Project Steve

 
Project Steve just added it's 800th person named Steve. If you don't know what Project Steve is then hop on over to the NCSE website and find out [Project Steve: n > 800].

John Wiley & Sons Apologizes to Shelley Batts

 
Read about it at Retrospectacle [VICTORY! A Happy Resolution].

Riboflavin (Vitamin B2), FMN and FAD

 
Monday's Molecule was Flavin Adenine Dinucleotide or FAD [Monday's Molecule #23]. The flavin moiety is the three ring structure at the top of the figure. It's attached to a sugar called ribitol drawn in an open chain conformation. The ribitol, in turn, is attached to a single phosphate group at the other end.

The structure shown in black is called flavin mononucleotide or FMN. The blue structure is an AMP group so the complete FAD molecule (black + blue) called a dinucleotide. FMN and FAD are important coenzymes that carry electrons from one reaction to another. We've already encountered FAD last week when we described the pyruvate dehdrogenase reaction. In that reaction the FAD molecule picked up two electrons from the lipoamide swinging arm and passed them on to NAD⁺.

FMN and FAD are required for important reactions in all species. They are made from riboflavin (right). Riboflavin can be synthesized in bacteria, protists, fungi, plants and some animals but mammals have lost the ability to make it. Instead, we have to obtain riboflavin from our food and that's why it's a vitamin in humans (vitamin B₂). (It's not a "vitamin" in other species since they can make it themselves.)

Riboflavin deficiency is quite rare because we can usually get enough from the bacteria that inhabit our intestines. The most common cases of riboflavin deficiency are seen in chronic alcoholics who often show deficiencies in many other vitamins as well.

FMN and FAD are tightly bound to the enzymes that require them as cofactors. These enzymes often have a characteristic yellow color because of the flavin. One of the most famous enzymes in biochemistry is a flavoprotein called "Old Yellow Enzyme," which turned out to be an NADPH oxidase.

FMN and FAD are cofactors that can carry one or two electrons as shown below. This makes them similar to ubiquinone. There are many reactions that exchange electrons between FMN/FAD and ubiquinone in short electron transport chains. The passage of electrons from one cofactor/coenzyme to another is governed by well-defined chemical rules developed by chemists and biochemists at the beginning of the last century.

Who Owns the Data?

 
Shelley Batts was threatened with legal action for posting a figure and a table from a scientific paper [When Fair Use Isn't Fair]. This is an important issue that's only going to get worse on science blogs. My own feeling is that it's fair use to post stuff from papers in the scientific literature as long as it is properly attributed.

One of the advantages of the online journals is that they specifically allow this. Here's the official word from the PLoS website.

Everything we publish is freely available online throughout the world, for you to read, download, copy, distribute, and use (with attribution) any way you wish. No permission required.

If large corporations like John Wiley & Sons are going to threaten to sick lawyers on bloggers like Shelley then we'll just have to ignore everything that's published in their journals. That's what I'm going to do from now on.

[Hat Tip: Gene Expression]

Tangled Bank #78

 
Tangled Bank #78 has been posted at About: Archaeology. There's a brief list of articles on the framing debate in case anyone hasn't had enough. Don't be turned off. There's lot of good stuff as well. In addition, there's a link to one of my articles but y'all have read that already.

Unintelligent Design

 
A reader send this. Thanks, Mike.


 

Regulating Pyruvate Dehydrogenase

 
There are three basic ways to regulate the activity of an enzyme. The cell can control the synthesis of the enzyme by regulating the expression of the gene; the enzyme activity can be modified by binding small effector molecules that alter the structure of the enzyme (allosteric regulation); or the activity can be changed by covalent modification.

The activity of the pyruvate dehydrogenase complex (PDC) is controlled by the most common form of covalent modification, phosphorylation. There's an enzyme called pyruvate dehydrogenase kinase (PDH kinase, PDHK) that attaches phosphate groups to the E₁ subunit of PDC. The phosphorylated form of PDC is inactive. Another enzyme called PDH phosphatase (PDP) removes the phosphate groups making the enzyme active again.

