Sandwalk

Tuesday, March 24, 2009

Monday's Molecule #114: Winners

UPDATE: The molecule is streptomycin, 5-(2,4-diguanidino-3,5,6-trihydroxy-cyclohexoxy)- 4-[4,5-dihydroxy-6-(hydroxymethyl) -3-methylamino-tetrahydropyran-2-yl] oxy-3-hydroxy-2-methyl-tetrahydrofuran-3-carbaldehyde. Streptomycin inhibits protein synthesis in bacteria. The Nobel Laureate is Selman Waxman.

This week's winners are Bill Chaney of the University of Nebraska and Elvis Cela of the University of Toronto.

Identify this molecule and briefly describe its function. You must supply the common name and one of the the formal IUPAC names.

I'm looking for the Nobel Laureate who discovered this molecule.

The first person to identify the molecule and the Nobel Laureate wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first won the prize.

There are seven ineligible candidates for this week's reward: Guy Plunket III from the University of Wisconsin, Deb McKay of Toronto, Maria Altshuler of the University of Toronto, David Schuller of Cornell University, Adam Santoro of the University of Toronto, Dima Klenchin from the university of Wisconsin, and Alex Ling from the University of Toronto.

Dima has offered to donate a free lunch to a deserving undergraduate so I'm going to continue to award an additional free lunch to the first undergraduate student who can accept it. Please indicate in your email message whether you are an undergraduate and whether you can make it for lunch.

THEME:

Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Prizes so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.

Correct responses will be posted tomorrow. I reserve the right to select multiple winners if several people get it right.

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

Let the Physicists Fix the Economy.

Chad Orzel at Uncertain Principles has an interesting idea on how to fix the current economic crisis. He thinks all traders and financial wizards should be fired because Physics Can Fix This.

And, seriously, do you really think that these transactions are too complicated for physicists to figure out? We're talking about people who have spent the last several years thinking about folding and twisting strings in eleven dimensions. Unless the transaction records are all encrypted in some private cipher, they'll have no trouble figuring it out. And even if they are encrypted, that will only slow things down a little-- given what we know about the rocket scientists on Wall Street, the cipher key is probably written on a Post-It stuck to the computer. With a magnet.

Better yet, they'll be cheap. We're talking about theoretical physics grad students and post-docs-- most of them are currently working for less than Vikram Pandit spends on shoes. The pre-bonus salary given to a typical financial executive is more money than they can reasonably expect to make in their current line of work. It'll be a major blow to the over-priced restaurant industry in lower Manhattan, but they'll rebound once they learn to mark up Ramen noodles a thousand percent.

And best of all, we don't have to worry about them getting greedy and wrecking the entire global economy in order to make some short-term gains. We're talking about people who, to this point, have completely sacrificed their financial well-being in pursuit of higher mathematical truth. They're used to working toward the long-term success of abstract goods.

Sounds good to me. It can't possibly be any worse.

Medical Care? - Canada Bad, America Great

OldFart is an American doctor who sometimes posts on M.D.O.D.. Here's what (s)he wrote last Friday [Natasha Richardson R.I.P.].

How do you think Natasha Richardson's family likes that socialized medicine in Canada??

Any 3rd year med student or an EMT worth his salt would know she was a set-up for an epidural hematoma. It is an incredibly classic story for it. And so easy to diagnose with an 8 second CT of the brain.

But in Canada I bet she was "put in queue" for a CT scan next week and had to fly to the US in order to get one in a real hospital's ED. But by then she was brain dead.

Still want Hussein's version of medicine here you fuckin' brain dead liberals?? Could save a lot of tax payor's dollars, huh? Everybody could get the "same access" to health care huh?

Just not when it's your family..

My prayers to Ms Richardson's family.

Every civilized country has socialized medicine because they think it's a fundamental right to get medical care without having to worry about how to pay for it. What is it about American doctors that they are so opposed to this concept?

M.D.O.D. is a group blog. Another American doctor, 911doc, has added this update ...

