How to Save Yourself in a Falling Elevator

 
Friday's Urban Legend: FALSE

Imagine the cable on your elevator breaks and you're in free fall for ten stories. What do you do? Maybe you should wait until the elevator is just about to hit the ground then jump up as high as you can?

Bible Skeptics Conference

 
Come with us to the Bible Skeptics Conference in Whitby (East of Toronto) on Friday Feb. 23 and Saturday Feb. 24.

What the heck is a Bible Skeptics Conference? It's not what you think ...

At this conference named after you, the skeptic, we hope to challenge your views on evolution and ultimately the meaning of life. We promise no singing (not that there's anything wrong with that), no offering plate and no pressure to join a denomination or church - just reasonable arguments for the existence of a creator - and that His book is the Bible.

It should be a barrel of fun! (The Institute for Creation Research will supply the barrels and the fish.)

Another Canuck Atheist

 

I had lunch at the Faculty Club today with a fellow atheist who lives in the Toronto area. Mike McCarron and I have a lot of things in common so we'll undoubtedly be seeing more of each other in the future. Meanwhile, check out his blog Mike's Weekly Skeptic Rant.

Gene HSPA5 Encodes BiP-a Molecular Chaperone

 
Molecular chaperones are proteins that help other proteins to fold properly (see Heat Shock and Molecular Chaperones). The most important chaperones were indentified as heat shock proteins because they were produced following exposure of cells to excess heat. Their role in heat shock is to repair misfolded proteins and their role in normal cells is to assist in the proper folding of newly synthesized proteins.

The most important chaperone is HSP70 (Heat Shock Protein, M_r=70,000). It is present in all normal cells where it binds to polypeptide chains as they are being synthesized. Most cells contain multpile versions of HSP70. The different members of the gene family occupy different cell compartments. For example, there are distinct HSP70 chaperones in mitochondria, chloroplasts and cytoplasm.

The endoplasmic reticulum (ER) is a network of membranes within eukaryotic cells. Proteins that cross the ER membrane end up inside the ER in a special compartment that's isolated from the cytpolasm. Most of these proteins are destined to be exported from the cells in vesicles that bud off of the ER.

Proteins that need to be imported into the lumen of the ER are synthesized on the membrane surface. As they exit the ribosome tunnel they pass directly through a pore in the membane. When they reach the interior of the ER they are helped to fold by a member of the HSP70 gene family called BiP (Binding Protein) or GRP78 (Glucose Regulated Protein). BiP binds to the newly synthesized peptide while it is being made and while it is passing through the ER pore complex.

The HSP70 chaperones are interesting because of the role they play in protein synthesis but they are also interesting because they are the most highly conserved proteins in all of biology. This makes them ideal candidates for studies of molecular evolution. Several thousand sequences are available (HSP70 Sequence Database). The BiP gene in mammals is called HSPA5—a name choice made by the HUGO (Human Gene Organization) Naming Committee [HSPA5]. (HUGO tends to ignore names given to homologues in other species and choose human specific names. The gene is called BiP in most other species.)

HSPA5 is located near the end of the long arm of chromosome 9 at 9q33-q34.1 (chromosome map NCBI, chromosome map UCSC Genome Browser). The Entrez Gene Locus is GeneID=3309 and it lists 7 different independently-cloned genomic sequences and 8 full-length cDNAs. My favorite site is the SwissProt database (P11021) because it combines all the sequence information from each clone into one annotated sequence.

The HSPA5 gene has 8 exons in a relatively compact gene spread out over 6.5kb (6,500 bp). See the sequence [here]. There's nothing particularly unusial about this gene other than the fact that the introns are smaller than normal. All of the mamalian genes have the same intron/exon organization but other eukaryotic BiP genes may have fewer introns or none ar all.


The gene encodes a proein of 654 amino acid residues with a relative molecular mass of 72,300 (close to 70kDa, which is typical for HSP70's). The protein contains an N-terminal leader sequence that controls its import into the ER and a C-terminal ER retention signal that keeps it in the ER lumen. The rest of the sequence closely resemble all of the other members of the HSP70 gene family.

Bush Flubs the Message

 
The Washington Post reports considerable skepticism about the upcoming war against Iran. Apparently there are people who are suspicious about the latest propaganda effort [Skepticism Over Iraq Haunts U.S. Iran Policy].

They have every reason to be suspicious, especially since President Bush can't seem to stay on message.

In yesterday's White House news conference, Bush grappled with the issue head-on. "What makes you so certain," a reporter asked Bush, of the military's charge that "the highest levels of Tehran's government" are responsible for shipments of lethal weapons to Iraq for use against U.S. troops?

Bush contradicted the military's account, saying, "We don't know . . . whether the head leaders of Iran ordered" it.

"But here's my point," he added. "Either they knew or didn't know, and what matters is, is that [the weapons] they're there."

Oops. That's not the right answer, Dubya. Once you're coerced the military leaders into sticking their necks out you've got to back up the big lie. You were supposed to say that you have secret information linking Iran's leaders to the killing of brave American soldiers.

