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Author: Subject: Bacterial resistance to antibiotics.
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[*] posted on 11-11-2014 at 07:57


There are antibiotics that can affect the replication of the bacteria by

-inhibiting transcription, thus preventing mRNA and inhibiting protein synthesis

-inhibit the activity of DNA/RNA grases/topoisomerases, preventing polymerase from replicating the DNA

for the most part, most antibiotics affect some aspect of cell wall synthesis, however, there are antibiotics such as Myxopyronin, which inhibit bacterial RNA polymerase.

one method to decrease antibiotic resistance, is to use an inhibitor for the protein that causes the antibiotic resistance, such as clavulanic acid which binds to beta-lactamase, which some bacteria produce to break down beta-lactam antibiotics.
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[*] posted on 11-11-2014 at 23:15


Quote: Originally posted by confused  
There are antibiotics that can affect the replication of the bacteria by

-inhibiting transcription, thus preventing mRNA and inhibiting protein synthesis

-inhibit the activity of DNA/RNA grases/topoisomerases, preventing polymerase from replicating the DNA

for the most part, most antibiotics affect some aspect of cell wall synthesis, however, there are antibiotics such as Myxopyronin, which inhibit bacterial RNA polymerase.

one method to decrease antibiotic resistance, is to use an inhibitor for the protein that causes the antibiotic resistance, such as clavulanic acid which binds to beta-lactamase, which some bacteria produce to break down beta-lactam antibiotics.
True, particularly for fluoroquinolones on gyrase/topos, which I failed to mention.
More sites of action as well. Really ridiculous how many there are. If it's different from a human, something likely targets it in concept.
Quote: Originally posted by Chemosynthesis  
However, there are antibiotics that inhibit DNA replication by specific bacterial DNA polymerase subunits, transcription, or bacterial ribosome translation specifically enough to be safe for use in people.


Small 30S ribosome targeting antibiotics include: neomycin, gentamycin and paromomycin.
Large 50S include erythromycin.
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[*] posted on 25-11-2014 at 04:44


Not sure how relevant this but I often wonder why the use of phages is not more widely used for antibiotic resistant microbes, although my own view is this is cost based. More money to be made with tweaking antibiotics.

EDIT
I did a quick search
PMCID: PMC4072922 Natural solution to antibiotic resistance: bacteriophages ‘The Living Drugs’
Havnt read it yet but looks interesting.

[Edited on 25-11-2014 by Little_Ghost_again]


For a good general look at resistance this looks to have some good info PMCID: PMC2937522
its a pretty big paper thouh


[Edited on 25-11-2014 by Little_Ghost_again]




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[*] posted on 25-11-2014 at 05:38


I actually have some professional experience with phage. It was looking big in Easter Europe and Russia back around the turn of the (technically previous now) century, however the emergence of sulfonamides allowed much cheaper and easier scaled production (at the time).

Antibiotics are actually fairly unprofitable. Phage are a lot cheaper to produce at marginal cost than antibiotics, and regulation is kind of burdensome since they have been treated like antibiotics.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400130/
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[*] posted on 25-11-2014 at 13:03


Quote: Originally posted by Chemosynthesis  
I actually have some professional experience with phage. It was looking big in Easter Europe and Russia back around the turn of the (technically previous now) century, however the emergence of sulfonamides allowed much cheaper and easier scaled production (at the time).

Antibiotics are actually fairly unprofitable. Phage are a lot cheaper to produce at marginal cost than antibiotics, and regulation is kind of burdensome since they have been treated like antibiotics.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400130/


I have seen a TV program a couple of years ago, it was based around a eastern European country (I cant remember which), The hospital had a lab where they would go with a glass jar to the sewer outlet and look for phages in the effluent, it had great promise for MRSA in the hospital there, I also remember it saying that phage treatment was more common in Veterinary uses.
There are some great papers on phages, really fascinating. I am still not sure what the OP is trying to do?? Is he trying to grow it or just looking into its production, maybe for some kind of school project??

