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Monday, June 16, 2008

Kansas vs Darwin

 
Jeff Tamblyn, the director of Kansas vs Darwin will be in town this week for the ReelHeART International Film Festival. The film will be shown on Thursday evening. Here's the trailer, details below ...


Kansas vs. Darwin screening Thursday, June 19, 7:00 PM
ReelHeART International Film Festival
RHIFF MAIN PROGRAM B Tickets $8
INNIS THEATER 222
Innis College, University of Toronto
2 Sussex Avenue [1 block south of Bloor Street, on St. George Street]
Toronto, ON M5S 1J5
Advance Sales on line April 21, 2008 at www.reelheart.com

Kansas vs. Darwin
Director, Jeff Tamblyn, USA

Kansas vs. Darwin is a smart, funny, feature-length documentary about the Kansas state school board hearings on evolution. Features intimate revealing interviews with all major players on both sides, and exclusive, multi-camera footage of the hearings. Far more than a political film, Kansas vs. Darwin skillfully weaves multiple themes into a gripping dialectic, putting you face to face with, and inside the heads of, those who oppose your most closely held beliefs. Challenging and entertaining, it’s packed with fascinating characters who will leave you in admiration and astonishment, embarrassment and exasperation, as they feverishly pursue their goals, sometimes stumbling over their own eagerness in the attempt to win the most important battle of their lives.
I'm going. Contact me if you plan to attend and you want to meet up for dinner before the show.


Sunday, June 15, 2008

Fernando

 
Fernando was one of ABBA's biggest hits. There's a lot of debate about which war it refers to. The song mentions crossing the Rio Grande and that prompts many people in America to think of the Mexican revolution of 1910-1920. However, there aren't many examples of fighting that took place near the Rio Grande and there aren't too many examples of revolutionaries who crossed into Mexico from the USA.

Most people assume the song is about the Spanish civil war and the reference to the Rio Grande is just a generic reference to a river. Keep in mind that ABBA is a European group and the Spanish Civil War is still fresh in the memories of many europeans. For many it was glorious, but losing, fight against fascism.

The song refers to Fernando, a man who fought on the losing side against tyranny and fascism. Fernando was a revolutionary and a guerrilla fighter. He is now old and gray like many of the freedom fighters from all over Europe who went to Spain in the 1930's.

John McCain likes ABBA. I hope he appreciates that this song is about people who fought to defend their country from foreign domination. (Franco was supported by Hitler and Mussolini.)




Friday, June 13, 2008

Bias Against Female First-Author Papers

 
This is a follow-up to a posting back in January where I mentioned a recently published article by Budden et al. (2008) [see Bias Against Women?]. That article claimed to show evidence of a systematic bias against papers with women as first authors. The bias was mitigated when a particular journal switched to a double-blind reviewing system. This resulted in a significant increase in the number of published papers with women as first authors.

I was first alerted to the problem when GrrlScientist posted a favorable review of the paper, agreeing with the conclusion that journal reviewers were biased against papers with female first authors [Women, Science and Writing].

My first reaction was skeptical. These are biology papers and it didn't seem plausible that reviewers would be biased against papers with female first authors. There might possibly be a bias against papers from a lab run by women but that's not the same thing. In the biological sciences the principle investigator is often the last author and not the first. Furthermore, in my experience there wasn't any discrimination against female scientists at this level (publication). Half of our graduate students are women—why would we be biased against papers with one of them as first author? The study just didn't make sense.

Many Sandwalk readers interpreted my skepticism as an attempt to dismiss all forms of sexism in science. That was not my intent. Far from it, in fact, because I was very much aware of a particular case of sexism that greatly troubled me. What makes me angry is that I know of overtly sexist behaviors that are not challenged by scientists in the same department who are, themselves, not sexist. The subject of sexism came up at SciBarCamp in February where there was a session organized by physics professors to discuss sexism in physics departments. There seems to be a major problem in physics.

If you read the comments in my January posting you'll see how difficult it was to separate out the issue of whether the particular study on double-blind reviews was a legitimate scientific study, and whether sexism is common in science.

