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Wednesday, July 18, 2007

Dead Soldier's Mother Asks Us to Support Troops

 
Here's one of those difficult situations that can cause much confusion. The Toronto Star recently reported on the funeral of a soldier killed in Afghanistan [Support troops, dead soldier's mother asks Canadians]. Here's what was printed in the newspaper.
The mother of a soldier recently killed in Afghanistan beseeched Canadians on the day of her son’s funeral to support the country’s troops in Afghanistan.

Shortly before an honour guard piped the flag-draped coffin of Pte. Lane Watkins into an open field today, his mother Wanda read a family statement that suggested people should be extremely proud of the military’s efforts in a country that desperately needs Canada’s help.

"We don’t want any family to experience the terrible pain of losing their son or daughter, but if Canada and NATO abandon the Afghan people, the sacrifices Lane, our family and others have made will be for nothing," Watkins said.

"They deserve your respect. In supporting them, you’ll make our loss much easier to bear."
It's statements like this that make supporting our troops more difficult [What Does the "Support Our Troops" Ribbon mean to You?]. While we can all understand Wanda Watkins' grief, she conflates supporting our soldiers with supporting the mission. Since this is a common mistake, it means that any overt support for our soldiers—such as putting a yellow ribbon on your car—will usually be interpreted as support for Canada's role in Afghanistan.

I do not support the mission in Afghanistan and I urge the Canadian government to withdraw as soon as possible. Does this mean that I don't support individual soldiers who are carrying out the role assigned to them to the best of their ability? No it doesn't. They're are doing exactly what they are supposed to be doing and they deserve our respect and support because it's a dangerous job. As a matter of fact, they deserve even more support, and sympathy, because they're involved in a messy situation that they don't necessarily agree with.

Ms. Watkins wants us to stay in Afghanistan because otherwise her son will have died in vain. Unfortunately there's no way to avoid the obvious. If we eventually recognize that it is a mistake to be in Afghanistan then we will not have achieved "victory" and it will be difficult to justify the sacrifice of her son and the dozens of others who have died. To be blunt, they will have died in vain because we made a mistake by sending them into a dangerous situation where victory wasn't possible.

We cannot let such passionate appeals dissuade us from withdrawing if that's the best course of action. What would be the point of staying in Afghanistan if more lives will be lost for no gain? How many have to die in vain before we call it quits?

[The image is from The Royal Canadian Regiment Kit Shop]

Nobel Laureates: Francis Crick, James Watson, and Maurice Wilkins

 
 
The Nobel Prize in Physiology or Medicine 1962.
"for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material"

Francis Harry Compton Crick (1916 - 2004), James Dewey Watson (1928 - ) and Maurice Hugh Frederick Wilkins (1916 - 2004) received the Nobel Prize in Physiology or Medicine for discovering the structure of DNA. This is one of the most notable and most deserving Nobel Prizes that has ever been awarded for a single discovery.

The presentation speech was delivered by Professor A. Engström of the Royal Caroline Institute.
Your Majesties, Your Royal Highnesses, Distinguished Audience.

An attempt to explain the significance of the discovery which has led to this year's Nobel Prize award in Physiology or Medicine could begin at a point which seems to be far from the precise world of biophysics and biochemistry. We could ask the question: «How do we define a fine portrait or a good caricature?»

A caricature is a drawing - or sometimes a sculpture, a piece of prose or poetry - in which the individual characteristics of the person being portrayed are emphasized. This something, strongly individual, could be a strange contour of the nose, a wild hair or a protruding chin. We all know, that we are very sensitive about the accuracy of the caricature. It must have qualities beyond those of a true picture. If the artist succeeds in producing the individual's specific variations of a common feature, the caricature becomes exciting and full of life, it is genuine. Thus, the artist must fuse the common general with the individual specific features.

