Human GULOP Pseudogene

Locus GULOP in the human genome is the site of a pseudogene called GULOP. In most mammals this is an active gene encoding the enzyme L-glucono-γ-lactone oxidase. This is the enzyme that catalyzes the last step in the synthesis of ascorbic acid (vitamin C). The gene is defective in humans and other primates so we can't make ascorbic acid and that causes scurvy if we don't get enough ascorbic acid in our food (Scurvy and Vitamin C).

The GenBank entry for this pseudogene is GeneID=2989. GULOP is located on chromosome 8 at p21.1 in a region that is rich in genes (map).

The human pseudogene was first identified by Nishikimi and Yagi (1991) using the intact rat gene (GeneID=60671) as a probe. They cloned and sequenced four exons that contained several deletions and several in-frame stop codons. This allowed them to conclude that the human pseudogene could not make a functional product. Several of these same mutations are found in chimpanzees, orangutans and macaques indicating that the inactive GULOP gene in all primates descends from a common ancestor that also had an inactive gene (Ohta and Nishkimi 1999).

Subsequent analysis on the GULOP locus in the human genome reveals that the pseudogene is missing most of the 5' exons that are present in the intact rat gene. In particular, exons I to VI are completely absent in the human genome. It is not known whether this deletion is responsible for the original inactivation of the GULOP gene in the primitive ancestral primate (Nishikimi et al. 1994; Ohta and Nishikimi 2003).


UPDATE: see: Creationists questioning pseudogenes: the GULO pseudogene

The human locus is also missing exon XI. In this case the deletion is probably due to recombination between Alu sequences that flank the site of the deletion. This deletion probably took place after the original inactivation event.

Inai, Y., Ohta. Y., and Nishikimi, M. (2003) The whole structure of the human nonfunctional L-gulono-gamma-lactone oxidase gene--the gene responsible for scurvy--and the evolution of repetitive sequences thereon. J Nutr Sci Vitaminol (Tokyo) 49:315-319.

Nishikimi, M. and Yagi, K. (1991) Molecular basis for the deficiency in humans of gulonolactone oxidase, a key enzyme for ascorbic acid biosynthesis. Am. J. Clin. Nutr. 54(6 Suppl):1203S-1208S.

Nishikimi, M., Fukuyama, R., Minoshima, S., Shimizu, N. and Yagi. K. (1994) Cloning and chromosomal mapping of the human nonfunctional gene for L-gulono-gamma-lactone oxidase, the enzyme for L-ascorbic acid biosynthesis missing in man. J. Biol. Chem. 269:13685-13688.

Ohta, Y. and Nishikimi, M. (1999) Random nucleotide substitutions in primate nonfunctional gene for L-gulono-gamma-lactone oxidase, the missing enzyme in L-ascorbic acid biosynthesis. Biochim. Biophys. Acta. 1472:408-411.

Nobel Laureate: Walter Norman Haworth

The Nobel Prize inChemistry 1937.

"for his investigations on carbohydrates and vitamin C"


Sir Norman Haworth won the Nobel Prize in 1937 for his work on the three-dimensional structure of carbohydrates in general and the structure of vitamin C in particular. The presentation speech summarizes his contribution to carbohydrate chemistry.

What has Haworth then accomplished within this domain? The answer may be thus formulated that he has, above all, made clear the chemical structure of vitamin C.

The chemical structure of substances is expressed by the so-called chemical formulas. By chemical analysis the percentage of the different elements - in this case of carbon, hydrogen, and oxygen - which enter into a compound may be ascertained. Further, the weight of the atoms of the different elements, expressed for instance in relation to the atom of hydrogen, has long been known, the hydrogen atom being the lightest of all the elements. It is likewise possible to determine the weight of a particle, or molecule, of a compound, expressed in the same measure. It is hence possible to indicate how many atoms of the different elements are entering into one molecule of the compound. Thus, the gross formula of the compound is obtained. This formula, in the case of vitamin C, is quite simple, considering that it represents a vitamin, viz.: C6H8O6. This formula tells us that one molecule of vitamin C consists of 6 atoms of carbon, 8 of hydrogen, and 6 of oxygen. It also indicates that vitamin C may be conceived as having originated through the elimination of 4 atoms of hydrogen from one molecule of grape-sugar.

But it is possible to advance still further. By ingenious adjustment or speculation, reminding us somewhat of the play of a puzzle, only perhaps a little more intricate, a firm conception has been formed about the order in which the atoms combine. If we conceive an ultra-enlarged model of a molecule, taken at a certain moment - because the atoms are not at a standstill within the molecule - and place a white screen on the one side of the model, while the other is exposed to light, a shadow-figure, also called a projection, of the molecule is obtained on the screen, showing the position of the atoms in their relation to each other. A formula which is intended to reproduce this situation, under the assumption that the atoms were placed on the same plane, is called a structural formula. Such formulas have proved capable of explaining with a high degree of clarity the properties of the compound, and the puzzle thus may be considered as having been solved.

In reality it is, however, hardly correct to suppose that all the atoms within a molecule should be placed on the same plane; if that were the case, even the largest molecules would have the shape of a leaf of paper, which is less than probable. There remains then their dispersion in space, the so-called configuration, which also may be expressed by a formula.

Such a formula for vitamin C has been proposed by Haworth and Hirst, as well as by von Euler and has been subsequently proved to be correct by Haworth.

Haworth's acceptance speech from 1937 contains a number of structures that will be very familiar to biochemistry students. For example, he shows the strucures of α-D-glucopyranose and β-D-glucopyranose.

We recognize these structures today because of the way Haworth drew them to show the three-dimensional configuration. In fact, we now call these figures "Haworth projections" after the man who deciphered the configurations and conformations and developed a way of projecting them on a two-dimensional page.

The final strucure of ascorbic acid (vitamin C) is also presented in Haworth's Nobel Lecture. In this case he choose to show it as a "Fischer projection" rather than the Haworth projection that he is famous for. (See Monday's Molecule #15 for the Haworth projection of vitamin C.)

The relationship between a properly drawn Fischer projection and a Haworth projection is the bane of biochemistry students since it comes up on countless exams. It's probably safe to say that the failure to appreciate Haworth's 1937 Nobel Prize is responsible for lowering the average grade of biochemistry students all over the world by 3-5%.

