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Post by lilsissy on Oct 8, 2014 13:47:48 GMT -5
Hi , been a while since I could research but this caught my attention....Lipid Rafts have been discussed so much in connection w Morgellons , I will try to find that article...Jen here, jvi.asm.org/content/84/14/7243.fullHow could Ebola virus GP block tetherin restriction without affecting the cell surface level of the protein and without targeting specific tetherin sequences? Previously, it has been reported that GP's anti-tetherin activity requires both its membrane anchor and proper trafficking to the cell surface (18), but that it does not require the mucin domain of the protein that has been implicated in the downregulation of a number of other cell surface proteins (37). GP also was reported to coimmunoprecipitate with tetherin, although the association only occurred with a less mature form of GP (18), so that a direct interaction between the mature forms of the proteins at the cell surface may not occur. In the absence of specific sequence requirements, it is possible that some other feature of tetherin is targeted by GP, for example, an association with lipid rafts. Ebola virus GP is itself located in lipid rafts, and its presence in these membrane regions could in some way alter virus assembly sites, perhaps creating an environment that is incompatible with tetherin trafficking to, or retention at, such sites. Additionally, GP could act as a nonspecific steric block to physically prevent tetherin from accessing the viral lipid envelope or forming the higher-order multimers that have been proposed as alternate mechanisms to account for tetherin restriction (39). If the action of GP impacted only a relatively small fraction of tetherin at a virus-budding site or caused tetherin surface redistribution rather than large-scale removal, then this could account for the lack of the effect on overall tetherin cell surface levels that we observed. Further experiments will be needed to distinguish between these different possibilities.
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Post by lilsissy on Oct 8, 2014 14:12:20 GMT -5
Lipid Rafts, Signalling and the Cytoskeleton Lipid rafts are specialised membrane domains enriched in certain lipids cholesterol and proteins. The existence of lipid rafts was first hypothesised in 1988 (Simons & van Meer, 1988; Simon & Ikonen, 1997), but what we know as "caveolae" were first observed much earlier (Palade, 1953; Yamada, 1955). Caveolae are flask shaped inv spottions on the cell surface that are a type of membrane raft, these were named "caveolae intracellulare" (Yamada, 1955). After a long argument (Jacobson & Dietrich, 1999), most now consider that these rafts actually exist, however, there is some confusion surrounding the classification of these rafts. It presently seems that there could be three types; caveolae, glycosphingolipid enriched membranes (GEM), and polyphospho inositol rich rafts. It may also be that there are inside rafts (PIP2 rich and caveolae) and outside rafts (GEM).
The fatty-acid chains of lipids within the rafts tend to be extended and so more tightly packed, creating domains with higher order. It is therefore thought that rafts exist in a separate ordered phase that floats in a sea of poorly ordered lipids. Glycosphingolipids, and other lipids with long, straight acyl chains are preferentially incorporated into the rafts.
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Post by lilsissy on Oct 8, 2014 14:45:52 GMT -5
interesting, feed back any one? www.ncbi.nlm.nih.gov/pubmed/24109237The cytoprotective enzyme heme oxygenase-1 suppresses Ebola virus replication. Hill-Batorski L1, Halfmann P, Neumann G, Kawaoka Y. Author information Abstract Ebola virus (EBOV) is the causative agent of a severe hemorrhagic fever in humans with reported case fatality rates as high as 90%. There are currently no licensed vaccines or antiviral therapeutics to combat EBOV infections. Heme oxygenase-1 (HO-1), an enzyme that catalyzes the rate-limiting step in heme degradation, has antioxidative properties and protects cells from various stresses. Activated HO-1 was recently shown to have antiviral activity, potently inhibiting the replication of viruses such as hepatitis C virus and human immunodeficiency virus. However, the effect of HO-1 activation on EBOV replication remains unknown. To determine whether the upregulation of HO-1 attenuates EBOV replication, we treated cells with cobalt protoporphyrin (CoPP), a selective HO-1 inducer, and assessed its effects on EBOV replication. We found that CoPP treatment, pre- and postinfection, significantly suppressed EBOV replication in a manner dependent upon HO-1 upregulation and activity. In addition, stable overexpression of HO-1 significantly attenuated EBOV growth. Although the exact mechanism behind the antiviral properties of HO-1 remains to be elucidated, our data show that HO-1 upregulation does not attenuate EBOV entry or budding but specifically targets EBOV transcription/replication. Therefore, modulation of the cellular enzyme HO-1 may represent a novel therapeutic strategy against EBOV infection.
