Genes for Hemophilia A & B and von Willebrand disease

 
The roles of Factor VIII and Factor IX in blood clotting are described in a recent posting [Blood Clotting: Intrinsic Activity]. Defects in the gene for Factor VIII cause a bleeding disorder called hemophilia A [OMIM 306700]. The gene is called F8 and it's located on the X chromosome at q28. The fact that it's X-linked means that males are more likely to be affected than females since females would have to be homozygous for the recessive allele. Heterozygous females are unaffected.

Deficiencies in Factor IX are caused by mutations in the F9 gene, which is also located on the X chromosome (q27.1-q27.2). The disease is called hemophilia B or Christmas disease. Factor IX used to be called Christmas factor after Stephen Christmas (1947-1993), the first patient with a known defect in this clotting factor [OMIM 306900]. It took some time, and a considerable amount of effort, to determine that there were two different genes on the X chromosome and hemophilia A was a different disease than hemophilia B.

The disease nomenclature is complicated by the fact that defects in the gene for von Willebrand Factor (vWF) are sometimes called hemophilia B. The correct name is von Willebrand disease. Recall that von Willebrand Factor associates with and stabilizes Factor VIII. Deficiencies of vWF are phenotypically equivalent to deficiencies in Factor VIII [OMIM 193400]. The gene for von Willibrand Factor is VWF and it's located at 12p13.3. The fact that it's autosomal means that the disease is not sex-linked.

Several of the VWF alleles confer a dominant phenotype. This is sometimes due to an insufficiently in the amount of von Willebrand Factor in blood plasma. The genetic term is haplo-insufficiency. It means that two functional alleles, one on each chromosome, are necessary in order to supply a sufficient amount of protein.

The Ann Coulter Hoax

 
I admit it. I was fooled by Ann Coulter. I thought her latest book was one of the standard IDiot attacks on evolution. The fact that it was so stupid was something I have come to expect from the Intelligent Design Creationists.

Now it turns out that the book was a satirical jab at the lack of intelligence on the political right. Peter Olofsson of The Skeptical Inquirer exposes the hoax [The Coulter Hoax: How Ann Coulter Exposed the Intelligent Design Movement].

Coulter has very cleverly written a fake criticism of evolution, much like the way NYU physicist Alan Sokal in 1996 published a fake physics article in a literary journal, an affair that has become known as the “Sokal hoax.” A self-proclaimed “old unabashed leftist,” Sokal was disturbed by the sloppily antiscientific, postmodernistic mentality that had started to replace reason and rationality within the academic left and ingeniously made his point by managing to get his nonsense article published by the very people he wished to expose.

Coulter’s aim at antiscience is at the other end of the political spectrum. An equally unabashed rightist, she is apparently disturbed by how factions within the political right abandon their normally rational standards when it comes to the issue of evolution. However, whereas Sokal revealed his hoax in a separate article, Coulter challenges her readers to find out the truth for themselves. Without claiming to do justice to Coulter’s multifaceted and sometimes subtle satire, I will attempt to outline some of her most amusing and salient points.

This is amazing. I congratulate Coulter on her expose of the Intelligent Design movement. She has cleverly pointed out every single flaw.

[Hat Tip: John Wilkins]

Coturnix on Framing Science

 
I don't have the time or the energy to read everything that's been written about the upcoming Mooney & Nisbet Science article. If you want to catch up then check out the Coturnix posting [Framing Science - the Dialogue of the Deaf] for all the latest links.

However, I would like to respond to some of the things that Coturnix writes. He's a defender of framing and he believes that science writers have to improve.

Here's what he says about frames.

Very short summary: words have effects beyond their dictionary definitions. Language evokes emotional responses: 'frames' (as in 'frames of mind'). There is no such thing as emotion-free language. If you can understand a piece of text (and that includes math, not just English), you will respond emotionally. The kind of response to language results in one accepting or rejecting the message (and the messenger). The kind of response to language is dependent on one's worldview - the same sentence will elicit different responses (and thus acceptance or rejection) in different people.

No argument there. People have different worldviews. but what does that mean for science writers?

