How 'molecular machines' kick start gene activation revealed

 
That's the title of a press release published on Biology News Net, and several other science news sites. Here's the opening sentence ...

How 'molecular machines' inside cells swing into action to activate genes at different times in a cell's life is revealed today (6 November) in new research published in Molecular Cell.

How could you not want to find out more? This sounds like a real breakthrough.

Try and guess what the new discovery is all about before reading on ...

From the website Biology News Net and Imperial College London ...

Genes are made of double stranded DNA molecules containing the coded information an organism's cells need to produce proteins. The DNA double strands need to be 'melted out' and separated in order for the code to be accessed. Once accessed, the genetic codes are converted to messenger RNAs (mRNA) which are used to make proteins. Cells need to produce particular proteins at different times in their lives, to help them respond and adapt to changes in their environment.

The new study outlines exactly how a molecular machine called RNA polymerase, which reads the DNA code and synthesizes mRNA, is kickstarted by specialised activator proteins. The scientists have discovered that RNA polymerase uses a tightly regulated internal blocking system that prevents genes from being activated when they are not needed.

I'm underwhelmed. How is science journalism ever going to be taken seriously if this is the sort of thing that university press offices publish?

We've known and understood the basics of transcription initiation by RNA polymerase and its activators for thirty years. This study concerns a minor variation of that process involving σ⁵⁴ in bacteria.

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Never Let Your Gas Tank Get Below Half Full

 
Friday's Urban Legend: True

How many of you have heard the story that you should always drive your car with the gas tank as full as possible? According to many, you should never let the gas in your tank fall below the half full mark on your gas gauge.

You probably thought this was a tale told by elderly wives—with apologies to old men who also tell tales.

Well, it turns out that there is actual, scientific, evidence to support this warning. Cliff Allen did the experiment according to the Sept. 13, 2008 issue of New Scientist [Petrol Gauge Challenge].

SLIGHTLY more practical routes to fuel economy occurred to Cliff Allen when he noticed that, according to his petrol gauge, the fuel in the top half of his tank lasted considerably longer than the bottom half. As any Feedback reader (and possibly only a Feedback reader) would, he investigated. Systematically.

Over several months he recorded the distances travelled using the fuel from the top and bottom halves. The average for the top was 400 kilometres (250 miles) and for the bottom a mere 300 kilometres (185 miles). Since then, he writes, "of course I have only used the top of my tank and have consistently achieved around 250 miles - I'm not stupid!"

Cliff was obviously keen to discuss this, at length, with his learned friends, "some of whom gained General Certificate of Secondary Education qualifications" at age 14. He was "mostly appalled at their incredulity and lack of interest".

However, his friend Alan suggested that the fact that petrol always comes out of the bottom of the tank causes it to use more petrol so we might benefit from turning the tank upside-down. John suggested the increased efficiency might be due to the height of the fuel, so the tank should be put on the roof. Mostyn proposed putting a brick in the tank, as this apparently works very well for saving water in toilet cisterns. Tony wants to make the top of the tank larger than the bottom, to increase the proportion of its volume at the top, and thinks a carrot shape would be optimal.

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P.S. for the irony impaired.

The Awesome Power of Prayer

 
James C. Dobson, Ph.D. is Founder and Chairman of Focus on the Family. He is not a fan of Barrack Obama and came to the realization that John McCain and Sarah Palin would be much better for the country.

Dobson urged his followers to pray [Dr. Dobson’s October Newsletter].

Regardless of your political views, I want to urge Christians everywhere to be in prayer about this election. There are many scriptural references wherein King David “inquired of God” when he was faced by troubling circumstances (1 Samuel 23:2,4; 30:8; 2 Samuel 2:1; 5:19,23). It is time for Christians everywhere to turn to Him for guidance and wisdom. Find some time to be still and listen to what He wants to tell you. The National Day of Prayer Task Force, led by my wonderful wife, Shirley, has embarked on a national campaign entitled “Pray for Election Day.” All around the country, individuals and groups are being encouraged to gather every Thursday leading up to Nov. 4 between 12 noon and 12:30 p.m. Spend time with the Lord, asking Him to guide and direct those privileged to cast a ballot. If you are able, I would also encourage you to fast and pray immed”ately before the election. After all, it was the Reverend Billy Graham who once said that “To get nations back on their feet, we must first get down on our knees.”20 Amen, Dr. Graham.

This election is about the future of the nation, but it will also go a long way toward determining the culture your children and grandchildren will come to know. I know you will vote with your children and your children’s children in mind. That certainly puts the election in a different light, doesn’t it?