EDITOR'S NOTE: OLDFART POSTED BELOW A FEW HOURS AGO AND SITTING HERE IN BED WITH THE WIFE I LEARNED, IN THAT REPUTABLE MEDICAL JOURNAL 'PEOPLE MAGAZINE', THAT MRS. RICHARDSON HAD INDEED REFUSED TRANSPORT AND MEDICAL CARE AFTER WHAT WAS A MINOR FALL ON A 'BUNNY SLOPE' (ON WHICH SHE WAS NOT WEARING A HELMET).

THOUGH I TOO WONDERED IF THE 'QUEUE UP' PROBLEM WAS AT PLAY HERE IT EVIDENTLY WAS NOT, AND SO WHILE WE WILL NO DOUBT HAVE OTHER OPPORTUNITY TO COMPARE THE ACCESS TO EMERGENCY CARE IN SOCIALIZED COUNTRIES TO THE ACCESS TO EMERGENCY CARE HERE, THIS IS NOT THE CASE TO DO IT WITH.

I WILL ASK THIS QUESTION OF ANY CANADIAN PHYSICIANS WHO HAPPEN BY HOWEVER. HOW QUICKLY CAN ONE GET A CT OF THE BRAIN IN A CASE SUCH AS THIS WHERE THERE APPARENTLY WAS NO OBVIOUS TRAUMA AND THE ONLY COMPLAINT ONE HOUR AFTER THE FACT WAS A WORSENING HEADACHE? HOW ABOUT FOR A INTERNATIONAL CELEBRITY?

I'm also curious. How easy is it to get a CT scan in the first aid station at the bottom of a ski slope in either country? How often are CT scans performed in the small town local hospitals? In the USA does it matter whether you have insurance or would everyone be given a CT scan after banging their head? Do celebrity actresses get treated differently than single mothers earning $35,000 per year with no health insurance?

And what does Hussein have to do with medical care in Canada?

[Hat Tip: Pure Pedantry]

Old Tools

Eva has posted some photos of old lab equipment and tools [Old Tools]. Check them out to see if you recognize anything.

Here's another contribution. This one is pretty easy but starting tomorrow they're going to get much harder. (Click to embiggen.)

Signals of Positive Selection in Humans?

Signals of recent positive selection in a worldwide sample of human populations is the title of a paper that has just been published in Genome Research (Pickrell et al. 2009).

These workers looked for signs of positive selection using techniques similar to those employed by Hawks et al. in their 2007 paper. That 2007 paper serves as one of the important bits of evidence in the recently published book, The 10,000 Year Explosion.

The idea is to pick out regions of the genome that have linked clusters of polymorphisms (SNPs = single nucleotide polymorphisms). These cluster are called haplotypes and they indicate that a region of the genome has not undergone much recombination in the recent past, because recombination tends to shuffle polymorphisms. One way this linkage could be preserved is when a part of the genome is under positive selection so its increase in frequency is rapid. This is called a selective sweep.

Pickrell et al. (2009) examined a database of 657,143 SNPs called the Human Genome Diversity-CEPH Panel (HGDP). These polymorphisms come from a global sample of 53 populations. The Hawks et al. (2007) paper examined the HapMap database of 3.1 million SNPs from three populations.

Pickrell et al. (2009) also detect a large number of regions that are candidates for positive selection. Their sites overlap those of the earlier study—about half of their sites were also identified by Hawks et al. (2007).

A number of candidates for positive selection are discussed in the paper but the authors note that many of the potential sites are not near any genes that have been well-characterized. It's important to look at individual cases in order to get a feel for the data, especially since the possibility of false positives is a concern.

Specific Examples

Here are a few of the single genes that were identified in one or more groups (e.g. Bantu, Europeans, native American etc.) They are from the top ten strongest signals so they presumably represent some of the best cases for selection.

