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Fidelity of target site duplication and sequence preference during XMRV integration

G

Gerwyn

Guest
I do not recall Germany doing a study on ME/CFS and XMRV. When was that published?

They did not it was for prostate cancer only.they have re presented the study as being new but it was published last Nov.I have highlighted the already published material on the Prague presentation thread if it helps
 

citybug

Senior Member
Messages
538
Location
NY
The science is excellent.It is what I have been hoping for. XMRV was originally found inserted within CREB genes.CREB genes are regulatory genes which affect systems all over the body. I have the hypothesis that XMRV does irs dirty work by causing the creb gene to malfunction.Untill this paper there was no actual evidence that XMRV could affect the CREB gene in this way.Insertional mutagenesis is such a mechanism.Xmrv can act as a duplication mutation or a deletion.Either way the proteins formed from CREB would be abnormal and affect their regulatory function.with this paper at last we have a mechanism how such a "simple" virus could cause multi systemic disease.We have an explanatory model ...

Ok this is my take home message(s)

Our automatic body processes are contolled by the autonomic nervous system.If this becomes dysfunctional then we are left with the neuroendocrine symptoms of ME sensitivity to lights sound ,high resting heartrate POTs poor temperature control and so on.The organic thermostat that controls all these functions is the hypothalamus.When any function such as heart rate strays outside the normal range this is detected by the hypothalamus and brought back into normal ranges by the action of the pituitaty gland and the Adrenal cortex(and medulla).If this control system breaks down our autonomic functions go haywire.

The "molecular thermostat" of the immune system is the NFATgene (amoung others).By inserting into this gene XMRV can act as a "molecular dimmer switch" for this gene and affect the levels of its activity and in turn the levels of various chemical components of the immune system

One eample would be that if the NFAT gene was upregulated by the "dimmer switch" being turned up then the level of circulating cytokines would be high.There would be chronic levels of inflammation in multiple body systems

This leads to a number of pretty horrible consequences.

Raised levels of abdominal fat

Impaired Glucose tolerance and increased insulin resistance

Altzheimers type symptoms and cardiovascular abnormalities increase risk of stroke and pots type symptoms impaired blood flow to brain.

these cytokine levels(interferon and interleukins) can lead to metabolic syndrome.

Raised interferon levels lead to hyper stimulation of TFN alpha gene. This can lead to high levels of Nitric oxide which in turn depletes glutathione directly and indirectly damaging mitochondria and creating a partial block in the methylation cycle.

Raised TFN alpha leads to muscle fatigue and pain .This also reduces BDFN gene expression(also caused by blocking creb) reducing fat oxidation and further compounding problems with fatigue cognitive problems like memory dyscalculia dyslexia and so on

CREB and NFAT co regulate each other just to make life really interesting!!!!

This is such a clear explanation. Are you or natasa really working on an article? It would be great to have an Explanatory Model, or Working Hypothesis of the effects of XMRV as an article, or for much bigger publication. I would think it would get a lot of doctors and patients behind the research.