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Tuesday, June 16, 2009

Nicholas Wade on the Origin of Life

Nicholas Wade is a science journalist who writes for the New York Times. His particular area of expertise is evolution and molecular biology and he is often mentioned as one of the best science writers in America.

That's not an opinion that I share, although it's true that he writes very well.

Wade's latest article is New Glimpses of Life’s Puzzling Origins. The focus of this article is on recent discoveries in chemistry and biology relating to the origin of life. These all support a scenario where complex molecules in a warm little pond give rise to replicating nucleic acids enclosed in a membrane vesicle. Not much attention is paid to the competing scenarios—especially the one I favor: Metabolism First and the Origin of Life.

Now don't get me wrong. There's no reason why Nicholas Wade can't prefer one particular scenario for the origin of life. After all, many scientists agree with him. The problem I have is that when it comes to informing those who read newspapers, they won't be getting the full story.

One of the "problems" in origin of life studies is the "chirality" problem. The idea is to explain why life prefers left-handed amino acids instead of right-handed amino acids. The "problem" arises when you postulate that life arose in a soup consisting of equal amounts of both types of amino acid.

Sandwalk readers will know my opinion on the "problem." I think it's a "non-problem" since life probably didn't arise from a pool of 20 different concentrated amino acids. I prefer a scenario where a few simple amino acids contributed to the first catalysts and expansion of the repertoire of amino acids resulted from synthesis of more complex ones from simple ones. Since this was "biological" synthesis, the complex amino acids were all left-handed forms from the beginning because the precursors were already left-handed [Can watery asteroids explain why life is 'left-handed'?].

Let's see how Nicholas Wade describes recent results.
Another striking advance has come from new studies of the handedness of molecules. Some chemicals, like the amino acids of which proteins are made, exist in two mirror-image forms, much like the left and right hand. In most naturally occurring conditions they are found in roughly equal mixtures of the two forms. But in a living cell all amino acids are left-handed, and all sugars and nucleotides are right-handed.

Prebiotic chemists have long been at a loss to explain how the first living systems could have extracted just one kind of the handed chemicals from the mixtures on the early Earth. Left-handed nucleotides are a poison because they prevent right-handed nucleotides linking up in a chain to form nucleic acids like RNA or DNA. Dr. Joyce refers to the problem as “original syn,” referring to the chemist’s terms syn and anti for the structures in the handed forms.

The chemists have now been granted an unexpected absolution from their original syn problem. Researchers like Donna Blackmond of Imperial College London have discovered that a mixture of left-handed and right-handed molecules can be converted to just one form by cycles of freezing and melting.
Hmmm ... I see two problems here. First, I'm not aware of any experiments by Donna Blackmond or anyone else that solves the chirality problem. Does anyone have a reference?

The second problem with Wade's description concerns the "handedness" of nucleotides. It's true that the sugar component of nucleotides is exclusively D-ribose (or D-deoxyribose) and not L-ribose. The nucleic acids that we know today (DNA and RNA) could not be made with L-ribose or L-deoxyribose. This is a "problem" that's similar to the one with amino acids; how do you get a pool of sugars that are all D- configurations? (Do you get them by synthesizing them all from D-glyceraldehyde?)

The terms syn and anti refer to different conformations of nucleotides and not different stereoisomers. Conformations are different three-dimensional shapes that a molecule can adopt in solution. They don't require the breaking of any chemical bonds. See Nucleotides Can Adopt Many Different Conformations for a discussion of these different shapes.

Here's a figure showing the anti and syn conformations of deoxyguanylate. (Click to embiggen.)


Free nucleotides can easily switch back and forth between the two forms since all it requires is rotation around the β-N-glycosidic bond—the one with the circular arrow around it. This has nothing to do with stereochemistry or the chirality problem.

In fact, nucleotides like deoxyguanylate can switch between the two conformations even while they are part of DNA. The anti conformation is found in normal B-DNA but the double helix can adopt a Z-DNA conformation under some circumstances and in that conformation the deoxyguanylate residues are in the syn conformation.

Mistakes like this are what makes science journalism difficult. I don't expect Nicholas Wade to be an expert in biochemistry—although if he'd had a copy of my textbook he could have avoided the error. What I do expect is a bit of fact-checking with other experts. Wade could have asked any biochemist to check this out.

Furthermore, Wade should probably have been suspicious when he realized that the syn and anti conformations of nucleotides don't come up in any other discussions about chirality. Indeed, nucleotides are rarely mentioned in such discussions.