Heat Shock Transcription Factor 2 (HSF2): This is one of two genes for the major heat shock transcription factor. The heat shock genes are highly conserved and so is their regulation. It's very unlikely that a mutation in the native North American population would be beneficial relative to the allele in all other populations.

succinate-CoA ligase, GDP-forming, β-subunit (SUCLG2) This is the gene for succinyl-CoA synthetase, one of the enzymes of the Krebbs cycle. The data suggest that an allele of this gene was positively selected in the population of Oceania (Pacific Ocean). This doesn't seem very likely.

oxoacyl-ACP synthase, mitochondrial (OXSM) This is the mitochondrial version of a β-ketoacyl synthetase, a standard enzyme required for fatty acid synthesis. An allele shows signs of positive selection in Eurasian populations but not in any other population. It doesn't seem likely that there's an allele conferring a beneficial effect that hasn't already become fixed in mammals over 100 million years ago.

mannosidase, alpha, class 2A, member 1 (MAN2A1) This is a mannosidase located in the Golgi. It's required for one of the last stages in the oligosaccharide maturation pathway—a pathway that's found in all eukaryotes. Pickrell et al. (2009) suggest that an allele of this gene has been selected in the pygmy and Bantu populations. Again, it isn't likely that a standard metabolic gene would be selected in this way.

False Positives?

The patterns of potential selective sweeps strongly suggest local and/or regional sweeps. Since this is the pattern you might expect from random genetic drift, it raises a question about false positives. The authors of the 2009 paper say, ...

Further exploration of the geographic patterns in these data and their implications is warranted, but from the point of view of identifying candidate loci for functional verification, the fact that putatively selected loci often conform to the geographic patterns characteristic of neutral loci is somewhat worrying. This suggests that distinguishing true cases of selection from the tails of the neutral distribution may be more difficult than sometimes assumed, and raises the possibility that many loci identified as being under selection in genome scans of this kind may be false positives. Reports of ubiquitous strong (s = 1-5%) positive selection in the human genome (Hawks et al. 2007) may be considerably overstated. [My emphasis-LAM]

It should come as no surprise that John Hawks disagrees. He has posted a rebuttal on his blog at: Overstating the obvious.

It's an interesting debate but let's not lose sight of the most important point—it is a scientific debate. The case for massive amounts of accelerated human evolution has not been proven in spite of what you might read in The 10,000 Year Explosion and in articles in the popular press.

UPDATE: See Razib's posting: Signals of recent positive selection in a worldwide sample of human populations...maybe

Hawks, J., Wang, E.T., Cochran, G.M., Harpending, H.C., and Moyzis, R.K. (2007) Recent acceleration of human adaptive evolution. Proc. Natl. Acad. Sci. (USA) 104:20753-20758. Epub 2007 [PubMed] [DOI:10.1073/pnas.0707650104]

Pickrell, J.K., Coop, G., Novembre, J., Kudaravalli, S., Li, J.Z., Absher, D., Srinivasan, B.S., Barsh, G.S., Myers, R.M., Feldman, M.W., and Pritchard, J.K. (2009) Signals of recent positive selection in a worldwide sample of human populations. Genome Research 23 published in advance March 23, 2009 [DOI: 10.1101/gr.087577.108]

Monday, March 23, 2009

Old Tools

Eva has posted some photos of old lab equipment and tools [Old Tools]. Check them out to see if you recognize anything.

Here's another contribution. How many readers know what this is and what it was used for in prehistoric times? (Click to embiggen.)

Fox News host apologizes

From the CTV website: Fox News host apologizes in face of Canadian outrage. [See the video at: Here's What Fox News Thinks of Canada's Military.]

The host of a Fox News program has apologized for a segment on the Canadian military that Defence Minister Peter MacKay called "disgusting" and "crass."

A group of pundits on "Red Eye with Greg Gutfeld," which airs weekdays at 3 a.m. on Fox News, each took turns trashing Canada and its military during an episode that aired on March 17.

...

Gutfeld issued an apology Monday afternoon saying, "I realize that my words may have been misunderstood. It was not my intent to disrespect the brave men, women and families of the Canadian military, and for that I apologize."

But the host also seemed to defend his program, adding "Red Eye is a satirical take on the news, in which all topics are addressed in a lighthearted, humorous and ridiculous manner."

I wonder if they've ever treated 9/11 in a "lighthearted, humorous and ridiculous" manner? What about the USA? Have they ever mocked their own country on this show?

Monday's Molecule #113

Dropping Courses

Chad Orzel of Uncertain Principles has started a discussion about when students should be allowed to drop courses [Academic Poll: Drop It Like It's Hot?].

Why not visit his blog and share your thoughts? I think this is an important issue. Universities may need to make changes.

