Greetings fellow travelers. This is just a short note to say thank you for all of you that came out to the Rowdy Rebel “event” last year and who have followed this blog for however long that may be over the last 12 years. That said, the following principle seems to apply amongst the birthing pains of these modern Orwellian times:
Unfortunately, as times are changing, and much of what we’ve discussed and predicted over the years is coming to fruition and at least partial implementation, so too must we come to advance and change in our efforts and methodologies to not only communicate but freely express. It pains me to announce that due to a combination of shadow-banning, censorship, erasure, cancelation, disappearance, trolling, douche-baggary (and whatever other colloquialism is being used for the unframing, defamatory efforts being utilized in the castigation of lone folks like me), it is time to put this blog to rest.
The reasons for this are clear to the most controversial tellers of truth, to whistle-blowers, and to anyone that has had the hand of the internet gods reach out and smack them into oblivion. However, it’s certainly much more difficult to see or even believe in this blatant censorship among those merely searching for content, content that has already been scrubbed from even the ability to be found. As an example, I highly recommend watching the following before moving on, at which point my reasoning will be explained and alternatives will be considered:
It would not surprise me if this is removed… unless those behind the international crimes exposed here value this “news” video as positive outcome propaganda, as fear porn, or as the valued content/propaganda of the mass of alternative “useful innocents” we all are considered, the adage that there is no bad press coming to mind. Even our own rhetoric can be used to steer us in the direction of our own obfuscate destruction.
That said, here are my grievances that have led to this inevitable change, a simple list to justify this futile attempt of a declaration of independence from such corrupt platforms.
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SHADOW-BANNING – It’s very difficult to explain just what shadow-banning is, but you certainly recognize it when you suddenly find your digital persona and works gazing out from within those digitally enforced shadows. When one cannot even pull up one’s own website (this one) in any of the popular (99% market-share) search engines, especially with such a uniquely, purposefully misspelled identifying title as realitybloger.wordpress.com, one recognizes that there is indeed an active problem. From these engines of algorithmic search terms comes page after page of results, none of which are connected to my site – the origin of the search term – bringing only the shadow of the website and title, but never the direct site. What does that mean? It means that everyone that has copied and actually given credit or links to my blog website are showing up in the search, but my actual site is not. This blog-site now exists only in the shadow of those that have linked and supported my works in the past. Of course, while a few clean and non-enculturated web crawlers certainly do bring up my site, collectively their market share is in totem less than 1%. I’m sure the trolls will link those search engines below to somehow appear to discredit me. Those not keen on or hip to this type of censorship, and even those that are, will of course continue to use these mainstream search engines, meaning those that censer truth-tellers, often without even knowing they use the same algorithms and blackballing pathos of censorships as Google, etc. So, the question arises once more… Would I not be crazy to keep doing the same thing while foolishly expecting any other result than that which has already befallen me?
UPDATE: I opened up my talk in Alabama with printouts of my Google searches, showing a complete ban of my own site, both the name and full website, on my own computer. I still have those printouts and the emails from other readers that also could not pull up my site. It now appears that Google has partially lifted the ban, perhaps realizing that not pulling up the site while searching the actual website is a bit rediculous to justify? Whatever the case, I’m done trying to keep upwith it and my blog numbers have gone from hundreds of hits per day to 25-50 a dayfor the last year because of it.Of course, the hard part for the average search engine user to understand is that, unless you already know my name or site name, you wont find it. If you don’t know me or my site, you wouldn’t be searching for me. But the banning is more topic specific — if you search for “CAFR School”, for instance, or “The Stockton Bankruptcy Lie”, titles only I ever used or published, as the exact titles of my blog posts, my blog will not come up in any way. However, the first result is this search brought up this: “Stockton Wasn’t Lying—It Really Is Bankrupt – Ca – AllGov”. LOL! If you don’t know me already, why would you search my name or exact website? You of course would not.Shadow-banning is more subtle than that. All my CAFR work is non-searchable, at least it has been for the last few months. Other exact titles are surprisingly findable, though not by the mere subject matter, only the EXACT title, which again, why would anyone be searching for that if they don’t already know it exists? The banning is systematically conniving and trying to explain and justify it is the last thing I need right now. So please don’t leave comments telling me I’m a liar or throwing myself a pity party. This shit is getting very real. Moving on…
HACKING AND REDIRECTION – Welcome to The Corporation Nation… at least, that’s what my website (thecorporationnation.com), which displayed all my documentaries, used to say. Today, however, it exists only in memory — and on the Way Back Machine, of course. After enough people complained about malware and porn sites appearing with every click they made on that documentary showcase site, finally in frustration and helplessness I had to just take it down, so that no one else’s pride or machinery would be harmed by it. I kept the domain name just in case I want more of the same abuse later on. Who knows…? Would it not be insane to reopen it and expect any different results?
YOUTUBE (GOOGLE) CENSORSHIP – It pains me to announce that Lethal Injection 1: The Story of Vaccination, which was posted in late 2011 and has had collectively over 800,000 views (on just Youtube), has been removed – disappeared, as if it never existed in the first place. This happened a few weeks ago, with no explanation. But that’s not all, folks! For, like a death squad came and went in the night, every instance of Lethal Injection (1) The Story of Vaccination was also scrubbed, disappeared, canceled… in one fail swoop. Of course, I specifically asked people to copy and repost it, which they eagerly did, in hopes that when this type of censorship came, the movie itself would be somewhat insured against such total annihilation. I was wrong. We were right. Insurance is as empty as the hope and debt currency it was invented on; as spiritually devoid as the fiat nothingness it’s formed by. Lethal Injection, both 1 & 2, are officially banned movies in the Youtube/Googlesphere. Makes me wonder, after 10 years, what could possibly be the reasoning now to pull such a fraudulent takedown? With Lethal Injection 3, the most important of all these films, coming out soon, would it not be a sign of insanity to attempt to post such a sequel upon that magical disappearing platform and expect different results?
EMAIL FRUSTRATION – My current email server (GoDaddy.com) labeled me as a spammer without informing me several months ago, so that all my emails inviting people to the conference failed in delivery. Why? Microsoft and Google algorithms control the vast majority of email success or failure in delivery. Needless to say, no one received a personal invite until I found the problem and begged Microsoft to forgive me. My crime? Sending out an email with more than one email as the destination. I would have to pay for that “service” and get a key to bypass Microsoft gatekeeping, though I’ve been sending thousands of emails for years in the same single session. Again, things have changed. And in this case, it would be insane to try and send a group email using my paid for GoDaddy mail account, simply because Microsoft’s virtual cock is shoved so extremely far up GoDaddy’s digitally compliant rectum. And Microsoft, apparently, only forgives a couple of times before a total banning of all email takes place. For three months all my personal, single emails were prevented delivery without knowledge.
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So what should I do?
Here are my immediate and future actions as planned, for the moment, and how you can help support my efforts to overcome this strangeness…
THIS BLOG – The future of this blog is simple and mostly stagnant. It will remain here for your benefit for as long as the digital gods allow its inconvenience to them. I will only post here when one of my major video documentary projects or Red Pill Sunday School is newly posted.
MY VIDEO SITE – While I will continue to post or attempt to post at Bitchute and Odysee, I will not risk posting at Youtube anymore. They don’t need my help in erasing my whole channel, which of course, is really their property, not mine and not yours. As Bitchute is extremely problematic with uploads, I am currently only updating my “RED PILL SUNDAY SCHOOL” channel on Odysee. (Link: https://odysee.com/@redpillsundayschool:e) If you are looking for my most recent radio appearances and Red Pill Sunday School videos, then Odyssey is the place. Youtube is no longer reliable, fair, or reasonable.
FUTURE DOCUMENTRIES – I will be posting three major projects this year, finishing out my older documentary series so as to make room to start fresh (see NEW BOOKS below). I will post these for free, as always, at least on Odysee. When finished with these projects – Wagging The Dog 2, Lethal Injection 3, and my current Red Pill Sunday School video on the fraud behind UCC / UNIDROIT / STRAWMAN / REDEMPTION and the “change of status” gurus that are misleading people into a stateless international commercial hell, I will at that point put all of my documentaries, from The Corporation Nation series on, onto a portable drive or thumb drive, which will either be for sale or free with donation, depending on what I can accomplish with your help and support over the next year.
EMAIL LIST OR FORUM GROUP – Here I am unsure of how to proceed, considering the initial video at the top that you hopefully watched before getting this far. As this blog is practically invisible and cast in the shadows, I see no point in continuing writing upon it. It can disappear completely at any time into the digital nether. Therefore, my plan is to form an email list and/or forum that I can inform you of my new works and how to get them.
BLOG PRESERVANCE / NEW BOOKS – As many of you know, I have 100’s of blog posts, many of them long enough to inhabit a small or medium book. And some of you know that I have 1000’s of pages of unpublished works and research that have never seen the light of digital day. Therefore, I have decided that once my video productions are finished, I will be printing (or self-publishing on-demand) my most important works, taking my blog and implementing the information within into rewritten and amended PERMENANT books. How these become available to you is up to you. I can risk the print on demand model with such corporate horrors as Amazon, Barnes and Noble, etc., knowing that they have the power to remove my book at any time just as my other sites have been virtually disappeared and relegated to the shadows. But I wonder if you might be interested in helping me keep all my stuff private, as my current STRAWMAN book is? Let me explain…
PRIVATE MEMBERSHIP ASSOCIATION AS A CHURCH/MONESTARY – I am considering some type of fund raiser so as to be able to join one of the private membership associations (PMA) designed to help me start my own PMA. However, the expense is very high, especially for me. The reason for this is to form a private religious association, one that I can continue to write and print books (and films) that would be private and donation-based, or in other words non-commercial and outside of the US jurisdiction. My upcoming RED PILL SUNDAY SCHOOL will explain why I have chosen to go in that direction, as opposed to what many people are being fooled into, that of changing status and falling into international, commercial purgatory. This video is in answer to all that have asked about the “national” status, the “state assemblies” concept, and what I thought about it. Well, you might not like my answer, but you will certainly know why it is absolutely a fraud and why UCC and other uniform codes are not meant for good and moral people, only voluntary debt slaves. That said, the PMA model is the private path, existing without permission or incorporation, outside of the nation-state called United States and outside of commercial rules and non-governmental treaty authority. But I will need financial support. Once this happens, the sky is the limit. Everything we do can be done in private, without the preview or legal constraint of the FDA, the IRS, and all the other commercial corporations of the de facto United States. I will need to raise the membership fee, if possible, of $10,000+ in order to do it right, to join and get the support of the right people. I will take no part or profit from what is raised. It is only to gain membership into a PMA that is designed to support my own PMA. If you are looking for something to invest in for your own future as well as mine and my ability to bring together (associate) like-minded True-Christian people, then please contact me privately at (clint@strawmanstory.info). I will endeavor to pay back any unconditional gifts given to this end. Unfortunately, this must be privately done, so I will not be opening a “fund-me” or other account. This is, in my belief and experience, the last chance we have. And I am willing to be the test animal to get it going, to put in the full-time research, and to do it right with the right mentor and membership. Please contact me if you can contribute to that end. For more information on the PMA I have potentially chosen, after searching many, please go here:(https://www.proadvocate.org/about/) and watch this video:
Unfortunately, Karl died a few years ago.
Regardless of what happens, I intend on preserving my work in the form of books, somehow, some way. I hope to do it privately in my own private non-incorporated church/monastery.
That said, above all else, I am choosing sanity. I will not be erased, disappeared, or censored that easily. I’ve spent much of my life trying to find this privacy model, that is, finding the greatest open secret since the CAFR!
I am open to suggestions on the email/forum and open to anyone that wishes to help set it up. I will post on this blog when I get that list and/or forum going, and will send out an initial private email with all the addresses I have, and getting permission for future mailings.
Be sure to watch the lengthy must see Red Pill Sunday School coming in the next week or two. It’s a deep dive like no other I’ve done, and will fill in many holes.
Again, I thank you for your continued support and viewership over the last decade. May we find the answer to our collective problem together, and soon!
All my love and friendship…
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Clint > Richard-son (realitybloger.wordpress.com) Tuesday, January 3rd, 2022
Well folks, after a tedious 3-day delay of over 70 hours, my new documentary has been “censored” by Youtube for “copyright” claim, despite the protection of law that declares fair use protection for non-profit and educational and critical (critique) works. No money earned, no legitimate copyright claim. Copyright, of course, only protects greed and gain. Yet again we see that money corrupts all things… Not ironically, all videos presented in Lethal Injection 2 are downloaded from Youtube in the first place.
And so here’s the new plan…
Firstly, watch my short 4 minute farewell video to the corrupt Youtube/Google garbage heap of monopolistic incorporation, which strangely enough it did not ban, here:
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Now, the good stuff:
Lethal Injection 2: A Corruption of Blood (Part 1) can now be seen on the following platforms. However, the film is still being uploaded and processed at Bitchute.
Please feel free to view and download these files freely as with all my works, or if you’d like to wait, a lower quality (smaller) file will be available within the next couple of days and posted above.
Please also share them freely as you see fit in both formats, remembering that the only thing that makes it lawful to do so is its perceived legal status, or in other words, please do not attempt to sell, rent, monitize, or profit from this movie in any way. Always keep it free and available to all people.
Future parts to come in 2021, if we live that long…
Have a spiritual, wonderful Christmas and enjoy.
All my love…
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–Clint > richard-son (realitybloger.wordpress.com) –Wednesday, December 23rd, 2020
On December 1, 2020, the ex-Pfizer head of respiratory research Dr. Michael Yeadon and the lung specialist and former head of the public health department Dr. Wolfgang Wodarg filed an application with the EMA, the European Medicine Agency responsible for EU-wide drug approval, for the immediate suspension of all SARS CoV 2 vaccine studies, in particular the BioNtech/Pfizer study on BNT162b (EudraCT number 2020-002641-42).
Dr. Wodarg and Dr. Yeadon demand that the studies – for the protection of the life and health of the volunteers – should not be continued until a study design is available that is suitable to address the significant safety concerns expressed by an increasing number of renowned scientists against the vaccine and the study design.
On the one hand, the petitioners demand that, due to the known lack of accuracy of the PCR test in a serious study, a so-called Sanger sequencing must be used. This is the only way to make reliable statements on the effectiveness of a vaccine against Covid-19. On the basis of the many different PCR tests of highly varying quality, neither the risk of disease nor a possible vaccine benefit can be determined with the necessary certainty, which is why testing the vaccine on humans is unethical per se.
Furthermore, they demand that it must be excluded, e.g. by means of animal experiments, that risks already known from previous studies, which partly originate from the nature of the corona viruses, can be realized. The concerns are directed in particular to the following points:
The formation of so-called “non-neutralizing antibodies” can lead to an exaggerated immune reaction, especially when the test person is confronted with the real, “wild” virus after vaccination.This so-called antibody-dependent amplification, ADE, has long been known from experiments with corona vaccines in cats, for example. In the course of these studies all cats that initially tolerated the vaccination well died after catching the wild virus.
The vaccinations are expected to produce antibodies against spike proteins of SARS-CoV-2. However, spike proteins also contain syncytin-homologous proteins, which are essential for the formation of the placenta in mammals such as humans. It must be absolutely ruled out that a vaccine against SARS-CoV-2 could trigger an immune reaction against syncytin-1, as otherwise infertility of indefinite duration could result in vaccinated women.
The mRNA vaccines from BioNTech/Pfizer contain polyethylene glycol (PEG). 70% of people develop antibodies against this substance – this means that many people can develop allergic, potentially fatal reactions to the vaccination.
The much too short duration of the study does not allow a realistic estimation of the late effects. As in the narcolepsy cases after the swine flu vaccination, millions of healthy people would be exposed to an unacceptable risk if an emergency approval were to be granted and the possibility of observing the late effects of the vaccination were to follow. Nevertheless, BioNTech/Pfizer apparently submitted an application for emergency approval on December 1, 2020.
CALL FOR HELP: Dr. Wodarg and Dr. Yeadon ask as many EU citizens as possible to co-sign their petition by sending the e-mail prepared here to the EMA.
End Excerpt.
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I’ve been wondering when sterilization would be found as a “side effect.” And while I will certainly feign no surprise, I will simply say that any woman that would get this vaccine before these questions are answered in triplicate is simply not human, not sane, wallowing in some twisted mix of Narcissism and Sociopathy. Sterilization is not an acceptable sacrifice for anything, let alone an unproven, apparently eugenic, experimental inoculation.
And, for both women and men, remember well what we learned from my Lethal Injection documentary – that reproductive organ xenotransplantation (inoculation) as a sterilization vaccine is used to sterilize wild horses and other animals, as well as human men and women, by creating the same type of antibody response against male and female reproductive organs, preventing spermatogenesis in males as well as birth control in females.
Haven’t seen Lethal Injection: The Story Of Vaccination?
Well then, now is a really good time to refresh your memory or see it for the first time. Why? Well, besides what is about to be sold to us in the form of a vaccine, as many of you know my new documentary Lethal Injection Part 2: A Corruption Of Blood is going to be posted very soon, likely by this weekend if I can do so. Much of the history covered in Part 1 will not be repeated, so I would recommend rewatching Part One as a primer for Part 2. And remember, this documentary will be a master class on the entire medical industry, totaling over several parts about 35-40 hours at best estimate. That means this first installment will barely even scratch the surface of the whole story behind this nightmare we are living through today. My promise to you: after watching this series, you will never again question what is the horrific story behind the story of vaccination, and will never again ask your doctor whether vaccination is right for you.
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Wow! I posted this in 2011. Imagine what I’ve uncovered since then!
Look for Lethal Injection 2, coming this month, and God-willing this weekend!
Oh, and by the way, when I searched for that same page from the US Geological Survey on horse sterilization, it was gone. In its place? An updated, less informative page on the subject. Here’s a couple highlights of what it says today…
…The U.S. Geological Survey and the Bureau of Land Management are cooperating on studies investigating the potential of fertility control drugs to reduce foaling rates.
Molecular tagging is a new application of molecular genetic techniques to traditional mark-recapture methodology designed to address situations where traditional methods fail. In such studies, non-invasively collected samples (such as feces, feathers, or fur) are used as a source of DNA that is then genotyped at multiple loci such that each individual animal can be uniquely identified. Thus, each individual’s DNA represents a unique tag analogous to a band or other mark used in traditional mark-recapture studies.