THEME:
Pyruvate
Dehydrogenase
PDH kinase binds to the E₂ subunits, specifically the lipoamide swinging arm [The Structure of the Pyruvate Dehydrogenase Complex]. There are four different PDH kinases and two different PDH phosphatases expressed in different tissues. Thus, the kinases and phosphatases are regulated, in part, at the level of gene expression. It turns out that they are also allosteric enzymes.

Knoechel et al. (2006) have looked at the structure of PHD kinase 2 (PDHK2) and located the sites of binding of several molecules that control activity of the kinase. One of the most important allosteric inhibitors is pyruvate. When pyruvate binds to PDH kinase 2 it blocks the kinase (phosphorylation) activity by changing the shape of the protein. Since phosphorylation of PDC doesn't occur, the pyruvate dehydrogenase complex remains active. Previously phosphorylated PDC becomes active because the phosphate is removed by PDH phosphatase.


The regulation makes sense. As pyruvate accumulates inside the cell you want to activate the pyruvate dehydrogenase complex in order to convert the pyruvate to acetyl CoA. As pyruvate levels fall the PDH kinase will no longer be inhibited and PDC will be inactivated by phosphorylation.

It wasn't possible to crystallize PDH kinase in the presence of pyruvate but it was possible to solve the structure of the enzyme with a similar molecule bound at the active site. The molecule is dichloroacetate (DCA) a molecule that inhibits PDH kinase by binding to the pyruvate site. Unlike pyruvate, DCA inhibition is pretty much irreversible.

Cancer cells often have inactivated pyruvate dehydrogenase complex for reasons that aren't clear (but see references in the link below). Treatment of cancer cells with DCA reactivates the pyruvate dehydrogenase complex and this leads eventually to the death of the cancer cells— at least in some cases. Unfortunately, dichloroacetate (DCA) is toxic so using it to treat cancer is a case of the cure being almost as bad as the disease.

This has not prevented growth of an underground economy in DCA by people who are desperate to cure their cancers. The situation is a mess. Read blogs by Abel Pharmboy at Terra Sigillata and Orac at Respectful Insolence for lots more information. There's a nice summary of their posts at Perversion of Good Science.

Pharmaceutical companies are very interested in finding a non-toxic inhibitor of PDH kinase 2. In fact, the paper by Knoechel et al. is mostly work done at Pfizer Ltd, in the UK. Their goal is to characterize as many inhibitors as possible.

Knoechel, T.R., Tucker, A.D., Robinson, C.M., Phillips, C., Taylor, W., Bungay, P.J., Kasten, S.A., Roche, T.E., and Brown, D.G. (2006) Regulatory roles of the N-terminal domain based on crystal structures of human pyruvate dehydrogenase kinase 2 containing physiological and synthetic ligands. Biochemistry 45:402-15. [doi: 10.1021/bi051402s]

Sequence Similarity and Intelligent Design Creationism

 
Logan Gage posted a message on Evolution News& Views where he discusses the interpretation of sequences similarity [What Exactly Does Genetic Similarity Demonstrate?].

As Francis Collins, head of the project which mapped the human genome, has written of DNA sequence similarities, “This evidence alone does not, of course, prove a common ancestor” because an intelligent cause can reuse successful design principles. We know this because we are intelligent agents ourselves, and we do this all the time. We take instructions we have written for one thing and use them for another. The similarity is not the result of a blind mechanism but rather the result of our intelligent activity.

This is an old argument. It ignores the fact that sequence similarities match the phylogenies determined independently from comparative morphology and the fossil record. This is the "twin nested hierachies" evidence for evolution and it's powerful evidence indeed. Furthermore, it ignores the fact that the differences in sequences correspond closely to what we expect from evolution by random genetic drift.

In order to sustain the argument that an intelligent designer is responsible for this data you pretty much have to argue that the designer (whoever that might be) went out of his way to deceive us into thinking it's due to evolution. But that's not why I'm commenting on this article.