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Post by lilsissy on Oct 8, 2014 15:43:59 GMT -5
Ebola actin polymerization,,,,hmmm , I recall that one to in connection with Morgellons, www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1001110Here we used replication-competent infectious ZEBOV as well as morphologically similar virus-like particles in specific infection and entry assays to demonstrate that in HEK293T and Vero cells internalization of ZEBOV is independent of clathrin, caveolae, and dynamin. Instead the uptake mechanism has features of macropinocytosis. The binding of virus to cells appears to directly stimulate fluid phase uptake as well as localized actin polymerization. Inhibition of key regulators of macropinocytosis including Pak1 and CtBP/BARS as well as treatment with the drug EIPA, which affects macropinosome formation, resulted in significant reduction in ZEBOV entry and infection. It is also shown that following internalization, the virus enters the endolysosomal pathway and is trafficked through early and late endosomes, but the exact site of membrane fusion and nucleocapsid penetration in the cytoplasm remains unclear. This study identifies the route for ZEBOV entry and identifies the key cellular factors required for the uptake of this filamentous virus. The findings greatly expand our understanding of the ZEBOV entry mechanism that can be applied to development of new therapeutics as well as provide potential insight into the trafficking and entry mechanism of other filoviruses.
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Post by lilsissy on Oct 8, 2014 16:14:36 GMT -5
Sky, do you remember my Morgellons Dream on Phosphorylation, following that key word, www.jbc.org/content/277/36/33099This shows up in many articles, Phosphorylation of VP30 Impairs Ebola Virus Transcription*
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Post by lilsissy on Oct 8, 2014 16:21:05 GMT -5
Okadaic acid is a toxin that accumulates in bivalves and causes diarrheal shellfish poisoning. The molecular formula of okadaic acid, which is a derivative of a C38 fatty acid, is C44H68O13.
History[edit]
Okadaic acid was named from the marine sponge Halichondria okadai, from which okadaic acid was isolated for the first time.[1] It has also been isolated from another marine sponge, H. malanodocia, as a cytotoxin. The real producers of okadaic acid belong to the algae group of the dinoflagellates, namely the benthic dinoflagellate Prorocentrum and the planktonic forms of Dinophysis,[2] for example Dinophysis acuminata and D. acuta.[3] Administration of okadaic acid has been shown to profoundly increase the secretion of nerve growth factor, and to also promote nerve growth factor gene transcription and the stability of mRNA in primary cultures of cortical astrocytes.[4]
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Post by skyship on Oct 14, 2014 1:24:34 GMT -5
Lil sis, There is the filovirus of skin they are downplaying........ "ABSTRACT VP30 is a phosphoprotein essential for the initiation of Ebola virus transcription. In this work, we have studied the effect of mutations in VP30 phosphorylation sites on the ebolavirus replication cycle by using a reverse genetics system. We demonstrate that VP30 is involved in reinitiation of gene transcription and that this activity is affected by mutations at the phosphorylation sites. " jvi.asm.org/content/82/24/12569.fullphosphorylation sites could be the "plaque" found on skin? where amyloid proteins misfold making inclusion bodies which harbor the ebola on the skin. So, would be a minor form but would explain the bruise like marks on the body under the skin, which look like lupus. So, a skin form of ebola? They do hit skin hair follicles and sweat glands as well.
