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Tuesday, June 10, 2008

Come to This Seminar!

 
Alex Palazzo of The Daily Transcript is giving a talk in our Department ....

Department of Biochemistry Special Seminar

"Beyond The Signal Sequence Hypothesis: Nuclear Export and Endoplasmic
Reticulum Targeting of mRNAs."


Dr. Alexander Palazzo Ph.D.
Department of Cell Biology
Harvard Medical School

Thursday, June 12th

Room 4171 MSB
11:00 a.m.

Dr. Palazzo is a candidate for a Faculty position in the Department
of Biochemistry.


Contact me by email if you want to meet Alex for lunch tomorrow.


One Million!!!

 
I'm fascinated by the statistics of blogging. Who reads blogs? Why do they read blogs? Do blogs serve a useful purpose or are they just for fun? What's the future of blogging?

Part of the fascination is looking at the data to see which postings attract the most attention and how many people regularly check in each day. Are some blogs better than others? Are some blogs more popular? Why?1

A few minutes ago somebody logged on to Sandwalk to view a page and registered the one millionth page view since this blog began collecting data. That's pretty interesting. It means that Sandwalk is an average science blog in terms of popularity, far behind the best ones that have one million views per month.



One of the interesting things about science blogging is that there's a 25% dropoff in readers during the months of May, June, July, and August. (Other bloggers see this too.) I assume this is mostly students who don't read blogs during the summer. Is it because they only have high speed internet access when they're at school or is it because they're not interested in blogs during the summer?


1. I wonder if there's a direct correlation between the number of readers and the number of postings per day? Some blogs put up lots of articles every day even though many of those articles don't take much effort. Does this build readership so that when you post something important it's more likely to get attention? That doesn't work for me as a reader. There are quite a few excellent blogs that I scan every day even though the postings are infrequent. On the other hand, when I've tried posting several times a day over a period of a few weeks, the number of visits does increase significantly.

Monday, June 09, 2008

Monday's Molecule #75

 
Some readers have been complaining that Monday's Molecule is too easy.1 That's why I've chosen a more difficult task for you today.

You have to examine the structure and figure out what's going on. The molecule you have to identify isn't even shown in the figure—only small fragments are depicted. You need to identify the invisible molecule and explain why this figure is so important. Its importance is mostly historical. The elucidation of what's happening is a defining moment in biochemistry and helped open up a whole new field of study.

There's a direct connection between today's molecule and a Nobel Prize. The prize was awarded for discovering exactly what the figure depicts. The first person to correctly identify the molecule, describe what the figure shows, and name the Nobel Laureate(s), wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first collected the prize. There are three ineligible candidates for this week's reward.

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 Laureate(s) so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box. [Hint: A co-recipient of this week's Nobel Laureates is already on the list.]

Correct responses will be posted tomorrow. I may select multiple winners if several people get it right. (Like that's going to happen this week!)

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

UPDATE: Turns out it wasn't as difficult as I thought. The winning answer arrived within one hour, followed shortly by several other correct answers. The image shows a small piece of RNA about to be cleaved in the active site of Ribonuclease A. The key residues are His12, His119, and Lys 41 and their interactions with the substrate are shown. Note how they form weak interactions with the phosphodiester linkage. This causes destabilization of the bonds in preparation for cleavage. The Nobel Laureates are Stanford Moore and William Stein who received the Nobel Prize in 1972 for working out the mechanism of Ribonuclease A. This was the first detailed demonstration of how enzymes worked at the molecular level.

The winner is Michael Clarkson. Congratulations Michael.


1. Okay, maybe not "some" readers. Maybe it's only one reader. In fact, maybe I'm the reader.

Gene Genie #33

 
The 33rd edition of Gene Genie has been posted at Neurophilosophy [Gene Genie 33].
Welcome to the 33rd edition of Gene Genie, the blog carnival devoted to genes and genetic diseases.

In this edition, there is a strong emphasis on cancer. There's also a focus on leukodystrophy, and a special section on personalized genetics.
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 .....
  1. Scienceroll
  2. Sciencesque
  3. Genetics and Health
  4. Sandwalk
  5. Neurophilosophy
  6. Scienceroll
  7. Gene Sherpa
  8. Eye on DNA
  9. DNA Direct Talk
  10. Genomicron
  11. Med Journal Watch
  12. My Biotech Life
  13. The Genetic Genealogist
  14. MicrobiologyBytes
  15. Cancer Genetics
  16. Neurophilosophy
  17. The Gene Sherpa
  18. Eye on DNA
  19. Scienceroll
  20. Bitesize Bio
  21. BabyLab
  22. Sandwalk
  23. Scienceroll
  24. biomarker-driven mental health 2.0
  25. The Gene Sherpa
  26. Sciencebase
  27. DNA Direct Talk
  28. Greg Laden’s Blog
  29. My Biotech Life
  30. Gene Expression
  31. Adaptive Complexity
  32. Highlight Health
  33. Neurophilosophy



Sunday, June 08, 2008

America: The Greatest Experiment in the History of Mankind

 
Here's one of the men who could be "leader of the free world." There's no doubt in his mind that Christianity is the superior religion. I wonder if the other candidate thinks differently?



