Optic disc hypoplasia, Zika virus, ACTH, melanocortin receptors, and other flaviviruses

Zika babies and optic disc hypoplasia eye issues
http://www.nbcnews.com/storyline/zika-virus-outbreak/babies-zika-linked-birth-defects-may-have-eye-trouble-too-n514876

ACTH and optic disc hypoplasia...like De Morsier syndrome?

If zika uses the ACTH receptor is it a problem with the pituitary gland or is it the mcr1 that all flaviviruses weakly bind?

Blindness and blood shot eyes:

the blood shot eyes that are associated with the flaviviruses are caused by inflammation of the ocular
http://emedicine.medscape.com/article/1192122-overview

mrc1 is expressed at the ocular (studies in red heads)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1180688/

Could the blindness occur when the virus has destroyed too many ocular cells? Does eye sight weaken after flavivirus infections in general?

dengue and blindness
https://www.evrs.eu/severe-blindness-a-rare-but-devastating-complication-of-dengue-fever/

westnile and blindness
http://www.ncbi.nlm.nih.gov/pubmed/16344453
http://www.ncbi.nlm.nih.gov/pubmed/15621074
http://forums.studentdoctor.net/threads/effects-of-west-nile-virus-on-vision.259316/

Zika and blindness

http://www.usnews.com/news/articles/2016-05-25/study-suggests-zika-causes-blindness

ocular melanoma and mcr1

http://www.ncbi.nlm.nih.gov/pubmed/17325166

Infected macrophages, TNF alpha, mast cells, and Neutrophils

M. fermatans infection lowers TNF alpha 60%
http://www.nature.com/cdd/journal/v11/n11/full/4401482a.html

RA has anti-TNFalpha

TNF alpha is released by macrophages when they are infected

Mycoplasmas, mycobacterias, and viruses do infect macrophages. (in the case of RA mycoplasmas are the suspects)

The mast cells respond to TNF alpha from infected macrophages with histamine and il-8 secretions
https://www.ncbi.nlm.nih.gov/pubmed/22502799

the histamine secreted by the mast cells induce exocytosis by macrophages
http://www.jimmunol.org/content/jimmunol/166/6/4083.full.pdf
(sort of requesting them to throw-up what they have and let the neutrophils take over)

the il-8 calls the neutrophils which are smaller than macrophages and are not APC

the tiny multilobed nucleus of the neutrophils barely function
https://www.ncbi.nlm.nih.gov/pubmed/25727365

Since the macrophages keep getting infected themselves the Neutrophils replace them. Neutrophils lack the complete transcriptional and translational machinery which in theory prevents the infection from using the cells resources. (limited functions) Hopefully trapping the infections inside if not destroying them.

Unfortunately this lac of DNA also means that the neutrophils are unable to be APC (antigen presenting cells)

Suicide, t.gondii tails, profolin, and the cytoskeleton

The suicidal tendencies of those infected with T.gondii could be caused by the parasite building it's flaggellum or tail from actin.

 T. gondii and suicide attempts in Denmark mothers
https://www.ncbi.nlm.nih.gov/pubmed/22752117

T. gondii and suicide
https://www.ncbi.nlm.nih.gov/pubmed/20010026

TLRs and t.gondii
http://www.nature.com/nri/journal/v14/n2/fig_tab/nri3598_F1.html

TLR11 binds profolin of T.gondii (a protein that polymerizes actin during the formation of tails)
https://www.ncbi.nlm.nih.gov/pubmed/18312842

There is a brain-derived-factor connected to suicide which is known to bind tropomyosin-related kinase B (TrkB)
http://www.hdbp.org/psychiatria_danubina/pdf/dnb_vol25_sup2/dnb_vol25_sup2_341.pdf

Tropomyosin is an actin binding regulator of the cytoskeleton
https://www.ncbi.nlm.nih.gov/pubmed/26315888

Could profolin like the brain-derived-factor disrupt the tropomyosin?