When the scientist tries to disclose the physical and chemical characteristics of living matter in order to understand and to explain the great variety of living forms, he must always bear in mind this combination of generality and individuality. He can distinguish a number of general properties which are common to all living forms, for example the ability to extract nutrition from the environment and to multiply so that the offspring is given a life pattern similar to that of the parents. Thus he sees an extreme regularity. Further, when the scientist studies the physical and chemical characteristics of the organism or of its cells he discerns new signs of strict organization and internal order. But he cannot neglect noticing that each individual in one or more respects differs from other individuals of the same species. Within the framework of strong order there must be space for individual irregularities.

The discovery of the three-dimensional molecular structure of the deoxyribonucleic acid - DNA - is of great importance because it outlines the possibilities for an understanding in its finest details of the molecular configuration, which dictates the general and individual properties of living matter. DNA is the substance which is the carrier of heredity in higher organisms.

Deoxyribonucleic acid is a high polymer composed of a few types of building blocks, which occur in large numbers. These building blocks are a sugar, a phosphate, and nitrogen-containing chemical bases. The same sugar and the same phosphate are repeated throughout the giant molecule, but with minor exceptions there are four types of nitrogenous bases. It is for the discovery of how these building blocks are coupled together in three dimensions that this year's Nobel Prize in Physiology or Medicine has been awarded to James Dewey Watson, Maurice Hugh Frederick Wilkins, and Francis Harry Compton Crick.

Wilkins investigated deoxyribonucleic acid of various biological origins by X-ray crystallographic techniques. Such techniques are the most powerful tools which can be used to investigate the molecular structure of matter. Wilkins' X-ray crystallographic recordings indicated that the very long molecular chains of deoxyribonucleic acid were arranged in the form of a double helix. Watson and Crick showed that the organic bases were paired in a specific manner in the two intertwined helices and showed the importance of this arrangement.

The deoxyribonucleic acid molecule can also be looked upon as two interwoven spiral staircases, forming one staircase. The outside of this staircase consists of the phosphate and sugar molecules. The steps are formed by the paired bases. If it were possible to stain each base separately, that is each half-step, and if it were also possible for a person to climb this staircase, this person would get an impression of a tremendous variety. Soon he would discover, however, that red always was coupled to blue, and black to white. Also, he would notice that the steps sometimes had black to the right, and white to the left, or the reverse, and that the same variation was true also for the red-blue steps. The climber, who in molecules of human deoxyribonucleic acid had to ascend millions of steps, would see an endless variation in the sequence of red-blue, blue-red, black-white, and white-black steps. He would ask, what is the meaning of this, and he would realize that the staircase contained a kind of message, the genetic code.

Deoxyribonucleic acid is no staircase in which one can climb; it is a very active biological substance. It has been shown that a number of the steps - most likely three - via another nucleic acid, ribonucleic acid, regulates which amino acids shall be coupled into a protein chain during its synthesis. Thus the order of amino acids in a protein is fundamentally determined by a certain sequence of bases in the nucleic acid. Thus the nucleic acid controls the production of the highly specific proteins, which are the specialized workers of the organism. All the various types of proteins produced take part in a team-work which is subordinated to the needs of the whole organism. Certain characteristics of this team-work, certain specific features in some of the proteins, make the individual unique.

The code contained in the deoxyribonucleic acid is transferred in cell division, that is in the normal growth of the organism, and also in the fusion of the sexual cells. In this way the code of the deoxyribonucleic acid can start and control the development of a new individual which has striking similarities with its parents.

Today no one can really ascertain the consequences of this new exact knowledge of the mechanisms of heredity. We can foresee new possibilities to conquer disease and to gain better knowledge of the interaction of heredity and environment and a greater understanding for the mechanisms of the origin of life. In whatever direction we look we see new vistas. We can, through the discovery by Crick, Watson and Wilkins, to quote John Kendrew, see «the first glimpses of a new world».

Dr. Francis Crick, Dr. James Watson, and Dr. Maurice Wilkins. Your discovery of the molecular structure of the deoxyribonucleic acid, the substance carrying the heredity, is of utmost importance for our understanding of one of the most vital biological processes. Practically all the scientific disciplines in the life sciences have felt the great impact of your discovery. The formulation of double helical structure of the deoxyribonucleic acid with the specific pairing of the organic bases, opens the most spectacular possibilities for the unravelling of the details of the control and transfer of genetic information.