BTW, how's that experiment working out?

See Jim Lippard's comment at McCain thinks the Constitution establishes a Christian nation. I don't think Jim is going to vote for this man!


[Hat Tip: Canadian Cynic]

Saturday, June 07, 2008

 
Stephen Jay Gould is one of my heroes. This video in six parts was made back in 1984 but most of it is as true and accurate today as it was back then. Thanks to Laelaps for finding it on YouTube.















How to Activate Your Junk DNA!

 
I suppose it was inevitable. Sooner or later a private company would figure out how to activate your junk DNA and turn you into a super being. At a price, of course.

A company called Mastery Life A.C. and/or DNA Perfection has learned the trick [Unleash Your Genetic Potential NOW!]. What you need to do is establish a mental connection to someone named Toby Alexander—this is done by mental telepathy. Your brainwave frequency will "entrain" to his and that's all it takes. Naturally it takes more than one session to achieve the best results. Four at least. The cost is $100 per session for a total minimum cost of only $400. (You can use PayPal.)

How does it work? Well, I must confess that the biology is too complicated for me so let me just quote from the website.
Most people know that DNA is the 'blueprint of life' and is located in every cell of the body. In addition to each chromosome's 2 strand double helix of DNA, there are an additional 10 etheric strands of DNA available to each human, which have been dormant since the beginning of recorded history. Each additional strand possesses attributes that permit the individual to perform greater human accomplishments. Scientists acknowledge that we currently only use 3% of our current 2 strand DNA. Thus we live in a society where people are sick, unhappy, stressed out, create wars, have difficulty experiencing love, and are totally disconnected with the universe. Most people have to meditate for many years just to have a so-called 'mystical' experience, that's how disconnected we are now. Imagine activating 100% of your 2 strand DNA, PLUS 10 additional strands! You will go from using 10% of your brain to becoming a multi-dimensional being with psychic, telepathic, and manifestation abilities beyond anything you've ever dreamed of. Plus, you will stop the aging process and actually start to rejuvenate to look and feel YOUNGER. This is the Original Divine Blueprint, what man USED to be. It has been written that Jesus had 12 strands of DNA activated. There have been children born throughout the history of humanity to raise the frequency of the planet that have more than 2 strands of DNA active - they are known as Indigo children. These are the incredibly intelligent, loving, and amazing children that are being mistakenly diagnosed as having A.D.D. because they are too smart to pay attention in class. Your DNA is your blueprint of life and is what controls every single function inside each of your cells. If you change your DNA, you really will change your life.
I strongly believe that George Hull David Hannum, in his famous comment to P.T. Barnum, grossly underestimated the number of suckers born every minute.


[Hat Tip: New Scientist, Feedback, My 17-23, 2008 p. 64]

Friday, June 06, 2008

D-Day

 
Today marks the 64th anniversary of the invasion of Normandy on June 6, 1944. British, Canadian and American forces opened the second front against Germany. On the eve of the invasion, General Dwight D. Eisenhower issued the following Order of the Day.

Soldiers, Sailors and Airmen of the Allied Expeditionary Force!

You are about to embark upon the Great Crusade, toward which we have striven these many months. The eyes of liberty loving people everywhere march with you. In company with our brave Allies and brothers in arms on other Fronts, you will bring about the destruction of the German war machine, the elimination of Nazi tyranny over the oppressed peoples of Europe, and security for ourselves in a free world.

Your task will not be an easy one. Your enemy is well trained, well equipped and battle hardened. He will fight savagely.

But this is the year 1944! Much has happened since the Nazi triumphs of 1940-41. The United Nations have inflicted upon the Germans great defeats, in open battle, man to man. Our air offensive has seriously reduced their strength in the air and their capacity to wage war on the ground. Our Home Fronts have given us an overwhelming superiority in weapons and munitions of war, and placed at our disposal great reserves of trained fighting men. The tide has turned! The free men of the world are marching together to Victory!

I have full confidence in your courage and devotion to duty and skill in battle. We will accept nothing less than full Victory! Good luck! And let us beseech the blessing of Almighty God upon this great and noble undertaking.

For baby boomers it means a day of special significance for our parents. In my case, it was my father who took part in the invasions. He was an RAF pilot flying rocket firing typhoons in close support of the ground troops. During the initial days his missions were limited to quick strikes and reconnaissance since Normandy was at the limit of their range from southern England. During the second week of the invasion his squadron landed in Normandy and things became very hectic from then on with several close support missions every day.

The photograph above shows a crew loading rockets onto a typhoon based just a few kilometers from the landing beaches in Normandy. Here's an example of the effectiveness of rocket-firing typhoons [Air Power Over the Normandy Beaches and Beyond].