My own view on drug production is a bit conflicting, on the one hand you have massive expense of trials etc that raise the cost of making a new drug, then on the other you want a safe drug... Then you have the situation where I am taking part in a trial for a new cancer drug, I may or may not be on the real drug or the placebo (judging by the improvement I think i am on the drug).
I also think alot of anti Biotic resistance is down to the antibiotics used in food production (see ref in earlier post for citation).
I have been lucky enough to see home scale, lab scale, and a trip around industrial scale bio reactors for M.O's, each completely different.
Which phage did you work on?





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[*] posted on 25-11-2014 at 13:27


Good question on the OP. Kind of an aside, but I agree about antibiotic use in veterinary CAFO/food industry use.

It's kind of awkward in a sense, though understandable, that so much effort goes into pre-clinical and clinical screening for toxicities when the most frequently occurring drug side effects and adverse reactions are those most commonly prescribed in hospitals (not to be confused with DAWN emergency room statistics). The sheer number of administrations and the law of averages is what leads to clinical pharmacology problems.

As far as phage, I'd prefer not to say specifically because I am still waiting on publications in various stages of submission. I've worked on 4 or so, having discovered one, which actually isn't as prestigious as I had hoped since apparently high school children are just as accomplished in that particular metric.
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[*] posted on 25-11-2014 at 18:26


Quote: Originally posted by Chemosynthesis  
Good question on the OP. Kind of an aside, but I agree about antibiotic use in veterinary CAFO/food industry use.

It's kind of awkward in a sense, though understandable, that so much effort goes into pre-clinical and clinical screening for toxicities when the most frequently occurring drug side effects and adverse reactions are those most commonly prescribed in hospitals (not to be confused with DAWN emergency room statistics). The sheer number of administrations and the law of averages is what leads to clinical pharmacology problems.

As far as phage, I'd prefer not to say specifically because I am still waiting on publications in various stages of submission. I've worked on 4 or so, having discovered one, which actually isn't as prestigious as I had hoped since apparently high school children are just as accomplished in that particular metric.


Fair enough, let me know when you have published though! I would love to read the papers. Publishing is a funny beast, like with my dad if does something gets excited then cant say much until the work gets published! I am working on getting my style right etc etc and hope next year to publish something, it might not happen but would be cool to do some original work and get it published.
Discovering a phage is cool! Having seen the work that goes into the isolation etc its no easy task. did you get to take a look with a SEM?
Microscopy is a real passion but I am still very amateur at slide prep etc, takes a good while to get the staining and mounting right, and although there is a microtome here I am not allowed near it, but then again having seen what the blades cost.........
Glasgow uni has some really cool electron microscopes, I have been a few times and had a go with there old SEM. maybe one day I will make enough to own one :D




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[*] posted on 26-11-2014 at 07:39


Quote: Originally posted by Little_Ghost_again  
Microscopy is a real passion but I am still very amateur at slide prep etc, takes a good while to get the staining and mounting right, and although there is a microtome here I am not allowed near it, but then again having seen what the blades cost.........


Well you might be able to make do without a microtome if you have a scapel and slide it extremely thinly. Im assuming you're refering to a normal histology H&E stain type of slide.

You might want to take a look at this though
[A novel method for preparing histology slides without a microtome.]
http://www.ncbi.nlm.nih.gov/pubmed/12479353

[Edited on 26-11-2014 by confused]

[Edited on 27-11-2014 by confused]
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[*] posted on 26-11-2014 at 07:41


Publishing sure is. I think the hardest pre-submission part is sometimes consensus among co-authors, or knowing when to hand it over to another party for opinions when you get stuck. I hope you do get to publish! You should take a lot of pride in your work.

I actually did get to isolate phage, grow out batches, set up my samples for the electron microscope techs (saw the image on a screen, but didn't operate it), try activating/deactivating lytic cycles, did some genomic work, etc.

Check Ebay. There is an untested Amray SEM going to 99 cents (USD) with two days to close. Shipping would be expensive for you, but perhaps you could get one soon.
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[*] posted on 26-11-2014 at 09:29


I think the reason phages are not used that often in medicine is because bacterial resistance is very, very easily acquired. In a population of 1 billion, the change of one being immune is about 1%. In a common infection that is almost a change of 100%. Especially with the very strong selection pressure of the phage itself this excludes phages from being used as a medicine.