[Figure is from Moran/Scrimgeour et al. Biochemistry 2nd ed. (1994) ©Neil Patterson Publishers/Prentice Hall.

Nobel Laureate: Robert Koch

 

The Nobel Prize in Physiology or Medicine 1905

"for his investigations and discoveries in relation to tuberculosis"

Robert Koch (1843 - 1910) won the Noble Prize in 1905 for demonstrating that specific bacteria can cause common diseases. Tuberculosis was the specific disease mentioned in the citation.

At the time of the award, Koch was already a very famous scientist. Part of his reputation was based on The Most Famous Speech in Medical History but he was also widely respected for identifying the bacteria causes of other diseases.

The most important part of the Presentation Speech is the part that emphasizes the general contribution of Koch to the study of bacteriology (see below). Koch is recognized as one of the founders of the modern field of microbiology. One of his co-workers, Paul Ehrlich, won the Nobel Prize three years after Koch [Nobel Laureate: Paul Ehrlich].
THEME:
Nobel Laureates
To start with, developing a general methodology is as valuable as finding the correct technique for every special case. Koch's genius has blazed new trails in this respect and has given present-day research its form. To give a detailed description of this is beyond the scope of this account. I only want to mention that he had moreover already given a significant development to techniques in staining and microscopic investigation as well as in the field of experiment in his earliest work. Shortly after this he produced the important method, which is still generally the usual one, of spreading the material under investigation in a solid nutrient medium to allow each individual among the micro-organisms present to develop into a fixed colony, from which it is possible, in further research, to go on to obtain what is known as a pure culture.

Shortly after the publication of his investigations into diseases from wound infections Koch was appointed to the new Institution, the «Gesundheitsamt» (Department of Health), in Berlin. There he started work on some of the most important human diseases, namely, tuberculosis, diphtheria and typhus. He worked on the former one himself. The two latter investigations he left to his first two pupils and assistants, Loeffler and Gaffky. For all three diseases the specific bacteria were discovered and studied in detail.

To give an account of the work which Koch carried out, or accomplished through his pupils, and also to mention the work which derives more indirectly from Koch, would nearly be the same as describing the development of bacteriology over the last few decades. I will content myself with naming some of the most important discoveries and items of research which, in addition to those already named, are more directly linked with Koch's name. At the head of the German Cholera Commission Koch investigated the parasitic aetiology of cholera in Egypt and India, and discovered the cholera bacillus and the conditions necessary for its life. Experience thus gained found practical application in the development of measures taken to prevent and combat this devastating disease. In addition Koch made important investigations concerning plague in humans, malaria, tropical dysentery, and the Egyptian eye disease (trachoma) among others, and now finally concerning typhus recurrens in tropical Africa. He has also carried out work of exceptional importance, concerning a host of destructive tropical cattle diseases, such as rinderpest, Surra disease, Texas fever, and finally concerning coast fever in cattle and the trypanosome disease carried by the tsetse fly.

Through the perfection he gave to methods of culturing and identifying micro-organisms, he has been able to carry out his work with regard to disinfectants and methods of disinfection so important for practical hygiene, and advice concerning the early detection and combating of certain epidemic diseases such as cholera, typhus and malaria.

[Image Credits: photograph:zgapa.pl/drawing: Wolsztyn - Wollstein/statue: Wikipedia/movie poster: Journal of Medicine and Movies]

The images of the Nobel Prize medals are registered trademarks of the Nobel Foundation (© The Nobel Foundation). They are used here, with permission, for educational purposes only.

Monday's Molecule #126: Winner

 
The molecules are: BMPR = Bone morphogenic bone receptor; BMP4 = Bone morphogenetic protein 4, CHD = Chordin, TGS = twisted gastrulation. These molecules play an important role in regulating development in the embryos of the amphibian (frog) Xenopus laevis.

BMP binds to its receptor (BMPR) on certain cells and acts as a signal leading to induction of a number of developmental genes. Most of them are involved in establishing dorsal-ventral polarity (the back and belly of the the tadpole). Chordin is an antagonist of BMP4 and it is secreted by another group of cells in the early embryo to inhibit the action of BMP4.

The discovery of specific cells that secreted morhogenic factors is mostly due to the pioneering work of Hans Spemann, who was awarded a Nobel Prize in 1935. This marked a turning point in the history of developmental biology because it signaled the transition from a descriptive science to an experimental/molecular/genetic science.