…This study involves developing a new method for estimating horse population sizes based on non-invasive techniques; using genetic analysis of fecal samples (dung) and mark-recapture population estimation models. This research is in collaboration with Colorado State University and BLM.
FORT scientists are leading collaborative research projects to provide the BLM with better tools for managing expanding wild horse and burro populations. We are assessing the carrying capacity of wild horse habitats, behavioral effects of spaying mares and gelding a proportion of a herd’s stallions, testing the efficacy of an intrauterine device for mares, and evaluating four fertility-control tools for burros. We are also developing aerial survey techniques for burros, testing the use of DNA extracted from dung to count wild horses, and evaluating effects of cattle versus horses on sage- grouse habitat. Collaborators include Colorado State University, BLM, Oklahoma State University, University of Massachusetts, and APHIS.
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Less info to be sure, but they are still up to their sterilization vaccine tricks. Again, see the first section of Lethal Injection Part 1 for the full detail on how sterilization vaccines work, which is the same reason this new vaccine will cause similar autoimmune sterilization.
It does however, point to a few studies that we should certainly take note of, which were the studies used to justify the continued use of these sterilization vaccines back in 2011. The first just happens to be the results of this previous sterilization campaign as originally covered by my documentary. Let’s see how their sterilization vaccine (an inoculation of pig ovary proteins [e.g. Porcine Zona Pellucida (PZP)] into the male and female horses faired…
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Foaling rates in feral horses treated with the immunocontraceptive porcine zona pellucida
Wildlife Society BulletinBy: J.I. Ransom, J.E. Roelle, B.S. Cade, L. Coates-Markle, and A.J. Kane
Locally abundant feral horses (Equus caballus) can rapidly deplete available resources. Fertility control agents present promising nonlethal tools for reducing their population growth rates.We tested the effect of 2 forms of the immunocontraceptive porcine zona pellucida (PZP) on foaling rates in 3 populations of feral horses in the western United States.A liquid form requiring annual boosters was administered at Little Book Cliffs Wild Horse Range, Mesa County (CO), and Pryor Mountain Wild Horse Range, Bighorn County (WY) and Carbon County (MT), and a time-release pellet form designed to produce 2 yr of infertility was administered at McCullough Peaks Herd Management Area, Park County (WY). Average foaling rates (foals born/mare-yr) from direct observation of untreated and treated female horses (mares), 2004-2008, were 60.1% (n = 153 mare-yr) versus 6.6% (n = 91 mare-yr) at Little Book Cliffs, and 62.8% (n = 129 mare-yr) versus 17.7% (n = 79 mare-yr) at Pryor Mountain, respectively. At McCullough Peaks, mean annual foaling rates from 2006 to 2008 were 75.0% (n = 48 mare-yr) for untreated mares and 31.7% (n = 101 mare-yr) for treated mares. Controlling for age of mares and pretreatment differences in fertility, PZP reduced foaling rates in all 3 herds. The pellets used at McCullough Peaks (produced by cold evaporation) were less effective than pellets used in a previous trial and produced by heat extrusion. Immunocontraception with PZP may be a useful tool in reducing fertility rates in some western United States feral horse herds, but population growth reduction will depend on timely access to mares for inoculation and the proportion of mares that can be successfully treated. ?? 2011 The Wildlife Society.
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In another study referenced, we find a different kind of “side effect” that perhaps we don’t speak of enough:
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Contraception can lead to trophic asynchrony between birth pulse and resources
PLoS ONE By: Jason I. Ransom, N. Thompson Hobbs, and Jason Bruemmer
Abstract
Abiotic inputs such as photoperiod and temperature can regulate reproductive cyclicity in many species. When humans perturb this process by intervening in reproductive cycles, the ecological consequences may be profound. Trophic mismatches between birth pulse and resources in wildlife species may cascade toward decreased survival and threaten the viability of small populations. We followed feral horses (Equus caballus) in three populations for a longitudinal study of the transient immunocontraceptive porcine zona pellucida (PZP),and found that repeated vaccinations extended the duration of infertility far beyond the targeted period. After the targeted years of infertility, the probability of parturition from post-treated females was 25.6% compared to 64.1% for untreated females, when the data were constrained only to females that had demonstrated fertility prior to the study. Estimated time to parturition increased 411.3 days per year of consecutive historical treatment. Births from untreated females in these temperate latitude populations were observed to peak in the middle of May, indicating peak conception occurred around the previous summer solstice. When the post-treated females did conceive and give birth, parturition was an estimated 31.5 days later than births from untreated females, resulting in asynchrony with peak forage availability. The latest neonate born to a post-treated female arrived 7.5 months after the peak in births from untreated females, indicating conception occurred within 24–31 days of the winter solstice. These results demonstrate surprising physiological plasticity for temperate latitude horses, and indicate that while photoperiod and temperature are powerful inputs driving the biological rhythms of conception and birth in horses, these inputs may not limit their ability to conceive under perturbed conditions. The protracted infertility observed in PZP-treated horses may be of benefit for managing overabundant wildlife, but also suggests caution for use in small refugia or rare species.
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Are these studies talking about horses, or us? Or both? It’s hard to say. For these PZP vaccines are used in human sterilization as well.
For more information, here’s another study on the subject, for those that have that I don’t believe this conspiracy stuff attitude, here you can instead believe the scientific data:
The basic principle of contraceptive vaccine is to generate either humoral and/or cell mediated immune response against hormones/proteins that are critical for reproduction, which will lead to interference in their biological activity resulting in inhibition of fertility. Basically, contraceptive vaccines can be broadly categorised as those i) inhibit production of gamete (spermatozoa, egg); ii) inhibit gamete functions such as fertilization; and iii) inhibit gamete outcome. GnRH primarily synthesized and secreted by the hypothalamus (though extra-hypothalamic sites for its secretion have been reported) acts on the anterior pituitary and in turn regulate the production of luteinizing hormone (LH) and follicle stimulating hormone (FSH). Both, LH and FSH secreted by pituitary, in turn acts on testes and ovaries leading to production of sperm and oocytes, respectively. Thus neutralization of GnRH, LH and FSH or blocking LH/FSH receptor by generating specific antibodies may lead to inhibition of gamete production.Generation of immune response against spermatozoa- and/or egg-specific proteins will interfere in their respective functions thereby leading to inhibition of fertilization. Post-fertilization, the embryo synthesize and secrete human chorionic gonadotropin (hCG), which has also been used as target for development of contraceptive vaccine for women (28). In the context of wildlife population management, contraceptive vaccines based on GnRH and zona pellucida (ZP) have been tried at the field level. Figure 1illustrates the basic principle and steps at which the GnRH and ZP-based contraceptive vaccines will act thereby leading to inhibition of fertility. In the present review, both GnRH- and ZP-based contraceptive vaccines will be briefly discussed with respect to their contraceptive efficacy and safety. In addition, the current limitations with respect to contraceptive vaccine delivery in free-ranging wildlife and plausible solutions will be discussed.
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When will you get it through your head, you live-stock, that your reproductive ability is a disease that needs an autoimmune vaccine against it? What more needs to be said? For now, ironically, you have it from the horses mouths – a former minister of health and a former Pharma head executive.
Or maybe they just retired to go into the conspiracy business…?
Please share this article with every and anyone you know that has or is expecting to have children in their lifetime. There is no turning back from this kind of reproductive harm.
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–Clint richard-son (Realitybloger.wordpress.com) –Tuesday, December 8th, 2020
I recently received yet another emailed inquiry regarding the three possible “exemptions” for vaccines. Probably more than any other subject this particular question rears its ugly head, and usually they reference religious exemption more than not. Now, I keep telling people not to ask me questions or listen to me if you don’t want the total, harsh reality that is the Truth, but they seem to want to be disappointed and disillusioned anyway. And so today I’m going to tell you that desire the Truth exactly how you can use religion as your sword against vaccination for you and your children.
First, though, let’s treat the other exemptions, those being medical excuse and conscientious objection.
Beginning with medical exemption, this particular legal exemption is a catch 22. In order to exempt yourself from a medical act, such as vaccination, you need a medical doctor’s letter. See the problem here? While in reason and truth any free-willed, neutral, educated medical doctor (an oxymoron) would exempt all his or her patients from the horrors of vaccination, the term “medical doctor” (MD) is not a real thing. It’s a flattering, legal title granted only to those willing to not act upon their conscience, and therefore possess and active ignorance and willingness to ignore actual science that shows the absolute ludicracy that is vaccination and the health epidemic it has caused. All that aside, the most important factor to understand for why this exemption is useless and revokable is because it is not an inherent right of any man. It is specifically a legal, man-made exemption that has nothing to do with God-given (Natural), inherent rights. All medical exemptions are powered by government permission to do so only, and the corporations that most doctors work for are known to fire without prejudice any nurse or doctor that either refuses vaccines for themselves or speaks publicly about the dangers of vaccines. In the near future, you will not find any doctor that will be willing to risk his or her career or funding just so you can protect yourself and your children from such dastardly pharmaceutical poisons. Because everyone in the world is technically qualified for a medical exemption when the actual research and studies are understood, it’s kind of like giving everyone in the world $1 million dollars: nothing would actually change, and in a few years most common people will have lost it anyway to the various schemes designed to legally steal it, such as medical billing, the #1 reason for bankruptcy in the United States. If everyone is exempt, then no-one is. This will make more sense as we continue…
The second exemption is conscientious objection. This one is about as realistic as it was in the draft for the Vietnam War. If a right is revokable, then again it’s not a Natural, inherent Right. If a right can be taken away, then it was never yours in the first place. And unfortunately, this applies to all three exemptions we are covering here. But more to the point, there is no real place for conscious objection in a legal system. The legal, civil law is strict. It is not up for contention. Follow it or be punished. Choice is an illusion when under the Roman (strict) matrix of legal law. Moral and conscientious thoughts are certainly allowed, but acting on them is a thought crime. It’s terrorism at best. If this wasn’t true, then government would fall tomorrow due to conscientious objections to its immoral policy of controlled chaos and madness. So the conscientious objection fallacy, while hopeful in its promise, is really just a cosmic joke. Just ask those who objected to the Vietnam War. You might need to go to Canada for that though… or visit them in prison.
To put this another way, we must understand that corporations, that is, legal persons, including individual citizenships of the United States, were invented in Roman times to be strictly exempt from moral and conscious responsibilities and actions. Corporations (persons) are designed by men to remove men from God’s Realm, from Nature, and therefore to pretend a legal (artificial) shelter from the moral Law, and equally from spiritual consciousness. The point is this: conscientious thought requires a spiritually and morally conscious man that acts by choice. This is impossible under and in the matrix of legal code. For there is no conscious in legal persons, places, or things. There is nothing. Emptiness. A void of anything Real, of anything Natural, of anything Created by God. Without choice, there can be no moral action. The legal law eliminates choice, leaving no ability to follow any alternative, moral path, and generally causes men to act against their religious, moral foundation. This is indeed the specific purpose of the legal system and the person-hood, the elimination of the need of men to choose at all times what Nature and Its Law requires. The legal law unbalances the scale, taking away the ability to spiritually measure right and wrong. A person that has no conscious cannot claim conscientious objection, for a legal person is property of the legal system, and like a video game character, is only allowed to exist by the rules of the legal game system and its masters (false gods). A pawn is ultimately moved by its master, headlong into oblivion, having no real choice except to go forward on the legal game board. No is not an option, and pawns have no exemptions or free will from their controllers. Real choice is simply not in the artificial code that makes up a legal person. A person is a construct of legal law. It has no conscious of its own. And the man that acts in legal person therefore surrenders any right to act on his or her own conscious, instead obeying strictly and under sanction the legal law of men without question, that is, without the right to act conscientiously.
And that leads us to the third legal exemption, that being a “religious” one. In this particular exemption we find a hint of the only True choice respected by government, the religious law. Sure, a medical exemption is respected, but doctors are agents of government, so once government removes the artificial, temporary right of doctors to exempt a patient and keep their jobs, then that exemption will be gone as well, as moral choice by the man acting as a “doctor” of government will no longer be an option. The difference between the medical and conscientious objection vs. the religious exemption is very simply that the legal law is in every case trumped by actual religious law.
The religious exemption, therefore, would seem to be the all powerful weapon to end all battles, right?
Wrong. And here’s why…
If you’ve ever seen a movie where the hero attempts to ward off evil spirits with a cross or crucifix, say in vampire movies or the fantastical films about Catholic priests committing exorcisms, you always find a recurring theme. They all say and warn the same thing: you have to have faith for that to work. In other words, to hold up an idol of anything and pretend that you have the power that that idol represents is what is called hypocrisy. If you want to harm a vampire or demon with a cross, then it is the power of God that does it, not some trinket made by the hands of men. But when actual religious faith comes into the soul bearing that idol, suddenly the power of God is behind it, and the mere idol turns into a weapon of unimaginable proportions.
This is, of course, merely the fiction of Hollywood. Or is it? Is there actually a moral lesson to learn from these fantasies? Can this concept be applied to the subject at hand, that is, vaccination exemption?
Absolutely. In fact, we can use it as a very understandable metaphor.
Let us pretend that the idol in these ridiculous Hollywood stories, the cross, is what we are holding up as our own figurative weapon of legal “religious exemption.” Can a self-proclaimed “atheist” possibly use religious exemption without believing in the very Source of that weapon? The answer in Reality, of course, is no. But the legal realm is not Reality, and so yes, strangely enough an atheist can use a legally invented idol called as religious exemption. In other words, the atheist can openly commit hypocrisy against his own false belief system, and the legal system is happy to protect that right of hypocrisy… until, that is, the governmental body of that legal system is ready to retract it. And that’s where most of us find ourselves today, watching helplessly as the administrators of the persons (property) of the legal matrix change its programming code to legally reflect that religious exemption is no longer an idol that is acceptable to be used.
But how can it do that?
Simple. These legal exemptions never existed in Reality in the first place for any man. Legalism is fiction. Legal law is fiction. And so any exemption that comes from a legal government (artificial person) was born and will die in fiction. And any religious claim you may make as a legal, artificial, fictional person dies with it.
You see, the whole time you’ve been that hero (actor) trying to use an idol that has nothing to do with what that symbol’s actual Source is. To use a True religious right, a man (male or female) must act as a religions man. Persons (legal fictions) cannot be religious nor act under the Higher religious law, because persons aren’t of Nature. They aren’t Real. They are not Creations of God. Thus, the vampiric demons of government, that is, attorneys in black moo-moos acting as false gods (magistrates/judges) have no revulsion to your false idol of religious exemption. You’ve gotta have faith for that to work…
Please watch these for your understanding, they are placed here by me for a purpose.
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Idolatry: the TV actor, Vincent, before True faith:
And the God-fearing man Vincent after True faith:
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The cross only represents the Law of God (Jesus Christ/Logos), but without faith, the Law of God is a useless idol in any form. Without following the Law, It has no power to protect you, and as a weapon it’s pointless. It’s just an idol for sinners pretending to worship God through Jesus Christ (Law). Might as well hold up a kitten without claws.
Keep in mind this is metaphoric, and that its meaning applies to defeating all things that are “evil” in the Bible, which essentially is anything man-made, including the legal matrix code. The vampire (attorney) must corrupt your blood in order to control you. The fangs of the vampire are the words of a legal contract. And personhood is to be bound under the spell (spelling of words) of the master of that contract, causing the agentic relationship of master and servant (volunteerism). The Law of God (Nature), represented by the symbol of the cross here, is that which defeats the vampire (attorney). The word of Truth (God) destroys the words of legal demons. The cross represents the implementation of moral choice. The vampires of government have no control over you unless you accept their initial, original sin, the corruption of blood (attainder) that places artificial status upon you in their own, invented society.
And this depiction of false faith in a false idol of god describes just about every “Christian” in the United States, and for that matter, the world. Legal religions (corporations) are institutionalized idolatry, causing men to attempt in vein to worship God while doing so in legal, fictional persona (mask), to bear the protection of God and Its Law while not following that law themselves, as if It is external from them. And this is why the Christian “church” has no power religiously or politically. A section 501 corporation is designed to take away religious rights and exemptions, not bestow them. Only a fool can possibly believe that God-given rights can be given by a legal corporation under the IRS code of government. Only a brainwashed man can be made to believe a corporation (artificial person) has anything to do with the Source of Nature and Its Law. Only a idolator can call himself a “Christian” while following the legal, antichrist, anti-God law of man. Only a slave cannot differentiate between the God of Nature and the false gods of legal government. For the actual, True church of the Bible is only a free and moral, private People, that is, men following the Law of God (Nature), which absolutely excludes and despises all legal code. But in legalism, the “church” is a legal term of art meaning a corporation, an artificial person in law, and has nothing to do with men. In other words, legally established religions are not in any way part of God’s Realm or Law. They are a legal simulation of the Real, and so are its members. Corporate religions bound completely under legal government is like a bug trap for men, burning our wings so that we cannot fly away, keeping us locked into the legal (anti-God) system of law even while allowing us to pretend in idolatry through flattering title (without True faith) that we are followers of the Law of the Bible, of the example of Jesus Christ. Worst of all, this is all warned about in the Bible, which calls us foolish hypocrites as the figurative dumb asses.
But here’s the kicker. Men are hypocrites toward the Law of God (Nature) in the Real world. But in the legal matrix, persons are simulators. Simulation and hypocrisy are the same term. Therefore, to act in legal persona (mask) under legal (anti-God) law in the legal simulation while at the same time pretending to be a True “Christian” equals the metaphor of being plugged into the matrix (lie) with or without contemplation of ones actual hypocrisy as a man. The “Christian” flattering title is merely ones “projected self-image” while trapped inside the legal matrix code. It’s idolatry. Simulation. But in Nature, from God’s perspective, if you will, simulation equals hypocrisy, two different words that mean the same thing in the two different realms.
