Invest in ME Conference 12: First Class in Every Way
OverTheHills wraps up our series of articles on this year's 12th Invest in ME International Conference (IIMEC12) in London with some reflections on her experience as a patient attending the conference for the first time.
Discuss the article on the Forums.

Community Symposium on molecular basis of MECFS! DISCUSSION THREAD!

Discussion in 'Latest ME/CFS Research' started by Ben H, Aug 9, 2017.

  1. Ben H

    Ben H OMF Correspondent

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    From the separate thread but thought all here would like to see the culmination as it were of the Symposium:


    Here is a roundup of the amazing MECFS17 Community Symposium that many of you watched and commented on :)


    [​IMG]
    [​IMG]
    Open Medicine Foundation (OMF)

    [​IMG]


    Ron Davis Gets Standing Ovation!
    Very rare for a scientific presentation!

    August 12 was an amazing day at OMF’s Community Symposium on the Molecular Basis of ME/CFS at Stanford University. The room was buzzing with positive energy. The researchers' presentations were incredible and showed great insights into this disease. There were renowned scientists from all over the world, and from related fields revealing interesting new insights into ME/CFS research. Patients, caregivers, clinicians, and other researchers attending interacted with these scientists during breaks, lunch and an evening reception, and there was so much excitement and optimism in the room.

    Here are some of the highlights from this amazing meeting (stay tuned for more!):
    • Additional comprehensive evidence that ME/CFS is a molecular disease was presented.(Yet another nail in the PACE coffin!)

    • Experts in metabolism, immunology, genomics, neurophysiology, electrical engineering and bioinformatics presented data.

    • We learned about innovative ways to find new pain drugs and saw elegant evidence of a clear connection between the immune system and the brain.

    • The scientists decided to continue as a “Working Group”, and are already planning multiple new ways to work together to facilitate and accelerate progress.

    • Nobel laureate Mario Capecchi noted how important patient participation is in studying any disease, and how impressed he was with the amount of ME/CFS patient participation!

    • In Ron Davis’ concluding remarks he stated that it is clear that what is missing is funding. He described ME/CFS as “a horribly underfunded disease”. Progress has been impressive despite the limited resources, but it is clear that more funding is needed to unravel this mystery and find treatments and a cure fast.
    We need your help to accelerate the pace!

    Every Donation of Every Size Brings Us Closer to A Cure.
    To End ME/CFS, the world is counting on brilliant researchers working collaboratively.

    If you have ever thought to donate to our End ME/CFS project, NOW IS THE TIME! We need to keep the momentum going and leverage the expanding interest in finding a cure.

    Thank you for giving what you can today.

    Sincerely,


    [​IMG]
    Linda Tannenbaum
    CEO/President

    PS - Please forward this message to family and friends. Encourage them to join you in your support of OMF's research for treatments and a cure.



    Thanks guys,


    B

    @Janet Dafoe (Rose49) @AshleyHalcyoneH
     
  2. AndyPR

    AndyPR Senior Member

    msf, soofke, TrixieStix and 7 others like this.
  3. Kati

    Kati Patient in training

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    The like button is too mild here, we need ♥️
     
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  4. MeSci

    MeSci ME/CFS since 1995; activity level 6?

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    :heart: (It comes under "more")
     
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  5. RuthT

    RuthT

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    Hi. New on the forum, and think menopause was part of the cluster of stuff, including a viral illness that triggered a renewed episode (first in 1990s) going on for 2 years now.
     
  6. Janet Dafoe (Rose49)

    Janet Dafoe (Rose49) Board Member

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    Roy S, soofke, Starlight and 24 others like this.
  7. Nickster

    Nickster Senior Member

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    True emotion. What a momentous occasion! Look how far you have come and how far you will continue to go.
    Thank you!
     
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  8. ash0787

    ash0787 Senior Member

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    I did not see every section of the talk, was there any mention of a plan to mass produce the nano needle thing ? could patients buy one to prove to disbelievers there is something fundamentally different ? or would it be useless without a cell seperation machine and various other laboratory tools to hand ?