Good news: most people are biconceptual, i.e., they possess both frames in their minds. By evoking the right frame by careful use of language, you gain trust and authority with the audience and as a result they believe that what you are saying is true. In other words, just saying the truth is not enough, as it is processed through ideological glasses. By invoking the correct frame, you allow the truth to penetrate and get accepted. By dismissing framing as method and by being careless in the use of language, you are bound to "buy into" the currently dominant Rightwing frames and will thus reinforce them while at the same time preventing your audience from accepting the truth. Since conservatism, religion and pseudoscience do not have the truth on their side, their frames are deceptive and Orwellian. Since our frames are backed up by truth, in a head-to-head competition we should win, but we cannot let the opposition frame the issues in the first place.

First things first.

Coturnix, you live in North Carolina. I live in Ontario. Please don't try and enforce your "frame" on me. I don't live in a society where right wing frames dominate the discourse so your lecture about catering to them is falling on deaf ears. Mooney and Nisbet make the same mistake. They assume that every science writer is only interested in writing for people in Texas or New Jersey. The irony here is that they are "framing" science based on a society that many of us don't recognize. (Think Richard Dawkins in England.)

Second, even if you live in a society where truth is not valued does that mean you have to abandon it in order to get your point across? I hope that's not what you're saying but it sure sounds like it.

Third, you argue that "we cannot let the opposition frame the issues" but that's exactly what you're doing. The entire justification for "framing," as far as I can see, is to modify your language and style to conform to the rules set by our opponents. The real words for that are cop-out and surrender. I guess "framing" is just a more politically correct term.

Coturnix goes on to explain two different meanings of framing.

The first meaning of 'framing' is the use of language to evoke pre-existing frames in a very small, limited audience for a quick and effective "conversion" for a cause that has immediate political consequences, i.e., the next bill in congress, or the next election, etc. You do not educate them in details of science - they are not interested, do not have enough background and it does not matter if they do or don't understand the fine points. The goal is to bring them over to your side and recruit them to do whatever is politically necessary to win a particular battle over the side of pseudoscience/religion/conservatism. This is what Matt and Chris are discussing.

If this is what Chris and Matt are discussing then it's not science education and it's not science writing in the sense that I understand it. It's polemical writing that just happens to be about science.

As I explained at the January meeting in North Carolina, the top three requirements for good science writing are scientific accuracy, scientific accuracy, and scientific accuracy. As soon as you sacrifice the attempt to convey good accurate science to the general public then you're not doing science writing. You're doing something else.

If you, Chris, and Matt truly believe that you don't need to educate the public about good science in order to win a political fight about science then we don't just have different worldviews, ... we're on different planets.

The second meaning of 'framing' is the use of language to introduce new frames into the public discourse and, as a result, change the entire intellectual landscape. This is necessarily a long-term project - as in: a couple of decades at best. By placing new frames into people's minds - more science-friendly or reality-friendly frames - it makes it easier in the future to recruit greater numbers of people to the cause-du-jour. A frame that is new now, and perhaps rejected by many as silly, will in ten or twenty years be a normal part of everyone's (especially the next generation's) emotional armamentarium. You put them in there now, and evoke them later when you need them. This is what PZ and Moran are talking about.

That's only part of what I'm talking about. What I'm really saying is that I value truth and honesty. If I believe in something I'm going to tell people about it. If that turns out to be a minority opinion then that's the way the cookie crumbles. I don't lie awake at night thinking about how the people of North Carolina might interpret my words. My worldview doesn't get "framed" by others. Does yours? Do you worry about how the average Canadian will look at your articles and then make appropriate adjustments to avoid offending them?

First rule: Know your audience.

Adjust your language to the audience. One language for fellow scientists, another for educated lay-people who are inclined to agree with you, another for people who are disinclined to agree with you, etc.

I write for intelligent lay-people, period. I don't change my style from day-to-day depending on whether I think most people will agree or disagree. Quite frankly, I usually assume that most will disagree. That's what curmudgeons do!

Second rule: Truth will not let you free.