It’s also called apostasy, and it’s the foundational purpose of corporate Christianity. It’s the opposite of being an apostle:
APOSTASY – In English law. The total renunciation of Christianity, by embracing either a false religion or no religion at all. This offense can only take place in such as have once professed the Christian religion. (–Black’s Law 2nd Edition)
APOSTASY – noun – [Gr. a defection, to depart.] 1.An abandonment of what one has professed;a total desertion, or departure from one’s faith or religion.2. The desertion from a party to which one has adhered… (–Webster’s 1828 Dictionary of the English Language)
APOSTATE – adjective – False; traitorous. (–Webster’s 1828 Dictionary of the English Language)
HYPOCRITE – noun – 1. One who feigns to be what he is not;one who has the form of godliness without the power,or who assumes an appearance of piety and virtue, when he is destitute of true religion. And the hypocrite’s hope shall perish. Job 8:1. 2.A dissembler;one who assumes a false appearance. Fair hypocrite you seek to cheat in vain. (–Webster’s 1828 Dictionary of the English Language)
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I go to church every Sunday (according to the legal Roman calendar, the Pope, and its legal system of secular law) and on legal holidays (which are not actually Holy Days) and therefore I’m a “Christian.” Time to call bullshit on that logical fallacy, isn’t it? It’s more like this: I don’t follow the Law of God by the example of the Christ allegory and instead have idolized the corporate churches false image of Jesus Christ as if Christ is God, and so I call myself as the Romans did, as a “Christian,” despite my membership to an apostate, corporate religion that makes its own doctrine and misleads me at every turn in simulation.
So how can you use religious exemption in the legal system? You can’t, dumb ass.
You’ve got to have faith for that to work.
But the legal system and its public institutions have caused you to not even know what faith is! And so here is where I will tell you how to religiously bypass any legal law that requires persons to vaccinate.
Ready?
Stop acting in legal person (artificial, legal status).
Stop taking benefits from the demons and vampires of legal (anti-God) governments, which require you to voluntarily act in legal person.
Stop being an idolator.
Stop believing you have inherent, Natural, God-given rights when you sold them long ago to become a legal citizenship and as you continue to simulate the part.
Stop believing the foolish notion that God’s (religious) Law can save you when you don’t have True religion and faith as your sword (reason) and shield (protection).
Lastly, we must understand just what an exemption is and why it doesn’t and cannot exist for men of God.
EXEMPTION – 1. Freedom from any service, charge, burden, tax, evil, or requisition, to which others are subject; immunity; privilege. Many cities of Europe purchased or obtained exemptions from feudal servitude. No man can claim an exemption from pain, sorrow or death. (–Webster’s 1828 Dictionary of Law)
EXEMPTION – Freedom from a general duty or service; immunity from a general burden, tax, or charge. A privilege allowed by law to a judgment debtor, by which he may hold property to a certain amount, or certain classes of property, free from all liability to levy and sale on execution or attachment. (–Black’s Law 2nd edition)
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Why are these exacting definitions important to comprehend?
This is key. To have an exemption from vaccination means one and only one thing — vaccines are already a requirement. In other words, the government considers it your duty as its citizen (subject to its legal law) to be vaccinated. The exemption is a temporary, revokable “freedom” from that duty, a permission to avoid that requirement of law. Vaccines are already required of persons (property), which are performance debt-slaves of government. If you claim exemption, you are actually acknowledging and respecting the false legal law and its gods by getting their permission to have freedom from it. Remember, in legalese, freedom is defined as franchise. It’s not True freedom under God to self-govern, but rather an artificial freedom bestowed temporarily to the fictional person that you currently respect and utilize as a status in legal society. Remember, all man-made things are temporary. Therefore, if the person is required to be vaccinated, then you as surety in bond of that person must obey in order to retain that franchise (legal freedom), in order to continue using that person (legal status). Those who refuse the legal law and end up punished, fined, or imprisoned for their illegal behavior (while acting in legal persona) have broken the rules of their franchise (citizenship). People in jail also have freedom (franchise) when they are on good behavior. Same thing, different prison. In the open-air debtor’s prison of the nation, citizens (prisoners, as public, non self-governing wards of the state) are given certain exemptions in their franchise, meaning they have certain artificially induced freedoms allowed to them by permission, licensure, permit, etc. Only a fool would believe those rights and freedoms are God-given, Natural rights.
Inversely, we can understand our Duty to God (Nature), including ones requirement of following God’s Law of Nature by the example of Jesus Christ (Logos personified), which in itself requires no respect of lies, fictions, persons, status, titles, false gods (magistrates), or anything else artificially placed over Nature (Truth) in a simulation of the Real. Again, there is simply no exemption from God’s Law. With any God-given, inherent right comes an equal duty to all other men. Lies are not exempt from Truth, they are diametrically opposed to Truth. And so it’s important to understand that legalism, that is citizenship under the nation, is specifically designed to fictionally exempt man from his Duty to God, to Nature, and that includes ones Duty to all other men. As this is in Reality impossible, the legal system depends on its ability to cloud and obscure any relation we may have to Nature and Its Law, offering the protection of the legal law and the false sense of forgiveness offered by the false “Christian” corporate church that is also under legal law, not God’s. To defeat God (Nature), the state simply replaced God with a fictional, corporate entity (idol) of its own invention, and then called it legally as religion.
RELIGIOUS – When religious books or reading are spoken of, those which tend to promote the religion taught by the Christian dispensation must be considered as referred to, unless the meaning is so limited by associated words or circumstances as to show that the speaker or writer had reference to some other mode of worship. (–Black’s Law 2nd Edition)
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In American law as a “Christian country” (referring to the free and private People of the States, not the United States legalist corporation as an open-air prison for publicly held-in-persona debt-slaves), the Bible is considered as the meaning of the term “religious” unless that word “religious” is intentionally twisted by the legal language to mean its opposite. Get it? In the United States district corporation, the word religious is a crime, but certain religious exemptions are allowed.
Allow me to quote my book, Strawman Volume 1, where True religion (action) of men and the legal franchise of limited, legal religious belief without practice (action) of US citizenships (persons) is differentiated:
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Begin excerpt:
This is one of the most important lessons in this work. Please ensure full comprehension between these two very different “freedoms” before you proceed with this work. For as a citizenship of the United States, the attachment to your strawman as property under the law of persons only allows you to fall under the “freedom of religion” as a limited legal outlet of commercial franchise. In other words, “Religious Freedom” is against the law of the United States for its subjects (persons).
RELIGIOUS FREEDOM – Within constitution embraces not only the right to worship God according to the dictates of one’s conscience, but also the right to do, or forbear to do, any act, for conscience sake, the doing or forbearing of which is not inimical to the peace, good order, and morals of society.(Black4)
FREEDOM OF RELIGION – Embraces the concept of freedom to believe and freedom to act,the first of which(belief)is absolute, but the second of which(action)remains subject to regulation for protection of society.(Black4)
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Now you tell me, what good is religious, moral belief if you are not allowed to act on it? To be clear, this state of confusion at bar is the very purpose of nations, to prevent self-governing, moral standing in men. For no moral man would allow a nation as this to continue in its abhorrent actions against God (Nature) and man. But the moral man is cowed and pacified by his surety to the law of his persona (false identity). We are so smitten and proud of our nationality, our personality in public that we don’t dare risk doing what is right in and under the Law of God. This is unmistakably and self-evidently the work of the devil (the attorney class) and his scribes.
These are completely separate definitions, on separate pages of the dictionary. They are not the same thing. As citizenships of the United States, you better damn well know the difference before proceeding herein, and before you try and act morally in a society that strictly forbids moral actions without license from the state.
Freedom of moral thought, but not freedom to act upon that conscious moral thought… This is what public, legal freedom (franchise) is when defined by the commercial gods — a legal corp-oration called government. It is not freedom of religion, but franchise of religion. These are as the rules set for employees (agents) by their employer (principal). This is not Natural freedom under God, which is described above as Religious Freedom. This is tyranny named (noun) as “freedom,” where the ability to practice religion is confounded and limited to the franchise it belongs to (of), as freedom (franchise) of (belonging to) religion (memberships to legal corporations, as the legal, anti-God definition of religion). In the United States, the lack of a moral standing in God’s Law (religious, spiritual Life) is the official state religion, as an enforced, amoral lack of It. Freedom is only a franchise allowed to fictional persons. Governments cannot control in totality your thought processes, only your actions (anti-pro-verb) while in its property. Specifically, we must recognize absolutely that the purpose of the legal law is to prevent man from acting upon his moral thoughts and beliefs.
“It’s impossible to have religious freedom in any nation where churches are licensed to the government.”
—Congressman George Hansen, quoted from “In Caesar’s Grip,” by Peter Kershaw
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“The framers of our Constitution meant we were to have freedom of religion, not freedom from religion.”
—Billy Graham
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The legal realm acknowledges only written and spoken words. It is immune, so to speak, from religious and moral (unwritten) controls, as legalism and religious action are foreign to each other. Man is only punished for his actions, and when his actions are in the person of another, he is not acting according to his own moral thoughts of Law.
By providing the fictional, legally “natural” person (strawman) with an insurance bond for a man’s operation in that fictional, commercial realm, government ensures that each individual man will act collectively according to civil law and not according to his own religious and moral thoughts. This is the separation of mind from the body, the killing of the spirit (soul). For the law is attached to the person, and thus the man in the fictional chains of surety to that person is bound by the public law of persons. By acceptation of that person as a commercial vessel (a citizen-ship) in surety, man tacitly agrees and consents (through assent) to abide by the legal law in direct opposition to God’s Law while acting in that fictional persona. He literally agrees to use his Real body as insurance to ensure that he will operate in fiction (evil) according to strictly written law, and if he does not, the man in surety will be judged and punished for the incorrect use of that corporate strawman (property of government). Thus the man’s moral mind does not control his Self (his body), for the law of persons controls his mind and therefore his actions, where the legal persona acts as the surrogate or second self. This is a lack of True Self-respect.
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“No man can enter into a strong man’s house, and spoil his goods, except he will first bind the strong man (through legal personhood); and then he will spoil his house.”
“Or else how can one enter into a strong man’s house, and spoil his goods, except he first bind the strong man? (through legal personhood) and then he will spoil his house.”
—Matthew 12: 29, Mark 3: 27, KJB (added by author for this excerpt)
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“My son, if thou be surety for thy friend, if thou hast stricken thy hand with a stranger, Thou art snared with the words of thy mouth, thou art taken with the words of thy mouth.”
“Go to the ant, thou sluggard; consider her ways, and be wise: Which having no guide, overseer, or ruler, Provideth her meat in the summer, and gathereth her food in the harvest.”
—Proverbs 6: 1-2 and 6-8, KJB
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This is the purpose and pretext of legal surety: insurance that the instigation of person-hood at birth into the nation will incite man’s actions to be in concordance with the legal law as opposed to being in respect of God’s Law and Nature. Incitement to evil acts without moral compass (direction). This is a binding relationship to fictional rulers under contractual terms (word magic), even by the shaking (striking) of hands. For a man’s feet never touch land while he sails his ship upon the virtual sea of that surety (security) of legal commercial fiction. The legal jurisdiction is an invisible, fictional barrier set upon Creation and its Law; a prophylactic barring man from his very own essence as part of that Oneness of Nature.
A fictional person simply cannot follow God’s Law, without exception, for a person is not a Creation of God. God bestows no status upon man but self-evidence. This untouchable essence of negativity towards any of man’s systems of positive law can never be taken away, though obviously we have been fooled into contractually selling those God-given attributes in exchange for fictional non-sense. A man acting in person is subject only to man’s utilitarian legal law of persons (status/condition), with strict prohibitions against God that we call as the doctrine of “freedom of religion.” Opposites attract. A man in public personhood does not need and is not expected to think in any way that is responsible or compos mentis, for the person is allowed only to follow man’s (its master’s) strict legal law when used by its autonomic user.
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“This word ‘person’ and its scope and bearing in the law, involving, as it does, legal fictions and also apparently [IN APPEARANCE ONLY] natural beings, it is difficult to understand; but it is absolutely necessary to grasp, at whatever cost, a true and proper understanding to the word in all the phases of its proper use.A person is here not a physical or individual person, but the status or condition with which he is invested. Not an individual or physical person, but the status, condition or character borne (carried) by physical persons.”
“The law of persons is the law of status or condition.”
—American Law and Procedure, Vol. 13, page 137, 1910
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End Excerpt.
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The Law of God is just as strict as the legal law. It is impossible to Obey the Law of Nature while also obeying the legal law that is designed to be opposed to God’s Law in every way. Claiming anything from religious Law while in personhood under legal, civil law is at best foolishness and at worst insanity. And worshiping God while acting in legal persona is like holding up a cross in idolatry without faith. It will never actually happen.
Religious exemption is a lie, just like any other exemption. It only exists in the legal realm, nowhere else. And in Truth, if you qualify for any type of legal exemption, then you have already fallen into the legal trap. There is no exemption from Reality. There is no exemption from God’s Law. There is only choice, free will, and you must choose which Law to follow.
Exemption, to be clear, is a post-requisite. One can only be exempt from legal law because of whatever legal status one already obtained that allows for exemption. But in the end, a debt-slave is really exempt from nothing, for all legal exemptions can be revoked by the false god that bestowed that artificial, legal right in the first place. The exemption never existed in Reality, being a non-inherent, unnatural right to man, and so it has no religious Law protection. God protects no man that claims exemption from anything, because to claim exemption one must already claim to be agent for a legal entity. Only persons can claim exemption, not men.
A religious man in the True sense needs no exemption. He just says no. Exemption implies that some higher power exists and that the man is pretending to be under that power and authority instead of that of Nature’s Law. You don’t need exemption if you are not under the legal law of the false gods of government. It’s this Higher consciousness that is voided through legal, religious and conscientious exemption. That is, to claim legal exemption one must already be accustomed through brainwashing and public education to believe that government already has power over you as a man (Creation) of God, and in this case, that you are already required to be vaccinated but currently, out of the good graces of the legal gods, have exemption from that legal duty to that government as a person (property) of it. A legal exemption is a claim against a legal thing. Filing a legal exemption is not protection against forced vaccination, it is a claim of artificial rights invented and bestowed upon a feudal tenant of government, which can be revoked or refused at any time for the protection, security, and continuity of government. You can exercise religious exemption while it is allowed my your master because it has nothing to do with True religion. But what you can’t do is practice religious faith to say no to vaccines by the power and authority of God (Nature).
The moral of this story is that unless you act morally, spiritually, and without legal persona, you have no actual inherent right of exemption, because there is no such thing in Nature (Reality). Exemption is a sign that one is in the lowest form of beggary, of slavery, of despotism, of employment (use as property), of dependence upon a legal, state-bestowed franchise of artificial freedom much like a rat in a cage. The power to say no comes not from legal words in the legal matrix code created by false gods. The power to say no comes only from following the Law of God (Truth), which absolutely forbids acting in and respecting other persons and flattering titles, especially the false gods of government. To be clear, if you are not a person, you cannot be forced to be vaccinated. But you cannot just merely claim not to be a person. It doesn’t work that way. Just ask any illegal alien. To act religiously is to obey God’s Law in its fullness. The state will not recognize a free man (son) of God unless that man is actually acting under and as a son of God, of the Law, without deviation, without depravation, without departing the faith (Law), and without defection.
Unfortunately, as the title of this writing appears to promise at first glance, there is no actual (True) religious exemption from vaccination. It’s a misnomer (misnamed). It’s like a magic spell (spelling), where the word and the reality do not jive, just as the entire legal language dresses up Truth with fiction and misdirection. The God-honest Truth is that if you want your children to remain free from these nurse and doctor-delivered vials of poison that induce fast and slow-growing autoimmune disease, you must leave Babylon and take your children with you. And that requires absolute Love and total sacrifice. The state has tricked you into claiming through birth registration the abandonment of your parental (Natural) rights, delivering (abandoning) your child into wardship and apprenticeship to the nation (as a goyim). We are all birthed through trickery into this legal matrix (artificial womb), like a roach motel, but never told how to escape, how to unplug from the addiction of legalism. The state calls every child (and adult) as property through legal person-hood. In order for that to happen, it must trick you into that abandonment. It must cause you to be confused as to what it is for a child to be an actual property of the parent. No, a child is never a piece of property, as the legal realm attempts to establish through attachment of persona (legal identity/status). Belief that the person is the man (i.e. a child) is key, for identity means sameness in law. In other words, we are all tricked into believing that the person is the same as the man, a logical fallacy of monumental, Biblical proportions.
In Nature (God’s Realm), the word property is not connotative of possession as it is in legalese, but rather refers to Source. Origin. Truth. Natural connection. Family. Like hydrogen is a property of water and water is a property of Earth and Earth a property of the Universe (God), your child is a property (part) of your own Existence, and therefore a property of God’s Creation (the Universe), being a carrier of your blood (figurative, spiritual immortality, bloodline). The child’s blood is a property (ingredient) reflective of its parents (procreation). Not legal property, which is always a lie, but actual property which is a self-evident Truth. We were all tricked into selling those God-given, Natural rights of paternity, fooled into believing that the source of our God-given Natural rights are our own, not a property of God.
Self-ownership without God (Source) is the grand, communist delusion of the ages, where men believe that all inherent rights extend from man, not God, and therefore the Law of God can be bypassed by the selling of those rights in exchange for legal ones, entering the fictional construct of the legal matrix by pretending to abandon Nature (God) and Its Law. Yet in Nature (under God) we can never actually be spiritually defeated unless we choose (volunteer) to, for we never actually leave God, a self-evident Truth which the Bible states that God (Nature and Its Highest Law) never leaves our side if we choose and act in It. In Truth, we cannot Exist or Live without Source, without being a property of God (Nature) and Its Law. But we pretend that the self-evident Truth of Existence (God) doesn’t exist, that God doesn’t exist, and therefore that the power and authority (Law) of God (Nature) doesn’t exist. The status (persona) of legalism merely clouds the Truth with a lie, but the Truth cannot ever die, for no legal fiction exists without claiming some Truth as its victim and host. The duty of parenthood is part of the Law of Nature, not a right. A DUTY TO GOD, not to the state. But the state tricks us into abandoning our God-given Duty by relabeling and calling it a “legal right” that can be imaginarily transferred as a legal property, a fictional title. And we believe this lie so fervently that we are willing to allow the agents of the legalized state (corporation) to literally steal our True property (child) from our homes, without a fight, based on its assumed, mistaken legal identity — by a name that is not God-given.