At the risk of encountering the same problem again, let's look at some recent events. A re-analysis of the original publication data has been published by Webb et al. (2008). They looked more carefully at the data from journals with double-blind review and from comparable journals that identify the authors. They found that the number of papers with women as first authors showed a general increase in most journals. The trend in the journal that initiated double-blind review back in 2001 was not significantly different. Thus, they conclude that there's no evidence of systemic bias against female first authors.

This is one of the points that I mentioned in the comments to my January posting but several other readers dismissed it. They implied that any attempt to question the data in the original paper was, itself, sexist.

The following correction appeared in the last week's (June 4th) issue of Nature.
The Editorial 'Working double-blind' (Nature 451, 605–606; 2008) referred to a study(1) that found more female first-author papers were published using a double-blind, rather than a single-blind, peer-review system. The data reported in ref. 1 have now been re-examined (2). The conclusion of ref. 1, that Behavioral Ecology published more papers with female first authors after switching to a double-blind peer-review system, is not in dispute. However, ref. 2 reports that other similar ecology journals that have single-blind peer-review systems also increased in female first-author papers over the same time period. After re-examining the analyses, Nature has concluded that ref. 1 can no longer be said to offer compelling evidence of a role for gender bias in single-blind peer review. In addition, upon closer examination of the papers listed in PubMed on gender bias and peer review, we cannot find other strong studies that support this claim. Thus, we no longer stand by the statement in the fourth paragraph of the Editorial, that double-blind peer review reduces bias against authors with female first names.
I believe that Nature has done the right thing in retracting their earlier claim. The problem of sexism in science is serious and needs to be addressed. But it doesn't do anyone any good if one side is supporting their claims with sloppy science. It would be good if we could get beyond that.

It may not be easy. The authors of the original paper have published a critique of the re-analysis (Budden et al. 2008b). They dispute the re-interpretation although they admit that their analysis is subject to different interpretations.

If the original paper was any other kind of scientific paper the criticism would be harsh. It will be interesting to see if any of the original strong supporters of the claim of sexist bias against female first authors are willing to reconsider their position on that particular issue.


[Hat Tip: R. Ford Dennison]

Budden, A., Tregenza, T., Aarssen, L., Koricheva, J., Leimu, R. and Lortie, C. (2008a) Women, Science and Writing. Trends in Ecology & Evolution, 23(1), 4-6. [PubMed] [doi:10.1016/j.tree.2007.07.008] (ref 1.)

Budden, A.E., Lortie, C.J., Tregenza, T., Aarssen, L., Koricheva, J., and Leimu, R. (2008b) Response to Webb et al.: Double-blind review: accept with minor revisions. Trends in Ecology and Evolution [doi:10.1016/j.tree.2008.04.001]

Webb, T. J., O'Hara, B. and Freckleton, R. P. (2008) Does double-blind review benefit female authors? Trends in Ecology and Evolution [doi:10.1016/j.tree.2008.03.003] (ref 2.)

Alex Palazzo in Toronto

 
Alex Palazzo of The Daily Transcript has been in Toronto for the past few days. We were able to get together for lunch on Wednesday and for some light liquid refreshments on Wednesday evening. It should come as no surprise that we were able to find several things we agree on and several more that we don't. It was a lot of fun. (I made a bet with Alex on Wednesday evening. He'll reveal it on his blog. He will lose.)

Yesterday's departmental seminar was very impressive. Alex has a nice story to tell about targeting mRNA to the endoplasmic reticulum. He has also discovered an unusual pathway for exporting certain mRNAs from the nucleus. This pathway seems to be specific for those mRNAs that encode secreted proteins.

I think everyone in the department was impressed. Maybe he'll be my colleague next year.


Alex Meets Toronto Bloggers

 
Alex Palazzo of The Daily Transcript met with Eva Amsen of easternblot, John Dupuis of Confessions of a Science Librarian, and Phillip Johnson of Biocurious.

Eva posted photos and a description of what they talked about [Science Bloggers].