We have a single winner this week. It's Ian Clarke of New England Biolabs Canada in Pickering ON, Canada.



Today's molecule is actually four molecules. Your task is to identify the four molecules shown in the cartoon. Explain what they are doing in the figure. Be sure to name the species or you won't get credit for a correct answer.

These molecules are directly connected to one of the most significant Nobel Prizes in the 20th century. The Nobel Laureate didn't know the names of these molecules but that doesn't diminish the achievement. Identify the Nobel Laureate and the connection between Monday's Molecules and the work for which the prize was awarded.

The first person to identify all four molecules and the Nobel Laureate, wins a free lunch at the Faculty Club. Previous winners are ineligible for six weeks from the time they first won the prize. Please note the change in the length of time you are ineligible. The idea is to give more more people a chance to win.

There are eight ineligible candidates for this week's reward: Dima Klenchin of the University of Wisconsin, Madison, Adam Santoro of the University of Toronto., Michael Clarkson of Waltham MA (USA), Òscar Reig of Barcelona, Maria Altshuler of the University of Toronto, Mike Fraser of the University of Toronto, Jaseon Oakley of the University of Toronto, and Bill Chaney of the University of Nebraska.

Bill Chaney has donated his 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(s) 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.

Comments will be blocked for 24 hours. Comments are allowed.


[Image Credit: De Robertis, E.M. and Kuroda, H. (2004)]

Monday, June 15, 2009

Creationism, ID and the Douchebaggery of Really Bad Arguments: An Evening with the Canadian Cynic

 
Join us at the Centre for Inquiry (Toronto) for Creationism, ID and the Douchebaggery of Really Bad Arguments: An Evening with the Canadian Cynic.

Sandwalk readers will be able to withstand the suspense since you already know who Canadian Cynic is.

Starts: Friday, July 3rd 2009 at 7:00 pm
Ends: Friday, July 3rd 2009 at 9:00 pm
Location: Centre for Inquiry Ontario, 216 Beverley St., Toronto

Creation Science, Intelligent Design and the Douchebaggery of Really, Really Bad Arguments

A polemic by the Canadian Cynic, aka ???

For over five years, the blogger "Canadian Cynic" has railed against the appalling idiocy of the right-wing wankersphere. Along with his carefully-acquired co-bloggers "LuLu" and "Pretty Shaved Ape", "CC" (as he is known to his readers) has struck fear into the hearts of Canada's wanks from coast to coast, using a combination of awesome intellect, devastating logic and, sometimes, just calling people "douchebags" when the situation calls for it.

And for the first time, he comes out publicly ... at the Centre for Inquiry.

The evening's presentation will consist of some war stories from many years back during CC's anti-creation science years, plus some updates on how, depressingly, nothing seems to have changed.

There will be a subsequent Q/A session, during which outraged audience members will be allowed to vent until told to put a sock in it, after which we will adjourn to a convenient pub that serves real beer, and you're buying.

Event admission: $5 regular, $4 student, FREE for Centre for Inquiry Friends of the Centre


Gene Evolution Process Discovered

 
This press release heralds a major breakthrough in evolution: Gene Evolution Process Discovered.
One of the mechanisms governing how our physical features and behavioural traits have evolved over centuries has been discovered by researchers at the University of Leeds.

Darwin proposed that such traits are passed from a parent to their offspring, with natural selection favouring those that give the greatest advantage for survival, but did not have a scientific explanation for this process.

In research published this week, the Leeds team reports that a protein known as REST plays a central role in switching specific genes on and off, thereby determining how specific traits develop in offspring.
The article is by Johnson et al. (2009). Here's the abstract.
Specific wiring of gene-regulatory networks is likely to underlie much of the phenotypic difference between species, but the extent of lineage-specific regulatory architecture remains poorly understood. The essential vertebrate transcriptional repressor REST (RE1-Silencing Transcription Factor) targets many neural genes during development of the preimplantation embryo and the central nervous system, through its cognate DNA motif, the RE1 (Repressor Element 1). Here we present a comparative genomic analysis of REST recruitment in multiple species by integrating both sequence and experimental data. We use an accurate, experimentally validated Position-Specific Scoring Matrix method to identify REST binding sites in multiply aligned vertebrate genomes, allowing us to infer the evolutionary origin of each of 1,298 human RE1 elements. We validate these findings using experimental data of REST binding across the whole genomes of human and mouse. We show that one-third of human RE1s are unique to primates: These sites recruit REST in vivo, target neural genes, and are under purifying evolutionary selection. We observe a consistent and significant trend for more ancient RE1s to have higher affinity for REST than lineage-specific sites and to be more proximal to target genes. Our results lead us to propose a model where new transcription factor binding sites are constantly generated throughout the genome; thereafter, refinement of their sequence and location consolidates this remodeling of networks governing neural gene regulation.
Correct me if I'm wrong, but haven't there been occasional rumors about other regulatory proteins (repressors and activators) that might play a role in regulating development? Haven't they sometimes been implicated in causing the differences between species? I seem to remember hearing something about "evo-devo"—does that ring any bells?

