Choline on the Brain? A Guide to Choline in Chronic Fatigue Syndrome
http://phoenixrising.me/research-2/the-brain-in-chronic-fatigue-syndrome-mecfs/choline-on-the-brain-a-guide-to-choline-in-chronic-fatigue-syndrome-by-cort-johnson-aug-2005
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Community Symposium on molecular basis of MECFS! DISCUSSION THREAD!

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

  1. A.B.

    A.B. Senior Member

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    @Janet Dafoe (Rose49) has Ron tried insulin or amino acids to see if they normalize results on the impedance test? The basic idea is to activate mTOR which is activated when there are nutrients.
     
  2. necessary8

    necessary8

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    I would actually very much like to hear about all the things Ron tried in that test which failed to bring any change - it could tell us just as much as the successes
     
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  3. mariovitali

    mariovitali Senior Member

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    @Janet Dafoe (Rose49)
    CC: @JaimeS @adreno

    Please forward this to Ron, i believe that this post gives some interesting hypotheses. In the end of this post you will find a list of gene names that i would kindly ask you to check with your CFS Cohorts. I have a list ready that i can share with you.

    See the following Network Analysis diagram where PPARalpha, PPARgamma, LXR, Oxysterols and CYP27A1 are shown :

    network6.png

    In essence, Network Analysis identifies Topics that are part of the pathway starting from CYP27A1, the subsequent creation of Oxysterols that activate LXR Receptor through PPARa and PPARg and as a consequence upregulate MERTK and GAS6. Importance of MERTK and GAS6 and its association with ER Stress, Autoimmunity and Phagocytosis were discussed in previous posts.


    Let' s hypothesise now regarding the importance of LXR,CYP27A1, Oxysterols and PPARs and see why they are being selected by the Algorithm :

    According to [1], regarding PPARs and LXR :

    "Peroxisome proliferator-activated receptors (PPARs) and (liver X receptors) LXRs are ligand-activated transcription factors that control lipid and glucose metabolism, as well as the inflammatory response. Because the macrophage plays an important role in host defense and immuno-inflammatory pathologies, particular attention has been paid to the role of PPARs and LXRs in the control of macrophage gene expression and function. Research over the last few years has revealed important roles for PPAR-α , PPAR-γ , and LXRs in macrophage inflammation and cholesterol homeostasis with consequences for atherosclerosis development"

    1) We note : Inflammation and Macrophages


    We will now try to hypothesise as to why Oxysterols and CYP27A1 appear as being central in the Network Graph.



    According to Wikipedia :

    "Oxysterols are oxidized derivatives of cholesterol, which may be important in many biological processes, including cholesterol homeostasis, atherosclerosis, sphingolipid metabolism, platelet aggregation, apoptosis, and protein prenylation"

    Additionaly, Oxysterols activate the LXR Receptor and bind and activate Chemokine receptors which belong to the family of the G-Protein Coupled Receptors [5]


    2) We note mentions on : G-Protein Coupled Receptors, Platelet aggregation, Sphingolipid Metabolism and the fact that Oxysterols interact with LXR

    In Naviaux et al [8] ,low levels of sphingolipids were found. Interestingly, LXR up-regulates Sphingolipid biosynthesis in hepatic cells [9]

    Furthermore in [5] we find associations of Oxysterols with :


    a) B and T Cells


    b) Specific G Protein-Coupled Receptors. As an example, we read that : "In addition to LXR-dependent mechanisms, oxysterols regulate crucial innate and adaptive immune cell functions through the engagement of GPCRs. For example, the oxysterol 7α,25-OHC can bind and activate the GPCR Epstein–Barr virus-induced 2 (EBI2), which is upregulated on B cells and T cells under specific conditions"


    c) MERTK, GAS6 (discussed in previous posts) since Oxysterols activate LXRα and LXRβ and both isoforms induce Mertk


    Moving forward now to the importance of CYP27A1 and CH25H.


