DNA repair

DNA mismatch repair (MMR) is the body’s system for recognizing and fixing mispaired bases (adenine with thymine, guanine with cytosine) that occur during genetic replication and recombination. It’s a vital process because it eliminates mutations that can result in defects and the development of different cancers.

It’s also a bit of a mystery, in part because no one has ever actually seen the system at work. Until now. In a paper published in the November 23 issue of the journal Cell, Richard Kolodner, PhD, a member of the Ludwig Institute for Cancer Research, professor of medicine and member of the Moores Cancer Center at UC San Diego School of Medicine and colleagues use fluorescent visualization techniques to show what’s happening in vivo for the first time.

The researchers studied live cells of Saccharomyces cerevisiae, or Baker’s yeast. “MMR in yeast and humans is exactly the same,” said Kolodner. “Yeast and humans use the same proteins and the repair process involves the same steps in each organism.”

They focused on the Msh2-Msh6 and Mlh1-Pms1 protein complexes, known to play a role in MMR. “We saw that the MMR protein that detects errors in the DNA linked to the proteins that replicate the DNA,” said Kolodner.  “We also saw that when the first MMR protein encountered an error in the DNA, it assembled a second MMR protein onto the DNA to initiate the repair process.”

The discovery reveals for the first time a key mechanism used by MMR proteins to find individual damaged sites in DNA among the vast numbers of non-damaged DNA sites in a cell. Having a better understanding of how DNA is repaired could ultimately lead to future therapies to assist the process or treat existing cancers.

“Inherited defects in MMR genes cause one of the most common forms of inherited cancer susceptibility known,” said Kolodner. “In addition, a significant number of non-inherited cancers have MMR defects that play a role in their development.  And sometimes in cancers that have become resistant to chemotherapy, the acquired resistance is due to selection for a MMR defect during treatment.”

Co-authors of the paper with Kolodner were Arshad Desai, Catherine E. Smith, Christopher S. Campbell and Hans Hombauer, all at the Ludwig Institute and UC San Diego School of Medicine.

TNQD Jumps on her Soapbox and Tackles Vaccine Myths

As some of you lovely followers might know, I have a passion for public health and infectious disease medicine, so I just can’t resist commenting on this latest CBS news article regarding the growing outbreak of measles in Orange County, California. People who refuse to vaccinate themselves and their children against diseases that are nearly 100% preventable drive me absolutely bonkers.

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What’s worse is that many of them espouse their completely unfounded and flat-out wrong pseudo-scientific beliefs all over the internet and television (Jenny McCarthy, you completely moronic, uncredentialed enemy of public health, I’m looking at you) scare countless other parents into not vaccinating their children. Kids shouldn’t have to die or suffer severe neurological disabilities for the rest of their lives simply because their parents were either A) Too ignorant to vaccinate them or B) In complete denial of all scientific evidence. 

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All right, let’s set the record straight once and for all regarding the MMR (measles, mumps and rubella) vaccine. 

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Much of the “debate”—if you could even call it that—is centered around the Andrew Wakefield MMR study that claimed to have found a link between autism and the MMR vaccine. It all began when fraudmeister numero uno and celebrities-turned-medical-experts-overnight published this book and received an absurd amount of media coverage:

At this point in time, his supporters are essentially composed of a cult of conspiracy theorists combined with helpless parents grasping at straws because they need an explanation for why their kid has a developmental or neurological disorder. I understand their desperation and need for an explanation, but their misdirected anger and vendetta against vaccines is literally killing innocent, young children who have no choice but to trust these anti-vaccine parents with their well-being. It is a completely avoidable tragedy. 

ANDREW WAKEFIELD IS A FRAUD. HE HAS BEEN STRIPPED OF HIS MEDICAL LICENSE FOR FALSIFYING RESEARCH DATA. I REPEAT, ANY WEBSITE, BOOK, OR PERSON YOU HEAR CITING HIS DATA IS EITHER DELUSIONAL, MISINFORMED, OR PURPOSEFULLY LYING TO YOU. ANDREW WAKEFIELD IS THE EPITOME OF:

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He was caught falsifying or altering all 12 of his study’s patient records. Also as a side note, it is extremely difficult to achieve statistically significant results from such a small sample size, so even if there was even a modicum of truth—WHICH THERE WAS NOT—his data would not have been significant enough to make any sort of definitive statement about the MMR vaccine’s alleged link to autism. 