Dick will not be happy. Now he'll have to go on the Sunday talk shows and drop hints about what he learned when he visited CIA headquarters.

The IDiots Confess to Deliberate Quote Mining

 
You won't believe this. Scordova has a posting on Uncommon Descent titled [quote mine] “we regard as rather regrettable the conventional concatenation of Darwin’s name with evolution”. Here's what he said,

Here is a quote mine for the day which I found in an article Bill referenced earlier (see: Start the revolution without ID). The quote is by one of the world’s leading scientists, Carl Woese:

we regard as rather regrettable the conventional concatenation of Darwin’s name with evolution

I agree. Let me suggest that if the conventional concatenation is “Darwinian evolution” a better concatenation would be “designed evolution” or even (hehe) “created evolution”.

Here's a copy of the original article with the "quote mine" underscored in red.

The IDiots have been told time and time again that there's more to evolution than just Darwinian natural selection. They've been told that use of the word "Darwinism" as a synonym for evolution is wrong. Now, they read an article where some prominent evolutionary biologists make the same point and even give one of the other mechanisms.

So, what do the IDiots do? They quote mine and then the announce to the world that they have deliberately taken a quote out of context. (That's what quote mining is.) Are they really as stupid as this suggests, or are they evil as Dawkins once feared?

I'm Spartacus

 
We are all Spartacus.

Can You Hear the Drums Beating?

 
The International Herald Tribune reports on how Bush defends buildup of pressure on Iran.

Under pressure to explain the buildup of American military and economic pressure on Iran, President George W. Bush said Wednesday that highly lethal explosives smuggled into Iraq had certainly come from an arm of the Iranian government, and that it did not much matter whether top Iranian government officials had sanctioned the smuggling.

Iran has WMD—weapons of minor destruction—and they're sneaking them into Iraq. Does this sound familiar? Who is providing this information about Iran? Is it the same people who told us about WMD's in Iraq and how Saddam Hussein was in cahoots with Al-Qaeda?

Where is Dick Cheney?

There's an old saying in Tennessee — I know it's in Texas, probably in Tennessee — that says, fool me once, shame on — shame on you. Fool me — you can't get fooled again.
                                                   George W. Bush 2002

The Anfinsen Experiment in Protein Folding

Disulfide bridges can be disrupted by treating a protein with 2-mercaptoethanol (HS-CH₂-CHOH). The bond between the two sulfurs in the protein is broken and a new bond is created between two sulfurs at the end of two molecules of 2-mercaptoethanol. (2-mercaptoethanol used to be called β-mercaptoethanol or βME.) Treatment with 2-mercaptoethanol is now standard procedure for denaturing proteins. For example, 2ME is always included when proteins are prepared for SDS polyacrylamide gel electrophoresis.

Anfinsen wanted to show that the information for protein folding resided entirely within the amino acid sequence of the protein. He choose ribonuclease A as his model for folding but he couldn't completely denature the protein unless he treated it with the denaturant urea plus 2ME to break the disulfide bridges.

Under those conditions, the protein unfolded. It would refold spontaneously once he removed urea and 2ME from the folding solution. Ribonuclease A regained biological activity under those conditions. This demonstrated that refolding could take place in vitro.

Anfinsen discovered that removing 2ME but not urea led to recovery of 1% of the activity. This is attributed to the formation of random disulfide bridges between the 8 cysteines present in the protein. There are 105 different possibilities (7x5x3x1) so the 1% recovery makes sense. It also shows that the correct three-dimensional conformation must be achieved fairly rapidly when urea is removed since most of the protein under those conditions becomes active.

However, recovery is not 100%. Mistakes are made in vitro and presumably in vivo as well. This led to the discovery of an enzyme called protein disulfide isomerase (PDI)—an enzyme that catalyzes reduction of incorrect disulfide bonds and allows a protein trapped in an incorrect conformation to unfold and try again.

PDI is a ubiquitous enzyme as expected from its important role in proper folding. The active site of the enzyme contains a disulfide (shown as two yellow sulfur atoms in the figure). Thus, the enzyme acts very much like 2-mercaptoethanol, catalyzing a disulfide exchange reaction where the incorrect disulfide bridge in the misfolded protein is reduced and PDI is oxidized. (The correct name of the protein is "thiol-disulfide oxidoreductase. Oxidoreductases form a large class of very important enzymes.)

The enzyme preferentially recognizes incorrect disulfide bridges since these tend to be exposed on the surface of the misfolded protein, whereas correct disulfide bridges are usually buried in the hydrophobic interior of the correctly folded protein.

Nobel Laureate: Christian B. Anfinsen

 
The Nobel Prize in Chemistry 1972.

