Wednesday, September 5, 2007

Ontarians Want Public, Catholic Schools to Merge

 
According to this CBC poll a majority of the citizens of Ontario want to end discrimination in our school systems by abolishing the Catholic school board [Ontarians want public, Catholic schools to merge: poll].

This is, of course, exactly the opposite of what the Progressive Conservative Party is proposing. They want to extend funding to all religious schools. We have just discovered that their leader, John Tory, has doubts about evolution and favors creationism [ John Tory Promotes Creationism].

With a bit of luck this will blow up in their faces and we'll be able to get rid of the parallel public and Catholic school boards. Maybe it's just the stimulus we needed. Thanks, John Tory, for being an IDiot.

[Hat Tip: Jeffrey Shallit at Recursivity (Stupid Tory Tricks: Religious Schools In Ontario Could Teach Creationism, Get Public Funds)]

John Tory Promotes Creationism

 
This man is John Tory. He's the leader of the Ontario Progressive Conservative Party. Right now he's the leader of the Opposition but he's hoping to become Premier after the election on October 10, 2007.

If elected, Tory promises to extend public funding to all religious schools in Ontario. Right now we fund the Roman Catholic Schools as a result of a deal struck at the time of Confederation. I favor abolishing this funding and restricting government funding to the public school system [One School System Network [OSSN]].

Today John Tory stuck his foot firmly in his mouth when he revealed his ignorance of evolution. John Cowan of The National Post—a conservative newspaper—reported it like this [John Tory on creationism, the theory of evolution and why ducks have wings].
It should be said that Ontario Progressive Conservative leader John Tory is usually a thoughtful, articulate guy. But this week, the man has had nothing but a mouthful of foot. First, he referred to the University of Ottawa as the “University of Zero.” Another stumble came today, during an event to promote Mr. Tory’s promise to extend public funding to faith-based schools. A radio reporter asked whether schools would be allowed to teach creationism. Mr. Tory responded: “The Christian-based school would have to teach the Ontario curriculum, which of course has a different explanation. It’s still called the theory of evolution, but they teach evolution in the Ontario curriculum, but they could also mention to children the fact that there are other theories out there that are part of some Christian beliefs.”
Hmmm ... where have we heard that before? Do you know anyone who emphasizes that it's only a theory who isn't a creationist? Tory is in big trouble. He might get away with this in another country but here in Ontario he's going to look like a real fool.

Fortunately for him, his handlers got on the job real quick.
What Mr. Tory did not say was whether evolution would be taught as part of science class or religious studies -- which is, we submit, a pretty important distinction. So important that late this afternoon, the Conservative campaign issued the following press release:
JOHN TORY 2007 CAMPAIGN
STATEMENT OF CLARIFICATION

(Toronto, ON) – In an interview with reporters earlier today, John Tory was asked whether ‘creationism’ could be taught in faith-based schools, if they wished to receive funding under his proposed policy.

POINTS OF CLARIFICATION:
1.) The Ontario curriculum does not allow for creationism (or any other religious theory) to be taught in science classes in Ontario’s public schools.
2.) Mr. Tory clearly stated that any school to be included in the proposal must teach the Ontario curriculum.
3.) Mr. Tory’s proposal would allow creationism to be discussed only as part of religious studies programming, as is now the practice in Ontario’s publicly-funded Catholic schools.
Nobody's going to buy that. Tory clearly questioned whether evolution is true by mentioning that it is a "theory" and other "theories" should be taught.

Tory is running against the current Education Minister Kathleen Wynne (Liberal) in the riding of Don Valley West (Toronto). According to this article in the Canadian Press [ On eve of Ontario election, Conservative leader muses about creationism in schools] she nailed him on the issue.
Education Minister Kathleen Wynne - who is running against Tory for her Toronto seat - said his comments prove his policy hasn't been properly thought out. Creationism is currently not part of the provincial science curriculum and isn't given the same weight as evolution, she said.

Catholic schools may talk about creationism, Wynne said, but only in the context of a broader religious discussion.

"It's useful for students to have the opportunity to know the ideas that are out there and are part of our history," Wynne said.

