Wednesday, August 1, 2018

Hormesis: A Failed Paradigm


There is a paradigm of radiation protection that emphasizes the body's resilient repair mechanisms, even when confronted with double-strand DNA breaks.

That paradigm is called hormesis.

There are many scientific challenges to hormesis. Here is a discussion of the latest challenge, which is derived from scientists' efforts to understand why CRISPR gene editing technology is producing genetic mutations that undermine the technology's utility.

CRISP technology promised precise gene editing capabilities but the results have disappointed as editing has been found to cause significant damage.  You can read about the errors caused by CRISPR here: https://techcrunch.com/2018/07/16/crispr-dna-editing-may-cause-serious-genetic-damage-researchers-warn/

It turns out that the body's failure to repair damage caused by editing is at issue.

Yesterday on Twitter I discovered a fascinating review article that interviews researchers who are seeking to understand these failures in DNA repair:
Robert Sanders (2018, July 30). DNA repair after CRISPR cutting not at all what people thought. University of California Berkeley. Available,http://news.berkeley.edu/2018/07/30/dna-repair-after-crispr-cutting-not-at-all-what-people-thought/

The article specifically addresses the challenge encountered by geneticists when trying to edit DNA using CRISPR-Cas9.

It seems that the problem lies in cellular repair processes. 


CRISPR technology relies on human cellular repair processes after CRISPR editing.
It turns out that fixing double-strand DNA breaks is more complicated than researchers anticipated. (Surprise, surprise).

Scientists from UC Berkeley's Innovative Genomic Institute investigating DNA repair processes discovered that a phenomenon known as the Fanconi anemia pathway is critical for repair of double strand DNA breaks.

The genes involved in the Fanconi anemia pathway produce 21 proteins that are critical for homologous double-strand DNA repair (one of two types of possible repairs, with the homologous form requiring insertion of DNA to replace damaged DNA as opposed to simply re-stitching it together).

Well, it turns out that not all cells have access to the Fanconi anemia pathway, as illustrated in the passage below, which points to some unresolved challenges with CRISPR technology:
The importance of the Fanconi anemia pathway in repairing CRISPR breaks throws into doubt some planned CRISPR treatments for the disease itself, however. Without an active Fanconi anemia pathway, cells may not be able to replace their mutated genes with normal genes after Cas9 makes a cut.
Some cells may not be able to replace their mutated genes with normal genes after being damaged because they lack access to this pathway.

If you are unfortunate enough to incur damage to the genes involved directly in this pathway you will likely develop unpleasant diseases such as leukemia.

Wikipedia identifies 17 genes involved in the Fanconi anemia pathway:
scientists have identified 17 FA or FA-like genes: FANCA, FANCB, FANCC, FANCD1(BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (BRIP1), FANCL, FANCM, FANCN (PALB2), FANCP (SLX4), FANCS (BRCA1), RAD51C and XPF. FANCB is the one exception to FA being autosomal recessive, as this gene is on the X chromosome. These genes are involved in DNA repair. https://en.wikipedia.org/wiki/Fanconi_anemia#Genetics
What are the implications?

First, the clear implication of this research is that double-strand DNA repair is not equally possible for all cells.

Second, homologous DNA repair is compromised if the genes involved in sequencing the proteins involved are themselves damaged.

Third, these findings throw another wrench into the HORMESIS idea that the body is infinitely resilient in its DNA repair mechanisms.

Not all double-strand DNA can be repaired. 

Hormesis cannot apply to cells that lack access to these genes.








17 comments:

  1. Majia is very smart and level-headed. This is a very good and article she wrote that makes a strong point without propagand and mumbo jumbo.

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    1. https://mobile.twitter.com/kenklippenstein/status/1024387421998342144

      90% penguins gone

      75% of insects gone in 3 decades

      Sooner probably than later, our atmosphere will be like venus. Pure fuking sulfuric acid. That is,  with all the sulfuric acid, the Trump administrations is using in the upper atmosphere to do geoengineering. 

      The oceans are becoming acidified. Massive amounts of co2, is supercatalyzing the release of the other greenhouse gasses, like methane. The net effect, is exponentially heating the earths atmosphere, upward.

      It is permanently changing the geochemistry, of the earth. Like venus was. It is causing the earth to be more volcanic. Like venus.

      Radionuclide contamination in the atmosphere, is destroying the ozone. Radionuclide pollution, is destroying the life-giving chemistry of biomolecules on earth. IT is increasing ocean acidification exponentially.

      Maybe that is why trump is supposedly, more antikoch and pro-monsanto now. Even with the lies of eugenics and hopes for genetic engineering, they think they can create disposable cyborg things, that are part machine to run other machines, after they have destroyed all life, and earth is uninhabitable.

