Deadly animal prion disease appears in Europe
nature.com
nature.com
> A protein as a standalone infectious agent stands in contrast to all other known infectious agents such as viruses, bacteria, fungi, and parasites, all of which contain nucleic acids (DNA, RNA, or both)
In my layman's understanding, they're like this bizarre edge case in the way proteins interact. Of all the myriad way a protien can fold, it happens to find one that induces the same malformation when it interacts with another protein. To me, it almost seems like as much of a mathematical/geometrical problem as a biological one. In any case, very interesting from the perspective of emergent behavior in complex systems.
"I imagine it started with all of the adapters which were thrown around in every meeting room. Everyone with a Macbook of some flavor needed a DVI to VGA adaptor in order to use the projectors, so they were plentiful. Somehow, someone probably damaged one of them and smooshed a couple of pins into places where they should not have gone.
"Then, someone else forced this into their Mac. Perhaps two pins tried to go into just the one socket. At any rate, it would now break the socket and get it all out of whack. That socket, used with another adapter in another room, would then break that adapter. This new broken adapter would then go on to break even more Macbook DVI connectors.
Thus, we had a hardware virus." [1]
The correct fix would be pins with a better length/width ratio.
What with the sockets and everything.
Ice-nine has been used as a model to explain the infective mechanism of mis-folded proteins called prions which are thought to catalyze the mis-folding of the corresponding normal protein leading to a variety of spongiform encephalopathies such as kuru, scrapie and Creutzfeldt–Jakob disease.
"One speculation that has resulted from the idea is that a strangelet coming into contact with a lump of ordinary matter could convert the ordinary matter to strange matter."
https://en.wikipedia.org/wiki/Strangelet#Dangers
Also mere ideas could also been seen as some mind-folding catalysts, language being the infective mechanism.
Variants of this trope often appear in literature (science-fiction or not).
For example in "Viruses of the Mind" : "Richard Dawkins analyzes the propagation of religious ideas and behaviors as a memetic virus"
It doesn't really "just happen", amyloids consist of peptides folded into beta-sheets and aggregates of these seem to be the most thermodynamically stable structures it is possible for polypeptide chains (regardless of sequence) to form:
"From a wide range of in vitro experiments on peptides and proteins we now know that the formation of amyloid structures is not a rare phenomenon associated with a small number of diseases but rather that it reflects a well-defined structural form of the protein that is an alternative to the native state — a form that may in principle be adopted by many, if not all, polypeptide sequences
[...]
These observations, therefore, have led to the remarkable conclusion that, at the concentrations present in living systems, the native states may not always represent the absolute free energy minima of the corresponding polypeptide chains — the native form of a protein could in some cases simply be a metastable monomeric (or functionally oligomeric) state that is separated from its polymeric amyloid form by high kinetic barriers" http://www.ncbi.nlm.nih.gov/pubmed/24854788
Edit:
I realized some people might not be aware of the connection to prions. Here it is from the same wikipedia page as cited by the parent:
"All known prions induce the formation of an amyloid fold, in which the protein polymerises into an aggregate consisting of tightly packed beta sheets." https://en.wikipedia.org/wiki/Prion
"Many of the characteristics of proteins that enable the avoidance of aggregation, and amyloid formation in particular, are encoded by their amino acid sequences116. The elucidation of this code has enabled the identification of factors that determine the intrinsic aggregation propensity of these molecules117, 118, 119. Hence, it has been realized that globular proteins fold into structures that sequester aggregation-prone regions in their interior; in addition, typical features of the folding process, such as very high cooperativity, generate considerable kinetic barriers to the conversion of folded proteins into aggregation-prone species50, 120. Furthermore, specific patterns of residues, such as alternating hydrophobic–hydrophilic stretches50, 121, that tend to favour the amyloid state are commonly selected against during evolution119, 121, 122 or are otherwise neutralized by the insertion of highly aggregation-resistant residues, which are known as 'gatekeepers' (Refs 50,123).
Other protective mechanisms against amyloid formation are associated with properties of the cellular environment, including the location of proteins within specific compartments124, 125, and the presence of a multitude of molecular chaperones and degradation processes, such as the ubiquitin–proteasome126, 127, 128 and the autophagy129, 130, 131 systems, which function to prevent the formation and accumulation of misfolded and aggregated polypeptide chains11, 132. Indeed, the major genetic risk factor for late-onset Alzheimer's disease is the presence of an apolipoprotein E variant that reduces the ability of cells to degrade the amyloid-β peptide133."