"for his work on ribonuclease, especially concerning the connection between the amino acid sequence and the biologically active conformation"

Christian B. Afinson won the Nobel Prize in 1972 for his studies on the folding of ribonuclease A and the role of disulfide bonds. (See Disulfide Bridges Stabilize Folded Proteins and The Anfinsen Experiment in Protein Folding.) Anfinsen made some of the key observations demonstrating that protein folding is spontaneous. Here's part of the presentation speech by Bo Malmström,

Every living organism has its own characteristic pattern of enzymes. It can also produce a copy of itself, and this progeny has the same enzymes. An important question concerns the source of the information which has to be passed on from generation to generation for the enzyme pattern to be preserved. We know, thanks to contributions which have led to earlier Nobel Prize awards, that a specific molecule, called DNA, serves as the carrier of the traits of inheritance. These traits are expressed by DNA controlling the synthesis of enzymes. DNA accomplishes this by determining the sequence of the amino acids making up a particular protein molecule. An active enzyme does not, however, consist just of a long chain of amino acids linked together, but the chain is folded in space in a way which gives the molecule a globular form. What is the source of the information responsible for this specific folding of the peptide chain? It is this question in particular which has been the concern of Anfinsen's investigations. In a series of elegant experiments he showed that the necessary information is inherent in the linear sequence of amino acids in the peptide chain, so that no further genetic information than that found in DNA is necessary.

Snow Day

 
Today's a snow day in my town. Here's what the kids are doing in the park at the end of our street.

Now the IDiots Don't Get Evolution

 
Bill Dembski says Start the Revolution without ID. He's got his knickers in a knot over a paper that was originally published in the Jan. 25, 2007 issue of Nature. An updated version is available [here]. The original reference is,

Goldenfeld, N. and Woese, C. (2007) Biology’s Next Revolution. Nature 445:369-371.

The paper discusses Carl Woese's ideas on early evolution. The same ideas that I covered in The Three Domain Hypothesis (part 6). This isn't new, lots of people have written about it over the past dozen years or so. The idea is that rampant horizontal gene transfer obscures early phylogeny and makes it difficult to distinguish the relationship between eukaryotes and primitive prokaryotes. (It means the Three Domain Hypothesis is dead.)

Dembski probably doesn't know any of this because he's scientifically illiterate, like most IDiots. However, he can read an abstract ...

ABSTRACT: The interpretation of recent environmental genomics data exposes the far-reaching influence of horizontal gene transfer, and is changing our basic concepts of organism, species and evolution itself.

That's enough to trigger the following knee-jerk reaction from an IDiot.

So here’s the deal: When trying to derail ID in the court of public opinion, say that there is NO controversy over evolution. Say that scientists have achieved a consensus and that evolution is as well established as the earth going around the sun. But when out of the public eye, feel free to publish on how the entire field of evolutionary biology is in disarray and in need of a “next revolution.”

No, Bill, you just don't get it. Nobody is questioning the fact of evolution. We're just trying to figure out exactly how it works. You know, science and all that? I though that's what you want us to do?

What Woese and others are doing is sorting out what happened at the beginning of life on this planet, approximately 3.8 billion years ago. That's pretty amazing when you think about. A few decades ago, nobody would have thought that science could address this problem. But that's not good enough for the likes of Bill Dembski. Dembski thinks we should have all the answers before we can say with confidence that life has evolved over the past 3 billion years.

The irony here is that Dembski and his fellow IDiots refuse to tell us anything about their explanation. Dembski is even being coy about whether the Earth is that old. According to Dembski's logic, Intelligent Design Creationism must be bankrupt because they can't even give us a simple description of how humans appeared, and when.

Oh, and concerning that little quip about "out of the public eye." This was published in Nature for God's sake. If even Dembski can find it, then it's hardly out of the public eye, is it?

A Must-read From Sean Carroll

 
Sean Carroll has just posted an article on Cosmic Variance that everyone just has to read—especially the appeasers who think that Richard Dawkins is harming the "cause." Read Thank You, Richard Dawkins right now and enjoy your St. Valentine's Day.

Best and Worst of the Year Awards

 
New Mexicans for Science and Reason have just announced their Best and Worst of the Year Awards for 2006. Two of the awards in the "worst" category were no-brainers.

The "New Word: Pignorant" Award goes to Jonathan Wells, whose new book "The Politically Incorrect Guide to Darwinism and Intelligent Design" contained so many egregious falsehoods that the scientific critics decided to shorten the phrase "Pig Ignorant" to simply "PIGNORANT" in order to cope (Sept.).

The "Last Nail in The Coffin of ID" Award goes to William Dembski, who absolutely destroyed any remaining credibility Intelligent Design may have had, when he responded to Judge John E. Jones' powerful ruling of December 2005, not by defending ID in science journals, nor in courts of law, but by parodying the judge's decision with an Internet video that featured animated farting sounds. The Awards Committee had the most trouble with this award, as several members wanted to name it the "Not So Noble Gas" Award. However, all members were agreed that Dembski edged out Wells and Coulter, and did the most damage to ID this year. (Dec.)

[Hat Tip: John Pieret of Thoughts in a Haystack]

Happy Valentine's Day