Do scientists have any responsibility to make sure their work is accurately reported by university press offices? I think they do.


Johnson, R., Samuel, J., Ng, C.K., Jauch, R., Stanton, L.W., and Wood, I.C. (2009) Evolution of the Vertebrate Gene Regulatory Network Controlled by the Transcriptional Repressor REST. Molecular Biology and Evolution 26:1491-1507. [doi:10.1093/molbev/msp058]

Science Scouts

 
Join Science Scouts and win cool badges! In case you don't know, the complete offical name of Science Scouts is "Order of the Science Scouts of Exemplary Repute and Above Average Physique." (They're lenient about the physique.)

This is one of my favorite badges. All you have to do is Science with no conceivable application (known among friends as the "useless" badge). I've done lots of that kind of science. I'm also eligible for the next level badge— for science that not only has no conceivable application but also isn't even interesting to fellow scientists.

This one's quite ordinary. It's the cloner badge. You can earn it just by cloning something. An advanced version is coming out next year. It's for people who have cloned something that terrorized a small village.

I'm really proud of this one. It's the "somewhat confused as to what scientific field I actually belong to" badge. When you put it on your CV you can refer to it by its more formal name: the transdiscplinary, interdiscplinary, multidisciplinary, or intradisciplinary (TIMI) badge.

Here are some of my other badges ...



[Hat Tip: Eva Amsen]

Who Is Canadian Cynic?

 
Blogger Canadian Cynic chose to remain anonymous. As most of you know, I prefer bloggers who are not anonymous but I respect the decision of my friends who disagree.

Some of Canadian Cynic's enemies don't respect his decision so they did some digging and outed him. Tsk, tsk, typical behavior for right-wing idiots.

Canadian Cynic is my old friend Rob Day from talk.origins. I'm secretly delighted that he can now be identified even though I deplore the behavior of his enemies.

He's probably going to be giving a talk in Toronto very soon so you can all come out and meet Canadian Cynic [You might want to keep Friday, July 3, open]. I have stories, and lots of photos! So do my daughter Jane and her husband Michael—they rented his house! We'll have a real "outing" party.

BTW, Rob doesn't want anyone to retaliate by outing the right-wing idiots who choose to remain anonymous [On outing].



Canada's Secret Plan for World Domination

 
The secret is out [Donuts To Dollars].
Our Friendly Neighbors In Canada Are About To Wage An International Food Fight Over Your Morning Coffee

(CBS) Americans are about to be dragged into an international food fight … and it's our friendly neighbors in Canada who are throwing down the gauntlet. Jeff Glor reports our Cover Story:
There was some chance that the story would be ignored since it only appeared on CBS News but that turned out to be a forlorn hope. John Pieret of Thoughts in a Haystack has taken on the role of a modern Paul Revere [Rally 'Round the Flag].

Now the whole world knows the secret.


Monday's Molecule #126

 
Today's molecule is actually four molecules. Your task is to identify the four molecules shown in the cartoon. Explain what they are doing in the figure. Be sure to name the species or you won't get credit for a correct answer.

These molecules are directly connected to one of the most significant Nobel Prizes in the 20th century. The Nobel Laureate didn't know the names of these molecules but that doesn't diminish the achievement. Identify the Nobel Laureate and the connection between Monday's Molecules and the work for which the prize was awarded.

The first person to identify all four molecules and the Nobel Laureate, wins a free lunch at the Faculty Club. Previous winners are ineligible for six weeks from the time they first won the prize. Please note the change in the length of time you are ineligible. The idea is to give more more people a chance to win.

