Price quote for a personal Androgen Receptor Silencing assay

[BP7667]

@Hope88

Without sounding like a smart ass but I think it is more likely to understand when you study biochemistry or have a degree in biochemistry.I think It is hard enough to study this subject without having PFS but studying it with this condition is probably almost impossible. But you’re right we need somebody who dedicate their life to research this condition instead of voluntarily doing it in their free time.

You don’t sound like a smart ass, because the fields are so closely linked there is essentially no difference. At the PhD level of academia, research can cross functional areas of study. The reason I say this is because not that we need someone studying it full time, we have that already. But we need someone who has the drive and passion behind it. Along with the research resources, and lab resources a full blown research university can offer.

Imagine if a PFS victim was doing a dissertation into the primary cause of PFS, doing genetic analysis, screening victims and control groups, imagine how much more motivated to get this information as soon as possible that person might be?

[xptriado]

Androgen Receptor Polymorphism in Exon 1 and lupus in men and women, and diabetes type 1 autoimmune disease.

Additionally, shorter Androgen Receptor CAG (n) allelles associated with earlier onset of autoimmune diseases and severity of Reumathoid Arthritis.

Maybe we have an epigenetic AR change that predisposes to autoimmune disease. That would explain a lot.

endocrineconnections.com/content/3/2/99.full

Variation in the androgen receptor gene exon 1 CAG repeat correlates with manifestations of autoimmunity in women with lupus

ncbi.nlm.nih.gov/pubmed/23388696

In conclusion, the androgen receptor (CAG)n polymorphism is not related to the development of SLE, but it could modulate the severity of the lupus chronic damages as well as the androgen levels in women.

connection.ebscohost.com/c/artic … thematosus

Expression of Humoral Autoimmunity is Related to Androgen Receptor CAG Repeat Length in Men with Systemic Lupus Erythematosus

researchgate.net/publicatio … _Arthritis

The results suggest the association of short AR (CAG)(n) alleles with earlier onset and a more aggressive course of RA.

eje-online.org/content/149/6/597.full.pdf

Androgen receptor gene exon 1 CAG repeat polymorphism in Finnish patients with childhood-onset type 1 diabetes

ncbi.nlm.nih.gov/pubmed/22466402

Shorter AR (CAG)n repeats may predispose for younger AD onset.

[Dubya_B]

@xptriado

@Dubya_B

-“Exon 1” might refer to the actual gene, or the corresponding RNA transcript.

-Exon 1 of the AR gene contains DNA/RNA coding for a ligand binding domain and a region responsible for dimerization of 2 recptors after nuclear localization.

Dubya does this invalidate what you said or is it still valid?

AR Exon 1 encodes the entire 538 amino acid AR NH2-terminal domain (NTD), exons 2 and 3 each encode one of the two zinc fingers constituting the 89 amino acid DNA binding domain (DBD), and exons 4–8 encode the 292 amino acid COOH-terminal domain (CTD) [13].

hindawi.com/journals/au/2012/781459/

Yeah, what I said is invalid, as a a matter of fact. I mistook “activation function domain” as describing the ligand binding domain.

Exon1 encodes 2 trans-activation domains and there is a naturally occurring isoform (AR-A) that is missing the amino acids encoded by exon1, but found to be created sometime after protein translation.

https://en.wikipedia.org/wiki/Androgen_receptor#Isoforms

Isoforms

Two isoforms of the androgen receptor (A and B) have been identified:[28]

[b]AR-A[/b] - 87 kDa - N-terminus truncated (lacks the first 187 amino acids), which results from in vitro proteolysis.[29]
[b]AR-B[/b] - 110 kDa - full length

Domains

Like other nuclear receptors, the androgen receptor is modular in structure and is composed of the following functional domains labeled A through F:[30]

[b]A/B)[/b] - N-terminal regulatory domain contains:[31]
    activation function 1 (AF-1) between residues 101 and 370 required for full ligand activated transcriptional activity
    activation function 5 (AF-5) between residues 360-485 is responsible for the constitutive activity (activity without bound ligand)
    dimerization surface involving residues 1-36 (containing the FXXLF motif where F = phenylalanine, L = leucine, and X = any amino acid residue) and 370-494, both  of which interact with the LBD in an intramolecular[32][33][34] head-to-tail interaction[35][36][37]
[b]C)[/b] - DNA binding domain (DBD)
[b]D)[/b] - Hinge region - flexible region that connects the DBD with the LBD; along with the DBD, contains a ligand dependent nuclear localization signal[38]
[b]E)[/b] - Ligand binding domain (LBD) containing
    activation function 2 (AF-2), responsible for agonist induced activity (activity in the presence of bound agonist)
    AF-2 binds either the N-terminal FXXFL motif intramolecularly or coactivator proteins (containing the LXXLL or preferably FXXFL motifs)[37]
    A ligand dependent nuclear export signal[39]

F) - C-terminal domain

The AR-A form is more highly expressed in “non-androgenic” tissues:

A and B forms of the androgen receptor are expressed in a variety of human tissues
http://www.sciencedirect.com/science/article/pii/0303720796038191

Androgen receptor isoforms AR-A and AR-B display functional differences in cultured human bone cells and genital skin fibroblasts
http://www.sciencedirect.com/science/article/pii/S0039128X03001831

[xptriado]

this is interesting… so basically AR-B is the one which should be mutated/silenced.