Astrology in The Toronto Star

I read The Toronto Star every day but I missed this article published last Friday [The vernal equinox: Science and mysticism].

Staff reporter Nick Aveling thought it would be fun to contrast the words of a scientist (Astronomer Randy Attwood) and an astrologer (Michael Barwick). The title of the article implies that this might be an attempt at humor but I'm not sure.

What are the implications of today's equinox?

Attwood: As the earth goes around the sun it appears that the overhead sun seems to be creeping towards the north. For the next three months it will continue to creep north until the first day of summer, when it's at its farthest point north. As the sun gets higher that means it's able to concentrate more heat on the ground.

Barwick: Somebody who's born at 0 degrees Aries – that's a particularly strong Aries person ... William Shatner, Captain Kirk, has kind of the ultimate Aries energy in a way: going forth, boldly going where no one has gone before, pioneering, being in command, leading intuitively. This is Aries.

Phil Plait of Bad Astronomy didn't think it was funny: Canada slips further into goofiness. Neither did any of the people who posted comments on the newspaper's website.

Old Tools

Eva has posted some photos of old lab equipment and tools [Old Tools]. Check them out to see if you recognize anything.

Here's my contribution. How many readers know what this is and what it was used for in prehistoric times? (Click to embiggen.)

Sunday, March 22, 2009

Gene Genie #44

The 44th edition of Gene Genie has been posted at Mary Meets Dolly [Gene Genie #44].

My first Gene Genie! For my Catholic readers, Gene Genie is the "blog carnival of genes and genetic conditions." (No rubbing of ancient oil lamp necessary.) I hope I shall do it justice.

The beautiful logo was created by Ricardo at My Biotech Life.

The purpose of this carnival is to highlight the genetics of one particular species, Homo sapiens.

Here are all the previous editions .....

SEED Reviews The 10,000 Year Explosion

The latest issue of SEED praises US President Obama's emphasis on science and offers a list of ideas "for revising the role of science in America." The number one recommendation is "Make Scientific Literacy a National Priority."

What's needed is better ways of fostering critical thinking and imagination not only in the nation's schools but among its citizenry.

Scientific literacy is not just about being able to weigh in on scientific debates of the day by parsing climate change or understanding the difference between a theory and a guess. The ability to empirically test one's ideas about the world and discard beliefs in light of new evidence is fundamental to the ideals of a just and democratic society; it brings people to the table to debate issues reasonably and with minimum rhetoric.

Good advice, although I wish they'd mentioned the importance of skepticism along with critical thinking. Scientifically literate citizens should not blindly accept every new breakthrough that appears in the scientific literature.

We must rely on good science journalism to inform the general public. Good science journalists will analyze and distill the latest scientific information and help put it in context. They will explain things that are controversial, but exciting, and avoid being swept up by the inevitable rhetoric that accompanies every new discovery.

T.J. Kelleher is a senior editor at SEED. In this same issue, Kelleher reviews The 10,000 Year Explosion a book by Gregory Cochran and Henry Harpending. Let's see whether the review is an example of critical thinking.

This is a trade book, not a scientific publication. The main thesis of the book is that humans are evolving rapidly. This thesis is supported by several lines of evidence.

A number of just-so stories from anthropology [see Examples of Accelerated Human Evolution]. Some of them are reasonable, many aren't.
A paper published in Dec. 2007 claiming there are thousands of human genes being selected in various populations (Hawks et al. 2007). To the best of my knowledge this analysis has not been independently replicated in the scientific literature and the technology is not without critics.
A paper by Hawks et al. (2008) claiming that human adaptive evolution has recently accelerated by acquiring genes from Neanderthals.
A claim that within the past 1,000 years the IQ of Ashkanazi Jews has increased relative to the general European population because medieval Ashkanazi Jews engaged in occupations that required high intelligence (Cochran et al. 2006). [See Race and Intelligence, Evolution in the Ashkenazi Jewish Population.]

All this makes for a very interesting book and an idea that's worth serious consideration. It will be interesting to discover, over the next few years, whether there are thousands of genes under positive selection, whether there are only hundreds and the rest are being influenced by random genetic drift, or whether the genetic analysis is subject to artifacts.