So now that Wakefield is out of the way, it’s time to discuss why MMR vaccines were targeted as a potential cause of autism in the first place. You see, there’s this little thing called correlation and it is NOT THE SAME THING AS CAUSATION. One of the best examples anyone has ever used to explain this to me goes like this (thank you Dr. Hunt and my virology class). 

Clearly we know today that polio and ice cream have absolutely nothing in common, except that their “popularity” is higher during the summer months. People eat ice cream to cool down, but they also take to public swimming pools and lakes, streams, etc. that are likely to be teeming with particulate feces that carry the polio virus in order to cool down as well. 

The same thing is happening with autism and the MMR vaccine. It’s simply temporal correlation. Developmentally, children begin showing apparent signs of autism right around the time they are supposed to receive their MMR vaccine. Statistically speaking, you’re bound to have a few kids in the Venn diagram that overlap between the categories of “Received MMR vaccine” and “Developed autism.” This is coincidence, not causation. 

Finally, the media coverage and science writing for this farcical “debate” has been abysmal and sensationalized. In this article, the journalist claims that “philosophical” differences are to blame for the MMR rise according to the CDC and that the “debate,” is still ongoing. This language is overly politically correct and soft in my opinion; it is blatantly pandering to a wider demographic for the sole sake of ratings, so let me be clear: there is about as much “debate” over MMR causing autism as there is about breaking mirrors causing seven years’ bad luck. Among respectable and ethical scientists and doctors, there is NO debate. They’ve done the studies and find nothing but temporal correlation, which DOES NOT IMPLY CAUSATION.

And don’t even get me started on herd immunity (although if you’d like to know more about how the anti-vacciners are contributing to the deaths of those who are unable to be vaccinated due to immunological and other health disorders, you can find a nice explanation here). 

And just for shits and giggles, I’m going to play devil’s advocate for a moment.

Even if we arbitrarily accept that vaccines are in fact, the true causal agent of some rare and severe health events that typically occur after immunization with the MMR vaccine, the numbers say statistically you’re much better off getting immunized. I repeat, you are less likely to die or be maimed by the MMR vaccine than you are to die and or be maimed by the measles virus, which is one of the most contagious diseases in all of human history.

Risk of a child suffering severe disease and dying from measles: “Measles can also result in serious complications including ear infections, pneumonia, and brain swelling — or encephalitis, which occurs in about one out of every 1,000 cases and may lead to death

Risk of a child suffering severe disease and dying from MMR vaccine: “Central nervous system (CNS) conditions, including encephalitis and encephalopathy, have been reported with a frequency of less than one per million doses administered. The incidence of encephalitis or encephalopathy after measles vaccination of healthy children is lower than the observed incidence of encephalitis of unknown etiology. This finding suggests that the reported severe neurologic disorders temporally associated with measles vaccination were not caused by the vaccine.”



1 in 1000 vs. < 1 in 1 million…I think I’ll take my chances with the vaccines, should I decide to have kids someday.

In Western cultures, we’re accustomed to framing every public issue as two-sided. People who refuse to acknowledge that there’s legitimacy to the other side are “unfair.” I think this viewpoint is really muddling the vaccine safety conversation. When the media presents scientists on one side, and Natural News on the other, it’s creating a false equivalency. The anti-vaxxers have no credible scientific evidence supporting their position, but placing them opposite a scientist makes it seem like there are two legitimate sides to this debate. There aren’t. The simple fact is that there’s overwhelming scientific consensus that the MMR vaccine doesn’t cause autism.
—  Jennifer Raff, The truth about vaccinations: Your physician knows more than the University of Google, available here at Violent Metaphors. The whole article is well worth reading, and she even cites her sources.
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@MadMoonRiot: Here it is, our indidegogo campaign! Enjoy and please donate! (x)

In Western cultures, we’re accustomed to framing every public issue as two-sided. People who refuse to acknowledge that there’s legitimacy to the other side are “unfair.” I think this viewpoint is really muddling the vaccine safety conversation. When the media presents scientists on one side, and Natural News on the other, it’s creating a false equivalency. The anti-vaxxers have no credible scientific evidence supporting their position, but placing them opposite a scientist makes it seem like there are two legitimate sides to this debate. There aren’t.

A well-written summary of the overwhelming scientific evidence against the anti-vaccination movement, including a particularly cringe-worthy video clip of kids suffering from whooping cough.

(And what a terrific article title, too!)

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