Any idea why LH normally isnt elevated in PFS patients? i think this should be the case if we have PAIS

[douglasmich]

If a epigenetic change is caused by wrong lifestyle or psychologic factors or a vice like abuse of some products you can reverse this changes by doing oposite. But if our epigenetic changes was caused by a chemical drug you can change this also with chemical drug, or a natural supplement that will interact at the level where damage was made. It is unlikely that a diet or changed lifestyle will reverse chemical induced epigenetic changes in so deep level. We need to know the cause and mechanism.

[zadig777]

why did no one invest money in this?
this is the most promising research,yet people are sleeeping
great…

[Greek]

Perhaps @moonman1 can let us know what happened.

[Ukguy82]

@xptriado

Any idea why LH normally isnt elevated in PFS patients? i think this should be the case if we have PAIS

Unusually amongst pfs patients my LH is high.

[moonman1]

Actually, AWOR talked me out of doing it. When I talked to him about this he responded with what is below. Do I regret following his advice? This was 3.5 years ago soo…Absolutely

This is absolute nonsense and a stupid idea. What are you expecting from this? This is exactly the line of investigation that is going on with the WBH (Harvard) study and Baylor. The cost of these studies are in the significant six digit arena (each). The reason we have founded the PFS Foundation is not only to finance but also to make sure that studies are working together in the highest degree of synergies possible.

If you want to help yourself, please help us by donating this money to the Foundation instead of trying to set up your own set up studies. We need to focus resources, and I am shocked that some PFS patients still don’t seem to get that.

It is possible that the results from the current investigations will create new questions which will require further investigation and money. If you guys go blowing your cash on some side track, this may well be the funds that will be missing to keep on moving on the main road.

Think about this again please…

Awor

[Greek]

Thabks for replying @moonman1. Awor’s point makes a lot of sense.

That the Baylor study has taken so long is disappointing, but ultimately, the amount of data that they are dealing with is, I believe, the reason.

Early next year we will have a LOT of data to work with.

Our own survey, the Baylor results and our 23andMe project would all inform our next steps and our ability to make extensive plans.

I can’t help but wonder what might have shown up, but I’d also say Awor’s message is even more important right now.

Unless you’ve won the lottery? Have you? I hope you have.

[kon93]

same, my LH came above range

[zadig777]

@moonman1 u should try to gather money again i think
although if its on dna methylation level we dont have agents to affect it
if its rna lvl there is a way

[zadig777]

awor aint god lol
why u all follow him so blindly omg…

[Dubya_B]

Some people spend the time and effort to develop a deep understanding of possible mechanisms behind persistent side effects.

Some people network with scientists and patient groups to help found a charitable organization devoted to funding research toward a deeper understanding of the mechanisms behind persistent side effects.

Some people put forth the time and effort to maintain a nice forum where those affected can vent, discuss their futures, and entertain themselves talking about treatments that usually don’t work.

That deserves a little bit of respect at least, don’t you agree?

[vkg1]

Everyone here should be contributing as much as they can afford to anything that advances us toward a cure. That’s the only way one will arrive. The best way to do that is probably by donating to the foundation, though other ways are good too, of course.

Sadly, I could easily see people here thinking that just because there are many of us then someone else surely must be forking over the cash (i.e. bystander effect). That’s an illusion. It’s up to each and every one of us to do our part.

There is not someone else who is going to do it for us. Helping a bunch of otherwise relatively well-off (ie could afford to indulge in taking hairloss drugs) men get their masculinity back is almost certainly at the bottom of the list of priorities of the medical community in the current sociopolitical climate.

The relative unpopularity of our demographic is also a reason why it’s essential we unify our cause with the PAS and PSSD groups (since they’re also comprised of women and children). But that’s another matter.

[zadig777]

ur not pragmatic enough
those “some people” may contribute years in vain
if i came here with a cure and a moronic attitude as i have,would u care about thr cure or the morronic attitude?
those some people tried 40 sec half life drug to demethylate their dna and those wide people discourage things like this so that’s it
so u should think about this also

[Northern_Star]

But those “people” did not contribute in vain. They put in a lot of research, created a theory that largely explains our condition, approached scientists to discuss the theory, convinced scientists that this theory holds merit and that the condition is worth exploring, created a foundation to fund studies into our condition and initiated ongoig studies by top class researchers. These “people” are the main reason that our condition is on the map, that we have the foundation and that there are serious investigations ongoing. That does not make them infallible, but it surely should buy a lot more credit than you are giving here. You are conveniently ignoring all this and go on about a failed experiment from 8 years ago, while adding very little yourself aside from a shitty attitude.

In addition to all the above, Awor is right. There is no reason for individuals going their own ways all the time. We need a coordinated effort to avoid duplicate work and to make sure that each step builds on previous steps and is supported by professionals who know what they are doing.