Intelligence information from ULTRA set up a particularly effective air strike on June 10. German message traffic had given away the location of the headquarters of Panzergruppe West on June 9, and the next evening a mixed force of forty rocket-armed Typhoons and sixty-one Mitchells from 2 TAF struck at the headquarters, located in the Chateau of La Caine, killing the unit's chief of staff and many of its personnel and destroying fully 75 percent of its communications equipment as well as numerous vehicles. At a most critical point in the Normandy battle, then, the Panzer group, which served as a vital nexus between operating armored forces, was knocked out of the command, control, and communications loop; indeed, it had to return to Paris to be reconstituted before resuming its duties a month later.






A Little Learning Is a Dangerous Thing

 
A little learning is a dangerous thing; drink deep, or taste not the Pierian spring: there shallow draughts intoxicate the brain, and drinking largely sobers us again.

Alexander Pope
An Essay on Criticism, 1709
Philip G. Altbach is Monan professor of higher education and director of the Center for International Higher Education at Boston College (USA). He has just published an article on Open Access in THE (Times Higher Education) [Hidden cost of open access].

Professor Altbach complains that the problem with Open Access is the absence of peer review.
Profit, competition and excess have spawned the open-access movement. Academics, librarians and administrators think it is the answer to monopolistic journals. But there are several problems with it. Chief among them is that peer review is eliminated - all knowledge becomes equal. There is no quality control on the internet, and a Wikipedia article has the same value as an essay by a distinguished researcher....

Essentially, open access means there is no objective way of measuring research quality. If the traditional journals and their peer-review systems are no longer operating, anarchy rules. Researchers will have no accurate way of assessing quality in a scholarly publication.
This is dead wrong, of course, and the comments on the website make it very clear that Professor Altbach has goofed.

I like this comment ...
Ah, sweet irony. If this article had undergone "peer review", or some other accuracy or quality checking critera, then it would never had seen the light of day...
Bora Zivkovic at A Blog Around the Clock is all over it 'cause he's the Online Community Manager at PLoS-ONE (Public Library of Science) [A really, truly bad article about Open Access]. The question is ... why would a Professor of higher education at Boston University write an article about Open Access without doing a little bit of investigation to find out about it?


Blacks Have Rhythm, Asians Aren't Creative, Whites Rule the World

 
Friday's Urban Legends

From time to time on Friday morning I post some examples of urban myths/legends. Today I've copied a comment from an old thread on Race and Intelligence. Someone named E.A. posted this comment two days ago and I thought it might be fun to pick out all the factual and logical errors in his/her comment. (Hint: there are more than three.) Most of them are due to bigotry of some sort or another, coupled to an excessive dose of political correctness. (E.A. provided a link to the blog True Newspaper).

It's appropriate to examine these false ideas today since this is an historic week in the USA. American Democrats have just nominated their first black man for President and no doubt there will be much discussion about race over the next six months.

First,
Jewish people are the most intelligent. They win almost 40% of the Nobel Prize's and they have a small population of only 14 million. So by far they exceed the other races in intelligence. The other races having huge numbers and such small contributions.

Second,
IQ tests, test intellectual conformity, not creativity and originality. This would explain the Asian high IQ's. They as a people are the ultimate conformists.

In IQ tests there is typically only one answer to the problem. That problem being a social conformity to reason. But everyone knows that Genius's and all of the greatest developments in the world are not the product of conformity. Conformity never breeds creativity. We can see this in the lack of influence the Asian population has had on Science. China used to be called the "sick man" of Asia. Their population is massive and their contribution to innovation is almost nil. We can see this lack of originality in their adoptation of European philosophies, I.e. Communism.

Friedrich Nietzsche and other Philosophers have critized Asians. Nietsche used the words "Pallid osification" to describe Orientals.

Pallid: lacking sparkle or liveliness.

Osification: The process of becoming set and inflexible in behavior, attitudes, and actions. Inflexible conformity, rigid unthinking acceptance of social conventions.

The reality is Asian people have yet to understand that laws and rules are arbitrary. Europeans make the rules and Asian's follow them.

It also doesn't make sense that Asian's are considered smart because of the fact that they have destroyed their own countries. This is due to over-population and their basic lack of enviromental understanding.

It is also common scientific fact that women who have many children are ignorant, and those who have less children are more intelligent. This has already been proven in studies. So it seems strange to say that Asians are smart when the obviousness of their backwards countries, and medieval lifestyle makes them contrary to that premise.

Europeans have the most advanced civilizations and every other race has yet to meet these levels other than the Japanese. The Japanese only being good at copying other people's inventions and making them better. Other than that their original creativity is lacking as well. They took American cars and made them better. They took the German camera and made it better. And they took German steel and made it better. Otherwise the greatest advances still come from Europeans and Jews. Other than that the Orientals have yet to produce an Einstein or a Thomas Edison.