The problem is that resistance against phages can be acquired trough down-regulation of non-essential proteins. All regulation is, randomly, up and down regulated by different bacteria within the population. They do this to make sure at least one of them survives... As they are all one in means of genes this gives the best change of survival of the genes (selfish gene theory).

Conventional antibiotics work on essential systems, making it a bit harder to gain resistance.

Edit: Definitely recommended literature: The selfish gene, Richard Dawkins 1976; explaining why altruism exists.

[Edited on 26-11-2014 by Tsjerk]
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[*] posted on 26-11-2014 at 10:31


Quote: Originally posted by Chemosynthesis  
Publishing sure is. I think the hardest pre-submission part is sometimes consensus among co-authors, or knowing when to hand it over to another party for opinions when you get stuck. I hope you do get to publish! You should take a lot of pride in your work.

I actually did get to isolate phage, grow out batches, set up my samples for the electron microscope techs (saw the image on a screen, but didn't operate it), try activating/deactivating lytic cycles, did some genomic work, etc.

Check Ebay. There is an untested Amray SEM going to 99 cents (USD) with two days to close. Shipping would be expensive for you, but perhaps you could get one soon.


Thanks for the paper! The scope is cool, but again it isnt the cost of getting one its the cost of running one lol. all that gold sputtering etc etc, We run on generators for electric, I wonder how much juice a SEM would use :D.
Bacteria are far less likely to aquire resistance to a phage than a drug, a drug enters the cell wall etc etc a phage (depending) looks for certain proteins or whatever (depending on the mechanism like lock and key etc etc), so I would be doubtful that bacteria would develop resistance to phages quicker than drugs.
Again like you cited the selfish gene...........I dont think much of that book but if you use it as an example then you would also need to apply the principle to the phage, so as the organism changed so would the phage.
Take MRSA some lab strain are just about totally resistant to antibiotics including the last chance saloon vancamicine, and yet there are still phages that will attack it.
Both Ireland and a eastern European country (I cant remember which one) have had good results treating MRSA with phages.
I agree drugs target critical systems but first the drug has to enter the organism, in many resistant cases the organism has changed the cell membrane and stops the drug or class of drugs, many phages just need the protein or whatever present, zoom in land and drill down into the bug (not all and way over simplified).
So before I get picked up on it, no I dont mean actually drill into it, but some look like a space ship and have a kind of spring loaded mechanism that fires down into the cell unloading its payload.
Anyway thanks for the link I might give that a try! I did find a cheap microtome but it needed a new blade, the super duper diamond ones are a little expensive and fragile, but seeing a cell nucleus cleanly cut in half shows you why they cost what they do.
Yeah and getting a tech to let you twiddle the knobs is no easy task! they all seem to be touchy with there scopes




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[*] posted on 26-11-2014 at 12:06


Never said anything about running an SEM at home, just getting one ;).

I have some phage papers in a filing cabinet around here on the selective pressures or likelihood of resistance somewhere. It definitely is considered more difficult to become resistant to a phage. Proper antibiotic use and dosing greatly diminishes the occurrence of resistance, and there are some potential VRSA treatments, but the specificity of phage also allows good drug targeting without impacting as much of the microbiome.
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[*] posted on 16-12-2014 at 21:12


One other thing I came across the other day, until pretty recently it was thought viruses did not exist in the marine environment, but turns out its full of them in the upper couple of mm of water and nearly all are actually phages!
Oh the ref for that is general microbiology fifth ed Roger Y.Stainer .




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[*] posted on 16-12-2014 at 22:36


Sounds like the Global Ocean Sampling Expedition.

Also, the FDA did happen to approve a fourth antibiotic for limited use before the new calendar year: ceftazidime-avibactam.
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[*] posted on 17-12-2014 at 05:39


Quote: Originally posted by Chemosynthesis  
Sounds like the Global Ocean Sampling Expedition.

Also, the FDA did happen to approve a fourth antibiotic for limited use before the new calendar year: ceftazidime-avibactam.