Some design proponents think the evidence for common ancestry is good (e.g., Michael Behe), while others—citing the fossil record, especially The Cambrian Explosion—do not. But neither group thinks that sequence similarity alone proves either common ancestry or the Darwinian mechanism, as so many science writers of our day seem eager to assume.

I congratulate Logan Gage for acknowledging that there are disagreements within the Intelligent Design Creationist camp. That's not something we see very often. However, I think he may be distorting Behe's position a little bit. Perhaps he means to place all the emphasis on "similarity alone" but that seems to be a quibble. Here's what Behe says in Darwin's Black Box on pages 175-177. Judge for yourself whether Behe thinks sequence analysis provides strong support for common descent.

When methods were developed in the 1950s to determine the sequences of proteins, it became possible to compare the sequence of one protein with another. A question that was immediately asked was whether analogous proteins in different species, like human hemoglobin and horse hemoglobin, had the same amino acid sequence. [The question was asked because it was a prediction of evolution-LAM]. The answer was intriguing: horse and human hemoglobins were very similar but not identical. Their amino acids were the same in 129 out of 146 positions in one of the protein chains of hemoglobin, but different in the remaining positions. When the sequences of the hemoglobins of monkey, chicken, frog, and others became available, their sequences could be compared with human hemoglobin and with each other. Monkey hemoglobin had 5 differences with that of humans; chickens had 26 differences; and frogs had 46 differences. These similarities were highly suggestive. Many researchers concluded that similar sequences strongly supported descent from a common ancestor.

For the most part it was shown that analogous proteins from species that were already thought to be closely related (like man and chimp, or duck and chicken) were pretty similar in sequence, and proteins from species thought to be distantly related (such as skunk and skunk cabbage) were not that similar. In fact, for some proteins one could correlate the amount of sequence similarity with the estimated time since various species were thought to have last shared a common ancestor and the correlation was quite good. Emile Zuckerkandl and Linus Pauling then proposed the molecular clock theory, which says that the correlation is caused by proteins accumulating mutations over time. The molecular clock has been vigorously debated since it was proposed, and many issues surrounding it are still contended. Overall, however, it remains a viable possibility....

The three general topics of papers published in JME [the Journal of Molecular Evolution]—the origin of life, mathematical models of evolution, and sequence analysis—have included many intricate, difficult, and erudite studies. Does such valuable and interesting work contradict this book's message? Not at all. To say that Darwinian evolution cannot explain everything in nature is not to say that evolution, random mutation, and natural selection do not occur, they have been observed (at least in cases of microevolution) many different times. Like the sequence analysts, I believe the evidence strongly supports common descent. But the root question remains unanswered: What has caused complex systems to form? No one has ever explained in detailed, scientific fashion how mutation and natural selection could build the complex, intricate structures discussed in this book.

The reason for bringing this up is to show that Behe accepts common descent and sequence similarity is strong evidence of common descent. It would be nice if the Intelligent Design Creationists acknowledged this and discussed the sum total of the evidence and not just the sound bite version of sequence similarity.

[I'd like to make it clear that I do not support everything Behe says. It's become clear to me recently that I need to add disclaimers such as this whenever I make a complicated point.]

Experimental Biology in Washington D.C.

 


I'm going to the Experimental Biology meeting in Washington this weekend. Is anyone else going to be there? Email me so we can get together.

Goodbye Mixing Memory

 
Chris over at Mixing Memory posted an article on the comparision between the Women's Suffrage Movement and other attempts to change public opinion [You're No Suffragist]. He completley misunderstood the point of what I was saying so I posted a comment to help direct him toward the truth. I also took a poke at him for deliberately mispelling my name in the first paragraph of his posting.

My comment didn't survive on his blog. Now you see the following comment from him.

First, my apologies to anyone who's responded to Larry's comment. I deleted it, because I don't want him dirtying up my blog.