    In [6] we read :

    "Cholesterol and components of the cholesterol biosynthetic pathway have fundamental roles in all mammalian cells. Hydroxylated forms of cholesterol are now emerging as important regulators of immune function. This involves effects on the cholesterol biosynthetic pathway and cell membrane properties, which can have antiviral and anti-inflammatory influences. In addition, a dihydroxylated form of cholesterol functions as an immune cell guidance cue by engaging the G protein-coupled receptor EBI2, and it is required for mounting adaptive immune responses. In this Review, we summarize the current understanding of the closely related oxysterols 25-hydroxycholesterol and 7α,25-dihydroxycholesterol, and the growing evidence that they have wide-ranging influences on innate and adaptive immunity."



    According to Wikipedia, CYP27A1 is required for the production of Oxysterol 27-HC :



    "27-Hydroxycholesterol (27-HC) is an endogenous oxysterol with multiple biological functions, including activity as a selective estrogen receptor modulator (SERM) (a mixed, tissue-specific agonist-antagonist of the estrogen receptor(ER) and as an agonist of the liver X receptor (LXR). It is a metabolite of cholesterol that is produced by the enzyme CYP27A1"

    In one of the first posts in my Blog, the importance of Bile Acid metabolism (as suggested by Machine Learning) was discussed. According to [7], CYP27A1 is the rate-limiting enzyme in the alternative bile acid synthetic pathway, and is also responsible for the side chain oxidation in the classic bile acid synthetic pathway :

    bileacids.jpg


    Please check the following genes in your cohorts: CYP27A1, LXR, PPARa, PPARg, GPR183, CH25H, HSD3B7

    Original post : http://bit.ly/2eIJIdb



    References
    [1]: https://www.ncbi.nlm.nih.gov/pubmed/18323516

    [2] : http://phoenixrising.me/research-2/rnase-l-deregulation-in-chronic-fatigue-syndrome/a-laymens-guide-to-chapter-six-of-chronic-fatigue-syndrome-a-biological-approach-edited-by-patrick-englebienne-ph-d-kenny-demeirleir-m-d-ph-d-crc-press-washington-d-c-2002

    [3] : https://www.ncbi.nlm.nih.gov/pubmed/21767321

    [4]:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3061224/

    [5]: http://onlinelibrary.wiley.com/doi/10.1002/eji.201344292/full

    [6] : http://www.nature.com/nri/journal/v14/n11/full/nri3755.html

    [7] : https://www.hindawi.com/journals/ppar/2009/501739/

    [8] : http://www.pnas.org/content/113/37/E5472.full

    [9] : https://www.sciencematters.io/articles/201611000022
     
    Last edited: Sep 1, 2017
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  4. mariovitali

    mariovitali Senior Member

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    @Janet Dafoe (Rose49)


    CC: @adreno @JaimeS @Snow Leopard


    There will be two more posts which will conclude my hypothesis on what is happening to CFS/ME and several other Syndromes. I am sending the information in parts because otherwise it may be difficult to follow.

    Please forward to Ron the following information. Also i would kindly ask from @Jonathan Edwards to comment below

    Professor Edwards, i am well aware that you do not agree with this kind of analysis but i would kindly ask you to comment if you believe that Dysregulation of the Pathways discussed (Bile Acids, LRX Receptor, ER Stress) due to a Liver stressor such as certain medications and viruses have the potential to dysregulate Immune function as seen in CFS.



    The original post can be read here : http://bit.ly/2vWvjQ7


    Beginning of post :

    It should be stressed that according to the hypotheses being generated by these methods it appears that there is a combination of factors at play. So far we presented many of these factors such as Bile Acid Homeostasis, Apoptosis of Cells, Endoplasmic Reticulum Stress, The Unfolded Protein Response, Myosins, etc).

    Please see below the following figure which is taken from a paper called "Impaired clearance of apoptotic cells in chronic inflammatory diseases: Therapeutic implications" : [1]



    fig1.png


    We now look at the same Figure but we annotate with a blue rectangle the Topics presented in this Blog that were selected with Machine Learning and / or Network Analysis. In red rectangles we have topics that were not selected by these methods as most of them have not been part of the input data (apart from Retinoids and RXR Receptor) :


    figure-annot.png


    We immediately see well known Topics as these were previously presented : PPARs, LXR, MERTK, Phagosomes, Macrophages, Actin, Phagocytosis, Oxysterols, Protein S (PROS1), GAS6 .