I have been reading the paper for that, I am not so sure why the rush with it? Interesting though that its so highly selective.

I am going to Glasgow University tomorrow with my dad, they are shutting down for Christmas and one the labs used for teaching is due for a DEEP CLEAN, so as its not going to be used for a bit and is getting gassed soon, I have been offered the chance to go and try some stuff out, I mentioned to chris (guy who operates the electron scopes) that I like phages, he has promised to show me some under both scopes! I love the structure and simple beauty of them.




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[*] posted on 25-7-2015 at 05:44
Millions of preventable deaths planned


We are now on the brink of entering into a new era of retro-medicine. Due to the evolution of antibiotic resistant bacteria , infections up till now easily cured with a few pills will become rampant once more. Treatments for infections that have not been practiced in over seven decades will soon become common again. Disfigurement and death due to inadequacy of surgical excision of infected tissue will mount into unheard tolls. Each year, an estimated 2 million people in the U.S. are infected with antibiotic-resistant bacteria of which at least 23,000 die , making this the primary emerging public health issue in the United States. Worldwide it's anybodies guess what the count will come to in succeeding years.

The ever expanding list of resistant infectious pathogens include , Tuberculosis , Staph most commonly MRSA , E-Coli , various other pathogenic bacteria's that have become difficult to treat. Recently evolved Acinetobacters superbugs are much more dangerous than the original bacteria. Brought back by wounded soldiers in Iraq , current versions have thousands of mutants that thrive in the jagged wounds made by modern weapons growing stronger with antibiotic exposure , resist most treatments , and can survive for weeks on hard surfaces like counters and equipment with no food. The consequence of acquiring an Acinetobacter infection ranges from a few more weeks in the hospital to severe suppression of the immune system that can exacerbate other illnesses and lead to death. Unless they are screening for routinely , doctors may not even know if a patient has been infected.

KPC is a genetically conferred attribute present in many infectious bacterial strains making them highly resistant to conventional antibiotic treatment. NDM-1 is a gene that turns bacteria resistant to almost all antibiotics. The resistance gene can pass from bacteria to bacteria, making common treatable infections suddenly untreatable. These occur as Multi , Extensive , and Pan drug resistant variants the Pan being entirely untreatable with drug regimens. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075864 , http://wwwnc.cdc.gov/eid/article/21/6/14-1504_article ,
http://www.pbs.org/wgbh/pages/frontline/health-science-techn...

It can easily cost up to a billion dollars to bring a new drug to the market. Drugs to treat chronic diseases that you must take for the rest of your life have the greatest return on investment. Antibiotics which are taken only for a short course of maybe a couple of weeks and then you stop , have just marginal profitability. Motivated by maximizing profit the dominant pharmaceutical companies have ended research and development on antibiotics , at precisely a time when new drugs to treat infectious disease are most needed. In March 2015 a feckless ' plan of action ' was enacted to play up administrative responses. Notably lacking is any provision to develop the needed new antibiotic treatments. QUOTE :
" Despite the urgent need for new antibiotics, the number of products in the drug-development pipeline is small and commercial interest remains limited." " Advancement of drug development will require intensified efforts to boost scientific research, attract private investment, ". In other words we're all going to be managed to death. Well a plaque on their house. Whatever comes around goes around. http://www.whitehouse.gov/sites/default/files/docs/national_...

These are the facts , draw your own conclusion , but if you think this just happened unexpectedly , you must believe everything people tell to you.
This had been anticipated , considered , and deliberately chosen as a course to follow to achieve radical population reduction.

Superbugs Resistant To Antibiotics

http://www.youtube.com/watch?v=JW1T_RP-1rQ

.

[Edited on 25-7-2015 by franklyn]




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[*] posted on 26-7-2015 at 16:36


So what do you do about it, franklyn? Have you ever failed to complete a course of antibiotics prescribed by a doctor? Have you ever taken antibiotics for a viral infection (cold, flu, ear infection, etc.)? Do you purchase meat from producers who overuse antibiotics? Do you use antibiotic hand washes for general purposes around your home? All of these things are amongst the primary reasons for the development of antibiotic resistance. They are also the reason that, even if new drugs come to market, resistance to those will often come about within just a few years.