Truth is not sufficient. Dry data will not sway non-scientists. Their eyes will glaze over and they'll move on. Reserve your precision for your papers, posters and talks. You can talk like that to your fellow scientists. But as soon as you leave that narrow circle you will have to adjust your language.

Truth may not be everything but it's so far ahead of whatever's in second place that it might as well be everything. Once you abandon truth you've lost.

Now I'm sure you really didn't meant to equate "truth" with "dry data" but for a posting that supposed to be about the precision of words, that's a serious slip. What you should have said is that science writers should always tell the truth about science but they don't necessarily need to explain every detail. This has nothing to do with framing. It's just part of the common sense of science writing.

In his article, Coturnix now launches into an extended discussion of how to lie to the public without calling it a lie. He claims that doing this is not dishonest. He claims that it's okay to abandon the essential principles of science; scientific accuracy, honesty, and integrity, in order to convince the public in some scientific debate.

It totally does not matter if the targets of your framing have no comprehension of evolution as long as they believe you when you tell them it is true and then act accordingly in the voting booth. This is not a sell-out to our high-minded principles: we will still adhere to our high standards of accuracy in the classroom and in our research reports. But not in our "Natural History Magazine" articles, or on our blogs, where that is inappropriate (at least in some types of blog-posts, like this one, for instance). That is why I, contra PZ and Larry, think that this movie is an excellent tool. It gets evolution wrong, but that is not the point. It visually frames evolution in a way that an uneducated, uninterested, ADHD-riddled layperson can "grok" it in about two minutes. The movie prepares the person for your carefully crafted spiel. And if the person ends up believing that evolution is a fact, it makes no difference if his/her conception of evolution is not 100% correct (hey, Dawkins and Dawkins get it wrong, so why not some Joe Schmoe?). If one out of a thousand viewers of the movie shows more interest, there are plenty of resources you can use to teach that person finer points and make his/her understanding better.

Coturnix, I will not follow you down that path. I do not adhere to a "high standard of accuracy" in the classroom and something else in my textbooks and my blog. If that's what you truly believe we should do, then you are on the verge of losing my respect. If that's what Mooney and Nisbet are saying then they are absolutely, totally wrong about science writing.

Arguing Against God

 
John Wilkins brings up an issue that just doesn't seem to go away [Disagreeing with PZ]. He argues that there's a stupid version of religion and a smart, sophisticated version of religion. Wilkins claims that "aggressive" atheists are picking on the stupid version and not addressing the smart version. He implies that it's harder to refute the smart version.

This is what I reject about the Dawkins/Moran/PZ aggressive atheism - it takes the most stupid version of religion, argues against it, and then claims to have given reasons for not being religious. At best (and here I concur) they have given reasons not to be stupid theists. But a good argument takes on the best of the opposing view, not the worst.

John, I debate the existence of God. I have not ignored any arguments for the existence of God that I know of. If you think there are good arguments for the existence of God that I have avoided then please make them known to me. I'm not interested in any of the baggage that comes along with accepting the existence of God. As far as I'm concerned they are completely meaningless unless you can prove that God exists.

I'm aware of the fact that, C.S.Lewis, Jerry Falwell, the Jesuits, and Francis Collins have different concepts of what must follow once you accept the existence of God. Some of those concepts are "sophisticated" and some are "stupid." I don't care. I'm only interested in whether or not there is a God in the first place.

Looking forward to seeing your list of "smart" arguments for the existence of God I am,

Your Agressive Atheist.

Blogroll

 
I'm new to blogging so please help me out with the controversy about blogrolling. Apparently there are some bloggers who amass a huge list of blogs in their "blogroll." There almost seems to be a contest to see who can list the most blogs. Coturnix is an example that comes to mind.

Meanwhile, there are some bloggers who want to clean up their list to include only active blogs or, perhaps, only the best blogs. This has prompted some debate. The latest entry is from Janet Stemwedel [Hierarchy, meritocracy, the blogosphere, and the real world]. It's all very confusing to this novice. Janet seems to think there's some powerful meaning behind whether someone is on your list of blogs or not. She seems to be implying that the "big" bloggers have a duty to list smaller bloogers.