Canadian Parliament Scraps Anti-terror Laws

 
Given a choice between trusting the "soft-on-terror" Liberals and the "crack-down-on-crime" Conservatives, I go with the softies every time.

OTTAWA, Feb 27 (Reuters) - Canada's Parliament scrapped two contentious anti-terror measures on Tuesday, angering the minority Conservative government, which accuses opposition legislators of being soft on terror.

The House of Commons voted 159-124 not to renew the provisions -- which expire on March 1 -- on the grounds that they had never been used.

One provision allows police to arrest people suspected of planning an imminent terrorist attack and hold them for three days without charge. The other provides for investigative hearings in which a judge can compel witnesses to testify about alleged terrorist activities.

The measures were introduced by the then-Liberal government after the Sept. 11, 2001, suicide attacks on the United States. In a bid to allay fears over human rights, Ottawa agreed the provisions would expire after five years.

The Conservative government controls just 125 of the 308 seats in the House and did not have the votes to extend the measures.

Prime Minister Stephen Harper, whose Conservatives won power in January 2006 on a platform that promised to crack down on crime, says the Liberals of Stephane Dion are soft on terror and cannot be trusted to keep Canadians safe.

Canada Parliament scraps two anti-terror measures

Short on Gas

 
There's a gasoline shortage in Ontario. The main cause was a fire last week at an Esso refinery near Hamilton. The ancillary cause is a CN Rail strike that prevented oil companies from bringing in gasoline from other provinces. Everyone filled up their tanks and this caused shortages everywhere. About 100 Esso gas stations are closed down for lack of fuel. Other stations have also run out of gas.

Ontario is by far the best province in Canada but for some reason the other provinces don't like us very much. This has given rise to a number of nasty comments about us. Nobody seems to be sympathetic to our plight.

Here's one of those mean things that people are saying. This one was sent to us by my wife's aunt who was also my grade 5 teacher. I'm sure you'll agree that this is really below the belt.

A lot of folks can't understand how we came to have an oil shortage here in Canada

Well, there's a very simple answer.

Nobody bothered to check the oil.

We just didn't know we were getting low.

The reason for that is purely geographical.

Our OIL is located in Alberta, Newfoundland, Saskatchewan and B.C.

Our DIPSTICKS are located in Ontario

Peter McKnight on the Marcus Ross Issue

 
One week ago I commented on an opinion piece in the Vancouver Sun. Peter McKnight wrote in support of giving Marcus Ross a Ph.D. in geosciences. I disagreed (Peter McKnight of the Vancouver Sun Weighs in on the Marcus Ross Incident).

I sent Peter a link to my blog and he replied. We've exchanged emails. I then asked permission to post his original message to see what kind of feedback it gets here. Peter has just given permission so here is his letter.

Hi Larry,

Thanks for notifying me of this. It is a worthwhile discussion you're having, but I still don't agree with you.

You say there's plenty of evidence there is something wrong with Ross's science, but you fail to say what that evidence is. Indeed, what you're really saying is that there's something wrong with him - that is, with his belief.

This might be, but it doesn't mean there's anything wrong with his science or his understanding of science. You say doctoral students must understand basic concepts and ideas and think on their feet and defend their ideas etc. Where is the evidence that Ross failed to do so? I assume he did exactly that in his oral exam.

It seems that you want nothing less than Ross's assent to an old Earth theory, which is, of course, a matter of belief, not understanding. And rather than launching into a discussion of epistemic conditions for belief, let me just say that I, for example, understand intelligent design theory quite well I think, and yet I don't believe a word of it.

And one need not be a postmodern relativist or a fundamentalist Christian (which, I've argued for a long time, amount to the same thing) to refuse to accept that that scientific theories are literally true - if by true we mean correspondent with reality. There are, after all, pragmatist philosophies of science that suggest scientific theories are "true" in so far as they work, but that they aren't true in the sense most people give to that term. I assume you reject these philosophies of science, but surely you wouldn't deny a student a doctorate because he doesn't subscribe to the correspondence theory of truth.

Look, I think Ross is dishonest, but I don't know that for a fact. For all I know, maybe he really is a radical relativist, who believes science and religion present two incommensurable paradigms. But either way, he's doing enormous damage to his religion, and it was the point of my column to make that case.

Best,

Peter

Scurvy and Vitamin C

 
Scurvy is a disease characterized by general lethargy and malaise. As the disease progresses the patient develops pain in the extremities, gingivitis, and ulcerations on the skin. Eventually the skin becomes fragile and starts bleeding, teeth fall out, and arteries and veins burst. Death follows. [OMIM 240400 HYPOASCORBEMIA]

Scurvy is caused by lack of vitamin C (Monday's Molecule #15). Vitamin C (ascorbic acid) can be easily oxidized to dehydroascorbic acid and it is this electron donor property that makes it an important biochemical molecule.

In humans there are about a dozen enzymes whose activity depends on ascorbic acid. The most important ones are the enzymes involved in hydroxylation of proline and lysine during the synthesis of collagen fibers (Collagen). In the absence of proper hydroxylation of these amino acids, the collagen molecules cannot be cross-linked and this leads to weaker skin and weaker lining of blood vessels.


In spite of the fact that ascorbic acid is essential in humans, we cannot synthesize it de novo. We need to get an adequate supply from our food—mostly fruits and vegetables. It was the lack of fresh fruit and vegetables that made scurvy so common in the past. Today the disease is rarely seen, except in alcoholics.

All primates have lost the ability to make ascorbic acid. Some other mammals have independently lost this function; guinea pigs and some fruit-eating bats are the best known examples.

Collagen

Collagen is the major protein component of the connective tissue of vertebrates; it constitutes about 25% to 35% of the total protein in mammals. Collagen molecules have remarkably diverse forms and functions. For example, collagen in tendons forms stiff, ropelike fibers of tremendous tensile strength; in skin, collagen takes the form of loosely woven fibers, permitting expansion in all directions.

The structure of collagen was worked out by G. N. Ramachandran (famous for his Ramachandran plots). The molecule consists of three left-handed helical chains coiled around each other to form a right-handed supercoil. Each lefthanded helix in collagen has 3.0 amino acid residues per turn and a pitch of 0.94 nm, giving a rise of 0.31 nm per residue.