The brains of suicide : disrupted cytoskeletons
https://www.researchgate.net/figure/234000212_fig3_Figure-3-The-protein-network-of-altered-cytoskeleton-proteins-in-the-brains-of-suicide


Tangent thoughts about T.gondii

T.gondii's infect macrophages and cause TNF to be released

Host cells's ER is used by T.gondii
https://www.ncbi.nlm.nih.gov/pubmed/9248995

T.gondii induces apoptosis via ER stress pathway
https://www.ncbi.nlm.nih.gov/pubmed/24612639

Dysfunction of the ER causes the IFNgamma to be expressed

Insulin, Cortisol, and Cataracts

Cortisol raises blood sugar while insulin lowers it which means when we inject ourselves with insulin our body would respond with an increase in cortisol.

Insulin tolerance tests reveal that the bodies response to high insulin levels is the production of cortisol (through ACTH)

some patients develop cataracts after insulin treatments (after 3 months)
http://abstracts.eurospe.org/hrp/0086/hrp0086P2-P308.htm

Are we giving these patients the cataracts?

Are the cataracts caused by the high waves of cortisol after injection?

Cortisone induced cataracts
http://www.medhelp.org/posts/Eye-Care-Archive/What-is-a-cortisone-induced-cataract/show/371756

I had previous looked at cataracts and the cortisol levels possibly raised by spirochete infections.
http://angelabiggs.blogspot.com/2016/04/anterior-cingulate-cortex-hoarding.html

In this post I had looked at panic and anxiety attacks in regard to cortisol

Panic attacks and cortisol
http://www.ncbi.nlm.nih.gov/pubmed/10698825

Anxiety disorder and cortisol
http://www.ncbi.nlm.nih.gov/pubmed/26934635

Insulin injections have been linked to possibly causing panic attacks in some patients
http://www.factmed.com/report-OPTICLIK%20(INSULIN%20INJECTION%20PEN)-causing-PANIC%20ATTACK.php

Pregnant women with diabetes also have an increased risk of having a child with a cleft palate
https://www.ncbi.nlm.nih.gov/pubmed/11716256

cortisone has been linked to causing cleft palate
http://dev.biologists.org/content/develop/5/2/201.full.pdf

Types of macrophages (reviewing)

The types of macrophages

M1 the classically activated macrophage (CAM) which participates in the Th1 pathway (IgG, IgM, and IgA...non hidden infections)

M2 the alternatively activated macrophage (AAM) which participates in the Th2 pathway (IgE hidden infections)  triggered by Il-4

TAM macrophages which have the TAM arms and are involved in the viral pathway
     http://angelabiggs.blogspot.com/2017/02/tam-receptors-and-ifns.html

TAM stands for : TYRO3, AXL, and MER

IFN alpha, MER, and TLR7 /TLR9 (mitochondria and nucleus)
https://arthritis-research.biomedcentral.com/articles/10.1186/ar4517

IFN beta, TYRO3, and TLR3 (cytosol)
https://www.ncbi.nlm.nih.gov/pubmed/26085147

IFN gamma, AXL, and natural killer cells (also TLR8 which is the ER)
https://www.ncbi.nlm.nih.gov/pubmed/18840707

MDSC are considered M2-like. Myeloid- Derived Suppressor Cells are triggered by the Natural killer pathway. They are not true macrophages. This pathway is triggered by the destruction of ER  by a virus within the cell...no markers are available at the infected cell's surface and these "naked" cells will be destroyed.

IFN gamma is critical in activating MDSC to suppress.
https://www.ncbi.nlm.nih.gov/pubmed/18607390

Note that the IFN gamma also suppresses the Th2 pathway where infectious pathogens are hiding (like parasitic worms) as well as stimulating the AXL hands of the TAM macrophages.

IFN gamma is made by TLR8 the nets of infected ER or Natural Killer cells....when surface proteins are not available to bind with AXL and very little HLA-C mailboxes will make it to the surface because the ER of the cell has a virus infection.   

Vit D receptor, Aflatoxin, ECGC (green tea), FoxP3 expression and ALS

black tea and aflatoxin
https://www.ncbi.nlm.nih.gov/pubmed/15582201

Coffee and tea interact with Vit D receptor !!!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478213/

vit D levels and tea
https://www.vitamindcouncil.org/tea-and-coffee-consumption-linked-to-vitamin-d-status/

Vit D3 promotes Foxp3 expression
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3358577/

ECGC induces Foxp3 expression
http://www.sciencedirect.com/science/article/pii/S0165247811001258

(FOXp3 suppresses the viral Tcell response)