    We now look at some of the topics that are being annotated with a Red rectangle :





    -DOCK180/DOCK1



    According to [2] :



    "This gene encodes a member of the dedicator of cytokinesis protein family. Dedicator of cytokinesis proteins act as guanine nucleotide exchange factors for small Rho family G proteins. The encoded protein regulates the small GTPase Rac, thereby influencing several biological processes, including phagocytosis and cell migration. Overexpression of this gene has also been associated with certain cancers."



    -ELMO1



    According to [3] :



    "The protein encoded by this gene interacts with the dedicator of cytokinesis 1 protein to promote phagocytosis and effect cell shape changes"



    and more importantly, let's look at what happens if a combination of mutations on both sites occurs :



    "Mutation of both interaction sites for DOCK180 on ELMO1 will lead to the disruption of the ELMO1-DOCK180 complex. ELMO1 complexed with both DOCK180 and CrkII leads to maximal efficiency of phagocytosis in the cell. This complex of molecules happens upstream of Rac during phagocytosis"


    -STAB2 (Stabilin-2)


    In [4] we find that Stabilin 2 is highly expressed in sinusoidal endothelial cells of liver, spleen and lymph nodes and interacts with GULP1 (also shown in the figure).



    In [2] we read :


    "Phagocytic receptors activate two evolutionary conserved pathways both converging on the activation of Rac-1, a small GTPase (45) (Figure 1). The first pathway is initiated by MerTk or integrin av/b5 receptors (46, 47), resulting in association of the adaptor protein ELMO with the Rac GEF DOCK180 forming a bipartite GEF (48). Recruitment of the ELMO/DOCK180 complex to the cell membrane might require the adaptor protein CrkII, but binding of ELMO to the carboxyl terminus of BAI1 also recruits DOCK180 to the phagocytic membranes (33). The second pathway activating the Rac is initiated by LRP1 (CD91) (49) or by stabilin-2 receptors followed by recruitment of the adaptor protein GULP"


    Therefore we see that we two different pathways exist that they ultimately activate Rac-1 (RAC1) :

    The first pathway involves : MERTK, ELMO1/DOCK180 and the second pathway uses CD91 or STAB2 and subsequently GULP





    -CD91/LRP1



    From [5] we read :



    "LRP1 is a member of the LDLR family and ubiquitously expressed in multiple tissues, though it is most abundant in vascular smooth muscle cells (SMCs), hepatocytes, and neurons.[8][9] LRP1 plays a key role in intracellular signaling and endocytosis, which thus implicate it in many cellular and biological processes, including lipid and lipoprotein metabolism, protease degradation, platelet derived growth factor receptor regulation, integrin maturation and recycling, regulation of vascular tone, regulation of blood brain barrier permeability, cell growth, cell migration, inflammation, and apoptosis, as well as diseases such as neurodegenerative diseases, atherosclerosis, and cancer"



    -Retinoids



    According to [1] :



    "Following engulfment, apoptotic cell derived lipids (oxysterols and fatty acids) trigger the lipid-sensing LXR and PPAR receptors leading to enhanced retinoid production. Retinoid receptors together with LXR and PPARs upregulate a number of phagocytic receptors to further enhance the engulfing capacity of macrophages under conditions when the rate of apoptosis is increased."



    As previously discussed, Retinoids and RXR have not been selected by any Algorithm or Network Analysis. However, it appears that they may be playing an important role to the Syndromes mentioned here particularly since they interact with LXR and PPARs.





    -SCARF1



    In [6] we read the following :



    "The clearance of apoptotic cells is critical for the control of tissue homeostasis; however, the full range of receptors on phagocytes responsible for the recognition of apoptotic cells remains to be identified. Here we found that dendritic cells (DCs), macrophages and endothelial cells used the scavenger receptor SCARF1 to recognize and engulf apoptotic cells via the complement component C1q. Loss of SCARF1 impaired the uptake of apoptotic cells"


    and :


    "Consequently, in SCARF1-deficient mice, dying cells accumulated in tissues, which led to a lupus-like disease, with the spontaneous generation of autoantibodies to DNA-containing antigens, activation of cells of the immune system, dermatitis and nephritis. The discovery of such interactions of SCARF1 with C1q and apoptotic cells provides insight into the molecular mechanisms involved in the maintenance of tolerance and prevention of autoimmune disease."



