I have a misfolded protein illness, and as a layman I was always told the endoplasmic reticulum was in charge of misfolded proteins, either by degrading them or triggering apoptosis (cell death) if ER stress gets too high because of an overabundance of misfolded proteins. As a result I've been doing my best to reduce my ER stress to give my body an edge against the illness.
Now reading this article it seems there's a million ways they get degraded.
So I'm wondering, if any expert wants to butt in, does this new discovery give us new potential methods to improve misfolded protein degradation?
There are a number of ways to reduce ER stress and I'm far from an expert, generally anti-oxidants do the trick, if you have a similar illness I'd look up studies for your specific illness, they often do in-vitro tests of specific compounds to test their effect on diseased cells.
In my case I try to avoid alcohol, and I supplement with high doses of rosemarinic acid extract.
Not in the field but I’ve heard that fasting allows the body to consume mis-formed/old cells. Is that something that would help in your case?
That and keeping mtor low perhaps?
You're looking at this from a healthy body's perspective, in case of an excess of misfolded proteins the ER stress increases which activates the unfolded protein response (UPR) which tells the cell to produce less proteins to let it chill out a bit, and then if the ER stress remains too high leads to apoptosis (cell death). That's the way the body normally functions and it's all good.
But if your body produces a majority of misfolded proteins you don't want your cells to freak out about it and kill themselves because you need those cells alive for your body to perform its normal physiological functions. At least it's an emerging theory that in some case the systematic destruction of the cells leads to worse outcomes than just having cells living and working with misfolded proteins.
Take all this with a great big grain on salt because it's the blind leading the blind. I'm not a biologist, I've just read a lot about my illness.
Nuclear waste (the kind we eukaryotes all make) get lumped into a garbage can that then gets fused to a cytoplasmic trash truck/digester called a vacuole or lysosome.
There is a lot of excitement in lysosomal processing if protein and polyglucosan aggregates in aging brain (work of Ralph Nixon). But still a very long haul for this work in yeast to applications, if any, in humans. Bravo anyway—after all, yeast are family.
“Tying that particular family of proteins and this aspect of vesicle traffic biology to protein clearance gives us a new way to look at Alzheimer’s, Parkinson’s, Huntington’s – all these neurodegenerative diseases,” said Sontag.
I have a feeling that biology research is stuck “at tiny scales”, with scale meaning not size of the components, but the amount of components.
Remember when researchers painstakingly designed by hand new algorithms to scale up pixel images and to remove compression artifacts, and it never looked that good? I read many papers from that effort. Man, the clever maths and techniques the researchers used, the new theories of perceptual sharpness and image quality. And, don’t read me wrong, all of it is still useful in one way or another.
But then neural networks came, and we had a full generic framework that was able to do upscaling really well, and a bunch of other things, and saying that you wanted grant money to code by hand a new upscaling algorithm using some clever wavelet technique you had in mind got you nowhere.
We need to have that moment in cell biology, when we stop having entire research groups looking at a single pathway or just a single protein conformation for years, and instead use a generic framework to solve a problem.
> But then neural networks came, and we had a full generic framework that was able to do upscaling really well, and a bunch of other things, and saying that you wanted grant money to code by hand a new upscaling algorithm using some clever wavelet technique you had in mind got you nowhere.
I wonder though, how "correct" that ANN upscaling really is. Does it reimplement clever ideas, that people came up with in a more computationally expensive way, plus some ANN specific extra stuff? Or does it make pixel values up "to make things look good" but actually moves away further from what reality was?
And what do we really learn from an ANN doing this well? Do we get to extract the algorithm back out of it, arriving at actual new knowledge, or will it remain a not understandable black box, with the only knowledge learned being "this kind of ANN works well for that kind of task"?
> We need to have that moment in cell biology, when we stop having entire research groups looking at a single pathway or just a single protein conformation for years, and instead use a generic framework to solve a problem.
I don't think it is that easy. Probably both is needed, work in painstaking detail and usage of generic methods/frameworks. Some ANN might by its nature not even consider a new method. Or its result might be not understandable and therefore risky to apply to humans.
I assume this wouldn't hold any value for prions (as the entropic anti-life tarpit that they are), and more value for "benign" and merely useless misfolds?
The team did these experiments in yeast cells, which are easy to grow and quick to reproduce. One next step is to investigate whether this same pathway is used in mammalian cells to clear human disease-related proteins.
pH derangement and salt derangement both promote protein misfolds. Someone please do a study on the possibility of reducing misfolds and encouraging refolds via correcting chemical derangement in the cell.
Or hopefully CWD. I feed about 40 deer a day, twice a day and they are at high risk of getting chronic wasting disease misfolded prions. I don't consume the deer but CWD can be passed from urine and feces so I wear dedicated shoes specifically for the purpose of feeding them and sterilize them with chemicals and UV light.
Every single game jurisdiction that has confirmed cases of CWD or confirmed cases of CWD nearby has instituted baiting/feeding bans. The predominate reason for this is because prions can be spread through bodily fluids, including saliva, which can be passed from animal to animal when they share a common feeding source. Making corn piles and letting them eat off of that could spread CWD instead of preventing it. If you truly want to feed these deer, plant food plots. Turnips, sugar beets, and pumpkins will keep them fed through deep winter. Prions cannot be killed, not with fire or chemicals, so your sanitizing routine is pointless.