When it comes to Black people. It makes sense that they have low intellectual comformity, I.e. IQ tests. They are far too creative to be trapped in this unoriginal form of conditioning. You can tell their creative capacity in their athletics, music, dance, and the way they talk. They by far exceed the Asiatic races in these areas. Being better singers, musicians ect. Blacks far exceed Asians in emotive expression. In all of North America there is only one or two famous high-paid Asian actors.

Reality, Europeans rule the world and they have allowed others to exist only out of desire for economic bennifet. They, (Europeans) are also the physically strongest, winning the Strongest Man competitions again and again.

The greater the conformity, the weaker the race. Thus we see the races as they are today. The wild animal being bred out of man, and the physically impotent, conformist thriving.

Otherwise "Group psychology" is the most destructive thing in the world. All these stereotypes are false when it comes to the individual. Individualism is the most important thing for this time. All countries, Religions, groups need to dissolve for man to live in peace.



Thursday, June 05, 2008

Our Galaxy Loses Two Arms

 
This is what the Milky Way actually looks like as shown on the Astronomy Picture of the Day for October 20, 2007.

Most of us have rarely never seen it like this because we live in light polluted areas where most stars have become invisible. We are seeing our galaxy from one of the spiral arms looking toward the central cluster of stars. Much of the center is obscured by dust clouds.

The model below shows what the Milky Way galaxy was supposed to look like when I was growing up [from Astronomical Adventures]. It has four large spiral arms and a large central blob of stars. The model is based on our view of other spiral galaxies and on observations that were made from Earth-based telescopes.

Our solar system is located in the Cruz arm. Other models were similar although the names of the arms were different. The basic plan was a spiral with four large arms (Norma, Scutum-Centaurus, Sagittarius and Perseus) projecting outward from a dense circular mass of stars at the center of the galaxy.

This view has been substantially altered over the past few decades. Astronomers now recognize that the Milky Way is a bar galaxy whose central mass of stars forms a bar shape with arms trailing off the ends of the bar.

Typical bar galaxies have only two main arms and recent results indicate that our galaxy conforms to this pattern [Two Of The Milky Way's Spiral Arms Go Missing]. The most recent model is shown below. As you can see, two of the four major arms have now disappeared or have been greatly reduced in size and importance.

The galaxy looks very different from the one I learned about as a child. Does anyone know where our solar system is located on the new model?

UPDATE: I replaced the old image (below) with one from Astronomy Picture of the Day from June 6, 2008. It shows where we are in the galaxy.




Wednesday, June 04, 2008

Nobel Laureates: Edward Kendall, Tadeus Reichstein and Philip Hench

 

The Nobel Prize in Physiology or Medicine 1950.
"for their discoveries relating to the hormones of the adrenal cortex, their structure and biological effects"


Edward Calvin Kendall (1886 - 1972), Tadeus Reichstein (1897 - 1996) and Philip Showalter Hench (1896 - 1965) received the Nobel Prize in Physiology or Medicine for their discoveries of the nature and function of hormones secreted by the adrenal glands in mammals. Their work led to the characterization of the cortical hormones produced by the adrenal cortex. We now know that cortosol or hydrocortisone is the most active of these steroid hormones.

The long presentation speech was given by Professor G. Liljestrand, member of the Staff of Professors of the Royal Caroline Institute

THEME:
Nobel Laureates
Your Majesties, Royal Highnesses, Ladies and Gentlemen.

In the year 1563 the Italian anatomist, Eustachi, described how, at the upper poles of the kidneys in man, he had found two gland-like organs, which had been overlooked up to that time, but are now known as the adrenals. Somewhat later, central cavities filled with fluid were observed in them. Nothing was known about the function of these bodies for a long time, and, with the then limited development of the methods of experimental medicine, it was to be about three centuries before any clarity was reached. It marked no great advance when in 1716 the Bordeaux Academy of Science announced the prize subject: «What is the importance of the adrenals?» None of the papers sent in, which gave evidence rather of lively imagination than of scientific criticism, found favour in the eyes of the prizeawarding judge, the later so famous philosopher Montesquieu, who remarked: «Perhaps chance will at some time give us what all our efforts have not been able to achieve.»

As late as in 1854 the German anatomist, Kölliker, was able to claim in a review of the subject that although the function of the adrenals was still unknown, yet in certain respects great advances had been made. For instance, they had been found in various groups of animals - actually they are met with throughout the whole series of vertebrates - and their more detailed structure had been elucidated. Two quite different parts were now distinguished, an outer part, a fairly firm cortex, and an inner, softer medulla, which in man readily disintegrates and is then the source of the fluid which had been observed earlier. Kölliker classified the adrenal cortices as ductless glands, which we now call the endocrine organs, assuming some co-operation with the nervous system for the medulla.