It is my humble duty to convey to you the warm congratulations of the Royal Caroline Institute and to ask you to receive this year's Nobel Prize for Physiology or Medicine from the hands of His Majesty the King.

Tuesday, July 17, 2007

Nucleotides Can Adopt Many Different Conformations

 
Individual nucleotides in solution can adopt many different conformations. For example, the deoxyribose sugars can bend and twist in many different ways. Two of the most stable conformations are shown on the left. They are the conformations found in some DNA structures.

The C-2′ endo conformation (top) allows the maximum separation between the oxygen atoms at the 5′ and 3′ positions. What this means is that any polynucleotide strand with sugars in this conformation will be extended. On the other hand, strands and helices with sugars in the C-3′ endo conformation will be much more compact with tighter helices.

If you look at all of the bonds that make up the sugar-phosphate backbone of a polynucleotide strand you will see that there are a lot of possible conformations. You can have free rotations around many of these bonds. Now, as it turns out, the structure of double-stranded DNA has a well-defined conformation where many of these bond angles are fixed but if you were handed two strands of DNA you would be hard pressed to bend them into the proper conformation of real DNA.

This is one of the reasons why it was so hard to predict the structure of DNA even though the chemical structure of the polynucleotides was known.

In addition to sugar puckers and bond rotations around the backbone, there are also many conformations of the base relative to the sugar. The two extreme conformations involve rotation around the β-N- glycosidic bond shown in green in the figures below. In the anti- conformation (left) the base is rotated so that it is as far from the sugar as possible. This is the most stable conformation and it's found in most DNAs. In the syn conformation (right) the base is rotated so that it's over the sugar leading to a much more compact structure.

When the structure of double-stranded DNA was being worked out, the conformations of the nucleotides were not known. It wasn't even obvious that the more stable anti conformation of free nucleotides would necessarily be the conformation in DNA. You can see that attempts to build a model of DNA without lots of additional information were doomed to failure. Several people tried and failed, including the greatest chemist of the day Linus Pauling.

©Laurence A. Moran 2007
[Figures are from Moran/Scrimgeour et al. Biochemistry 2nd ed. (1994) ©Neil Patterson Publishers/Prentice Hall.]

The Calvin Cycle: Regeneration

 
Nobody took me up on the offer to become an intelligent designer. The goal was to figure out a way of converting the five products of the Rubisco reaction into three new substrate molecules [The Calvin Cycle]. The five products are three carbon (3C) compounds and the three new substrate molecules are five carbon (5C) compounds. Here's how it's done ...

Two 3C molecules are joined to make one six carbon (6C) compound (fructose). Then two of the carbon atoms from fructose are transferred to another 3C molecule to make the first of the five carbon products (red, ribulose). This leaves a 4C molecule that is joined to another one of the 3C molecules to produce a seven carbon (7C) sugar called sedoheptulose. Two carbon are transferred from sedoheptulose to the last 3C molecule to produce a second 5C molecule. This leaves the third and last 5C molecule.

Of course there's a lot of fiddling in the pathway to get the molecules into the right form for these reactions. Here's the complete Calvin Cycle in all its glory. Click on it to see a bigger picture.



You can simplify the pathway a great deal by writing it like this ...

This shows you that, in spite of the complexity, the overall pathway takes three molecules of carbon dioxide and converts it to one molecule of glyceraldehyde 3-phosphate. That's the purpose of the Calvin Cycle, it fixes carbon.

The pathway is expensive. It uses two types of energy currency, ATP and NADPH, but these are produced in abundance by photosynthesis. It's a fair bet that this particular reaction is the ultimate source of 99% of the carbon atoms in your food.