1) You can tell whether a protien has this viral property by looking at its amino acid sequence
2) Looking at this seqence has shown several reasons why proteins don't often go viral
- The relevant region ends up on the interior of the structure
- The relevant structure is not mechanically likely
- Evolution has come up with tons of biological tricks to prevent it
> The elucidation of this code has enabled the identification of factors that determine the intrinsic aggregation propensity of these molecules
I'd have a hard time coming up with a sentence that feels more inside-out than that.
Supposedly (I have no idea how well it works), but here is an example of such a tool: http://aias.biol.uoa.gr/AMYLPRED/
>"2) Looking at this seqence has shown several reasons why proteins don't often go viral"
Yes, but to clarify a bit: It looks like all proteins have this ability, but not all are just as likely to get into that state for the reasons mentioned. IE, it should be possible to find some way to make amyloids/prions out of any protein in the lab. It just requires figuring out the necessary conditions for that protein.
>"The elucidation of this code has enabled the identification of factors that determine the intrinsic aggregation propensity of these molecules"
Translation: Being able to get the amino acid sequence of proteins and predict what type of structures such a sequence leads to has allowed researchers to also predict which are likely to form aggregates.
DNA gets transcripted into RNA before it codes proteins, so an original RNA moelcule, being both a catalyst and a data store, eventually developed variations that in turn also produced pure catalysts (proteins) and a pure data store (DNA). But it's still the lynchpin of the reproduction process.
Perhaps a tenuous analogy can be made to information storage in transistors versus magnetic media. Transistors can serve as storage medium as well as logic gates. Yet power fluctuations can corrupt their function. Magnetic storage however can be read many times and is more durable with respect to environmental insults. Of course the most durable form of storage might be laser etching defects in a diamond disc but at the cost of a slow energy intensive process.
I would rather say life is the result of an optimization process.
1) The normal form (PrPc) is mostly helical, while the diseased form (PrPsc) is mostly beta-sheet. 2) PrPsc catalyses the switch from helix to sheet.
I find the first to be more surprising. After all, chaperones (https://en.wikipedia.org/wiki/Chaperone_(protein)) exist to catalyse folding of proteins - although that is from partly folded to fully folded.
"Incineration is possible, but it isn't as easy as burning the carcass in a fire. Temperatures of more than 1,100 degrees Fahrenheit — sometimes up to 1,800 degrees — are required to effectively neutralize prions. Unlike most bacteria, regular cooking won't help at all. "Disposal issues are tough," says Barbara Powers, director of Colorado State University's Veterinary Diagnostic Laboratory."
You need about 20 minutes, a pressurized autoclave, and some nasty chemicals to do this effectively. There is research into other methods but I really don't know anything about them.
The only reliable method that I'm aware of to denature proteins without making the whole thing inedible is hydrolysis. Gelatin is made from collagen in the skin, bones, and connective tissues of various animals, but Jell-O is generally considered safe.
"Protein" in food really means "amino acids" as far as nutrition is concerned; even if the protein isn't denatured by cooking (and at least some proteins are), it will be broken down to amino acids by your digestive system before being absorbed into your body. Your body uses the amino acids to build its own proteins.
http://www.ncbi.nlm.nih.gov/books/NBK22600/
"Proteins ingested in the diet are digested into amino acids or small peptides that can be absorbed by the intestine and transported in the blood."
If by "animal-source protein strings" you mean "small peptides", then yes. But in general they still have to be resynthesized into the proteins used by the body. There might be a few useful proteins that are small enough to fall into the "small peptide" range and would therefore be absorbed and used as-is.
Prions have a little over 200 amino acids, so they are on the large side to be considered "small peptides" (which AFAIK are typically a few to a couple of dozen amino acids). They appear to be resistant to the enzymes that normally digest proteins, and it doesn't appear to be clearly understood how they get from the digestive tract into the bloodstream. See, for example, here:
plants can be a vector for prions. When researchers fed hamsters grass that grew on ground where a deer that died with Chronic wasting disease (CWD) were buried, the hamsters became ill with CWD, suggesting that prions can bind to plants, which then take them up into the leaf and stem structure, where they can be eaten by herbivores, thus completing the cycle. It is thus possible that there is a progressively accumulating number of prions in the environment
Are you afraid yet? ;-)
Are there proteins that cause looping multiple-step reactions as well? Maybe that's what this is and I need to read more :p.