I don't get it. My list is simply a list of blogs that I like to read. Nothing more, nothing less. Janet's blog Adventures in Ethics and Science is on my list. Sandwalk is not on her list. Should I be upset?

How to Communicate Science

 
EurekAlert has posted a short press release from an unknown source concerning an upcoming article that's about to be published in Science magazine [Scientists must improve communication tactics, Science article proclaims].

The article is by Chris Mooney and Matthew Nisbet and it concerns science communication. Here's what the press release says about the authors.

Mooney is a regular columnist for Seed, covering the intersection of science and politics. His blog, “The Intersection”, is a part of the ScienceBlogs network, a Seed Media Group venture. He is the author of two books, The Republican War on Science and the forthcoming Storm World: Hurricanes, Politics, and the Battle Over Global Warming (Harcourt, July 2007).

Dr. Nisbet contributes the “Framing Science” blog to the ScienceBlogs network. He is a professor in the School of Communication at American University. His research focuses on the intersections between science, media and politics, and he is the author or co-author of more than a dozen peer-reviewed studies in the area.

Seed Media Group is a leading science media and communications company. Headquartered in New York, with correspondents across the globe, Seed Media Group’s brands include the critically acclaimed science magazine Seed, and ScienceBlogs, the leading digital community dedicated to science. For more information, please visit www.seedmediagroup.com.

I enjoy reading Chris' blog and I think he does a good job of explaining some aspects of science. However, I must admit to being a little bit nervous when non-scientists tell me how to write about science. I don't see overwhelming evidence that non-scientists are doing a good job ... with some notable exceptions.

I'm also disturbed about the emphasis on Seed Media Group. I'll wait until I see the actual article—it isn't available yet—but I'll be surprised if Mooney and Nisbet list their affiliation as "Seed Media Group." What do the ScienceBlog bloggers say about this? Do you see yourselves as employees or representatives of Seed Media Group?

Here's what the press release says about their article.

“In writing this article together, we argue that scientists shouldn’t exclusively blame politicians and journalists for gridlock on issues like climate change,” says Mooney. “Part of the problem is that scientists carry with them the wrong assumptions about what makes for effective communication.”

The authors point out that when scientists discuss science-related policy questions in technical language, many members of the public tune it out. Moreover, even while continuing to employ traditional modes of communication, scientists themselves have come under increasing attack for being too atheistic, too self-interested and/or too liberal. Scientists can improve their communication skills by applying research on “framing” and other work in the social sciences. As the article puts it, “Frames organize central ideas in a debate, defining a controversy so that it will resonate with core values and assumptions. Frames pare down complex issues by giving some aspects greater emphasis than others. They allow citizens to rapidly identify why an issue matters, who might be responsible and what should be done.”

“Our suggestions should not be confused with spin; rather, we are advocating the conscious adoption of more effective (and thus, more informative) communication techniques,” said Dr. Nisbet. “Already, influential sectors of the scientific community are beginning to realize that new public engagement strategies are desperately needed.”

That's one way of looking at it. However, I prefer not to hide my atheism and my liberal viewpoint under a bushel. I don't know what "framing" is—and reading the blog isn't much help—but it sounds an awful lot like spin to me.

I think I'll try and emulate Isaac Asimov, Dick Lewontin, Carl Sagan, Francis Crick, Richard Dawkins, PZ Myers, Peter Medawar, Niles Eldredge, and Stephen Jay Gould. They're scientists who, in my opinion, communicate pretty effectively and they attracted lots of readers. They didn't have to disguise their atheism or their liberalism in order to get a point across. I don't think they took lessons on "framing."

Chris Mooney [I Have a Paper in Science] and Matt Nisbet [At the journal Science] have already blogged about the upcoming article. Let the debate begin!

100,000 Visits

 
I forgot to mention that the 100,000th visit to Sandwalk happened a few days ago. I appreciate eveyone who has paid me a visit over the past five months. Please keep coming. I promise not to try anything as complicated as blood clotting for at least another year!

Evolution for Idiots

 
Here's a short video that has just been posted on The Panda's Thumb. You can read the comments over there or watch the video here. Let's make our own list of everything that's wrong with it. Sometimes I wonder whether these things help or hurt the cause of science education. Today I'm leaning towards "hurt."