There are eight ineligible candidates for this week's reward: Dima Klenchin of the University of Wisconsin, Madison, Adam Santoro of the University of Toronto., Michael Clarkson of Waltham MA (USA), Òscar Reig of Barcelona, Maria Altshuler of the University of Toronto, Mike Fraser of the University of Toronto, Jaseon Oakley of the University of Toronto, and Bill Chaney of the University of Nebraska.

Bill Chaney has donated his 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(s) 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.

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


[Image Credit: De Robertis, E.M. and Kuroda, H. (2004)]

Saturday, June 13, 2009

I can't wait to see this ...

 
This looks really good, judging from the trailer. Like PZ Myers I'm a little nervous about how it will turn out but I'll certainly be watching it as soon as it's available.





Amway sells genetic tests?

 
Many blogs have been shamelessly promoting genetic testing and giving free advertising to the for-profit companies that have been exploiting the technology. Some of the bloggers are indirectly or directly associated with those companies.

Of course we all know where this is going. It's only a matter of time before a rash of private companies catch on to this get-rich scheme and decide to reap the profits.

Daniel MacArthur of Genetic Future has identified one of these companies: Amway sells genetic tests?. Read his posting and read the response from the company (Interleukin Genetics) in the comments.

This is just the tip of the iceberg. It's going to get much worse. I wonder if the cheerleader bloggers are going to take the lead in calling for government controls?


The British Chiropractic Associates Issues a Warning

 
The British Chiropractic Associates (BCA) is the group that sued science journalist Simon Singh for pointing that their practices were not evidence based. Although the initial court ruling was favorable to the BCA, the subsequent fall-out is probably making them regret their decision to silence critics.

The latest round has the BCA sending out the following warning to their members—a warning that should not have been necessary if chiropractors have been behaving like they should.
he BCA would remind members of their obligations under the Advertising Standards Authority (ASA) section 50 (relating to Health & Beauty Products and Therapies: see

Members are strongly encouraged to review their current marketing materials (whether they are paper- or web-based to ensure that they are compliant with both ASA and GCC requirements. Note that the ASA has no jurisdiction over editorial materials placed on members own websites.

When reviewing your materials it may be helpful to consider the following:

1. Are there any claims made that cannot be justified by reference to evidence? Remember, the GCC requires chiropractors to practice evidence based care, which is defined as "clinical practice that incorporates the best available evidence from research, the preferences of the patient and the expertise of practitioners (which includes the individual chiropractor himself).

2. Be mindful of making promises that you cannot be sure of delivering on;

3. Be wary of listing conditions that are controversial and away from mainstream chiropractic care e.g. dyslexia/dyspraxia unless you have research to back this up. If you have made references to prolonged crying, sleep and feeding problems, breathing difficulties and frequent infections, as these are symptoms rather than condition specific, we suggest you remove these references.

4. Do not refer to yourself as a specialist in any particular form of chiropractic;

5. Do not use unfamiliar words for common conditions;

6. Do not unjustly criticise other healthcare professionals;

7. If you refer to subluxations, provide information to explain what they are.

8. Take care in the use of the Doctor title. Ensure that there is no way there can be any doubt that you are a chiropractor, and not a registered medical practitioner. Do not use the doctor title in paper advertising without explicitly stating that you are a chiropractor.
How much of this controversy is going to spill over into North America? Isn't it time that American and Canadian chiropractors started to feel the heat?

Here's an example of a "wellness clinic" in my neighborhood: Erin Mills Optimum Health. They offer chiropractic (Dr. Peever, Dr. Caven, Dr. Cote), chiropody/foot care, naturopathy (including homeopathy) (Dr. Almond), massage therapy, and reflexology.

As of today (June 13, 2009) the home page on their website contains the following testemonial.
I have Irritable Bowel Syndrome and began researching on the internet for anyway I could get any relief from my symptoms. A co-worker of mine recommended me to see a Chiropractor after I had missed a couple of days of work. With my regular adjustments and my regulated diet, I noticed a positive change in my health. I am feeling better and more comfortable with myself. I would recommend to anyone who suffers from IBS to come in and see a Chiropractor, you have nothing to lose.
The British Chiropractic Associates would not be pleased.


Friday, June 12, 2009

Richard Brown Defends Chiropractic

 
Read In defense of chiropractic by chiropractor Richard Brown in New Scientist.
SINCE the British Chiropractic Association (BCA) decided to sue science writer Simon Singh for libel, scientists and journalists have unleashed a torrent of criticism against chiropractic. Much of this is misinformed and needs to be corrected.