    We therefore further hypothesise that Genes being mentioned here could also be important to the syndromes discussed but also -given specific combinations of mutations- to several other diseases as well.




    References





    [1] : https://www.ncbi.nlm.nih.gov/pubmed/25136342



    [2] : http://www.genecards.org/cgi-bin/carddisp.pl?gene=DOCK1&keywords=DOCK180



    [3] : https://en.wikipedia.org/wiki/ELMO1



    [4] : http://www.uniprot.org/uniprot/Q8WWQ8



    [5] : https://en.wikipedia.org/wiki/LRP1



    [6] : http://www.nature.com/ni/journal/v14/n9/full/ni.2670.html
     
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  5. Jill

    Jill Senior Member

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    I'm sorry , I'm not sure where to put this article. It is about exercise - endothelial function and I thought it may be useful for someone to contact this research group in Leeds if it's of any relevance . Moderators please move if it should go somewhere else. Am more disabled than usual and using a new device so technically challenged somewhat too! Thanks
     

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  6. mariovitali

    mariovitali Senior Member

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    @Janet Dafoe (Rose49) one more for Ron, we are getting there :)


    I would like now to describe the potential importance of Sulfation to CFS/ME (and several other syndromes) . We look at :

    -Heparan Sulfates and the importance of Syndecans (more specifically Syndecan-2)
    -Connection of Sulfation with CD8+ T-Cells (through DHEAS and also SULT2B1+LXR)

    I would also like to confirm that Suramin was recently added and has been selected algorithmically as being relevant :

    algorun3.png


    You can see the original post here : http://bit.ly/2wETpRA


    In [1] we read :

    "Sulfation is involved in a variety of biological processes, including detoxification, hormone regulation, molecular recognition, cell signaling, and viral entry into cells. It is among the reactions in phase II drug metabolism, frequently effective in rendering a xenobiotic less active from a pharmacological and toxicological standpoint, but sometimes playing a role in the activation of xenobiotics (e.g. aromatic amines, methyl-substituted polycyclic aromatic hydrocarbons). Another example of biological sulfation is in the synthesis of sulfonated glycosaminoglycans, such as heparin, heparan sulfate, chondroitin sulfate, and dermatan sulfate. Sulfation is also a possible posttranslational modification of proteins"


    Bile Acids (the importance of was discussed in previous posts) are transformed to a less toxic form through Sulfation [2].



    The Wikipedia entry on Sulfation talks about Heparan sulfate which deserves a closer inspection :



    In [2] we read :



    "The heparan sulfate chains due to their vast structural diversity are able to bind and interact with a wide variety of proteins, such as growth factors, chemokines, morphogens, extracellular matrix components, enzymes, among others. There is a specificity directing the interactions of heparan sulfates and target proteins, regarding both the fine structure of the polysaccharide chain as well precise protein motifs. Heparan sulfates play a role in cellular signaling either as receptor or co-receptor for different ligands, and the activation of downstream pathways is related to phosphorylation of different cytosolic proteins either directly or involving cytoskeleton interactions leading to gene regulation."


    We note that Heparan sulfates are associated with cytosolic proteins involving cytoskeleton interactions. (The importance of proper cytoskeleton functioning was discussed in previous posts).