Blood Clotting: Intrinsic Activity

 
Blood clotting is initiated by the extrinsic activity which is localized to the surfaces of tissue factor (TF) bearing cells. These cells are located at the site of injury [Blood Clotting: Extrinsic Activity and Platelet Activation]. The initial steps result in activation of some blood coagulation factors and activation of platelets.

The next step in coagulation requires an amplification of thrombin production so that clotting can proceed rapidly. The amplification stage is referred to as intrinsic activity, or the intrinsic pathway. These reactions take place on the surface of activated platelets. Activated platelets aggregate at the site of injury [Blood Clotting: Platelets].

The ultimate goal in the amplification stage is to create a prothrombinase activity on platelet surfaces. Prothrombinase will cleave prothrombin to make thrombin and thrombin is the enzyme that cuts fibrinogen to make fibrin for clot formation [Blood Clotting: The Basics]. The platelet prothrombinase activity is the same as the activity on TP-bearing cells: it’s formed from Xa and membrane-bound Va. The difference between the two pathways (extrinsic and intrinsic) is the way in which factor X (ten) is activated to form Xa. The platelet enzyme is called “tenase” (cleaves factor “ten”) and it’s formed from Factor VIIIa and Factor IXa.

The final steps are shown in the figure below. Large amounts of thrombin are generated and large amounts of fibrin are produced.


Tenase activity is formed when VIIIa binds to the platelet membrane. VIIIa is produced by thrombin cleavage of factor VIII in the extrinsic part of the pathway. Factor VIII is the factor that associates with von Willebrand factor (vWF). The most common hereditary bleeding disorder is caused by a deficiency of von Willebrand factor (von Willebrand diseases). In the absence of vWF, factor VIII is unstable and platelets cannot form the tenase enzyme. Hemophilia A is the X-linked form of hemophilia that was common in European royal families descending from Queen Victoria. It is caused by a deficiency of Factor VIII.

IXa, the active component of tenase, is produced when XIa cleaves the precursor factor IX. Deficiencies in factor IX cause hemophilia B. IX is another factor that contains a γ-carboxyglutamyl residue that chelates a Ca⁺⁺ ion.

A little bit of IXa is made in the extrinsic pathway but the major amplification on platelet cell surfaces requires XIa. The pathway leading to formation of XIa is shown on the left. HMWK stands for “high molecular weight kininogen.” It binds to and stabilizes XIa and kallikren.

Thanks to my colleague Marion Packham for answering some questions about platelets. I recommend the Hemostasis & Thrombosis chapter in Harper's Illustrated Biochemistry 27th ed. written by my colleagues Marg Rand and Bob Murray.

Devlin, T.H. (ed.) (2006) Textbook of Biochemistry with Clinical Correlations 6th ed., Wiley-Liss, Hoboken, N.J. (USA)

Rand, M.L. and Murray, R.K. (2006) Hemostasis & Thrombosis in Harper's Illustrated Biochemistry 27th ed., R.K. Murray, D.K. Granner, and V.W. Rodwell eds. McGraw Hill Lange, Toronto Canada.

Wolberg, A.S. (2007) Thrombin generation and fibrin clot structure. Blood Reviews Jan. 5 2007. [PubMed]

Blood Clotting: Extrinsic Activity and Platelet Activation

 
We've seen that blood clots are formed when fibrin molecules aggregate at the site of injury to form a fibrous clot. Fibrin is produced by cleaving the precursor fibrinogen. The enzyme that cuts the protein is a protease called thrombin [Blood Clotting: The Basics].

Thrombin is the active form of the protease enzyme. It is derived from a precursor called prothrombin and the production of thrombin at the site of injury requires an enzyme to cleave prothrombin. This enzyme is called prothrombinase. Like thrombin, prothrombinase is a protease only its substrate is prothrombin instead of fibrinogen.