To my knowledge, 2005 was when the most recent new class of antibiotics was introduced to the market - tigecycline, which was specifically designed to overcome the then-current mechanisms of resistance to tetracyclines. And yet, even before it was developed, there were species - some Pseudomonads, for example - which already had a mechanism by which they could be resistant (an efflux pump). Ultimately, all new antibiotics are stopgaps - resistance WILL emerge sooner or later (usually sooner - and the more the drug is used, the faster resistance will emerge), and may already exist anyway. For perspective, E. coli replicates every 20 minutes, and about 1 in 1000 bacteria will experience a mutation in every generation, and a colony a couple mm in diameter contains a few billion cells. At that rate, how long do you think it will take for a mutant to spring up when there's a strong selection pressure around?

As for "evil pharma, who's only interested in making a profit" - yuh, that's what companies do. I would have thought that you, with your libertarian, capitalist, anti-socialist bent, would know that, in a free market, a business should and will do whatever it is allowed to do in order to maximise profits. Antibiotics are NOT profitable drugs in the first place - people take them for a short period of time, often just a few days, rarely more than a couple of months - and any new antibiotic which reaches the market will also be used only as a last resort in order to slow the emergence of resistance to the drug. Despite that, antibiotics are no cheaper to develop than any other class of drug. So why should any company do something that is against its interests? I mean, a company taking on a burden in order to do something which has limited potential for profit (in fact, probably a financial loss) just because it's a "benefit to society" - isn't that scarily like socialism?

Of course, we could push for our governments to provide incentives to drug manufacturers - extended patent protection, perhaps, or even simply chipping in on some of the R&D costs - but then again, the government should probably keep its nose out of the market and not "prop up" unprofitable sections of industry.

A lot of public institutions have people who work towards the development of new antibiotics. Of course, funding for science - particularly the type of "low level" R&D involved in early-stage drug discovery - is getting harder and harder to come by, since funding basic research is no longer seen as a public good, and besides, those dodgy academics are just going to sell their discovery to big pharma and pocket the cash anyway, so why should the public fund that?

As for "This had been anticipated , considered , and deliberately chosen as a course to follow to achieve radical population reduction." Sure, that's possible - insofar as there are no formal logical fallacies that I can see in the statement. And after all, a pandemic of antibiotic resistant infections would probably do a reasonable job of reducing the population. Also, NDM-1, the big scary at the moment, was named for New Delhi, where it was first isolated - and India does have a big population...

Of course, it could also just be a consequence of human nature. As you said, we have known for a long time about the emergence of antibiotic resistance - the first report of antibiotic resistance came about a year after the first antibiotic. And yet, stubborn agribusinesses refuse to improve their practices in order to reduce their reliance on antibiotic prophylaxis or as growth promoters (hey, why should they? I mean, sure, society would benefit, but the companies would lose money. You just keep your socialist nose out of it and let the market take care of... oh); patients still whinge that they "need" antibiotics for their cold, because they "know [their] bodies" and "this is the worst cold ever, it must be something else". Then when they get better after two days (because that's how the common cold works), they "don't need these antibiotics any more," so they tuck the half pack back in the cupboard for next time they get the sniffles (because hey, they "worked" for this cold, so what do those doctors know, eh?). Heck, I've personally seen someone give a friend their leftovers, because "this helped me, you should try it."

So, the problem COULD be a concerted effort at population reduction; alternatively, it COULD be the well documented effects of greed, stubbornness and cognitive biases.
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[*] posted on 26-7-2015 at 17:04


Quote: Originally posted by ziqquratu  


As for "This had been anticipated , considered , and deliberately chosen as a course to follow to achieve radical population reduction." Sure, that's possible - insofar as there are no formal logical fallacies that I can see in the statement. And after all, a pandemic of antibiotic resistant infections would probably do a reasonable job of reducing the population. Also, NDM-1, the big scary at the moment, was named for New Delhi, where it was first isolated - and India does have a big population...



