Zinc Finger Nucleases: Connection to Gene Knockout/Knockin

[Rid]

Curious, @Helen, if you think gene knockout/knockin may have a role in our conditions.

It would make sense that fin/sp/ad/etc would cause epigenetic changes that could "knockout" certain gene expressions in those susceptible and it seems like all of the credible recoveries follow a similar protocol that could be enough to cause another similar, but opposite "knockin" where the proper gene expression is resumed. I have a very basic understanding of all of this, but as we know, zinc finger and gene expression have a lot of connections and I just recently learned that gene-knockout/knockin can be mediated by zinc finger nucleases. Think there's anything here? Is a large part of permanent, sustained recovery a matter of getting the proper expression of whatever genes we may have fucked up?

Here's a wiki for anyone interested in reading some more. Don't wanna connect anything that isn't there but I thought it was interesting that zinc finger is used in gene-knockout to stop expression of whatever genes you're targeting.

Gene knockout - Wikipedia

 

[Helen]

Curious, @Helen, if you think gene knockout/knockin may have a role in our conditions.

It would make sense that fin/sp/ad/etc would cause epigenetic changes that could "knockout" certain gene expressions in those susceptible and it seems like all of the credible recoveries follow a similar protocol that could be enough to cause another similar, but opposite "knockin" where the proper gene expression is resumed. I have a very basic understanding of all of this, but as we know, zinc finger and gene expression have a lot of connections and I just recently learned that gene-knockout/knockin can be mediated by zinc finger nucleases. Think there's anything here? Is a large part of permanent, sustained recovery a matter of getting the proper expression of whatever genes we may have fucked up?

Here's a wiki for anyone interested in reading some more. Don't wanna connect anything that isn't there but I thought it was interesting that zinc finger is used in gene-knockout to stop expression of whatever genes you're targeting.

Gene knockout - Wikipedia

Rid, I think I have been writing about this for a year almost NON STOP

and zinc finger theory, and gene expression.

https://hackstasis.com/threads/epig...ion-of-demethylating-enzymes.1402/#post-44064


Plus the first theory on this forum was that zinc finger was impaired and it does not connect AR to the DNA.

this is why I fed cysteine to people.


but also dont forget that usually taking hormones like cortisol causes the body to lose zinc or steroids.

So if the receptor is overxpressed then zinc will be lost into the urine.

which I tested with many PFS people and zinc was very high in the urine in some people.

It is like pyroluria.


this is why I suggested pyroluria protocol for some people which is zinc b1 , b6 sodium butyrate , magnesium. etc


read the thread that I posted it explains better the connection.


it goes like this with the hormonal reception

1) binding part LBD

2) then AR moves into the center of the cell nucleous.

3) then it binds to AREs with zinc finger.

4) then you need acetylated and methylated histones. Acetylation usually increases Gene expression, methylation of histones can do both.

and then you have methylation of DNA( which can silences the genes. IF for some reason the signal is too strong.


As we know number and density of the ARs, are very high in PFS in the nucleous. that means that binding part or AR expression is not a problem.

the problem can lay in the zinc finger motif.

of methylation , or acetylation.

or if the receptor signal is too strong, it can be silenced by methylation of DNA.

As we see that folate and methylation seems to be down, in PFS.

so it is NADPH system is what causing the problem. IMO

NADPH system depends on potassium.


this is why people crash while on fin, when they already had low NADPH system. or were g6pd deficient.

since the minute you bind NADPH you go into hemolytic anemia

and then you just crash, like people with g6pd deficiency.

and NADPH is needed to make folinic acid, and without it you cant protect Bh4 and you cant make nitric oxide.

and without it glutathione is down. and body has to use cysteine to make new glutathione , instead of recirculating it.

 

[Rid]

I guess I knew this was what you were talking about, I just didn't want to incorrectly assume because I've never heard you directly reference gene knockout before. It's pretty fucking hardcore this whole thing. like how they use it on rats to fundamentally change their DNA. I know how fucked a lot of us are, we all feel it, but we've literally changed our FUCKING GENES and now we're just scrambling to turn that shit back on. I guess I knew this, it's just different when you find it upon your own research.

you know, I've read a lot of what you have written, sometimes dozens of times over. You've repeated yourself also many times, as you have to. I've probably read over almost all of your earlier writings and it a lot of it makes sense, but with someone with no medical/biological background, it's hard to see how it all fits together sometimes. I can logically understand a lot of what you are saying, but it's still like we've just got bits and pieces. I imagine a lot of people here ask the same damn questions over and over because even though it seems obvious to you, it's not obvious to the average person. I apologize on behalf of those people who are ignorant to what you are trying to teach us, it's just easy to circle back and repeat or regurgitate what you are saying when we don't have any formal training in even interpreting all this crazy shit.