    Furthermore in [3] we read :



    "Heparan sulfate proteoglycans (HSPGs) are glycoproteins, with the common characteristic of containing one or more covalently attached heparan sulfate (HS) chains, a type of glycosaminoglycan (GAG) (Esko et al. 2009). Cells elaborate a relatively small set of HSPGs (∼17) that fall into three groups according to their location: membrane HSPGs, such as syndecans and glycosylphosphatidylinositol-anchored proteoglycans (glypicans), the secreted extracellular matrix HSPGs (agrin, perlecan, type XVIII collagen), and the secretory vesicle proteoglycan, serglycin"



    According to [4] Syndecan-2 (a subtype of Syndecans - Gene name SDC2 ) plays an important role for the actin cytoskeleton :

    "Syndecans, a family of transmembrane heparan sulphate proteoglycans, contribute to various biological processes, including adhesion, motility, proliferation, differentiation and morphogenesis. We document here the involvement of syndecan-2 acting alone or co-operatively with integrin alpha5beta1, for regulation of actin-cytoskeletal organization on cell adhesion to fibronectin, using fibronectin-recombinant polypeptides containing the ligands for either or both of these receptors as substrata. "


    We could then hypothesize that impaired Sulfation leads to impaired production of Heparan Sulfate ProteoGlycans which in turn affect Syndecans (and more importantly Syndecan-2 in our case).


    However Sulfation has yet one more important role : Oxysterol Sulfation. In [5] we read :


    "Oxysterol sulfation as a regulatory pathway has grown out of recent studies in the past seven years, including discovery of a novel oxysterol sulfate, identification of a key enzyme hydroxysterol sulfotransferase 2B1b (SULT2B1b) involved in oxysterol sulfate synthesis, and investigation into the role of oxysterol sulfates in regulation of lipid metabolism, inflammatory responses, and cell proliferation. Ten years ago, our laboratories began investigating the role of intracellular cholesterol transport proteins in the regulation of bile acid synthesis and cholesterol degradation (68,75). We found that bile acid synthesis via the acidic, “alternative”, pathway was limited by mitochondrial cholesterol uptake. This barrier could be overcome by increasing expression of the intracellular cholesterol transporter StarD1 (68,73,75). This suggests a physiological role for StarD1. Increases in StarD1 expression also led to upregulation of biliary cholesterol secretion and downregulation of cholesterol, fatty acid, and triglyceride biosynthesis"


    Gene SULT2B1 (of which SULT2b1b is an isoform) is -interestingly- associated with LXR. More specifically in [5] we read :


    "LXR signaling from proliferation, directly linking sterol homeostasis to the anti-proliferative action of LXR. Mice lacking LXRβ exhibit lymphoid hyperplasia and enhanced responses to antigenic challenge, indicating that proper regulation of LXR- dependent sterol metabolism is important for immune responses. These data implicate LXR signaling in a metabolic checkpoint that modulates cell proliferation and immunity"



    but more importantly we see a connection of LXR Receptor and Sterol Metabolism to regulate T Cell function :


    "Antigen-specific CD8+ T cells were enumerated ex vivo one week post immunization by intracellular IFN-γ and TNF-α staining after a short term in vitro restimulation with the E1B antigen E1B192-200 (VNIRNCCYI) (Toes et al., 1998). Remarkably, FACS analysis indicated that the frequency of antigen-specificLxrβ null IFN-γ + (p=0.02) or TNFα+ (p=0.01) CD8+ T cells was 2–3 fold higher than their WT counterparts (Fig. 7C,D). Thus, antigen-driven expansion of CD8+ T cells is negatively regulated by LXRβ in WT mice. Taken together, these data establish LXR-dependent sterol metabolism as a novel signaling pathway regulating T cell function and immune responses."


    In previous posts we discussed about the importance of CYP27A1. In [7] we read :


    "The rate-limiting step controlling CYP27A1 activity is the flux of cholesterol from the outer to the inner mitochondrial membrane, via a mitochondrial cholesterol trafficking complex (discussed below). Mitochondrial oxysterols therefore act as key cell signalling molecules, the levels of which can be moderated by sulfation (SULT2B1b), esterification (ACAT-1) or metabolism to soluble bile acid derivatives "

    So we have likely evidence of SULT2b1b being of particular importance for further investigation. Note also that SULT2b1b is responsible for Cholesterol Sulfate production.