The collagen triple helix is stabilized by interchain hydrogen bonds. The sequence of the protein in the helical region consists of multiple repeats of the form –Gly–X–Y–, where X is often proline and Y is often a modified proline called 4-hydroxyproline. The glycine residues are located along the central axis of the triple helix, where tight packing of the protein strands can accommodate no other residue. For each –Gly–X–Y– triplet, one hydrogen bond forms between the amide hydrogen atom of glycine in one chain and the carbonyl oxygen atom of residue X in an adjacent chain. Hydrogen bonds involving the hydroxyl group of hydroxyproline may also stabilize the collagen triple helix. Unlike the more common α helix, the collagen helix has no intrachain hydrogen bonds.

In addition to hydroxyproline, collagen contains an additional modified amino acid residue called 5-hydroxylysine. Some hydroxylysine residues are covalently bonded to carbohydrate residues, making collagen a glycoprotein. The role of this glycosylation is not known.

Hydroxyproline and hydroxylysine residues are formed when specific proline and lysine residues are hydroxylated after incorporation into the polypeptide chains of collagen. The hydroxylation reactions are catalyzed by enzymes and require ascorbic acid (vitamin C).

Collagen triple helices aggregate in a staggered fashion to form strong, insoluble fibers. The strength and rigidity of collagen fibers result in part from covalent cross-links. The groups of the side chains of some lysine and hydroxylysine residues are converted enzymatically to aldehyde groups producing allysine and hydroxyallysine residues. Allysine residues (and their hydroxy derivatives) react with the side chains of lysine and hydroxylysine residues to form Schiff bases, complexes formed between carbonyl groups and amines. These Schiff bases usually form between collagen molecules.

Collagen molecules associate to form long thick fibres with a characteristic banded appearance. These thick fibres confer strength and flexibility to many tissues.

(Collagen molecular image originally produced by J.W. Schmidt for Wikepedia. GNU Free Documentation License)

(Text from Horton et al. Principles of Biochemistry 4th ed.© Pearson Prentice Hall, Inc.)

Joke of the Day: Jonathan Wells

 
Your dose of humor for today comes from an article by Jonathan Wells on the Discovery Institute website [Alchemy, Marxism, and the future of Darwinism]. With a title like that you can expect a good laugh. Normally these jokes begin with "a priest, a rabbi, and a preacher walked into a bar." But if you're an IDiot you start with "I was talking to a physics student and a biochemistry student ...." Here's the set-up ...

I recently found myself in a conversation with two college undergraduates, both of them seniors in the natural sciences (physics and biochemistry, respectively). At one point we were discussing alchemy, which they knew as a pre-modern attempt to transmute lead into gold. I asked them whether they could name any famous alchemists. They could not, though one of them dimly recalled hearing of “someone whose name began with A.”

I then predicted that Darwinian evolution would eventually fade into the same obscurity that now shrouds alchemy. Although I knew from previous conversations that my young friends were skeptical of Darwinian theory, they expressed considerable surprise at my prediction, if only because Darwinism is presently held in such high esteem by their professors.

So I proceeded to explain the basis for my prediction.

An American Rhodes Scholar in Biochemistry

 
Nick Anthis at The Scientific Activist writes about the Rhodes Scholar experience in Oxford [It's OK to Nibble, but Don't Bite Off the Hand that Feeds You]. He discusses an important point, namely the push to finish a Ph.D. in only three years. Is this in the best interests of biochemistry graduate students in general and Rhodes Scholars in particular? I think not, and so does Nick Anthis.

Shift Happens

 
This is interesting. I don't agree with everything—especially the idea that things are going to change that much in the next 15 years but it's worth a look. We can discuss the content.

Just-So Stories

Fanciful evolutionary explanations that have little connection to facts are called "just-so" stories after the collection of stories by Rudyard Kipling. I just found a website with all of the the just so stories [Just So Stories]. It's worth reading a few to get some idea of what we're talking about when we say that the "explanations" of evolutionary psychology, for example, are no better than just-so stories.

The illustration is from The Elephant's Child, a story about how the elephant got its trunk.

'Come hither, Little One,' said the Crocodile, 'for I am the Crocodile,' and he wept crocodile-tears to show it was quite true.

Then the Elephant's Child grew all breathless, and panted, and kneeled down on the bank and said, 'You are the very person I have been looking for all these long days. Will you please tell me what you have for dinner?'

'Come hither, Little One,' said the Crocodile, 'and I'll whisper.'

Then the Elephant's Child put his head down close to the Crocodile's musky, tusky mouth, and the Crocodile caught him by his little nose, which up to that very week, day, hour, and minute, had been no bigger than a boot, though much more useful.

'I think,' said the Crocodile--and he said it between his teeth, like this--'I think to-day I will begin with Elephant's Child!'

At this, O Best Beloved, the Elephant's Child was much annoyed, and he said, speaking through his nose, like this, 'Led go! You are hurtig be!'

The Genetics of Eye Color

The genetics of blood type is a relatively simple case of one locus Mendelian genetics—albeit with three alleles segregating instead of the usual two (Genetics of ABO Blood Types).

Eye color is more complicated because there's more than one locus that contributes to the color of your eyes. In this posting I'll describe the basic genetics of eye color based on two different loci. This is a standard explanation of eye color but, as we'll see later on, it doesn't explain the whole story. Let's just think of it as a convenient way to introduce the concept of independent segregation at two loci. Variation in eye color is only significant in people of European descent.

At one locus (site=gene) there are two different alleles segregating: the B allele confers brown eye color and the recessive b allele gives rise to blue eye color. At the other locus (gene) there are also two alleles: G for green or hazel eyes and g for lighter colored eyes.

The B allele will always make brown eyes regardless of what allele is present at the other locus. In other words, B is dominant over G. In order to have true blue eyes your genotype must be bbgg. If you are homozygous for the B alleles, your eyes will be darker than if you are heterozygous and if you are homozygous for the G allele, in the absence of B, then your eyes will be darker (more hazel) that if you have one one G allele.

Here's the Punnett Square matrix for a cross between two parents who are heterozygous at both alleles. This covers all the possibilities. In two-factor crosses we need to distinguish between the alleles at each locus so I've inserted a backslash (/) between the two genes to make the distinction clear. The alleles at each locus are on separate chromosomes so they segregate independently.^*


As with the ABO blood groups, the possibilities along the left-hand side and at the top represent the genotypes of sperm and eggs. Each of these gamete cells will carry a single copy of the Bb alleles on one chromosome and a single copy of the Gg alleles on another chromosome.