Apparently God was listening. He answered their prayers on Tuesday. Here's how Tom Hess describes the result [‘We Need to Continue to be in Prayer for America’].

With an Obama administration forthcoming, Focus Action’s Tom Minnery says, “We’ve got a big challenge ahead of us.”

He and FRC Action President Tony Perkins encouraged CitizenLink viewers to remain hopeful of what God might do in the next four years — and to be in prayer.

“For those who have been praying for weeks, our responsibility does not end today,” Perkins said. “In Luke 18, Jesus said men should not lose heart, but they should pray. We need to continue to be in prayer for America.”

Minnery pointed out that in the Bible, God worked through pagan rulers such as Nebuchadnezzar, Darius and Cyrus to accomplish his purposes, and that values voters ought to begin praying for President-elect Obama.

“God can use any president for his own purposes,” Minnery said.

You can't make this stuff up.

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[Hat Tip: Primordial Blog]

It's Her Last Saturday in the Lab

 
Eva Amsen blogs at Expression Patterns on the Nature Network [Last Saturday]. My department will miss her when she leaves.

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Small Science Is Good Science?

 
I've been thinking a lot lately about what's wrong with science in the 21st century. Part of the problem is sloppy thinking that becomes apparent when you realize how many widely believed models are inconsistent with what we know about biology. I assume that similar problems occur in other disciplines.

One wonders if the proliferation of papers with huge numbers of authors is part of the problem. Maybe this fad of "multidisciplinary" science is part of the problem and not part of the solution? Is it possible to be an expert in two or more different disciplines?

I've seen plenty of example of biochemists and molecular biologists who publish papers about evolution without knowing much about evolution. Is this an isolated example?

Speaking of "big science," I was reminded of a paper published by Bruce Alberts back in 1985 in Cell. The title was "Limits to growth: In biology, small science is good science" (Alberts 1985).

These days, many people grow up believing that bigger is better. Giant factories that produce Wonder Bread have replaced thousands of corner bakeries, driven by the increased efficiency of scale. There is an unfortunate tendency to extend this view to the biological research community, and I have on occasion heard a major symposium speaker introduced in glowing terms as the coauthor of more than fifty papers per year. While I can admire the energy and management skills required to maintain a very large laboratory, the best biology is rarely done in this way. With a few notable exceptions, the biochemists and molecular biologists I most respect run relatively small laboratories and publish when they have something important to report. As I shall argue here, doing good science is very different from producing bread, and there are compelling reasons why large laboratories are in general less efficient and less interesting than smaller ones. To reflect this fact, I believe that changes in funding patterns and expectations would be useful in the biological sciences.

Some "big science" is good. The sequencing of the human genome, and other genomes, for example, was a big science project that benefited the entire biological community. But I'm not sure that significant advances in our understanding of how life works come from big labs. Does anyone have examples? What are the most significant conceptual advances to come out of big labs?

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Alberts, B.M. (1985) Limits to growth: In biology, small science is good science. Cell 41:337-338. [PubMed] [doi:10.1016/S0092-8674(85)80001-5]

Ignore, Reject, Answer? What to Do about Student Email Messages

 
Some of my colleagues are running courses where they ask students to write essays on science subjects. Part of the assignment is to contact a Professor in the discipline and get them to help with the scientific content of the essay. The idea is for the students to make sure they have their facts correct. A side benefit is that it gets the students in touch with active researchers.

Some of us object to this procedure on the grounds that if it became widespread there would be hundreds of students looking for Professors to help them on their assignment. Most Professors have other priorities, like teaching their own classes. To some extent, our colleagues who engage in this practice are downloading their teaching responsibilities onto others.

From 1992-2000 I ran a molecular biology course where the students had to write a major essay. They were told to do the research themselves but the instructors would be available if they need help with the interpretation of some papers. If necessary, we would put them in touch with an expert but only after the student had done enough work to ask intelligent questions on difficult material.

Here's an email message that was sent to my Sandwalk address last night. How should I respond? I don't feel comfortable ignoring the message. I will feel awkward if I refuse to help. I don't had time to answer the question—it's complicated and, besides, it's not my area of expertise.

Dear Professor Moran,

As part of a University assignment, I have been asked to email a group of experts to request their professional opinion on a particular question.

I have come to understand that a child with Dyspraxia should supplement their diet with a high dose of essential fatty acids. However, as non-Dyspraxic people age it is advised that they also should supplement their diet with these oils to combat age-related memory loss. Does this mean that people with Dyspraxia should augment their intake yet again when they age? If so, could this have an adverse effect on their health?

As your organisation came up in an internet search as being reputable, your answer to this question would be much appreciated.