      The Trumpsters, and greed guts, can call earth verthus, before they fry from the hell on earth, they are reinforcing.

      The greedguts and gulpers, wall street, goldman sachs, the oligarchs and billionairs will still have something to speculate on and keep their fake money moving, their insatiable appetite for fraaud, death, speculative casinos going, as all life is destroyed on earth and it becomes a superheated inferno, like venus.

      They can speculate on genetically engineered andy yet-imperfect, disposable cyborgs, that live in orbit and shoot nuclear missles at each other.

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  2. It is almost always the case that a few persons know X about Z but are prevented from saying so publicly. Then it may take years or decades before the information is allowed out. I believe Marie Curie ended up with radiation burnt hands over a century ago. So we have known collectively for well over a century tht radiation is harmful to human flesh. The details can be interesting but the basic idea is not novel. I remember several years ago an emeritus professor of physics at Cambridge wrote something about the energizing & beneficial effects of radiation on humans which I suppose a few took for veritable truth. At some point society will manage again to value the importance of reason and facts. Meanwhile . . . anything goes.

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  3. I have a list in mind of the necessities of a decent society/nation.

    1. plentiful decent jobs
    2. a good judiciary not the two tiered system we have as Glenn Greenwald has written about
    3. an adequate military
    4. a fair political culture
    5. Etc.

    Unfortunately money does count for a lot which is why I would rather live in Norway than Sudan or Chad. Want a clean environment? You need money. Poor people can not afford the luxury of going after polluters. So jobs and prosperity first, then all the refinements like fairness in the legal system, clean water, safety, etc. People at the survival level can not value these things as their lives hurt too much. This should be obvious but isn't. And you can not generate real wealth out of thin air which is why Communists nations have resorted to slave labor. As people used to say, if wishes were horses then beggars would ride.

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    1. 'Kill Them All': This Right-Wing Extremist's Violent Rhetoric Features on Trump-Endorsed Radio Show

      He once declared that former President Barack Obama “deserves to be hung.”

      By Jonathan Hutson / Salon

      July 31, 2018, 2:32 PM GMT


      Suppose there were a best-selling author, historian, essayist, public speaker, TV commentator, adviser to Ron Paul, secessionist advocate, Christian nationalist, Vladimir Putin apologist and expert on terrorism who was married to a senior intelligence official. Suppose he were a frequent commentator on an influential radio show with close ties to President Donald Trump, his family and his administration.

      Suppose this Trump-connected radio show routinely directed its listeners to this person’s blog, on which he wrote that it was “quite near time” for “well-armed citizens who voted for Trump” to “kill those seeking to impose tyranny,” of whom there was a “long and very precise list” that included journalists, activists, pundits, abortion providers, Republican and Democratic elected officials, federal judges, law professors, FBI agents, intelligence officials and Justice Department officials, along with “all who support them.”

      There is such a man, and such a show, on which he has declared that former President Barack Obama “deserves to be hung.” The broadcast promotes his blog (archived here), where for years, he has advocated the right of, and the approaching “necessity” for, “armed rebellion” by citizens seeking to “end the tyranny of their elected representatives,” and listed people cast as “tyrants” and “expendables” whom Trump voters should prepare to “eliminate” by stockpiling arms and ammunition.

      Michael Frank Scheuer, 66, of McLean, Virginia, a former CIA intelligence official and the author of four books, is the man. And John Fredericks Radio is the influential, nationally syndicated talk radio show.

      Trump whole heartedly supports nuclear weapons, nuclear power and using nuclear weapons. Cannot gaslight that

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    2. The new deep-state right-wing conspiracy troll memes: laser energy weapons are torching houses in california and elsewhere. It is not from the record high temperatures in those areas that have created drought, scorched the earth and st off wildfires.

      The other big lie is that Trump and republicans have been against nuclear.
      1.they gave 200millions for small reactors

      2. They started Uranium Mining in the Grand Canyon and that area and opened up an area there for another huge uranium mine

      3. They are intent on implementing a multitrillion dollar nuclear space force.

      4. They introduced 56 billion package to subsidize old reactors that could be shut down and deregulate supervision of older dangerous reactors.

      5. Trump allocated a trillion dollars to upgrade the nuclear arsenal

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    3. Your reply makes no sense in terms of my comment which has nothing to do with a president or talks shows. I am pointing out what should be a very obvious fact that only prosperous persons have the time and energy to involve themselves in promoting the public good. That seems to be hard for many people to grasp. Why not move to Sudan and see how your stuff goes over with impoverished folk. Take out a big life insurance policy though so that someone can benefit from your likely sacrifice! Good luck.