But hey, who wants to give up that free public babysitting called education. After all, your lifestyle of free leisure time and employment are way more important than that of your health and that of your child, right? And everybody knows that the pursuit of happiness requires the pursuit of money, the root of all evil, right? Of course, your love of money is way more powerful and important than the health of yourself or your child, which is why the legal system runs on money, and why government is the printer, copywriter, lawmaker, enforcer, and banker of money, resting its whole international identity on the false valuation and respect of the evil that money represents. And that’s why, when government soon fulfills the already written requirement that all legal persons (citizenships) of the United States and other nations of goyim must be vaccinated, you will voluntarily and without hope take that poison as a mark that you are a beast of that legal system, that your love of money is more powerful than the love of your child, than your love or purity, than your love of God, and that you are indeed a Godless human without the ability to self-govern and use the gift of Free Will that God gave you. And your children’s children will follow in your weak and defeated example, that is, if the vaccines you allowed them to be tainted with don’t sterilize or destroy them as they’re designed to do.
But by all means, continue in this lunacy of trying to protect the legally bestowed religious exemption of fictional persons as if its already your own inherent right and not just an inconvenient leftover of the legalist thought of some damned outdated, idealistic moral inclusion by some past, slave-holding, false god.
No really, do as though wilt. That’s what they want, as long as it’s legal, and as long as you never actually act out based on any religious, moral thought. Think about it all you want, just don’t act on it without permission, licensing, and an approved, raised corporate seal under tax section 501.
If you want religious exemption, start acting religiously, and stop acting legally. Because using a legal persona is like wearing a condom… the legal persona is a prophylactic to Truth (God). You’ve no access to the Law of Nature, of Truth, from the fictional disposition of a legal (anti-God) persona. And that includes the actual moral choice you seek through legal “religious” exemption.
Heck, that’s such a simple concept that your kids will probably get it faster than you can. And you know what? If you are using your kids as an excuse, don’t. They can adjust way easier than you can to giving up the legal fiction. They’ll be much happier in Nature. They won’t be spoiled anymore. And they won’t suffer from the public school, Common Core blues.
It’s all on you, not them. You are their parent and protector. Start acting like it. It’s your God-given duty, and choice regarding such a Duty to God and to your child is a legally induced illusion for parents. You cannot shirk your responsibility and then pretend to have the very parental power you abandoned through legal birth certification and registration. You made a grevious error based on generational ignorance. Fix it or accept your own chosen, voluntary fate. Find God or remain in abandonment to your Source. Be a Natural and self-Existent property of God or remain a legal property of the state. And to fix the status of your child (property), which can only be a reflection of your own status, then you must first fix your own. You must be the one to sacrifice your false, secular lifestyle and perceived monetary wealth (mammon) therein, as the Bible tells you, crucifying it (the legal, fictional person) so as to be free and self-governing under the Highest Law. For a slave can never elevate its own issue (offspring) higher in law than his or her own legal status. A debt-slave can only bear another debt-slave, for status of an issue (property) depends upon the status of source. You cannot make gold from iron.
Or keep on pretending this knowledge doesn’t exist as you have your whole life. After all, a lifestyle of blatant hypocrisy in the legal matrix ain’t so bad… But I guarantee that it will require vaccination at some point.
The truth is, when you actually become a religious man, in your actions, in your mind body and soul, you won’t need any exemption. You won’t need to dodge bullets because they don’t exist except in the legal fiction matrix, and they can only harm the legal person of those men acting in agency and therefore in bond and surety to those legal persons, not men (sons) of God. The law of the legal matrix simply wouldn’t apply to you, because it’s finally beneath you and you refuse to plug in to any of its properties. You would, by your True religion, refuse to act in, believe in, or respect the persons, places, and things of the legal, commercial realm of mammon. You would see all things only as they really Exist, without artifice, without fiction, including those colored pieces of paper and their digital representations pretending to be money and credit/debt.
So please don’t send me any more inquiries about how to use legal exemptions against anything, unless you are first willing to fact the harsh Truth about your legally induced status (person-hood). I cannot help anyone that will not help themself. You seek legal power yet have none. It’s not Real, and neither, apparently, are you. Ironically, the power you seek Exists only in the Real, in that Realm of Nature and Its Law which you have voluntarily abandoned and continue to deny, that you continue to pretend to worship while wearing a spiritual condom (legal person), a fruitless effort that the Bible over and over tells you to avoid.
I’m sure your next question is how? How do I follow this seemingly impossible path back into Truth? Well, the answer is in the question. To Exist in Truth is to deny all lies, all fiction, all legalism, and all feigned power and delusion. The answers are laid out perfectly in the Bible, which provides metaphorical story after story to answer your questions. It’s why I wrote my book. I am not your judge, nor am I your guide or savior. You are. God (Nature/Truth) and Its Law is your destination, not some idol to worship falsely. But ignorance certainly guides no man of God, only lighting the path for the errands of fools.
Now you know.
Sorry to burst your bubble.
Not really.
.
–Clint richard-son (realitybloger.wordpress.com)
–Red Pill Sunday, August 25th, 2019
“When men differ, both sides ought to equally be heard by the public, for when truth and error have fair play, the former is always an overmatch for the latter.”
–Benjamin Franklin
–=–
Greetings programs…
Here is the first teaser trailer for my new audio/video book/documentary.
They know… Congress is well-aware that doctors (through prescription and medical error)
are openly shown to actually be the #1 killer of Americans.
–=–
Please note that this is a new youtube channel, created for the purposes of my new radio shows and for trailers for this audio/visual book. I doubt very much the final video will be allowed to be posted and played without being censored, and so please keep this channel handy for updates and to learn how to receive this video offline (free and not for profit), most likely on a thumb drive that you can pass out in activism.
About the project: I’m trying something new. This is not your typical movie or documentary, it is in fact a resource book designed to be listened to and watched, an 40? hour audio/visual experience not before attempted as far as I know, and therefore breaking all the rules of brainwashing and control that keeps us dumbed down through 10 minute memes and popular culture. It will make you laugh and cry, like seeing the (secular) world for the first time. This is a book that you don’t have to read because I’m reading all of their studies and information to you. It is a PHD course in medicine and pharmaceuticals, eugenics (now “genetics”) and its source in university syndicalism and their patents, chemical/biological weapons, drugs in the military, the truth about the proven effects of toxic metals as ingredients and adjuvants, and will prove without a doubt the connection of drugs and vaccines to all modern disease states, drugs impossible to acquire without a doctors prescription (iatrogenic/doctor-caused harm and death). It will expose the Truth behind a most heinous and extreme fallacious lie – that doctors in fact do not take any official oath to do no harm, and certainly not the Hypocritical oath. And it will show the history of doctors and nurses promoting every unhealthy, cancer-causing, recreational and illicit drug as a “cure-all” from cigarettes to methamphetamine, cocaine to speed, alcohol to canibus. Most importantly, this is an attempt to preserve the history of what is fallaciously labeled as the anti-vaccination movement, from its satiric beginnings against mandated vaccines with cow pus (pox) to its now almost completely censored attempts to educate and use science to help people make educated choices, and to prevent the same catastrophes caused by the mandated inoculations of the past.
In the end, my intention is not only to end any debate about the harm caused by inoculation, but to place all the pieces of the puzzle into one undeniable, inarguable master class, revealing 100’s of their own studies and publicly unspoken knowledge of the well-documented harm (side-effects) they have caused, including all the players, good and evil, that complete the puzzle once and for all. In this way, I hope to preserve all the efforts of all of us that have publicly fought this fight and suffered the consequences and censorship of blowing the proverbial whistle.
You’ll be shocked at what I’ve put together, and your suspicions will either be verified or disproven… or you will find the Truth to be much stranger than the fictions you’ve been led to believe. This project is the nuclear bomb to end this foolish world war of willful, institutionalized ignorance and outright, provable lies.
Please help me to get this new youtube channel out there by sharing it and this blog, and either copying or embedding these trailers anywhere you can find them a willing home. Remember, no permission is required to copy, quote, use, and repost my works, ever.
The working, most likely final title? Exactly what it is: Lethal Injection: A Corruption Of Blood
Thanks to all,
.
–Clint > richard-son (realitybloger.wordpress.com)
–Saturday, August 2nd, 2019 (on the artificial roman timeline)
Just a quick post here to share an amazing, published fact with those who may still have doubts about the virtually unlimited disease states deliverable through vaccinations and other injectable, pharmaceutical drugs… you know, the ones on TV commercials that warn of side effects like death, cancers, heart attack, high cholesterol, prion-type disease, etc? But today, we are simply going to look at a rather popular vaccine insert for a vaccine targeted for infants and children under 7 years old only. That vaccine is called Tripedia®, Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP), (Sanofi Pasteur Inc.). We find the following statement on page 3 of the actual insert, located at the bottom of the page, last paragraph:
TRIPEDIA: Package Insert and Label Information (Page 3 of 4)
“…Adverse events reported during post-approval use of Tripedia vaccine include idiopathic thrombocytopenic purpura, SIDS, anaphylactic reaction, cellulitis, autism, convulsion/grand mal convulsion, encephalopathy, hypotonia, neuropathy, somnolence and apnea. Events were included in this list because of the seriousness or frequency of reporting. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequencies or to establish a causal relationship to components of Tripedia vaccine.”
I need not say any more here, for the proof is definitely in the pudding. This cannot be denied in any sane capacity. And it has sparked me even further into mentally preparing to make another vaccine documentary.
It occurs to me that any doctor that has recommended or delivered this particular vaccine while also assuring parents of the safety and non-relation to autism when it is printed right in the insert should be sued immediately for malpractice and fraud to have his license taken away, for whether it was pure ignorance or a manufactured lie, neither of these are good excuses. An ignorant, compartmentalized doctor is the most dangerous, licensed killer on earth. In fact, according to statistics tallied by the Journal of the American Medical Association (JAMA) and many other journal and governmental sources in consideration of death by iatrogenic (doctor/medicine-related) causes, doctors are the third leading cause of death in the United States! Reported at many sources, this is from US News.com:
Medical Errors Are Third Leading Cause of Death in the U.S.
“10 percent of U.S. deaths are due to preventable medical mistakes.”
“…MEDICAL ERRORS ARE THE third leading cause of death in the U.S., after heart disease and cancer, causing at least 250,000 deaths every year, according to an analysis out Tuesday indicating that patient safety efforts fall far short…”
“…Throughout the world, medical error leading to patient death is an under-recognized epidemic,” Makary and his co-author, Dr. Michael Daniel, also of Johns Hopkins, write in Tuesday’s British Medical Journal. They define medical errors as lapses in judgment, skill or coordination of care; mistaken diagnoses; system failures that lead to patient deaths or the failure to rescue dying patients; and preventable complications of care.
Their report comes nearly two decades after “To Err is Human,” a report by the Institute of Medicine, asserted that medical mistakes are rampant in health care. The IOM, a quasi-public think tank made up of leading scientists, drew on existing data to estimate that 44,000 to 98,000 people die in U.S. hospitals each year. Even then, some researchers claimed the estimates were low and based on outdated information.
The new estimate is drawn from more-recent studies indicating the number may be much higher. For instance, a report published in the journal Health Affairs in 2011 calculated that just over 1 percent of hospital patients die each year because of medical errors. When applied to the more than 35 million people hospitalized each year, Makary and Daniel say, this would “translate into 400,201 deaths per year, more than four times the original IOM report estimate.”
The Hopkins team used evidence from four studies that analyzed medical death rate data from 2000 to 2008, including one by the U.S. Department of Health and Human Services’ Office of the Inspector General and the Agency for Healthcare Research and Quality. Using these data, they were able to calculate a mean death rate for medical errors in U.S. hospitals. Applying this rate to the 35 million admissions in 2013, they calculated that 251,454 deaths resulted from medical mistakes…”
As a final note, let us not confuse this with the pointless debate on whether vaccines work or not. That is not the issue in any way here. The only issue is that the extra ingredients in vaccines and other injectable drugs, specifically metals and animal or human proteins and cancer viruses too small to filter out of the final product, are what is causing these seemingly unrelated diseases. And these “slow” diseases can happen days, months, years, or decades after one receives a vaccine. Please look beyond the mainstream debate and into the completely arbitrary and usually unnecessary ingredients list. These extraneous ingredients are listed above (in the insert) as “COMPONENTS” of the vaccine.
Please share this with any and all you can. This cannot go unspoken.
Is it possible that, in our efforts to create synthetic drugs (for profit) in order to artificially mimic or replace the body’s natural health and healing processes, even while suppressing the body’s immune response to those drugs so that they may fool the natural system, we have inadvertently created a permanent state of dis-ease as the average human condition?
Let’s take an obscene example.
Over half a century ago, while researching the efficiency of the vaccine for smallpox, Japanese virologists working for the Institute For Infectious Diseases at University of Tokyo published their findings (1954) that some “viral inhibitory factor” was inhibiting the growth of their purposefully induced viral infection of laboratory research rabbits. In other words, the tiny rabbit bodies were having the natural immune response they should, which interferes with the capability of a foreign zoological pathogen to propagate (grow and reproduce) after injection. But they also discovered through isolation of this unknown and naturally occurring preventative substance that it was not originated from antibodies. The desired immunization process of antibody stimulation through vaccination was being profoundly prevented.
Three years later, at the National Institute for medical Research in London, virologists discovered similar causal effects on the growth if influenza virus in chicken egg membranes. Something was again naturally interfering with the growth of the virus after purposeful (unnatural) injection. In their research paper they coined this viral inhibitory factor as “Interferon“.
At the same time, back at the University of Tokyo, those same Japanese virologists finally discovered the essense of what they originally coined as “Viral Inhibitory Factor (VIF)”, and both research branches agreed that this anti-viral substance was caused by the same class of factors, and eventually these became officially known in medical science as “Interferon” (multiple types).
Further study revealed that these Interferon proteins reside in different human chromosomes, and a purification process of biologically active beta interferon was finally isolated in 1977. By the early 1980’s interferon protein types were isolated and cloned to show conclusive proof that indeed interferons were responsible for interfering with viral reproduction. Eventually, these interferon isolates were used as a treatment for viral infections.
So what are these naturally interfering produced factors, and why do pharmaceutical corporations hate them so much that they seek to interfere with their pre-programmed interference?
Clinically defined, Interferons (IFNs) are proteins (glycoproteins called cytokines) made and released by healthy host cells (naturally occurring cells in your body) in response to the presence of pathogens such as viruses, bacteria, parasites, or tumor cells. They literally act as communication devices traveling as RNA messengers, allowing cells to communicate with each other like micro text messages, creating a trigger effect to “interfere” with disease and viral replication by turning on the protective defensive structure of the immune system that is responsible for activating immune cells (natural killer cells, macrophages, etc.). Interferons also increase the ability of uninfected host cells in their ability to resist new infection by virus (an invading parasite to the host cell), and communicate the known presence of tumor cells to the immune system, up-regulating antigens to T lymphocytes.
A lymphocyte is one of 3 cells from the vertebrate’s immune system found in the lymphatic system called NK (natural killer) cells, B cells, or T cells. There are currently identified 10 distinct interferons (IFN’s), 7 of which are found in humans. These are further broken down by classes (types 1, 2, and 3). All of these IFN’s are vital for the body’s defense against disease states and infections as well as prevention of tumor growth.
In layman’s terms, we could say that all of the body’s naturally healthy cells send out cell-phone calls in the form of amino acids (proteins), which float through the body as if upon a wirelessly fluid Ethernet, directly connecting to the body’s receiving phone-line like a 911 emergency call; thus literally summoning the body’s first responders in the form of the immune system to send out little firefighter cells (Natural Killer, B, and T-cell lymphocytes) to stop the spread of the fire caused by viral, bacterial, parasitic, or tumor causing pathogens that are invading the host cells.
–=– Those Pesky Little Interferons –=–
While interferons have been used in some cases as a breakthrough yet totally underutilized treatment for the slowing or halting of certain disease growth in humans, we find a much more sinister reason for such research and identification of interferons in modern medicine and vaccine production. You see, the original discovery of interferons was not an altruistic attempt to isolate and synthesize an amino acid compound that would treat disease. In fact, far from it…
Back in 1956, those Japanese and British virologists were not trying to cure disease. No, they were trying to induce disease within their animal subjects for research purposes and spread it into chicken eggs so as to grow the disease for vaccination and “other” purposes; chicken embryo substrates being the most popular method for disease culture growth. But as they learned through continuous interference from the host subjects, something kept getting in the way of their purposeful disease infection of those hosts – an at the time unknown intracellular function of the body as of yet unknown, later to be named as Interferon.
Please understand… in order to vaccinate against disease, these scientists believed that they had to stop the bodies own natural defense against the very disease these scientists were trying to purposefully infect their test subjects with. Some might call this a paradox… or just insanity. In order for their pseudo-science to supposedly work, those virologists had to figure out a way to cut the cell-phone signaling process (now known as interferon) caused by their purposeful inoculate infection of the hosts. They needed to cause the body to cease in its perfectly natural capacity to fight the very disease they were injecting into it, so as to grow the disease within that host body. This would seem to the average person to be, on the surface and rightly so, a counter-productive effort on their part. But then the average person could never comprehend what was happening behind the scenes, let alone the true purpose of funding such experimental “science” as medicine.
Let’s take the phenomenon known as Auto-Immune Deficiency Syndrome (AIDS) for example…
What are its symptoms?
Rare cancerous tumors, viral-like infection, wasting syndrome, and general immune-supression of the lymphatic system.
Sound familiar? Like maybe the body’s phone-lines are down?
The body works though a system of communication devices in bilogical form. When one part or system of the body needs to communicate with another, it does so through a highly advanced structure of expressive signaling and transduction; the release of various types of cells, proteins, and other substances that trigger each inter-dependent system to respond in kind. It is this body-wide platform of cellular communication that is being attacked and blocked by the introduction of inhibiting factors like infectious prions and other melevolent substances.
The body works just fine until it is stung and thus injected (vaccinated) with foreign proteins, DNA, RNA, and other ingreedients that in no other way would ever be able to insert themselves into the body of man (or rabbit).
The main issue with AIDS patients is the lack of the body’s immune response regarding the production of T Lymphocytes, commonly called T-cells. For some reason, despite the body’s many dis-ease states as symptoms of the AID-syndrome, the body just isn’t getting the hint to produce the very thing that it needs to fight infection. It seems we have a failure to communicate here… For some reason the emergency 911 cell-phone lines seem to be cut, and the first responders (T-cells) are just not being called into action by the healthy cells that are under attack. Their chemical screams for help are going unheard. It’s as if the immune system labor union went on strike, and these “AIDS” symptoms are the resulting chaos and unrest that ensues throughout the body.