(Where A/A' are different forms of the same structure and A(B)->C means A acts on B to make C).
Stuart Kauffman wrote some things about this, but here is a counterpoint from Leslie E Orgel:
http://journals.plos.org/plosbiology/article?id=10.1371/jour...
How did school manage to make biology so boring? They did it with math too, so I shouldn't be surprised, but damn.
Would love resources on an intro to bio for the CS folk. I'm sure there are some good ones out there.
Sounds like a kill switch to me.
The most recent Radiolab was about an idea that the existence of cellular organelles are the product of an extremely unlikely merging of two cells that didn't immediately die afterwards.
Stemming from the observation that we had an extremely long period of simple life, coupled with a sudden explosion where life rapidly increased in size and complexity.
A 0.0...01% likelihood event will still happen, given an entire planet of simple cells and hundreds of millions of years.
Another example of distributed costs, concentrated benefits really screwing us over in the long-run.
The point being, that we may not be able to measure risk at this time, because the prions may be latent in people. (Cue spooky music.)
I was raised to do it, but I am now barred due to the note on the eligibility sheets. I talked to a Red Cross area administrator about it and he said that, even though it has been over 20 years, they are unlikely to lift the ban until effective testing and treatments are found. Since there are no tests, they can't risk the blood supply.
[1] Check the details of the Creutzfeldt-Jakob Disease, Variant (vCJD); "Mad Cow Disease" option: http://www.redcrossblood.org/donating-blood/eligibility-requ...
• Use vaccination to train the host's immune system deal with it, should it ever encounter the full version.
• Use special drugs to slow down their replication to let the host's immune system deal with the rest.
Prions have no special, prion-only replication strategy we can target, and I'm not sure whether the immune system can be trained to attack only prions and not their regular protein equivalents.
A prion tends to be vastly different than the original protein. I thought the bigger problem was that prions are the metaphorical tanks of the protein world. Just look at what it takes to denature a prion compared to other proteins.
The most terrifying thing about prions is that they are infectious but not life: they can't be "killed" in the normal sense
While viruses are generally not considered to be alive, they are considered to be instances of life, aren't they?
Everyone has their own definition though. I remember reading a novel where life was defined simply as heredity, mutation, and adaptation. The second definition makes more sense to me, and implicitly includes viruses.
The good news is that some people are "immune" to developing an infectious prion disease. Turns out that certain mutations prevent normal proteins from interacting with a complementary prion in a way that would cause them to become misfolded.
Learning other languages or instruments is probably useful from a brain health standpoint regardless of your genetics (even if you already have early-stage AD you can slow progression), but they are just proxies for activity. I would guess that learning something that interests you is more important than what that thing actually is.
Keep in mind I'm no expert, but this seems to be a reasonable assumption.
http://www.doctortipster.com/11968-new-vaccine-against-metha...
http://www.livescience.com/21132-cocaine-vaccine-cure-addict...
http://www.voanews.com/content/scientists-develop-experiment...
This method may be a little bit costly (relative to promised returns of solving a problem that does not directly affect humans) and with limited effect, but still, it may be a way worth investigating.
Dry heat will inactivate prions, but you need 200C for 4 hours or more which is more than most plastics can handle.
Edit: Actually, Carl Sagan wrote his memes in metal (and shot them into the universe) so I take that back.
Prions are a single component. They are proteins with the same amino acid sequence as a protein normally produced by an organism. Except they have been misfolded. The geometry of the misfolded protein is such that it becomes a catalyst to reproduce the same misfolding error. There are no "brains" in them. They can arise entirely accidentally. They're a bit like the ice-nine from Vonnegut's _Cat's Cradle_, in which a crystal of a novel form of solid water that melts at a higher temperature can recruit liquid water to grow the crystal without limit. Each individual prion can misfold any number of same-sequenced amino acid chains.
And like the ice-nine, which melted at a temperature above human body temperature, the prion may be able to survive through more extreme conditions than other forms of the protein.
In the best case scenario, the prion does little more than cause a deficiency of the normally-folded protein forms in the body. In the worst-case scenario, it poisons some other process within the body in its misfolded form.