Let's see what T.J. Kelleher thinks of all this. Here's the first two paragraphs of the review.

"The 10,000 Year Explosion" would be important even if it were only about population genetics and evolutionary biology, but Gregory Cochran and Henry Harpending, a physicist turned biologist and a biological anthropologist, respectively, at the University of Utah, have written something more. This book is a manifesto for and an example of a new kind of history, a biological history and not just of the prehistoric era. Covering broad ground over human history and prehistory, the authors argue for the singular importance of genes in human history, not just as markers but also as makers.

The first four of the book's seven chapters serve as something of a preamble to the final three. Cochran and Harpending first present the evidence for recent, accelerated human evolution after the invention of agriculture. In its own right that argument is a fairly revolutionary proposition, bit one with clear data, both skeletal and genetic, to back it up: investigations of the human genome undertaken as part of the International Hap Map Project and elsewhere have clearly demonstrated that selection has been ongoing and has accelerated over time. This has been a landmark finding in human biology, and Cochran and Harpending, building on their own work and that of others, including John Hawks of the University of Wisconsin-Madison, convincingly tie the advent of architecture—and the stresses resulting from the new diets. new modes of habitation, new animal neighbors, and new modes of living that agriculture made possible—to this accelerated evolution. It is work destined to launch a thousand careers.[My emphasis-LAM]

Is this an example of critical thinking? Is this the best way to enhance scientific literacy?

Cochran, G., Hardy, J., and Harpending, H. (2006) Natural history of Ashkenazi intelligence. J. Biosoc. Sci. 38:659-93.

Hawks, J., Cochran, G., Harpending, H.C., and Lahn, B.T. (2008) A genetic legacy from archaic Homo. Trends Genet. 24:19-23. Epub 2007 Dec 3. [PubMed] [DOI: 10.1016/j.tig.2007.10.003 ]

Hawks, J., Wang, E.T., Cochran, G.M., Harpending, H.C., and Moyzis, R.K. (2007) Recent acceleration of human adaptive evolution. Proc. Natl. Acad. Sci. (USA) 104:20753-20758. Epub 2007 [PubMed] [DOI:10.1073/pnas.0707650104]

New Scientist Sheds its Last Ounce of Credibility

Many of us were upset last month when New Scientists published some old news about the early tree of life and sensationalized it on their cover [Darwin Was Wrong?]. They claimed that "Darwin Was Wrong" when, in fact, Charles Darwin didn't even know about molecular evolution or the relationships of bacterial species.

The New Scientist editors admitted that the cover was designed to sell magazines and they seemed to be aware of the problem [Explaining the New Scientist Cover].

They even published a critical letter from Daniel Dennett, Richard Dawkins, Jerry Coyne, and PZ Myers [Blunt Talk from Four Evolutionists].

New Scientists has now begun an ad campaign to attract new subscribers and guess which cover they choose? Jerry Coyne and PZ Myers are advocating a scientific (Coyne) or personal (PZ) boycott of New Scientist. I'm conflicted about that. In spite of its recent errors, New Scientist is far superior to SEED and Discover as a science magazine. If we really want to punish the worst of the popular science magazines then SEED is a much better target.¹

1. The monthly column by PZ Myers in SEED is the exception, not the rule.

Here's What Fox News Thinks of Canada's Military

The ignorance in this segment makes me very angry. Can anyone tell me what the US military is protecting Canada from? The Iraqis? Cubans? The people of Granada or Panama? Kosovo? Afghanistan? Lebanon? Maybe the Somalis, or the Vietnamese?

Canada has only been invaded once in its history (1812) and it wasn't by any of those countries.

Does this embarrass any of my American friends, especially those who like to defend the American media?