Next, Matt, I have nothing but contempt or the nouveau atheists (I use that phrase to convey their tackiness, in case that wasn't apparent). I have been saying as much for about 6 months now, and will continue to do so. I won't apologize for it, either. They deserve nothing but contempt. And it should be noted that contempt for a relatively small, privileged group does not entail contempt for anyone else (I do have contempt for other groups, of course, but most people on the planet I'm OK with) or a broad sense of superiority. Do I feel superior to them? Anyone who's read a few books would. Do I feel superior to everyone else? Certainly not.

Mike, atheists should respond by pointing out how insane that kind of talk is. They should note that saying a group is not really American, or doesn't matter, sounds more and more like, say, Nazi antisemitic rhetoric when it's used by people in power (and that includes people in the media, who are, obviously, in positions of power). Of course, one doesn't have to call all religious people stupid, and advocate for the eradication of religion (which, I should add, also sounds a lot like Nazi rhetoric) to do so. I have nothing against being mean by itself. I have something against being mean, stupid, and totalitarian (little "t").

Richard, my point is that, by and large, they aren't even being "rude" in the same way. Instead, what they're trying to do is force their narrow world view on the entire rest of the world (go read Moran and others' talk of ridding the world of superstition, by which they mean all religious beliefs, on their blogs), through aggression and violence. Granted, it's rhetorical aggression and violence, but it's still aggression and violence. And perhaps worst of all, it is rhetoric with no obligation to facts or truth. Perhaps a better name for the nouveau atheists would be "evangelical" or "proselytizer" atheists.

I've decided not to read Mixing Memory any more. I'm thinking that Chris has gone off the rails and I don't want to be the one that tips him over the edge.

Monday's Molecule #23

 
Name this molecule. It's related to last week's theme on pyruvate and pyruvate dehydrogenase.

As usual, there's a connection between Monday's molecule and this Wednesday's Nobel Laureate. This one's got something to do with the type of reactions that involve today's molecule. The prize (free lunch) goes to the person who correctly identifies both the molecule and the Nobel Laureate. (Previous free lunch winners are ineligible for one month from the time they first won.)

Comments will be blocked for 24 hours. Comments are now open.

Google Earth View of the Sandwalk

 

 
John Spraggs sent me this Google Earth view of the Sandwalk behind Down House (upper right). The Sandwalk path follows the line of trees at the bottom of the garden to the small woods at the lower left.

Thanks, John.

Suffragettes

 
I started a little controversy over on Greg Laden's blog when I responded to the umteenth claim that militant approaches to a debate never achieve anything [Larry Moran]. I said,

Everyone keeps repeating this mantra as though it were the gospel truth. The historical evidence says otherwise. There are dozens of examples of things that used to be “militant” approaches that have become accepted standards today.

Here’s just one example. Do you realize that women used to march in the streets with placards demanding that they be allowed to vote? At the time the suffragettes were criticized for hurting the cause. Their radical stance was driving off the men who might have been sympathetic to women’s right to vote if only those women had stayed in their proper place.

Now I’m not saying that all militant approaches are going to win in the end. Far form it. Most of them are destined for the dustheap of history. What I am saying is that trying to shut down the “militants” on the grounds that they are counter-productive is not logical. It’s a way of “framing” the discussion to make it sound like your opposition to the militants has a scientific basis.

PZ liked the suffragette idea and expanded on it [We Aim to Misbehave] and [Rude Ladies].

Now Amanda Marcotte has picked it up at Pandagon [They didn’t realize that you got it the third time you asked with a pretty please]. Read her blog to find out just how "gentile" those women were one hundred years ago.

I see the Feminists For Life and their horrible project of trying to rewrite history so that suffrage-era feminists come across as pleasantly enamored of servitude is going well. It’s hard to generalize at all about suffragists, since, you know, the struggle went on for decades and incorporated thousands of women. One thing you can say with certainty is they were rude and offensive by definition, since for a woman to be proper, she had to accept second class citizenship uncomplainingly. But seriously, atheists aren’t even waving placards, much less holding hunger strikes, firebombing, or whipping some jujitsu on some cops.