They force other crystals to be of the same size and shape.
(That's why creamed honey producers put a "starter" crystal in, which is tiny, that forces the honey to produce other tiny crystals.)
Pet peeve of mine, but it looks like you slept through English class as well. The plural of "virus" in English is "viruses". "virus" in latin is a mass word and has no plural, like "sugar" and "air".
Anyway, this is hackernews.
For those of us who grew up in internet hacking communities of the early 90's "virii" was the plural form in the lingua franca. As a descriptivist of great habit, I will continue to use that form.
How about this argument then: "virii" is f*ckin ugly? No? Darn. :-)
Just because a noun is a mass word in one language, it doesn't mean it has to be in other languages that have borrowed the word.
For example, in my language, "lego" is a mass word, and to make a plural you would have to say something like "pieces of lego", but in English, the plural of "lego" is "legos".
[There's a "species" that spread around the Andes and eventually reached itself on the other side---and could no longer breeed with "itself". Genes could still in theory travel all the way around and back to the discontinuous point, however.]
edit: http://i.stack.imgur.com/4VsFW.png will make this less confusing, and quite unintentionally :).
An object is considered to be alive if it consumes energy to create or maintain its own order (in opposition to the general effect of the second law of thermodynamics in the wider system in which it finds itself).
Although this doesn't exclude crystals..! :/
"You Can't Kill What's Not Alive: Prions cannot be destroyed by boiling, alcohol, acid, standard autoclaving methods, or radiation. In fact, infected brains that have been sitting in formaldehyde for decades can still transmit spongiform disease. Cooking your burger until it is well done will not destroy the prions!" http://learn.genetics.utah.edu/content/molecules/prions/
"Eating human brains helped Papua New Guinea tribe resist disease, research shows." https://www.theguardian.com/science/2015/jun/10/brains-helpe...
Original name for the prions was "trembling in fear" - or Kuru: https://en.m.wikipedia.org/wiki/Kuru_(disease)
One sci-fi horror series had an episode where the plot was that some mass produced chickens were getting ill because the feed was made from other chickens and they eventually discovered that it involved a prion that was dangerous to humans as well. This was discovered after massive numbers of those chickens had been consumed in large quantities by society.
This is not quite correct, the disease is believed to be transmittable to humans, but we're not in the practice of eating deer brains, so there are no confirmed cases. All of the states with CWD have advisories on reducing the risk with consumption. Eg: http://www.dgif.virginia.gov/wildlife/diseases/cwd/deer-carc...
Given that we don't really know how CWD is transmitted among animals it is still pretty worrying.
Apparently it's been shown that spiker monkeys can contract it but it hasn't (yet) been shown to be transmitted to humans.
They did a harvest of deer in a small area near where CWD had been found (in an Elk, actually) and found a staggering number of the deer were infect, I think it was 36%.
There's virtually no way to get rid of it, apparently.
Anyway, the map is slightly out-of-date.
How does CWD spread?
The method of CWD transmission is unknown, however there is strong evidence to suggest that abnormally-shaped proteins called "prions" are responsible. The agent responsible for this disease may spread directly through animal to animal contact or indirectly through soil or other surface to animal contact. It is thought that the most common mode of transmission from an infected animal is via saliva and feces. A recent study confirms that CWD prions can be shed into the enviroment in feces from animals showing no clinical signs of the disease and can contaminate the soil, leading to infection in other animals. CWD can be spread from region to region by the movement of captive deer or through the improper disposal of a harvested deer transported from a CWD infected area.
For someone who had an endoscope recently, that's really scary.
If anyone knows any other good resources or intros, please share as well.
Or am I misunderstanding?
There is a paper roughly in this area (polyphosphates and peptides in an autocatalytic cycle) here :
As far as I know, sporadic CWD is relatively uncommon, but given CWD is caused by the PrP protein, and there are a number of known mutations in PrP which can increase its likelihood of undergoing prion-conversion, I'd hope they're going to sequence this animal's PrP gene to see it it shed's some light on the etiology.
Irrespective, this could still mean that CWD is now endemic in Europe.
>>>
Updated for clarity and extra info/context (thanks pbhjpbhj!)
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CWD: Chronic Wasting Disease (deer-based prion disease - main topic of article)
PrP: The specific prion protein involved here. Note that (confusingly!) prions are both a 'class' of proteins but also refers to a specific protein (PrP).