But now at last the «chance» of which Montesquieu had spoken was to present itself; all that was needed was a research worker who could seize the opportunity when it did present itself and understand its implication. Thomas Addison, the English doctor, observed a rare disease with a fatal course, which was characterized chiefly by anemia, general weakness and fatigue, disturbances in the digestive apparatus, enfeebled heart activity and a peculiar dark pigmentation of the skin. He was able to show that this morbid picture made its appearance in persons the greater part of whose adrenals was destroyed. Addison's work, characterized by himself as «a first and feeble step» which «doubtless both the physiologist and anatomist will be inclined to welcome and regard with indulgence», was published in 1855 and constitutes one of the basic contributions to our knowledge of the internal secretion in general and to the part played by the adrenals in particular.

In its turn it led to comprehensive experiments on animals, from which it emerged that removal of the adrenals led to speedy death, the symptoms recalling those known from Addison's disease.

The next step in the course of development was that attempts were made to obtain from the adrenals that active substance whose absence might be assumed to lead to the grave symptoms referred to. In 1894 Oliver and Schäfer proved that the injection of a watery extract from the adrenals had extremely pronounced effects. Within a few years adrenaline had been produced from the extract, its composition had been ascertained, and its artificial production accomplished. The more detailed analysis showed effects of the same kind as those resulting on increased activity of the so-called sympathetic nervous system, which innervates internal organs such as the heart and vessels, the intestinal canal, etc. Since the adrenaline is produced by the medulla, there was thus a connection between this part and the nervous system, even though of a different nature from that apprehended by Kölliker. However, attempts to prevent by means of adrenaline the deficiency symptoms following on the removal of the adrenals failed completely. The explanation of this was given when Biedl and others showed that it is the cortex which is of vital importance, not the medulla. Thus the two parts are also different in respect of their functions in the body. It may be said that the medulla and cortex constitute independent bodies, which as a rule are combined in one organ.

Towards the end of the 1920's and the beginning of the 1930's, several American research groups announced that they had been successful in producing from the cortex a more or less pure extract, which when injected proved to prolong the life of animals from which the adrenals had been removed, and also had a favourable effect on patients suffering from Addison's disease. As long as efforts were confined chiefly to soaking out the active factor, or the cortin as it was called, with water, the results obtained were uneven and none too convincing. The demonstration of the fact that the active principle also passes into many organic solvents, such as alcohol, ether, benzene, etc., guided Swingle and Pfiffner to a method for producing the cortin, which yielded a product by means of which the experimental animals could easily be kept alive for months. With that the foundation was laid for further research, and it now seemed possible to produce the cortin in pure form and establish its nature.

The isolation of the cortin proved to be a difficult task, calling for the combined efforts of a number of research workers. Particularly important contributions were made in this field by Wintersteiner and Pfiffner, and also by Edward Kendall at the Mayo Clinic in Rochester, and Tadeus Reichstein in Basel, and their co-workers. As early as in 1934, Kendall and his group succeeded in preparing from cortex extract what was at first assumed to be pure cortin in crystalline form. They found that it contained carbon, hydrogen, and oxygen, and indicated its empirical formula. But that was only a beginning. There was as yet no reason to suspect that the cortin was not homogeneous; further experiments proved clearly, however, that it was not. In reality Kendall and his co-workers had produced a mixture of different substances closely related to one another, and their work represents the early steps in the crystallization of a whole series of cortin substances. Even within the immediately succeeding years the number found totalled about twenty, and at the present time nearly thirty are known. The task of distinguishing between these chemically very closely related substances has been associated with immense difficulties, as they are found in the cortex in extremely small quantities and readily form mixed crystals. At least six of the substances have proved to have a more or less active effect on animals whose adrenals have been removed. Half of these were first isolated by Reichstein, closely followed by Kendall, the latter coming in first in the race to find a fourth. Still one more was first produced by Reichstein by a semisynthetic method from a derivative of bile acid and thus being readily available, it has been a valuable remedy in cases of Addison's disease and certain other cases of reduced function of the cortex. The latter was proved by Reichstein in the adrenal cortex also. There remains at least one active cortical substance - the best known of them all, first named Compound E and now called cortisone or cortone - which was isolated at four different laboratories, among them Kendall's and Reichstein's. The remaining inactive substances with very similar structures will probably be preliminary stages or conversion products of the active ones.

Side by side with the production in pure form of the cortin substances, their chemical structures were elucidated. Reichstein was able to convert one of them into a substance which biological tests proved to possess effects of the same nature as those of the male sex hormone, and he also established chemically the resemblance in structure to the latter. This acquires a special interest in view of numerous observations which showed that the cortex of the adrenals can materially affect the sex characters. Among other things it was known that the cortex is enlarged during pregnancy, and that tumours there can give rise to abnormally early sexual development and a reversal to some extent of such development. As all the cortin substances are closely related to one another, Reichstein's finding implies that, like the sex hormones, they belong to the large and important group of steroids. The D vitamins and the bile acids, like our most important heart remedies, the active substances in Digitalis leaves and Strophanthus seeds, are also intimately associated with the steroids.