More to the point, suffragists didn’t actually get very far until they did in fact start openly insulting men. Mere equality between men and women wasn’t considered reason enough to extend the franchise to women, but when the purity movement latched onto suffrage and started pushing the message that women were better than men, then things changed. Men were considered drunken, violent assholes who needed women’s civilizing hand to get them in shape. It was a sorry thing that it had to get to that point in order for women to get the vote, and hopefully the lesson has been learned for future reference.* Now, as PZ notes, the way different levels of oppression certainly demanded different reactions, so there’s no reason to fault the suffragists for any radical action they had to take in order to obtain justice. But it’s silly to think of them as sweet little old ladies who’d never hurt a fly. They put up with a lot of shit, from having vegetables pelted at them in public to having police arrest them in ways that maximized the violence and humiliation.

Please don't lose sight of the main point about the comparison between the women's suffrage movement and atheists like Dawkins, PZ, and me. We're not trying to justify our position by comparing it to that of the suffragettes (suffragists). All we're trying to do is destroy this silly myth that all social change came about by speaking softly and being nice to everyone. There are lots of examples where "militant" behavior triggered social change. It doesn't always justify "militant' behavior but if you're going to fight Dawkins then at least use sensible arguments.

Gene Genie #5

 
The Neurophilosopher has just posted Gene Genie #5. There are posts from Hsein-Hsein Lei at Genetics & Health; Leslie, who writes a blog called Paternal Age and De Novo Single Gene Disorders etc.; Bertalan at Scienceroll; Grrl Scientist, who blogs at Living the Scientific Life; Tim at Sciencesque; and me.

I think we knocked off another dozen genes or so. Only about 23,500 to go.

Framing Framing

 
If, like me, you're confused about the message that Mooney and Nisbet are conveying then I urge you to listen to this podcast [Matthew Nisbet]. Here's the introduction on the Point of Inquiry website.

In this discussion with D.J. Grothe, Nisbet explores the issue of “framing science” in the public mind, how scientists may be failing at effectively communicating the importance of the implications of science for society, and steps the science community may take to more expertly sell their science to a disinterested public. He also argues about Richard Dawkins and his effect on the public appreciation of science, and the impact of linking atheism with science for issues such as stem-cell research, teaching evolution in the public schools, and global warming.

Nisbet links to the podcast on his website [Podcast: More on Framing (and Dawkins)] where he says,

In this week's show, host DJ Grothe and I engage in a lively forty-five minute discussion. You can listen here.

I offer more details on:

--> the nature of framing and media influence.
--> does framing mean false spin?
--> the likely negative impact of Dawkins.
--> communication strategy specific to the teaching of evolution in schools.
--> what the Discovery Institute understood about framing (also see this post.)
--> the role of framing in the debates over climate change and stem cell research.
--> the use of "science navigators" in communication campaigns.
-->an effective means for engaging the broader American public on atheism.

I take that to mean that Nisbet thinks he did a good job of explaining these things during the interview.

I urge everyone who has an interest in this debate to take the time (45 minutes) to listen to the interview. At the end of it you should have a very good idea of the issues. Nisbet tries to frame the framing debate to make it look like it's all about "proper" media communication. He sets himself up—along with Chris Mooney—as the social scientist who really understands how society works. Scientists are the social bumpkins who need a lot of coaching from the "experts."

It doesn't work for me. To me it reveals that Nisbet is simply expressing his own personal opinion about many issues. For example, he makes it very clear that, in his opinion, Dawkins is harming the cause of science education. The interview is full of spin framing about how unimportant it is that Dawkins has a book on the bestseller list. Some of the contortions that Nisbet puts us through are actually quite funny. The interviewer (Grothe) really has him twisting in the wind at several points.

After listing to the interview I think I now know enough about Nisbet to ignore him from now on. He doesn't have anything useful to say as far as I'm concerned so this is the end of my involvement in this debate. The fans of framing will no doubt be ecstatic about the interview.

I'm reminded of the two cultures debates in the 1960's. If you don't know what I'm talking about then please follow the link to the Wikipedia article.