Prothrombinase is a multisubunit enzyme composed of two different polypeptide chains. One of them is an activated form of Factor V (factor five) called FVa or just Va. The "a" signifies an activated form of a clotting factor. The other subunit of prothrombinase is an activated form of Factor X called FXa (activated factor ten). Xa plus Va together make the prothrombinase that cleaves prothrombin to make thrombin. This leads directly to blood clotting.

In order for this cascade to be initiated there has to be some trigger that leads to formation of prothrombinase (Xa + Va). This trigger has to be localized to the region where a blood vessel is damaged so that the blood clot forms at the right place. The initiation step is called the extrinsic activity.


The cells lining blood vessels contain a membrane protein called tissue factor (TF). It is sometimes referred to by its old name Factor III. TF is normally masked but it becomes exposed when the cells are damaged. Factor VII (VII) binds to exposed TF to form a protease that cleaves Factor X to Xa. Xa plus Va then cleaves prothrombin to thrombin and thrombin activates a number of other factors that will enhance the clotting. There is always a little bit of Va circulating in the blood stream and it binds to TF-bearing cells when the membrane is exposed.

VII is one of the proteins containing a γ carboxyglutamyl residue. This is a modification that requires vitamin K [Vitamin K, Nobel Laureates: Dam and Doisy]. The γ carboxyglutamyl residue binds to calcium ions (Ca⁺⁺). Calcium is an important cofactor in clot formation because there are several factors with γ-carboxyglutamyl resides. They must bind Ca⁺⁺ because the postive charges allow the proteins to interact with negatively charged (anionic) surfaces such as those that are exposed when membranes are disrupted. The binding to anionic molecules explains why heparin (Monday's Molecule #20) inhibits clotting but we'll get to that another day.

The important activation steps that are catalyzed by thrombin are the conversion of Factor VIII to VIIIa and Factor IX to IXa. These contribute to the activation of platelets as we will see in the next posting. Factor VIII circulates in blood plasma as a complex with von Willebrand factor (vWF) but upon cleavage of VIII to VIIIa vWF dissociates. As you can see from the diagram, the first thrombin that is formed also cleaves Factor V to Va and this greatly increases the concentration of Va, which bind to the TF-bearing cells. This, in turn, leads to more prothrombinase being produced and more thrombin—an example of positive feedback.

The VIIa/TF complex also cleaves Factor IX to IXa. This serves to stimulate activated platelets.

Thrombin will also cleave some fibrinogen to fibrin initiating clot formation. However, the rate of fibrin formation that results from extrinsic activity is not sufficient to support the formation of a large clot. An additional step called intrinsic activity is needed to amplify the production of thrombin. This requires active platelets.

Active platelets look very different from the inactive forms. The active versions have a much more irregular shape and they have many extensions. It is the active platelets that aggregate to form a plug at the site of injury and the enhanced clotting activities take place on the platelet membrane surfaces.


[The clotting pathways are modified versions of figures from Wolberg, 2007]

Blood Clotting: Platelets

 
Platelets are small bits of cells that aid in the formation of blood clots and help seal breaks in blood vessels.

They are formed by pinching off small bits of a large cell called a megakaryocyte. Megakaryocytes are found in bone marrow. The platelets contains mitochondria and cytoplasm but no nuclei.

Platelets have a number of enzymes and factors that promote wound healing and their membranes are studded with various receptors and factors that promote blood clotting at the site of injury. Normal blood has a very high concentration of platelets (200,000 per microliter) - this is the platelet count that's a common diagnostic test for many medical problems. Platelets have a half life of about ten days so they need to be continuously produced in the bone marrow.

When a blood vessel is injured a patch of endothelial cells are destroyed exposing the underlying collagen matrix. Platelets bind to collagen and then to each other leading to an aggregation of platelets and formation of a plug that stops the bleeding. The platelet plug also stimulates blood clotting at the site of injury because many of the factors that promote clotting are carried by platelets.

This process is shown in the electron micrograph on the right. The platelets are the small dark cell-like objects. Some of them have adhered to the collagen matrix on the far right and this stimulates other platelets to bind to the ones that first arrived at the lesion. A platelet plug is building.