ALS and a fungal infection that has an aflatoxin like compound
http://angelabiggs.blogspot.com/2016/10/amyotrophic-lateral-sclerosis-hla-c.html

aflatoxin binds the Vit D receptor
https://www.citeab.com/publication/1455664-25483621-toxicity-of-aflatoxin-b1-towards-the-vitamin-d-rece

ECGC and ALS?? mouse models?
https://www.ncbi.nlm.nih.gov/pubmed/16356650

I need to look at these models

Vit D inhibits Th1 and Th17 yet favors Th2...the route to the IgE response of allergic reaction
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425186/

vit D in atopic dermatitis, asthma, and allergic disease
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2914320/

ECGC inhibited Th1 and Th17
https://portal.nifa.usda.gov/web/crisprojectpages/0220019-green-tea-egcg-and-t-cell-function-in-autoimmune-inflammation.html

People can have allergic responses to ECGC (green tea factory workers) and people can have allergic responses to vit D3

Pondering TNF alpha

How do mycobacterias increase the THF alpha?

Adding TNF alpha decreased mycobacteria?
https://www.ncbi.nlm.nih.gov/pubmed/10211990

Is this because the mycobacteria are "hiders" moving into macrophages and embedding into white adipose tissue? The macrophages are favoring the Th17 route of hidden pathogens by increasing THF alpha?

Macrophages take up mycobacterias but then the mycobacterias survive inside the macrophage?
https://www.ncbi.nlm.nih.gov/pubmed/11358719

Looking at the diseases I have linked to mycobacterias they all appear to have increased TNF alpha

THF alpha and parkinson's
https://www.ncbi.nlm.nih.gov/pubmed/8015728

THF alpha and multiple sclerosis
http://www.medscape.com/viewarticle/583080_9

TNF alpha and psoriasis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924720/

TNF alpha and type 2 diabetes
https://www.ncbi.nlm.nih.gov/pubmed/12532159/
http://www.nature.com/ijo/journal/v27/n1/full/0802187a.html

Increased TNF alpha has also been linked to IBD and major depression
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229361/
those on anti-TNF for the IBD developed depression

TNF alpha blockers have been shown to worsen TB. Use of blockers made the illness worse. Is this because the macrophages are hiding?

Hypothesis: Macrophages release TNF at high rates when they themselves have become infected by mycobacterias or viruses

TNF and viruses
https://www.ncbi.nlm.nih.gov/pubmed/8832967

Sendai virus infecting macrophages
https://www.ncbi.nlm.nih.gov/pubmed/168154

flu viruses and macrophages
http://www.futuremedicine.com/doi/pdf/10.2217/fvl.14.65
https://www.ncbi.nlm.nih.gov/pubmed/22894921
https://www.ncbi.nlm.nih.gov/pubmed/26423941

RA patients taking TNF blockers develop something that looks like psoriasis

High TNF alpha also seems to be involved in skin tumors.

HPV which uses cannabinoid receptors causes tumors.

Cannabinoid receptors can cause an increase in TNF alpha
https://www.ncbi.nlm.nih.gov/pubmed/19047095 (is this the same for skin cells?)

Green tea's EGCG seems to inhibit mycobacteria growth. How does that work?

Green tea's ECGC inhibits mycobacteria cell growth
https://www.ncbi.nlm.nih.gov/pubmed/25495515

Green tea attacks the mycobacteria that are inside macrophages
https://www.ncbi.nlm.nih.gov/pubmed/16352457

Further EGCG would help nerve growth....Less TNF alpha and more nerve growth factor.

Nerve growth factor/ TNF alpha receptors are on nerve endings and these receptors are in the same "family" of receptors

mycobacteria and white adipose tissue

Previous blog connect Fatty liver disease and type 2 diabetes to the cGMP of mycobacteria
http://angelabiggs.blogspot.com/2015/12/mycobacterias-possible-connection-to.html

Mycobacteria use cGMP as a quorum when establishing biofilms to hold them in place
https://www.ncbi.nlm.nih.gov/pubmed/25546058

mycobacteria hide in white adipose tissue
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1762355/

Are they, mycobacterias, picking white because brown would use the mycobacteria's signal cGMP ?

cholesterol is stored as white adipose tissue
http://www.jlr.org/content/15/5/491.full.pdf

Which means this state of high cholesterol causes not just obesity but lots of places for mycobacteria.