    Also any plans to treat whitney in the short term ? suramin or something ? I think I heard ritximab did not help
     
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  9. CFS_for_19_years

    CFS_for_19_years Hoarder of biscuits

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    As has mine. Very noticeable decline.:(
     
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  10. valentinelynx

    valentinelynx Senior Member

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    :hug:
     
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  11. valentinelynx

    valentinelynx Senior Member

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    :rofl: I can see that now. However, I'm pretty sure she's wiping away tears of gratitude...
     
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  12. mariovitali

    mariovitali Senior Member

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    @Janet Dafoe (Rose49)

    As discussed in our messages, i am sending you the latest findings. i would kindly ask from Dr Davis to review this information.


    cc : @JaimeS @A.B. @Snow Leopard @alex3619 @Jonathan Edwards

    I am CC ing you because i feel that -hopefully- this is a very important post.

    The role of Endoplasmic Reticulum Stress, Myosins, Liver X Receptor, Unfolded Protein Response , Autophagy, TAM Receptors, D3 (CYP27A1 and GC Genes) and T Cells activation.

    Some excerpts :


    Regarding VDBP/ GCMAF according to [6] :

    VDBP, a glycosylated-globulin, plays an important role not only in transporting vitamin D and circulating metabolites, but also in other biological functions to affect carcinogenesis. It is a member of the circulating actin scavenger system that prevents formation of F-actin networks and harmful effects following from cell or tissue damage12. VDBP is involved in macrophage activation by converting as group-specific component protein derived macrophage activating factor (GcMAF) and neutrophil chemotaxis by enhancing the chemotactic effect of complement-derived peptides

    LXR Receptor - TAM Receptors - T Cells

    From [1] we read :

    “Additionally, cholesterol-dependent activation of Liver X receptor (LXR) transcription factors has been shown to upregulate the expression of Mer in macrophages as a positive feedback mechanism promoting engulfment of apoptotic cells and immunosuppression

    “Thus, TAM receptors are responsible for creating an anti-inflammatory and reparative setting around apoptotic sites that prevents inflammatory responses towards self-derived antigens and restores tissue homeostasis.”


    TAM receptors regulate the bilateral communication between dendritic and lymphoid T cells in different immunostimulatory conditions. Once activated, adaptive immune cells must communicate back with innate cells to avoid uncontrolled and chronic activation of the immune system”

    You may also see the Liver X Receptor in Network Analysis here (posted on May 2017) :

    [​IMG]


    MYOSINS

    Please note : The first mention of MYO9B on Phoenix Rising :


    http://forums.phoenixrising.me/inde...e-treatment-for-cfs.37244/page-85#post-759322


    Myosins comprise a superfamily of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other motility processes in eukaryotes. They are responsible for actin-based motility

    In [3] we find yet another association of MERTK with phagocytosis and Myosin :


    Mertk can drive redistribution of dynamic protein, myosin II, from F-actin bundles to the sites of phagocytic cup [27]. A large body of evidence shows that Mertk plays an essential role in phagocytosis through activation of its downstream signaling which is critical for cytoskeletal rearrangement during phagocytosis.”

    Interestingly, MYO9B is also found to be associated with impaired Phagocytosis as found in [5] :

    “The rapid recruitment of phagocytic cells to inflammatory “hot spots” is a basic function of the innate immune system. Given the profound effect of Myo9b deficiency on membrane protrusive activity and motility, it would be reasonable to expect that monocyte recruitment is impaired in vivo. Indeed, we found that the accumulation of monocytes and macrophages in the peritoneal cavity of Myo9b−/− mice intraperitoneally injected with the chemoattractant C5a was severely blunted. Hence, Myo9b clearly has an important function in innate immune responses. Another essential function of professional “big eaters” such as macrophages is phagocytosis. Rho-family GTPases are intimately involved in controlling the cytoskeletal dynamics during phagocytosis (44), and we would predict that Myo9b is also important for the local coordination of membrane extensions and particle internalization.”


    It is time now to look at the involvement on how Endoplasmic Reticulum Stress, Misfolded Proteins and the Unfolded Protein Response is pertinent to the information shown above :


    According to [8] :

    In response to the challenge of misfolded proteins, autophagy has a crucial function as an adaptive ‘self-eating’ process by which cellular components are encapsulated within autophagosomes and degraded. Similarly to the unfolded protein response (UPR), autophagy can result in either cell survival or cell death167,168. The mechanisms by which the UPR induces autophagy are incompletely understood, but probably involve signalling through PKR-like ER kinase (PERK)–eukaryotic translation initiation factor 2α (eIF2α) and inositol-requiring enzyme 1α (IRE1α)169.


