants would amount to murder. Our nails go on growing for a long time after there is no hope for revival as a human.

3. First life. For anyone but Direct Creationists, we believe life arose out of non-living material through the process of evolution. It seems likely that the transition through the grey zone between non-life to life was gradual, not instant. Nobody thinks that a bacteria or an amoeba just all fell together in one go.

(Aside NB Even for Fundamenalist Christian Creationists human life arose that way as the Genesis account tells us we are fashioned directly by God from the mud of the earth, and even there we have some kind of non-life to life transition in the mud itself. If we are willing to step into that world view it is a fair question to ask if Adam came suddenly alive at one instant in that process, or did he become gradually alive as God did the modelling)

4. Food. We eat something that is clearly dead (eg cooked meat containing no prions), it is dismantled inside our intestines and re-assembled as us. When does it become alive again?

5. Some components of our bodies are clearly alive in their own right (eg most cells), others would be better described as not alive but part of a living process (eg a single glucose molecule). At what point in that spectrum do you put the boundary? Is a red blood cell for example alive (as it has active biochem going on in its protoplasm) or non-life (as it has no nuclear DNA).

6. Computer viruses. Have some characteristics of life, eg autonomous replication

I would say that in each of the cases 1 - 5 the question "is it alive" is not an enlightening one at all - at most we are looking at where we draw our artificial line through what is really a continuous gradation.

In case 6, the question "is it alive" is asking where we should draw the line - in this case it is enlightening precisely because it points out an unexpected direction where life could appear, or not, according to our definitions.

The idea that there is no hard and fast natural line between live and non-live is hard to take at first. Among other things it challenges ethical systems (which respond by tightening up definitions, eg in the UK brain death counts as dead for the purpose of making transplants legal even tho the other organs have to be alive to make the procedure worth doing).

R~~
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Message 30895 - Posted: 10 Nov 2006, 9:25:10 UTC - in response to Message 30850.  


... I've been told that, in the case of infected meats, that normal cooking methods would not get rid of prions. Aside from doing research on them, what are the current known methods of getting rid of prions? I've seem to be hitting a brick wall with my teacher regarding them, and just want to know what to say about them and how they react to the environment (ie. heat, acidicity, radiation, etc).


Prions are proteins. All the normal ways of totally destroying a protein will make them safe. The problem with prions in food is that whatever we do to make the prion non-infective also removes the food value of the other proteins as protein. Grill your steak till it is charcoal all the way from top to bottom and it is safe - but it is no longer edible.

Grilling a steak till it is black and charred on the outside only will not protect against any prions that are thought to be inside the steak - if infected meat still looks and tastes like meat then it is still infected.

Charring the steak well *does* protect you if your only or major concern is about prions from other tissues that might have got onto the surface of the steak during preparation (at home or in the abbatoir).

In the UK, anti-BSE good practice was based on this assumption, trying to keep to a minimum the possibility of lean meat coming into contact with connective tissue and bones. Therefore the traditional Texan "grill it till its black on the outside" approach might have been a rational extension of this set of practices.

Whether a steak cooked that way is worth eating at all can also be debated as a culinary question, of course... ;-)

A T-bone was particularly frowned on at that time, as the bones and connective tissue round them are cooked along with the meat and cannot be charred. For a while at the peak of the crisis it was illegal here to sell a T-bone steak.

Certainly too, coming from this perspective, there would be less risk to a steak than to a burger (where any accidental contaminant can get thoroughly integrated in the processes of mincing grinding and mixing) - but this is about reducing risk of prions being present, not about deactivating prions to make them safe.

R~~
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Message 31020 - Posted: 12 Nov 2006, 23:21:03 UTC - in response to Message 30892.  

If a prion can be considered as "less living than Viruses", how can life be labelled as living or non-living? I'm not sure if I'm using the right words here or not, but how can something be considered as living or not? It almost sounds like there is a fine line between living and not living. What can be considered to be that fine line?

My view on this (as a physicist not a bio) is that there is no simple duality between life and non-life.

Bacteria, amoeba and upwards are clearly life

Rocks, cars, etc are clearly non-life

And then there is a grey zone between that exists because we created the duality with our minds oud of what is, in the real world, a continuous spectrum. Five examples of the grey zone are...