There's a neat trick we can do with this reaction. We can use it to estimate the cost of synthesizing acetyl CoA—the substrate for the citric acid cycle and the product of the pyruvate dehydrogenase reaction. The pathway from glyceraldehyde 3- phosphate to acetyl CoA is coupled to the synthesis of two molecules of NADH and two molecules of ATP. If we subtract these from the cost of making glyceraldehyde 3-phosphate then the total cost of synthesizing acetyl CoA from CO2 is 7 ATP + 4 NAD(P)H. This can be expressed as 17 ATP equivalents since each NADH is equivalent to 2.5 ATP.

Since the net gain from complete oxidation of acetyl CoA by the citric acid cycle is 10 ATP equivalents, the biosynthesis pathway is more expensive than the energy gained from catabolism. In this case, the "efficiency" of acetyl CoA oxidation is only about 60% (10/17 = 59%) but this value is misleading since it is actually the biosynthesis pathway (costing 17 ATP equivalents) that is complex and inefficient.

Tautomers of Adenine, Cytosine, Guanine, and Thymine

 
The four bases of DNA can exist in at least two tautomeric forms as shown below. Adenine and cytosine (which are cyclic amidines) can exist in either
amino or imino forms, and guanine, thymine, and uracil (which are cyclic amides) can exist in either lactam (keto) or lactim (enol) forms. The tautomeric forms of each base exist in equilibrium but the amino and lactam tautomers are more stable and therefore predominate under the conditions found inside most cells. The rings remain unsaturated and planar in each tautomer.


Fifty years ago it wasn't clear whether the amino or imino forms of the purines were stable under physiological conditions. (Or the lactam lactim forms.) As we will see, this uncertainty played a significant role in events leading up to the discovery of the structure of DNA.

We now know that all of the bases in the common nucleotides can participate in hydrogen bonding. The amino groups of adenine and cytosine are hydrogen donors, and the ring nitrogen atoms (N-1 in adenine and N-3 in cytosine) are hydrogen acceptors (see below). Cytosine also has a hydrogen acceptor group at C-2. Guanine, cytosine, and thymine can form three hydrogen bonds. In guanine, the group at C-6 is a hydrogen acceptor, and N-1 and the amino group at C-2 are hydrogen donors. In thymine, the groups at C-4 and C-2 are hydrogen acceptors, and N-3 is a hydrogen donor. (Only two of these sites, C-4 and N–3, are used to form base pairs in DNA.) The hydrogen-bonding patterns of bases have important consequences for the three-dimensional structure of nucleic acids.



©Laurence A. Moran and Pearson/Prentice Hall 2007

DNA Is a Polynucleotide

 
DNA is composed of nucleotides strung together to make a long chain called a polynucleotide. There are four basic nucleotides in DNA. They are; deoxyadenylate (A), deoxyguanylate (G), deoxycytidylate (C), and deoxythymidylate (thymidylate) (T).


There are a few things you need to know about the nucleotides in order to properly understand the structure of double-stranded DNA.

First, a nucleotide is composed of a base (adenine, guanine, cytosine, thymine) attached to a sugar (deoxyribose) to form a nucleoside. The nucleoside has an attached phosphate group and that makes it a nucleotide. The name of the nucleoside containing the base adenine is deoxyadenosine and if the phosphate group is attached at the carbon numbered 5′ (five prime) then the formal name of the nucleotide is 2′deoxyadenosine 5′-monophosphate (dAMP).

Those little numbers are important. The phosphate group can also be attached to the 3′ carbon to make another kind of nucleotide called 2′-deoxyadenosine 3′-monophosphate.

Normally the carbon atoms of the sugar are numbered 1, 2, 3 etc. but in a nucleoside the numbering of the nitrogen and carbon atoms of the base takes precedence. Thus, the sugar carbon atoms are numbered 1′, 2′ 3′ etc as shown on the left.

If you want to follow the discussion about DNA you have to take a bit of time right now and get familiar with the numbering of the sugar carbon atoms. Note that there's no attached hydroxyl group on the 2′ carbon atom. That's why this is 2′-deoxyribose.