Friday the 13th in Port Dover

 
It's Friday the 13th and the bikers are gathering in Port Dover. This year they're hoping to set a new Guinness record for the most bikes (>10,000).




Friday the 13th

 
Friday's Urban Legend: FALSE

[reposted from April 13, 2007]

Having a morbid fear of Friday the 13th—paraskevidekatriaphobics—is one of the most widespread superstitious beliefs in western industrialized nations. Believe it or not, there are many people who refuse to leave their house on Friday the 13th because they fear that bad luck will befall them if they venture outside. (Apparently, the bad luck doesn't find them in their homes.)

Personally, I like the attitude of the "eccentric" (rational?) men in the photo.
Members of the Eccentric Club of London at their annual Friday the 13th lunch in 1936 – surrounded by objects that are connected with superstitions. Picture: Getty Images [Unlucky roots of Friday the 13th].
There is no evidence to support the irrational fear of Friday the 13th, with the single exception of a study published 14 years ago in the British Medical Journal [Is Friday the 13th bad for your health?]. That study showed an increase in accidents on Friday the 13th compared to Friday the 6th.

According to scholars, the fear of Friday the 13th is a recent invention. There is no mention of it before 1900 [Why Friday the 13th Is Unlucky]. It seems that people simply combined a fear of the number 13—triskaidekaphobia—with an obscure dead of Fridays. Nobody knows for sure why the number 13 is considered unlucky but there are several popular myths. The most common are a Norse myth about having 13 people at dinner and a Christian myth about the Last Supper.

There is no significant historical record documenting a widespread irrational fear of Fridays although there are plenty of minor examples of Friday avoidance. Some people thought it was bad luck to be married on a Friday or to set sail on a ship. In Christian cultures the day is associated with the fact that Jesus was crucified on a Friday and Friday is the day that Adam was tempted by Eve to eat the forbidden fruit.


Thursday, June 12, 2008

Tangled Bank #107

 
The latest issue of Tangled Bank is #107. It's hosted at Syaffolee [Tangled Bank #107: The CYOA Edition].
You're trapped on a cruise ship in the South Pacific, bored out of your mind. The swimming pool holds no appeal. Gambling is pointless because the advantage is on the house. The books you brought with you have long been finished. You've even resorted to registering for a cha-cha class to relieve your ennui. But that's no fun, because the instructor is always yelling at you for having two left feet.

Then on a Wednesday morning, the ship docks on a small island. Travelers are allowed to go on land for the day. You debark and after wandering past the marketplace filled with locals hawking loud jewelry and ceremonial masks (probably manufactured in Taiwan), you find yourself in a small clearing with several paths meandering off into the undergrowth. There's a sign nearby saying:

"Welcome to the one hundred and seventh edition of Tangled Bank."

At the foot of the sign is a machete.

If you want to submit an article to Tangled Bank send an email message to host@tangledbank.net. Be sure to include the words "Tangled Bank" in the subject line. Remember that this carnival only accepts one submission per week from each blogger. For some of you that's going to be a serious problem. You have to pick your best article on biology.

Religulous

 
Coming to theaters near you in October [Religulous].




[Hat Tip: Brian Larnder at Primordial Blog]

Graduation

 
With 72,000 students, you can appreciate that graduation ceremonies need to be spread out over several weeks at the University of Toronto. At this time of year we have graduations every day and sometimes twice a day.

Today it was the turn of St. Michael's College. It was such a beautiful day that I couldn't resist taking a picture of the graduating class as they walked across the front campus to Simcoe Hall. There were about 500 students in this line.

How many of you went to your graduation? I did.


Charles McVety Visits the ROM

 
I was taking Bryant Ing1 to lunch today when we decided to check out what was happening at the Royal Ontario Museum. There was supposed to be a big anti-racism rally led by "Dr." Charles McVety. He's the man who claims that Charles Darwin was a racist [Canadian Creationist: Charles McVety].