Since there are four possible genotypes at each locus, there are sixteen possible combinations of alleles at the two loci combined. All possibilities are equally probable. The tricky part is determining the phenotype (eye color) for each of the possibilities.

According to the standard explanation, the BBGG genotype will usually result in very dark brown eyes and the bbgg genotype will usually result in very blue-gray eyes. See the examples in the eye chart at the lower-right and upper-left respectively. The combination bbGG will give rise to very green/hazel eyes. The exact color can vary so that sometimes bbGG individuals may have brown eyes and sometimes their eyes may look quite blue. (Again, this is according to the simple two-factor model.)

The relationship between genotype and phenotype is called penetrance. If the genotype always predicts the exact phenotpye then the penetrance is high. In the case of eye color we see incomplete penetrance because eye color can vary considerably for a given genotype. There are two main causes of incomplete penetrance; genetic and environmental. Both of them are playing a role in eye color. There are other genes that influence the phenotype and the final color also depends on the environment. (Eye color can change during your lifetime.)

One of the most puzzling aspects of eye color genetics is accounting for the birth of brown-eyed children to blue-eyed parents. This is a real phenomenon and not just a case of mistaken fatherhood. Based on the simple two-factor model, we can guess that the parents in this case are probably bbGg with a shift toward the lighter side of a light hazel eye color. The child is bbGG where the presence of two G alleles will confer a brown eye color under some circumstances.

^*If the two genes were on the same chromosome this assumption might be invalid because the two alleles on the same chromosome (e.g., B + g) would tend to segregate together. Linked genes don't obey Mendel's Laws and this is called linkage disequilibrium.

I Agree With Denyse O'Leary!

 
Calm down. The world has not come to an end. I don't agree with everything Denyse O'Learly says but there's one issue where we can see eye-to-eye.

Denyse thinks that Theistic Evolution is a cop-out [Theistic evolutionism and the new militant atheism]. She claims that Theistic Evolutionists have to surrender too much of their religion.

However, much of what is called theistic evolution today is simply an attempt to sell Darwinism, the creation story of materialism, to people who are not materialists. I call that "accommodationist" theistic evolution - it attempts to accommodate spiritually directed institutions to rule by materialists....

Usually, Christians (or other theists or people who accept that there is meaning and purpose in the universe) are urged to "accept" - in broad terms - "evolution." Darwinism, which nakedly refutes everything the theist believes, is the form of evolution that the sponsors are actually interested in promoting, to judge from their other activities. But they do not spell out its implications with the candor that the anti-God Darwinists do.

I agree that the middle ground position of Theistic Evolution is untenable [Theistic Evolution: The Fallacy of the Middle Ground]. In my case it's not because the Theistic Evolutionists (e.g., Ken Miller, Francis Collins, Simon Conway-Morris) are giving up too much religion; it's because they are giving up too much of science.

In typical IDiot fashion, Denyse O'Leary continues to use the term "Darwinism" to define her enemy. But if we overlook that particular bit of dissembling for the moment, she has a point. Science in general, and evolutionary biology in particular, tells us that there's no meaning or purpose in the universe. Theistic Evolutionists say that there is but they have no evidence to back up their claim. That's anti-science.

Denyse and I agree that Theistic Evolutionists are trying to have their cake and eat it too.

The Felt Effect of Gravity

 
Phil Plait answers the question, "Just how strong is the gravity from the Moon compared to someone right next to you?". The answer will probably surprise you. It certainly surprised me.

As a bonus, you'll find out the most distant start you can see with the naked eye. An even greater bonus is finding out whether astrology is true. I won't reveal the answer. You'll have to watch the video.

Monday's Molecule #15

 
Name this molecule. You must be specific. We need the correct scientific name.

As usual, there's a connection between Monday's molecule and this Wednesday's Nobel Laureate. Bonus points for guessing Wednesday's Nobel Laureate(s).

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

President of University of Toronto Receives Order of Canada

 
David Naylor is the President of the University of Toronto. He's one of the best Presidents we've had for several decades. A few weeks ago he received the Order of Canada in recognition of his work in Medicine and the University.

That's our Governor General Michaelle Jean beside him in the picture. As the Queen's representative in Canada she is our Head of State. The awards ceremony was at her house, Rideau Hall, in Ottawa.

It's comforting to know that Conservative Prime Minister Stephen Harper can't do a lot of damage to the country as long as Michaelle Jean is Governor General and the Rt. Hon. Chief Justice of Canada is Beverley McLachlin.

What Kind of "Intelligent" Am I?

 

Your Dominant Intelligence is Logical-Mathematical Intelligence

You are great at finding patterns and relationships between things. Always curious about how things work, you love to set up experiments. You need for the world to make sense - and are good at making sense of it. You have a head for numbers and math ... and you can solve almost any logic puzzle. You would make a great scientist, engineer, computer programmer, researcher, accountant, or mathematician.

What Kind of Intelligence Do You Have?

Jan Betker Loses to Kelley Scott

 
My (distant^*) cousin Jan Betker from Saskatchewan just lost the final of the Scotties Tournament of Hearts to last year's champion Kelly Scott of British Columbia, playing as Team Canada.

Too bad. Well done Jan and good luck next year.

Jan is a three time Canadian champion (1993, 1994, 1997), a three time World champion (1993, 1994, 1997) and an Olympic Gold Medal winner in 1998.

^* Jan's grandfather was my grandmother's brother. Does this make her a second cousin or a third cousin?

More on the Marcus Ross Case

 
Read what Janet Stemwedel has to say in Scientific and unscientific conclusions: now with pictures!.

It's going to take me a while to figure out how to respond but I think she's make a big step toward clarifying the issue. What it boils down to is this. Is it possible to be a scientist and hold "beliefs" that flatly contradict scientific evidence? Janet suggests that it is possible because your "beliefs" can be entirely separated from doing good science.

But, it seems to me that the aim of the scientific enterprise is to find ways to draw inferences that move beyond the beliefs of any individual scientist. Leaving the "belief" boxes out of the flowchart doesn't seem to remove any of the steps required for building sound scientific conclusions. Scientific conclusions may well affect the belief structures of individual scientists, but that's a matter of their own personal growth, not required step in the construction of the shared body scientific knowledge.