Not ironically, these are the same symptoms of what is known as Gulf War Syndrome, a known vaccine induced disease state thought by many researchers to be caused by vaccine adjuvants like squalene and other ingredients injected into the guinea pig soldiers of our military.
But what could possibly cause such a chain reaction throughout the body’s immune-supressive system?
What could possibly have been introduced within the body to prevent its ability to make a protein phone call, just like in those poor test-rabbits so many decades ago?
What is preventing interferon from interfering with the disease process, defeating its attempts to transmit its signal for help to the imune system?
Enter bioengineering and the novel prion…
So how could this novel disease state be simultaniusly spread
throughout Africa and eventually the first world?
.
–=– Altering Gene Expression: Just A Little Pinprick –=–
.
“The genetic code is universal…. The complete word-for-word universality of the genetic dictionary is, for the taxonomist, too much of a good thing.”
–Evolutionist Richard Dawkins, in his book, ‘The Blind Watchmaker’ (1986, p. 270)
–=–
“It is recognized by molecular biologists that the genetic code is universal, irrespective of how different living things are in their external appearances.”
–Creationist Robert Kautz, in his book,
‘The Origin of Living Things’ (1988, p. 44)
–=–
“The construction and metabolism of a cell are thus dependent upon its internal ‘handwriting’ in the genetic code. Everything, even life itself, is regulated from a biological viewpoint by the information contained in this genetic code. All syntheses are directed by this information.”
–A.E. Wilder-Smith, United Nations scientist (1976, p. 254).
–=–
“It may seem a platitude to say that the offspring of buttercups, sparrows and human beings are buttercups, sparrows and human beings… What then keeps them, and indeed living things in general, “on the right lines?” Why are there not pairs of sparrows, for instance, that beget robins, or some other species of bird: why indeed birds at all? Something must be handed on from parent to offspring which ensures conformity, not complete but in a high degree, and prevents such extreme departures. What is it, how does it work, what rules does it obey and why does it apparently allow only limited variation? Genetics is the science that endeavours to answer these questions, and much else besides. It is the study of organic inheritance and variation, if we must use more formal language.”
–British geneticist, E.B. Ford, ‘Understanding Genetics’ (1979, p. 13).
–=–
“Tablets of stone prepared by the Babylonians some 6,000 years ago have been interpreted as showing pedigrees of several successive generations of horses, thus suggesting a conscious effort toward improvement. Other stone carvings of the same period illustrate artificial cross-pollination of the date palm as practiced by the early Babylonians. The early Chinese, many years before the Christian era, improved varieties of rice. Maize was cultivated and improved in the western hemisphere by the American Indians, beginning at an early period in their history. In another era, Hippocrates, Aristotle, and other Greek philosophers made observations and speculations suggesting genetic principles.”
–Eldon Gardner, ‘The History of Biology’ (1972, pp. 399-400)
–=–
“And God said, let the earth put forth grass, the herb
yielding seed, and the fruit tree yielding fruit after its kind,
wherein is the seed thereof upon the earth, and it was so.
And the earth brought forth grass, the herb yielding seed and
the fruit tree yielding fruit after its kind whose seed was in itself.”
–The Bible, Genesis 1:11-12
–=–
“In the first chapter of Genesis, however, because it is a matter of the greatest religious importance, the Bible speaks clearly and finally on a matter of biology. After its kind is the statement of a biological principle that no human observation has ever known to fail. The most ancient human records engraved on stone or painted on the walls of caves bear witness to the fact that horses have ever been horses, bears have ever been bears, geese have ever been geese, reindeer have ever been reindeer. The most desperate and subtle efforts of man in modern times have been unable to alter this divine decree. The Bible teaches that from the beginning there have been a large number of types of living things, man included, which were so created as to remain true to their particular type throughout all generations…. The latest results of modern biological research, Mendel’s Laws, agree exactly with what was written by Moses three thousand years ago—and they also elucidate it…”
Byron Nelson, ‘After Its Kind’, (1967, pp. 3,103)
–=–
“…once a fertilized, (a) single human cell begins to develop, the original plans are faithfully copied each time the cell divides (a process called mitosis) so that every one of the thousand million million cells in my body, and in yours, contains a perfect replica of the original plans for the whole body”.
–Evolutionist John Gribbin (1981, p. 193)
–=–
“The Nobel laureate, F.H. Crick has said that if one were to
translate the coded information on one human cell into book form,
one would require one thousand volumes each of five hundred pages to do so.
And yet the mechanism of a cell can copy faithfully at cell division
all this information of one thousand volumes each of
five hundred pages in just twenty minutes.”
–Dr. Wilder-Smith (1976, p. 258).
–=–
“Every organism has in it a store of what is called genetic information… I will refer to an organism’s genetic information store as its Library…. Where is the Library in such a multicellular organism? The answer is everywhere. With a few exceptions every cell in a multicellular organism has a complete set of all the books in the Library. As such an organism grows its cells multiply and in the process the complete central Library gets copied again and again…. The human Library has 46 of these cord-like books in it. They are called chromosomes. They are not all of the same size, but an average one has the equivalent of about 20,000 pages…. Man’s Library, for example, consists of a set of construction and service manuals that run to the equivalent of about a million book-pages together.”
“It is an indication of the sheer complexity of E. coli
that its Library runs to a thousand page-equivalent”
–A.G. Cairns-Smith (1985, pp. 9,10,11)
“The DNA in living cells contains coded information. It is not surprising that so many of the terms used in describing DNA and its functions are language terms. We speak of the genetic code. DNA is transcribed into RNA. RNA is translated into protein. Protein, in a sense, is coded in a foreign language from DNA. RNA could be said to be a dialect of DNA. Such designations are not simply convenient or just anthropomorphisms. They accurately describe the situation.”
–Lester and Bohlin (1984, pp. 85-86)
–=–
Further, consider that human beings have learned to store information on clay tablets, stone, papyrus, paper, film, cassettes, microchips, etc. Yet ‘human technology has not yet advanced to the point of storing information chemically as it is in the DNA molecule‘
“It is not possible for a code, of any kind, to arise by chance or accident. The laws of chance or probability have been worked out by mathematics… A code is the work of an intelligent mind. Even the cleverest dog or chimpanzee could not work out a code of any kind. It is obvious then that chance cannot do it… This could no more have been the work of chance or accident than could the “Moonlight Sonata” be played by mice running up and down the keyboard of my piano! Codes do not arise from chaos”
–Professor Andrews (1978, pp. 28,29).
–
–=– Prions:
Infecting The World
Through Vaccination –=–
So what happens when man comes clumsily and irresponsibly into the age of molecular science, where he begins to intermix species through inoculation? How can man know if his limits truly are what is written in the ancient scriptures and philosophies of moral men unless he seeks the answers by destroying the perfection of nature’s mathematical equations of the biology of life? How can we know the limits of genetically altered life if we don’t push those limits to the very brink of extinction of species, including our own?
Ancient warnings are for pussies!!!
In my previous research, I have postulated the horrifyingly evidence-based theory that all modern disease states, from the dementia’s to cancer to AIDS, have been induced through the vaccination process via the direct bodily injection of foreign “infectious” proteins called prions. Further research has all but confirmed the reality of this notion, showing that the inherent protective foundation of these cellular proteins in cell health (before infection) are essential to life itself.
Prion protein aids bone marrow
New study findings point to possible stem cell role for normal form of protein
By Charles Choi | January 31, 2006
The normal form of prion protein (PrP) appears necessary for bone marrow stem cells to renew themselves, scientists reported online this week in the Proceedings of the National Academy of Sciences. These findings suggest a potential physiological function in stem cells for the normal form of the widely expressed protein. “Prior to this work there was no hint that PrP had a function in stem cell biology,” co-author Andrew Steele at the Whitehead Institute for Biomedical Research in Cambridge, Mass., told The Scientist. “We are now looking into PrP function in other adult stem cells, particularly neural stem cells.” Prions are infamous for being associated with transmissible spongiform encephalopathies (TSEs) such as mad cow disease, but the function of PrP — the normal, widespread and highly conserved form of prions — remains a mystery. In preliminary studies, co-author Cheng Cheng Zhang discovered 40% of adult mouse bone marrow cells expressed PrP on their surfaces. More than 80% of these PrP-marked cells werered blood cells or their developmental precursors, suggesting PrP might be a marker for long-term hematopoietic stem cells, which can give rise to the entire adult blood system. To determine if PrP was a marker for long-term hematopoietic stem cells, the researchers took bone marrow cells from wild-type mice and purified them into fractions, some of which expressed PrP. Six months after transplantation into lethally irradiated mice, the researchers saw both short- and long-term engraftment in mice that received PrP-containing cells, but only short-term engraftment activity in mice receiving non-PrP cells. While PrP is a marker for long-term hematopoietic stem cells in wild-type mice, PrP-knockout mice still possess these cells, as well as relatively normal levels of their derived progeny. To determine what function PrP might normally have in hematopoietic stem cells, the researchers carried out several rounds of bone marrow implantations. First they transplanted bone marrow from either wild-type mice or a PrP-null strain into lethally irradiated mice. When the engrafted marrow flourished and generated peripheral blood cells, the researchers implanted the newly reconstituted bone marrow into another lethally irradiated mouse group, then repeated the process a third time. In each round after the first, bone marrow originating from PrP-null mice experienced a dramatically reduced ability to renew itself,while cells from the wild-type mice did not. Retroviral infections that expressed PrP in recipients of PrP-null bone marrow rescued this defective process, suggesting PrP is necessary for hematopoietic stem cell self-renewal. Odile Kellerman at the Pasteur Institute in Paris, who did not participate in this study, noted prions often trigger neuron death in TSEs after long incubation periods,” similarly, PrP only impacted hematopoietic stem cells over the long term. “In both cases, PrP appears to contribute to the long-lasting adaptation of cells to injury,” she told The Scientist. Kellerman suggested that when PrP function is disrupted, cells try to adapt, “but in the long term, this turns out to be detrimental.” The exact mechanism behind how PrP might contribute to hematopoietic stem cell renewal remains unknown. Co-author Harvey Lodish speculated PrP might bond to and concentrate a hormone on the cell surface, or help stem cells adhere to neighboring cells or extracellular matrix. “It should prove fairly straightforward to see if it is adhering to other proteins or any known or unknown hormones,” he told The Scientist. William Stanford at the University of Toronto, who did not participate in this study, noted that PrP is tethered to cell membranes via a glycosylphosphatidylinositol (GPI) anchor, similar to hematopoietic stem cell marker Sca-1. “This suggests these GPI-anchored proteins, which have similar functions, may operate through a common mechanism,” Stanford told The Scientist. Future experiments could investigate whether overexpressing PrP in hematopoietic stem cells increases self-renewal, and rescues self-renewal defects such as in the Sca-1 deficient mouse, Stanford added — or if genetically substituting PrP with a different GPI-anchored protein rescues the self-renewal defect seen in PrP-null mice. cqchoi@nasw.org Links within this article C.C. Zhang et al. “Prion protein is expressed on long-term repopulating hematopoietic stem cells and is important for their self-renewal.” PNAS Early Edition.
Neurons and Astrocytes Respond to Prion Infection by Inducing Microglia Recruitment
Abstract
The accumulation and activation of microglial cells at sites of amyloid prion deposits or plaques have been documented extensively. Here, we investigate the in vivorecruitment of microglial cells soon after intraocular injection of scrapie-infected cell homogenate (hgtsc+) using immunohistochemistry on retinal sections. A population of CD11b/CD45-positive microglia was specifically detected within the ganglion and internal plexiform retinal cell layers by 2 d after intravitreal injection of hgtsc+. Whereas no chemotactism properties were ascribed to hgtsc+ alone, a massive migration of microglial cells was observed by incubating primary cultured neurons and astrocytes with hgtsc+ in a time- and concentration-dependent manner. hgtsc+ triggered the recruitment of microglial cells by interacting with both neurons and astrocytes by upregulation of the expression levels of a broad spectrum of neuronal and glial chemokines. We show that, in vitro and in vivo, the microglia migration is at least partly under the control of chemokine receptor-5 (CCR-5) activation, because highly specific CCR-5 antagonist TAK-779 significantly reduced the migration rate of microglia. Activated microglia recruited in the vicinity of prion may, in turn, cause neuronal cell damage by inducing apoptosis. These findings provide insight into the understanding of the cell-cell communication that takes place during the development of prion diseases.
In vitro infectivity study in Cell stirs tempest in a test tube
By Brendan Maher (bmaher@the-scientist.com) | April 21, 2005
Protein aggregates generated in a test tube infected wildtype hamsters with a disease much like scrapie, according to an article appearing this week in Cell. Such a demonstration has, in the past, been called the gold standard of proof for the prion hypothesis, Stanley Prusiner’s Nobel-winning assertion that infectious, self-replicating protein isoforms are the culprit in transmissible spongiform encephalopathies (TSEs) like scrapie, Creutzfeldt-Jakob disease, and mad cow disease.
Study coauthor Claudio Soto, said that this demonstration, together with a paper published by Prusiner’s group last summer, should allay most doubts. “There is really little room for skepticism,” he told The Scientist.
But the study has done little to quiet prion hypothesis skeptics. “I’m not going to abandon alternative hypotheses for the time being,” said Robert A. Somerville of the Institute for Animal Health, Edinburgh.
While Prusiner’s group had successfully infected a mouse with a recombinant protein derived from bacteria, some argued that their use of transgenic mice susceptible to the disease undercut the power of the demonstration. In the new study, researchers at the University of Texas Medical Branch, Galveston, Universidad Autonoma, Madrid, and the University of Chile in Santiago fine-tuned a cyclical process for amplifying aggregated protein from an infected hamster brain. Through serial dilutions, they were able to infect a wildtype hamster with in vitro–produced aggregates without any traces of the original infectious brain. But skeptics, including a member of Prusiner’s group, argue that using material from a diseased hamster brain could have resulted in residual contamination.
Soto’s group has been using a process that they call protein misfolding cyclic amplification (PMCA), which aids the aggregation of the normal cellular protein PrPc into the misfolded, polymer-forming PrPres that is associated with TSE pathology. The process works in a fashion similar to polymerase chain reaction (PCR) amplification of oligonucleotides. After seeding PrPc with PrPres, the solution is incubated and sonicated. “Once the aggregates become long enough, we split them into smaller pieces so that in a new conversion, a new incubation, they are able to convert more and more of the normal protein,” Soto explained.
Crucially, however, the PrPres “seed” comes from infected hamster brain homogenate, while the normal PrPc comes from healthy hamster brain homogenate. “They actually started from infectious material, and we didn’t,” said Giuseppe Legname, of the University of California, San Francisco, and co-author on the Prusiner paper. “It’s an alternative approach to demonstrate thatyou might make prions, but to say that these are synthetic prions, it’s very difficult.”
Soto insisted that serial dilutions between rounds of PMCA reduce scrapie brain homogenate to an amount equivalent to a 10 to the minus 10th and a 10 to the minus 20th–fold dilution. Infectivity generally drops off after 10 to the minus 9th, according to the paper. “We’ve completely ruled out the possibility that the infectivity is still remaining from… the original brain,” Soto said...
While the article continues to criticize the control group results, which you may read at the link above, the important point here is that scientists are creating prions and making them purposefully more infectious. They are testing them in various substances and frequencies. And through the ultra-sound sonic vibration described above as protein misfolding cyclic amplification (PMCA), they are able to excite the growth factor of infectious prions so that they take over (mis-fold) healthy brain tissue much quicker. This PMCA process is used in autopsy to detect prion disease.
I have my own concerns that these ultra-sound frequencies are the same as used in cell-phone towers and in the process of ultra sound for unborn infants and other medical procedures, as well as other frequencies unknown via smart meters, radio waves, etc. We are playing with the fuel for the fire and there is virtually no escaping this permanent state of sonic bombardment…
It is also interesting to note that two men wsere cured of AIDS symptoms by receiving a bone marrow transfusion not so long ago…
(CBS News) Two men who’ve had HIV for years may now be free of the disease following bone marrow transplants, researchers at Brigham and Women’s Hospital in Boston announced Thursday.
The new research has some attendees at the XIX International AIDS Conference in Washington, D.C. hopeful for a cure.
Both patients were being treated for cases of cancer. One of the patients underwent a bone marrow transplant two years ago at the Dana-Farber/Brigham and Women’s Cancer Center in Boston, the other had the procedure done four years ago at the same hospital. NBCNews.com reports that one of the patients is in his 50s and has been infected since the early 1980s towards the beginning of the AIDS epidemic and the other man, in his 20s, was infected at birth.
Both stayed on their antiretroviral medication regimens, the standard treatment of HIV, following the transplants.
The researchers discovered that overtime as the patients’ cells were replaced by cells from the donor, evidence of HIV in the patients’ blood tests disappeared. The researchers also said both patients have no signs of HIV in their DNA or RNA and levels of their disease-fighting antibodies have also decreased. The researchers think the medications helped allow these cells to be replaced.
“This gives us some important information,” one of the researchers Dr. Daniel Kuritzkes, an infectious disease specialist at the hospital and Harvard Medical school said in a press release. “It suggests that under the cover of antiretroviral therapy, the cells that repopulated the patient’s immune system appear to be protected from becoming re-infected with HIV.”
The researchers themselves won’t call it a cure yet, saying they still need to check more tissues for traces of the disease. But they were surprised to see no signs of HIV beyond what’s seen in a blood test.
“We expected HIV to vanish from the patients’ plasma,but it is surprising that we can’t find any traces of HIV in their cells,” said co-resarcher Dr. Timothy Henrich, also of BWH and Harvard. “The next step is to determine if there are any traces of HIV in their tissue.”
The researchers’ announcement comes days after Timothy Ray Brown, the man known as the “Berlin Patient,” held a press conference in Washington, D.C., to say he’s still cured of AIDS five years after undergoing a bone marrow blood transplant…
It is important to note that the chemokine receptor-5 (CCR-5) antagonist prevents the cellular binding of the HIV-1 virus, as is explained in this video:
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And how do these prions effect disease states?