Here he is (left) speaking to his supporters right in front of the museum where the Charles Darwin exhibit is housed. One of his supporters handed us a leaflet explaining why Darwin was a racist. (I'm sure you all know the quotes and I'm sure you all know that Darwin was very enlightened for a man of his time.)

We didn't stay long. McVety was going on about the title of Darwin's famous book. He was making the point that the book is about the preservation of favoured races.2 There were at least three or four people nodding their heads in agreement.

Toronto's finest were there in full riot gear to keep the huge crowd under control. You can see from the photo that they were very suspicious of Bryant and me. Some of them seem to be reaching for their weapons. You can click on the photo to see a larger version where their facial expression tells all.

The last photograph (below) is a view of the entire crowd. I figure there were about ten McVety sycophants supporters present and about ten passers-by who were curious about what was going on. There were almost as many reporters and camera crews. It was a non-event. We went to the Faculty Club for a nice lunch. Mmmmmm, fish and chips!




1. Winner of Monday's Molecule #66.

2. The actual title is On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life.

Canadian Creationist: Charles McVety

 
"Dr."1 Charles McVety is President of Canada Christian College in Toronto.

McVety is currently promoting the movie Expelled in Canada. He claims that it exposes the racism behind "Darwinism" as well as revealing how universities repress academic freedom by firing creationists.

I presume that Canada's Christian College is one of the last bastions of academic freedom where academics are allowed to say and think whatever they believe without fear of reprisal or dismissal. I assume this must be true because McVety feels so strongly about the importance of academic freedom. Evolutionists must be welcome at McVety's college.

The protection of academic freedom is probably behind this statement from the Canada Christian College website on college standards ...
Canada Christian College strives to maintain a distinctly Christian living and learning environment conducive to a rigorous study of God’s Word. Membership in Canada Christian College is obtained through application and invitation. Those who accept an invitation to join the College agree to uphold its standards of conduct. In return, they gain the privilege of enjoying the benefits of college membership and undertake to work for the best interests of the whole community (Phil. 2:4).

Compliance with these standards is simply one aspect of a larger commitment by students, staff, and faculty to live as responsible citizens, to pursue biblical holiness, and to follow an ethic of mutual support, Christian love in relationships, and to serve the best interests of each other and the entire community. Individuals who are invited to become members of this community but cannot with integrity pledge to uphold the application of these standards are advised not to accept the invitation and to seek instead a living-learning situation more acceptable to them.
In an effort to be much more respectful of creationists, no matter how stupid they might be, I will refrain from calling them names, like IDiot. This posting adheres to this new policy. I hope it pleases my atheist friends who favor accommodation.

Larry Moran
Surprising as it might seem, there are some people who don't like Charles McVety and his activities. A recent posting from Kady O'Malley on Macleans.ca blogs isn't all that complimentary [The opposite of YPF?]. (Macleans is a Canadian newsmagazine similar to Time and Newsweek.)
Perhaps he was inspired by the turnout for Young People Fucking, or maybe he misses all that media attention he got after taking credit for getting C-10 through the House with nary a peep over the controversial changes to the film tax rebate. Whatever the reason, Reverend Charles McVety is headed back to the capital to co-host a private screening of a very different kind of film: Expelled: The Movie, the controversial anti-Darwin documentary that purports to expose a sinister anti-creationism bias within the mainstream scientific community.

Interestingly, in his come-one-come-all invite to the film - which was forwarded to all MPs and staffers via parliamentary email by Conservative MP Maurice Vellacott - McVety doesn’t even mention the religious aspect of the debate; instead, he accuses Darwin of “overt racism”, and calls on Canadians to “blot out out this terrible scourge in our society.”
McVety and his friend(s) are holding an anti-racism rally today at 12:30 outside the Darwin exhibit at the Royal Ontario Museum, Toronto. You'd better get there early if you want to be at the front of the crowd where you can touch the great man. I assume traffic on Bloor Street will be tied up for hours.