I wonder if this point of view can be extended to philosophy? Janet talks about Popper in her posting. She doesn't mention Kuhn. Lets imagine a philosophy student who is preparing a thesis in epistemology. Assume that the student writes all the right things about Popper and Kuhn in her thesis. Assume that this students then gives public lectures where she claims that Popper advocated scientific revolutions and Kuhn was really a proponent of falsifiability. In other words, points of view that are contrary to fact.

Is it fair to ask this student about her "beliefs" during her Ph.D. oral? Is it fair to say that she is a good philosopher as long as she keeps her strange contrary-to-fact beliefs separate from the work she does on campus?

What Kind of English Do YOu Speak?

 
Canadian doesn't seem to be one of the choices. (I wonder which 10% of my English is "Dixie"!)

Your Linguistic Profile:

45% General American English

35% Yankee

10% Dixie

5% Upper Midwestern

0% Midwestern

What Kind of American English Do You Speak?

Canada's Supreme Court Strikes Down Anti-terror Law

 
Reuters reports that Canada's top court strikes down anti-terror law. It's all over the radio stations and in all the newspapers (Toronto Star, Globe and Mail).

The decision was unanimous. As Thomas Walkom puts in it the Toronto Star,

Canada is on its way to becoming a civilized country again. The Supreme Court has ruled that if the government wants to lock up people indefinitely without charge, it has to at least let them muster a defence.

In the post-9/11 world, this counts as progress.

Yesterday's court ruling deals with what are known as security certificates. These are ministerial orders that allow the government to jail non-citizens without charge and then deport them.

But it's worth noting that the court did not invalidate the entire security certificate regime. It just told the government it has to be more respectful of the Constitution. More important, the top court has yet to address the most controversial element of Canada's immigration laws – the question of what to do to those that the government wants to deport as security risks even though it knows they will almost certainly face torture in their homelands.

That question is due to be addressed by a lower court, probably later this year.

Still, yesterday's decision does go some way to clearing up a law that has become a searing embarrassment for Canada.

Since 2001, it has allowed the government to jail any foreigner, whether legally or illegally in the country, that it deems a security risk.

The reason this decision is important is because the Americans are holding Canadian citizens without charging them. Canada has been in a weak position to criticize this practice since we have also been violating the rights of foreigners.

The Supreme Court declared that the six terrorist suspects who are now in detention must be allowed their day in court. Chief Justice Beverley McLachlin wrote the unanimous decision, which said that the present law violates the fundamental right to a fair trial that's part of Canada's constitution.

The First Americans

 
 
In an article published in this week's Nature, Heidi Ledford asks Who Were the First American?.

For decades many archaeologists have believed that the first Americans belonged to what is called the Clovis culture — hunter-gatherers who lived in parts of North America roughly 13,000 calendar years ago.

A new study counters this notion by showing that the Clovis culture is nearly 500 years younger than previously thought, and may have lasted for as little as 200 years. There is evidence of other cultures in the Americas well before this new date.

Wait a minute? I thought America was a Christian nation? Now we're told that it was founded by primtive stone age hunter-gatherers who weren't even as advanced as the Clovis culture?

Hmmm ... makes sense to me.

Can Your Dog Die of Chocolate?

 
Friday's Urban Legend: PARTLY TRUE

Will your dog die if it eats chocolate? No, not unless it eats a lot of chocolate. It's true that chocolate contains theobromine and in high doses this can be lethal to dogs. However, according to an article in Scientific American (Fact or Fiction: Chocolate Is Poisonous to Dogs) ...

A small dog should be belly-up after eating a handful M&M's, at least according to conventional wisdom. But watching "Moose," a friend's five-pound Chihuahua, race around a living room after his sweet snack makes one wonder: Is chocolate truly poisonous to dogs? ....

The hazard, however, is probably overblown, says Tim Hackett, a veterinarian at Colorado State University. Chocolate's danger to dogs depends on its quantity and quality. Large dogs can usually handle a small amount of chocolate whereas the same helping could cause problems for Moose and his pint-size kin....

Around every confection-centered holiday—Valentine's Day, Easter and Christmas—at least three or four dogs are hospitalized overnight in the animal medical center at Colorado State. But in 16 years as an emergency and critical care veterinarian, Hackett has seen just one dog die from chocolate poisoning, and he suspects it may have had an underlying disease that made it more vulnerable to chocolate's heart-racing effect.

It's probably better to be safe than sorry. If you have a dog then it's a good idea to remove all chocolate from the house. If you have a dog and a wife/girlfriend then you have to make a hard choice.

PZ Myers Slept Here

 
Milton is a small city not too far from where I live. Jennifer Smith of Runesmith's Canadian Content lives there. I've just discovered her blog.

On January 30th (the date is important) she wrote about Small Town Tax Dollars At Work. Apparently the powers that be in Milton decided it was time to replace the welcome sign.

The new sign is one of those fancy electronic pixel boards that can scroll text, blink on and off, simulate fireworks, and do all kinds of other cool effects. Unfortunately it’s only half the size of the old sign, making the glowing letters difficult to read from across the intersection. And even with the letters that small you still wouldn’t be able to fit in as much text as before.

This doesn’t look like it’s going to be a problem, though, since all the new sign has said since it went online a month ago is… ‘Happy New Year!’ Then the date. And the time. And the temperature. Then ‘Happy New Year!’ again.

I suppose we should just be grateful that it isn't blinking '12:00'.

Jennifer probably doesn't realize that Milton is famous because PZ Myers slept there in the summer of 2005.

Baghdad Burning

 
Would you like to read about the government of Iraq? You know, the one Dick Cheney props up as a beacon of freedom and democracy in the Middle East?

See Baghdad Burning, a blog written by an Iraqi woman.

As expected, Al Maliki is claiming the rape allegations are all lies. Apparently, his people simply asked the officers if they raped Sabrine Al Janabi and they said no. I'm so glad that's been cleared up.

[Hat Tip: Canadian Cynic]

Canadian Cynic

 
Check out Canadian Cynic.

Random thoughts from an unarmed (but reality-based) Canadian. These views are not necessarily the same views held by Canadians in general. But they should be.

More on "24" Torture

 
Steve Watson alerted me to a column on the CBC News website from last Monday. Heather Mallick discusses the torture scenes in "24" (see Less Torture in "24").

The column is wonderful. Here's are some excerpts.