Let’s take for example Multiple Sclerosis:
“The etiology of Multiple Sclerosis (MS) is unknown. Existing epidemiologic data suggests that MS can be an infectious disease. MS used to be classified as one of the ‘slow infections‘–many of these are caused byprions. Prions are small, proteinaceous, infectious particles–distinguished from viruses by the absence of intrinsic nucleic acids. In a contrast to the ‘classic’ prional diseases (Kuru, Scrapie or Creutzfeldt-Jacob Disease) that in CNS affect primarily neurons, the ‘target’ cell in MS is an oligodendrocyte. This may explain differences in disease presentation. This paper presents a pathophysiological model of MS based on the assumption that MS is a prional disease. Processes leading to the demyelination in Multiple Sclerosis seem also to involve lymphocytes, astrocytes and macrophages as well as the interferon system…”
NOTE: The protein that prions are made of (PrP) is found throughout the body, even in healthy people and animals, and necessarily protects cells from infections. However, PrP found in infectious material has a different structure and is resistant to proteases, the enzymes (proteins) in the body that can normally break down other proteins. The normal form of the protein is called PrPC, while the infectious form is called PrPSc — the C refers to healthy ‘cellular‘ PrP, while the Sc refers to infectious ‘scrapie‘, the prototypic prion disease, occurring in sheep. The infectious isoform of PrP, known as PrPSc, is able to convert normal PrPC proteins in humans into this infectious isoform by changing their conformation, or shape. This, in turn, alters the way the proteins interconnect, creating symptoms like transmissible spongiform encephalopathy (holes in the human brain like mad cow disease). PrPSc always causes prion disease. In the end, no cellphone call can be made if the interferon protein is infected and mis-folded before it is able to reach its receiving protien that would activate T-Cells or other immune responses. Another word for mis-fold might be easier to understand as to misinform. The immune system is being lied to in a strange, chemically unbalanced way due to prion protein infections (mis-folding). Sheep blood (serum) is a popular vaccine substrate to grow vaccines for humans upon, and the protein and DNA cannot be filtered out of the final vaccine product. There are no other viable explanations why infectious prions from animals would intermingle within a human body (xenotransplantaion/xenografting).
This interference that infectious prions cause to interferon and other protein-based signaling and transcription cells is shown in the research studies below. For those with the gumption, let’s play a biological game of connect the dots.
Continued…
RESULTS
Prion infection is accelerated in (interferon type 3) IRF3-deficient mice…
The IRF3-dependent pathway is protective against prion infection in cell culture.
We tested whether over-expression of IRF3 (interferon) could affect the production of PrPSc (infectious/mis-folded prions) in the cell culture models. The level of PrPC (healthy prions) was not affected by the transient expression of the genes in uninfected N2a58 cells (data not shown). PrPSc was significantly decreased by overexpression of IRF3 in the 22L-N2a58 cells (Fig. 5A). We confirmed that the activated form of IRF3 (phosphorylated at Ser396 of IRF3) increases in a dose-dependent manner after transfection of the IRF3 gene in both 22L-N2a58 cells (Fig. 5A) and uninfected N2a58 cells (data not shown), indicating that the upregulation of IRF3 phosphorylation seen in the Fig. 5A is most likely due to an increase in the level of IRF3 protein after transfection.
To investigate the effect of downregulation of IRF3 in the 22L-N2a58 cells, we performed knockdown experiments using small interferingRNAs (siRNAs). IRF3 expression was significantly decreased by two types of siRNAs against IRF3, whereas β-actin expression, as the internal standard, was not changed (Fig. 5B)… These data suggest that IRF3 has an inhibitory effect on the production of PrPSc in the 22L-N2a58 cells.
To further evaluate the protective effect of IRF3… After incubation with 22L-infected BH (22L-BH), the cell clones were subcultured for five passages and analyzed by Western blotting with anti-PrP antibodies. The values of the PrPSc/PrPC ratio were inversely correlated with the values of the IRF3/beta-actin ratio (Fig. 5C), indicating that enhanced expression of IRF3 effectively blocks new prion infection.
DISCUSSION
In the present study, we found that a geneticdeficiency of IRF3 accelerates the progression of TSE(transmissable prion disease) following i.p. transmission in mice and that the accumulation rate of PrPSc in the spleen is increased in the IRF3−/− mice. Furthermore, we demonstrated that IRF3 has an inhibitory effect on PrPSc accumulation and that the levels of IRF3 are inversely correlated withresistance to prion infection in cell culture.
IRF3 is known to be constitutively expressed in many tissues and cells (6, 22, 45). Indeed, we confirmed the expression of IRF3 in brains (data not shown) and N2a58 cells (Fig. 5). Furthermore, not only glial cells but also neurons express most innate immunity-related genes and produce type I IFN in response to virus infection (11). Although the role of IRF3 in prion propagation into the CNS is still unclear, we speculate that an absence of IRF3 signaling leads to increased prion replication not only in peripheral tissues but also in the CNS. It would be of great value to examine this further using neuron-specific IRF3-disrupted mice or neuron-specific IRF3-expressing mice.
It was reported in prion infection that genetic disturbance of TLR4 (36) or interleukin-10 (IL-10) (41) leads to shorter incubation periods of prion infection. Since these, respectively, are an upstream and a downstream factor of the IRF3-mediated pathway, the findings may be due in part to functional changes in IRF3-mediated signaling.
Based on these results, two hypothetical models are proposed to explain the inhibitory effect of IRF3 on the prion infection. The first is that MyD88-independent pattern recognition receptors (PRRs), such as TLR3, TLR4, or RIG-I/MDA5, might recognize prion, and the resulting activation of IRF3 could induce various IRF3-responsive genes that may participate in the protective effect. The fact that the in vivo administration of IFNs (interferons), a representative of the IRF3-responsive genes,previously failed to show inhibitory effects on TSE (13, 16) suggests that IRF3-responsive genes other than IFNs may be important for the inhibitory effect of IRF3 on prion infection. Of note, the protective effect of IRF3 against several viruses has been suggested to be largely independent of the production of type I IFN and is probably responsible for the antiviral actions of specific IRF3-responsive genes (10, 18, 21). Peritoneal macrophages from wild-type mice moderately induced tumor necrosis factor alpha (TNF-α) or IL-6 following exposure to PrPSc-mimicking PrP peptides (PrP residues 106 to 126 or PrP residues 118 to 135), whereasTLR4 signaling-mutant mice were impaired in their ability to produce these cytokines (36), supporting in part the hypothesis that some PRRs may sense PrPSc as a sort of PAMP. On the other hand, it should be noted that the MyD88-independent pathway activates both NF-κB and IRF3. Although the induction of proinflammatory cytokines essentially depends upon NF-κB, it was unclear whether the activation of IRF3 was induced by these PrP peptides. In fact, the hallmarks of IRF3 activation, such as phosphorylation, dimerization, and cytoplasm-to-nucleus translocation of IRF3 in 22L-N2a58 cells, were not detected (data not shown). Moreover, it was previously reported that IFNs were not detected in the serum, spleens, or brains of mice infected with scrapie (44). In addition, IFN-β mRNA does not increase in the brains of CJD (human prion disease) patients (7) or mice infected with ME7 prion strain (14). Hence, these results argue against the notion that the IRF3-mediated signaling is activated by prion infection, but it remains to be determined whether transient and weak responses are evoked at an early phase in the infection. The question as to whether IRF3-mediated signaling directly suppresses the production of PrPSc or increases its degradation also remains open.
Another explanation is that prion infection itself may have little effect on the pathway but that the basal activity of IRF3 may have some degree of inhibitory effect on prion propagation. It has been reported that IRF3 can be activated not only by viruses but also by multiple activators such as cellular stress and DNA damage (24, 34). Accordingly, it is possible that constitutive activation of IRF3, albeit at a low level, occurs in the brain even in the absence of a pathogen. This notion is further supported by the fact that constitutive,weak IFN signaling in the absence of viral infection plays a role in modifying cellular responsiveness in the immune and other biological systems (38, 40). Accumulating evidence indicates that many viruses have evolved to evade the innate immune system, including IRF3-mediated signaling (15, 23). For instance, an active mutant of IRF3 has been reported to exert a markedly suppressive effect on cellular HIV-1 infection, and administration of poly(I·C) potently inhibits HIV-1 replication in microglia through a pathway requiring IRF3. Nonetheless, HIV-1 itself does not activate IRF3 but, rather, decreases IRF3 protein in HIV-1-infected cells (12, 37). Likewise, prion infection might disturb the activation of IRF3 even though prion is considered to be largely composed of PrPSc. We are currently investigating this possibility. Furthermore, an analogy can be made between the role of IRF3 in prion infection and that of IL-10. The levels of IL-10 are not increased in the brains of scrapie-infected mice (14, 42), whereas IL-10 knockout mice are highly susceptible to the development of scrapie (41).
In conclusion, we have shown that IRF3, a key transcription factor of the MyD88-independent pathways, operates in the host defense machinery against prion infection. The findings provide new insight into understanding of the innate immunity to prion infection.
Interleukin-10 (IL-10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine. In humans, IL-10 is encoded by the IL10 gene.[1]
Gene and protein structure
The IL-10 protein is a homodimer; each of its subunits is 178-amino-acid long.[2]
IL-10 is classified as a class-2 cytokine, a set of cytokines including IL-19, IL-20, IL-22, IL-24 (Mda-7), and IL-26, interferons (IFN-alpha, -beta, -epsilon, -kappa, -omega, -delta, -tau, and -gamma)and interferon-like molecules (limitin, IL-28A, IL-28B, and IL-29).[3]
Expression and synthesis
In humans, IL-10 is encoded by the IL10 gene, which is located on chromosome 1 and comprises 5 exons,[1] and is primarily produced by monocytes and, to a lesser extent, lymphocytes, namelytype 2 T helper cells (TH2), mastocytes, CD4+CD25+Foxp3+regulatory T cells, and in a certain subset of activated T cells and B cells.
In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolocules like proteins or nucleic acids. It is a quaternary structure of a protein.
A homo-dimer would be formed by two identical molocules (a process called homodimerization). A hetero-dimer would be formed by two different macromolecules (called heterodimerization).
Most dimers in biochemistry are not connected by covalent bonds. An example of a non-covalent heterodimer would be the enzyme reverse transcriptase, which is composed of two different amino acid chains.[1] An exception is dimers that are linked by disulfide bridgessuch as the homodimeric protein NEMO.[2]
Some proteins contain specialized domains to ensure dimerization (dimerization domains).
Examples of Homodimer include anti-bodies and Factor VII.
Microglia are a type of glial cell that are the resident macrophages of the brain and spinal chord,and thus act as the first and main form of active immune defense in the central nervous system (CNS).
Microglia constitute 10-15% of the total glial cell population within the brain.[1] Microglia (and astrocytes) are distributed in large non-overlapping regions throughout the brain and spinal cord.[2][3]Microglia are constantly scavenging the CNS for plaques, damaged neurons and infectious agents.[4]The brain and spinal cord are considered “immune privileged” organs in that they are separated from the rest of the body by a series of endothelial cells known as the blood-brain barrier, which prevents most infections from reaching the vulnerable nervous tissue. In the case where infectious agents are directly introduced to the brain or cross the blood–brain barrier, microglial cells must react quickly to decrease inflammation and destroy the infectious agents before they damage the sensitive neural tissue. Due to the unavailability of antibodies from the rest of the body (few antibodies are small enough to cross the blood brain barrier), microglia must be able to recognize foreign bodies, swallow them, and act as antigen-presenting cells activating T-cells. Since this process must be done quickly to prevent potentially fatal damage, microglia are extremely sensitive to even small pathological changes in the CNS.[5] They achieve this sensitivity in part by having unique potassium channels that respond to even small changes in extracellular potassium.
Microglial cells differentiate in the bone marrow from hematopoietic stem cells, the progenitors of all blood cells. During hematopoiesis, some of these stem cells differentiate into monocytes and travel from the bone marrow to the brain, where they settle and further differentiate into microglia.[6]
Monocytes can also differentiate into myeloid dendritic cells and macrophages in the peripheral systems. Like macrophages in the rest of the body, microglia use phagocytic and cytotoxic mechanisms to destroy foreign materials. Microglia and macrophagesboth contribute to the immune response by acting as antigen presenting cells, as well as promoting inflammation and homeostatic mechanisms within the body by secreting cytokines and other signaling molecules.
In their downregulated form, microglia lack the MHC class I/MHC class II proteins, IFN-γ cytokines, CD45 antigens, and many other surface receptors required to act in the antigen-presenting, phagocytic, and cytotoxic roles that hallmark normal macrophages. Microglia also differ from macrophages in that they are much more tightly regulated spatially and temporally in order to maintain a precise immune response.[7]
Another difference between microglia and other cells that differentiate from myeloid progenitor cells is the turnover rate. Macrophages and dendritic cells are constantly being used up and replaced by myeloid progenitor cells which differentiate into the needed type. Due to the blood brain barrier, it would be fairly difficult for the body to constantly replace microglia. Therefore, instead of constantly being replaced with myeloid progenitor cells, the microglia maintain their status quo while in their quiescent state, and then, when they are activated, they rapidly proliferate in order to keep their numbers up. Bone chimera studies have shown, however, that in cases of extreme infection the blood-brain barrier will weaken, and microglia will be replaced with haematogenous, cart-marrow derived cells, namely myeloid progenitor cells and macrophages. Once the infection has decreased the disconnect between peripheral and central systems is reestablished and only microglia are present for the recovery and regrowth period.
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Transport of prion protein across the blood–brain barrier
Abstract
The cellular form of the prion protein (PrPc) is necessary for the development of prion diseases and is a highly conserved protein that may play a role in neuroprotection. PrPc is found in both blood and cerebrospinal fluid and is likely produced by both peripheral tissues and the central nervous system (CNS). Exchange of PrPc between the brain and peripheral tissues could have important pathophysiologic and therapeutic implications, but it is unknown whether PrPc can cross the blood–brain barrier (BBB). Here, we found that radioactively labeled PrPccrossed the BBB in both the brain-to-blood and blood-to-brain directions. PrPc was enzymatically stable in blood and in brain, was cleared by liver and kidney, and was sequestered by spleen and the cervical lymph nodes. Circulating PrPc entered all regions of the CNS, but uptake by the lumbar and cervical spinal cord, hypothalamus, thalamus, and striatum was particularly high. These results show that PrPc has bidirectional, saturable transport across the BBB and selectively targets some CNS regions. Such transport may play a role in PrPc function and prion replication.
Introduction
Cellular prion protein (PrPc) is perhaps best known as a source for the misfolded protein PrPsc (Prusiner, 1997) and as a prerequisite for the development of prion diseases (Mallucci et al., 2000). However, PrPc itself likely has important biological functions. It is found circulating in blood (Volkel et al., 2001) and is found in even higher levels in the cerebrospinal fluid (CSF) (Picard-Hagen et al., 2006). After ischemic events, PrPc levels increase in blood (Mitsios et al., 2007) and in neurons and brain endothelial cells in the peri-infarct region (Mitsios et al., 2007; Weise et al., 2004). These increases may reflect cytoprotective and neuroprotective roles for PrPc as recently reviewed (Roucou & LeBlanc, 2005). PrPc null mice have larger infarct volumes after ischemic events (Weise et al., 2006; Nasu-Nishimura et al., 2008) and more neuronal apoptosis after viral infections (Nasu-Nishimura et al., 2008) than wild type mice. In comparison, mice that overexpress PrPc have smaller infarcts and better neurological outcomes than wild type mice after ischemic events (Shyu et al., 2005). These protective events are likely mediated by PrPc through activation of anti-apoptotic (Spudich et al., 2005) and anti-oxidant pathways (White et al., 1999).
Sources of circulating PrPc likely include platelets (Robertson et al., 2006), endothelial cells (Simak et al., 2002), and lymphocytes (Politopoulou et al., 2000). Among lymphocytes, CD3 and CD8 lymphocytes have especially high levels which increase with aging (Politopoulou et al., 2000). All these cells have membrane bound PrPc that apparently can be released into the circulation. Platelet activation (Robertson et al., 2006) or endothelial apoptosis (Simak et al., 2002), for example, results in release of PrPc from those cells.
Thus, PrPc occurs in both blood and in CSF with levels that are likely responsive to disease states. This raises the question of whether PrPc can cross the blood–brain barrier (BBB). Such passage could link the two pools of PrPc and the events that control their levels. Here, we examined the ability of PrPc to cross the BBB in both the blood-to-brain and the brain-to-blood directions.
Capillary depletion
Capillary depletion as modified for use in the mouse (Triguero et al., 1990; Gutierrez et al., 1993) was used to determine the degree to which PrPc was sequestered and retained by the vascular bed of the brain.
I-PrPc was also taken up by the peripheral tissues of spleen, liver, kidney and cervical lymph nodes (Table 2)… there was a statistically significant decrease in the Ki for brain: F(1,8) = 7.97, p <0.05. This demonstrates that transport of PrPc across the BBB involves a saturable transport system.
Fig. 4 shows values for brain and spinal cord regions. Statistical comparison of the whole brain value to brain regions and olfactory bulb (spinal cord regions excluded) showed a statistically significant variation: F(22,62) = 18.3, p <0.001. The hypothalamus, thalamus, and striatum showed statistically (p <0.01) greater uptake in comparison to whole brain. The highest uptake, however, was into the lumbar region of the spinal cord. Inhibition of uptake by unlabeled PrPc (Table 3; p <0.05) was found for whole brain, olfactory bulb, 4 of the 10 brain regions (occipital cortex, thalamus, striatum, and midbrain) and two of the spinal cord regions (cervical and lumbar)…
Fig. 5 Brain-to-blood efflux of PrPc after icv injection. Half-time clearance from brain was 15.7 min. Inset shows that inclusion of unlabeled PrPc in the icv injection increased retention of radioactively labeled PrPc by brain, demonstrating a saturable component…
Does aluminum in vaccines have a more sinister plot that is stated?
Differential effect of aluminum on the blood-brain barrier transport of peptides, technetium and albumin.