Canadian Cynic might be there. (Warning! If you follow the link to Canadian Cynic you might be disappointed 'cause Canadian Cynic doesn't adhere to my new policy of accommodating accommodationists. Neither does PZ Myers who uses a rude word in referring to McVety and his somewhat misleading interpretation of Charles Darwin.


1. Here's a description of Charles McVety's degree Degree or Not Degree?.

Spring in Nova Scotia

 
One of my colleagues, David Tinker, has retired and moved to the Annapolis valley in Nova Scotia (Canada). He sent me a picture of a woodland path and it's so beautiful that I thought I'd share it with Sandwalk readers. Another one of my colleagues, Michael Paul, just retired and left yesterday to live near David in the Annapolis Valley. I can see why.




Wednesday, June 11, 2008

Nobel Laureates: Stanford Moore and William Stein

 

The Nobel Prize in Chemistry 1972.

"for their contribution to the understanding of the connection between chemical structure and catalytic activity of the active centre of the ribonuclease molecule"


Stanford Moore (1913 - 1983) and William Stein (1911 - 1980) were awarded the 1972 Nobel Prize in Chemistry for working out the role of amino acid side chains in the mechanism of catalysis by bovine ribonuclease A [see How Enzymes Work].

This is one of the most important achievements in biochemistry although it could hardly have been considered a breakthrough since the result was widely anticipated and predicted. Many other enzymes were being studied at the time and the award was, in a sense, a recognition of the general concept and not the particular contributions of Moore and Stein. Moore and Stein also developed the technique of automated amino acid analysis of proteins and peptides.

Moore and Stein shared their Nobel Prize with Christian Anfinsen.

The presentation speech was delivered by Professor Bo Malmström of the Royal Academy of Science.THEME: Nobel Laureates
Your Royal Highnesses, Ladies and Gentlemen,

The key substances of life are called enzymes. Everything we humans undertake - if we sit here enjoying the splendour of a Nobel ceremony, if we perform work, or even if we simply feel joy or sorrow - occurs by means of enzyme reactions. The phenomenon described as life is a network of coupled enzymatic processes. In chemical terminology the enzymes are catalysts, i.e. substances which accelerate chemical reactions without being consumed themselves. The concept of catalysis was introduced about 150 years ago by the great Swedish chemist Jöns Jacob Berzelius, who also, with astonishing intuition, suggested that the tissues of a living organism have catalytic activity. Around the turn of the century scientists started to associate this catalytic effect with specific substances, enzymes. This year's three Nobel Prize winners in Chemistry, Christian B. Anfinsen, Stanford Moore and William H. Stein, have performed fundamental studies with the enzyme ribonuclease making it possible for us now to approach the problem of enzymatic activity on a molecular level.

From a chemical point of view enzymes are proteins. These are built up of 20 different amino acids which are linked together into long chains. Despite the fact that proteins have only 20 building blocks, there are thousands of enzymes, each with its specific properties. This large degree of variation becomes possible because the number and sequence of the amino acids in the chain can be varied. Ribonuclease was the first enzyme for which the complete amino acid sequence was determined thanks to contributions from Anfinsen and from Moore and Stein.

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.

The contributions of Moore and Stein concern another fundamental question regarding ribonuclease, namely the basis for its catalytic activity. The reacting substances, the substrates, are bound to an enzyme in what is generally called its active site. In the complex so formed there is an interaction between enzyme and substrate leading to a changed reactivity of the substrate. Knowledge about the structure of an enzyme is of little help in understanding this interaction if it is not possible to find the active site and to determine the chemical groups in it. Moore and Stein discovered as an important principle that the active site contains amino acids with an anomalously high reactivity compared to the same amino acids in free form. This high reactivity is of direct importance for the catalytic activity of the enzyme, but Moore and Stein also found it possible to utilize it to label two amino acids in the active site by chemical modification. In this way the position of these amino acids in the long peptide chain could be unambigously determined. Through these investigations Moore and Stein were able to provide a detailed picture of the active site of ribonuclease long before the three-dimensional structure of the enzyme had been determined.