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Post by skyship on Oct 14, 2014 20:17:57 GMT -5
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Post by skyship on Oct 14, 2014 21:01:51 GMT -5
Lipid raft microdomains: a gateway for compartmentalized trafficking of Ebola and Marburg viruses. Bavari S1, Bosio CM, Wiegand E, Ruthel G, Will AB, Geisbert TW, Hevey M, Schmaljohn C, Schmaljohn A, Aman MJ. Author information Abstract Spatiotemporal aspects of filovirus entry and release are poorly understood. Lipid rafts act as functional platforms for multiple cellular signaling and trafficking processes. Here, we report the compartmentalization of Ebola and Marburg viral proteins within lipid rafts during viral assembly and budding. Filoviruses released from infected cells incorporated raft-associated molecules, suggesting that viral exit occurs at the rafts. Ectopic expression of Ebola matrix protein and glycoprotein supported raft-dependent release of filamentous, virus-like particles (VLPs), strikingly similar to live virus as revealed by electron microscopy. Our findings also revealed that the entry of filoviruses requires functional rafts, identifying rafts as the site of virus attack. The identification of rafts as the gateway for the entry and exit of filoviruses and raft-dependent generation of VLPs have important implications for development of therapeutics and vaccination strategies against infections with Ebola and Marburg viruses. www.ncbi.nlm.nih.gov/pubmed/11877482
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Post by lilsissy on Oct 24, 2014 17:48:47 GMT -5
www.jbc.org/content/282/37/27306 cut, Our results also reveal that EBO16 can interact with detergent-resistant membrane fractions and strongly suggest that Trp-8 and Phe-12 are important for structure maintenance within the membrane bilayer. Replacement of tryptophan 8 with alanine (W8A) resulted in dramatic loss of helical structure, proving the importance of the aromatic ring in stabilizing the helix. Molecular dynamics studies of the interaction between the peptide and the target membrane also corroborated the crucial participation of these aromatic residues. The aromatic-aromatic interaction may provide a mechanism for the free energy coupling between random coil-helical transition and membrane anchoring. Our data shed light on the structural “domains” of fusion peptides and provide a clue for the development of a drug that might block the early steps of viral infection.
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Post by lilsissy on Oct 25, 2014 15:47:51 GMT -5
Very good article on Ebola,https://microbewiki.kenyon.edu/index.php/Infection_Mechanism_of_Genus_Ebolavirus
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Post by AQT on Oct 26, 2014 12:00:11 GMT -5
Lilsis,
Kathrn and I met over the word PHOSPHORYLATION.................
waaaaaay back in the very beginning of researching this information....
Thank you for all you do.... your insights are priceless, your information always relevant and your love is felt over the miles that separate us.