"What we teach as the truth is the question. The scientific truths are the ones that are included in the Ontario curriculum. That's the curriculum that we support."
The Canadian press is all over this: See this article from the Globe & Mail [Creationism raised as Ont. election issue], and this from Canada.com [John Tory grilled on faith-based schools proposal], and this from The Toronto Star [Tory ignites debate over creationism in schools].

It will be interesting to see what happens tomorrow.

What is the latest theory of why humans lost their body hair?

 
This is the question asked in this month's issue of Scientific American. Mark Pagel, head of the evolutionary biology group at the University of Reading in England and editor of The Encyclopedia of Evolution gives three adaptationist explanations.

Now, here's the question of the day for all you adaptationists. Why didn't he mention neoteny? Do you think it's because he has carefully reviewed all the evidence and reaches the conclusion that there's more data to support running on the savannah?

Nobel Laureate: Richard Kuhn

 

The Nobel Prize in Chemistry 1938.

"for his work on carotenoids and vitamins"



In 1938, Richard Kuhn (1900-1967) won the Nobel Prize in Chemistry for his work on the structure of several different vitamins, including the carotenoids [Vitamin A (retinol)] and the B6 family [Pyridoxal Phosphate and the Vitamin B6 Family].

The award overlaps considerably with the prize for the previous year [Nobel Laureate: Paul Karrer], which suggests that the prize committee may have been pressured to recognize Kuhn after slighting him in favor of Karrer. The two men were friendly competitors for many years and much of their work is similar.

Kuhn was not able to accept the prize in 1938 because at the time he was working at Heidelberg University and the political situation did not allow him to travel to Sweden. There was no formal presentation speech but the following account of his work is posted on the Nobel Prize website.
When Richard Kuhn in 1926 took over the Chair for General and Analytical Chemistry at the Federal Institute of Technology Zurich he set in motion a comprehensive series of investigations into the so-called conjugated double bonds which make up the essential arrangement of the atoms of the polyenes.

The group of the diphenylpolyenes had at this time aroused especial interest because the presence in the carotenoid Crocetin of a chain of double bonds had been successfully demonstrated. Kuhn's sixth report on conjugated double bonds already contains structure determinations of polyene dyes from vegetable materials. With his syntheses of over 300 new materials belonging to this group Kuhn has by no means sought merely to liberate new substances. In this work he was much more concerned to clarify the general relationships between the chemical structure of these unsaturated substances and their optical, dielectric, and magnetic properties. The results which he has obtained in this respect form the starting-point for new lines of development in organic chemistry.

Kuhn's work on polyenes led him straight into the chemistry of the carotenoids. In 1930 Karrer clarified the constitution of carotene. The elementary composition of carotene, C40H56, had previously been ascertained by Willstätter. In 1931, R. Kuhn (at that time already Professor at Heidelberg), Karrer in Zurich, and Rosenheim in London discovered simultaneously and independently of each other the fact that the carotene in carrots consists of two separate components: one of these, b-carotene, rotates the plane of polarized light to the right, while the other, a-carotene is optically inactive. In 1933 Kuhn discovered a third carotene isomer which was called g-carotene.

The great physiological and biological significance of carotene lies in the fact that it is hydrolysed in the liver of certain animals so that from one molecule of b-carotene or from two molecules of a-carotene two molecules of Vitamin A, Axerophtol, are formed. This substance is necessary for growth in higher animals and especially for maintaining the normal condition of the mucous membranes.

With several collaborators Kuhn carried out a large number of investigations into the occurrence of carotenoids in the animal and vegetable kingdoms. Among his most important results, his discoveries of the following carotenoids and their structure determination should be mentioned:

Physalien from berries of species of Physalis, Helenien, Flavoxanthin, isolated from species of Ranunculus, Violaxanthin from Viola tricolor, unstable Crocetin from saffron, Taraxanthin, Cryptoxanthin from Zea Mays Rubixanthin.

Kuhn also had an important share in establishing the composition of Rodoxanthin and Astaxanthin as well as in discovering the connection of this latter carotenoid with the chromoproteids of the Crustaceans.

Of great interest also are the many contributions Kuhn and his school have made to the perfection of the chromatographic method which is one of the most important aids to the isolation and synthesis of the different representatives of the carotenoid group.