Dr. Anfinsen,

I have tried to explain your pioneering investigations showing that the linear sequence of amino acids in the enzyme ribonuclease determines the biologically active conformation of this enzyme. This finding has profound implications for our understanding of the way in which active enzyme molecules are formed in living cells.

Drs. Moore and Stein,

I have attempted to summarize your fundamental contributions to our understanding of the relationship between chemical structure and catalytic activity in the enzyme ribonuclease. In particular, I have stressed your studies leading to the localization of two specific histidine residues in the active site of the enzyme. It is for these pioneering experiments that the Royal Academy of Sciences has decided to award this year's Nobel Prize in Chemistry to you together with Dr. Anfinsen.

Drs. Anfinsen, Moore and Stein,

On behalf of the Royal Academy of Sciences I wish to convey to you our warmest congratulations, and I now ask you to receive your Prizes from the hands of His Royal Highness the Crown Prince.


How Enzymes Work

Enzymes are protein catalysts that speed up reactions. In the most extreme cases the catalyzed reaction will take place 1023 times faster than the rate of the uncatalyzed reaction. Typical values are about 1014. What this means is that a reaction that would normally take years can occur within a second inside the cell because the reaction is catalyzed by an enzyme.

How do enzymes do this? The answer is surprisingly complicated. Let's look at a simple reaction forming part of the glycolysis pathway.


In this reaction, one molecule of DHAP is converted to one molecule of G3P, and vice versa (the reaction is readily reversible). The reaction is catalyzed by a famous enzyme called triose phosphate isomerase or TPI.

As the reaction proceeds, there will be a point when neither DHAP or G3P exist. Instead, there will be a transition state whose structure is somewhere in between that of the product and the substrate. This transition state only exists for a nanosecond or less. One of the things that enzymes do is to create a pocket where the binding of the transition state intermediate1 is favored. What this does is to lower the activation energy between the reactant and product making the transition from one to the other much easier. The net effect is to speed up the process by many order of magnitude.

Transition state stabilization is one of the most important mechanisms of enzyme catalysis. There are very few direct proofs of this in the scientific literature because the hypothetical transition state is so unstable and transient. However, there is a huge number of indirect experiments that confirm the importance of this mechanism. They include the binding of more stable transition state analogues and the modeling of hypothetical transition states into the active site of an enzyme.

Another important mechanism of catalysis is substrate binding. The role of an enzyme is to recruit reactants such as DHAP into the active site of the enzyme where it is precisely positioned for the subsequent reaction. In the example show here, the reactant has bound to the active site of trisose phosphate isomerase where it aligned with two important amino acid side chains: histidine (His, dark blue) and glutamate (Glu, red). In this case, a single reactant is oriented correctly for the subsequent reaction. In other cases the role of binding is more obvious since two different reactions are correctly positioned to react with each other.

The enzyme serves as a stable platform for aligning the substrates in the correct orientation. The arrangement of the active site pocket and the surrounding channel can greatly increase the probability that the reaction will take place. In solution, without enzyme, many collisions between molecules will be nonproductive.

In addition to transition state stabilization, and substrate binding effects, enzymes also exhibit catalytic effects on acceleration of reactions. There are many different kinds of catalytic effects but the main ones are ionization effects, acid-base catalysis, and covalent catalysis. In all cases, the effect is mediated by the side chains of amino acid at the active site.

An example of acid-base catalysis in triose phosphate isomerase is shown in the diagram on the right. You don't need to follow the specifics of the reaction. The idea is that a histidine side chain (His-95) forms a hydrogen bond with the substrate while a glutamate residue (Glu-165) acts as an acid-base catalyst to extract a proton from DHAP.

The role of amino acid side chains in catalysis and substrate binding was mostly worked out the 1970's when the first enzyme structures were being solved. One of the first examples was ribonuclease A [Monday's Molecule #75]. Stanford Moore and William Stein received the Nobel Prize in 1972 for being among the very first biochemists to demonstrate how enzyme work at the molecular level.


1. A transition state is not an intermediate. The difference is too technical for this posting. I just want to make sure we don't get any quibbles in the comments section.