[Hat Tip: Canadian Cynic]

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Quotations

The old argument of design in nature, as given by Paley, which formerly seemed to me to be so conclusive, fails, now that the law of natural selection has been discovered. We can no longer argue that, for instance, the beautiful hinge of a bivalve shell must have been made by an intelligent being, like the hinge of a door by man. There seems to be no more design in the variability of organic beings and in the action of natural selection, than in the course which the wind blows.Charles Darwin (c1880)

Although I am fully convinced of the truth of the views given in this volume, I by no means expect to convince experienced naturalists whose minds are stocked with a multitude of facts all viewed, during a long course of years, from a point of view directly opposite to mine. It is so easy to hide our ignorance under such expressions as "plan of creation," "unity of design," etc., and to think that we give an explanation when we only restate a fact. Any one whose disposition leads him to attach more weight to unexplained difficulties than to the explanation of a certain number of facts will certainly reject the theory.

Charles Darwin (1859)

Science reveals where religion conceals. Where religion purports to explain, it actually resorts to tautology. To assert that "God did it" is no more than an admission of ignorance dressed deceitfully as an explanation...

Peter Atkins

Quotations

The world is not inhabited exclusively by fools, and when a subject arouses intense interest, as this one has, something other than semantics is usually at stake. Stephen Jay Gould (1982)
I have championed contingency, and will continue to do so, because its large realm and legitimate claims have been so poorly attended by evolutionary scientists who cannot discern the beat of this different drummer while their brains and ears remain tuned to only the sounds of general theory. Stephen Jay Gould (2002) p.1339
The essence of Darwinism lies in its claim that natural selection creates the fit. Variation is ubiquitous and random in direction. It supplies raw material only. Natural selection directs the course of evolutionary change. Stephen Jay Gould (1977)
Rudyard Kipling asked how the leopard got its spots, the rhino its wrinkled skin. He called his answers "just-so stories." When evolutionists try to explain form and behavior, they also tell just-so stories—and the agent is natural selection. Virtuosity in invention replaces testability as the criterion for acceptance. Stephen Jay Gould (1980)
Since 'change of gene frequencies in populations' is the 'official' definition of evolution, randomness has transgressed Darwin's border and asserted itself as an agent of evolutionary change. Stephen Jay Gould (1983) p.335
The first commandment for all versions of NOMA might be summarized by stating: "Thou shalt not mix the magisteria by claiming that God directly ordains important events in the history of nature by special interference knowable only through revelation and not accessible to science." In common parlance, we refer to such special interference as "miracle"—operationally defined as a unique and temporary suspension of natural law to reorder the facts of nature by divine fiat. Stephen Jay Gould (1999) p.84

Quotations

My own view is that conclusions about the evolution of human behavior should be based on research at least as rigorous as that used in studying nonhuman animals. And if you read the animal behavior journals, you'll see that this requirement sets the bar pretty high, so that many assertions about evolutionary psychology sink without a trace.

Jerry Coyne
Why Evolution Is True

I once made the remark that two things disappeared in 1990: one was communism, the other was biochemistry and that only one of them should be allowed to come back.

Sydney Brenner
TIBS Dec. 2000

It is naïve to think that if a species' environment changes the species must adapt or else become extinct.... Just as a changed environment need not set in motion selection for new adaptations, new adaptations may evolve in an unchanging environment if new mutations arise that are superior to any pre-existing variations

Douglas Futuyma

One of the most frightening things in the Western world, and in this country in particular, is the number of people who believe in things that are scientifically false. If someone tells me that the earth is less than 10,000 years old, in my opinion he should see a psychiatrist.

Francis Crick

There will be no difficulty in computers being adapted to biology. There will be luddites. But they will be buried.

Sydney Brenner

An atheist before Darwin could have said, following Hume: 'I have no explanation for complex biological design. All I know is that God isn't a good explanation, so we must wait and hope that somebody comes up with a better one.' I can't help feeling that such a position, though logically sound, would have left one feeling pretty unsatisfied, and that although atheism might have been logically tenable before Darwin, Darwin made it possible to be an intellectually fulfilled atheist

Richard Dawkins

Another curious aspect of the theory of evolution is that everybody thinks he understand it. I mean philosophers, social scientists, and so on. While in fact very few people understand it, actually as it stands, even as it stood when Darwin expressed it, and even less as we now may be able to understand it in biology.

Jacques Monod

The false view of evolution as a process of global optimizing has been applied literally by engineers who, taken in by a mistaken metaphor, have attempted to find globally optimal solutions to design problems by writing programs that model evolution by natural selection.

Richard Lewontin

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