I would like to thank you for taking the time to read this email and I hope to hear from you soon.

Yours sincerely,

This makes me angry. No matter what I do, I'm going to be disappointing a student who might really benefit from a reply. In my opinion the student's Professor is at fault for assigning such a task to the students.

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Barack Obama Will Save Religion in America

 
Frank Scaheffer writes in The Huffington Post [President Obama: Bad News For the New Atheists and Other Fundamentalists].

The Obama presidency is great news for almost everyone. It's bad news for some odd ideological bedfellows: the Religious Right and the so-called New Atheists.

Into the all or nothing culture wars, and the all or nothing wars between the so-called New Atheists and religion the election of President elect Obama reintroduces nuance. President elect Obama's ability to believe in Jesus, yet question, is going to rescue American religion in general and Christianity in particular, from the extremes.

There is no way to understand President elect Obama's victory as anything less than the start of not just a monumental political change but a spiritual revolution as well.

Who knew? I bet all atheists and agnostics are feeling pretty stupid right now knowing that they've been tricked by the slick-talking Obama.

And what is the "nuanced" spiritual revolution going to look like?

To the New Atheists who think that with the resounding defeat of the Religious Right, we are entering a secular age, think again. Obama will block your path. He'll do it for the same reason he'll make the Religious Right's paranoid fantasies about him soon seem shamefully ridiculous. That's because President elect Obama is that rarest of all rare people: a thoughtful, compassionate and likable statesman who also is a thoughtful, compassionate and likable religious believer.

Sounds like trouble. President Obama is going to block the path to a secular society. Gosh. I knew that American Presidents were leaders of the free world and the most powerful men (no women so far) on the planet but even I had no idea they were that powerful.

President-elect Obama brings another perspective to faith . It goes something like this:

How do cultures define themselves if not through ritual? In the "big moments" of life; birth, marriage, sickness, death "who" -- in the inimitable words of Ghost Busters -- "you gonna call?" As President elect Obama has said, and I paraphrase: Strip the human race of our spiritual language and what do we tell each other about hope?

As President elect Obama has pointed out, a world of all math but no poetry is not fit for human habitation. If everything feels flat and dull, stripped of mystery and meaning who will bother to do the science? Why bother, if all we're doing is serving those selfish genes for another round of meaningless propagation?

So does this faith always make "sense?" No. Because our perspective is from the inside, something like paint contemplating the painting of which it's a part. We're all in the same boat, all stuck on the same "canvas."

Ohmygod. Frank Shaeffer and Barack Obama have discovered the atheist dirty little secret. All of us atheists are flat and dull—we can't be born, get married, or die without calling upon God to help us.

Does anyone actually believe this stuff?

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[Hat Tip: RichardDawkins.net]

Evolution by Gene Duplication

Chymotrypsin (Monday's Molecule #95), trypsin, and elastase are enzymes that digest proteins in the stomach and intestine. All three enzymes have a similar mechanism of hydrolysis characterized by the presence of a catalytic triad of amino acid side chains consisting of aspartate, histidine, and serine residues. The serine side chain is directly involved in catalyzing the cleavage of proteins and that's why these enzymes are called serine proteases.

The three enzymes differ in specificity. Chymotrypsin cleaves foreign proteins primarily at tyrosine (Tyr) resides, trypsin is specific for cleavage at arginine (Arg) or lysine (Lys) resideus, and elastin cleaves at alanine (Ala) residues.

The genes for the three enzymes are homologous and the structures of the three enzymes are very similar as shown below (left: chymotrypsin [PDB 5CHA], middle: trypsin [PDB 1TLD], right: elastase [PDB 3EST]).


The active sites of the enzymes are slightly different so that specificity depends on which amino acid side chains of the substrate protein fit into the binding pocket.


It's reasonable to suppose that the primitive enzyme could bind weakly to many different substrates and cleave many different kinds of proteins inefficiently. An ancient gene duplication allowed one copy of the gene to evolve toward a much more active enzyme that cleaved only at certain residues. A second gene duplication gave rise to a third enzyme that cleaved at another residue. Finally the remaining gene evolved into a very active enzyme that cut at a third position.

The end result was a set of three enzymes that could cut up any protein into small peptides that can be taken up by the cells lining the intestine. The original non-specific enzyme was slower and less efficient.

This is an example of evolution by gene duplication and the important point is that the ancestral gene probably encoded a non-specific enzyme that could carry out several different reactions with different substrates. It's not a question of the duplicated copy evolving an entirely new specificity. Instead, the duplicated gene usually "perfects" an already existing minor activity by becoming more specific. Meanwhile, the other copy can also be selected for enhanced specificity for another substrate.