So assuming that feeding myself cysteine and histidine has been working well in managing my symptoms- could that be enough alone to eventually "turn on" the genes that are no longer being expressed? I feel like, from my limited knowledge of gene expression- we are only tackling one side of the issue. We can feed ourselves all this medicine, but it wont take hold if we aren't COMPLETELY changing our lifestyles. I know you've said this before as well, but shouldn't this be of more emphasis? Like the fact that all of us must fundamentally and completely change our lifestyles- in eating, exercise, socializing, thinking and beyond to even think about our gene expression changing?

my knowledge of gene expression is limited, but I do know a bit about it. And I remember it being rooted deeply in both the biological (ie what your expertise is) but also just as importantly in the lifestlyes choices and habits that we have, that, let's face it, are incredibly difficult to completely rewire when they have been part of many of our routines, sometimes unconsciously, for much of our lives. should we be putting more emphasis on what we are spending our days doing?

 

[bruschi11]

should we be putting more emphasis on what we are spending our days doing?

Yes it’s part of the process. TEI is essentially shortcut for this as you get healthier via nutrition unlike anyone else would which allows your body to be free from pathogens, toxicities, viruses etc.

But then we have our non-TEI/cdsnuts guys who work on the gut very hard for long time like English/chi. They are making system like TEI because their digestion is so robust. With great digestion now we are getting nutrients and using them correctly.

So it all ties in together. Recoveries make sense now pretty much every single one I’ve ever read lol.

It is amazing the gene factor. I’m not shocked by it though. Like you, I’ve been major beneficiary of zinc finger. It’s like you become different person when you go from goodness to badness while practicing with it.

I just know how good the good feels. This whole journey is worth it for that x10000000.

 

[Rid]

Yes it’s part of the process. TEI is essentially shortcut for this as you get healthier via nutrition unlike anyone else would which allows your body to be free from pathogens, toxicities, viruses etc.

But then we have our non-TEI/cdsnuts guys who work on the gut very hard for long time like English/chi. They are making system like TEI because their digestion is so robust. With great digestion now we are getting nutrients and using them correctly.

So it all ties in together. Recoveries make sense now pretty much every single one I’ve ever read lol.

It is amazing the gene factor. I’m not shocked by it though. Like you, I’ve been major beneficiary of zinc finger. It’s like you become different person when you go from goodness to badness while practicing with it.

I just know how good the good feels. This whole journey is worth it for that x10000000.

man, it's insane how deep this thing goes. those good days make all the bad ones make sense.

 

[wuf]

Rid, I think I have been writing about this for a year almost NON STOP

and zinc finger theory, and gene expression.

https://hackstasis.com/threads/epig...ion-of-demethylating-enzymes.1402/#post-44064


Plus the first theory on this forum was that zinc finger was impaired and it does not connect AR to the DNA.

this is why I fed cysteine to people.


but also dont forget that usually taking hormones like cortisol causes the body to lose zinc or steroids.

So if the receptor is overxpressed then zinc will be lost into the urine.

which I tested with many PFS people and zinc was very high in the urine in some people.

It is like pyroluria.


this is why I suggested pyroluria protocol for some people which is zinc b1 , b6 sodium butyrate , magnesium. etc


read the thread that I posted it explains better the connection.


it goes like this with the hormonal reception

1) binding part LBD

2) then AR moves into the center of the cell nucleous.

3) then it binds to AREs with zinc finger.

4) then you need acetylated and methylated histones. Acetylation usually increases Gene expression, methylation of histones can do both.

and then you have methylation of DNA( which can silences the genes. IF for some reason the signal is too strong.


As we know number and density of the ARs, are very high in PFS in the nucleous. that means that binding part or AR expression is not a problem.

the problem can lay in the zinc finger motif.

of methylation , or acetylation.

or if the receptor signal is too strong, it can be silenced by methylation of DNA.

As we see that folate and methylation seems to be down, in PFS.

so it is NADPH system is what causing the problem. IMO

NADPH system depends on potassium.


this is why people crash while on fin, when they already had low NADPH system. or were g6pd deficient.

since the minute you bind NADPH you go into hemolytic anemia

and then you just crash, like people with g6pd deficiency.

and NADPH is needed to make folinic acid, and without it you cant protect Bh4 and you cant make nitric oxide.

and without it glutathione is down. and body has to use cysteine to make new glutathione , instead of recirculating it.

From a pharmacological point of view, G6PDH is inhibited in a non-competitive and fairly specific manner by the steroid dehydroepiandrosterone and its halogenated derivatives. The vanadate anion, on the other hand, inhibits the enzyme competitively. The drug metformin used in the treatment of type II diabetes is able to activate the enzyme in a way that has not yet been discovered; however, it could represent a positive secondary effect given that the pentose phosphate pathway produces NADPH which regenerates glutathione, a natural antioxidant that is lowered in diabetics.

This study says that metformin can rise NADPH.Is this a way to try?

 

[bruschi11]

We want to inhibit nadph per @Helen not increase.

 

[Troy]

From a pharmacological point of view, G6PDH is inhibited in a non-competitive and fairly specific manner by the steroid dehydroepiandrosterone and its halogenated derivatives. The vanadate anion, on the other hand, inhibits the enzyme competitively. The drug metformin used in the treatment of type II diabetes is able to activate the enzyme in a way that has not yet been discovered; however, it could represent a positive secondary effect given that the pentose phosphate pathway produces NADPH which regenerates glutathione, a natural antioxidant that is lowered in diabetics.