truthfully,
aqt
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Post by lilsissy on Oct 29, 2014 18:34:14 GMT -5
Thanks guys, not sure where this is going but here thatsbasicscience.blogspot.com/2011/11/ebola-blocker.htmlMoreover, Côté et al. identified a drug that stopped Ebola from employing this trapdoor, albeit with one caveat. The efficacy of this drug was tested in a cell culture system rather than in a living animal3. However, the other study by Carette et al. found that mice lacking the NPC1 gene were resistant to Ebola and its cousin, the lethal Marburg virus. Thus, this latter study provides some evidence that targeting NPC1 works in a living organism. These novel findings provide new hope for eradicating this destructive pathogen. en.wikipedia.org/wiki/Niemann%E2%80%93Pick_disease,_type_C
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Post by lilsissy on Oct 29, 2014 18:34:45 GMT -5
and here,http://wwwnc.cdc.gov/eid/article/20/10/14-0430_article
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Post by lilsissy on Oct 29, 2014 20:32:12 GMT -5
finding some connections to TGFB...Situs Inversus...lefty B...cytokines and a new approach on Ebola. 3C syndrome...heart lung condition and 1Q42 Situs inversus pages from the rare disease N.I.H. had C.D.C. the Morgellons warnings paragraphs on them as documented On Jan Smith's site. medical-dictionary.thefreedictionary.com/EBAFcut, LEFTY2 A gene on chromosome 1q42.1 that encodes a member of the transforming growth factor beta (TGFB) family of cytokines that plays a role in determining left-right asymmetry during organogenesis and may also play a role in endometrial bleeding. Molecular pathology LEFTY2 mutations are associated with left-right axis malformations, especially in the heart and lungs www.ncbi.nlm.nih.gov/pubmed/24942569cut,Pathway overrepresentation analysis and functional network analysis of kinome data revealed that transforming growth factor (TGF-β)-mediated signaling responses were temporally modulated in response to EBOV infection. Upregulation of TGF-β signaling in the kinome data sets correlated with the upregulation of TGF-β secretion from EBOV-infected cells. Kinase inhibitors targeting TGF-β signaling, or additional cell receptors and downstream signaling pathway intermediates identified from our kinome analysis, also inhibited EBOV replication. Further, the inhibition of select cell signaling intermediates identified from our kinome analysis provided partial protection in a lethal model of EBOV infection.... ......Administration of kinase inhibitors targeting signaling pathway intermediates identified in our kinome analysis inhibited viral replication in vitro and reduced EBOV pathogenesis in vivo. Further analysis of our data also demonstrated that EBOV infection modulated TGF-β-mediated signaling responses and promoted "mesenchyme-like" phenotypic changes. Taken together, these results demonstrated that EBOV infection specifically modulates TGF-β-mediated signaling responses in epithelial cells and may have broader implications in EBOV pathogenesis.
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Post by lilsissy on Oct 29, 2014 21:31:05 GMT -5
Interesting reply from my now deceased sister here. Remember Ebola started out a disease of plants that spread to animals,http://www.morgellons-disease-research.com/Morgellons-Message-Board/Thread-CDC-Morgellons-solved-Chromosome-1-q42-Hidden-Webpage?page=2
cut,
kritters,
I think, and I underline the word think, tha it is only contagious if the individual infected with Lyme also has a 1q42 genetic defect. Most of us wouldn't know if we do or not. I know for sure I could have because on my niece who has situs inveress complete. This and several other diseases are associated with that particular gene defect. Cystic Fibrosis, schitzophrenia and others. So the genetic defect opens the door for the GMO to add plant DNA to us. What I meant is that the CDC already had this on a hidden webpage so they have known for a while at the very least and I guess that they have known for quite some time.
Karen W
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Post by lilsissy on Oct 29, 2014 22:20:23 GMT -5
Also remembering that Karen used Capsaicin cream after anti-biotic cream to make the fibers appear from her knees. Also read that Capsaician would make misfolded protein more infective perhaps by driving it out? www.reddit.com/r/ebola/comments/2gfzpz/could_capsaicin_be_a_possible_mechanism_that/Could Capsaicin be a possible mechanism that enables the people in Gabon to have a natural resistance to Ebola? (self.ebola) submitted 1 month ago by glowsindark The people of Gabon have been found to have a higher level of antibodies for Ebola than other countries yet they rarely have any cases of Ebola (http://en.ird.fr/the-media-centre/scientific-newssheets/337-possible-natural-immunity-to-ebola) and (http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0009126#pone.0009126-Ksiazek1). The later study concludes “These findings provide significant