Eventually I quit 24 cold turkey. It wasn't hard; I just couldn't take the same plot device 48 times. It's the "ticking time bomb" scenario where all of California will be deleted by a nuclear bomb unless Sutherland's Jack Bauer, the smartest agent in American counterterrorism, can torture the password out of an unnervingly calm, prescient Muslim madman about to destroy the American landmass with a team of three.

The problem, as Jane Mayer pointed out in the New Yorker this week, is that ticking time bombs almost never happen in real life. How embarrassing then that it occurs once a week every season of 24, which means 24 weeks of presenting the case that torture is necessary and indeed good.

It wasn't as easy for me to give up "24". I couldn't quit "cold turkey." In fact I still watch a bit of some episodes—at least until the torture starts.

Joel Surnow, the creator of the show, is a right-wing, torture-approving "patriot" who thrills to parties with Rush Limbaugh, Lynne Cheney, Karl Rove, Tony Snow et al. He's a strange, cold man who attended Beverly Hills High, a notoriously cruel collection of stars' and billionaires' children. Surnow's dad was a travelling carpet salesman. The family lived in a crappy apartment and Surnow slept on a cot. His schoolmates knew that.

Back to Orwell, who also once wrote "probably the greatest cruelty one can inflict on a child is to send it to school among children richer than itself." Orwell came out of school with a hatred of others' suffering, while taking a bleak enjoyment in his own. Surnow came out of school with a black heart.

I was at a fundraiser with the wonderful actress Shirley Douglas, whom I know and adore. Her face in profile is flat yet perfectly formed. She is a genuine beauty. Her mouth is the mouth all women should have. She is the daughter of Tommy Douglas, father of Medicare, and the man I thank when I stagger into emergency saying "Oooooh, it hurts." Good socialists all. She is the mother of Sutherland, who earns $10 million a year playing the torturer Bauer.

Sutherland is a left-wing dual-citizenship Canadian and a truly great actor. But he is the Republican Party's performing flea. Imagine that.

American Justice in Italy

 
Steve Watson was kind enough to supply me with two links that I otherwise would have missed. The first is to a column by Neil Macdonald on the CBC News website [Exceptions are U.S.]. Macdonald makes a point that Candians and Europeans are very familiar with; namely, the fact that America has little respect for the laws of other nations.

Here's the outline of the case. You'll have to read the rest of the column to see the outrage.

Nobody in the Italian government thought Osama Moustafa Hassan Nasr was clean. The Italian police had for some time been building a case against the Islamic cleric for spreading extremism.

Prosecutors in Milan believed he was a jihadist who had fought in Afghanistan and Bosnia, and, further, that he was in Italy recruiting fighters for radical Islamic causes. They intended to bring him to trial.

But the Americans were watching, and they had no patience with the pace and procedures of Italian law enforcement.

On Feb. 17, 2003, a squad of agents grabbed Nasr off a Milan street as he walked to a nearby mosque. He was, allegedly, taken to the U.S. air force base in Aviano, Italy, and flown to Germany, from where he was transshipped to his native Egypt. There, prison and the tender mercies of Egyptian interrogators awaited.

Nasr says he was tortured during his four years behind bars. Given the Egyptian government's pitiless attitude toward the radical Muslim Brotherhood and its many affiliates, that is not a claim many people doubt. The Nasr case was, say critics of the Bush administration, yet another case of America quietly subcontracting torture to deal with its enemies.

But two things happened last week to move this case out of the shadows: An Egyptian court freed Nasr, saying his imprisonment was "unfounded." And in Italy, a democratic U.S. ally, a judge indicted 26 Americans, most of them agents of the CIA, for kidnapping the cleric. The spies will almost certainly be tried in absentia. They've all left the country.

Genetics of ABO Blood Types

Now that we understand the biochemistry behind the ABO blood types [ABO Blood Types] it's time to look at the genetics. Recall that the human ABO gene on chromosome 9 has three common variants of the gene. Different variants are called alleles. The A allele encodes N-acetylaminogalactosyltransferase and this enzyme makes the A antigen that confers blood type A. The B allele encodes a variant enzyme that makes B antigen and gives rise to blood type B. The O allele encodes a defective enzyme that doesn't make either antigen. In the absence of both A antigen and B antigen your blood type will be O.

Vestigial Structures Are Evidence of Evolution

 
Bill Dembski writes in Vestigial Structures by Design ....

Vestigial structures in biology are commonly cited as evidence for evolution, and it may well be that they did evolve. But if it is evidence of evolution, it is evolution in the wrong direction — it’s not the sort of function enhancing/innovating evolution that is supposed to give evolutionary theory its bite. Vestigial structures, after all, are structures that have lost their function. If all of evolution proceeded in this fashion, we’d quickly descend to a world of nonfunctionality.

Dear IDiot,

You can't have your cake and eat it too.

Either vestigial structures are evidence of evolution or they aren't. You don't get to pick and choose whatever fairy tale version of evolution you like whenever it takes your fancy. The fact that some whales have tiny pelvis bones and tiny legs buried deep under their skin tells us something about evolution. It tells us that whales are descended from ancestors that had hind limbs. The fossil record confirms this.

How does the wonderful scientific theory of Intelligent Design Creationism explain this?

Australia: Dick Loves You, He Really Loves you!

 
Cheney praises Howard's loyalty.

The alliance between Australia and America was strong because both nations worked at it and respected each other as equals, United States Vice-President Dick Cheney said today.

In a major speech to the Australian-American leadership dialogue in Sydney, Mr Cheney said the deep affinity between the countries had grown into a great alliance over time.

"Australia and America share an affinity that reaches to our souls," he said.

"Over time, that deep affinity has grown into a great alliance.

You must be so proud. He never says that about Canada.

Human ABO Gene

The human ABO gene encodes N-acetylgalactosaminyltransferase. This is the enzyme that determines the ABO blood types (see ABO Blood Types). This gene is found in all mammals, which makes it unfortunate that HUGO choose such a human-centered name [ABO Gene]. The gene will have a very different name in other species.

The GenBank website for this gene is GeneID=28. The ABO gene islocated at 9q34.1-q34.2 on chromosome 9. This is in approximately the same region as the HSPA5 gene but don't let that fool you. The genes are very far apart. [map]

There are many variants of this gene [OMIM 110300]. The DNA used in the human genome project came from people with different blood types so all three major variants (A, B, O) are present. Many of the other known variants have also been sequenced. You can look at the sequences in the Evidence Viewer on the Entrez Gene website [Evidence Viewer ABO Gene. Here's a bit of the sequence from the O allele and the A allele.