How about, who would benefit from such a 'cull'? (The idea of a deliberate cull is of course the stuff Alex Jones/Jeff Rense websites is made of, in itself a good reason to distrust these 'theories'). And who's the Bond Villain in this piece? :o

To avoid catastrophe and assuming Big Pharma sees no profit motive in solving the crisis, then logically Governments will have to take action (on several levels). A political illiterate would protest such a benevolent intervention with the usual hysterical shrieks of 'That's Socialism!' but one must hope the ADULTS with cooler heads will prevail.

[Edited on 27-7-2015 by blogfast25]




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[*] posted on 29-7-2015 at 01:44
watch the next 3 minutes


http://www.youtube.com/watch?v=Hgyztsj7O6M&t=50m35s



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[*] posted on 29-7-2015 at 05:44


Quote: Originally posted by franklyn  
http://www.youtube.com/watch?v=Hgyztsj7O6M&t=50m35s


And NUTTIN' about teh chemtrailz! Very disappointing...





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[*] posted on 29-7-2015 at 06:58


The truth behind every Internet conspiracy theory. A good video by "Cracked"
https://youtu.be/8HezndRzDBQ




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[*] posted on 29-7-2015 at 09:56


Quote: Originally posted by Bot0nist  
The truth behind every Internet conspiracy theory. A good video by "Cracked"
https://youtu.be/8HezndRzDBQ


Good vid!

Flat Earth Society: Going Tinfoil since 2004!




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[*] posted on 29-7-2015 at 15:16
I've said before


Truth is elemental , it cannot be created nor destroyed , it can only be suppressed or adulterated.
Precluded by it's nature from doing the former , your only recourse is to perpetrate the latter.

Availed to you are tired old communist disinformation methods which identify you as what you are
http://www.sciencemadness.org/talk/viewthread.php?tid=22410#...

National Security Study Memorandum 1974 , alias Kissinger Report shown before here _
http://www.sciencemadness.org/talk/viewthread.php?tid=19102&...
is your shadow government's ( certainly not mine ) institutional excrement.
Readily available from the Nixon Library ( NSSM 200 )
http://www.nixonlibrary.gov/virtuallibrary/documents/nationa...

Implications of Worldwide Population Growth for U.S. Security and Overseas Interests
http://www.nixonlibrary.gov/virtuallibrary/documents/nssm/ns...
FULL TEXT
http://pdf.usaid.gov/pdf_docs/PCAAB500.pdf

The casual reader must make a judgement. Do they believe what they can see for themselves ,
or do they believe what others tell them about what they don't want them to see.
The last word from the same source _
http://www.youtube.com/watch?v=Hgyztsj7O6M&t=1h26m18s


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Techniques to Disrupt, Deviate and Seize Control of an Internet Forum In case you wonder W T F ! is going on here ?
www.zerohedge.com/contributed/2012-10-28/cointelpro-techniques-dilution-misdirection-and-control-internet-forum https://web.archive.org/web/20120814124000/www.washingtonsblog.com/2012/08/the-15-rules-of-internet-disinformation.html
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aga
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[*] posted on 29-7-2015 at 15:21


To be fair, the human population is out of control.

Nature was already taking action, long before any 'plans' were conceived.

Only China has ever had the balls to face the problem head-on.

The North (including Australia) opted for Junk Food as the main birth/death rate modulator.

The South had little choice and ended up with war/disease/famine.

All still not working out very well though, so expect Severity.

It dunt look good peeps.

[Edited on 29-7-2015 by aga]




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blogfast25
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[*] posted on 29-7-2015 at 15:34


Quote: Originally posted by franklyn  
Truth is elemental , it cannot be created nor destroyed , it can only be suppressed or adulterated.



Once again it's you that accepts low level sources as if they are Gospel truth, with no room for error, doubt or interpretation.

You find an 'explanation' for 'something' on the Tinkerwebs and your critical faculties leave you altogether. We've been here before, see your water car thread, aka 'you can't argue with success' (LOL).

I've read more interesting stuff on David Icke's site, franklyn.

Your main raison d'être on this forum seems to be to annoy others with ever more third rate phantasmagoria...

[Edited on 29-7-2015 by blogfast25]




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