new insights into ZEBOV circulation and human exposure, and raise important questions as to the human pathogenicity of ZEBOV and the existence of natural protective immunization. “ If you look at the diet of the people of Gabon, it includes a lot of capsaicin (http://foodspring.com/content/gabon/) especially in the preparation of wild meats. One of the mechanisms that Ebola uses is the release of cytokines from macrophage cells “as a decoy to absorb neutralizing antibodies” and “studies have implicated a role of sGP in immune system evasion. During viral infection, large amounts of proinflammatory cytokines like tumor necrosis factor alpha (TNF-α) are secreted from infected macrophages and cause disruption of the endothelial barrier “ (https://microbewiki.kenyon.edu/index.php/Infection_Mechanism_of_Genus_Ebolavirus) . Macrophage cells “can decrease immune reactions through the release of cytokines” ( en.wikipedia.org/wiki/Macrophage). Capsaicin has been found to inhibit the production of cytokines in natural killer cells that work with macrophages. (https://www.researchgate.net/publication/261757178_Attenuation_of_natural_killer_cell_functions_by_capsaicin_through_a_direct_and_TRPV1-independent_mechanism?ev=pub_cit_inc). I am proposing that capsaicin in the diet of the people of Gabon might be limiting the release of cytokines from macrophage cells which in turn allows leucocytes to come in and do their job,
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Post by skyship on Nov 13, 2014 1:42:09 GMT -5
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Post by skyship on Nov 13, 2014 2:21:05 GMT -5
So, what does HIV have to do with Ebola raft? The interferon-inducible, transmembrane protein BST-2 (CD317, tetherin) directly holds fully formed enveloped virus particles to the cells that produce them, inhibiting their spread. BST-2 inhibits members of the retrovirus, filovirus, arenavirus and herpesvirus families. These viruses encode a variety of proteins to degrade BST-2 and/or direct it away from its site of action at the cell surface. Viral antagonism has subjected BST-2 to positive selection, leading to species-specific differences that presented a barrier to the transmission of simian immunodeficiency viruses (SIVs) to humans. This barrier was crossed by HIV-1 when its Vpu protein acquired activity as a BST-2 antagonist. Here, we review this new host–pathogen relationship and discuss its impact on the evolution of primate lentiviruses and the origins of the HIV pandemic. www.sciencedirect.com/science/article/pii/S0966842X10001125Is there a link?
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Post by skyship on Nov 17, 2014 2:10:29 GMT -5
Lil sis,
I keep coming back to this thread...................
Maybe not HIV but close..........
Okay what if this raft is ebola? It could be triggered at will of the damn computer? right?
So the lesions could hold the ebola raft? Raft is related to the micelles and what I have found out about red algae.........it is still and danger and always will be. .............
If we are Solutrean Basques then we can surmise what is going on......can we not?
More on that issue later, but we are def targeted,because we have the genes that surpass all others.
Which means we are a selected few........... Maybe sounds weird......but.....we are losing melanin, and why is that? are we the true white man? woman? we know we are fading fast. yet, we know from whence we came. We are not the phoneys we are the real deal. and if we can get past this attempt to destroy us, then we will know.
God Bless us each and everyone, for we know of the real giants, and they came as gentiles..........
Love you all, Kathryn (Skyship) for we know where this ship will go.................~!~!~!~!~!~!
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Post by skyship on Nov 17, 2014 2:34:37 GMT -5
Lil Sis,
Is that "higher order" Us? the morgies?
I am starting to believe this.......we are def targeted, by computer, by gene, by ethnicity.....We are the remaining "white giants" those who truly believe and are selected for their genes........... We are the true gentiles............not the 144,ooo jews........we are the real message and we are being attacked.
Why? Because we have the real message, and the lesions and the fibers have no significance other than to torture us.~!~!~!~! By knowing that eBOV was used to set the stage for a genocide......we are letting them know that we REJECT their ploy........For we know where the truth lies, and it is not with these phoney man made nano particles, evolutionary lab experiments, we know from whence we come. We are not stupid, and yet we have more grit than can be imagined by these false tech last effect controllers and psychos have in their pockets. They are smart, but, they never anticipated our survival and seeing what is being done. We came to bring the message, and no matter what is done, we will continue to throw it back in their sorry faces~!~!~!~!~!~!
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