    Moreover, SULT2A1 and SULT1E1 are responsible for sulfonation of DHEAS [6]. In [8] we find yet one more indirect association of Sulfation -because of DHEAS- with CD3+ and CD8+ T Cells : (@adreno Thanks)


    "There were significant and positive correlations between serum DHEAS and serum zinc and the mitogen-induced expression of the CD69 molecule on CD3+CD8+ T cells (an indicator of early T cell activation). There was a significant and negative correlation between serum DHEAS and the increase in the serum alpha-2 protein fraction (an inflammatory marker). Serum IGF1, but not DHEAS, was significantly and inversely correlated to age. The results show that CFS is accompanied by lowered levels of DHEAS and that the latter may play a role in the immune (defect in the early activation of T cells) and the inflammatory pathophysiology of CFS"

    Note that SULT2A1 sulfonates DHEA and Pregnenolone (among others), SULT2B1a sulfonates Pregnenolone and SULT2B1b is involved with Cholesterol Sulfonation [8]

    The following Genes are proposed for further investigation : STS, SULT1A1, SULT2A1, SULT2B1, STARD1,SDC2



    As discussed, Sulfation is an extensive subject which deserves a closer look in future posts.





    References







    [1] : https://en.wikipedia.org/wiki/Sulfation



    [2] : https://www.ncbi.nlm.nih.gov/pubmed/19131563



    [3] : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3119907/



    [4] : https://www.ncbi.nlm.nih.gov/pubmed/11931647



    [5] : https://www.ncbi.nlm.nih.gov/pubmed/18614014



    [6] : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591525/



    [7] : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4438467/


    [8] : http://cdn.intechopen.com/pdfs/41042/InTech-The_biological_roles_of_steroid_sulfonation.pdf
     
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  7. FMMM1

    FMMM1 Senior Member

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    Jonas Bergquist presented data at the symposium showing inflammation (pro inflammatory markers) in cerebrospinal fluid samples in ME/CFS and fibromyalgia. The technique used, proximity ligation assay, can detect single protein molecules. He expressed an interest in looking at steroids using Mass Spectrometry.

    Ron Davis presented data showing that something in the plasma, possibly a protein, affects cell metabolism in ME/CFS. Could it be elevated pro inflammatory proteins? Could the affect of pro inflammatory proteins be investigated by adding them to control plasma?

    So the tools necessary to investigate the disease, and evaluate possible treatments, may now be available.

    How do we get the funding to support this work? Should we lobby our elected representatives e.g. members of the European parliament, or US senators? Should we lobby via public electronic forums? Can we co-ordinate with other related groups e.g. fibromyalgia and Lyme disease?
     
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  8. Janet Dafoe (Rose49)

    Janet Dafoe (Rose49) Board Member

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    You are spot-on here! We are doing everything we can think of to get funding with the help of OMF. We are hoping fervently that we get one of the NIH Center grants. Any help and ideas about funding are appreciated! Thank you!
     
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  9. AndyPR

    AndyPR Senior Member

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  10. FMMM1

    FMMM1 Senior Member

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    I've had a brief look on the European Parliament website i.e. at the Parliamentary Questions.

    Richard Howitt, Reading United Kingdom, has asked a question re Fibromyalgia. The question included the following "Will the Commission launch research into the speed of diagnosis, state of care and support services for people living with fibromyalgia and benchmark the level of care?". He also spoke in the "Implementation of the UN Convention on the Rights of Persons with Disabilities (debate)".

    Frederique Ries, Belgium, has asked a question re Lyme. The question included the following "Lyme disease is still controversial, even among medical professionals.

    One of the most unfortunate problems linked to this disease is that its complexity and its range of symptoms (chronic fatigue, rheumatic pain, severe headaches) make it very difficult to diagnose, the result being that an alarming number of sufferers go untreated. Patients are sent from pillar to post in search of a cure.

    Can the Commission say whether research projects focusing on Lyme disease have been launched under Horizon 2020 or the previous Framework Programme for Research and Development?"


    Anyone in the above constituencies who's interested in proposing that the MEP submits a similar question re ME/CFS? Is it better to put the request on Facebook (i.e. publicly accessible medium) as well as email (i.e. personal communication)?

    In terms of potential research areas, Fluge and Mella discovery that something in ME/CFS patients' blood was affecting cell metabolism; Jonas Bergquist proposed work on steroids [both on the Youtube video]. Both work in EU countries and are therefore fundable under Horizon 2020, the EU's research and innovation programme [total budget approx €78.6bn].