The six definitely active cortical hormones are characterized, inter alia, by a double bond in the steroid skeleton; if this double bond disappears, inactive substances are obtained. They differ very inconsiderably from each other chemically. They are built up of 21 carbon atoms, but the number of oxygen atoms in the molecule is three, four, or five. The position of the additional oxygen atoms in the molecule was first established by Reichstein and Kendall, and thus a way was opened for semisynthetic production e.g. from the more easily obtainable bile acids or material from a certain species of Strophanthus. This is of particular importance, since the yield from the adrenals is very poor, at most about 1:1,000,000.

It had gradually been realized that, in cases of Addison's disease, a number of symptoms make their appearance in addition to those which were known from the classic description, and corresponding changes had also been proved in animals after the adrenals had been removed. The most serious disturbances affect the metabolism and the function of the kidneys. The former manifest themselves in, inter alia, a reduced conversion of protein into sugar, and resultant difficulties in the storing of sugar, in the form of the starch-like glycogen, in the liver and muscles, in addition to which the sugar content of the blood may be reduced. Generally the combustion processes decline, muscular work is less satisfactorily performed, and the body temperature is apt to fall. The disturbances in the kidneys manifest themselves in the retention in the body of the nitrogenous waste products and also the potassium salts, while common salt is excreted in increased amounts. In this way the salt and fluid balance is disturbed. The more profound knowledge of the deficiency symptoms in the case of decreased internal secretion from the adrenals raised the question whether the different active cortical steroids have the same effect. Not least thanks to the work of Kendall and his school, it has emerged that the comparatively inconsiderable dissimilarities in the matter of the structure of the cortical hormones are accompanied by material differences in respect of the effect. Thus some act especially strongly on the metabolism of sugar, others on the salt and fluid balances, and there are also several other differences. This was illustrated when Compound E was first tested. Pfiffner and Wintersteiner, like the Reichstein group, found that the substance had no, or extremely inconsiderable, life-prolonging effects on animals deprived of the adrenals. On the other hand, Ingle, Kendall's coworker, observed that it stimulated the muscular work of such animals very strongly.

With regard to the practical test of the cortical steroids on sick people it was of great importance that, for military purposes, large-scale experiments should be started in U.S.A. to produce some of them artificially from simpler compounds. In that connection the greatest interest attaches to Compound E, the structure of which was definitely known, thanks to Reichstein and Kendall. Many steps in the synthesis were extremely difficult, and in respect of a couple of them Kendall and his co-workers showed the way. Further, a distinguished contribution was also made by Sarett.

The testing which was now initiated was directed in the first place on chronic rheumatoid arthritis, and this was not a matter of chance. For a couple of decades, Philip Hench, now at the Mayo Clinic, had been studying the improvements in chronic troubles in the joints which made their appearance during pregnancy or in cases of jaundice. He conceived the possibility of some common factor in that connection and apprehended the morbid disturbances as an expression of changes in metabolism and not, as had been widely assumed earlier, as a result of infection. During pregnancy increased amounts of sex hormones are given off, while in jaundice the bile acids are retained in the body. As there is a relationship between the latter and the cortin substances, it appeared probable to him that the morbid changes might be connected with disturbances in the function of the adrenals. A similar line of thought had also been developed by Selye. In conjunction with Kendall, Hench began to treat cases of chronic rheumatoid arthritis with cortin, but without success. Thus, when cortisone became available, it was natural that they should try their fortunes again. In the April of 1949, Hench, Kendall, Slocumb and Polley published their experiences in respect of the dramatic effects of cortisone in cases of chronic rheumatoid arthritis. A rapid improvement set in, pains and tenderness in the joints abated or disappeared, mobility increased, so that patients who had previously been complete invalids could walk about freely, and their general condition was also favourably affected. Similar results were obtained with a preparation from the anterior lobe of the pituitary, the so-called ACTH (Adreno-Cortico-Tropic Hormone), which, as the name indicates, stimulates the adrenal cortex to increased activity. Unfortunately if the improvement is to last, further supplies of the remedy are necessary, and during the process more or less serious secondary effects in the form of fullness of the face, the growth of hair on the face in women, nervous symptoms, etc., often develop in consequence of disturbances in the endocrine balance. Cortisone also has a good effect in cases of acute rheumatic fever, and this applies as well to some other illnesses, probably also to burns.

The reliability of the Mayo School's results has been confirmed from many quarters in the world. Even if it is still too early to judge what role cortisone and ACTH may play in the future as a remedy for cases of rheumatoid arthritis, it is already beyond all doubt that our knowledge of the nature of these illnesses and of the role of the cortical hormones has been materially advanced by the results of Hench and his co-workers. Perhaps we are even on the verge of a new epoch in the treatment of one of the groups of diseases which, from the social point of view, are among the most important and the most difficult to cure.

The value of a discovery lies not only in the immediate practical results, but equally much in the fact that it points out new lines of research. This is strikingly illustrated by the research during the last few decades into the cortical hormones, which has already led to unexpected and important new results within widely different spheres.