Kuhn's second great field of activity concerns the clarification of the Vitamin B complex. Kuhn has the great merit, together with von Szent-Györgyi and Wagner-Jauregg, of having been the first to isolate the extraordinarily important substance Vitamin B2 (Lactoflavin or Riboflavin). He has made very important contributions to the elucidation of the chemistry of this substance.

From 5,300 litres skim milk Kuhn and his collaborators succeeded in liberating about 1g of a pure yellow substance, Lactoflavin, whose composition was found to be C17H20O6N4. A breakdown product of the Lactoflavin, which was called Lumiflavin, could be identified with a substance previously prepared from the yellow ferment occurring in yeast. By drawing up a structural formula for Lumiflavin later confirmed in various ways, Kuhn furnished a key to the chemical clarification of Lactoflavin. He himself demonstrated the Lumiflavin formula, which had been found by analytical methods, by a synthesis - namely through the condensation of an odiaminobenzene derivative with Alloxan.

At the beginning of 1939 Kuhn made his second significant discovery in relation to the Vitamin B complex. Together with Wendt, Andersag, and Westphal, he succeeded in isolating that component of the Vitamin B complex which is designated Vitamin B6, the antidermatitis vitamin, and in a remarkably short time he was able to establish its chemical composition and structure (Ber., 71 (1938) 1534; 72 (1939) 309). The substance which Kuhn thus elucidated, which he called Adermin, proved to be 2-methyl-3-hydroxy-4,5 -dihydroxymethylpyridine.

The Role of Ultraconserved Non-Coding Elements in Mammalian Genomes

Ultraconserved elements are stretches of DNA that are 100% identical in mouse, rat, and human genomes. In order to qualify as an ultraconserved element, the length has to be greater than 200 bp. This eliminates most sequences that might be identical by chance.

The most interesting elements are those that fall outside of coding regions. These ultraconservative elements are most likely to be involved in regulating gene expression or some other essential feature of non-coding DNA. The fact that they are identical in species who last shared a common ancestor 100 million years ago is powerful evidence of adaptation.

Ahitiv et al. (2007) set out to test this hypothesis by selecting four examples of ultraconservative elements for further analysis. They discovered that the elements function as tissue specific enhancers in a test designed to look at how they control expression of a maker gene in mouse embryos. The results are shown in Figure 1 (left) of their paper, which was just published in the open access journal PLoS Biology.

The figure shows the genomic location of the four ultraconserved elements; uc248 (222 bp), uc329 (307 bp), uc467 (731 bp), and uc482 (295 bp).

Of these, uc467 is the most remarkable because it is 731 bp in length and resides in the last intron of the DNA polymerase alpha 1 gene (POLA1) on the human X chromosome. The enhancer trap experiment shows that this segment of conserved DNA directs expression of the marker gene in embryonic brain cells (shown as the dark blue area in the embryo above the 467 site). This is usually taken as evidence of specific regulatory sequences that bind transcription factors.

Ahituv et al. then deleted the four ultraconserved sequences from the mouse genome using standard knockout technology. Mice that were homozygous for the knockouts showed no evidence of any defect compared to wild-type mice. In other words, the ultraconserved elements seemed to be completely dispensable—a result that is not consistent with their extreme conservation.

THEME:
Junk DNA

What are the possible explanations? It's possible that the authors missed a phenotype that can only be detected outside the laboratory. It's also possible that the sequences really aren't conserved because they perform an important function but for another reason. Here's how the authors explain their results,
Based on the compelling evidence that ultraconserved elements are conserved due to functional constraint, it has been proposed that their removal in vivo would lead to a significant phenotypic impact [7,8]. Accordingly, our results were unexpected. It is possible that our assays were not able to detect dramatic phenotypes that under a different setting, for instance, outside the controlled laboratory setting, would become evident. Moreover, possible phenotypes might become evident only on a longer timescale, such as longer generation time. It is also possible that subtler genetic manipulations of the ultraconserved elements might lead to an evident phenotype due to a gain-of-function-type mechanism. All four elements examined in this study demonstrated in vivo enhancer activity when tested in a transgenic mouse assay (Figure 1) [6], which would suggest regulatory element redundancy as another possible explanation for the lack of a significant impact following the removal of these specific elements. Just as gene redundancy has been shown to be responsible for the lack of phenotypes associated with many seemingly vital gene knockouts, regulatory sequence redundancy [22] can similarly provide a possible explanation for the lack of a marked phenotype in this study. While our studies have not defined a specific need for the extreme sequence constraints of noncoding ultraconserved elements, they have ruled out the hypothesis that these constraints reflect crucial functions required for viability.
[UPDATE: Ryan Gregory at Genomicron discusses the same paper with a more thorough coverage of the background information and the relevance to junk DNA (Ultraconserved non-coding regions must be functional... right?). R. Ford Denison at This Week in Evolution has some thoughts on the paper (If it's junk, can we get rid of it?")]