Abstract
Aluminum is a neurotoxin capable ofaltering membrane structure and function. We investigated whether aluminum also can affect saturable transport across membranes using the blood-brain barrier as our model. Mice were given i.p. or i.v. aluminum (up to 100 mg/kg) as the chloride salt and the disappearance from the brain of several centrally administered substances was measured. We found that aluminum rapidly and profoundly inhibited the saturable system that transports the small, N-tyrosinated peptides Tyr-MIF-1 and the enkephalins from the brain to the blood by acting as a noncompetitive inhibitor. In contrast, the disappearance from the brain of technetium pertechnetate (a substance also transported out of the brain by a different saturable system), albumin or D-Tyr-MIF-1 (a stereoisomer of Tyr-MIF-1 that was confirmed not to be transported by the carrier system) was not affected by aluminum. Aluminum also did not alter either the saturable or nonsaturable component of the uptake of Tyr-MIF-1 by erythrocytes. These findings suggest that one mechanism by which aluminum may induce neurotoxicity is byselective alteration of the transport systems of the blood-brain barrier.
An enkephalin is a pentapeptide involved in regulating nociception in the body. The enkephalins are termed endogenous ligands, as they are internally derived and bind to the body’s opioid receptors. Discovered in 1975, two forms of enkephalin were revealed, one containing leucine (“leu”), and the other containing mathione (“met”). Both are products of the proenkephalin gene.
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Endogenous opioid peptides
There are three well-characterized families of opioid peptides produced by the body: enkephalins, endorphines, and dynorphins. The met-enkephalin peptide sequence is coded for by the enkephalin gene; the leu-enkephalin peptide sequence is coded for by both the enkephalin gene and the dynorphin gene.[3] The proopiomelanocortin gene (POMC) also contains the met-enkephalin sequence on the N-terminus of beta-endorphin, but the endorphin peptide is not processed into enkephalin.
Enkephalin receptor
Main article: Opioid recepter
The receptors for enkephalin are the delta opioid receptors. Opioid receptors are a group of G-protein-coupled receptors, with other opioids as ligands as well. The other endogenous opioids are dynorphins (that bind to kappa receptors), endorphines (mu receptors), endomorphins, and nociceptin/orphanin FQ. The opioid receptors are ~40% identical to somatostatin receptors (SSTRs).
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Endomorphins, Met-Enkephalin, Tyr-MIF-1, and the P-glycoprotein Efflux System
Abstract
The P-glycoprotein (P-gp) transport system, responsible for the efflux of many therapeutic drugs out of the brain, recently has been shown to transport the endogenous brain opiate endorphin. We used P-gp knockout mice (Mdr1a) and their controls to determine where P-gp is involved in the saturable efflux systems of four other endogenous opiate-modulating peptides across the blood-brain barrier (BBB). After injection of endomorphin-1 (Tyr-Pro-Trp-Phe-NH2), endomorphin-2 (Tyr-Pro-Phe-Phe-NH2), Met-enkephalin (Tyr-Gly-Gly-Phe-Met-OH), and Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) into the lateral ventricle of the mouse brain, residual radioactivity was measured at 0, 2, 5, 10, and 20 min later. The results showed no difference in the disappearance of any of these peptides from the brains of knockout mice compared with their controls. This demonstrates that unlike endorphin and morphine, P-gp does not seem to be required for the brain-to-blood transport of the endomorphins, Met-enkephalin, or Tyr-MIF-1 across the BBB.
Footnotes
This work was supported by the United States Army Medical Research Acquisition Activity (DAMD17-00-0113) and the Department of Veterans Affairs.
Endorphins (“endogenous morphine”) are endogenous opioid inhibitory neuropeptides. They are produced by the central nervous system and pituitary gland. The term implies a pharmacological activity (analogous to the activity of the corticosteroid category of biochemicals) as opposed to a specific chemical formulation. It consists of two parts: endo- and -orphin; these are short forms of the words endogenous and morphine, intended to mean “a morphine-like substance originating from within the body.”[1]
History
Opioid neuropeptides were first discovered in 1974 by two independent groups of investigators:
John Hughes and Hans Kosterlitz of Scotland isolated — from the brain of a pig — what some called enkephalins (from the Greek εγκέφαλος, cerebrum).[2][3]
Around the same time, in a calf brain, Rabi Simantov and Solomon H. Snyder of the United States found[4] what Eric Simon (who independently discovered opioid receptors in vertebral brains) later termed “endorphin” by an abreviation of of “endogenous morphine”, meaning “morphine produced naturally in the body”.[1] Importantly, recent studies have demonstrated that human and diverse animal tissues are in fact capable of producing morphine itself, which is not a peptide.[5][6]
Mechanism of action
Beta-endorphin (β-endorphin) is released into blood from the pituitary gland and into the spinal cord and brain from hypothalamic neurons. The β-endorphin that is released into the blood cannot enter the brain in large quantities because of the blood-brain barrier, so the physiological importance of the β-endorphin that can be measured in the blood is far from clear. β-endorphin is a cleavage product of pro-opiomelanocortin (POMC), which is also the precursor hormone for adrenocorticotrophic hormone (ACTH). The behavioural effects of β-endorphin is exerted by its actions in the brain and spinal cord, and it is presumed that the hypothalamic neurons are the major source of β-endorphin at those sites. In situations where the level of ACTH is increased (e.g., Cushing’s disease), the level of β-endorphin also increases slightly.
β-endorphin has the highest affinity for the μ1 opioid receptor, slightly lower affinity for the μ2 and δ opioid receptors, and low affinity for the κ1 opioid receptors. μ-Opioid receptors are the main receptor through which morphine acts. In the classical sense, μ opioid receptors are presynaptic, and inhibit neurotransmitter release. Through that mechanism, they inhibit the release of the inhibitory neurotransmitter GABA, and disinhibit the dopamine pathways, causing more dopamine to be released. By hijacking this process, exogenous opioids cause inappropriate dopamine release, and can lead to aberrant synaptic plasticity, which can cause dependency. Opioid receptors have many other and more important roles in the brain and periphery; however, modulating pain, cardiac, gastric and vascular function as well as possibly panic and satiation. Also, receptors are often found at postsynaptic locations as well as at presynaptic locations…
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Morphine preconditioning reduces lipopolysaccharide and interferon-γ-induced mouse microglial cell injury via δ1 opioid receptor activation
Abstract
Microglial cells play an important role in the inflammatory response of a broad range of brain diseases including stroke, brain infection and neurodegenerative diseases. However, there is very little information regarding how to protect microglial cells. Here, we showed that incubation of the C8-B4 mouse microglial cells with lipopolysaccharide (LPS) plus interferon-γ (IFNγ) induced cytotoxicity as assessed by the amount of lactate dehydrogenase (LDH) released from the cells. Preconditioning the cells with morphine for 30 min concentration-dependently reduced LPS plus IFNγ-induced cell injury. This morphine preconditioning effect was abolished by naloxone, a general opioid receptor antagonist, by naltrindole, a selective δ opioid receptor antagonist and by 7-benzylidenenaltrexone maleate, a selective δ1 opioid receptor antagonist. However, this protective effect was not affected by β-funaltrexamine, a selective μ opioid receptor antagonist, nor-binaltorphimine, a selective κ opioid receptor antagonist or naltriben, a selective δ2 opioid receptor antagonist. LPS plus IFNγ induced the expression of inducible nitric oxide synthase (iNOS), which was not affected by morphine preconditioning. Our results suggest that morphine induced a preconditioning effect in microglial cells. This effect may be mediated by δ1 opioid receptors and may not be through inhibiting the expression of iNOS, a potentially harmful protein.
Prion peptide PrP106-126 induces inducible nitric oxide synthase (iNOS) and proinflammatory cytokine gene expression through the activation of NF-kB in macrophage cells
The inflammatory response in prion diseases is dominated by microglia activation. The molecular mechanisms that lie behind this inflammatory process are not very well understood. In the present study, we examined the activation of nuclear factor-kappa B (NF-κB) upon exposure to PrP106-126 and its role in PrP106-126-induced upregulation of inducible nitric oxide synthase (iNOS) and proinflammatory cytokines (interleukin [IL]-1β, tumor necrosis factor [TNF]-α, IL-6) in Ana-1 macrophages. The results showed that iNOS and proinflammatory cytokine release was significantly elevated in Ana-1 macrophages upon exposure to PrP106-126; that PrP106-126 treatment led to a significant NF-κB activation; that proinflammatory cytokines gene expression was elevated in macrophages upon exposure to PrP106-126; and that NF-κB inhibition significantly abrogated PrP106-126-induced upregulation of iNOS and inflammatory cytokine mRNA expression. These results suggest that treatment with neurotoxic prion peptides leads to the activation of transcription factor NF-κB, which in turn stimulates gene expression of iNOS and proinflammatory cytokines in Ana-1 macrophages.
The Transcription Factor Nuclear Factor-kappa B and Cancer
Abstract
Since the discovery of nuclear factor-kappa B (NF-κB) in 1986, many studies have been conducted showing the link between the NF-κB signalling pathway and control of the inflammatory response. Today it is well known that control of the inflammatory response and apoptosis is closely related to the activation of NF-κB. Three NF-κB activation pathways exist. The first (the classical pathway) is normally triggered in response to microbial and viral infections or exposure to pro-inflammatory cytokines that activate the tripartite IKK complex, leading to phosphorylation-induced IκB degradation and depends mainly on IKKβ activity. The second (the alternative pathway), leads toselective activation of p52:RelB dimers by inducing the processing of the NF-κB2/p100 precursor protein, which mostly occurs as a heterodimer with RelB in the cytoplasm. This pathway is triggered by certain members of the tumour necrosis factor cytokine family, through selective activation of IKKα homodimers by the upstream kinase NIK. The third pathway is named CK2 and is IKK independent. NF-κB acts through the transcription of anti-apoptotic proteins, leading to increased proliferation of cells and tumour growth. It is also known that some drugs act directly in the inhibition of NF-κB, thus producing regulation of apoptosis; some examples are aspirin and corticosteroids. Here we review the role of NF-κB in the control of apoptosis, its link to oncogenesis, the evidence of several studies that show that NF-κB activation is closely related to different cancers, and finally the potential target of NF-κB as cancer therapy.
Nuclear factor kappa B (NF-κB) in multiple sclerosis pathology
Highlights
• NF-κB signaling in MS patients and animal models of MS.
• NF-κB signaling controls peripheral immune activation at multiple levels.
• NF-κB controls inflammatory responses locally in the CNS.
• NF-κB as a therapeutic target for the treatment of MS.
The nuclear factor kappa B (NF-κB) signaling cascade plays a critical role in the regulation of immune and inflammatory responses and has been implicated in the pathogenesis of autoimmune demyelinating diseases such as multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), the main animal model of MS. NF-κB is essential for peripheral immune cell activation and the induction of pathology, but also plays crucial roles in resident cells of the central nervous system (CNS) during disease development. Here we review recent evidence clarifying the role of NF-κB in the different cell compartments contributing to MS pathology and its implications for the development of therapeutic strategies for the treatment of MS and other demyelinating pathologies of the CNS.
NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a protein complex that controls transcription of DNA. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet radiation, oxidized LDL, and bacterial or viral antigens.[1][2][3][4][5] NF-κB plays a key role in regulating the immune response to infection (k light chains are critical components of immunoglobulins). Incorrect regulation of NF-κB has been linked to cancer, inflammatory, and autoimmune diseases, septic shock, viral infection, and improper immune development. NF-κB has also been implicated in processes of synaptic plasticity and memory.[6][7][8][9][10]
In brief, NF-κB can be understood to be a protein responsible for cytokine production and cell survival.
Structure
All proteins of the NF-κB family share a Rel homology domain in their N-terminus. A subfamily of NF-κB proteins, including RelA, RelB, and c-Rel, have a transactivation domain in their C-termini. In contrast, the NF-κB1 and NF-κB2 proteins are synthesized as large precursors, p105, and p100, which undergo processing to generate the mature NF-κB subunits, p50 and p52, respectively. The processing of p105 and p100 is mediated by the ubiquitin/proteasome pathway and involves selective degradation of their C-terminal region containing ankyrin repeats. Whereas the generation of p52 from p100 is a tightly regulated process, p50 is produced from constitutive processing of p105.[12][13] The p50 and p52 proteins have no intrinsic ability to activate transcription and thus have been proposed to act as transcriptional repressors when binding κB elements as homodimers.[14][15] Indeed, this confounds the interpretation of p105-knockout studies, where the genetic manipulation is removing an IκB (full-length p105) and a likely repressor (p50 homodimers) in addition to a transcriptional activator (the RelA-p50 heterodimer).
Members
NF-κB family members share structural homology with the retroviral oncoprotein v-Rel, resulting in their classification as NF-κB/Rel proteins.[1]
There are five proteins in the mammalian NF-κB family:[16]
Species distribution and evolution
In addition to mammals, NF-κB is found in a number of simple animals as well.[17] These include cnidarians (such as sea anemones, coral and hydra), porifera (sponges), the single-celled eukaryote Capsaspora owczarzaki and insects (such as moths, mosquitoes, and fruit flies). The sequencing of the genomes of the mosquitoes A. aegypti and A. gambiae, and the fruitfly D. melangaster has allowed comparative genetic and evolutionary studies on NF-κB. In those insect species, activation of NF-κB is triggered by the Toll pathway (which evolved independently in insects and mammals) and by the Imd (immune deficiency) pathway.[18]
Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single, membrane-spanning, non-catalytic receptors usually expressed in sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes. Once these microbes havebreached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cell responses…
Signaling
Activation
NF-κB (green) heterodimerizes with RelB (cyan) to form a ternary complex with DNA (orange) that promotes gene transcription.[19]
NF-κB is important in regulating cellular responses because it belongs to the category of “rapid-acting” primary transcription factors, i.e., transcription factors that are present in cells in an inactive state and do not require new protein synthesis in order to become activated (other members of this family include transcription factors such as c-Jun, STATs, and nuclear hormone receptors). This allows NF-κB to be a first responder to harmful cellular stimuli. Known inducers of NF-κB activity are highly variable and include reactive oxygen species (ROS), tumor necrosis factor alpha (TNFa), interleukin 1-beta (IL1β), bacterial lipopolysaccharides (LPS), isoproterenol, cocaine, and ionizing radiation.[20]
Receptor activator of NF-κB (RANK), which is a type of TNFR, is a central activator of NF-κB. Osteoprotegerin (OPG), which is a decoy receptor homolog for RANK ligand, inhibits RANK by binding to RANKL, and, thus, osteoprotegerin is tightly involved in regulating NF-κB activation.[21]
Many bacterial products and stimulation of a wide variety of cell-surface receptors lead to NF-κB activation and fairly rapid changes in gene expression.[1] The identification of Toll-like receptors(TLRs) as specific pattern recognition molecules and the finding that stimulation of TLRs leads to activation of NF-κB improved our understanding of how different pathogens activate NF-κB. For example, studies have identified TLR4 as the receptor for the LPS component of Gram-negative bacteria.[22]TLRs are key regulators of both innate and adaptive immune responses.[23]
Unlike RelA, RelB, and c-Rel, the p50 and p52 NF-κB subunits do not contain transactivation domains in their C terminal halves. Nevertheless, the p50 and p52 NF-κB members play critical roles in modulating the specificity of NF-κB function. Although homodimers of p50 and p52 are, in general, repressors of κB site transcription, both p50 and p52 participate in target gene transactivation by forming heterodimers with RelA, RelB, or c-Rel.[24] In addition, p50 and p52 homodimers alsobind to the nuclear protein Bcl-3, and such complexes can function as transcriptional activators.[25][26][27]
Inhibition
In unstimulated cells, the NF-κB dimers are sequestered in the cytoplasm by a family of inhibitors, called IκBs (Inhibitor of κB), which are proteins that contain multiple copies of a sequence called ankyrin repeats. By virtue of their ankyrin repeat domains, the IκB proteins mask the nuclear localization signals (NLS) of NF-κB proteins and keep them sequestered in an inactive state in the cytoplasm.[28]
IκBs are a family of related proteins that have an N-terminal regulatory domain, followed by six or more ankyrin repeats and a PEST domain near their C terminus. Although the IκB family consists of IκBα, IκBβ, IκBε, and Bcl-3, the best-studied and major IκB protein is IκBα. Due to the presence of ankyrin repeats in their C-terminal halves, p105 and p100 also function as IκB proteins. The c-terminal half of p100, that is often referred to as IκBδ, also functions as an inhibitor.[29][30] IκBδ degradation in response to developmental stimuli, such as those transduced through LTβR, potentiate NF-κB dimer activation in a NIK dependent non-canonical pathway.[29][31]
Activation of the NF-κB is initiated by the signal-induced degradation of IκB proteins. This occurs primarily via activation of a kinase called the IκB kinase (IKK). IKK is composed of a heterodimer of the catalytic IKKα and IKKβ subunits and a “master” regulatory protein termed NEMO (NF-κB essential modulator) or IKK gamma. When activated by signals, usually coming from the outside of the cell, the IκB kinase phosphorylates two serine residues located in an IκB regulatory domain. When phosphorylated on these serines (e.g., serines 32 and 36 in human IκBα), the IκB inhibitor molecules are modified by a process called ubiquitination, which then leads them to be degraded by a cell structure called the proteasome.