Every single game jurisdiction that has confirmed cases of CWD or confirmed cases of CWD nearby has instituted baiting/feeding bans.
Agreed but it is not banned in my area. The game warden does discourage it for the reasons you mentioned but the real undocumented reason is they don't want the obligation of paying for running a deer/elk food pantries. They do have a few of them for the elk. There are about 100 elk not far from me that they feed whereas I only have two elk on my property. I create N+2 piles of food to minimize saliva swapping but they do still move each other around at the start of winter. After a couple of weeks they stop swapping and fighting and the ones that have been here before don't even start with the swapping.
The plants you mention do not grow here in the winter outside of a greenhouse. People here that can afford to do so feed them pellets. On the other side of my county all the deer are dying because nobody is feeding them.
Never feed corn to deer, especially during the winter. It will give them diarrhea and dehydrate them. If you see someone feeding them corn try to get them to stop and use nutrient dense pellets and occasionally some oats to assist their digestion.
> The plants you mention do not grow here in the winter outside of a greenhouse
You're right, they don't. That's why you plant them in the late summer, with a mix of kale, chicory, rape, and other brassicas. The deer and elk eat the greens above ground right up until snowfall and then they dig the turnips and beets out of the ground over the winter as needed. They usually leave the pumpkins for last, but come late January they'll eat every last one.
The deer migrate away from here during the summer. I would have to plant them up in the mountains which I am not opposed to doing if they give me permission. That might be a fun little project and an excuse to do some off-roading.
My corn piles are only for squirrels, coons, beavers, possums, and squatches, and are clearly labeled as such. Any deer, found engorging itself on my corn, will be shot.
I'm not sure what the risk of spontaneous CWD development in deer is (extremely low?), but I'm also not sure that your sterilization protocol is sufficient either.
> 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 [1]
How do you spot a diseased animal, and what's your protocol for dealing with it?
How do you spot a diseased animal, and what's your protocol for dealing with it?
It's tricky because the symptoms may not manifest for up to a year and sometimes even longer. This time of year is extra tricky because I get deer that show up late in winter and are emaciated from a lack of food, but it could also be disease. If I suspect a deer is infected I call the game warden and they would come out to put it down and get the lymph nodes tested. There is no other way. Thus far I have not had to do this. The only deer I have lost thus far was one that for sure was starving for too long in the hills and took too long to find his way to me and several last year that played chicken in the highway but that has stopped since I started feeding them twice a day.
I could actually see formaldehyde preserving the prions. I am curious what ph of acid they used. I would be surprised if the bleach I use does not decompose the prions but maybe I have been going through the wrong process all this time. If you can suggest a better procedure I will look into it. I'm not worried about ruining boots.
I forgot to add, the reason I know the 3 emaciated deer are not in that condition from disease but rather from malnutrition is that 2 of them are making a recovery. One was too far gone.
Maybe. [1] I have several Protease in capsule form and consume them daily. I would imagine that would have to be made into a paste to work on the boots.
Honestly I think bleach is fine. There is nothing inherently special about prions. They are just proteins and bleach will rapidly disassemble and denature proteins of any kind out of their 3D structure, some slower than others. I leave it on over night and with heat applied.
They are not overpopulated here. The weather has been killing them off in droves. They are not pests here at all. There are natural predators here but we try to keep their numbers down. The biggest predator this year has been the snow, ice and wind. The pests here are coyotes and yellow bellied marmots. The bigger predators stay further up the mountains unless there is a drought.
I can find no evidence of a protein that can survive bleach. Please cite sources of proteins that can survive heated bleach for extended periods of times. The sources will need to include the concentration of sodium hypochlorite, the temperature and the length of time the proteins were saturated.
Statistically, yes. There’s thousands of risks you don’t even consider that are more dangerous. So probably not rational to worry about collagen.
There is no definite proof that gelatin can contain infectious prions, as long as it is manufactured according to industry standards. It’s theoretically possible. But your odds of getting struck by lightning are far higher in any given year. I wouldn’t worry about it.
A friend of mine got infected with prions. Well, it’s what the doctors believe since all other tests came up negative. They aren’t 100% sure but have documented it as that.
It’s amazing how quickly he degenerated. He was feeling weird physically and mentally and went to a doctor. Within a few months he was a different person but could recognize friends. He needed assistance for living. Within a year he was completely mentally gone. Just a different person with no means of communicating or doing anything for himself. Just completely sad.
You can spontaneously misfold a protein yourself. After a quick look on Wikipedia for Creutzfeldt-Jakob disease: "An EU study determined that "87% of cases were sporadic, 8% genetic, 5% iatrogenic and less than 1% variant."[22]"
No one has any idea. He wasn’t exposed to anything that would be high risk for it, if that’s even a thing. As another person commented here, it sounds like it’s spontaneous in many cases. Or at least that’s our best answer.
You’ll need to sterilize everything with a 50% solution of bleach. Not by spraying it like a domestic cleaning agent, mind you, but by submersing or covering it for five minutes. That should be enough to denature prions on the surfaces of everyday objects - but not tissue like food!
If this concerns you, look into hydrolyzed collagen (aka collagen peptides). I assume since they are broken down its a bit different, but can't back up my assumption.
Now reading this article it seems there's a million ways they get degraded.
So I'm wondering, if any expert wants to butt in, does this new discovery give us new potential methods to improve misfolded protein degradation?