You can string together a bunch of nucleotides to make single-stranded DNA. Inside the cell it's the job of DNA polymerase to make polynucletides from nucleotides. The structure of a typical polynucleotide (right) shows that the individual units are attached through their phosphate groups. The phosphate group on one 5′ carbon atom is attached to the 3′ carbon atom of the nucleotide above it.

This gives rise to the characteristic sugar-phosphate backbone of DNA. This linkage is called a 3′-5&prime (three prime, five prime) phosphodiester linkage. The bases are not involved in the covalent linkages between nucleotides.

This single-stranded polynucleotide chain has a free 5′ end at the top and a free 3′ end at the bottom and that's going to be true for all single-stranded chains. We're often interested in describing the directionality of this chain because it's important in synthesis and in degradation by nucleases. For example, the chain is synthesized in the 5′→3′ (five prime to 3 prime) direction. Which means that incoming nucleotides are added to the bottom of the chain during elongation.

By convention, the directionality is determined by reading across an individual nucleotide residue. In practice this means reading across a single deoxyribose sugar. Thus, reading from the top to the bottom of the strand shown above you cross the sugar carbons in the order 5′, 4′ and 3′. The direction is 5′→3′ (five prime to three prime). If you're talking about the direction from bottom to top then you read across the sugar in the order 3′, 4′, and 5&prime and the direction is 3′→5′ (three prime to five prime).

Are You a Non-Conformist?

 
You Are 79% Non Conformist

You are a pretty serious non conformist. You live a life hardly anyone understands.
And while some may call you a freak, you're happy with who you are.


[Hat Tip: Mike, of course. It's scary to note that I'm slightly more of a non-conformist than he is.]

Monday, July 16, 2007

The Oldest Organisms on Earth

 
Today's Botany Photo of the Day is Pinus longaeva, bristlecone pine. Trees of this species are generally considered to be "the longest-lived of all sexually reproducing, nonclonal species." Many of them are over 4000 years old including this one, from Wheeler Peak in Nevada.

It is located in the same area as the oldest known tree, the 4,862 year old tree formerly known as "Prometheus" before it was cut down [The Martyred One].

If the world was created in 4004 B.C. then the deluge can be reliably dated to about 2450 B.C., which means that Prometheus was living for 400 years before the flood and must have survived it. Isn't that amazing?

The Calvin Cycle

Are You an Intelligent Designer?

The Rubisco reaction results in fixation of carbon dioxide and the production of two molecules of glyceraldehyde 3-phosphate each of which contains three caron atoms [Fixing Carbon: the Rubisco Reaction]. The starting substrate is ribulose 1,5- bisphosphate, a 5-carbon sugar derivative [Monday's Molecule #34]. Here's a schematic diagram of the reaction showing the carbon skeletons with the newly incorporated carbon atom in blue.
In order for this to become a cycle you have to regenerate the original substrate—a five-carbon compound. And in order for it to be a biosynthesis pathway you have to have net synthesis of one of the products. It was the working out of this stoichiometry that got Melvin Calvin the Nobel Prize in 1961 [Nobel Laureate: Melvin Calvin]. Do you think you can figure out the strategy for regenerating the five-carbon substrate? Here are the rules.
  1. You start with three cycles of the Rubisco reaction, using up three 5C molecules and producing six 3C molecules. One of the 3C molecules enters the normal metabolic pathways and the other five are used to regenerate three 5C molecules (5 x 3C = 3 x 5C).
  2. You can fuse molecules to create larger ones (e.g., 3C + 3C = 6C).
  3. You can cleave large molecules to create smaller ones (e.g. 6C = 3C + 3C) as long as there are no intermediates with only one carbon (1C) or two carbons (2C).
  4. You can swap 2C units between molecules provided that no products are 1C or 2C (e.g, 7C + 3C = 5C + 5C is allowed).
  5. You can swap 3C units between molecules provided that no products are 1C or 2C (e.g, 7C + 3C = 4C + 6C is allowed).
Here's an outline of the Calvin Cycle. Your task, should you choose to accept it, is to design the regeneration pathway beginning with five molecules of glyceraldehyde 3-phosphate (5 x 3C) and ending with three molecules of ribulose 1,5- bisphosphate (3 x 5C). You just need to account for the carbon shuffling reactions.