Dr. Hench, Professor Kendall, and Professor Reichstein. The Caroline Institute has decided to award this year's Nobel Prize in Physiology or Medicine to you jointly, for your discoveries regarding the hormones of the adrenal cortex, their structure, and biological effects.

Your work is a splendid example of close co-operation between representatives for physiology, biochemistry, and clinical medicine, as well as between scientists belonging to different countries. Once again it emphasizes the international character of scientific research.

Professor Edward Kendall. You and your collaborators have greatly contributed to the isolation and identification of the cortical hormones, and you have facilitated the artificial production of some of these substances. You have shown conclusively that their biological actions differ all according to their chemical structure. By your work you have very considerably increased our knowledge in this field and also stimulated and enabled the practical application of the new discoveries.

Professor Tadeus Reichstein. To you and your co-workers we owe the first isolation of four active hormones from the adrenal cortex, the first synthesis of one of them, the proof of the steroid nature of said hormones, and numerous details on the structure and properties of these important bodies. In this way the wearisome road to synthesis was smoothed, and new medicaments created. Your discoveries in this field are of fundamental importance.

Doctor Philip Hench. Your brilliant investigations in respect of the beneficial effects of pregnancy and jaundice on rheumatoid arthritis have been the starting-point for the famous discovery during «the preceding year» that these diseases and some others are favourably influenced by hormones from the adrenal cortex. Thereby new therapeutic possibilities have been opened up, and a deeper insight into the nature of these conditions and the role of the adrenal cortex has been gained.

Gentlemen. It is well known that Alfred Nobel felt a personal interest in the study of the processes going on in the body in health and disease, as well as in the practical methods of healing. These two sides of medical research are intimately linked together in the discoveries that are honoured by this year's award.

On behalf of the Caroline Institute I proffer you the hearty congratulations of your colleagues, and I express the hope that you will be able successfully to continue your work which has already resulted in such outstanding achievements.

I have the honour of asking you to accept the Nobel Prize for 1950 from the hands of His Gracious Majesty the King.


Why Atheists Annoy Katie Kish

 
Katie Kish has posted a list of things that annoy her about atheists [Why Atheists Annoy Me]. Remember that Katie is an atheist.

Reading her list makes me sad. Many of us are passionately interested in the conflict between rationalism and superstition. We tend to be outspoken in our advocacy of rationalism and our opposition to superstition. In that sense, we are no different than lots of others who feel strongly about a particular social issue.

But there's a big difference between this particular issue and most others. When it comes to criticizing superstition there are many potential allies (i.e., other atheists) who think that religion/spiritualism deserves some special status. Those potential allies demonstrate a visceral hatred of the vocal atheists that they don't extend to vocal proponents of environmentalism, socialism, feminism or gay/lesbian rights.

For example, here's how Katie Kish describes her feelings about Richard Dawkins ...
3. Dawkins. I think I’ve made it pretty clear in the past that I don’t like Dawkins. I really don’t want Dawkins, Harris and Hitchens to be the voice of my atheism. Because it’s not the voice of many people’s atheism, and it gives people a dangerous path to follow in their atheism. It makes them intolerant, gives them a reason not even try to understand and makes it impossible to have conversations with them. It’s like a hardcore theist - their theism leads them to dangerous places (mentally and physically), their beliefs give them reason to not listen to anyone else and they’re almost always impossible to talk to. The person I want to speak for my atheism is willing to listen, understands if you choose to be religious (and respects that) and attempts to have conversations (where they’re not shoving things down the other person’s throat).
This is really harsh. I don't think Dawkins is unwilling to listen to believers and I don't he fails to understand their point of view. He just disagrees—as I do.

If believers make the effort to engage in the debate then they should be prepared for a real debate with all that entails. I fear that Katie is falling into the trap of assuming that believers deserve some special form of respect just because we're talking about their beliefs. It's as if Dawkins and others are supposed to metaphorically tie one hand behind their back when they debate believers because it's not fair to use all the debating skills at their disposal.

Here's one item on her list that could just as easily be about me as any other vocal atheist. It accuses us of being close-minded because we challenge the views of those believers who voluntarily enter the debate on the blogs.
6. Closed minded - This stands for most of my “liberal” friends as well. They can’t see things from the other side. A good example is something going on at a blog I was reading where people just can’t wrap their head around the fact that people can be spiritual, and not be religious. Religion implies some sort of formality, and doesn’t always include a really deep connection to things. I know a lot of people who are religious. They go to church, and they go through the motions but they have no connection to it. Then I know a lot of people who never go to church, who don’t claim to believe in God or even know what God is - but they have this deep connection to what they usually call “something” and they feel like it strengthens their spirit. And gives them a deeper connection to things and whatever that “something” is. And I respect that. They’re not religious. They’re not following any sort of religious dogma, or religious traditions, or even claiming belief in God. They’re developing what they call their spirituality. And I think there is a fine line between spirituality and religion - but a line nonetheless.
Katie, I'm delighted that you have such a deep understanding of spirituality and what it means. I don't, and that's why I like to discuss it with believers who are willing to debate the issue. The only way for me to find out about the line between religion and spirituality is to ask questions and challenge the answers, just as those believers ask about and challenge my atheism. That's what debate and discussion is all about.