These platelets will also become activated for formation of fibrin blood clots at this site. Many of the proteins on the cell surface will aid in generating thrombin from prothrombin. Thrombin cleaves fibrinogin to produce the clotting protein, fibrin [Blood Clotting: The Basics].

Gary Carlson has created a number of very impressive images of platelets. Click on the images of aggregating platelets and blot clots forming at a wound.

(Electron micrograph is from Platelets)

Nobel Laureate: Arne Tiselius

 

The Nobel Prize in Chemistry 1948.



Arne Wilhelm Kaurin Tiselius (1902-1971): "for his research on electrophoresis and adsorption analysis, especially for his discoveries concerning the complex nature of the serum proteins"

Arne Tiselius won the Nobel Prize in 1948 for discovering how to separate protein by electrophoresis. Beginning in the early 1930's, Tiselius developed techniques for separating proteins on the basis of their migration in an electric field. Positively charged proteins move toward the cathode and negatively charged proteins move toward the anode. The trick was to detect the proteins as they move in a solution (the "moving boundary"). By the late 1930's, Tiselius had constructed a complex apparatus that detected bands of protein by recording changes in the refractive index of the solution as the boundary moved past a lens ("schlieren" method).

He used this technique to analyze the protein in blood plasma showing for the first time that the mixture was very complex and heterogeneous. The figure below is from his presentation speech. It shows that the most important proteins in human serum are albumin, various globulins (antibodies) and fibrinogen. Fibrinogen is the protein required for blood clotting.

These days electrophoresis is a common technique in biochemistry labs, especially using a gel matrix. Undergraduates easily separate complex mixtures at a resolution that Tiselius never dreamed of when he began his work 80 years ago.

The power of the technique, even with the clumsy apparatus of the 1940's was widely appreciated and that's why the Nobel Prize presenter said,

The value of the new methods which have been briefly described here, is especially brought to light by their use, which is nowadays general, in international research in biochemistry and in medicine. Tiselius' apparatuses for electrophoresis and analysis by adsorption nowadays form part of the normal equipment of a great number of laboratories and medical institutes not only in Sweden but also abroad. One notices continually in chemical periodicals new experiments made by using Tiselius' methods.

Tiselius really is the father of electrophoresis and his contribution to modern biochemistry needs to be more widely appreciated.

Religion in the United Kingdom

 
See below the fold for an explanation of the categories and more data.

Regular churchgoers:15% of UK adults go to church at least once a month. This is equivalent to 7.6 million regular churchgoers
in the UK.

Fringe churchgoers: 3% of UK adults go to church less than monthly but at least six times a year. This is equivalent to 1.6 million fringe churchgoers in the UK.

Occasional churchgoers: 7% of UK adults go to church less than six times a year but at least once a year. This is equivalent to 3.4 million occasional churchgoers in the UK.

Open de-churched: 5% of UK adults do not go to church* but they used to attend in the past and are very or fairly likely to go to church in future. This is equivalent to 2.3 million adults in the UK who are open de-churched.

Closed de-churched: 28% of UK adults do not go to church*, used to attend in the past but say they are not very or not at all likely to go to church in future. This is equivalent to 13.7 million adults in the UK who are closed de-churched.

Open non-churched: 1% of UK adults have never been to church in their life, apart from weddings, baptisms or funerals yet say they are very or fairly likely to go to church in future. This is equivalent to 0.6 million adults in the UK who are open non-churched.

Closed non-churched: 32% of UK adults have never been to church in their life, apart from weddings, baptisms or funerals and are not very or not at all likely to go to church in future. This is equivalent to 15.6 million adults in the UK who are open closed non-churched.

Other religions: 6% of UK adults, equivalent to 3.2 million people, belong to religions other than Christianity.

Unassigned: Only 162 respondents (2%) were “unassigned” because they did not answer the question on prior church attendance, although none of these had been to church in the last 12 months. A third of them attended church less than once a year or never, whilst two thirds declined to state their frequency of attendance.

* never attend or go less than once a year.

This is what a modern secular society looks like [Churchgoing in the UK]. People in Canada and the USA need to be aware of these numbers because that's where we're headed, especially in Canada. The executive summary says it all.