With the degradation of IκB, the NF-κB complex is then freed to enter the nucleus where it can ‘turn on’ the expression of specific genes that have DNA-binding sites for NF-κB nearby. The activation of these genes by NF-κB then leads to the given physiological response, for example, an inflammatory or immune response, a cell survival response, or cellular proliferation. NF-κB turns on expression of its own repressor, IκBα. The newly synthesized IκBα then re-inhibits NF-κB and, thus, forms an auto feedback loop, which results in oscillating levels of NF-κB activity.[32] In addition, several viruses, including the AIDS virus HIV, have binding sites for NF-κB that controls the expression of viral genes, which in turn contribute to viral replication or viral pathogenicity. In the case of HIV-1, activation of NF-κB may, at least in part, be involved in activation of the virus from a latent, inactive state.[33]YopP is a factor secreted by Yersinia pestis, the causative agent of plague, that prevents the ubiquitination of IκB. This causes this pathogen to effectively inhibit the NF-κB pathway and thus block the immune response of a human infected with Yersinia.[34]
Inhibitors of NF-κB activity
Concerning known protein inhibitors of NF-κB activity, one of them is IFRD1, which represses the activity of NF-κB p65 by enhancing the HDAC-mediated deacetylation of the p65 subunit at lysine 310, by favoring the recruitment of HDAC3 to p65. In fact IFRD1 forms trimolecular complexes with p65 and HDAC3.[35][36]
Non-canonical
A select set of cell-differentiating or developmental stimuli, such as lymphotoxin-α, BAFF or RANKL, activate the non-canonical NF-κB pathway to induce NF-κB/RelB:p52 dimer in the nucleus. In this pathway, activation of the NF-κB inducing kinase (NIK) upon receptor ligation led to the phosphorylation and subsequent proteasomal processing of the NF-κB2 precursor protein p100 into mature p52 subunit in an IKK1/IKKa dependent manner. Then p52 dimerizes with RelB to appear as a nuclear RelB:p52 DNA binding activity and regulate a distinct class of genes.[37] In contrast to the canonical signaling that relies upon NEMO-IKK2 mediated degradation of IκBα, -β, -ε, the non-canonical signaling critically depends on NIK mediated processing of p100 into p52. Given their distinct regulations, these two pathways were thought to be independent of each other. However, recent analyses revealed that synthesis of the constituents of the non-canonical pathway, viz RelB and p52, is controlled by the canonical IKK2-IκB-RelA:p50 signaling.[38] Moreover, generation of the canonical and non-canonical dimers, viz RelA:p50 and RelB:p52, within the cellular milieu are also mechanistically interlinked.[38] These analyses suggest that an integrated NF-κB system network underlies activation of both RelA and RelB containing dimer and that a malfunctioning canonical pathway will lead to an aberrant cellular response also through the non-canonical pathway.
In immunity
NF-κB is a major transcription factor that regulates genes responsible for both the innate and adaptive immune response. Upon activation of either the T- or B-cell receptor, NF-κB becomes activated through distinct signaling components. Upon ligation of the T-cell receptor, protein kinase Lck is recruited and phosphorylates the ITAMs of the CD3 cytoplasmic tail. ZAP70 is then recruited to the phosphorylated ITAMs and helps recruit LAT and PLC-γ, which causes activation of PKC. Through a cascade of phosphorylation events, the kinase complex is activated and NF-κB is able to enter the nucleus to upregulate genes involved in T-cell development, maturation, and proliferation.[39]
In the nervous system
In addition to roles in mediating cell survival, studies by Mark Mattson and others have shown that NF-κB has diverse functions in the nervous system including roles in plasticity, learning, and memory. In addition to stimuli that activate NF-κB in other tissues, NF-κB in the nervous system can be activated by Growth Factors(BDNF, NGF) and synaptic transmission such as glutamate.[7] These activators of NF-κB in the nervous system all converge upon the IKK complex and the canonical pathway.
Recently there has been a great deal of interest in the role of NF-κB in the nervous system. Current studies suggest that NF-κB is important for learning and memory in multiple organisms including crabs,[9][10] fruit flies,[40] and mice.[7][8]NF-κB may regulate learning and memory in part by modulating synaptic plasticity,[6][41]synapse function,[40][42][43]as well as by regulating the growth of dendrites[44]and dendritic spines.[43]
Genes that have NF-κB binding sites are shown to have increased expression following learning,[8]suggesting that the transcriptional targets of NF-κB in the nervous system are important for plasticity. Many NF-κB target genes that may be important for plasticity and learning include growth factors (BDNF, NGF)[45] cytokines (TNF-alpha, TNFR)[46] and kinases (PKAc).[41]
Despite the functional evidence for a role for Rel-family transcription factors in the nervous system, it is still not clear that the neurological effects of NF-κB reflect transcriptional activation in neurons. Most manipulations and assays are performed in the mixed-cell environments found in vivo, in “neuronal” cell cultures that contain significant numbers of glia, or in tumor-derived “neuronal” cell lines. When transfections or other manipulations have been targeted specifically at neurons, the endpoints measured are typically electrophysiology or other parameters far removed from gene transcription. Careful tests of NF-κB-dependent transcription in highly purified cultures of neurons generally show little to no NF-κB activity.[47][48] Some of the reports of NF-κB in neurons appear to have been an artifact of antibody nonspecificity.[49] Of course, artifacts of cell culture—e.g., removal of neurons from the influence of glia—could create spurious results as well. But this has been addressed in at least two coculture approaches. Moerman et al.[50] used a coculture format whereby neurons and glia could be separated after treatment for EMSA analysis, and they found that the NF-κB induced by glutamatergic stimuli was restricted to glia (and, intriguingly, only glia that had been in the presence of neurons for 48 hours). The same investigators explored the issue in another approach, utilizing neurons from an NF-κB reporter transgenic mouse cultured with wild-type glia; glutamatergic stimuli again failed to activate in neurons.[51] Some of the DNA-binding activity noted under certain conditions (particularly that reported as constitutive) appears to result from Sp3 and Sp4 binding to a subset of κB enhancer sequences in neurons.[52]This activity is actually inhibited by glutamate and other conditions that elevate intraneuronal calcium. In the final analysis, the role of NF-κB in neurons remains opaque due to the difficulty of measuring transcription in cells that are simultaneously identified for type. Certainly, learning and memory could be influenced by transcriptional changes in astrocytes and other glial elements. And it should be considered that there could be mechanistic effects of NF-κB aside from direct transactivation of genes.
Clinical significance
Overview of signal transduction pathways involved in apoptosis.
Cancers
NF-κB is widely used by eukaryotic cells as a regulator of genes that control cell proliferation and cell survival. As such, many different types of human tumors have misregulated NF-κB: that is, NF-κB is constitutively active. Active NF-κB turns on the expression of genes that keep the cell proliferating and protect the cell from conditions that would otherwise cause it to die via apoptosis.
Defects in NF-κB results in increased susceptibility to apoptosis leading to increased cell death. This is because NF-κB regulates anti-apoptotic genes especially the TRAF1 and TRAF2 and, therefore, checks the activities of the caspase family of enzymes, which are central to most apoptotic processes.[53]
In tumor cells, NF-κB is active either due to mutations in genes encoding the NF-κB transcription factors themselves or in genes that control NF-κB activity (such as IκB genes); in addition, some tumor cells secrete factors that cause NF-κB to become active. Blocking NF-κB can cause tumor cells to stop proliferating, to die, or to become more sensitive to the action of anti-tumor agents. Thus, NF-κB is the subject of much active research among pharmaceutical companies as a target for anti-cancer therapy.[54]
However, caution should be exercised when considering anti-NF-κB activity as a broad therapeutic strategy in cancer therapy, even though convincing experimental data have identified NF-κB as a critical promoter of cancer development, creating a solid rationale for the development of antitumor therapy that suppresses NF-κB activity. Data have also shown that NF-κB activity enhances tumor cell sensitivity to apoptosis and senescence. In addition, it has been shown that canonical NF-κB is a Fas transcription activator and the alternative NF-κB is a Fas transcription repressor.[55] Therefore, NF-κB promotes Fas-mediated apoptosis in cancer cells, and thus inhibition of NF-κB may suppress Fas-mediated apoptosis to impair host immune cell-mediated tumor suppression.
Inflammation
Because NF-κB controls many genes involved in inflammation, it is not surprising that NF-κB is found to be chronically active in many inflammatory diseases, such as inflammatory bowel disease, arthritis, sepsis, gastritis, asthma, atherosclerosis[56] and others. It is important to note though, that elevation of some NF-κB inhibitors, such asosteoprotegerin(OPG), are associated with elevated mortality, especially fromcardiovascular diseases.[57][58] Elevated NF-κB has also been associated with schizophrenia.[59] Recently, NF-κB activation has been suggested as a possible molecular mechanism for the catabolic effects of cigarette smoke in skeletal muscle and sarcopenia.[60]
Non-drug inhibitors
Many natural products (including anti-oxidants) that have been promoted to have anti-cancer and anti-inflammatory activity have also been shown to inhibit NF-κB.[61][62] There is a controversial US patent (US patent 6,410,516)[63] that applies to the discovery and use of agents that can block NF-κB for therapeutic purposes. This patent is involved in several lawsuits, including Ariad v. Lilly. Recent work by Karin,[64] Ben-Neriah[65] and others has highlighted the importance of the connection between NF-κB, inflammation, and cancer, and underscored the value of therapies that regulate the activity of NF-κB.[66]
Extracts from a number of herbs and dietary plants are efficient inhibitors of NF-κB activation in vitro.[67][68][69]
The circumsporozoite protein of Plasmodium falciparum has been shown to be an inhibitor of NF-κB.[70]
As a drug target
Aberrant activation of NF-κB is frequently observed in many cancers. Moreover, suppression of NF-κB limits the proliferation of cancer cells. In addition, NF-κB is a key player in the inflammatory response. Hence methods of inhibiting NF-κB signaling has potential therapeutic application in cancer and inflammatory diseases.[71][72]
The discovery that activation of NF-κB nuclear translocation can be separated from the elevation of oxidant stress[73] gives an important hint to the development of strategies for NF-κB inhibition.
A new drug called denosumab acts to raise bone mineral density and reduce fracture rates in many patient sub-groups by inhibiting RANKL. RANKL acts through its receptor RANK, which in turn promotes NF-κB,[74] RANKL normally works by enabling the differentiation of osteoclasts from monocytes.
Disulfiram, olmesartan and dithiocarbamates can inhibit the nuclear factor-κB (NF-κB) signaling cascade.[75]
Anatabine’s antiinflammatory effects are claimed to result from modulation of NF-κB activity.[76] However the studies purporting its benefit use abnormally high doses in the millimolar range (similar to the extracellular potassium concentration), which are unlikely to be achieved in humans.
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NF-kB
Nuclear factor NF-kappa-B p105 subunit is a protein that in humans is encoded by the NFKB1 gene.[1]
This gene encodes a 105 kD protein which can undergo cotranslational processing by the 26S proteasome to produce a 50 kD protein. The 105 kD protein is a Rel protein-specific transcription inhibitor and the 50 kD protein is a DNA binding subunit of the NF-kappaB (NF-kB) protein complex. NF-κB is a transcription factor that is activated by various intra- and extra-cellular stimuli such as cytokines, oxidant-free radicals, ultraviolet irradiation, and bacterial or viral products. Activated NF-κB translocates into the nucleus and stimulates the expression of genes involved in a wide variety of biological functions; over 200 known genes are targets of NF-κB in various cell types, under specific conditions. Inappropriate activation of NF-κB has been associated with a number of inflammatory diseases while persistent inhibition of NF-κB leads to inappropriate immune cell development or delayed cell growth.[2]
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Signal Transduction Through Prion Protein
The cellular prion protein PrPc is a glycosylphosphatidylinositol-anchored cell-surface protein whose biological function is unclear. We used the murine 1C11 neuronal differentiation model to search for PrPc-dependent signal transduction through antibody-mediated cross-linking. A caveolin-1–dependent coupling of PrPc to the tyrosine kinase Fyn was observed. Clathrin might also contribute to this coupling. The ability of the 1C11 cell line to trigger PrPc-dependent Fyn activation was restricted to its fully differentiated serotonergic or noradrenergic progenies. Moreover, the signaling activity of PrPc occurred mainly at neurites. Thus, PrPc may be a signal transduction protein.
Science 15 September 2000: Vol. 289 no. 5486 pp. 1925–1928 DOI:10.1126/science.289.5486.1925
A cellular gene encodes scrapie PrP 27-30 protein.
Abstract
A clone encoding PrP 27-30, the major protein in purified preparations of scrapie agent, was selected from a scrapie-infected hamster brain cDNA library by oligonucleotide probes corresponding to the N terminus of the protein. Southern blotting with PrP cDNA revealed a single gene with the same restriction patterns in normal and scrapie-infected brain DNA. A single PrP-related gene was also detected in murine and human DNA. PrP-related mRNA was found at similar levels in normal and scrapie-infected hamster brain, as well as in many other normal tissues. Using antisera against PrP 27-30, a PrP-related protein was detected in crude extracts of infected brain and to a lesser extent in extracts of normal brain. Proteinase K digestion yielded PrP 27-30 in infected brain extract, but completely degraded the PrP-related protein in normal brain extract. No PrP-related nucleic acids were found in purified preparations of scrapie prions, indicating that PrP 27-30 is not encoded by a nucleic acid carried within the infectious particles.
Identification of Chemoattractive Factors Involved in the Migration of Bone Marrow-Derived Mesenchymal Stem Cells to Brain Lesions Caused by Prions
ABSTRACT
Bone marrow-derived mesenchymal stem cells (MSCs) have been reported to migrate to brain lesions of neurodegenerative diseases; however, the precise mechanisms by which MSCs migrate remain to be elucidated. In this study, we carried out an in vitro migration assay to investigate the chemoattractive factors for MSCs in the brains of prion-infected mice. The migration of immortalized human MSCs (hMSCs) was reduced by their pretreatment with antibodies against the chemokine receptors, CCR3, CCR5, CXCR3, and CXCR4 and by pretreatment of brain extracts of prion-infected mice with antibodies against the corresponding ligands, suggesting the involvement of these receptors, and their ligands in the migration of hMSCs. In agreement with the results of an in vitro migration assay, hMSCs in the corpus callosum, which are considered to be migrating from the transplanted area toward brain lesions of prion-infected mice, expressed CCR3, CCR5, CXCR3, and CXCR4. The combined in vitro and in vivo analyses suggest that CCR3, CCR5, CXCR3, and CXCR4, and their corresponding ligands are involved in the migration of hMSCs to the brain lesions caused by prion propagation. In addition, hMSCs that had migrated to the right hippocampus of prion-infected mice expressed CCR1, CX3CR1, and CXCR4, implying the involvement of these chemokine receptors in hMSC functions after chemotactic migration. Further elucidation of the mechanisms that underlie the migration of MSCs may provide useful information regarding application of MSCs to the treatment of prion diseases.
INTRODUCTION
Prion diseases are fatal neurodegenerative disorders in humans and animals that are characterized by the accumulation of a disease-specific isoform of the prion protein (PrPSc), astrocytosis, microglial activation, spongiosis, and neuronal cell death in the central nervous system (CNS). Although the etiology of the diseases is not clear, conversion of the normal prion protein to PrPSc plays a key role in the neuropathological changes (44). Therefore, compounds that inhibit PrPSc formation are considered as therapeutic candidates of the diseases, and many compounds have been reported to inhibit PrPSc formation in cell cultures and cell-free systems (reviewed in reference 56). However, only a few of these inhibitors, such as amphotericin B and its derivative (13), pentosan polysulfate (14), porphyrin derivatives (27), certain amyloidophilic compounds (25), and FK506 (37) have been reported to prolong the survival of prion-infected mice even when administered in the middle-late stage of infection but still before clinical onset. We recently reported that intraventricular infusion of anti-PrP antibodies (50) slowed down the progression of the disease even when initiated just after clinical onset. However, in addition to inhibition of PrPSc formation, the protection of neurons or restoration of degenerated neurons is thought to be important for functional recovery.
Bone marrow-derived mesenchymal stem cells (MSCs) differentiate into cells of mesodermal origin such as adipocytes, osteoblasts, and endothelial and muscle cells (41, 43). In addition, MSCs are known to transdifferentiate into neuronal and glial cells. MSCs have been shown to migrate to damaged neuronal tissues and to alleviate the deficits in experimental animal models of cerebral ischemia (10), spinal cord injury (20), Parkinson’s disease (19, 33), and amyotrophic lateral sclerosis(59). MSCs also secrete various neurotrophic factors that may protect neuronal tissues from degradations, as well as stimulate the activity of endogenous neural stem cells (38). Therefore, despite their mesodermal origin, MSCs are considered to be a candidate for cell-mediated therapy for neurodegenerative diseases. One of the characteristics of MSCs is their migration to brain lesions caused by neurodegenerative diseases, including prion diseases (10, 19, 39, 51). This feature may be of further use for cell-mediated therapy of neurodegenerative diseases, particularly for prion diseases, Multiple sclerosis and Alzheimer’s disease, which have diffuse pathological lesions.
Since many cytokines, chemokines, and adhesion molecules are involved in the homing of immune cells (9, 36, 53), evidence that a variety of chemokines and growth factors, as well as their cognate receptors, have a pivotal role in the migration of MSCs has been accumulated. These factors include CXCL12 and its receptor CXCR4 (30, 40; reviewed in reference 52), CCL2 (15, 62, 66), CCL3 (62), interleukin-8 (48, 62), hepatocyte growth factor (16), platelet-derived growth factor AB (PDGF-AB), insulin-like growth factor 1 (IGF-1), CCL5 and CCL22 (42), and integrin β1 (23). Regarding the migration of MSCs to injury in the CNS, the involvement of CCL2 (61), CXCL12/CXCR4, and CX3CL1/CX3CR1 (24) has been reported. However, knowledge of the mechanism by which MSCs migrate to pathological lesions of neurodegenerative diseases is insufficient, and further efforts are required to elucidate this mechanism.
We recently reported that human MSCs (hMSCs) migrate to CNS lesions and prolong the survival of mice infected with prions (51). In the present study, we investigated factors that are involved in the migration of hMSCs to brain lesions of prion diseases.
To say that the body is one giant communication system is an understatement. The expression of genes and the ability for host cells to operate normally and to chemically call for help when faced with an antigen is esential to health. As discussed above, these prion interferors with the interferon and other defensive signaling processes must be injected to bypass the mucosus and the skin. This can only be accomplished through innoculation and vaccination.
The introduction of foreign proteins and DNA/RNA into the otherwise healthy body is certainly described here as the cause of most disease states in modern times. And from the time that this interferon was discovered, these psychopathic scientists have been working overtime to prevent our bodies from being able to fight what they inject.
What you have just read is the cause and cure for AIDS, cancers, dementias, and a host of other modern medically-induced disease states that revolve around prion infection and misfolding of the signal processing of the body. It is not so much a cure as an acknowledgement of the cause, for when disease is purposefully caused, the word cure seems trivial in practice, and allows the culprits to literally get away with murder.
It was caused by them…
Will we sit by helplessly and hope for a cure to these purposefully caused diseases by the very perpetrators of them?
Isn’t that the American way though?
For as we wait, they merely perfect their science of biological aggression and warfare…
(Note: all unlinked data as descriptions above from Wikipedia, which are well-sourced within that site.)
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–Clint Richardson (realitybloger.wordpress.com)
–Thursday, December 4rth, 2014
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