This study says that metformin can rise NADPH.Is this a way to try?

@Helen also interesting is that androsterone inhibits g6pdh.

 

[Walker]

yes!!
and that is what I exactly used that fucked me up!
I guess since having already PFS, as I used it it destroyed my enzyme to ZERO.

No you didn't. I've corrected you multiple times on Swole Source and I will here as well. This provides misinformation to those who are on the fence of trying proper treatments.

I like you, but androsterone (R-Andro, Andro Hard, etc.) didn't crash you. The supplement you linked me to on Swole Source was high in DHEA proper, not R-DHEA.

 

[wuf]

No you didn't. I've corrected you multiple times on Swole Source and I will here as well. This provides misinformation to those who are on the fence of trying proper treatments.

I like you, but androsterone (R-Andro, Andro Hard, etc.) didn't crash you. The supplement you linked me to on Swole Source was high in DHEA proper, not R-DHEA.

yes you are right . that is why i deleted my last post.
delete this one as well if you wish, cause it is useless.
thank you my friend.

 

[Walker]

yes you are right . that is why i deleted my last post.
delete this one as well if you wish, cause it is useless.
thank you my friend.

Thanks man - not trying to be an asshole, I promise. Just like to make sure those who are reading, but not necessarily asking the questions, can read correct information.

 

[wuf]

Thanks man - not trying to be an asshole, I promise. Just like to make sure those who are reading, but not necessarily asking the questions, can read correct information.

you are 200% right. I twisted the name. My fault. Thanks!

 

[wuf]

We want to inhibit nadph per @Helen not increase.

From helen:

this is why people crash while on fin, when they already had low NADPH system. or were g6pd deficient.

since the minute you bind NADPH you go into hemolytic anemia

and then you just crash, like people with g6pd deficiency.

and NADPH is needed to make folinic acid, and without it you cant protect Bh4 and you cant make nitric oxide.

and without it glutathione is down. and body has to use cysteine to make new glutathione , instead of recirculating it.

 

[vicecaz]

@Helen also interesting is that androsterone inhibits g6pdh.

Interesting, where did you see that?

 

[Troy]

Interesting, where did you see that?

In wuf’s study in his post above

 

[freeflow]

Rid, I think I have been writing about this for a year almost NON STOP

and zinc finger theory, and gene expression.

https://hackstasis.com/threads/epig...ion-of-demethylating-enzymes.1402/#post-44064


Plus the first theory on this forum was that zinc finger was impaired and it does not connect AR to the DNA.

this is why I fed cysteine to people.


but also dont forget that usually taking hormones like cortisol causes the body to lose zinc or steroids.

So if the receptor is overxpressed then zinc will be lost into the urine.

which I tested with many PFS people and zinc was very high in the urine in some people.

It is like pyroluria.


this is why I suggested pyroluria protocol for some people which is zinc b1 , b6 sodium butyrate , magnesium. etc


read the thread that I posted it explains better the connection.


it goes like this with the hormonal reception

1) binding part LBD

2) then AR moves into the center of the cell nucleous.

3) then it binds to AREs with zinc finger.

4) then you need acetylated and methylated histones. Acetylation usually increases Gene expression, methylation of histones can do both.

and then you have methylation of DNA( which can silences the genes. IF for some reason the signal is too strong.


As we know number and density of the ARs, are very high in PFS in the nucleous. that means that binding part or AR expression is not a problem.

the problem can lay in the zinc finger motif.

of methylation , or acetylation.

or if the receptor signal is too strong, it can be silenced by methylation of DNA.

As we see that folate and methylation seems to be down, in PFS.

so it is NADPH system is what causing the problem. IMO

NADPH system depends on potassium.


this is why people crash while on fin, when they already had low NADPH system. or were g6pd deficient.

since the minute you bind NADPH you go into hemolytic anemia

and then you just crash, like people with g6pd deficiency.

and NADPH is needed to make folinic acid, and without it you cant protect Bh4 and you cant make nitric oxide.

and without it glutathione is down. and body has to use cysteine to make new glutathione , instead of recirculating it.

Folinic Acid Stops My Hair Loss

"Within a day I noticed my hair shedding had stopped. Its been a week now of 800mcg per day, and I've had no hair loss. Even more interesting is that Folinic Acid causes my skin to become extremely soft, has smoothed out my Keratosis Pilaris, and significantly reduced my addictive behaivours."

 

[vicecaz]

In wuf’s study in his post above

Isn't the study talking about dehydroepiandrosterone? Which is DHEA and not androsterone as in R andro, I think

 

[Troy]

Isn't the study talking about dehydroepiandrosterone? Which is DHEA and not androsterone as in R andro, I think

My mistake, I thought that was androsterone.

 

[wuf]

Isn't the study talking about dehydroepiandrosterone? Which is DHEA and not androsterone as in R andro, I think

Yes that's why I told to @Walker that was the product which fucked me up, so I was right. That stuff shutted down the enzyme even further