The nucleotide sequence of the O allele is shown at the top with the amino acid sequence. (It's hard to see at this scale. Go to the evidence viewer for a better view.) Note the presence of a single nucleotide deletion. This shifts the reading frame of the coding region so that it ends shortly after the deletion in a stop codon (*). The O allele produces a truncated defective protein.

The nucleotide sequence of the active gene (A allele) has a "G" (small red blob) at that position. The reading frame continues uninterrupted beyond the region shown and a functional enzyme is produced from this allele.

The ABO gene has seven exons, some of them are quite short. There are six introns and one of them is large so the total length of the gene is over twice as long as the length of the coding region.

Less Torture in "24"

 
We used to watch "24" every week but a couple of years ago we stopped because of the torture scenes. I just don't enjoy watching programs where people are tortured. Once or twice might be okay but it was getting to the point where every show had a scene where someone was tortured.

We weren't alone. Quite a few of our friends also stopped watching. It's not that we're opposed to violence on television—far from it. I think there's lot of shows where violence is quite appropriate and good entertainment. (I feel the same way about sex, by the way.) But I don't have to watch if I don't like it and I choose not to watch "24".

Gail Shister now reports in the Philadelphia Inquirer ['24' tamps down the torture] that the show is cutting back on the violence.

Fox's 24 will become less torturous, but not because the U.S. military, human rights groups and children's advocates want it to....

The decision to cut back on torture is driven by creativity, not criticism, according to Gordon. In its sixth season, 24 has become so torture-heavy that it borders on cliche, he says.

"What was once an extraordinary or exceptional moment is starting to feel a little trite. The idea of physical coercion or torture is no longer a novelty or surprise.

"It's not something that we, as writers, want to use as a crutch. We'd like to find other ways for Jack to get information out of suspects," says Gordon. "Our appetite has decreased. Personally, I think the audience may be tiring of it as well. My wife says it's too much."

"Cliché?" That's a strange word to use. The audience that I know hasn't gotten "tired" of torture. We've gotten disgusted by it.

I hope they stick to their promise. If they really are going to cut back on the torture (but not necessarily other violence) then I'll start watching again.

Jury Duty: Day #3

 
Dismissed at 9:50 AM. Services no longer required. "See you in three years!"

Wikipedia Bad - Conservapedia Good

 
Did you know that Wikipedia was anti-Christian and (gasp!) anti-American? Next thing they'll be telling us that it favors gays, drugs, and premarital sex. Not to worry. Help is at hand.

Conservapedia is a much-needed alternative to Wikipedia, which is increasingly anti-Christian and anti-American. On Wikipedia, many of the dates are provided in the anti-Christian "C.E." instead of "A.D.", which Conservapedia uses. Christianity receives no credit for the great advances and discoveries it inspired, such as those of the Renaissance. Read a list of many Examples of Bias in Wikipedia.

Conservapedia is an online resource and meeting place where we favor Christianity and America. Conservapedia has easy-to-use indexes to facilitate review of topics. You will much prefer using Conservapedia compared to Wikipedia if you want concise answers free of "political correctness".

We can all sleep better now, especially us furriners. Now we know where to go to learn about the real America.

Google Co-founder Shows His Ignorance

 
According to Reuters, Google co-founder Larry Page made a fool of himself in front of a bunch of scientists [ Google co-founder: Science needs entrepreneurs]. Here's what Reuters says,

Scientists need more entrepreneurial drive and could benefit by doing more to promote solutions to big human problems, Google Inc. co-founder Larry Page told a meeting of academic researchers.

I hope readers of this blog will recognize that Page isn't talking about science. He's talking about technology. It's sad that he doesn't know the difference.

[Hat Tip: Shelley Batts]

ABO Blood Types

I described glycoproteins in a previous posting (Glycoproteins). Recall that these are proteins with long oligosaccharide chains attached to them. The oligosaccharides are normally put on as the proteins are being processed for export to the exterior of the cell. The process involves attaching a “core” oligosaccharide then modifying it once it is bound to the glycoprotein. The modifications include removing some sugar residues and adding others.

The cell surface of blood cells is covered with glycoproteins and the carbohydrate chains project out into the blood stream where they can easily be recognized by antibodies. We make antibodies to all sorts of things but the ones that attack our own cells are removed before they can do any harm. This anti-self screening of antibodies is one of the things that goes wrong in auto-immune diseases.

The proteins on the erythrocyte cell surface contain a wide variety of different oligosaccharides that are attached in various ways to the protein. However, it spite of this variation, there are a few structures that are very common. One of the most common “core” structures is something called H-antigen. It is composed of many different sugars but the outside end of the H-antigen structure always consists of a fucose (Fuc) residue, a galactose residue (Gal), and an N-acetylglucosamine (GlcNAc) residue.

In most primates, including humans, this core oligosaccharide is subsequently modified by adding an N-acetylgalactosamine (Monday’s Molecule #14) residue to form a branched structure at the end of the oligosaccharide (see diagram below). The enzyme that catalyzes this reaction is called N-acetylaminogalactosyltransferase or A enzyme. The gene for this enzyme is located on chromosome 9. The OMIN (Online Mendelian Inheritance in Man) entry for the ABO blood group is 110300. It contains a wealth of information on the topic.

If your red blood cells have oligosaccharides with a terminal GalNAc then you have blood type A. If you have a completely defective gene for A enzyme then your cells will have the unmodified H antigen structure and your blood type will be O. People with blood type A will not have antibodies to H antigen since this is the normal precursor to A antigen and there will always be some on the cell surface. In other words, the H antigen will be recognized as self.

Normal red blood cells are recognized as “self” so we don’t have antibodies against our own cells. However, we will have antibodies against the red blood cells of other people’s blood if their cell surface carbohydrates are different from ours. This is the basis of ABO blood group and it’s why we have to match blood types in a blood transfusion.

The ABO blood group was discovered over one hundred years ago by Karl Landsteiner (Nobel Laureate: Karl Landsteiner). The biochemical basis was only elucidated in the 1970’s when the technology for examining the carbohydrate structure of glycoproteins was worked out.