I can only assume that these are questions that you have already resolved. Apparently, you have learned enough about the meaning of spirituality that you no longer feel curious about it. Apparently, as soon as someone says they are spiritual and not religious, that's the end of the discussion for you. Fine, I respect that, but I think it's wrong for you to demand that the rest of us can't explore the topic.

UPDATE: See Sabrina's list of 10 things I love about being an Atheist!


Tuesday, June 03, 2008

Minimum Centromere Size in Plants

In an earlier posting we examined the structure and organization of centromere DNA. In mammals, the centromere consists of multiple tandem repeats of a 180 bp sequence. There are usually thousands of these repeats at each of the 23 centromeres giving an average size of about 3 Mb (3000 Kb) per centromere. The total amount of centromeric DNA amounts to about 2% of the entire human genome [Centromere DNA].

We assumed that all of this DNA was essential and none of it is junk DNA. However, we know that's not a correct assumption since there are many variants at each centromere. If we were to take the minimum size for each functional centromere, the total amount of essential DNA would be much less (probably <1% of the genome). Many workers are trying to figure out how much DNA is required in order to have a functional centromere. One approach is to identify abnormal chromosomes that segregate normally at mitosis with only a small number of repeats at their centromeres. THEME

Genomes & Junk DNA

Total Junk so far

    54%
In the latest issue of PNAS, Murata et al. (2008) looked at small minichromosomes in the plant Arabidposis thaliana. The minichromosomes were produced as a by-product of a transformation experiment that inserted T-DNA into the centromere of chromosome 2.

The five standard chromosomes of Arabidopsis each have centromeres consisting of about 1600 copies of a 180 bp repeat (avergae size 2.7 Mb - 3.0 Mb. The four minichromosomes, α, β, γ, and δ, have centromeres ranging in size from 0.5 Mb to 2.3 Mb. The δ minichromosome appears to segregate normally with only 500 Kb of centromere DNA (about 2800 repeats). This may be close to the minimum size required to assemble a kinetochore.

If this minimum size is true in mammals well—a reasonable assumption—then perhaps only 15-20% of centromere DNA is actually essential and the rest is excess junk DNA produced by unequal cross-overs and DNA replication slippage. Because expansion and contraction of repetitive DNA is unavoidable, there will be considerable variation within a population. Individuals that have close to the minimum amount of DNA at any one centromere will be underrepresented in the population because many of their offspring will have died. Individuals with a large excess of centromere DNA will be overrepresented because their lineages are less likely to encounter lethal deletions. (Provided that there is no fitness penalty for carrying excess DNA.)

Thus, in a certain sense, some of the "excess" centromeric DNA is required as a buffer against the possibility of future deletions. The extra DNA does not contribute to the viability of the individual carrying it but it does contribute to the survival of that individual's offspring. At some point, the potential advantage in terms of offspring survival will become too small to have any influence on the lineage of an individual. This will define the maximum amount of "excess" DNA at the centromere. I wonder if it is possible to model the effect of having extra centromeric DNA?


Murata, M., Yokota, E., Shibata, F. and Kashihara, K. (2008) Functional analysis of the Arabidopsis centromere by T-DNA insertion-induced centromere breakage. Proc. Natl. Acad. Sci. (USA) 105:7511-7516. [PubMed] [doi:10.1073/pnas.0802828105]

Monday, June 02, 2008

Monday's Molecule #74

 
This is an important molecule for some species but not for others. You need to identify the molecule, give its correct common name and the formal IUPAC name. Pay attention to the correct names because there are several similar compounds

There's an direct connection between today's molecule and a Nobel Prize. The prize was awarded for purifying the molecule, determining its structure, and figuring out what it does. The first person to correctly identify the molecule and name the Nobel Laureate(s) wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first collected the prize. There are four ineligible candidates for this week's reward.

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 Laureate(s) 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 may select multiple winners if several people get it right.

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

UPDATE: The molecule shown above is cortosol or hydrocortisone (11,17,21- trihydroxy-,(11β)- pregn-4-ene-3,20- dione) [8R, 9R, 10R, 11S, 13S, 14S,17R)-11,17- dihydroxy-17- (2-hydroxyacetyl)-10,13- dimethyl- 2, 6, 7, 8, 9, 11, 12, 14, 15, 16-decahydro-1H-cyclopenta[a]phenanthren-3-one]. The Nobel Laureates are Edward Kendall, Tadeus Reichstein, and Philip Hench (1950).

The first person to get it right was Matt Wagner, a student at Queen's University in Kingson ON (Canada).

University of Toronto students aren't doing so well these days, although, in fairness, there were two who got it right this time. They were late sending in their answers, presumably because they were up all night doing experiments and didn't see my posting until noon hour.