Many critics - including Edzard Ernst (New Scientist, 30 May, p 22) - hark back to the origins of chiropractic. This has the clear intention of suggesting that modern chiropractors cling to the 19th century idea that spinal misalignments are responsible for the majority of diseases. While a tiny minority retain this view, most are aware that such claims have long since been debunked.
This is the same Richard Brown who works at The Landsdown Clinic in Gloucestershire, UK. Here's a list of the treatments they offer at that clinic ....
Aromatherapy

Aromatherapy is the use of essential oils, extracts from the flowers, fruits, leaves, stems and roots of flowers, shrubs and trees. The therapeutic use of aromatic oils dates back to ancient times and was particularly popular in Ancient Egypt and the Far East. Aromatherapy massage is a gentle, flowing treatment that may help to relieve pain and alleviate tension and fatigue. The use of essential oils creates a feeling of calming energy and has a powerful effect on both body soul.

Reflexology

Reflexology is a complementary therapy that uses pressure points on the feet to help activate the circulation and nervous system. By using the feet as a map of the whole body, reflexology consists of the application of manual techniques to enhance a state of physical and mental balance.

Therapeutic Massage

Therapeutic massage is the use of hands to manipulate soft tissues of the body, particularly muscles. It can be used for relaxation, stimulation or rehabilitation of the whole body or part of it. Particularly effective in managing stress-related tension, massage promotes suppleness, aids flexibility and stimulates circulation. Therapeutic massage may be beneficial for a range of body systems and as well as treating muscular aches and pains, it can be useful in helping circulation and digestion.

Hot Stone Therapeutic Massage

Despite it being one of the fastest-growing massage techniques, hot stone therapy is an ancient healing art. It uses a combination of warm stones and various massage techniques which provide deep therapeutic effects and create harmony and balance.

Hopi Ear Candling

Being a hollow tube, the centre of an ear candle is simply a column of air rather than a solid mass. When lit at the top, the rising air column inside the candle begins to heat up. As the candle burns down, it continues to heat up the top of the rising air column of the centre of the candle. The rising air column creates a very mild suction action at the base, which help loosen compacted earwax. This experience is a gentle, relaxing treatment for everyone, including children.

Indian Head Massage

Indian Head Massage is a traditional touch therapy, which has been practised for thousands of years. It is gentle, yet firm and powerful, therapeutic massage of the shoulders, arms, neck, scalp, ears, hair and face which will leave you feeling soothed and rebalanced. This is an extremely enjoyable and deeply relaxing treatment that gives you a sense of calm and relaxation.
It's certainly NOT the Richard Brown at the Brown Chiropractic Center in Brockon, MA (USA) south of Boston. That practice offers to help you with allergies, asthma, bedwetting, pregnancy and a host of other problems.

I wonder if the British Richard Brown, who is never referred to as "doctor" on his website, would approve of the American "Dr." Richard Brown? I wonder if the American "Dr." Brown is aware of the fact that some of these 19th century claims have been debunked?


Thursday, June 11, 2009

Nobel Laureate: Jens Skou

 

The Nobel Prize in Chemistry 1997.

"for the first discovery of an ion-transporting enzyme, Na+, K+ -ATPase"




Jens C. Skou (1918 - ) won the Nobel Prize in Chemistry his work on the Na+,K+ ATPase (sodium potassium ATPase). He discovered that this membrane protein pumped sodium ions out of cells and pumped potassium ions into cells. The pump was driven by hydrolysis of ATP.

Skou shared the Nobel Prize with Paul Boyer and John Walker who worked out the mechanism of ATP synthase—the enzyme that makes ATP.

The press release describes Skou's work in some detail.
THEME:
Nobel Laureates
Na+, K+-ATPase, the first molecular pump to be discovered

It was known as early as the 1920s that the ion composition within living cells is different from that in the surroundings. Within the cells the sodium concentration is lower and the potassium concentration higher than in the liquid outside. Through the work of the Englishmen Richard Keynes and Alan Hodgkin at the beginning of the 1950s (Hodgkin received the Nobel Prize in 1963) it was known that when a nerve is stimulated sodium ions pour into the nerve cell. The difference in concentration is restored by sodium being transported out once again. That this transport required ATP was probable since the transport could be inhibited in the living cell by inhibiting the formation of ATP.