There’s an allele of the A enzyme gene that involves only a very small number of mutations but the result is to switch the enzyme from one that transfers GalNAc to one that transfers galactose (Gal). The variant enzyme is called B enzyme (galactosyltransferase) and the B antigen structure has a terminal galactose (Gal) instead of a terminal GalNAc.

If you are homozygous for the B allele on chromosome 9 then all of your red blood cells will have the B antigen oligosaccharide on their surface. You will not make antibodies against this structure because it’s “self.” You also won’t have antibodies against H-antigen for the reasons explained earlier. But you won’t recognize A antigen as self so your antibodies will attack any foreign cells that come from people with the normal wild-type allele (A).

People with blood type A will have antibodies against B antigen. They can receive blood from people with O blood type but they will reject blood from people with B blood type. You now have all the information you need to figure out who can give and receive blood from every possible combination of alleles: AA, AO, AB, BO, and OO.

There are no known natural effects of these differing blood types. People with A, B, AB and O phenotypes do not differ in fitness in any major way that we have been able to detect. This suggests that the complete absence of the enzyme (null mutation) is neutral in the current human population and so is the switch from one form of the enzyme to another. (Suggestions that blood type determines susceptibility to some infections are common in the scientific literature. Most of them have not held up. The best correlation is a possible association between blood type O and susceptibility to cholera. This looks pretty good but the cause-and-effect relationship is still up in the air.)

The ABO alleles seem to be segregating in the human population by random genetic drift. The O allele (non-functional enzyme) is the most common allele. The B allele is the least common—probably because it arose more recently. Some Native American populations are homogeneous for the O allele; in those populations everyone has blood type O. (For maps of the frequencies A and B alleles see Distribution of Blood Types.)

Jury Duty: Day 2

 
There were a lot fewer potential jurors in the assembly room this morning. That’s because Panel #13 was told not to come in today so only my panel (#14) was there. There are about 100 people on each panel.

Yesterday we watched the video on the monitors hanging from the ceiling. We might be selected for either a Civil trial or a Criminal trial. There are six jurors in a civil case and twelve in a criminal case. A typical case lasts two or three days. Potential jurors wait in the assembly room until a trial that’s already in progress needs a jury. A subgroup of us will be selected and shuffled off to the courtroom where jury selection takes place.

At 9:20 the Sheriff’s Official began taking attendance in the assembly room. She read out everyone’s name and we had to shout out “here” if we really were here. It was just like grade two, including the few who shouted out “present” just to be different. Since we have to pass by the Sheriff’s desk as we enter the room, it’s not clear to me why we couldn’t just have signed in when we arrived instead of wasting 12 minutes in a roll call. A sign-in would have spared us having to listen to someone mispronounce our names. You have to wonder why someone who does this every single day wouldn’t have learned how to pronounce “Nguyen” by now.

At 10:30 another Sheriff’s Official showed up. She had just received word from the judge that jury selection in her trial was going to be delayed due to legal issues. Since that was the only trial that might have required a jury we were dismissed for today. (There are 50 courtrooms and 40,000 cases per year. This gives you some idea of how few of them require a jury.)

Come back tomorrow at 9AM.

Nobel Laureate: Karl Landsteiner

The Nobel Prize in Physiology or Medicine 1930.

"for his discovery of human blood groups"


Karl Landsteiner won the Nobel Prize in 1930 for his discovery of the ABO blood groups. He showed that individuals could be A,B, AB, or O blood group and identified each type by their agglutinating properties. (He didn't actually discover type O - that came a few years after Landsteiner's original work on the AB types.)

His work is described in the presentation speech.

In order to avoid, in the publication of research on this subject, detailed descriptions which would otherwise be necessary - of the four blood groups and their appropriate cell structures, certain short designations for the blood groups and corresponding specific cell structures have been introduced. Thus, one of the two specific cell structures, characterizing the agglutinating properties of human blood is designated by the letter A and another by B, and accordingly we speak of «blood group A» and «blood group B». These two cell structures can also occur simultaneously in the same individual, and this structure as well as the corresponding blood group is described as AB. The fourth blood-cell structure and the corresponding blood group is known as O, which is intended to indicate that people belonging to this group lack the specific blood characteristics typical of each of the other blood groups. Landsteiner had shown that under normal physiological conditions the blood serum will not agglutinate the erythrocytes of the same individual or those of other individuals with the same structure. Thus, the blood serum of people whose erythrocytes have group structure A will not agglutinate erythrocytes of this structure but it will agglutinate those of group structure B, and where the erythrocytes have group structure B the corresponding serum does not agglutinate these erythrocytes but it does agglutinate those with group structure A. Blood serum of persons whose erythrocytes have structures A as well as B, i.e. who have structure AB, does not agglutinate erythrocytes having structures A, B, or AB. Blood serum of persons belonging to blood group O agglutinates erythrocytes of persons belonging to any of the groups A, B, or AB, but erythrocytes of persons belonging to blood group O are not agglutinated by normal human blood serum. These facts constitute the actual basic principles of Landsteiner's discovery of the blood groups of mankind.

By the time the Nobel Prize was awarded it was known that the ABO human blood types were genetic traits that segregated according to "Mendel's Laws."

The group characteristics are handed down in accordance with Mendel's laws. The characteristics of blood groups A, B, and AB are dominant, and opposing these dominant characteristics are the recessive ones which characterize blood group O. An individual cannot belong to blood group A, B, or AB, unless the specific characteristics of these groups are present in the parents, whereas the recessive characteristics of blood group O can occur if the parents belong to any one of the four groups. If both parents belong to group O, then the children never have the characteristics of A, B, or AB. The children must then likewise belong to blood group O. If one of the parents belongs to group A and the other to group B, then the child may belong to group A or B or it may possess both characteristics and therefore belong to group AB. If one of the parents belongs to group AB and the other to group O, then in accordance with Mendel's law of segregation the AB characteristic can be segregated and the components can occur as separate characteristics in the children. If a child has the A-group structure (either A or AB), then the A-group characteristic must be present in at least one of the parents, i.e. one of them must belong to group A or AB. If the child belongs to group AB, then one of the parents must belong to group A and the other to group B, or one of the parents must belong to group AB and the other to group A or B, or else both parents must belong to group AB. Application of the discovery of blood groups in questions relating to the establishing of paternity is based on these principles governing the hereditary transmission of blood groups.

See [ABO Blood Groups] for a modern description of the biochemistry.