R~~


Getting into philosophical questions here, but it seems that in order for something to be "alive" it needs to be mostly self sufficient. You allude to this in your distinction between "living" and "part of a living process."

Humans are alive because even though they rely on food and water to cotinue to function as humans, they have the ability to go out and find what they need.

Cells are slightly less alive because their functions are mostly self contained but they still rely on their environment to provide required materials. They are unable to find a better environment if they need to.

A dying person is ceasing to be alive because it can no longer continue to maintain itself. Tissues within the body continue to be alive for some time afterward because they are able to continue performing their functions without an outside force causing them to do so.

Food is not alive. It must be dismantled and reconstructed before once again becoming part of life.

glucose molecules are not alive because they rely directly on the environment for conditions that cause them to do things.

Computer viruses are tricky. If they require a person to open a file, they are probably not very alive. If they need no human input and are able to seek out new hosts without being directed to do so, they are probably pretty much alive.

Again, there is no solid distinction. It requires an observer to determine how much something is reliant on outside conditions and inputs. Just an idea about how to look at the issue.

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Message 31587 - Posted: 22 Nov 2006, 21:54:16 UTC - in response to Message 30895.  


Prions are proteins. All the normal ways of totally destroying a protein will make them safe. The problem with prions in food is that whatever we do to make the prion non-infective also removes the food value of the other proteins as protein. Grill your steak till it is charcoal all the way from top to bottom and it is safe - but it is no longer edible.

Grilling a steak till it is black and charred on the outside only will not protect against any prions that are thought to be inside the steak - if infected meat still looks and tastes like meat then it is still infected.

Charring the steak well *does* protect you if your only or major concern is about prions from other tissues that might have got onto the surface of the steak during preparation (at home or in the abbatoir).

In the UK, anti-BSE good practice was based on this assumption, trying to keep to a minimum the possibility of lean meat coming into contact with connective tissue and bones. Therefore the traditional Texan "grill it till its black on the outside" approach might have been a rational extension of this set of practices.

Whether a steak cooked that way is worth eating at all can also be debated as a culinary question, of course... ;-)

A T-bone was particularly frowned on at that time, as the bones and connective tissue round them are cooked along with the meat and cannot be charred. For a while at the peak of the crisis it was illegal here to sell a T-bone steak.

Certainly too, coming from this perspective, there would be less risk to a steak than to a burger (where any accidental contaminant can get thoroughly integrated in the processes of mincing grinding and mixing) - but this is about reducing risk of prions being present, not about deactivating prions to make them safe.

R~~


So, to sum up here, prions can "survive" in super-harsh conditions. Brings up another question regarding BSE: How extensive is the testing? I realise that this could depend greatly on location (ie. Canada, USA, Ireland, etc.), and the risks of catching Creutzfield-Jacobs (sp???) Disease as a result would be remote (in theory, at least). But with the amount of beef-related products I eat, I'd have to wonder about that as well.

Also, if a substance is capable of self-replicating, couldn't that be considered as a function of life, or is it more complicated that that (ie. needing to copy DNA and/or RNA)?

Wow. Starting to think paranoia here (Get 'em off! GET 'EM OFF!!! hehe). Ah well, no such thing as a stupid question (except ones that are never asked).

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Message 34830 - Posted: 15 Jan 2007, 14:33:48 UTC

Another question here regarding Prions. Actually, in proteins in general:

My "simplistic" understanding is is that protein is supposed to be good for you. Why are things that are supposed to be "good" for you can be so bad? I'm not sure if I'm asking the right questions here, but it's hard to imagine so small to be so deadly.

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Message 34839 - Posted: 15 Jan 2007, 15:56:19 UTC

The protein that's good for you is used to build muscles. But proteins exist throughout your cell structure, and the structures of disease. For example a virus cell will have specific proteins around it's cell walls. This is why Rosetta is studying "docking" work sometimes. They are working to model the interaction between these proteins the surround a virus cell (such as HIV) and see how we might model another protein that would chemically lock on to it (and NOT lock on to other cells).
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