This model also explains the evolution of lactate dehydrogenase and malate dehydrogenase (Evolution and Variation in Folded Proteins) and the pyruvate dehydrogenase family (Pyruvate Dehydrogenase Evolution).

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Nobel Laureate: John Howard Northrop

 

The Nobel Prize in Chemistry 1946.

"for their preparation of enzymes and virus proteins in a pure form"



John Howard Northrop (1891 - 1987) was a renowned protein chemist who developed techniques for purifying and crystallizing enzymes.

He shared the prize with James Sumner, who first showed that proteins could be crystallized and with Wendell Stanley who crystallized tobacco mosaic virus.

Most biographers note that Northrop was very interested in genealogy and was proud to point out that he was a direct descendant of Joseph Northrop who settled in New Milford Connecticut in 1636 (John H. Northrop). I don't know if any other Nobel Laureates can trace their North American ancestors back 400 years.

The significanc of Northrops work is summarized in this excerpt from the presentation speech on the Nobel Prize website.

THEME:
Nobel Laureates

Doctor John Northrop. You and your collaborators have developed the crystallization of enzymes and other active proteins into an art, of which you are the masters. The conditions for successful work in this field were explored by you, and in the course of that work interesting relationships between enzymes and related proteins were discovered, which may ultimately afford a clue to a fuller understanding of the mode of action of these substances.

We now know that trypsin, pepsin, and chymotrypsin are similar proteases that cleave other proteins. We also know that the active enzymes are derived from inactive precursors called zymogens. The zymogens (pepsinogen, trypsinogen, and chymtrypsinogen) are cleaved to remove part of the protein making the remainder into an acive enzyme. It's interesting to see how John H. Northrop described this discovery in his acceptance speech.

Formation of enzymes from their precursors. Pepsin, trypsin, and chymotrypsin are derived from inactive precursors. These precursors were isolated and crystallized and the formation of the active enzyme studied. The formation of pepsin from pepsinogen and trypsin from trypsinogen are autocatalytic reactions. These enzymes may therefore be "propagated", just as are bacteria. The formation of trypsin from trypsinogen may also be catalyzed by enterokinase, an enzyme of the digestive tract, or by an enzyme produced by a mold (Penicillium.) The formation of chymotrypsin from chymotrypsinogen is catalyzed only by trypsin, so far as is known. In all these reactions the increase in enzymatic activity is accompanied quantitatively by the appearance of the new enzyme protein which is quite different in all its properties from the original precursor. It seems to me that these results are perhaps the most convincing evidence that the enzymatic activity is actually a property of the protein molecule.

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What Does Change Look Like?

 
I'm glad Barrack Obama won the election. He is much less conservative than John McCain and much more likely to do good things for America.

Change is in the air, everybody is talking about a new direction for America under Barack Obama. What kind of changes can we expect? Here's a sample from last night's vote on several propositions [CNN.com].

This measure would amend the state constitution so that only a union between one man and one woman would be valid or recognized as a marriage in the state. A similar measure was on the ballot in 2006 but failed.

According to the exit poll [Arizona Prop.102], 67% of Protestants voted to ban gay marriage as did 51% of Catholics. About 13% of voters said they had no religion and 69% of them voted against Proposition 102.

This measure would prohibit unmarried "sexual partner[s]" from adopting children or from serving as foster parents. The measure specifies that the prohibition applies to both opposite-sex as well as same-sex couples.

According to the exit poll [Arkansas Initiative 1], the voters are evenly split between Democrats, Republicans, and Independents. Democrats voted against the initiative (52%) but the other two groups voted in favor of the ban. A majority of college graduates (52%) and those with postgraduate education (54%) voted in favor of the ban on adoptions.

This measure would amend the state constitution to specify that only marriages between one man and one woman would be recognized as valid in the state. If passed, the measure would trump a May 2008 ruling by the California Supreme Court that legalized same-sex marriage.

According to the exit poll [California Proposition 8], a majority of whites (53%) and Asians (53%) voted against Proposition 8 while a majority of African-Americans (70%) and Latinos (51%) voted in favor of the ban. Democrats (65%) and Independents (56%) were against the ban but 81% of Republicans voted in favor of the ban on gay marriage.

This measure would amend the state constitution to define the term "person" to include "any human being from the moment of fertilization." This definition would be applied to all aspects of the state constitution, including the provisions that ensure that no person has his or her life, liberty, or property taken away without due process of law. Thus, the measure would essentially have the effect of banning abortion.

According to the exit poll [Colorado Amendment 48], this amendment should have been approved by a substantial majority.