Prions (class) are proteins which can exist in one of two states. In their soluble form they're happy-go-lucky proteins that are monomeric (i.e. exist as a single unit). However, these soluble-form prions can undergo a conformational change (re-arrange their shape) into a different conformation (the infectious form). The infectious form of the prion can do two specific things: 1) Aggregate (so all the previous soluble prion proteins get stuck into a big wad of protein) 2): Catalyze the conversion of soluble-form prion into the infectious form. Herein lies their infectivity - you get an exponential growth in the number of proteins in the infectious state.
Prions (PrP) is a specific protein found in many higher-order multicellular organisms that is the SPECIFIC protein that causes a range of prion diseases (Creutzfeldt-Jakob Disease (CJD), BSE [mad cow], CWD, Scrapie etc). There are species barriers to these diseases, even though the proteins are pretty similar (i.e. humans cannot catch CWD from deer, even though the PrP protein misfolds in CWD and the same human version misfolds in CJD). These species barriers are convenient (!!) but very poorly understood, which is somewhat concerning.
Finally - it's worth point out prions aren't always bad. Fungi use them as a mechanism to facilitate non-genetic heritability/diversity [1], and we're increasingly finding examples of prion-like mechanisms that facilitate fast and irreversible signalling in cells (e.g. in the inflammation response [2])
[1] True, H. L. & Lindquist, S. L. A yeast prion provides a mechanism for genetic variation and phenotypic diversity. Nature 407, 477–483 (2000).
[2] Cai, X. et al. Prion-like polymerization underlies signal transduction in antiviral immune defense and inflammasome activation. Cell 156, 1207–1222 (2014).
Where does alzheimer's disease fit into this? Are there instances where plaque build up is caused by protein misfolding, or are there other causes?
I'm guessing it's in the article, but, well, y'know ...
http://www.pbs.org/wgbh/nova/next/body/phage-alzheimers-cure...
I'm not feeling lucky: https://www.google.com/search?q=reindeer+brain&tbm=isch
Or just, you know, a disease that kills you if you eat brains? Because that's kind of the exact opposite of what zombies do.
The protein would probably also have to effect the olfactory glands, creating an attraction to uninfected humans.
I haven't found onen that discusses love of cats as a result, sadly.
[0] last section here: https://en.wikipedia.org/wiki/Toxoplasma_gondii
Romero's Night of the Living Dead also plays with the otherness theme, but the dead are numb and more ghoulish than vampiric.
28 Days Later finally has something I would agree is rabies inspired. It probably contributed to the frantic behavior of zombies in several recent movies.
from wsj
"The roots of the vampire myth stretch back nearly as far. Tales of vampire-like creatures, formerly dead humans who return to suck the blood of the living, date to at least the Greeks, before rumors of their profusion in Eastern Europe drifted westward to capture the popular imagination during the 1700s.
In its original imagining, though, the premodern vampire differed from today's in one crucial respect: His condition wasn't contagious. Vampires were the dead, returned to life; they could kill and did so with abandon. But their nocturnal depredations seldom served to create more of themselves.
All that changed in mid-19th century England—at the very moment when contagion was first becoming understood and when public alarm about rabies was at its historical apex. Despite the fact that Britons were far more likely to die from murder (let alone cholera) than from rabies, tales of fatal cases filled the newspapers during the 1830s. This, too, was when the lurid sexual dimension of rabies infection came to the fore, as medical reports began to stress the hypersexual behavior of some end-stage rabies patients. Dubious veterinary thinkers spread a theory that dogs could acquire rabies spontaneously as a result of forced celibacy.
Thus did rabies embody the two dark themes—fatal disease and carnal abandon—that underlay the burgeoning tradition of English horror tales. Britain's first popular vampire story was published in 1819 by John Polidori, formerly Lord Byron's personal physician. The sensation it caused was due largely to the fact that its vampire, a self-involved, aristocratic Lothario, distinctly resembled the author's erstwhile employer."
"The Plague Behind the Zombies The undead didn't always breed by biting. For that, the mythmakers needed rabies." http://www.wsj.com/articles/SB100014240527023033434045775189...
Imagine if lions eat a few kg of meat from an anteople, and then the rest of the antelope turned into another lion.