Two thirds of UK adults (66%) or 32.2 million people have no connection with church at present (nor with another religion). These people are evenly divided between those who have been in the past but have since left (16 million) and those who have never been in their lives (16.2 million). This secular majority presents a major challenge to churches. Most of them - 29.3 million - are unreceptive and closed to attending church; churchgoing is simply not on their agenda.

Apologists will argue that not going to church is not the same as disbelieving in God. This is true but it's a pretty good indication of how committed one is to religion.

Britain is still a country that believes in God whereas belief in a personal God has declined markedly. More than 2 in 3 (67%) of people in Britain today believe in God while 1 in 4 (26%) believe in a personal God.

In other words, 33% don't believe in God and less than half of all believers believe in a personal God. If you're a God person then the demographics does not look promising.

Making Universal Donor Type O Blood

 
An advance report that will soon be published in Nature Biotechnology describes progress toward artificially creating type O blood from A, AB, and B blood donors. The advantage is that type O blood can be given to any patient who needs a blood transfusion. If you can convert all donated blood to the universal donor then the blood supply becomes much more flexible.

The ABO blood types are determined by the presence or absence of sugar groups on proteins bound to the outer surface of red blood cells [ABO Blood Types]. A single gene is responsible for the different blood types [Human ABO Gene] and the genetics is well understood [Genetics of ABO Blood Types].

Liu et al. (2007) screened 2,500 fungus and bacterial species for enzymes that could remove the A antigens and B antigens from red blood cells.

The rationale is illustrated in this figure from their paper.

All red blood cells have H antigen. In people with type A blood the H antigen is converted to A antigen through the action of the enzyme α1,3-N- galactosaminyl transferase (GTA). GTA adds N-acetyl- galactosamine (GalNAc) to the H antigen structure. If you have blood type B then a different version of the enzyme (GTB) adds galactose (Gal) to make B antigen [see ABO Blood Types]. If neither version of the enzyme is present then H antigen will not be modified and you will have blood type O.

The authors discovered several enzymes (A-zyme) that remove GalNAc converting type A blood back to type O blood. They decided to characterize an enzyme from the flavobacterium Elizabethkingia meningoseptum that had previously been identified—and patented—in 2002. Liu et al. constucted recombinant versions of the E. meningoseptum gene and expressed it in Escherichia coli. They were able to make large quantities of active enzyme which led to crystallization and solving the structure.

A version of B-zyme was identified in the common gut bacterium Bacteroides fragilis. The gene for this enzyme was also cloned and expressed in E. coli. A modified version with high activity was selected for further study.

The two purified enzymes were used to treat blood from A, AB, and B donors. All traces of A- and B-antigens were removed as demonstrated by the lack of reactivity against anti-A and anti-B antibodies. Thus, the treated blood was effectively type O and was suitable to use as universal donor. The authors are confident that the process can be scaled up.

Accordingly, we believe that automated cost-effective processes can be developed for practical use in transfusion medicine.

Several of the authors are associated with ZymeQuest Inc. of Beverly MA (USA) and the project was funded, in part, by ZymeQuest. The authors declare their competing interest in a statement that can only be accessed from the full text version of the paper on the website. Here's the statement,

Declaration: Authors (except for G.S., J.M.N., W.S.L. and Y.V.) are employees, consultants and/or shareholders in Zymequest Inc., which holds patents covering the described technologies.

Liu, Q.P., Sulzenbacher, G., Yuan, H., Bennett, E.P., Pietz, G., Saunders, K., Spence, J., Nudelman, E., Levery, S.B., White, T., Neveu, J.M., Lane, W.S., Bourne, Y., Olsson, M.L., Henrissat, B. and Clausen, H. (2007) Bacterial glycosidases for the production of universal red blood cells. Nature Biotechnology Published online: 1 April 2007; | doi:10.1038/nbt1298.

Creationists Invade Ottawa

 
Two regulars from talk.origins have a blog called Thinking for Free. Each of them has published a report on a Creationsts meeting in Ottawa last February. Read Eamon Knight's version at Creationistist Forum -- Eamon's View and Theo Bromine's version at Creationist Forum - Theo's view.