    I didn't find any questions re ME/CFS on the European Parliament website and I'd guess that the level of funding was very low. I've tried to raise this before, without success, and I'd appreciate assistance since I feel that I've annoyed some of those overseeing the Horizon 2020 program (unconscous/conscious bias).

    If you do try to persuade your MEP to raise a question then you may wish to inform the European ME Alliance and your national ME/CFS organisations of the fact.

    I haven't checked but I guess all other legislatures (eg. the senate) operate similar systems.

    Sorry for the long reply
     
  11. FMMM1

    FMMM1 Senior Member

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    Thanks for this.

    From memory Jonas Bergquist, at the Invest in ME Research International ME Conference (2015?), presented Mass Spectrometry data which (he suggested) indicated that some people with ME/CFS had a glycoprotein disorder [haven't watch the conference DVD in some time].

    Neil McGregor at this symposium presented genetic data which indicated that some people with ME/CFS may have a (genetic) G-protein couple receptor protein disorder.

    Anyone out there care to comment on whether there is potentially a link between a glycoprotein disorder and a genetic G-protein couple receptor protein disorder? Are "G-protein" and "glycoproteins" the same thing?
     
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  12. lansbergen

    lansbergen Senior Member

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  13. mariovitali

    mariovitali Senior Member

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    @FMMM1

    CC : @Jesse2233

    In the Wikipedia entry on Glycoproteins, N-Linked Glycosylation (a type of Glycosylation) is discussed :

    and (note mention of Rituximab) :

    N-Linked Glycosylation was first discussed in the "Unfolded Protein Response" Thread in 2015:

    Although quite outdated by now, it was described how Endoplasmic Reticulum Stress and the Unfolded Protein response may be parts of the ME/CFS Puzzle. To the best of my knowledge, these areas have not been looked at from OMF Researchers to this day. One of the supplements the Thread mentions is NAG (N-Acetyl Glucosamine aka GlcNac).

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5257256/

    Perhaps @Hip may also want to comment about N-Acetyl Glucosamine
     
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  14. mariovitali

    mariovitali Senior Member

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    @FMMM1

    I forgot to mention that the Analytical Methods i use have selected GRK5 (A G-Protein coupled receptor) as potentially relevant to ME/CFS.

    I do not know if this type of receptor was found to be relevant by Neil McGregor. A quick search on Phoenix Rising shows no previous mentions regarding this particular receptor.
     
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  15. FMMM1

    FMMM1 Senior Member

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    Thank you for replying.

    After writing my post it occurred to me that the possible genetic groups, identified by Neil McGregor, could be compared with the protein data, from Jonas Bergquist's study of 50 Swedish people with ME/CFS. I.e. compare the genetic data with the proteins.

    It's interesting that there may even be potential treatments.

    One of the difficulties appears to be getting the money to investigate e.g. genetic groups and their protein profiles. Horizon 2020 has a budget of €80 billion; there are approximately 1 million people in European Union with ME/CFS. How come research of this type doesn't get funded under Horizon 2020 (or NIH)?





     
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  16. wastwater

    wastwater Senior Member

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    I liked the presentation about G-proteins worth a watch on youtube
     
  17. FMMM1

    FMMM1 Senior Member

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    Thanks.

    Could you provide a link to the youtube video or if it's part of this symposium post the time.
     
  18. wastwater

    wastwater Senior Member

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    Think it’s part 6 of the symposium on YouTube
    I’m not sure how to do links on the phone
    I wondered if it ties up with dr Kerr’s work many years ago
     
  19. FMMM1

    FMMM1 Senior Member

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    Thanks for this. I don't know of Dr Kerr's work but the list of symptoms listed in Dr McGregor's talk looks familiar.
     
  20. Learner1

    Learner1 Forum Support Assistant

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    Pacific Northwest
    Is this the Dr. Kerr? If so, it does look like there may be some overlap, though one would have to look at which subgroups golf patients heceas looking at.

    http://phoenixrising.me/archives/25982
     

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