    Relevant Genes :


    GAS6 , MERTK, GGCX, VKORC1,TYRO3,PLCG1, FASLG, MYO9B, SH2B3, RHOA,PROS1,GC,NR1H3, CYP27A1, NR1H4


    Example run using Machine Learning : We notice how the ML Algorithm identifies Liver disease, FAS Ligand, Phagocytosis, T Cells, Vitamin D3 as relevant.

    [​IMG]
    [​IMG]

    Original post : http://algogenomics.blogspot.com/2017/08/new-findings-myosin-d3-actins.html



    References



    [1]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5082387/

    [2] : https://www.ncbi.nlm.nih.gov/pubmed/25624460

    [3]: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0117787

    [4] : http://www.rug.nl/research/portal/p...on(4efdb8a4-b704-4d42-8ea2-f9d875ddab89).html

    [5] : http://www.pnas.org/content/107/27/12145.full

    [6[ : https://www.nature.com/articles/srep07956

    [7] : https://www.ncbi.nlm.nih.gov/pubmed/10891358

    [8] : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310224/
     
    Last edited: Aug 19, 2017
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  13. Janet Dafoe (Rose49)

    Janet Dafoe (Rose49) Board Member

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    I sent this to Ron.
     
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  14. Michael_venice

    Michael_venice

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    Mike VanElzakker talks about the same difficulty in how to look into the idea, because is not possible to biopsy the vagus.
     
  15. valentinelynx

    valentinelynx Senior Member

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    Indicates the necessity of autopsy studies of ME/CFS patients. I am ignorant in this area: what is the best way to increase the likelihood of one's body being donated for specific research purposes? Is there a pathway or pathways for donating to a tissue bank for ME/CFS study?
     
  16. mariovitali

    mariovitali Senior Member

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    I just received a message from a CFS/ Fibromyalgia patient saying that her Fibroscan has shown an F3 Fibrosis stage. (8.6 kPa). She will send me the actual test results later today and i will post them,.


    @Janet Dafoe (Rose49)

    I am quoting you only if i believe that it is absolutely necessary. I will post one more important (brand new) piece of Information - shortly after this. Please forward to Dr Davis :



    From [1] , see References at bottom:



    DATE : December 1st 2005

    https://link.springer.com/article/10.1186/1471-2377-5-22




    You will also recall we discussed about Actins in : http://algogenomics.blogspot.com/2017/08/new-findings-myosin-d3-actins.html


    A Google search in Phoenix Rising finds this :

    Link :

    http://phoenixrising.me/research-2/...irleir-m-d-ph-d-crc-press-washington-d-c-2002

    We note "actin fragmentation" and gelsolin is being mentioned. But apparently MERTK comes to the rescue :


    http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0117787




    References

    [1] : Autophagy, Volume 8, ISBN: 978-0-12-802937-4
     
  17. soofke

    soofke

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    Dutchy
    since I seem to be overlooked on twitter, and here, I'm throwing my bodyparts in the mix ;)

    [​IMG]

    this is happening all along the nervus vagus or HPA-axis or whatever it's called, in my brain it's releasing neurotransmitters, it started after (alternative) treatment of several common bugs, ergo my ME is a blockage of nerve endings, or rather was because I'm improving slowly but steadily
     
    mattie and MEMum like this.
  18. mariovitali

    mariovitali Senior Member

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    Just received the following Fibroscan from a CFS Patient. Yet one more patient with Liver Fibrosis (this one is F2)

    See attached file (sorry for the duplicate file)

    Has anyone else here performed a Fibroscan?
     

    Attached Files:

    Last edited: Aug 23, 2017
  19. msf

    msf Senior Member

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    I might be wrong, but I don´t think the HPA axis is actually a physical axis.
     
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  20. soofke

    soofke

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    Dutchy
    well it is now :p
     
    Last edited: Aug 24, 2017

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