Ahituv, N,, Zhu, Y., Visel, A., Holt, A., Afzal, V., Pennacchio, L.A., and Rubin, E.M. (2007) Deletion of Ultraconserved Elements Yields Viable Mice. PLoS Biol 5(9): e234 doi:10.1371/journal.pbio.0050234.

Denyse O'Leary's New Book

 
We've been waiting with baited bated* breath but the big day has finally arrived. Denyse O'Leary announces that we can now buy her new book The Spiritual Brain [ Just released - a neuroscientist's case for the existence of ... the soul!].

The first author is Mario Beauregard, a scientist at the Université de Montréal (Canada). According to Denyse, Beauregard is one of the "One Hundred Pioneers of the Twenty-First Century" selected by World Media Net. What the heck is "World Media Net"? Canadian Cynic also wants to know The hilarity just never ends].

Beauregard (and O'Leary) have solved the mind-body problem. It turns out that there's more going on inside the brain than just the firing of neurons. Apparently, your brain is capable of contacting a different reality during intense religious experiences.
Beauregard uses the most sophisticated technology to peer inside the brains of Carmelite nuns during a profound spiritual state. His results and a variety of other lines of evidence lead him to the surprising conclusion that spiritual experiences are not a figment of the mind or a delusion produced by a dysfunctional brain.
I'm not going the buy the book. If someone wants to read it I'd be happy to see a review from a real scientist.

* I actually knew that "baited" was wrong but I typed it anyway. For an explanation of what "bated" means see World Wide Words.

Tuesday, September 4, 2007

Pyridoxal Phosphate and the Vitamin B6 Family

 
Vitamin B6 is actually a family of related molecules consisting of a six-membered ring with a single nitrogen atom. The various members differ only in the group attached to position 4 of the ring. The ring is called a pyridine ring and the various derivatives are named after the pyridine ring (see below and Monday's Molecule #41). The most common vitamin B6 molecules are pyridoxal or pyridoxamine. They are widely available from plant and animal sources and it's unusual for human diets to be deficient in vitamin B6.


By definition, a vitamin is a compound that humans can no longer synthesize. Some vitamins act directly as cofactors or coenzymes but many them serve as precursors for the synthesis of the final product. This is true of the B6 vitamins. They are rapidly converted to pyridoxal 5′-phosphate (PLP). Humans have retained the ability to catalyze this conversion.

PLP is a cofactor that's bound to many enzymes in the cell where it participates in a number of different reactions. The most important reactions are those involving transfer of amino groups from one molecule to another. There is a large class of transaminases that require PLP.

The transaminases are required for amino acid synthesis and for synthesis of many neurotransmitters such as serotonin and epinephrine. An example of a transamination reaction is shown below. Note that PLP is covalently bound to the enzyme through a lysine side chain. An amino acid donates its amino group to PLP in an exchange reaction giving rise to pyridoxamine phpsphate (PMP), which remains firmly bound to the enzyme. The entire sequence of reactions can then be reversed using any α-keto acid as a substrate to generate a new amino acid.

Many of the transaminases are evolutionarily related. Similarly, the transaminases are often related to enzymes that catalyze different PLP-reactions such as isomerizations and decarboxylations. The evidence indicates that a primitive PLP-enzyme gave rise to a number of different enzymes that make use of the basic mechanism shown below. The enzymes differ in a few amino acids that bind the substrates.