TAM receptors and IFNs

TAM receptors: TYRO3 (T), AXL(A), MER (M)

These are a family of tyrosine kinases with 2 Ig like motifs and 2 fibronectin III motifs. They are the arms of phagocytosis used by macrophages for viral infections.

Each IFN favors a different TAM.

IFNalpha which is sent after TLR7 or TLR9  are triggered means a viral or foreign infection of the mitochondria or nucleus.  Induces cells to make HLA-A and HLA-B.

IFNbeta which is sent after TLR3 which means a viral infection of the cytosol. HLA-Ds are made.

IFNgamma....tends to be made more by natural killer cells.  TLR8 which when triggered makes IFNgamma often never gets through.  This is the condition of a viral or foreign infection of the endoplasmic reticulum which means the HLAs may never make it to the surface.

Here is the previous post if you want references:
http://angelabiggs.blogspot.com/2017/01/tlrs-toll-like-receptors-summary.html

Now if you look at the TAMS you can see a similar pattern of expression.

IFN alpha, MER, and TLR7 /TLR9
https://arthritis-research.biomedcentral.com/articles/10.1186/ar4517

IFN beta, TYRO3, and TLR3
https://www.ncbi.nlm.nih.gov/pubmed/26085147

IFN gamma, AXL, and natural killer cells
https://www.ncbi.nlm.nih.gov/pubmed/18840707

What is interesting about this is that AXL is considered the TAM for "do not eat me" which is worn by growing neurons, placentas, and even cancer cells.  Is this actually a "don't bother with phagocytosis" marker? There is nothing for the TAM to grab onto. The ER of the infected cell can't make the correct grab proteins. Because moving/growing cells would attract macrophages does the Axl stop them...almost pretending to be another macrophage?

In the state of endoplasmic reticulum infection very little GAS6 or S proteins will be visible on the surface of the infected cell.

(cytosol net) TLR3                    IFN beta      HLA-D (mailbox cytosol)
                                                                       tyro-3 (macrophage hands)


(nuclear net) TLR7                     IFN alpha    HLA-A (mailbox nuclear)
(mitochondria net) TLR9                               HLA-B (mailbox mitochondria)
                                                                         MER (macrophage hand)


TLR-8                                       IFN gamma   HLA-C (endoplasmic reticulum)
(endoplasmic reticulum net)                         AXL (macrophage hand of don't bother eating)
or Natural Killer cells

So when a net catches something foreign in this region it sends an IFN signal which causes the correct mailbox for the area to be made and the same signal tells the macrophages which arms to wear.

Pondering: what is the difference between tyro3 and mer? Do nuclear viruses require more containment ?

MER is also involved in apoptosis.

MER has been located in the nucleus.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0031635

Does MER shut down or slow the DNA processes, like transcription, temporarily so DNA viruses can't use them?

Does Tyro3 interfere with RNA and ribosome processes since it is linked to RNA viruses of the cytosol?

Tyro3 may have a synaptic function
http://europepmc.org/articles/pmc2231337

The ribosomes at the synapse....is their translation altered on and off by tyro3?

Tyro3 was involved in the altered location of RNA
http://dmm.biologists.org/content/dmm/early/2017/01/11/dmm.027433.full.pdf

Curious possibilities:

Does MER also have a DNA transcription job because of it's link to DNA viruses?
Does  tyro3 also have an RNA translation job because of it's link to RNA viruses?

Because AXL is involved with endoplasmic reticulum viruses does it therefore increase transcription to help the odds of something getting through the ER mess?

AXL has been found in Cancer and embryo genesis
http://www.clinsci.org/content/122/8/361 (AXL review)

AXL has been found to be involved with vascular repair
http://circres.ahajournals.org/content/83/7/697

In both of these states one might see an increase in transcription.

Enveloped viruses in an attempt to stop macrophages bind the TAM ligands : removing the immune response

http://www.cell.com/cell-host-microbe/abstract/S1931-3128(13)00253-9?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1931312813002539%3Fshowall%3Dtrue

http://www.cell.com/cell-host-microbe/fulltext/S1931-3128(13)00262-X

Note that all 3 TAMs bind the "growth arrest specific" gene Gas-6 and protein S
https://www.ncbi.nlm.nih.gov/pubmed/21057587