This measure would amend the state constitution to define marriage as a union between one man and one woman. In order to amend the Florida constitution, 60 percent of voters must vote in favor of the amendment.

According to the exit poll [Florida Amendment 2], 71% of Protestants and 66% of Catholics voted in favor of the amendment to ban gay marriage. A majority of Whites (60%), African-Americans (71%), and Latinos (64%) voted for the ban.

This measure would prohibit all abortions in the state except in cases where mother's life or health is at risk or in cases of rape or incest for pregnancies of less than 20 weeks. A similar measure that did not include exceptions for rape or the health of the mother was on the ballot in 2006, but was rejected by voters 44 to 56 percent.

According to the exit poll [South Dakota Initiative 11], only evangelical born-again Christians and conservative Republicans supported the initiative. A majority of all other groups voted against it.

This measure would allow terminally ill, competent, adult residents of the state to request and self-administer lethal medication prescribed by a physician. The person requesting to end his or her life must be medically predicted to have six months or less to live.

According to the exit poll [Washington Initiative 1000], this initiative was supported by liberals (81%) and moderates (63%) and opposed by conservatives (66%). There are more liberals (29% of the voters) than in most states. Republicans (63%) voted against the initiative while Democrats (75%) and Independents (59%) voted for it.

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Asses on Panda's Thumb

 
It's probably not a coincidence that Panda's Thumb published a photo of a pair of asses today. See them at Equus asinus.

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Ken Ham and Jesus Visit Toronto

 
I forgot to mention that "Ken Ham" and "Jesus" were at P.Zed's talk on Friday night. Theo Bromine has photographic proof on the blog Thinking for Free [PZed Myers comes to TO].

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Anonymous Students and Their Grades

 
In Ontario we have to conform to the Freedom of Information and Protection of Privacy Act (FIPPA). What this means is that we cannot publish student names and grades. The University of Toronto guidelines are very clear on this matter [Q and A for Instructors under FIPPA]. We shouldn't even be publishing student numbers with grades.

I just checked with one of my colleagues to find out what the policy was when she graduated in 1949. She showed me the booklet put out by the university in 1949. Her name and grades were listed there. Furthermore, the names and rankings of all student were published in the newspaper.

I asked one of my students who attended high school in Europe. Her name and grades were published in the newspaper. I'm told that this practice continues in some European countries. Another of my colleague learned his medical school grades by reading the Glasgow newspaper in the early 1950s.

Assuming that FIPPA does not apply to the publication of university grades (an invalid assumption), should we publish student names and grades? What are the non-legal arguments for and against this policy?

I like the idea of publishing student's names and grades because it helps make them take responsibility for their activities at university. Very few people agree with me. They all think that a student has a right to privacy. Most of these people don't have a problem with publishing Professor's salaries and course evaluation results because the public has a right to know this information.

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[Photo Description: This is a photograph of the wall on the ground floor of my building. You can see the names and photographs of every student in the medical school graduating class.]

Today Is a Very Important Day

 
It's Sandwalk's second birthday. It was two years ago today that I posted the first message on Sandwalk [Welcome to my Sandwalk].

I started Sandwalk when PZ Myers convinced me that blogging wasn't just a fad. There was a real opportunity to discuss science, and other things, in the blogosphere. Since Nov. 4, 2006 I have published 2,253 postings—some of them have been quite popular and a few of them have been quite good (IMHO).

Sandwalk has grown into a moderate-sized blog with a number of regular readers. I'm particularly excited about the people who comment. They teach me a lot. I'm impressed by the quality of the discussion that goes on in the comments section of Sandwalk postings. This was something that I was hoping for when I started this blog.

A big thank-you to everyone who reads and comments. You've made it all worthwhile.

Here are the latest numbers.

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Please Help Me with My Homework

 
I get email messages like this on a regular basis ...

Hi Mr. Moran, My name is XXX and I am a student at YYY and I would like your help in my English Research Paper.

My task is to write a research paper about something that matters in America today, and I believe the situation surrounding the ID movement is something that really matters. I was wondering where would I be able to get the best information pretaining to the anti-ID, and I thought, why not get it from talk origins?

So Mr. Moran, I would greatly appreciate you helping me in my research paper by outlining and detailing why ID should not be allowed in classrooms or directing me to some one who can.

Thank you for your time, it is greatly appreciated.

I wonder how his teachers define "research"? Back in the olden days we used to read books and articles in order to prepare to write a research paper. Some of you may be familiar with books.

Why have things changed? Why do today's students think they can ask someone else to do all the work for them? Has it got something to do with entitlement, or is it more closely related to intelligence?

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