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    4. Threats from the troll. The topic is hormesis. The troll does not believe in democracy. It is a hateful bigot. It is a pronuke troll. It hates women, nonwhites, millenials, teachers, professors, democrats, nonfscist republicans. It is a hater through and through. Supports rightwing death squads and hate and tyranny. Does not believe in democracy or commons, or education.

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    5. No, I am accounting for the problem by giving background. The article is technical but the problem is simple. It would not occur were it not for the kinds of people that appear in a rather bad society. During the past 60 years America has become home to a less cultured, less educated and less moral peoples. You have no idea who I am and are simply projecting the same usual junk . . . develop some intellect.

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    6. Listen operative troll this is about nuclear. It is about genetic damage from nuclear. About the ongoing poisoning and degradation of the environment. There is no need for nuclear, at all. Yur first post about curie as ok. Then u started bsing and gaslighting and bsmuoa about trump. Most do not wanna read yur mansplaining, on the perfect fascist society

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    7. What have you done about this besides comment? Have you published a book on the subject? Spoken with your Senator and Congressman? Gotten the education necessary to work towards of practical solution--law school, graduate degree in science, medical school? Or do you just call anyone who does not agree with you a fascist? Do you know anything at all about fascism? About communism? Do you read thick books with big words?

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  4. The United States Is The Largest Prison Camp In The World | Global Research – Centre for Research on Globalization

    Quote August 2, 2018 A Green Road Daily News Leave a comment
    The United States Is The Largest Prison Camp In The World | Global Research – Centre for Research on Globalization

    The United States has the highest incarceration rates in the world. The US not only has a far higher percentage of its population in prison than allegedly “authoritarian” governments, but also has a larger total number of citizens imprisoned than China, a country with four times the US population. The US is by far the largest prison camp in the world.

    The conditions, such as solitary confinement, in which many US prisoners are kept are strictly illegal under international law, but that means nothing to “freedom and democracy America.” Solitary confinement, especially confinement inside tiny cells, is like being buried alive. Yet, “freedom and democracy America” is subjecting more than 100,000 citizens to this horror as I write. We hear so much about “America’s moral conscience,” but where is this conscience?

    Other prisoners are used as a cheap work force for US military and consumer industries. Prison labor and the privatization of prisons have created an enormous demand for prisoners. American citizens are shoveled into the profit-making prison system regardless of innocence or guilt.

    There is no doubt that a large percentage of US prisoners are innocent or imprisoned for victimless crimes, such as drug use. According to official US government statistics, 97 percent of all felonies are settled with plea bargains. Consequently, the police evidence and prosecutor’s case is never tested in court. Not even the innocent want a trial, because the jurors are brainwashed and biased against everyone charged, and the punishments that result from trial conviction are much harsher than those given to a compliant defendant who agrees to a plea bargain. Despite the US Constitution’s prohibition of self-incrimination, the US prison population consists of people coerced into self-incrimination. There is no justice whatsoever in the US criminal justice (sic) system.

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  5. Most southern state are antebellum. They have dispropotionally large amounts, of the millions of prisoners in Murica. Crooked county sherrifs, get 6 figure allocations from states to feed people, jailed, for nonsense.

    The sherrifs take the money and buy beachhouses, while preganant women, teenagers, and men starve in their ghetto dungeons.

    The millions of prisoners in southern states have no air conditioning, or cooling in their work farm prisons, where the temps can be 105 F w 90 percent humidity.

    Most of the Produce, at supermarkets in the Southern United States, at Pigley-Wiggleys, Harvest Food, Kroger, HEB etc comes from prison farms. Aint murica GREAT!

    They also have poor to nil medical care, like most muricans will soon have under Trump

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  6. You might like this Majia. It is long. It presents interesting arguements about economics and the impending failure of the American Empire.

    https://astutenews.com/2018/08/01/erratic-empire-downfalling/

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    1. Thank you for the link. The article makes some interesting arguments but its strokes are over broad I think, leading to conclusions that I believe are highly unlikely to occur.

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    2. You maybe right. It is a different perspective, though. There is a link in there, for another article. I am getting off, the internet. It is getting strange. Too many people, talking about violence and threats. Much information, is very questionable. Do not feel, it is a viable source of anything anymore. Good luck Majia! Thanks for your blog

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  7. The internet is not so great for mental health or politics, in oh so many ways. Maybe it is a sign of the death knell, of this empire, and the fake society it generated

    Https://www.washingtonpost.com/blogs/post-partisan/wp/2018/08/02/what-makes-qanon-so-scary/?utm_term=.292f7de935a8&wpisrc=nl_az_most&wpmk=1&noredirect=on

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