Monday's Molecule #35

 
This is a very common chemical found in most biochemistry labs. There's a very familiar form of this molecule and most of you will know it by the name of the salt. You need to supply the correct IUPAC name in order to win the prize.

There's an extremely obvious, but indirect, connection between this Monday's Molecule and Wednesday's Nobel Laureate(s).

The reward (free lunch) goes to the person who correctly identifies the molecule and the Nobel Laureate(s). Previous free lunch winners are ineligible for one month from the time they first collected the prize. There are no ineligible candidates for this Wednesday's reward since many recent winners haven't collected their prize. The prize is a free lunch at the Faculty Club.

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Casy Luskin Gets it Wrong (Again)

 
This is getting to be really annoying. What is it about the concepts of junk DNA and Darwinism that confuse the IDiots? It's not rocket science.

In today's posting on the Discovery Institute anti-science website, Casey Luskin leads off an anti-evolution posting with,
It’s beyond dispute that the false “junk”-DNA mindset was born, bred, and sustained long beyond its reasonable lifetime by the neo-Darwinian paradigm.
Let me try and make this simple for the IDiots.
  1. Junk DNA is here to stay. It's a lie to claim that the concept has been abandoned by scientists. True, there are some stupid scientists who don't understand what's going on but they do not represent the consensus.

  2. The concept of junk DNA is anti-Darwinian. There's no possible way that a true Darwinist could accept junk DNA. It is incredibly ignorant to claim that the idea of junk DNA was "born, bred, and sustained" by the neo-Darwinian paradigm. On the contrary, it has helped overturn that paradigm, replacing it with a more pluralistic approach to evolution.
It goes without saying that Intelligent Design Creationists think they have a better "paradigm" than real scientists. Luskin is amazed by recent discoveries that some heritable diseases are caused by mutations in regulatory sequences, which he, in his ignorance, thinks are equivalent to junk DNA.
How much earlier might these non-coding “junk” DNA causes of disease have been recognized had scientists operated under an intelligent design paradigm rather than a Neo-Darwinian one?
Me, me, me (pumping his hand in the air). I know the answer ...

Poufs of Art

 
Leslie (Mrs. Sandwalk) has a friend, Carmi, who lives in a small town north of Toronto.* She makes these wonderful things called poufs of art. Here's the description from her Etsy site [Carmi's Art].
Cushion is "pouf" in French.

These are tiny "poufs of art" that I create to celebrate my love of vintage imagery, fabric, beads, embellishments, sewing and quotes. Together, I use all these items to create one-of-a-kind keepsakes. They are handmade by me and no two will ever be alike.

I think these are perfect gifts to commemorate a special birthday, achievement or life event. No doubt, you will think of someone in particular when you read the quotes. They can be displayed on a picture stand, hung from a hook or light fixture or simply displayed in a box.

They are each approximately 2½ X 2 ½ inches wide. I will ship them in very pretty wrapping in a bubble wrap envelope.
Leslie has just ordered a bunch of them. Here's my favorite, I hope she bought it for me ...


Carmi also has a couple of blogs. Carmi's Art/Life World is about her life as an artist [see poufs to go] and My Napoleon Obsession is about Napoleon Bonaparte [Big Head's Crib].

* Kleinburg, for those of you who know the area.

Sunday, July 15, 2007

A Strange Molecule

 
Last Wednesday an image of strange base pair was published on Discovering Biology in a Digital World [Puzzle]. We were asked to figure out what was so strange about his base pair (see below). I got part of the answer but not the complete answer.



The answer has already been posted but I won't link to it just yet in order to give you a chance to figure it out. Please don't comment if you've already seen the answer.

Here's another view that promises to be a lot more helpful.

Gene Genie #11

 
The 11th edition of Gene Genie has been published at Med Journal Watch [Gene Genie #11].

Get on over there to find out where this photograph comes from.

Saturday, July 14, 2007