With this as the starting point Jens C. Skou searched for an ATP-degrading enzyme in the nerve membrane that could be associated with ion transport. In 1957 he published the first article on an ATPase, which was activated by sodium and potassium ions (Na + , K + -ATPase). He was the first to describe an enzyme that can promote directed (vectored) transport of substances through a cell membrane, a fundamental property of all living cells. Numerous enzymes have since been demonstrated to have essentially similar functions.

Skou used as experimental material finely ground crab nerve membranes. The ATP-degrading enzyme found in the preparation required the presence of magnesium ions and was stimulated with increasing quantities of sodium ions up to a certain limit. Above this Skou was able to obtain further stimulation if he added small quantities of potassium ions. An indication that the enzyme was coupled to the ion pump was that maximal stimulation was obtained at the concentrations of sodium and potassium that normally occur in the nerve. In his further studies of the enzyme mechanism Skou showed that sodium ions and potassium ions bind with high affinity to different places in the enzyme. In addition he showed that the phosphate group separated from ATP also binds to ATPase. This is described as a phosphorylation of the enzyme. The enzyme is dependent on sodium ions when it is phosphorylated and on potassium ions when it is dephosphorylated. Substances known to inhibit sodium/potassium transport are certain digitalis alkaloids, e.g. oubain, and Skou showed that oubain interferes in the enzyme's activation by sodium.

The picture that slowly emerged from Skou's and others' work is that the enzyme consists of two subunits, alpha and beta. The first carries the enzyme's activity and the other presumably stabilises the structure. The enzyme molecules are located in the cell membrane, often in twos, and expose surfaces to the outside as well as the inside. Three sodium ions and ATP bind to the interior surface. A phosphate is then transferred from ATP to an amino acid in the enzyme, aspartic acid, whereupon the ADP is liberated and the enzyme changes form so that the sodium ions are transported to the outside. Here they are released and two potassium ions attach instead. When the phosphorus that is bound to the enzyme is removed the potassium ions are transported into the cell and when new ATP binds to the enzyme they are rejected.

As a result of the action of the Na + , K + -ATPase, the cell keeps a high concentration of potassium in its inside. As the cell membrane is rather permeable for potassium ions, a few of these potassium ions leak out, leaving unpermeable, negative charges on the inside of the cell. Therefore, the inside of the cell membrane becomes electrically negatively charged, as compared to the outside.

This difference in potential across the membrane is necessary for a nerve stimulation to propagate along a nerve fibre or a muscle cell. This is why a shortage of nourishment or oxygen in the brain rapidly leads to unconsciousness since the ATP formation ceases and the ion pump stops. The pump is also important for maintaining cell volume. If the pump stops, the cell swells. The difference in sodium concentration between the interior and the exterior is the driving force in the uptake of important nutrients necessary to the cell, e.g. glucose and amino acids. It can also be used for transport of other ions through the cell membrane. Thus sodium ions that enter can be exchanged for calcium ions that exit.

Following the discovery of Na + , K + -ATPase other ion pumps have been discovered with similar structures and functions. Examples are Ca 2+ >-ATPase in skeletal muscle, which participates in the control of muscle contraction and H + , K + -ATPase which produces hydrochloric acid in the stomach. It is the latter enzyme that is specifically inhibited in modern treatment of stomach ulcers. Corresponding enzymes are also found in lower organisms, for example in yeast where an H + -ATPase secretes hydrogen ions formed during fermentation. As a common name these enzymes are nowadays termed P-type ATPases since they are phosphorylated during the course of the reaction.

The images of the Nobel Prize medals are registered trademarks of the Nobel Foundation (© The Nobel Foundation). They are used here, with permission, for educational purposes only.

Time Tree: The Timescale of Life

 
Check out the Time Tree website. You can type in any two species and find out when they diverged.

This is a great learning tool. Try it with Homo sapiens (that's us) and ....
Gallus gallus (chicken)
Danio rerio (some kind of fishy thing)
Strongylocentrotus purpuratus (purple sea urchin)
Drosophila melanogaster (fruit fly)
Caenorhabditis elegans (nematode)
Saccharomyces cerevisiae (baker's yeast)
Arabidopsis thaliana (flowering plant)
Plasmodium falciparum (protozoan, causes malaria)
Escherichia coli (bacterium)
Keeping in mind that the Cambrian explosion happened about 550 million years ago, try and guess when the lineage leading to these species diverged from the lineage leading to humans. Check your guess on the website.

Where you right? Why, or why not?


[Hat Tip: ERV]